<?xml version="1.0" encoding="utf-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.0 20120330//EN" "JATS-journalpublishing1.dtd">
<article article-type="review-article" dtd-version="1.0" xml:lang="hr" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">LV</journal-id>
<journal-id journal-id-type="nlm-ta">Lijec Vjesn</journal-id>
<journal-title-group>
<journal-title>Lijecnicki Vjesnik</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Lijec. Vjesn.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="ppub">0024-3477</issn>
<issn pub-type="epub">1849-2177</issn>
<publisher><publisher-name>Croatian Medical Association</publisher-name></publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">LV-146-77</article-id>
<article-id pub-id-type="doi">10.26800/LV-146-3-4-1</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Guidelines</subject></subj-group>
</article-categories>
<title-group>
<article-title>Smjernice za lije&#x010D;enje benignih bolesti anorektalne regije</article-title>
<trans-title-group xml:lang="en">
<trans-title>Guidelines for treatment of benign diseases of anorectal region</trans-title>
</trans-title-group>
</title-group>
<contrib-group>
<contrib contrib-type="author"><name><surname>Karlovi&#x0107;</surname><given-names>Damir</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff9"><sup>a</sup></xref><xref ref-type="aff" rid="aff10"><sup>b</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3128-4830</contrib-id><name><surname>Kr&#x0161;ul</surname><given-names>Dorian</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff9"><sup>a</sup></xref><xref ref-type="aff" rid="aff10"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bori&#x0107;</surname><given-names>Matija</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff9"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Quien</surname><given-names>Damir</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff9"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bar&#x010D;ot</surname><given-names>Ognjen</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff9"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ibuki&#x0107;</surname><given-names>Amir</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff9"><sup>a</sup></xref><xref ref-type="aff" rid="aff12"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ma&#x010D;ki&#x0107;</surname><given-names>Monika</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff9"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bakovi&#x0107;</surname><given-names>Josip</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="aff" rid="aff9"><sup>a</sup></xref><xref ref-type="aff" rid="aff10"><sup>b</sup></xref><xref ref-type="aff" rid="aff12"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stipan&#x010D;i&#x0107;</surname><given-names>Igor</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="aff" rid="aff9"><sup>a</sup></xref><xref ref-type="aff" rid="aff10"><sup>b</sup></xref><xref ref-type="aff" rid="aff12"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bogdani&#x0107;</surname><given-names>Branko</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref><xref ref-type="aff" rid="aff9"><sup>a</sup></xref><xref ref-type="aff" rid="aff12"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kekez</surname><given-names>Tihomir</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref><xref ref-type="aff" rid="aff9"><sup>a</sup></xref><xref ref-type="aff" rid="aff12"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tadi&#x0107;</surname><given-names>Mario</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref><xref ref-type="aff" rid="aff8"><sup>8</sup></xref><xref ref-type="aff" rid="aff11"><sup>cd</sup></xref><xref ref-type="aff" rid="aff12"></xref></contrib><contrib contrib-type="author"><name><surname>Hauser</surname><given-names>Goran</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref><xref ref-type="aff" rid="aff11"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zeli&#x0107;</surname><given-names>Marko</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff9"><sup>a</sup></xref><xref ref-type="aff" rid="aff10"><sup>b</sup></xref></contrib>
<aff id="aff1"><label>1</label><institution content-type="dept">Zavod za digestivnu kirurgiju, Klinika za kirurgiju, Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Rijeci</institution>, <institution>KBC Rijeka</institution></aff>
<aff id="aff2"><label>2</label><institution content-type="dept">Zavod za abdominalnu kirurgiju, Klinika za kirurgiju, Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Splitu</institution>, <institution>KBC Split</institution></aff>
<aff id="aff3"><label>3</label><institution content-type="dept">Odjel za torakalnu i abdominalnu kirurgiju, Klinika za kirurgiju</institution>, <institution>KBC Sestre milosrdnice</institution></aff>
<aff id="aff4"><label>4</label><institution content-type="dept">Zavod za abdominalnu kirurgiju, Klinika za kirurgiju</institution>, <institution>KB Dubrava</institution></aff>
<aff id="aff5"><label>5</label><institution content-type="dept">Zavod za onkolo&#x0161;ku kirurgiju, Klinika za kirurgiju</institution>, <institution>KBC Zagreb</institution></aff>
<aff id="aff6"><label>6</label><institution content-type="dept">Zavod za gastroenterologiju, Klinika za unutarnje bolesti</institution>, <institution>KB Dubrava</institution></aff>
<aff id="aff7"><label>7</label><institution content-type="dept">Zavod za gastroenterologiju, Klinika za unutarnje bolesti, Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Rijeci</institution>, <institution>KBC Rijeka</institution></aff>
<aff id="aff8"><label>8</label>Farmaceutsko-biokemijski fakultet Sveu&#x010D;ili&#x0161;ta u Zagrebu</aff>
<aff id="aff9"><label>a</label><institution content-type="dept">Hrvatsko dru&#x0161;tvo za digestivnu kirurgiju</institution>, <institution>HLZ</institution></aff>
<aff id="aff10"><label>b</label><institution content-type="dept">Hrvatsko dru&#x0161;tvo za endoskopsku kirurgiju</institution>, <institution>HLZ</institution></aff>
<aff id="aff11"><label>c</label>Hrvatsko gastroenterolo&#x0161;ko dru&#x0161;tvo</aff>
<aff id="aff12"><label>d</label>Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Zagrebu</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">Adresa za dopisivanje: Dorian Kr&#x0161;ul, dr. med., <ext-link ext-link-type="uri" xlink:href="https://orcid.org/0000-0002-3128-4830">https://orcid.org/0000-0002-3128-4830</ext-link>, Zavod za digestivnu kirurgiju, Klinika za kirurgiju, Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Rijeci, KBC Rijeka, Kre&#x0161;imirova 42, Rijeka, e-po&#x0161;ta: <email xlink:href="dorian.krsul@hotmail.com">dorian.krsul@hotmail.com</email></corresp>
<fn fn-type="con">
<p content-type="fn-title">DOPRINOS AUTORA</p>
<p>K<sc>oncepcija</sc> <sc>ili</sc> <sc>nacrt</sc> <sc>rada</sc>: DK, DK, MB, DQ, OB, AI, MM, JB, IS, BB, TK, MT, GH, MZ</p>
<p>P<sc>rikupljanje</sc>, <sc>analiza</sc> <sc>i</sc> <sc>interpretacija</sc> <sc>podataka</sc>: DK, DK, MZ, MB, DQ, OB, AI, MM, JB, IS, BB, TK, MT, GH, MZ</p>
<p>P<sc>isanje</sc> <sc>prve</sc> <sc>verzije</sc> <sc>rada</sc>: DK, DK, MB, DQ, OB, AI, MM, JB, IS, BB, TK, MT, GH, MZ</p>
<p>K<sc>riti&#x010D;ka</sc> <sc>revizija</sc>: DK, DK, MZ</p>
</fn>
</author-notes>
<pub-date date-type="pub" publication-format="electronic"><month>06</month><year>2024</year></pub-date>
<pub-date date-type="pub" publication-format="print"><month>06</month><year>2024</year></pub-date>
<volume>146</volume>
<issue>3-4</issue>
<fpage>77</fpage>
<lpage>90</lpage>
<permissions>
<copyright-statement>Croatian Medical Association</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Croatian Medical Association</copyright-holder>
<license xlink:href="https://creativecommons.org/licenses/by-nc-nd/4.0/" specific-use="CC BY-NC-ND 4.0"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND) 4.0 License.</license-p></license>
</permissions>
<abstract>
<title>SA&#x017D;ETAK</title>
<p>Benigne bolesti anorektalne regije, u koje ubrajamo analne apscese, analne fistule, analne fisure i hemoroidalnu bolest, &#x010D;esta su stanja koja susre&#x0107;u lije&#x010D;nici obiteljske medicine kao i bolni&#x010D;ki specijalisti. Unato&#x010D; rasprostranjenosti patologije, jo&#x0161; uvijek ne postoje jasne smjernice za adekvatno lije&#x010D;enje navedenih stanja, koje se jo&#x0161; uvijek &#x010D;esto svodi na preporuke koje nemaju upori&#x0161;te u medicini temeljenoj na dokazima. Zbog toga je ekspertna skupina, u kojoj su sudjelovali &#x010D;lanovi Hrvatskog dru&#x0161;tva za digestivnu kirurgiju kojima je u&#x017E;e podru&#x010D;je interesa koloproktologija, odlu&#x010D;ili sastaviti ove smjernice s namjerom da se standardizira lije&#x010D;enje benignih bolesti anorektalne regije, kako na primarnoj tako i na tercijarnoj razini.</p>
</abstract>
<trans-abstract xml:lang="en">
<title>SUMMARY</title>
<p>Benign anorectal illnesses, of which anal abscesses, anal fistulae, anal fissures and hemoroidal disease are a part of, are common conditions frequently encountered by general medicine practitioners and hospital specialists alike. Despite the prevalence of the pathology, there are still no clear guidelines for the adequate treatment of the mentioned conditions, which is still often reduced to recommendations that have no basis in evidence-based medicine. For this reason, the expert group, which included members of the Croatian Society for Digestive Surgery, with coloproctology as their area of interest, decided to compile these guidelines with the intention of standardizing the treatment of benign diseases of the anorectal region, both at the primary and tertiary levels.</p>
</trans-abstract>
<kwd-group kwd-group-type="author"><kwd>Deskriptori ANALNE BOLESTI &#x2013; dijagnoza, lije&#x010D;enje</kwd><kwd>APSCES &#x2013; kirurgija</kwd><kwd>ANALNE FISTULE &#x2013; dijagnoza, kirurgija</kwd><kwd>ANALNI KANAL &#x2013; kirurgija</kwd><kwd>ANALNE FISURE &#x2013; dijagnoza, farmakoterapija</kwd><kwd>HEMOROIDI &#x2013; dijagnoza, lije&#x010D;enje</kwd><kwd>HEMOROIDEKTOMIJA</kwd><kwd>SMJERNICE</kwd><kwd>HRVATSKA</kwd></kwd-group>
<kwd-group kwd-group-type="translator" xml:lang="en"><title>Descriptors </title><kwd>ANUS DISEASES &#x2013; diagnosis, therapy</kwd><kwd>ABSCESS &#x2013; kirurgija</kwd><kwd>RECTAL FISTULA &#x2013; diagnosis, surgery</kwd><kwd>ANAL CANAL &#x2013; surgery</kwd><kwd>FISSURE IN ANO &#x2013; diagnosis, drug therapy</kwd><kwd>HEMORRHOIDS &#x2013; diagnosis, therapy</kwd><kwd>HEMORRHOIDECTOMY</kwd><kwd>PRACTICE GUIDELINES AS TOPIC</kwd><kwd>CROATIA</kwd></kwd-group>
</article-meta>
</front>
<body>
<sec sec-type="other1">
<title>Metode rada</title>
<p>U prosincu 2022. u organizaciji Hrvatskog dru&#x0161;tva za digestivu kirurgiju odr&#x017E;an je inicijalni sastanak radne skupine digestivnih kirurga i gastroenterologa za izradu smjernica za lije&#x010D;enje benignih bolesti anorektalne regije.</p>
<p>U radu su sudjelovali &#x010D;lanovi Hrvatskog dru&#x0161;tva za digestivnu kirurgiju te Hrvatskog dru&#x0161;tva za endoskopsku kirurgiju koji djeluju pod Hrvatskim lije&#x010D;ni&#x010D;kim zborom i &#x010D;lanovi Hrvatskoga gastroenterolo&#x0161;kog dru&#x0161;tva.</p>
<p>U pripremi sastanka analizirana je relevantna i suvremena medicinska literatura kao i trenutna klini&#x010D;ka praksa te su se &#x010D;lanovi skupine podijelili prema patologiji tako da je jedna radna grupa obra&#x0111;ivala problematiku analnih fisura, druga analnog apscesa, tre&#x0107;a analnih fistula i &#x010D;etvrta problematiku hemoroidalne bolesti. Svoje zaklju&#x010D;ke pojedine su grupe predstavile na sastanku radnih skupina te su isti raspravljeni od strane ostalih &#x010D;lanova skupa. Kona&#x010D;ni zaklju&#x010D;ci su ukomponirani u obliku ovih smjernica.</p>
<p>Za vrijeme formiranja smjernica &#x010D;lanovi radne skupine bili su u kontaktu elektroni&#x010D;kim putem.</p>
<p>Razina dokaza i stupanj preporuka navedeni su sukladno sustavu GRADE (engl. <italic>Grading of Recommendation, Assessment, Development and Evaluation</italic>). Smjernice su tematski podjeljene prema patologiji koju obra&#x0111;uju sa zasebnim sekcijama za analni apsces, analne fistule, analnu fisuru i hemoroidalnu bolest.</p>
<p>Izrada smjernica nije bila financijski potpomognuta.</p>
</sec>
<sec id="sec1" sec-type="other2">
<label>1.</label><title>Smjernice za lije&#x010D;enje analnog apscesa (<xref ref-type="fig" rid="f1">Figure 1</xref>)</title>
<fig id="f1" position="float" fig-type="figure"><label>Figure 1</label><caption><p>Hodogram lije&#x010D;enja analnog apscesa / Anal abscess treatment algorithm</p></caption><graphic xlink:href="LV-146-77-f1"></graphic></fig>
<p>Anorektalni apscesi nastaju iz inficirane &#x017E;lijezde analne kripte. U razini nazubljene linije, cirkumferentno unutar analnog kanala nalazi se 8 &#x2013; 10 anal-</p>
<p>nih kriptnih &#x017E;lijezda. &#x017D;lijezde prodiru kroz unutarnji sfinkter iz intersfinkteri&#x010D;nog prostora gdje se nalaze do spomenute nazubljene linije. Apsces se razvija kada se &#x017E;lijezda analne kripte za&#x010D;epi ostatcima debrisa, &#x0161;to dovodi do rasta bakterija. Neki apscesi se &#x0161;ire distalno (aboralno) u intersfinkteri&#x010D;noj ravnini, prema perianalnoj ko&#x017E;i, gdje se manifestiraju kao osjetljiva, fluktuiraju&#x0107;a masa. Drugi slijede put najmanjeg otpora u druge prostore (intersfinkteri&#x010D;ni, ishiorektalni, supralevatorni).</p>
<p>Anorektalni apscesi su &#x010D;esta bolest, s prosje&#x010D;nom incidencijom oko dva slu&#x010D;aja na 10.000 stanovnika godi&#x0161;nje. Medijan pojave bolesti je 40 godina (raspon 20 do 60). Mu&#x0161;karci imaju dvostruko ve&#x0107;u vjerojatnost da &#x0107;e razviti anorektalni apsces u usporedbi sa &#x017E;enama. (<xref ref-type="bibr" rid="r1"><italic>1</italic></xref>&#x2013;<xref ref-type="bibr" rid="r7"><italic>7</italic></xref>)</p>
</sec>
<sec id="sec1.1" sec-type="other3">
<label>1.1</label><title>Kod sumnje na anorektalni apsces, &#x0161;to treba napraviti? (sna&#x017E;na preporuka temeljena na dokazima niske kvalitete, 1C)</title>
<p>Kod bolesnika koji imaju sumnju na anorektalni apsces potrebno je uzeti detaljnu anamnezu i u&#x010D;initi kompletan fizikalni pregled, uklju&#x010D;uju&#x0107;i i digito-rektalni pregled. Ako postoje znakovi sepse potrebno je odrediti kompletnu krvnu sliku, markere upale (npr. C-reaktivni protein, prokalcitonin, laktate). (<xref ref-type="bibr" rid="r1"><italic>1</italic></xref>&#x2013;<xref ref-type="bibr" rid="r7"><italic>7</italic></xref>)</p>
</sec>
<sec id="sec1.2" sec-type="other4">
<label>1.2</label><title>Kod sumnje na anorektalni apsces, koje dijagnosti&#x010D;ke metode treba u&#x010D;initi? (sna&#x017E;na preporuka temeljena na dokazima umjerene kvalitete, 1B)</title>
<p>Nema potrebe za rutinskim kori&#x0161;tenjem dijagnosti&#x010D;kih metoda. (<xref ref-type="bibr" rid="r2"><italic>2</italic></xref>&#x2013;<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>) Kod nejasnih slu&#x010D;ajeva, recidivnih ili kompleksnih analnih fistula, imunosuprimiranih bolesnika, kao i kod bolesnika s Crohnovom bolesti mo&#x017E;e se u&#x010D;initi kompjutorizirana tomografija (CT), magnetska rezonancija (MRI) i/ili endoanalni ultrazvuk (EUS). Izbor dijagnosti&#x010D;ke metode ovisi o dostupnosti radiologa i radiolo&#x0161;ke opreme. (<xref ref-type="bibr" rid="r2"><italic>2</italic></xref>&#x2013;<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>, <xref ref-type="bibr" rid="r6"><italic>6</italic></xref>&#x2013;<xref ref-type="bibr" rid="r12"><italic>12</italic></xref>)</p>
</sec>
<sec id="sec1.3" sec-type="other5">
<label>1.3</label><title>Kod bolesnika s anorektalnim apscesom, koje su indikacije za kirur&#x0161;kim lije&#x010D;enjem i kada je optimalno vrijeme za zahvat? (sna&#x017E;na preporuka temeljena na dokazima niske kvalitete, 1C)</title>
<p>Jedini izbor lije&#x010D;enja anorektalnog apscesa jest kirur&#x0161;ki zahvat (incizija i drena&#x017E;a). Kirur&#x0161;ki zahvat treba u&#x010D;initi &#x0161;to je prije mogu&#x0107;e. Prilikom kirur&#x0161;kog zahvata bolesnik treba biti u ginekolo&#x0161;kom polo&#x017E;aju u op&#x0107;oj ili regionalnoj anesteziji.</p>
<p>Incizija apscesa treba biti dovoljno velika kako bi se mogao adekvatno drenirati gnojni sadr&#x017E;aj. Minimalna veli&#x010D;ina incizije treba biti &#x0161;irine prsta operatera. Operater treba prstom eksplorirati cijelu apscesnu &#x0161;upljinu te prekinuti eventualno prisutne septe. Apscesnu &#x0161;upljinu treba dobro isprati fiziolo&#x0161;kom otopinom. Nakon ispiranja u apscesnu &#x0161;upljinu mo&#x017E;e se postaviti dren ili tamponada, ovisno o procjeni operatera. Pri inciziji obvezna je inspekcija analnog kanala retraktorom zbog eventualnog verificiranja unutarnjega fistuloznog otvora. (<xref ref-type="bibr" rid="r2"><italic>2</italic></xref>&#x2013;<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>, <xref ref-type="bibr" rid="r13"><italic>13</italic></xref>, <xref ref-type="bibr" rid="r14"><italic>14</italic></xref>)</p>
<p>Pozicija apscesa odre&#x0111;uje tip drena&#x017E;e (unutarnji ili vanjski). Intersfinkteri&#x010D;ne apscese treba drenirati kroz intersfinkteri&#x010D;nu ravninu ili u analni kanal. Supralevatorne apscese koji su nastali &#x0161;irenjem intersfinkteri&#x010D;nog apscesa treba drenirati unutarnjom incizijom rektuma, kako bi se sprije&#x010D;ilo formiranje fistule. Supralevatorni apsces, koji je nastao zbog &#x0161;irenja ishiorektalnog (ishioanalnog) apscesa, trebalo bi drenirati izvana kroz perianalnu ko&#x017E;u. (<xref ref-type="bibr" rid="r2"><italic>2</italic></xref>&#x2013;<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>, <xref ref-type="bibr" rid="r13"><italic>13</italic></xref>)</p>
<p>Punkcija apscesa se ne preporu&#x010D;uje! Tako&#x0111;er treba izbjegavati &#x201E;mikroincizije&#x201C; zbog prevencije razvoja analne fistule! (<xref ref-type="bibr" rid="r15"><italic>15</italic></xref>)</p>
<p>Bolesnici sa znakovima sepse i imunokompromitirani bolesnici zahtijevaju daljnje bolni&#x010D;ko lije&#x010D;enje. Ostali bolesnici mogu biti lije&#x010D;eni kroz dnevnu kirurgiju. (<xref ref-type="bibr" rid="r2"><italic>2</italic></xref>&#x2013;<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>)</p>
</sec>
<sec id="sec1.4" sec-type="other6">
<label>1.4</label><title>Je li potrebno uzimati briseve tijekom kirur&#x0161;kog zahvata? (slaba preporuka temeljena na dokazima umjerene kvalitete, 2B)</title>
<p><italic>Nema potrebe za rutinskim uzimanjem briseva.</italic> (<xref ref-type="bibr" rid="r16"><italic>16</italic></xref>) Kod bolesnika koji su imunokompromitirani, imaju ponavljaju&#x0107;e (recidivne) apcese, rane koje ne cijele, preporu&#x010D;uje se uzeti briseve na aerobne i anaerobne mikroorganizme, kao i gljivice. (<xref ref-type="bibr" rid="r2"><italic>2</italic></xref>&#x2013;<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>)</p>
</sec>
<sec id="sec1.5" sec-type="other7">
<label>1.5</label><title>&#x0160;to ako je uz anorektalni apsces prisutna fistula? (slaba preporuka temeljena na dokazima niske kvalitete, 2C)</title>
<p>Kod bolesnika s anorektalnim apscesom i fistulom predla&#x017E;emo u&#x010D;initi fistulotomiju u isto vrijeme kada i drena&#x017E;u apscesa, ali samo kada se radi o jednostavnoj fistuli, koja ne zahva&#x0107;a sfinkter. Ako je apsces posljedica akutizacije analne fistule ili se vidi jasan otvor u analnom kanalu potrebno je postaviti <italic>loose seton</italic> s ciljem maturiranja analne fistule te njezinog zbrinjavanja u drugom aktu. Ako se prilikom pregleda i/ili operativnog zahvata ne prikazuje fistula, ne preporu&#x010D;uje se eksploracija glavi&#x010D;astom sondom, kako bi se izbjegle jatrogene komplikacije, odnosno kako bi se izbjeglo stvaranje artificijelnog (umjetno stvorenog) otvora. (<xref ref-type="bibr" rid="r2"><italic>2</italic></xref>&#x2013;<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>, <xref ref-type="bibr" rid="r17"><italic>17</italic></xref>, <xref ref-type="bibr" rid="r18"><italic>18</italic></xref>)</p>
</sec>
<sec id="sec1.6" sec-type="other8">
<label>1.6</label><title>Je li potrebna antimikrobna terapija kod bolesnika s anorektalnim apscesom? (slaba preporuka temeljena na dokazima umjerene kvalitete, 2B)</title>
<p>Postoperativna antibiotska terapija mo&#x017E;e zna&#x010D;ajno smanjiti incidenciju pojavnosti analne fistule. Predla&#x017E;emo davanje ciprofloksacina 2 x 500 mg i metronidazola 3 x 400 mg tijekom 5 &#x2013; 7 dana. (<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>, <xref ref-type="bibr" rid="r19"><italic>19</italic></xref>)</p>
</sec>
<sec id="sec1.7" sec-type="other9">
<label>1.7</label><title>Kakva je postoperativna skrb nakon operativnog lije&#x010D;enja? (slaba preporuka temeljena na dokazima niske kvalitete, 2C)</title>
<p>Nakon operativnog lije&#x010D;enja bolesniku treba dati jasne upute o analgeziji (&#x010D;esto na bazi opijata), preporu&#x010D;iti prehranu bogatu vlaknima, kao i provo&#x0111;enje tu&#x0161;iranja rane vi&#x0161;e puta dnevno i nakon svake stolice. Kod bolesnika s recidivnim anorektalnim apscesima, kao i prisutnim fistulama, preporu&#x010D;uje se u&#x010D;initi gastroenterolo&#x0161;ku/infektolo&#x0161;ku obradu i pregled proktologa. Zbog visoke stope recidiva sve bolesnike treba pratiti do potpunog ozdravljenja, &#x0161;to mo&#x017E;e potrajati i do osam tjedana. (<xref ref-type="bibr" rid="r2"><italic>2</italic></xref>&#x2013;<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>)</p>
</sec>
<sec id="sec2" sec-type="other10">
<label>2.</label><title>Smjernice za lije&#x010D;enje analne fistule (<xref ref-type="fig" rid="f2">Figure 2</xref>)</title>
<fig id="f2" position="float" fig-type="figure"><label>Figure 2</label><caption><p>Hodogram lije&#x010D;enja analne fistule / Anal fistula treatment algorithm</p></caption><graphic xlink:href="LV-146-77-f2"></graphic></fig>
<p>Analna fistula je kroni&#x010D;ni abnormalni spoj izme&#x0111;u analnog kanala i perianalne ko&#x017E;e. Radi se o kanalu oblo&#x017E;enom granulacijskim tkivom koje potpoma&#x017E;e kroni&#x010D;nu upalu. Incidencija ove bolesti je oko 10 slu&#x010D;ajeva na 100.000 osoba s odnosom izme&#x0111;u mu&#x0161;karaca i &#x017E;ena 2:1. U ve&#x0107;ini slu&#x010D;ajeva nastaje kao posljedica analnog apscesa (kriptoglandularne etiologije), iako mo&#x017E;e biti povezana s upalnim bolestima crijeva (Crohnova bolest), traumom i malignim oboljenjima. (<xref ref-type="bibr" rid="r20"><italic>20</italic></xref>, <xref ref-type="bibr" rid="r21"><italic>21</italic></xref>)</p>
<p>Koriste se razli&#x010D;ite klasifikacije kako bi se prikazao odnos fistule prema analnom sfinkternom kompleksu, a najra&#x0161;irenija je Parksova klasifikacija. (<xref ref-type="bibr" rid="r22"><italic>22</italic></xref>) Tako&#x0111;er &#x010D;esto kori&#x0161;tena podjela, a relevantnija za klini&#x010D;ke prosudbe, jest podjela na jednostavne i kompleksne fistule. Jednostavne analne fistule su one &#x010D;iji kanal prolazi manje od 30% vanjskoga analnog sfinktera te su najjednostavnije. Ostale fistule se klasificiraju kao kompleksne te ih karakterizira zahva&#x0107;anje vi&#x0161;e od 30% analnog sfinktera, vi&#x0161;estruki kanali, anteriorni smje&#x0161;taj u &#x017E;ena, rekurencija i povezanost s upalnim bolestima crijeva. Kompleksnim fistulama mo&#x017E;emo smatrati i one koje zahva&#x0107;aju manje od 30% analnog sfinktera uz postojanje ranijeg stupnja fekalne inkontinencije. Fistule povezane s upalnim bolestima crijeva predstavljaju zasebnu problematiku te nisu obuhva&#x0107;ene ovim smjernicama.</p>
</sec>
<sec id="sec2.1" sec-type="other11">
<label>2.1</label><title>Kako uzeti adekvatnu anamnezu i obaviti fizikalni pregled? (sna&#x017E;na preporuka temeljena na dokazima niske kvalitete, 1C)</title>
<p>Anamnezom se moraju saznati simptomi povezani sa samom bole&#x0161;&#x0107;u, vrijeme trajanja bolesti, ranije tegobe vezane za analnu fistulu te eventualna mogu&#x0107;a povezanost s upalnim bolestima crijeva (IBD). Pregled se vr&#x0161;i kombinacijom digitorektalnog pregleda i sondiranjem glavi&#x010D;astom sondom. U slu&#x010D;aju bolnog pregleda ili neadekvatne vizualizacije, <italic>pregled bi se morao u&#x010D;initi u anesteziji</italic>. Prilikom opisivanja tipa fistule potrebno je razlikovati radi li se o jednostavnoj ili kompleksnoj fistuli. Tako&#x0111;er adekvantno opisati poziciju fistule koriste&#x0107;i <italic>&#x201E;orijentaciju po satu&#x201C; s tim da je 12 sati uvijek anteriorno, 6 sati posteriorno, 3 sata lijevo, 9 sati desno, neovisno o polo&#x017E;aju pregleda bolesnika</italic> (litotomijski, Simsov, &#x201E;koljeno-lakat&#x201C;)! (<xref ref-type="bibr" rid="r23"><italic>23</italic></xref>, <xref ref-type="bibr" rid="r24"><italic>24</italic></xref>)</p>
</sec>
<sec id="sec2.2" sec-type="other12">
<label>2.2</label><title>Koje dijagnosti&#x010D;ke metode koristiti za analnu fistulu kada je sam fizikalni pregled nejasan ili nepotpun? (sna&#x017E;na preporuka temeljena na dokazima umjerene kvalitete, 1B)</title>
<p>RTG fistulografija je zastarjela dijagnosti&#x010D;ka metoda jer ne pokazuje korelaciju fistule s analnim sfinkterom te se kao takva ne bi smjela vi&#x0161;e koristiti. (<xref ref-type="bibr" rid="r25"><italic>25</italic></xref>) Mogu&#x0107;e opcije za verifikaciju korelacije fistule s analnim sfinkterom jesu: CT fistulografija, endoanalni ultrazvuk i MR fistulografija.</p>
<p>CT fistulografija je to&#x010D;nija u slu&#x010D;ajevima povezanima s akutnom inflamacijom (analni apsces), ali je neprecizna u slu&#x010D;ajevima maturirane fistule. Endoanalni ultrazvuk je vrlo dobra dijagnosti&#x010D;ka opcija koja mo&#x017E;e vizualizirati i sfinkterni kompleks i grananja fistule, ali je ovisna o izvoditelju pretrage. (<xref ref-type="bibr" rid="r25"><italic>25</italic></xref>&#x2013;<xref ref-type="bibr" rid="r28"><italic>28</italic></xref>)</p>
<p>Zlatni standard za klasifikaciju i dijagnostiku analnih fistula jest magnetna rezonancija (MR). MR ne samo da precizno prikazuje pro&#x0161;irenost bolesti, ve&#x0107; slu&#x017E;i i za predikciju ishoda, planiranje terapeutskih metoda, postoperativno pra&#x0107;enje bolesnika ili u slu&#x010D;aju rekurentnih fistula ili fistula u sklopu Crohnove bolesti. (<xref ref-type="bibr" rid="r29"><italic>29</italic></xref>&#x2013;<xref ref-type="bibr" rid="r33"><italic>33</italic></xref>)</p>
</sec>
<sec id="sec2.3" sec-type="other13">
<label>2.3</label><title>Kako lije&#x010D;iti jednostavne fistule? (sna&#x017E;na preporuka temeljena na dokazima umjerene kvalitete, 1B)</title>
<p>Lije&#x010D;enje jednostavnih analnih fistula u prvom redu uvijek je operacijski zahvat. Lije&#x010D;e se tzv. tehnikama &#x201E;lay-open&#x201D; odnosno fistulotomijom ili fistulektomijom. Ovakve metode lije&#x010D;enja jednostavnih fistula imaju zanemariv utjecaj na poreme&#x0107;aj fekalne kontinencije, a uspje&#x0161;nost im je do 96%. (<xref ref-type="bibr" rid="r34"><italic>34</italic></xref>&#x2013;<xref ref-type="bibr" rid="r36"><italic>36</italic></xref>)</p>
</sec>
<sec id="sec2.4" sec-type="other14">
<label>2.4</label><title>Kako lije&#x010D;iti kompleksne fistule? (sna&#x017E;na preporuka temeljena na dokazima umjerene kvalitete, 1B)</title>
<p>Lije&#x010D;enje kompleksnih analnih fistula u prvom redu uvijek je operacijski zahvat.</p>
<p>Ako se kompleksne fistule lije&#x010D;e <italic>lay-open</italic> tehnikama javlja se velika incidencija nekog oblika postoperativne fekalne inkontinencije. (<xref ref-type="bibr" rid="r34"><italic>34</italic></xref>) Pokazalo se da je prosje&#x010D;na incidencija poreme&#x0107;aja kontinencije nakon lije&#x010D;enja kompleksnih fistula &#x201E;<italic>cutting setonom</italic>&#x201C; do 12%, koja je i vi&#x0161;a u slu&#x010D;ajevima kada bi fistula zahva&#x0107;ala ve&#x0107;i dio analnog sfinktera. (<xref ref-type="bibr" rid="r37"><italic>37</italic></xref>) Nakon kori&#x0161;tenja tehnika <italic>lay-open</italic> primijetila se incidencija inkontinencije za vjetrove ili teku&#x0107;u stolicu u 20 &#x2013; 25% pacijenata. (<xref ref-type="bibr" rid="r35"><italic>35</italic></xref>) Rezultat toga bio je da je primjena ovih tehnika postala nepo&#x017E;eljna za lije&#x010D;enje kompleksnih analnih fistula te je po&#x017E;eljno stvaranje minimalno invazivnih metoda lije&#x010D;enja, po&#x0161;tednih za sfinkter.</p>
<p>Jedan od koraka u lije&#x010D;enju kompleksnih analnih fistula kao privremeno rje&#x0161;enje do definitivnog zahvata jest plasiranje loose setona. <italic>Loose-seton</italic> treba postaviti kroz kanal fistule bez zatezanja, &#x0161;to potpoma&#x017E;e smanjenje sepse i sazrijevanje kanala fistule te u tom slu&#x010D;aju to obilje&#x017E;ava prvu fazu u rje&#x0161;avanju problema analne fistule. (<xref ref-type="bibr" rid="r38"><italic>38</italic></xref>, <xref ref-type="bibr" rid="r39"><italic>39</italic></xref>)</p>
<p>Definitivni zahvat s intencijom lije&#x010D;enja kompleksnih analnih fistula treba u&#x010D;initi nekom od tzv. sfinkter-po&#x0161;tednih tehnika &#x010D;ija je glavna karakteristika da sprje&#x010D;avaju ili uvelike smanjuju svaku mogu&#x0107;nost postoperativne fekalne inkontinencije. U njih spadaju postupak laserskog lije&#x010D;enja (engl. FiLaC&#x00AE; &#x2013; <italic>fistula laser closure</italic>), lije&#x010D;enje fibrinskim ljepilom, VAAFT postupak (engl. <italic>video-assisted anal fistula treatment</italic>), LIFT postupak (engl. <italic>ligation of intersphincteric fistula tract</italic>), lije&#x010D;enje analne fistule stanicama trombocita (engl. PRP &#x2013; <italic>platelet rich plasma</italic>), RAF (engl. <italic>rectal advancement flap</italic>) i drugi. (<xref ref-type="bibr" rid="r40"><italic>40</italic></xref>&#x2013;<xref ref-type="bibr" rid="r48"><italic>48</italic></xref>) Hibridne sfinkter-po&#x0161;tedne tehnike (kombinacija vi&#x0161;e tehnika) mogu se koristiti kako bi se izbjegli nedostatci jedne i iskoristile prednosti druge tehnike. (<xref ref-type="bibr" rid="r49"><italic>49</italic></xref>, <xref ref-type="bibr" rid="r50"><italic>50</italic></xref>)</p>
<p>Bolesnike s kompleksnim analnim fistulama trebaju lije&#x010D;iti kirurzi upoznati sa sfinkter-po&#x0161;tednim metodama lije&#x010D;enja, te bi u slu&#x010D;aju nemogu&#x0107;nosti lije&#x010D;enja kompleksnih analnih fistula u najbli&#x017E;im zdravstvenim ustanovama bolesnici trebali biti upu&#x0107;eni u centre gdje se takvi zahvati izvode radi prevencije rizika postoperativne fekalne inkontinencije. Jedna od mogu&#x0107;nosti lije&#x010D;enja kompleksnih fistula koju mogu vr&#x0161;iti i kirurzi koji nisu iskusni sa sfinkter-po&#x0161;tednim tehnikama jest i ekskohleacija kanala fistule te plasiranje <italic>loose setona</italic>.</p>
</sec>
<sec id="sec2.5" sec-type="other15">
<label>2.5</label><title>Kako lije&#x010D;iti analnu fistulu u Crohnovoj bolesti? (sna&#x017E;na preporuka temeljena na dokazima niske kvalitete, 1C)</title>
<p>Lije&#x010D;enje analnih fistula u sklopu Crohnove bolesti izrazito je kompleksno te zahtjeva multidisciplinarni pristup (u prvom redu gastroenterologa i kirurga). Asimptomatske fistule u bolesnika s Crohnovom bole&#x0161;&#x0107;u ne zahtjevaju kirur&#x0161;ko lije&#x010D;enje, ve&#x0107; je potrebno ambulantno pratiti klini&#x010D;ku sliku.</p>
<p>Bolesnici koji imaju jednostavne fistule u sklopu Crohnove bolesti trebaju biti tretirani fistulotomijom (oprez u slu&#x010D;aju ranijih operacija zbog dodatne ozljede analnog sfinktera!).</p>
<p>Jedno od kirur&#x0161;kih rije&#x0161;enja u lije&#x010D;enju analne fistule u Crohnovoj bolesti jest i plasiranje <italic>loose setona</italic> zbog kontrole sekrecije i smanjenja lokalne upale te tako&#x0111;er postoji mogu&#x0107;nost pristupa lije&#x010D;enju kompleksnih analnih fistula u sklopu Crohnove bolesti tehnikama po&#x0161;tednim za sfinkter.</p>
</sec>
<sec id="sec2.6" sec-type="other16">
<label>2.6</label><title>Treba li razmi&#x0161;ljati o kolostomi ili proktektomiji i kada? (sna&#x017E;na preporuka temeljena na dokazima niske kvalitete, 1C)</title>
<p>U slu&#x010D;aju nekontrolirane forme bolesti s razvojem celulitisa, Fournierove gangrene ili sepse treba razmisliti o formiranju kolostome radi fekalne diverzije, odnosno o proktektomiji u krajnjem slu&#x010D;aju. (<xref ref-type="bibr" rid="r51"><italic>51</italic></xref>&#x2013;<xref ref-type="bibr" rid="r55"><italic>55</italic></xref>)</p>
</sec>
<sec id="sec3" sec-type="other17">
<label>3.</label><title>Smjernice za lije&#x010D;enje analne fisure (<xref ref-type="fig" rid="f3">Figure 3</xref>)</title>
<fig id="f3" position="float" fig-type="figure"><label>Figure 3</label><caption><p>Anal fissure treatment algorithm</p></caption><graphic xlink:href="LV-146-77-f3"></graphic></fig>
<p>Analna fisura je benigno stanje koje ozna&#x010D;ava uzdu&#x017E;ni ili ovalni rascjep u podru&#x010D;ju analnog kanala, od analnog ruba do nazubljene linije. Uzrok nastanka analne fisure nije u potpunosti razja&#x0161;njen, no smatra se da je vode&#x0107;i razlog trauma analnog kanala, bilo zbog prolaska tvrde stolice, lokalne iritacije proljevom, anorektalnih kirur&#x0161;kih postupaka ili pak analnih seksualnih odnosa. (<xref ref-type="bibr" rid="r56"><italic>56</italic></xref>)</p>
<p>Vode&#x0107;i simptom je bol u predjelu anusa koja se pogor&#x0161;ava defekacijom te mo&#x017E;e perzistirati i nekoliko sati nakon defekacije. (<xref ref-type="bibr" rid="r57"><italic>57</italic></xref>) Osim navedenog, klini&#x010D;ka slika tako&#x0111;er mo&#x017E;e biti obilje&#x017E;ena i anorektalnim krvarenjem, naj&#x010D;e&#x0161;&#x0107;e manjeg obima. Ve&#x0107;ina fisura je smje&#x0161;tena u predjelu stra&#x017E;nje komisure (&#x201E;na 6 sati&#x201C;). (<xref ref-type="bibr" rid="r58"><italic>58</italic></xref>&#x2013;<xref ref-type="bibr" rid="r60"><italic>60</italic></xref>) Lateralno smje&#x0161;tene fisure te multiple fisure smatraju se atipi&#x010D;nima te zahtijevaju temeljitu obradu zbog mogu&#x0107;e povezanosti s HIV-infekcijom, sifilisom, Crohnovom bolesti, tuberkulozom i hematolo&#x0161;kim malignim bolestima. Akutne fisure tipi&#x010D;no traju kra&#x0107;e od osam tjedana i imaju izgled uzdu&#x017E;nog rascjepa. Kroni&#x010D;ne fisure ozna&#x010D;ene su trajanjem simptoma duljim od osam tjedana. Analni pseudopolip, hipertrofija sluznice u oralnom dijelu, vidljiva mi&#x0161;i&#x0107;na vlakna analnog sfinktera obilje&#x017E;ja su kroni&#x010D;nog tijeka analne fisure. Kroni&#x010D;na analna fisura je &#x010D;esto stanje i poga&#x0111;a sve dobne skupine s jednakom pojavno&#x0161;&#x0107;u u oba spola. (<xref ref-type="bibr" rid="r61"><italic>61</italic></xref>)</p>
</sec>
<sec id="sec3.1" sec-type="other18">
<label>3.1</label><title>Koje su neoperacijske metode lije&#x010D;enja? (sna&#x017E;na preporuka temeljena na dokazima umjerene kvalitete, 1B) a.&#x2002;Konzervativno lije&#x010D;enje</title>
<sec id="sec3.1a">
<label>a.</label><title>Konzervativno lije&#x010D;enje</title>
<p>Konzervativne mjere lije&#x010D;enja poput lokalnih anestetika, sitz-kupki, unos vlakana te topikalna primjena glukokortikoida i dalje se smatraju prvim izborom u lije&#x010D;enju analne fisure. Cilj ovih mjera je smanjenje bolnosti i poticanje cijeljenja fisure. U&#x010D;inkovitost konzervativnih mjera lije&#x010D;enja kre&#x0107;e se prema studijama u rasponu od 43% (lignokain) do gotovo 87% (<italic>sitz</italic>-kupke i vlakna). (<xref ref-type="bibr" rid="r62"><italic>62</italic></xref>&#x2013;<xref ref-type="bibr" rid="r64"><italic>64</italic></xref>) Produ&#x017E;eni peroralni unos vlakana tako&#x0111;er ima u&#x010D;inak na smanjenje stope recidiva analne fisure. (<xref ref-type="bibr" rid="r65"><italic>65</italic></xref>) Primjena ovih mjera ima malu stopu nuspojava i op&#x0107;enito se dobro tolerira od strane pacijenta. Cochraneov pregled ipak nagla&#x0161;ava da su studije o ovoj vrsti lije&#x010D;enja (lignokain, hidrokortizon, <italic>sitz</italic>-kupke, dilatacija ili hrana bogata vlaknima) uglavnom starijeg datuma zbog njihove opsoletnosti. (<xref ref-type="bibr" rid="r66"><italic>66</italic></xref>)</p>
</sec>
<sec id="sec3.1b">
<label>b.</label><title>Topikalna primjena nitrata</title>
<p>U lokalnoj terapiji analne fisure primjena nitrata temelji se na relaksaciji glatkih mi&#x0161;i&#x0107;a, &#x0161;to dovodi do popu&#x0161;tanja pritiska u analnom kanalu i olak&#x0161;ava cijeljenje fisure. Prema podatcima iz vi&#x0161;e studija stopa cijeljenja analne fisure iznosi oko 63% nakon osam tjedana topikalne primjene nitrata. (<xref ref-type="bibr" rid="r66"><italic>66</italic></xref>, <xref ref-type="bibr" rid="r67"><italic>67</italic></xref>) Najve&#x0107;i problem u primjeni nitrata jesu nuspojave terapije, prvenstveno glavobolja, koja se javlja do u 30% pacijenata, te je &#x010D;esti razlog prekida lije&#x010D;enja ovim pripravkom. (<xref ref-type="bibr" rid="r68"><italic>68</italic></xref>, <xref ref-type="bibr" rid="r69"><italic>69</italic></xref>)</p>
</sec>
<sec id="sec3.1c">
<label>c.</label><title>Blokatori kalcijskih kanala</title>
<p>Blokatori kalcijskih kanala (dilitiazem, nifedipin) imaju sli&#x010D;an mehanizam djelovanja kao nitrati, dovode do relaksacije glatkih mi&#x0161;i&#x0107;a i pobolj&#x0161;anja prokrvljenosti te posljedi&#x010D;no pobolj&#x0161;anja cijeljenja fisure. Iako i ova skupina lijekova ima sposobnost uzrokovati sli&#x010D;ne glavobolje kao i nitrati, pojavnost ovoga ne&#x017E;eljenog fenomena zna&#x010D;ajno je ni&#x017E;a. (<xref ref-type="bibr" rid="r70"><italic>70</italic></xref>&#x2013;<xref ref-type="bibr" rid="r72"><italic>72</italic></xref>)</p>
<p>Blokatori kalcijskih kanala mogu se primijeniti topikalnim i oralnim putem. Stopa cijeljenja nakon primjene dilitiazema topikalno iznosila je 66% u razdoblju od dvanaest tjedana. (<xref ref-type="bibr" rid="r73"><italic>73</italic></xref>) Topikalna primjena dilitiazema tako&#x0111;er je povezana s br&#x017E;om regresijom simptoma u odnosu na nitrate kao prva linija terapije. (<xref ref-type="bibr" rid="r74"><italic>74</italic></xref>) Topikalna primjena blokatora kalcijskih kanala ima bolji u&#x010D;inak na cijeljenje od oralne primjene i optere&#x0107;ena je s manje nuspojava uz jednake stope recidiva fisure te se zbog toga preferira. (<xref ref-type="bibr" rid="r75"><italic>75</italic></xref>)</p>
</sec>
<sec id="sec3.1d">
<label>d.</label><title>Botulinum toksin</title>
<p>Botulinum toksin opu&#x0161;ta popre&#x010D;no-prugastu muskulaturu te se kao takav koristi u lije&#x010D;enju mi&#x0161;i&#x0107;ne hipertonije i nekih kozmetskih poreme&#x0107;aja. (<xref ref-type="bibr" rid="r76"><italic>76</italic></xref>) Injekcije botoxa u unutarnji analni sfinkter uklanjaju mi&#x0161;i&#x0107;ni spazam blokiraju&#x0107;i neurotransmisiju. Tako se provodi reverzibilna kemijska sfinkterotomija i prekida ciklus bol &#x2013; spazam &#x2013; bol. (<xref ref-type="bibr" rid="r77"><italic>77</italic></xref>, <xref ref-type="bibr" rid="r78"><italic>78</italic></xref>) Osim smanjenja/uklanjanja mi&#x0161;i&#x0107;nog spazma, aplikacija botoxa dokazano djeluje i na ubla&#x017E;avanje analne boli. (<xref ref-type="bibr" rid="r79"><italic>79</italic></xref>) U direktnoj usporedbi botulinum toksina s 0,2% i 1% topikalnim/lokalnim nitroglicerinom i 0,2% topikalnim/lokalnim nifedipinom, botulinum toksin omogu&#x0107;ava stopu cijeljenja od 18% do 71% unutar devetotjednog tretmana, &#x0161;to je usporedno ili &#x010D;ak bolje od same lokalne terapije. (<xref ref-type="bibr" rid="r80"><italic>80</italic></xref>, <xref ref-type="bibr" rid="r81"><italic>81</italic></xref>) Treba spomenuti i povezanost upotrebe botulinum toksina i manje incidencije nuspojava. Aplikacija je siguran postupak, dobro se podnosi te se kao takav obavlja kod ambulantnih bolesnika. (<xref ref-type="bibr" rid="r77"><italic>77</italic></xref>, <xref ref-type="bibr" rid="r82"><italic>82</italic></xref>)</p>
<p>U usporedbi s kirur&#x0161;kim zahvatom, preporu&#x010D;uje se kori&#x0161;tenje botulinum toksina u starije populacije kao i u ostalih s visokim rizikom fekalne inkontinencije. (<xref ref-type="bibr" rid="r83"><italic>83</italic></xref>)</p>
</sec>
</sec>
<sec id="sec3.2" sec-type="other19">
<label>3.2</label><title>Koje su operacijske metode lije&#x010D;enja? (sna&#x017E;na preporuka temeljena na dokazima umjerene kvalitete, 1B)</title>
<sec id="secA">
<label>A)</label><title>Lateralna unutarnja sfinkterotomija (LIS)</title>
<p>Lateralna unutarnja sfinkterotomija (LIS) kirur&#x0161;ka je metoda lije&#x010D;enja kroni&#x010D;ne analne fisure. Mo&#x017E;e se provoditi u op&#x0107;oj, regionalnoj ili lokalnoj anesteziji. Bilo da se radi otvorenom ili zatvorenom metodom, potrebno je unutarnji analni sfinkter presje&#x0107;i do razine nazubljene linije. Ova tehnika superiorna je u odnosu na konzervativne metode lije&#x010D;enja analne fisure. S obzirom na provedena istra&#x017E;ivanja LIS je prihva&#x0107;en kao zlatni standard lije&#x010D;enja analne fisure kada se konzervativni ili lokalni tretman poka&#x017E;e neuspje&#x0161;nim. (<xref ref-type="bibr" rid="r66"><italic>66</italic></xref>, <xref ref-type="bibr" rid="r84"><italic>84</italic></xref>) Istra&#x017E;ivanja su pokazala stopu izlje&#x010D;enja ovom metodom od preko 85% pa &#x010D;ak i do 100%, dok je fekalna inkontinencija oko 10%. (<xref ref-type="bibr" rid="r69"><italic>69</italic></xref>, <xref ref-type="bibr" rid="r85"><italic>85</italic></xref>, <xref ref-type="bibr" rid="r86"><italic>86</italic></xref>) Budu&#x0107;i da je ipak dugoro&#x010D;no gledano fekalna kontinencija i kvaliteta &#x017E;ivota odr&#x017E;ana u najve&#x0107;eg broja bolesnika nakon LIS-a, ova metoda se mo&#x017E;e ponuditi bolesnicima s kroni&#x010D;nom analnom fisurom, a koji nemaju podle&#x017E;e&#x0107;e znakove fekalne inkotinencije bilo kojeg stupnja niti upalnu bolest crijeva, prethodno nisu bili podvrgnuti anorektalnoj operaciji i nemaju dokumentiranu raniju ozljedu analnog sfinktera.</p>
<p>Otvorena i zatvorena tehnika u vi&#x0161;estrukim komparativnim studijama nisu pokazale zna&#x010D;ajne razlike u ishodima. (<xref ref-type="bibr" rid="r87"><italic>87</italic></xref>&#x2013;<xref ref-type="bibr" rid="r89"><italic>89</italic></xref>)</p>
<p>Kao zasebna tehnika lateralne unutarnje sfinkterotomije opisuje se i &#x201E;prilago&#x0111;ena&#x201C; (engl. <italic>tailored</italic>) sfinkterotomija koja ozna&#x010D;ava sfinkterotomiju do &#x201E;vrha&#x201C; fisure. Randomizirana klini&#x010D;ka istra&#x017E;ivanja ipak pokazuju bolju stopu cijeljenja nakon tradicionalnog zahvata. (<xref ref-type="bibr" rid="r90"><italic>90</italic></xref>&#x2013;<xref ref-type="bibr" rid="r92"><italic>92</italic></xref>)</p>
</sec>
<sec id="secB">
<label>B)</label><title>Anokutani re&#x017E;anj</title>
<p>Dugoro&#x010D;ni u&#x010D;inak postsfinkterotomijske analne inkontinencije nije zanemariv sa stopom od 9 &#x2013; 14% u dvije recentne metaanalize. (<xref ref-type="bibr" rid="r85"><italic>85</italic></xref>, <xref ref-type="bibr" rid="r86"><italic>86</italic></xref>) Da bi se sa&#x010D;uvao netaknut sfinkter, kroni&#x010D;na analna fisura mo&#x017E;e se lije&#x010D;iti i fisurektomijom (FIS) ne o&#x0161;te&#x0107;uju&#x0107;i analnu kontinenciju. (<xref ref-type="bibr" rid="r93"><italic>93</italic></xref>) Taj pak zahvat kao manjkavost ima ote&#x017E;ano i dugotrajno cijeljenje koje ponekad mo&#x017E;e potrajati &#x010D;ak izme&#x0111;u 10 i 15 tjedana. (<xref ref-type="bibr" rid="r94"><italic>94</italic></xref>, <xref ref-type="bibr" rid="r95"><italic>95</italic></xref>) Zbog toga je kao kirur&#x0161;ki pandan LIS-u i dalje prisutno kirur&#x0161;ko formiranje anokutanog (dermalnog) re&#x017E;nja. (<xref ref-type="bibr" rid="r96"><italic>96</italic></xref>) Kako bi se skratilo vrijeme cijeljenja, primarno zatvaranje rane nakon fisurektomije mo&#x017E;e se izvesti s anokutanim ili mukokutanim re&#x017E;njem. (<xref ref-type="bibr" rid="r97"><italic>97</italic></xref>&#x2013;<xref ref-type="bibr" rid="r99"><italic>99</italic></xref>)</p>
<p>Formiranje re&#x017E;nja prvenstveno se savjetuje u rekurentnih kroni&#x010D;nih analnih fisura koje su prethodno lije&#x010D;ene LIS-om, kao i kod vi&#x0161;erotkinja i &#x017E;ena koje su nedavno rodile te kao takve imaju sni&#x017E;en bazalni analni tlak. (<xref ref-type="bibr" rid="r100"><italic>100</italic></xref>)</p>
</sec>
</sec>
<sec id="sec3.3" sec-type="other20">
<label>3.3</label><title>&#x0160;to u&#x010D;initi s atipi&#x010D;nim analnim fisurama? (slaba preporuka temeljena na dokazima niske kvalitete, 2C)</title>
<p>Fisure u bolesnika s Crohnovom bolesti lije&#x010D;e se primarno konzervativnim pristupom s naglaskom na lije&#x010D;enje osnovne bolesti, ako se smatra da je fisura manifestacija upalne bolesti crijeva. Literatura je oskudna, no terapija za lije&#x010D;enje aktivne upalne bolesti crijeva u najve&#x0107;eg broja bolesnika koji na nju pozitivno odgovore ujedno je i terapija koja izlije&#x010D;i i fisuru. (<xref ref-type="bibr" rid="r101"><italic>101</italic></xref>&#x2013;<xref ref-type="bibr" rid="r103"><italic>103</italic></xref>)</p>
<p>Lije&#x010D;enje analne fisure koja je posljedica spolno prenosive bolesti prvenstveno je odre&#x0111;eno otkrivanjem uzro&#x010D;nika biopsijom fisure ili serolo&#x0161;kim pretragama. Ovisno o uzro&#x010D;niku lije&#x010D;enje je razli&#x010D;ito. Primjerice, analna fisura koja je nastala u oboljelog od HIV-a mo&#x017E;e dugoro&#x010D;no imati pozitivne u&#x010D;inke antiviralne terapije. (<xref ref-type="bibr" rid="r104"><italic>104</italic></xref>, <xref ref-type="bibr" rid="r105"><italic>105</italic></xref>)</p>
<p>U akutnoj fazi &#x201E;<italic>low-pressure</italic>&#x201C; analne fisure &#x010D;esto su prisutne u &#x017E;ena koje su u postpartalnom razdoblju. Lije&#x010D;enje bi trebalo biti usmjereno prema konzervativnijim metodama, strogo izbjegavaju&#x0107;i metode koje utje&#x010D;u na dodatno o&#x0161;te&#x0107;enje sfinktera. (<xref ref-type="bibr" rid="r106"><italic>106</italic></xref>) U kroni&#x010D;noj fazi kirur&#x0161;ke metode su usmjerene prema manje radikalnima, primjerice pokazana je prednost kori&#x0161;tenja anokutanog re&#x017E;nja. (<xref ref-type="bibr" rid="r97"><italic>97</italic></xref>)</p>
</sec>
<sec id="sec4" sec-type="other21">
<label>4.</label><title>Smjernice za lije&#x010D;enje hemoroidalne bolesti (<xref ref-type="fig" rid="f4">Figure 4</xref>)</title>
<fig id="f4" position="float" fig-type="figure"><label>Figure 4</label><caption><p>Hemorrhoidal disease treatment algorithm</p></caption><graphic xlink:href="LV-146-77-f4"></graphic></fig>
<p>Hemoroidi su sastavni dio ljudske anatomije koji sudjeluje u regulaciji kontinencije. Razlikujemo unutra&#x0161;nju i vanjsku komponentu hemoroida. Unutra&#x0161;nji hemoroidi uglavnom se javljaju u formi od tri jastu&#x010D;i&#x0107;a smje&#x0161;tena u analnom kanalu iznad nazubljene linije. Sastoje se od elasti&#x010D;nog i vezivnog tkiva, glatkih mi&#x0161;i&#x0107;nih niti te vaskularnih struktura koje najbli&#x017E;e odgovaraju arterio-venskim fistulama u submukozi i same mukoze. (<xref ref-type="bibr" rid="r107"><italic>107</italic></xref>)</p>
<p>Hemoroidalna bolest je progresivna degenerativna bolest koja zahva&#x0107;a oba spola sa najve&#x0107;om incidencijom izme&#x0111;u 45. i 65. godine &#x017E;ivota. (<xref ref-type="bibr" rid="r108"><italic>108</italic></xref>, <xref ref-type="bibr" rid="r109"><italic>109</italic></xref>) Osnovni simptomi kojima se bolest prezentira jesu svijetlocrveno krvarenje, prolaps, analni svrbe&#x017E; i bol kao posljedica tromboze, upale ili strangulacije.</p>
</sec>
<sec id="sec4.1" sec-type="other22">
<label>4.1</label><title>Kako se dijagnosticira hemoroidalna bolest? (Sna&#x017E;na preporuka temeljena na dokazima niske kvalitete, 1C)</title>
<p>Hemoroidalna bolest se dijagnosticira na osnovi anamneze i klini&#x010D;kog pregleda koji obvezno uklju&#x010D;uje anoskopiju.</p>
<p>Sama dijagnoza i lije&#x010D;enje zasnivaju se na dva osnovna principa:</p>
<list id="L1" list-type="order"><list-item><p>potrebno je isklju&#x010D;iti druge bolesti debelog crijeva i rektuma;</p></list-item>
<list-item><p>lije&#x010D;e se tegobe vezane uz hemoroidalnu bolest, a ne tip hemoroida.</p></list-item></list>
<p>Za klasifikaciju hemoroidalne bolesti naj&#x010D;e&#x0161;&#x0107;e se koristi Goligherova klasifikacija na &#x010D;etiri stupnja bolesti. Iako je ova klasifikacija rigidna i bazira se samo na jednom simptomu &#x2013; prolapsu, i danas se naj&#x010D;e&#x0161;&#x0107;e koristi unato&#x010D; pojavi sve vi&#x0161;e novih klasifikacija koje kombiniraju vi&#x0161;e simptoma i same anamnesti&#x010D;ke podatke (<xref ref-type="table" rid="t1">Table 1</xref>). (<xref ref-type="bibr" rid="r110"><italic>110</italic></xref>)</p>
<table-wrap id="t1" position="float">
<label>Table 1</label><caption><title>Internal hemorrhoids classification according to local status (Goligher classification)</title>
</caption>
<table frame="hsides" rules="groups">
<col width="15.89%"/>
<col width="84.11%"/>
<thead>
<tr>
<th valign="middle" align="left" scope="col" style="border-left: solid 0.75pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Stupanj<break/>Stage</th>
<th valign="middle" align="left" scope="col" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Lokalni nalaz<break/>Local status</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">I</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Vidljiv hemoroid bez prolapsa<break/>/ Visible hemorrhoid without prolapse</td>
</tr>
<tr>
<td valign="middle" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">II</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Prolaps na Valsalvin manevar sa spontanom redukcijom / Prolapse upon performing Valsalva maneuver with spontaneous reduction</td>
</tr>
<tr>
<td valign="middle" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">III</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Prolaps na Valsalvin manevar koji zahtijeva manualnu repoziciju / Prolapse upon performing Valsalva maneuver that requires manual repositioning</td>
</tr>
<tr>
<td valign="middle" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt" scope="row">IV</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.75pt">Kroni&#x010D;no prolabirani hemoroidi koji se ne mogu manualno reponirati / Chronic prolapse of hemorrhoids that can&#x2019;t be repositioned</td>
</tr>
</tbody></table></table-wrap>
</sec>
<sec id="sec4.2" sec-type="other23">
<label>4.2</label><title>Je li potrebna dodatna endoskopska evaluacija bolesnika s hemoroidalnom bole&#x0161;&#x0107;u i kada? (Sna&#x017E;na preporuka temeljena na dokazima umjerene kvalitete, 1B)</title>
<p>Kompletna endoskopska evaluacija debelog crijeva i rektuma indicirana je u odabranih pacijenata s hemeroidalnom bole&#x0161;&#x0107;u i krvarenjem (<xref ref-type="table" rid="t2">Table 2</xref>). (<xref ref-type="bibr" rid="r111"><italic>111</italic></xref>, <xref ref-type="bibr" rid="r112"><italic>112</italic></xref>)</p>
<table-wrap id="t2" position="float">
<label>Table 2</label><caption><title>Indications for total colonoscopy</title>
</caption>
<table frame="hsides" rules="groups">
<col width="100%"/>
<thead>
<tr>
<th valign="middle" align="left" scope="col" style="border-left: solid 0.75pt; border-top: solid 0.75pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">1.<break/>Dob &#x2265; 50 godina ako u zadnjih 10 godina nije u&#x010D;injena kolonoskopija<break/>/ Age &#x2265; 50 if no colonoscopy was performed in last 10 years</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">2.<break/>Dob &#x2265;40 godina ili 10 godina manje od dobi dijagnoze kolorektalnog karcinoma &#x010D;lana obitelji u prvom koljenu ili uznapredovalog adenoma kolorektuma &#x010D;lana obitelji u prvom koljenu dobi &lt; 60 godina / Age &#x2265;40 years or 10 years less than the age of diagnosis of colorectal cancer in a family member<break/>in the first generation or advanced colorectal adenoma in a family member in the first generation age &lt; 60 years</td>
</tr>
<tr>
<td valign="middle" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">3.<break/>Dob &#x2265; 40 godina ili 10 godina manje od dobi dijagnoze kololorektalnog karcinoma ili uznapredovalog adenoma kolorektuma u dva &#x010D;lana obitelji u drugom koljenu<break/>/ Age &#x2265; 40 years or 10 years less than the age of diagnosis<break/>of colorectal cancer or advanced colorectal adenoma<break/>in two family members in the second generation</td>
</tr>
<tr>
<td valign="middle" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.75pt">4.<break/>Pozitivan test na okultno krvarenje<break/>/ Positive test for occult bleeding</td>
</tr>
</tbody></table></table-wrap>
</sec>
<sec id="sec4.3" sec-type="other24">
<label>4.3</label><title>Kakav utjecaj na bolest ima promjena prehrane? (Sna&#x017E;na preporuka temeljena na dokazima umjerene kvalitete, 1B)</title>
<p>Iako nije to&#x010D;no ustanovljen uzrok nastanka hemoroidalne bolesti pa time nije mogu&#x0107;e ni samo etiolo&#x0161;ko lije&#x010D;enje, korekcija prehrane prestavlja uz medikamentozno lije&#x010D;enje osnovu konzervativnog lije&#x010D;enja.</p>
<p>Modifikacija prehrane zasniva se na adekvatnom unosu teku&#x0107;ine te primjerenom unosu vlakana s ciljem regulacije defekacije. Preporu&#x010D;uje se dnevni unos vlakana u koli&#x010D;ini od 25 g za &#x017E;ene do 38 g za mu&#x0161;karce uz adekvatan unos vode. (<xref ref-type="bibr" rid="r113"><italic>113</italic></xref>, <xref ref-type="bibr" rid="r114"><italic>114</italic></xref>)</p>
</sec>
<sec id="sec4.4" sec-type="other25">
<label>4.4</label><title>Kakav je utjecaj topikalne i peroralne terapije na hemoroidalnu bolest? (Slaba preporuka temeljena na dokazima umjerene kvalitete, 2B)</title>
<p>Konzervativno lije&#x010D;enje hemoroidalne bolesti predstavlja heterogenu grupu na&#x010D;ina lije&#x010D;enja koja s minimalnom &#x0161;tetom donosi pristojan potencijal za umanjenje tegoba same bolesti.</p>
<p>Topikalna terapija, iako &#x0161;iroko rasprostranjena, nema velikog upori&#x0161;ta u medicini zasnovanoj na dokazima. Iako studije ne pokazuju neki zna&#x010D;ajan benefit od lokalne terapije postoje pacijenti koji navode odre&#x0111;eno pobolj&#x0161;anje nakon njezine primjene. (<xref ref-type="bibr" rid="r115"><italic>115</italic></xref>)</p>
<p>Oralna terapija flavonoidima bazirana na pove&#x0107;anju tonusa krvnih &#x017E;ila, smanjenju kapilarne permeabilnosti, pobolj&#x0161;anju limfne drena&#x017E;e te protuupalnom djelovanju pokazala je zna&#x010D;ajan u&#x010D;inak u smanjenju boli, krvarenja i svrbe&#x017E;a. Flavonoidi se tako&#x0111;er preporu&#x010D;uju u postoperacijskom periodu nakon kirur&#x0161;kog lije&#x010D;enja. (<xref ref-type="bibr" rid="r116"><italic>116</italic></xref>)</p>
</sec>
<sec id="sec4.5" sec-type="other26">
<label>4.5</label><title>&#x0160;to kada ne dolazi do pobolj&#x0161;anja simptoma na primijenjenu konzervativnu terapiju?</title>
<p>Kada usprkos konzervativnoj terapiji kod bolesnika s hemoroidalnom bole&#x0161;&#x0107;u nije do&#x0161;lo do regresije simptoma, indicirano je lije&#x010D;enje postupcima koji se mogu podijeliti na ambulantne (nekirur&#x0161;ke) zahvate (procedure), koje je mogu&#x0107;e obavljati u za to specijaliziranim ambulantama i invazivne (kirur&#x0161;ke) zahvate koji se vr&#x0161;e u operacijskoj sali.</p>
</sec>
<sec id="sec4.6" sec-type="other27">
<label>4.6</label><title>Koje su ambulantne metode lije&#x010D;enja hemoroidalne bolesti i kada ih primijeniti? (Stupanj preporuke: sna&#x017E;na preporuka, utemeljena na visokokvalitetnim dokazima, 1A)</title>
<p>Ve&#x0107;ina bolesnika s I. i II. stupnjem hemoroidalne bolesti (prema Goligherovoj skali), kao i selektirani bolesnici s III. stupnjem, mogu su uspje&#x0161;no lije&#x010D;iti tzv. ambulantnim metodama lije&#x010D;enja. Ambulantne metode su podvezivanje hemoroidnih klastera gumenim (Barronovim) ligaturama, skleroterapija uporabom razli&#x010D;itih otopina za sklerozaciju hemoroida te sklerozacija hemoroidnih klastera pomo&#x0107;u koagulacije izazvane valovima infracrvenog spektra. Va&#x017E;no je naglasiti da se ambulantne tehnike lije&#x010D;enja bolesti hemoroida primjenjuju isklju&#x010D;ivo na unutarnje hemoroide. (<xref ref-type="bibr" rid="r117"><italic>117</italic></xref>&#x2013;<xref ref-type="bibr" rid="r120"><italic>120</italic></xref>)</p>
<sec>
<title>Podvezivanje hemoroida gumenim &#x201E;Barronovim&#x201C; ligaturama</title>
<p>Ova metoda se smatra superiornom u usporedbi naspram ostalih ambulantnih metoda, a za cilj ima uzrokovati nekrozu prolapsa tkiva hemoroida kao posljedicu ishemije zbog podvezivanja gumenim ligaturama. Na zavr&#x0161;etku procesa na mjestu podvezivanja nakon nekroze razvija se o&#x017E;iljak koji za stijenku analnog kanala fiksira preostalo tkivo hemoroida. (<xref ref-type="bibr" rid="r117"><italic>117</italic></xref>) Bolesnicima je potrebno objasniti da su stope recidiva nakon ovog zahvata varijabilne, kao i da postoji mogu&#x0107;nost potrebe ponavljanja procedure. (<xref ref-type="bibr" rid="r117"><italic>117</italic></xref>, <xref ref-type="bibr" rid="r121"><italic>121</italic></xref>) Uzimanje antikoagulacijske i antiagregacijske medikamentozne terapije smatra se kontraidikacijom za izvo&#x0111;enje ovog zahvata. (<xref ref-type="bibr" rid="r118"><italic>118</italic></xref>) Naj&#x010D;e&#x0161;&#x0107;a komplikacija uklju&#x010D;uje postoperativnu bol (5,8%) i krvarenje (1,8%), dok je u&#x010D;estalost infekcije zabilje&#x017E;ena je u 0,05%. (<xref ref-type="bibr" rid="r122"><italic>122</italic></xref>)</p>
</sec>
<sec>
<title>Skleroterapija</title>
<p>U tehnici sklerozacije hemoroida koriste se razli&#x010D;iti agensi; naj&#x010D;e&#x0161;&#x0107;e se koriste otopine fenola u biljnom ulju ili natrij tetradecil sulfat, koje se apliciraju u apeks hemoroida. Zatim se razvija fibroza tkiva submukoze, &#x0161;to posljedi&#x010D;no uzrokuje fiksaciju hemoroidnog tkiva za stijenku analnog kanala. Opisane nuspojave ovog zahvata jesu prolazna bakterijemija, ulceracije mukozne sluznice, nekroza i rijetke epizode perianalne sepse (<xref ref-type="bibr" rid="r123"><italic>123</italic></xref>, <xref ref-type="bibr" rid="r124"><italic>124</italic></xref>) pa je kod bolesnika s povi&#x0161;enim rizikom razvitka komplikacija indicirana profilakti&#x010D;na antibiotska terapija. (<xref ref-type="bibr" rid="r124"><italic>124</italic></xref>)</p>
</sec>
<sec>
<title>Infracrvena koagulacija</title>
<p>Izravnom primjenom infracrvenih valova uzrokuje se nekroza proteina tkiva hemoroida. Ova tehnika se naj&#x010D;e&#x0161;&#x0107;e primjenjuje za I. i II. stupanj bolesti unutarnjih hemoroida, me&#x0111;utim recentne studije pokazuju porast u&#x010D;inkovitosti tehnike usporediv s tehnikom podvezivanja gumenim ligaturama. Stopa recidiva je generalno vi&#x0161;a u odnosu na ostale ambulatne metode lije&#x010D;enja hemoroida. (<xref ref-type="bibr" rid="r119"><italic>119</italic></xref>)</p>
</sec>
</sec>
<sec id="sec4.7" sec-type="other28">
<label>4.7</label><title>Koje su naj&#x010D;e&#x0161;&#x0107;e komplikacije ambulantnih procedura?</title>
<p>Sveukupno, rijetke su komplikacije nakon izvo&#x0111;enja ambulantnih procedura lije&#x010D;enja hemoroidalne bolesti. Me&#x0111;utim, stanja poput perianalne sepse, postproceduralne hemoragije i urinarne disfunkcije treba hitno lije&#x010D;iti, s obzirom na to da neka od ovih stanja mogu &#x017E;ivotno ugroziti bolesnika. (<xref ref-type="bibr" rid="r125"><italic>125</italic></xref>&#x2013;<xref ref-type="bibr" rid="r128"><italic>128</italic></xref>)</p>
</sec>
<sec id="sec4.8" sec-type="other29">
<label>4.8</label><title>Koje su kirur&#x0161;ke metode lije&#x010D;enja hemoroidalne bolesti? (Sna&#x017E;na preporuka temeljena na dokazima visoke kvalitete, 1A)</title>
<p><italic>Kirur&#x0161;ko operacijsko lije&#x010D;enje ili hemoroidektomija preporu&#x010D;uje se bolesnicima sa simptomima koji su uzrokovani vanjskim hemoroidima ili kombinacijom vanjskih i unutarnjih hemoroida s prolapsom (III. i IV. stupanj)</italic>. (<xref ref-type="bibr" rid="r129"><italic>129</italic></xref>)</p>
<sec>
<title>Kirur&#x0161;ka ekscizija</title>
<p>Kirur&#x0161;ka ekscizija hemoroida je metoda izbora za lije&#x010D;enje pacijenata kojima uspjeh lije&#x010D;enja nije postignut tzv. ambulantnim metodama i za lije&#x010D;enje pacijenata koji imaju vanjske i unutarnje hemoroide III. i IV. stupnja prema Goligherovoj klasifikaciji. (<xref ref-type="bibr" rid="r129"><italic>129</italic></xref>)</p>
<p>Konvencionalna hemoroidektomija sastoji se od otvorene hemoroidektomije (Milligan-Morgan) i zatvorene hemoroidektomije (Ferguson). Glavna razlika zatvorene hemoroidektomije u odnosu na otvorenu hemoroidektomiju jest zatvaranje kirur&#x0161;ke rane, odnosno mukoze rektuma.</p>
<p>Prema literaturi, zatvorena hemoroidektomija je povezana s manjim postotkom postoperativne boli i br&#x017E;im cijeljenjem rane (<xref ref-type="bibr" rid="r130"><italic>130</italic></xref>, <xref ref-type="bibr" rid="r131"><italic>131</italic></xref>), a otvorena hemoroidektomija s ni&#x017E;om stopom morbiditeta. (<xref ref-type="bibr" rid="r132"><italic>132</italic></xref>)</p>
</sec>
<sec>
<title>DG HAL (engl. doppler-guided haemorrhoid artery ligation with recto-anal repair)</title>
<p>Dopplerom vo&#x0111;eno podvezivanje grana hemoroidalnih arterija mo&#x017E;e se koristiti za lije&#x010D;enje pacijenata kojima uspjeh lije&#x010D;enja nije postignut ambulantno te kod pacijenata s hemoroidima II. i III. stupnja prema Goligherovoj klasifikaciji. (<xref ref-type="bibr" rid="r133"><italic>133</italic></xref>) Tijekom izvo&#x0111;enja procedure DG HAL koristi se anoskop s Dopplerovom sondom za identifikaciju svake hemoroidalne arterije koja se i podve&#x017E;e. Prednosti tehnike su manja ekscizija tkiva i manja postoperativna bol. Me&#x0111;utim, u preglednim &#x010D;lancima navedene su komplikacije: postoperativna bol (18,5%), hemoroidalni prolaps (9%), krvarenja (7,8%) i bolnost pri defekaciji (4,7%). (<xref ref-type="bibr" rid="r129"><italic>129</italic></xref>)</p>
</sec>
</sec>
<sec id="sec4.9" sec-type="other30">
<label>4.9</label><title>Kako lije&#x010D;iti trombozirane hemoroide? (Slaba preporuka, utemeljena na dokazima niske kvalitete, 2C)</title>
<p>Klini&#x010D;ka slika akutno tromboziranih inkarceriranih vanjskih hemoroida karakterizirana je naglim razvojem intenzivnih bolova. Prema dostupnim studijama, prvi tretman izbora je kirur&#x0161;ka ekscizija tromboziranog hemoroida, zatim topikalna aplikacija 0,2% nitroglicerinske masti, a kao najmanje uspje&#x0161;na metoda pokazala se trombektomija. Me&#x0111;utim, simptomatsko ubla&#x017E;avanje bolova mjesec dana nakon hitne intervencije jednako je za sve tri grupe. Uporaba flebotonika (flavonoida) mo&#x017E;e pomo&#x0107;i u regresiji simptoma. (<xref ref-type="bibr" rid="r133"><italic>133</italic></xref>)</p>
</sec>
<sec id="sec4.10" sec-type="other31">
<label>4.10</label><title>Koja je u&#x010D;estalost hemoroidalne bolesti u trudno&#x0107;i te koja je metoda izbora lije&#x010D;enja? (Slaba preporuka temeljena na dokazima niske kvalitete, 2C)</title>
<p>Prevalencija hemoroidalne bolesti u&#x010D;estalija je u populaciji trudnica, neke studije navode pojavnost od 25 &#x2013; 35% (<xref ref-type="bibr" rid="r134"><italic>134</italic></xref>) te pristup lije&#x010D;enju trudnica mora biti multidisciplinaran, uklju&#x010D;uju&#x0107;i specijaliste ginekologije i kirurgije.</p>
<p>Metoda izbora u lije&#x010D;enju hemoroidalne bolesti u trudnica jesu konzervativne metode koje uklju&#x010D;uju higijensko-dijetalne mjere, upotrebu laksativa, Kegelove vje&#x017E;be, le&#x017E;anje na lijevom boku i kupke. (<xref ref-type="bibr" rid="r135"><italic>135</italic></xref>, <xref ref-type="bibr" rid="r136"><italic>136</italic></xref>) U slu&#x010D;aju perzistiranja simptoma lije&#x010D;enje mo&#x017E;e obuhva&#x0107;ati i kombinirane topikalne pripravke kortikosteroida i analgetika, no djelovanje topikalnih pripravaka na fetus jo&#x0161; uvijek je predmet prou&#x010D;avanja studija. (<xref ref-type="bibr" rid="r136"><italic>136</italic></xref>) U trudnica koje ne reagiraju na simptomatsku terapiju uz pojavu komplikacija tipa krvarenja, bolova i tromboziranih hemoroida izbor lije&#x010D;enja je hemoroidektomija. (<xref ref-type="bibr" rid="r137"><italic>137</italic></xref>)</p>
</sec>
<sec id="sec4.11" sec-type="other32">
<label>4.11</label><title>Kako lije&#x010D;iti bolesnike na antikoagulantnoj ili antitrombotskoj terapiji?</title>
<p>Zbog antikoagulantne/antitrombotske medikamentozne terapije &#x010D;esta je komplikacija krvarenje koje u ve&#x0107;ini slu&#x010D;ajeva spontano prestaje bez potrebe za intervencijom. Bolesnici s hemoroidalnom bole&#x0161;&#x0107;u I. i II. stupnja pokazuju dobar odgovor na konzervativnu terapiju. U slu&#x010D;aju perzistiraju&#x0107;eg krvarenja izbor lije&#x010D;enja je sklerozacija. Kod simptomatskih hemoroida IV. stupnja indicirana je hemoroidektomija uz prestanak uzimanja antikoagulantne/antitrombotske terapije sedam dana prije zahvata. Ligacija hemoroida nije metoda izbora u navedenih pacijenata zbog povi&#x0161;enog rizika od postproceduralnog krvarenja. (<xref ref-type="bibr" rid="r138"><italic>138</italic></xref>)</p>
</sec>
<sec id="sec5" sec-type="other33">
<label>5.</label><title>Ostali topikalni preparati kao mogu&#x0107;nost konzervativne terapije</title>
<p>Preparat natrijeva hijaluron butirata u kombinaciji s dimetikonom u klini&#x010D;koj praksi pokazao se kao dobar topikalni preparat za lije&#x010D;enje odnosno smanjenje simptoma razli&#x010D;itih patolo&#x0161;kih stanja u proktologiji (npr. analna fisura, hemoroidalna bolest, ragade, proktitis) iako su iskustva vi&#x0161;e anegdotalna i nisu bazirana na randomiziranim studijama. Primarna uloga navedene kombinacije lijekova jest pomaganje u procesima ponovne epitelizacije i normalizacije analne sluznice na takav na&#x010D;in da stvara mehani&#x010D;ku barijeru oko rektalne sluznice. Natrijev hijaluron butirat obnavlja fiziolo&#x0161;ko stanje i funkciju rektalne sluznice te odr&#x017E;ava njezin integritet, dok dimetikon stvara sluzoadhezivni gel koji djeluje kao barijera na sluznici i time &#x0161;titi tkivo rektuma/anusa.</p>
<p>Dokazani su benefiti dimetikona kod lije&#x010D;enja postinkontinencijskog dermatitisa perineuma. (<xref ref-type="bibr" rid="r139"><italic>139</italic></xref>)</p>
<p>(Slaba preporuka temeljena na dokazima niske kvalitete, 2C)</p>
</sec>
</body>
<back>
<fn-group>
<fn fn-type="conflict">
<p content-type="fn-title">INFORMACIJE O SUKOBU INTERESA</p>
<p>Autori nisu deklarirali sukob interesa relevantan za ovaj rad.</p>
</fn>
<fn fn-type="financial-disclosure">
<p content-type="fn-title">INFORMACIJA O FINANCIRANJU</p>
<p>Za ovaj &#x010D;lanak nisu primljena financijska sredstva.</p>
</fn>
</fn-group>
<ref-list>
<title>LITERATURA</title>
<ref id="r1"><label>1</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gosselink</surname><given-names>MP</given-names></name><name><surname>van Onkelen</surname><given-names>RS</given-names></name><name><surname>Schouten</surname><given-names>WR</given-names></name></person-group>. <article-title>The cryptoglandular theory revisited.</article-title> <source>Colorectal Dis</source>. <year>2015</year>;<volume>17</volume>(<issue>12</issue>):<fpage>1041</fpage>&#x2013;<lpage>3</lpage>. <pub-id pub-id-type="doi">10.1111/codi.13161</pub-id><pub-id pub-id-type="pmid">26547817</pub-id></mixed-citation></ref>
<ref id="r2"><label>2</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gaertner</surname><given-names>WB</given-names></name><name><surname>Burgess</surname><given-names>PL</given-names></name><name><surname>Davids</surname><given-names>JS</given-names></name><name><surname>Lightner</surname><given-names>AL</given-names></name><name><surname>Shogan</surname><given-names>BD</given-names></name><name><surname>Sun</surname><given-names>MY</given-names></name><etal/></person-group> <article-title>The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Anorectal Abscess, Fistula-in-Ano, and Rectovaginal Fistula.</article-title> <source>Dis Colon Rectum</source>. <year>2022</year>;<volume>65</volume>(<issue>8</issue>):<fpage>964</fpage>&#x2013;<lpage>85</lpage>. <pub-id pub-id-type="doi">10.1097/DCR.0000000000002473</pub-id><pub-id pub-id-type="pmid">35732009</pub-id></mixed-citation></ref>
<ref id="r3"><label>3</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tarasconi</surname><given-names>A</given-names></name><name><surname>Perrone</surname><given-names>G</given-names></name><name><surname>Davies</surname><given-names>J</given-names></name><name><surname>Coimbra</surname><given-names>R</given-names></name><name><surname>Moore</surname><given-names>E</given-names></name><name><surname>Azzaroli</surname><given-names>F</given-names></name><etal/></person-group> <article-title>Anorectal emergencies: WSES-AAST guidelines.</article-title> <source>World J Emerg Surg</source>. <year>2021</year>;<volume>16</volume>(<issue>1</issue>):<fpage>48</fpage>. <pub-id pub-id-type="doi">10.1186/s13017-021-00384-x</pub-id><pub-id pub-id-type="pmid">34530908</pub-id></mixed-citation></ref>
<ref id="r4"><label>4</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amato</surname><given-names>A</given-names></name><name><surname>Bottini</surname><given-names>C</given-names></name><name><surname>De Nardi</surname><given-names>P</given-names></name><name><surname>Giamundo</surname><given-names>P</given-names></name><name><surname>Lauretta</surname><given-names>A</given-names></name><name><surname>Realis Luc</surname><given-names>A</given-names></name><etal/></person-group> <article-title>Evaluation and management of perianal abscess and anal fistula: SICCR position statement.</article-title> <source>Tech Coloproctol</source>. <year>2020</year>;<volume>24</volume>(<issue>2</issue>):<fpage>127</fpage>&#x2013;<lpage>43</lpage>. <pub-id pub-id-type="doi">10.1007/s10151-019-02144-1</pub-id><pub-id pub-id-type="pmid">31974827</pub-id></mixed-citation></ref>
<ref id="r5"><label>5</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Adamo</surname><given-names>K</given-names></name><name><surname>Gunnarsson</surname><given-names>U</given-names></name><name><surname>Eeg-Olofsson</surname><given-names>K</given-names></name><name><surname>Strig&#x00E5;rd</surname><given-names>K</given-names></name><name><surname>Br&#x00E4;nnstr&#x00F6;m</surname><given-names>F</given-names></name></person-group>. <article-title>Risk for developing perianal abscess in type 1 and type 2 diabetes and the impact of poor glycemic control.</article-title> <source>Int J Colorectal Dis</source>. <year>2021</year>;<volume>36</volume>(<issue>5</issue>):<fpage>999</fpage>&#x2013;<lpage>1005</lpage>. <pub-id pub-id-type="doi">10.1007/s00384-020-03818-1</pub-id><pub-id pub-id-type="pmid">33336291</pub-id></mixed-citation></ref>
<ref id="r6"><label>6</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vogel</surname><given-names>JD</given-names></name><name><surname>Johnson</surname><given-names>EK</given-names></name><name><surname>Morris</surname><given-names>AM</given-names></name><name><surname>Paquette</surname><given-names>IM</given-names></name><name><surname>Saclarides</surname><given-names>TJ</given-names></name><name><surname>Feingold</surname><given-names>DL</given-names></name><etal/></person-group> <article-title>Clinical Practice Guideline for the Management of Anorectal Abscess, Fistula-in-Ano, and Rectovaginal Fistula.</article-title> <source>Dis Colon Rectum</source>. <year>2016</year>;<volume>59</volume>(<issue>12</issue>):<fpage>1117</fpage>&#x2013;<lpage>33</lpage>. <pub-id pub-id-type="doi">10.1097/DCR.0000000000000733</pub-id><pub-id pub-id-type="pmid">27824697</pub-id></mixed-citation></ref>
<ref id="r7"><label>7</label><mixed-citation publication-type="book">Beck DE. WSRJ. Gordon and Nivatvongs&#x2019; Principles and Practice of Surgery for the Colon, Rectum, and Anus. 4. izd. New York: Thieme Medical Publishers; 2019.</mixed-citation></ref>
<ref id="r8"><label>8</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Garcia-Granero</surname><given-names>A</given-names></name><name><surname>Granero-Castro</surname><given-names>P</given-names></name><name><surname>Frasson</surname><given-names>M</given-names></name><name><surname>Flor-Lorente</surname><given-names>B</given-names></name><name><surname>Carre&#x00F1;o</surname><given-names>O</given-names></name><name><surname>Esp&#x00ED;</surname><given-names>A</given-names></name><etal/></person-group> <article-title>Management of cryptoglandular supralevator abscesses in the magnetic resonance imaging era: a case series.</article-title> <source>Int J Colorectal Dis</source>. <year>2014</year>;<volume>29</volume>(<issue>12</issue>):<fpage>1557</fpage>&#x2013;<lpage>64</lpage>. <pub-id pub-id-type="doi">10.1007/s00384-014-2028-2</pub-id><pub-id pub-id-type="pmid">25339133</pub-id></mixed-citation></ref>
<ref id="r9"><label>9</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Orsoni</surname><given-names>P</given-names></name><name><surname>Barthet</surname><given-names>M</given-names></name><name><surname>Portier</surname><given-names>F</given-names></name><name><surname>Panuel</surname><given-names>M</given-names></name><name><surname>Desjeux</surname><given-names>A</given-names></name><name><surname>Grimaud</surname><given-names>JC</given-names></name></person-group>. <article-title>Prospective comparison of endosonography, magnetic resonance imaging and surgical findings in anorectal fistula and abscess complicating Crohn&#x2019;s disease.</article-title> <source>Br J Surg</source>. <year>1999</year>;<volume>86</volume>(<issue>3</issue>):<fpage>360</fpage>&#x2013;<lpage>4</lpage>. <pub-id pub-id-type="doi">10.1046/j.1365-2168.1999.01020.x</pub-id><pub-id pub-id-type="pmid">10201779</pub-id></mixed-citation></ref>
<ref id="r10"><label>10</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Buchanan</surname><given-names>GN</given-names></name><name><surname>Halligan</surname><given-names>S</given-names></name><name><surname>Bartram</surname><given-names>CI</given-names></name><name><surname>Williams</surname><given-names>AB</given-names></name><name><surname>Tarroni</surname><given-names>D</given-names></name><name><surname>Cohen</surname><given-names>CRG</given-names></name></person-group>. <article-title>Clinical Examination, Endosonography, and MR Imaging in Preoperative Assessment of Fistula in Ano: Comparison with Outcome-based Reference Standard.</article-title> <source>Radiology</source>. <year>2004</year>;<volume>233</volume>(<issue>3</issue>):<fpage>674</fpage>&#x2013;<lpage>81</lpage>. <pub-id pub-id-type="doi">10.1148/radiol.2333031724</pub-id><pub-id pub-id-type="pmid">15498901</pub-id></mixed-citation></ref>
<ref id="r11"><label>11</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wise</surname><given-names>PE</given-names></name><name><surname>Schwartz</surname><given-names>DA</given-names></name></person-group>. <article-title>The Evaluation and Treatment of Crohn Perianal Fistulae: EUA, EUS, MRI, and Other Imaging Modalities.</article-title> <source>Gastroenterol Clin North Am</source>. <year>2012</year>;<volume>41</volume>(<issue>2</issue>):<fpage>379</fpage>&#x2013;<lpage>91</lpage>. <pub-id pub-id-type="doi">10.1016/j.gtc.2012.01.009</pub-id><pub-id pub-id-type="pmid">22500524</pub-id></mixed-citation></ref>
<ref id="r12"><label>12</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Caliste</surname><given-names>X</given-names></name><name><surname>Nazir</surname><given-names>S</given-names></name><name><surname>Goode</surname><given-names>T</given-names></name><name><surname>Street</surname><given-names>JH</given-names></name><name><surname>Hockstein</surname><given-names>M</given-names></name><name><surname>McArthur</surname><given-names>K</given-names></name><etal/></person-group> <article-title>Sensitivity of computed tomography in detection of perirectal abscess.</article-title> <source>Am Surg</source>. <year>2011</year>;<volume>77</volume>(<issue>2</issue>):<fpage>166</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1177/000313481107700214</pub-id><pub-id pub-id-type="pmid">21337873</pub-id></mixed-citation></ref>
<ref id="r13"><label>13</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yano</surname><given-names>T</given-names></name><name><surname>Asano</surname><given-names>M</given-names></name><name><surname>Matsuda</surname><given-names>Y</given-names></name><name><surname>Kawakami</surname><given-names>K</given-names></name><name><surname>Nakai</surname><given-names>K</given-names></name><name><surname>Nonaka</surname><given-names>M</given-names></name></person-group>. <article-title>Prognostic factors for recurrence following the initial drainage of an anorectal abscess.</article-title> <source>Int J Colorectal Dis</source>. <year>2010</year>;<volume>25</volume>(<issue>12</issue>):<fpage>1495</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1007/s00384-010-1011-9</pub-id><pub-id pub-id-type="pmid">20640431</pub-id></mixed-citation></ref>
<ref id="r14"><label>14</label><mixed-citation publication-type="book">Smith SR, Pearce LE, Newton K, Dumville JC, Smith JA, Barrow PJ, et al. Internal dressings for healing perianal abscess cavities. U: Smith SR, ur. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley &amp; Sons, Ltd; 2014.</mixed-citation></ref>
<ref id="r15"><label>15</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>S&#x00F8;rensen</surname><given-names>KM</given-names></name><name><surname>M&#x00F6;ller</surname><given-names>S</given-names></name><name><surname>Qvist</surname><given-names>N</given-names></name></person-group>. <article-title>Needle aspiration treatment vs. incision of acute simple perianal abscess: randomized controlled study.</article-title> <source>Int J Colorectal Dis</source>. <year>2021</year>;<volume>36</volume>(<issue>3</issue>):<fpage>581</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1007/s00384-021-03845-6</pub-id><pub-id pub-id-type="pmid">33447866</pub-id></mixed-citation></ref>
<ref id="r16"><label>16</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Seow-En</surname><given-names>I</given-names></name><name><surname>Ngu</surname><given-names>J</given-names></name></person-group>. <article-title>Routine operative swab cultures and post-operative antibiotic use for uncomplicated perianal abscesses are unnecessary.</article-title> <source>ANZ J Surg</source>. <year>2017</year>;<volume>87</volume>(<issue>5</issue>):<fpage>356</fpage>&#x2013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1111/ans.12936</pub-id><pub-id pub-id-type="pmid">25413131</pub-id></mixed-citation></ref>
<ref id="r17"><label>17</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pearce</surname><given-names>L</given-names></name><name><surname>Newton</surname><given-names>K</given-names></name><name><surname>Smith</surname><given-names>SR</given-names></name><name><surname>Barrow</surname><given-names>P</given-names></name><name><surname>Smith</surname><given-names>J</given-names></name><name><surname>Hancock</surname><given-names>L</given-names></name><etal/></person-group> <article-title>Multicentre observational study of outcomes after drainage of acute perianal abscess.</article-title> <source>Br J Surg</source>. <year>2016</year>;<volume>103</volume>(<issue>8</issue>):<fpage>1063</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1002/bjs.10154</pub-id><pub-id pub-id-type="pmid">27061287</pub-id></mixed-citation></ref>
<ref id="r18"><label>18</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cox</surname><given-names>SW</given-names></name><name><surname>Senagore</surname><given-names>AJ</given-names></name><name><surname>Luchtefeld</surname><given-names>MA</given-names></name><name><surname>Mazier</surname><given-names>WP</given-names></name></person-group>. <article-title>Outcome after incision and drainage with fistulotomy for ischiorectal abscess.</article-title> <source>Am Surg</source>. <year>1997</year>;<volume>63</volume>(<issue>8</issue>):<fpage>686</fpage>&#x2013;<lpage>9</lpage>.<pub-id pub-id-type="pmid">9247434</pub-id></mixed-citation></ref>
<ref id="r19"><label>19</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ghahramani</surname><given-names>L</given-names></name><name><surname>Minaie</surname><given-names>MR</given-names></name><name><surname>Arasteh</surname><given-names>P</given-names></name><name><surname>Hosseini</surname><given-names>SV</given-names></name><name><surname>Izadpanah</surname><given-names>A</given-names></name><name><surname>Bananzadeh</surname><given-names>AM</given-names></name><etal/></person-group> <article-title>Antibiotic therapy for prevention of fistula in-ano after incision and drainage of simple perianal abscess: A randomized single blind clinical trial.</article-title> <source>Surgery</source>. <year>2017</year>;<volume>162</volume>(<issue>5</issue>):<fpage>1017</fpage>&#x2013;<lpage>25</lpage>. <pub-id pub-id-type="doi">10.1016/j.surg.2017.07.001</pub-id><pub-id pub-id-type="pmid">28822559</pub-id></mixed-citation></ref>
<ref id="r20"><label>20</label><mixed-citation publication-type="book">Mappes HJFE. Anal abscess and fistula. U: Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwardt; 2001.</mixed-citation></ref>
<ref id="r21"><label>21</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>H&#x00E4;m&#x00E4;l&#x00E4;inen</surname><given-names>KPJ</given-names></name><name><surname>Sainio</surname><given-names>PA</given-names></name></person-group>. <article-title>Incidence of fistulas after drainage of acute anorectal abscesses.</article-title> <source>Dis Colon Rectum</source>. <year>1998</year>;<volume>41</volume>(<issue>11</issue>):<fpage>1357</fpage>&#x2013;<lpage>61</lpage>. <pub-id pub-id-type="doi">10.1007/BF02237048</pub-id><pub-id pub-id-type="pmid">9823799</pub-id></mixed-citation></ref>
<ref id="r22"><label>22</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Parks</surname><given-names>AG</given-names></name><name><surname>Gordon</surname><given-names>PH</given-names></name><name><surname>Hardcastle</surname><given-names>JD</given-names></name></person-group>. <article-title>A classification of fistula-in-ano.</article-title> <source>Br J Surg</source>. <year>1976</year>;<volume>63</volume>(<issue>1</issue>):<fpage>1</fpage>&#x2013;<lpage>12</lpage>. <pub-id pub-id-type="doi">10.1002/bjs.1800630102</pub-id><pub-id pub-id-type="pmid">1267867</pub-id></mixed-citation></ref>
<ref id="r23"><label>23</label><mixed-citation publication-type="book">Karlovi&#x0107; D, Kr&#x0161;ul D, Jerkovi&#x0107; A, Ba&#x010D;i&#x0107; &#x0110;, Zeli&#x0107; M. Anal Fistula: Contemporary View of Complex Problem. U: Benign Anorectal Disorders &#x2013; An Update. IntechOpen; 2023.</mixed-citation></ref>
<ref id="r24"><label>24</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schwartz</surname><given-names>DA</given-names></name><name><surname>Wiersema</surname><given-names>MJ</given-names></name><name><surname>Dudiak</surname><given-names>KM</given-names></name><name><surname>Fletcher</surname><given-names>JG</given-names></name><name><surname>Clain</surname><given-names>JE</given-names></name><name><surname>Tremaine</surname><given-names>WJ</given-names></name><etal/></person-group> <article-title>A comparison of endoscopic ultrasound, magnetic resonance imaging, and exam under anesthesia for evaluation of Crohn&#x2019;s perianal fistulas.</article-title> <source>Gastroenterology</source>. <year>2001</year>;<volume>121</volume>(<issue>5</issue>):<fpage>1064</fpage>&#x2013;<lpage>72</lpage>. <pub-id pub-id-type="doi">10.1053/gast.2001.28676</pub-id><pub-id pub-id-type="pmid">11677197</pub-id></mixed-citation></ref>
<ref id="r25"><label>25</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Halligan</surname><given-names>S</given-names></name><name><surname>Stoker</surname><given-names>J</given-names></name></person-group>. <article-title>Imaging of Fistula in Ano.</article-title> <source>Radiology</source>. <year>2006</year>;<volume>239</volume>(<issue>1</issue>):<fpage>18</fpage>&#x2013;<lpage>33</lpage>. <pub-id pub-id-type="doi">10.1148/radiol.2391041043</pub-id><pub-id pub-id-type="pmid">16567481</pub-id></mixed-citation></ref>
<ref id="r26"><label>26</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ratto</surname><given-names>C</given-names></name><name><surname>Grillo</surname><given-names>E</given-names></name><name><surname>Parello</surname><given-names>A</given-names></name><name><surname>Costamagna</surname><given-names>G</given-names></name><name><surname>Doglietto</surname><given-names>GB</given-names></name></person-group>. <article-title>Endoanal Ultrasound-Guided Surgery for Anal Fistula.</article-title> <source>Endoscopy</source>. <year>2005</year>;<volume>37</volume>(<issue>8</issue>):<fpage>722</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1055/s-2005-870155</pub-id><pub-id pub-id-type="pmid">16032490</pub-id></mixed-citation></ref>
<ref id="r27"><label>27</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tantiphlachiva</surname><given-names>K</given-names></name><name><surname>Sahakitrungruang</surname><given-names>C</given-names></name><name><surname>Pattanaarun</surname><given-names>J</given-names></name><name><surname>Rojanasakul</surname><given-names>A</given-names></name></person-group>. <article-title>Effects of preoperative endoanal ultrasound on functional outcome after anal fistula surgery.</article-title> <source>BMJ Open Gastroenterol</source>. <year>2019</year>;<volume>6</volume>(<issue>1</issue>):<elocation-id>e000279</elocation-id>. <pub-id pub-id-type="doi">10.1136/bmjgast-2019-000279</pub-id><pub-id pub-id-type="pmid">31139426</pub-id></mixed-citation></ref>
<ref id="r28"><label>28</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>West</surname><given-names>RL</given-names></name><name><surname>Dwarkasing</surname><given-names>S</given-names></name><name><surname>Felt-Bersma</surname><given-names>RJ</given-names></name><name><surname>Schouten</surname><given-names>WR</given-names></name><name><surname>Hop</surname><given-names>WC</given-names></name><name><surname>Hussain</surname><given-names>SM</given-names></name><etal/></person-group> <article-title>Hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and endoanal magnetic resonance imaging in evaluating perianal fistulas.</article-title> <source>Eur J Gastroenterol Hepatol</source>. <year>2004</year>;<volume>16</volume>(<issue>12</issue>):<fpage>1319</fpage>&#x2013;<lpage>24</lpage>. <pub-id pub-id-type="doi">10.1097/00042737-200412000-00014</pub-id><pub-id pub-id-type="pmid">15618839</pub-id></mixed-citation></ref>
<ref id="r29"><label>29</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lunniss</surname><given-names>PJ</given-names></name><name><surname>Armstrong</surname><given-names>P</given-names></name><name><surname>Barker</surname><given-names>PG</given-names></name><name><surname>Reznek</surname><given-names>RH</given-names></name><name><surname>Phillips</surname><given-names>RKS</given-names></name></person-group>. <article-title>Magnetic resonance imaging of anal fistulae.</article-title> <source>Lancet</source>. <year>1992</year>;<volume>340</volume>(<issue>8816</issue>):<fpage>394</fpage>&#x2013;<lpage>6</lpage>. <pub-id pub-id-type="doi">10.1016/0140-6736(92)91472-K</pub-id><pub-id pub-id-type="pmid">1353557</pub-id></mixed-citation></ref>
<ref id="r30"><label>30</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Maier</surname><given-names>AG</given-names></name><name><surname>Funovics</surname><given-names>MA</given-names></name><name><surname>Kreuzer</surname><given-names>SH</given-names></name><name><surname>Herbst</surname><given-names>F</given-names></name><name><surname>Wunderlich</surname><given-names>M</given-names></name><name><surname>Teleky</surname><given-names>BK</given-names></name><etal/></person-group> <article-title>Evaluation of perianal sepsis: Comparison of anal endosonography and magnetic resonance imaging.</article-title> <source>J Magn Reson Imaging</source>. <year>2001</year>;<volume>14</volume>(<issue>3</issue>):<fpage>254</fpage>&#x2013;<lpage>60</lpage>. <pub-id pub-id-type="doi">10.1002/jmri.1181</pub-id><pub-id pub-id-type="pmid">11536402</pub-id></mixed-citation></ref>
<ref id="r31"><label>31</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Buchanan</surname><given-names>GN</given-names></name><name><surname>Halligan</surname><given-names>S</given-names></name><name><surname>Bartram</surname><given-names>CI</given-names></name><name><surname>Williams</surname><given-names>AB</given-names></name><name><surname>Tarroni</surname><given-names>D</given-names></name><name><surname>Cohen</surname><given-names>CRG</given-names></name></person-group>. <article-title>Clinical Examination, Endosonography, and MR Imaging in Preoperative Assessment of Fistula in Ano: Comparison with Outcome-based Reference Standard.</article-title> <source>Radiology</source>. <year>2004</year>;<volume>233</volume>(<issue>3</issue>):<fpage>674</fpage>&#x2013;<lpage>81</lpage>. <pub-id pub-id-type="doi">10.1148/radiol.2333031724</pub-id><pub-id pub-id-type="pmid">15498901</pub-id></mixed-citation></ref>
<ref id="r32"><label>32</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Morris</surname><given-names>J</given-names></name><name><surname>Spencer</surname><given-names>JA</given-names></name><name><surname>Ambrose</surname><given-names>NS</given-names></name></person-group>. <article-title>MR Imaging Classification of Perianal Fistulas and Its Implications for Patient Management.</article-title> <source>Radiographics</source>. <year>2000</year>;<volume>20</volume>(<issue>3</issue>):<fpage>623</fpage>&#x2013;<lpage>35</lpage>. <pub-id pub-id-type="doi">10.1148/radiographics.20.3.g00mc15623</pub-id><pub-id pub-id-type="pmid">10835116</pub-id></mixed-citation></ref>
<ref id="r33"><label>33</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Horsthuis</surname><given-names>K</given-names></name><name><surname>Lavini</surname><given-names>C</given-names></name><name><surname>Bipat</surname><given-names>S</given-names></name><name><surname>Stokkers</surname><given-names>PCF</given-names></name><name><surname>Stoker</surname><given-names>J</given-names></name></person-group>. <article-title>Perianal Crohn Disease: Evaluation of Dynamic Contrast-enhanced MR Imaging as an Indicator of Disease Activity.</article-title> <source>Radiology</source>. <year>2009</year>;<volume>251</volume>(<issue>2</issue>):<fpage>380</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1148/radiol.2512072128</pub-id><pub-id pub-id-type="pmid">19401571</pub-id></mixed-citation></ref>
<ref id="r34"><label>34</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Whiteford</surname><given-names>MH</given-names></name><name><surname>Kilkenny</surname><given-names>J</given-names></name><name><surname>Hyman</surname><given-names>N</given-names></name><name><surname>Buie</surname><given-names>DW</given-names></name><name><surname>Cohen</surname><given-names>J</given-names></name><name><surname>Orsay</surname><given-names>C</given-names></name><etal/></person-group> <article-title>Practice Parameters for the Treatment of Perianal Abscess and Fistula-in-Ano (Revised).</article-title> <source>Dis Colon Rectum</source>. <year>2005</year>;<volume>48</volume>(<issue>7</issue>):<fpage>1337</fpage>&#x2013;<lpage>42</lpage>. <pub-id pub-id-type="doi">10.1007/s10350-005-0055-3</pub-id><pub-id pub-id-type="pmid">15933794</pub-id></mixed-citation></ref>
<ref id="r35"><label>35</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Atkin</surname><given-names>GK</given-names></name><name><surname>Martins</surname><given-names>J</given-names></name><name><surname>Tozer</surname><given-names>P</given-names></name><name><surname>Ranchod</surname><given-names>P</given-names></name><name><surname>Phillips</surname><given-names>RKS</given-names></name></person-group>. <article-title>For many high anal fistulas, lay open is still a good option.</article-title> <source>Tech Coloproctol</source>. <year>2011</year>;<volume>15</volume>(<issue>2</issue>):<fpage>143</fpage>&#x2013;<lpage>50</lpage>. <pub-id pub-id-type="doi">10.1007/s10151-011-0676-6</pub-id><pub-id pub-id-type="pmid">21431388</pub-id></mixed-citation></ref>
<ref id="r36"><label>36</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>G&#x00F6;ttgens</surname><given-names>KWA</given-names></name><name><surname>Janssen</surname><given-names>PTJ</given-names></name><name><surname>Heemskerk</surname><given-names>J</given-names></name><name><surname>van Dielen</surname><given-names>FMH</given-names></name><name><surname>Konsten</surname><given-names>JLM</given-names></name><name><surname>Lettinga</surname><given-names>T</given-names></name><etal/></person-group> <article-title>Long-term outcome of low perianal fistulas treated by fistulotomy: a multicenter study.</article-title> <source>Int J Colorectal Dis</source>. <year>2015</year>;<volume>30</volume>(<issue>2</issue>):<fpage>213</fpage>&#x2013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1007/s00384-014-2072-y</pub-id><pub-id pub-id-type="pmid">25421101</pub-id></mixed-citation></ref>
<ref id="r37"><label>37</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ritchie</surname><given-names>RD</given-names></name><name><surname>Sackier</surname><given-names>JM</given-names></name><name><surname>Hodde</surname><given-names>JP</given-names></name></person-group>. <article-title>Incontinence rates after cutting seton treatment for anal fistula.</article-title> <source>Colorectal Dis</source>. <year>2009</year>;<volume>11</volume>(<issue>6</issue>):<fpage>564</fpage>&#x2013;<lpage>71</lpage>. <pub-id pub-id-type="doi">10.1111/j.1463-1318.2008.01713.x</pub-id><pub-id pub-id-type="pmid">19175623</pub-id></mixed-citation></ref>
<ref id="r38"><label>38</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mitalas</surname><given-names>LE</given-names></name><name><surname>van Wijk</surname><given-names>JJ</given-names></name><name><surname>Gosselink</surname><given-names>MP</given-names></name><name><surname>Doornebosch</surname><given-names>P</given-names></name><name><surname>Zimmerman</surname><given-names>DDE</given-names></name><name><surname>Schouten</surname><given-names>WR</given-names></name></person-group>. <article-title>Seton drainage prior to transanal advancement flap repair: useful or not?</article-title> <source>Int J Colorectal Dis</source>. <year>2010</year>;<volume>25</volume>(<issue>12</issue>):<fpage>1499</fpage>&#x2013;<lpage>502</lpage>. <pub-id pub-id-type="doi">10.1007/s00384-010-0993-7</pub-id><pub-id pub-id-type="pmid">20645104</pub-id></mixed-citation></ref>
<ref id="r39"><label>39</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hong</surname><given-names>KD</given-names></name><name><surname>Kang</surname><given-names>S</given-names></name><name><surname>Kalaskar</surname><given-names>S</given-names></name><name><surname>Wexner</surname><given-names>SD</given-names></name></person-group>. <article-title>Ligation of intersphincteric fistula tract (LIFT) to treat anal fistula: systematic review and meta-analysis.</article-title> <source>Tech Coloproctol</source>. <year>2014</year>;<volume>18</volume>(<issue>8</issue>):<fpage>685</fpage>&#x2013;<lpage>91</lpage>. <pub-id pub-id-type="doi">10.1007/s10151-014-1183-3</pub-id><pub-id pub-id-type="pmid">24957361</pub-id></mixed-citation></ref>
<ref id="r40"><label>40</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Giamundo</surname><given-names>P</given-names></name><name><surname>Esercizio</surname><given-names>L</given-names></name><name><surname>Geraci</surname><given-names>M</given-names></name><name><surname>Tibaldi</surname><given-names>L</given-names></name><name><surname>Valente</surname><given-names>M</given-names></name></person-group>. <article-title>Fistula-tract Laser Closure (FiLaC<sup>TM</sup>): long-term results and new operative strategies.</article-title> <source>Tech Coloproctol</source>. <year>2015</year>;<volume>19</volume>(<issue>8</issue>):<fpage>449</fpage>&#x2013;<lpage>53</lpage>. <pub-id pub-id-type="doi">10.1007/s10151-015-1282-9</pub-id><pub-id pub-id-type="pmid">25724967</pub-id></mixed-citation></ref>
<ref id="r41"><label>41</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ommer</surname><given-names>A</given-names></name><name><surname>Herold</surname><given-names>A</given-names></name><name><surname>Joos</surname><given-names>A</given-names></name><name><surname>Schmidt</surname><given-names>C</given-names></name><name><surname>Weyand</surname><given-names>G</given-names></name><name><surname>Bussen</surname><given-names>D</given-names></name></person-group>. <article-title>Gore BioA Fistula Plug in the treatment of high anal fistulas--initial results from a German multicenter-study.</article-title> <source>Ger Med Sci</source>. <year>2012</year>;<volume>10</volume>:<fpage>Doc13</fpage>.<pub-id pub-id-type="pmid">22984363</pub-id></mixed-citation></ref>
<ref id="r42"><label>42</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McGee</surname><given-names>MF</given-names></name><name><surname>Champagne</surname><given-names>BJ</given-names></name><name><surname>Stulberg</surname><given-names>JJ</given-names></name><name><surname>Reynolds</surname><given-names>H</given-names></name><name><surname>Marderstein</surname><given-names>E</given-names></name><name><surname>Delaney</surname><given-names>CP</given-names></name></person-group>. <article-title>Tract Length Predicts Successful Closure With Anal Fistula Plug in Cryptoglandular Fistulas.</article-title> <source>Dis Colon Rectum</source>. <year>2010</year>;<volume>53</volume>(<issue>8</issue>):<fpage>1116</fpage>&#x2013;<lpage>20</lpage>. <pub-id pub-id-type="doi">10.1007/DCR.0b013e3181d972a9</pub-id><pub-id pub-id-type="pmid">20628273</pub-id></mixed-citation></ref>
<ref id="r43"><label>43</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Meinero</surname><given-names>P</given-names></name><name><surname>Mori</surname><given-names>L</given-names></name></person-group>. <article-title>Video-assisted anal fistula treatment (VAAFT): a novel sphincter-saving procedure for treating complex anal fistulas.</article-title> <source>Tech Coloproctol</source>. <year>2011</year>;<volume>15</volume>(<issue>4</issue>):<fpage>417</fpage>&#x2013;<lpage>22</lpage>. <pub-id pub-id-type="doi">10.1007/s10151-011-0769-2</pub-id><pub-id pub-id-type="pmid">22002535</pub-id></mixed-citation></ref>
<ref id="r44"><label>44</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zeli&#x0107;</surname><given-names>M</given-names></name><name><surname>Karlovi&#x0107;</surname><given-names>D</given-names></name><name><surname>Kr&#x0161;ul</surname><given-names>D</given-names></name><name><surname>Ba&#x010D;i&#x0107;</surname><given-names>&#x0110;</given-names></name><name><surname>Warusavitarne</surname><given-names>J</given-names></name></person-group>. <article-title>Video-Assisted Anal Fistula Treatment for Treatment of Complex Cryptoglandular Anal Fistulas with 2 Years Follow-Up Period: Our Experience.</article-title> <source>J Laparoendosc Adv Surg Tech A</source>. <year>2020</year>;<volume>30</volume>(<issue>12</issue>):<fpage>1329</fpage>&#x2013;<lpage>33</lpage>. <pub-id pub-id-type="doi">10.1089/lap.2020.0231</pub-id><pub-id pub-id-type="pmid">32412822</pub-id></mixed-citation></ref>
<ref id="r45"><label>45</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rojanasakul</surname><given-names>A</given-names></name></person-group>. <article-title>LIFT procedure: a simplified technique for fistula-in-ano.</article-title> <source>Tech Coloproctol</source>. <year>2009</year>;<volume>13</volume>(<issue>3</issue>):<fpage>237</fpage>&#x2013;<lpage>40</lpage>. <pub-id pub-id-type="doi">10.1007/s10151-009-0522-2</pub-id><pub-id pub-id-type="pmid">19636496</pub-id></mixed-citation></ref>
<ref id="r46"><label>46</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lara</surname><given-names>FJP</given-names></name><name><surname>Serrano</surname><given-names>AM</given-names></name><name><surname>Moreno</surname><given-names>JU</given-names></name><name><surname>Carmona</surname><given-names>JH</given-names></name><name><surname>Marquez</surname><given-names>MF</given-names></name><name><surname>P&#x00E9;rez</surname><given-names>LR</given-names></name><etal/></person-group> <article-title>Platelet-Rich Fibrin Sealant as a Treatment for Complex Perianal Fistulas: A Multicentre Study.</article-title> <source>J Gastrointest Surg</source>. <year>2015</year>;<volume>19</volume>(<issue>2</issue>):<fpage>360</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1007/s11605-014-2698-7</pub-id><pub-id pub-id-type="pmid">25421358</pub-id></mixed-citation></ref>
<ref id="r47"><label>47</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Balciscueta</surname><given-names>Z</given-names></name><name><surname>Uribe</surname><given-names>N</given-names></name><name><surname>Balciscueta</surname><given-names>I</given-names></name><name><surname>Andreu-Ballester</surname><given-names>JC</given-names></name><name><surname>Garc&#x00ED;a-Granero</surname><given-names>E</given-names></name></person-group>. <article-title>Rectal advancement flap for the treatment of complex cryptoglandular anal fistulas: a systematic review and meta-analysis.</article-title> <source>Int J Colorectal Dis</source>. <year>2017</year>;<volume>32</volume>(<issue>5</issue>):<fpage>599</fpage>&#x2013;<lpage>609</lpage>. <pub-id pub-id-type="doi">10.1007/s00384-017-2779-7</pub-id><pub-id pub-id-type="pmid">28247060</pub-id></mixed-citation></ref>
<ref id="r48"><label>48</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ozuner</surname><given-names>G</given-names></name><name><surname>Hull</surname><given-names>TL</given-names></name><name><surname>Cartmill</surname><given-names>J</given-names></name><name><surname>Fazio</surname><given-names>VW</given-names></name></person-group>. <article-title>Long-term analysis of the use of transanal rectal advancement flaps for complicated anorectal/vaginal fistulas.</article-title> <source>Dis Colon Rectum</source>. <year>1996</year>;<volume>39</volume>(<issue>1</issue>):<fpage>10</fpage>&#x2013;<lpage>4</lpage>. <pub-id pub-id-type="doi">10.1007/BF02048261</pub-id><pub-id pub-id-type="pmid">8601343</pub-id></mixed-citation></ref>
<ref id="r49"><label>49</label><mixed-citation publication-type="book">Kr&#x0161;ul D, Karlovi&#x0107; D, Ba&#x010D;i&#x0107; &#x0110;, Zeli&#x0107; M. Sphincter Preserving Techniques in Anal Fistula Treatment. U: Current Topics in Colorectal Surgery. IntechOpen; 2021:33&#x2013;44.</mixed-citation></ref>
<ref id="r50"><label>50</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Karlovi&#x0107;</surname><given-names>D</given-names></name><name><surname>Kr&#x0161;ul</surname><given-names>D</given-names></name><name><surname>Ba&#x010D;i&#x0107;</surname><given-names>&#x0110;</given-names></name><name><surname>Zeli&#x0107;</surname><given-names>M</given-names></name></person-group>. <article-title>Video&#x2010;assisted anal fistula treatment in combination with ligation of the intersphincteric fistula tract in the treatment of complex transsphincteric fistulas &#x2013; a video vignette.</article-title> <source>Colorectal Dis</source>. <year>2020</year>;<volume>22</volume>(<issue>9</issue>):<fpage>1204</fpage>&#x2013;<lpage>5</lpage>. <pub-id pub-id-type="doi">10.1111/codi.15050</pub-id><pub-id pub-id-type="pmid">32198908</pub-id></mixed-citation></ref>
<ref id="r51"><label>51</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhong</surname><given-names>Q</given-names></name><name><surname>Yuan</surname><given-names>Z</given-names></name><name><surname>Ma</surname><given-names>T</given-names></name><name><surname>Wang</surname><given-names>H</given-names></name><name><surname>Qin</surname><given-names>Q</given-names></name><name><surname>Chu</surname><given-names>L</given-names></name><etal/></person-group> <article-title>Restorative resection of radiation rectovaginal fistula can better relieve anorectal symptoms than colostomy only.</article-title> <source>World J Surg Oncol</source>. <year>2017</year>;<volume>15</volume>(<issue>1</issue>):<fpage>37</fpage>. <pub-id pub-id-type="doi">10.1186/s12957-017-1100-0</pub-id><pub-id pub-id-type="pmid">28153025</pub-id></mixed-citation></ref>
<ref id="r52"><label>52</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Galandiuk</surname><given-names>S</given-names></name><name><surname>Kimberling</surname><given-names>J</given-names></name><name><surname>Al-Mishlab</surname><given-names>TG</given-names></name><name><surname>Stromberg</surname><given-names>AJ</given-names></name></person-group>. <article-title>Perianal Crohn Disease: predictors of need for permanent diversion.</article-title> <source>Ann Surg</source>. <year>2005</year>;<volume>241</volume>(<issue>5</issue>):<fpage>796</fpage>&#x2013;<lpage>801</lpage>. <pub-id pub-id-type="doi">10.1097/01.sla.0000161030.25860.c1</pub-id><pub-id pub-id-type="pmid">15849515</pub-id></mixed-citation></ref>
<ref id="r53"><label>53</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gu</surname><given-names>J</given-names></name><name><surname>Valente</surname><given-names>MA</given-names></name><name><surname>Remzi</surname><given-names>FH</given-names></name><name><surname>Stocchi</surname><given-names>L</given-names></name></person-group>. <article-title>Factors affecting the fate of faecal diversion in patients with perianal Crohn&#x2019;s disease.</article-title> <source>Colorectal Dis</source>. <year>2015</year>;<volume>17</volume>(<issue>1</issue>):<fpage>66</fpage>&#x2013;<lpage>72</lpage>. <pub-id pub-id-type="doi">10.1111/codi.12796</pub-id><pub-id pub-id-type="pmid">25306934</pub-id></mixed-citation></ref>
<ref id="r54"><label>54</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>L&#x00F6;ffler</surname><given-names>T</given-names></name><name><surname>Welsch</surname><given-names>T</given-names></name><name><surname>M&#x00FC;hl</surname><given-names>S</given-names></name><name><surname>Hinz</surname><given-names>U</given-names></name><name><surname>Schmidt</surname><given-names>J</given-names></name><name><surname>Kienle</surname><given-names>P</given-names></name></person-group>. <article-title>Long-term success rate after surgical treatment of anorectal and rectovaginal fistulas in Crohn&#x2019;s disease.</article-title> <source>Int J Colorectal Dis</source>. <year>2009</year>;<volume>24</volume>(<issue>5</issue>):<fpage>521</fpage>&#x2013;<lpage>6</lpage>. <pub-id pub-id-type="doi">10.1007/s00384-009-0638-x</pub-id><pub-id pub-id-type="pmid">19172284</pub-id></mixed-citation></ref>
<ref id="r55"><label>55</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sauk</surname><given-names>J</given-names></name><name><surname>Nguyen</surname><given-names>D</given-names></name><name><surname>Yajnik</surname><given-names>V</given-names></name><name><surname>Khalili</surname><given-names>H</given-names></name><name><surname>Konijeti</surname><given-names>G</given-names></name><name><surname>Hodin</surname><given-names>R</given-names></name><etal/></person-group> <article-title>Natural History of Perianal Crohn&#x2019;s Disease After Fecal Diversion.</article-title> <source>Inflamm Bowel Dis</source>. <year>2014</year>;<volume>20</volume>(<issue>12</issue>):<fpage>2260</fpage>&#x2013;<lpage>5</lpage>. <pub-id pub-id-type="doi">10.1097/MIB.0000000000000216</pub-id><pub-id pub-id-type="pmid">25230164</pub-id></mixed-citation></ref>
<ref id="r56"><label>56</label><mixed-citation publication-type="other">Beaty J, Shashidharan M. Anal Fissure. Clin Colon Rectal Surg. 2016;29(01):030&#x2013;7.</mixed-citation></ref>
<ref id="r57"><label>57</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hananel</surname><given-names>N</given-names></name><name><surname>Gordon</surname><given-names>PH</given-names></name></person-group>. <article-title>Re-examination of clinical manifestations and response to therapy of fissure-in-ano.</article-title> <source>Dis Colon Rectum</source>. <year>1997</year>;<volume>40</volume>(<issue>2</issue>):<fpage>229</fpage>&#x2013;<lpage>33</lpage>. <pub-id pub-id-type="doi">10.1007/BF02054993</pub-id><pub-id pub-id-type="pmid">9075762</pub-id></mixed-citation></ref>
<ref id="r58"><label>58</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schouten</surname><given-names>WR</given-names></name><name><surname>Briel</surname><given-names>JW</given-names></name><name><surname>Auwerda</surname><given-names>JJA</given-names></name></person-group>. <article-title>Relationship between anal pressure and anodermal blood flow.</article-title> <source>Dis Colon Rectum</source>. <year>1994</year>;<volume>37</volume>(<issue>7</issue>):<fpage>664</fpage>&#x2013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1007/BF02054409</pub-id><pub-id pub-id-type="pmid">8026232</pub-id></mixed-citation></ref>
<ref id="r59"><label>59</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gibbons</surname><given-names>CP</given-names></name><name><surname>Read</surname><given-names>NW</given-names></name></person-group>. <article-title>Anal hypertonia in fissures: Cause or effect?</article-title> <source>Br J Surg</source>. <year>2005</year>;<volume>73</volume>(<issue>6</issue>):<fpage>443</fpage>&#x2013;<lpage>5</lpage>. <pub-id pub-id-type="doi">10.1002/bjs.1800730609</pub-id><pub-id pub-id-type="pmid">3719268</pub-id></mixed-citation></ref>
<ref id="r60"><label>60</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Klosterhalfen</surname><given-names>B</given-names></name><name><surname>Vogel</surname><given-names>P</given-names></name><name><surname>Rixen</surname><given-names>H</given-names></name><name><surname>Mittermayer</surname><given-names>C</given-names></name></person-group>. <article-title>Topography of the inferior rectal artery.</article-title> <source>Dis Colon Rectum</source>. <year>1989</year>;<volume>32</volume>(<issue>1</issue>):<fpage>43</fpage>&#x2013;<lpage>52</lpage>. <pub-id pub-id-type="doi">10.1007/BF02554725</pub-id><pub-id pub-id-type="pmid">2910660</pub-id></mixed-citation></ref>
<ref id="r61"><label>61</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sajid</surname><given-names>MS</given-names></name><name><surname>Whitehouse</surname><given-names>PA</given-names></name><name><surname>Sains</surname><given-names>P</given-names></name><name><surname>Baig</surname><given-names>MK</given-names></name></person-group>. <article-title>Systematic review of the use of topical diltiazem compared with glyceryltrinitrate for the nonoperative management of chronic anal fissure.</article-title> <source>Colorectal Dis</source>. <year>2013</year>;<volume>15</volume>(<issue>1</issue>):<fpage>19</fpage>&#x2013;<lpage>26</lpage>. <pub-id pub-id-type="doi">10.1111/j.1463-1318.2012.03042.x</pub-id><pub-id pub-id-type="pmid">22487078</pub-id></mixed-citation></ref>
<ref id="r62"><label>62</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jensen</surname><given-names>SL</given-names></name></person-group>. <article-title>Treatment of first episodes of acute anal fissure: prospective randomised study of lignocaine ointment versus hydrocortisone ointment or warm sitz baths plus bran.</article-title> <source>Br Med J (Clin Res Ed)</source>. <year>1986</year>;<volume>292</volume>(<issue>6529</issue>):<fpage>1167</fpage>&#x2013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1136/bmj.292.6529.1167</pub-id><pub-id pub-id-type="pmid">3011180</pub-id></mixed-citation></ref>
<ref id="r63"><label>63</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gupta</surname><given-names>P</given-names></name></person-group>. <article-title>Randomized, controlled study comparing sitz-bath and no-sitz-bath treatments in patients with acute anal fissures.</article-title> <source>ANZ J Surg</source>. <year>2006</year>;<volume>76</volume>(<issue>8</issue>):<fpage>718</fpage>&#x2013;<lpage>21</lpage>. <pub-id pub-id-type="doi">10.1111/j.1445-2197.2006.03838.x</pub-id><pub-id pub-id-type="pmid">16916391</pub-id></mixed-citation></ref>
<ref id="r64"><label>64</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shub</surname><given-names>HA</given-names></name><name><surname>Salvati</surname><given-names>EP</given-names></name><name><surname>Rubin</surname><given-names>RJ</given-names></name></person-group>. <article-title>Conservative treatment of anal fissure.</article-title> <source>Dis Colon Rectum</source>. <year>1978</year>;<volume>21</volume>(<issue>8</issue>):<fpage>582</fpage>&#x2013;<lpage>3</lpage>. <pub-id pub-id-type="doi">10.1007/BF02586401</pub-id><pub-id pub-id-type="pmid">738173</pub-id></mixed-citation></ref>
<ref id="r65"><label>65</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jensen</surname><given-names>SL</given-names></name></person-group>. <article-title>Maintenance Therapy with Unprocessed Bran in the Prevention of Acute Anal Fissure Recurrence.</article-title> <source>J R Soc Med</source>. <year>1987</year>;<volume>80</volume>(<issue>5</issue>):<fpage>296</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1177/014107688708000513</pub-id><pub-id pub-id-type="pmid">3039130</pub-id></mixed-citation></ref>
<ref id="r66"><label>66</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nelson</surname><given-names>RL</given-names></name><name><surname>Thomas</surname><given-names>K</given-names></name><name><surname>Morgan</surname><given-names>J</given-names></name><name><surname>Jones</surname><given-names>A</given-names></name></person-group>. <article-title>Non surgical therapy for anal fissure.</article-title> <source>Cochrane Database Syst Rev</source>. <year>2012</year>;<volume>2012</volume>(<issue>2</issue>):<elocation-id>CD003431</elocation-id>.<pub-id pub-id-type="pmid">22336789</pub-id></mixed-citation></ref>
<ref id="r67"><label>67</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Boland</surname><given-names>PA</given-names></name><name><surname>Kelly</surname><given-names>ME</given-names></name><name><surname>Donlon</surname><given-names>NE</given-names></name><name><surname>Bolger</surname><given-names>JC</given-names></name><name><surname>Larkin</surname><given-names>JO</given-names></name><name><surname>Mehigan</surname><given-names>BJ</given-names></name><etal/></person-group> <article-title>Management options for chronic anal fissure: a systematic review of randomised controlled trials.</article-title> <source>Int J Colorectal Dis</source>. <year>2020</year>;<volume>35</volume>(<issue>10</issue>):<fpage>1807</fpage>&#x2013;<lpage>15</lpage>. <pub-id pub-id-type="doi">10.1007/s00384-020-03699-4</pub-id><pub-id pub-id-type="pmid">32712929</pub-id></mixed-citation></ref>
<ref id="r68"><label>68</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Berry</surname><given-names>SM</given-names></name><name><surname>Barish</surname><given-names>CF</given-names></name><name><surname>Bhandari</surname><given-names>R</given-names></name><name><surname>Clark</surname><given-names>G</given-names></name><name><surname>Collins</surname><given-names>GV</given-names></name><name><surname>Howell</surname><given-names>J</given-names></name><etal/></person-group> <article-title>Nitroglycerin 0.4% ointment vs placebo in the treatment of pain resulting from chronic anal fissure: a randomized, double-blind, placebo-controlled study.</article-title> <source>BMC Gastroenterol</source>. <year>2013</year>;<volume>13</volume>(<issue>1</issue>):<fpage>106</fpage>. <pub-id pub-id-type="doi">10.1186/1471-230X-13-106</pub-id><pub-id pub-id-type="pmid">23815124</pub-id></mixed-citation></ref>
<ref id="r69"><label>69</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nelson</surname><given-names>RL</given-names></name><name><surname>Manuel</surname><given-names>D</given-names></name><name><surname>Gumienny</surname><given-names>C</given-names></name><name><surname>Spencer</surname><given-names>B</given-names></name><name><surname>Patel</surname><given-names>K</given-names></name><name><surname>Schmitt</surname><given-names>K</given-names></name><etal/></person-group> <article-title>A systematic review and meta-analysis of the treatment of anal fissure.</article-title> <source>Tech Coloproctol</source>. <year>2017</year>;<volume>21</volume>(<issue>8</issue>):<fpage>605</fpage>&#x2013;<lpage>25</lpage>. <pub-id pub-id-type="doi">10.1007/s10151-017-1664-2</pub-id><pub-id pub-id-type="pmid">28795245</pub-id></mixed-citation></ref>
<ref id="r70"><label>70</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bielecki</surname><given-names>K</given-names></name><name><surname>Kolodziejczak</surname><given-names>M</given-names></name></person-group>. <article-title>A prospective randomized trial of diltiazem and glyceryltrinitrate ointment in the treatment of chronic anal fissure.</article-title> <source>Colorectal Dis</source>. <year>2003</year>;<volume>5</volume>(<issue>3</issue>):<fpage>256</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1046/j.1463-1318.2003.00440.x</pub-id><pub-id pub-id-type="pmid">12780888</pub-id></mixed-citation></ref>
<ref id="r71"><label>71</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kocher</surname><given-names>HM</given-names></name><name><surname>Steward</surname><given-names>M</given-names></name><name><surname>Leather</surname><given-names>AJM</given-names></name><name><surname>Cullen</surname><given-names>PT</given-names></name></person-group>. <article-title>Randomized clinical trial assessing the side-effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure.</article-title> <source>Br J Surg</source>. <year>2002</year>;<volume>89</volume>(<issue>4</issue>):<fpage>413</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1046/j.0007-1323.2001.02042.x</pub-id><pub-id pub-id-type="pmid">11952579</pub-id></mixed-citation></ref>
<ref id="r72"><label>72</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Perrotti</surname><given-names>P</given-names></name><name><surname>Bove</surname><given-names>A</given-names></name><name><surname>Antropoli</surname><given-names>C</given-names></name><name><surname>Molino</surname><given-names>D</given-names></name><name><surname>Antropoli</surname><given-names>M</given-names></name><name><surname>Balzano</surname><given-names>A</given-names></name><etal/></person-group> <article-title>Topical Nifedipine With Lidocaine Ointment vs. Active Control for Treatment of Chronic Anal Fissure.</article-title> <source>Dis Colon Rectum</source>. <year>2002</year>;<volume>45</volume>(<issue>11</issue>):<fpage>1468</fpage>&#x2013;<lpage>75</lpage>. <pub-id pub-id-type="doi">10.1007/s10350-004-6452-1</pub-id><pub-id pub-id-type="pmid">12432293</pub-id></mixed-citation></ref>
<ref id="r73"><label>73</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sanei</surname><given-names>B</given-names></name><name><surname>Mahmoodieh</surname><given-names>M</given-names></name><name><surname>Masoudpour</surname><given-names>H</given-names></name></person-group>. <article-title>Comparison of Topical Glyceryl Trinitrate with Diltiazem Ointment for the Treatment of Chronic Anal Fissure: a Randomized Clinical Trial.</article-title> <source>Acta Chir Belg</source>. <year>2009</year>;<volume>109</volume>(<issue>6</issue>):<fpage>727</fpage>&#x2013;<lpage>30</lpage>. <pub-id pub-id-type="doi">10.1080/00015458.2009.11680524</pub-id><pub-id pub-id-type="pmid">20184056</pub-id></mixed-citation></ref>
<ref id="r74"><label>74</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pardhan</surname><given-names>A</given-names></name><name><surname>Azami</surname><given-names>R</given-names></name><name><surname>Mazahir</surname><given-names>S</given-names></name><name><surname>Murtaza</surname><given-names>G</given-names></name></person-group>. <article-title>Diltiazem vs. glyceryl tri-nitrate for symptomatic relief in anal fissure: a randomised clnical study.</article-title> <source>J Pak Med Assoc</source>. <year>2014</year>;<volume>64</volume>(<issue>5</issue>):<fpage>510</fpage>&#x2013;<lpage>3</lpage>.<pub-id pub-id-type="pmid">25272534</pub-id></mixed-citation></ref>
<ref id="r75"><label>75</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sahebally</surname><given-names>SM</given-names></name><name><surname>Ahmed</surname><given-names>K</given-names></name><name><surname>Cerneveciute</surname><given-names>R</given-names></name><name><surname>Iqbal</surname><given-names>A</given-names></name><name><surname>Walsh</surname><given-names>SR</given-names></name><name><surname>Joyce</surname><given-names>MR</given-names></name></person-group>. <article-title>Oral versus topical calcium channel blockers for chronic anal fissure-a systematic review and meta-analysis of randomized controlled trials.</article-title> <source>Int J Surg</source>. <year>2017</year>;<volume>44</volume>:<fpage>87</fpage>&#x2013;<lpage>93</lpage>. <pub-id pub-id-type="doi">10.1016/j.ijsu.2017.06.039</pub-id><pub-id pub-id-type="pmid">28629764</pub-id></mixed-citation></ref>
<ref id="r76"><label>76</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Serrera-Figallo</surname><given-names>MA</given-names></name><name><surname>Ruiz-de-Le&#x00F3;n-Hern&#x00E1;ndez</surname><given-names>G</given-names></name><name><surname>Torres-Lagares</surname><given-names>D</given-names></name><name><surname>Castro-Araya</surname><given-names>A</given-names></name><name><surname>Torres-Ferrerosa</surname><given-names>O</given-names></name><name><surname>Hern&#x00E1;ndez-Pacheco</surname><given-names>E</given-names></name><etal/></person-group> <article-title>Use of Botulinum Toxin in Orofacial Clinical Practice.</article-title> <source>Toxins (Basel)</source>. <year>2020</year>;<volume>12</volume>(<issue>2</issue>):<fpage>112</fpage>. <pub-id pub-id-type="doi">10.3390/toxins12020112</pub-id><pub-id pub-id-type="pmid">32053883</pub-id></mixed-citation></ref>
<ref id="r77"><label>77</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yiannakopoulou</surname><given-names>E</given-names></name></person-group>. <article-title>Botulinum toxin and anal fissure: Efficacy and safety systematic review.</article-title> <source>Int J Colorectal Dis</source>. <year>2012</year>;<volume>27</volume>(<issue>1</issue>):<fpage>1</fpage>&#x2013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1007/s00384-011-1286-5</pub-id><pub-id pub-id-type="pmid">21822595</pub-id></mixed-citation></ref>
<ref id="r78"><label>78</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amorim</surname><given-names>H</given-names></name><name><surname>Santoalha</surname><given-names>J</given-names></name><name><surname>Cadilha</surname><given-names>R</given-names></name><name><surname>Festas</surname><given-names>MJ</given-names></name><name><surname>Barbosa</surname><given-names>P</given-names></name><name><surname>Gomes</surname><given-names>A</given-names></name></person-group>. <article-title>Botulinum toxin improves pain in chronic anal fissure.</article-title> <source>Porto Biomed J</source>. <year>2017</year>;<volume>2</volume>(<issue>6</issue>):<fpage>273</fpage>&#x2013;<lpage>6</lpage>. <pub-id pub-id-type="doi">10.1016/j.pbj.2017.04.005</pub-id><pub-id pub-id-type="pmid">32258781</pub-id></mixed-citation></ref>
<ref id="r79"><label>79</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bibi</surname><given-names>S</given-names></name><name><surname>Zutshi</surname><given-names>M</given-names></name><name><surname>Gurland</surname><given-names>B</given-names></name><name><surname>Hull</surname><given-names>T</given-names></name></person-group>. <article-title>Is Botox for anal pain an effective treatment option?</article-title> <source>Postgrad Med</source>. <year>2016</year>;<volume>128</volume>(<issue>1</issue>):<fpage>41</fpage>&#x2013;<lpage>5</lpage>. <pub-id pub-id-type="doi">10.1080/00325481.2015.1081047</pub-id><pub-id pub-id-type="pmid">26308909</pub-id></mixed-citation></ref>
<ref id="r80"><label>80</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Berkel</surname><given-names>AEM</given-names></name><name><surname>Rosman</surname><given-names>C</given-names></name><name><surname>Koop</surname><given-names>R</given-names></name><name><surname>van Duijvendijk</surname><given-names>P</given-names></name><name><surname>van der Palen</surname><given-names>J</given-names></name><name><surname>Klaase</surname><given-names>JM</given-names></name></person-group>. <article-title>Isosorbide dinitrate ointment <italic>vs</italic> botulinum toxin A (Dysport<sup>&#x00AE;</sup>) as the primary treatment for chronic anal fissure: a randomized multicentre study.</article-title> <source>Colorectal Dis</source>. <year>2014</year>;<volume>16</volume>(<issue>10</issue>):<fpage>O360</fpage>&#x2013;<lpage>6</lpage>. <pub-id pub-id-type="doi">10.1111/codi.12615</pub-id><pub-id pub-id-type="pmid">24629060</pub-id></mixed-citation></ref>
<ref id="r81"><label>81</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lysy</surname><given-names>J</given-names></name><name><surname>Israeli</surname><given-names>E</given-names></name><name><surname>Levy</surname><given-names>S</given-names></name><name><surname>Rozentzweig</surname><given-names>G</given-names></name><name><surname>Strauss-Liviatan</surname><given-names>N</given-names></name><name><surname>Goldin</surname><given-names>E</given-names></name></person-group>. <article-title>Long-Term Results of &#x201C;Chemical Sphincterotomy&#x201D; for Chronic Anal Fissure: A Prospective Study.</article-title> <source>Dis Colon Rectum</source>. <year>2006</year>;<volume>49</volume>(<issue>6</issue>):<fpage>858</fpage>&#x2013;<lpage>64</lpage>. <pub-id pub-id-type="doi">10.1007/s10350-006-0510-9</pub-id><pub-id pub-id-type="pmid">16741641</pub-id></mixed-citation></ref>
<ref id="r82"><label>82</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wald</surname><given-names>A</given-names></name><name><surname>Bharucha</surname><given-names>AE</given-names></name><name><surname>Cosman</surname><given-names>BC</given-names></name><name><surname>Whitehead</surname><given-names>WE</given-names></name></person-group>. <article-title>ACG Clinical Guideline: Management of Benign Anorectal Disorders.</article-title> <source>Am J Gastroenterol</source>. <year>2014</year>;<volume>109</volume>(<issue>8</issue>):<fpage>1141</fpage>&#x2013;<lpage>57</lpage>. <pub-id pub-id-type="doi">10.1038/ajg.2014.190</pub-id><pub-id pub-id-type="pmid">25022811</pub-id></mixed-citation></ref>
<ref id="r83"><label>83</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arroyo</surname><given-names>A</given-names></name><name><surname>P&#x00E9;rez</surname><given-names>F</given-names></name><name><surname>Serrano</surname><given-names>P</given-names></name><name><surname>Candela</surname><given-names>F</given-names></name><name><surname>Lacueva</surname><given-names>J</given-names></name><name><surname>Calpena</surname><given-names>R</given-names></name></person-group>. <article-title>Surgical versus chemical (botulinum toxin) sphincterotomy for chronic anal fissure: Long-term results of a prospective randomized clinical and manometric study.</article-title> <source>Am J Surg</source>. <year>2005</year>;<volume>189</volume>(<issue>4</issue>):<fpage>429</fpage>&#x2013;<lpage>34</lpage>. <pub-id pub-id-type="doi">10.1016/j.amjsurg.2004.06.045</pub-id><pub-id pub-id-type="pmid">15820455</pub-id></mixed-citation></ref>
<ref id="r84"><label>84</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Emile</surname><given-names>SH</given-names></name><name><surname>Elgendy</surname><given-names>H</given-names></name><name><surname>Elfeki</surname><given-names>H</given-names></name><name><surname>Magdy</surname><given-names>A</given-names></name><name><surname>Abdelmawla</surname><given-names>AA</given-names></name><name><surname>Abdelnaby</surname><given-names>M</given-names></name><etal/></person-group> <article-title>Does the duration of symptoms of anal fissure impact its response to conservative treatment? A prospective cohort study.</article-title> <source>Int J Surg</source>. <year>2017</year>;<volume>44</volume>:<fpage>64</fpage>&#x2013;<lpage>70</lpage>. <pub-id pub-id-type="doi">10.1016/j.ijsu.2017.06.044</pub-id><pub-id pub-id-type="pmid">28629768</pub-id></mixed-citation></ref>
<ref id="r85"><label>85</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ebinger</surname><given-names>SM</given-names></name><name><surname>Hardt</surname><given-names>J</given-names></name><name><surname>Warschkow</surname><given-names>R</given-names></name><name><surname>Schmied</surname><given-names>BM</given-names></name><name><surname>Herold</surname><given-names>A</given-names></name><name><surname>Post</surname><given-names>S</given-names></name><etal/></person-group> <article-title>Operative and medical treatment of chronic anal fissures-a review and network meta-analysis of randomized controlled trials.</article-title> <source>J Gastroenterol</source>. <year>2017</year>;<volume>52</volume>(<issue>6</issue>):<fpage>663</fpage>&#x2013;<lpage>76</lpage>. <pub-id pub-id-type="doi">10.1007/s00535-017-1335-0</pub-id><pub-id pub-id-type="pmid">28396998</pub-id></mixed-citation></ref>
<ref id="r86"><label>86</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Garg</surname><given-names>P</given-names></name><name><surname>Garg</surname><given-names>M</given-names></name><name><surname>Menon</surname><given-names>GR</given-names></name></person-group>. <article-title>Long-term continence disturbance after lateral internal sphincterotomy for chronic anal fissure: a systematic review and meta-analysis.</article-title> <source>Colorectal Dis</source>. <year>2013</year>;<volume>15</volume>(<issue>3</issue>):<fpage>e104</fpage>&#x2013;<lpage>17</lpage>. <pub-id pub-id-type="doi">10.1111/codi.12108</pub-id><pub-id pub-id-type="pmid">23320551</pub-id></mixed-citation></ref>
<ref id="r87"><label>87</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kortbeek</surname><given-names>JB</given-names></name><name><surname>Langevin</surname><given-names>JM</given-names></name><name><surname>Khoo</surname><given-names>REH</given-names></name><name><surname>Heine</surname><given-names>JA</given-names></name></person-group>. <article-title>Chronic fissure-in-ano.</article-title> <source>Dis Colon Rectum</source>. <year>1992</year>;<volume>35</volume>(<issue>9</issue>):<fpage>835</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1007/BF02047868</pub-id><pub-id pub-id-type="pmid">1511641</pub-id></mixed-citation></ref>
<ref id="r88"><label>88</label><mixed-citation publication-type="book">Nelson RL. Operative procedures for fissure in ano. U: Nelson RL, ur. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley &amp; Sons, Ltd; 2005.</mixed-citation></ref>
<ref id="r89"><label>89</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arroyo</surname><given-names>A</given-names></name><name><surname>P&#x00E9;rez</surname><given-names>F</given-names></name><name><surname>Serrano</surname><given-names>P</given-names></name><name><surname>Candela</surname><given-names>F</given-names></name><name><surname>Calpena</surname><given-names>R</given-names></name></person-group>. <article-title>Open versus closed lateral sphincterotomy performed as an outpatient procedure under local anesthesia for chronic anal fissure: Prospective randomized study of clinical and manometric longterm results1.</article-title> <source>J Am Coll Surg</source>. <year>2004</year>;<volume>199</volume>(<issue>3</issue>):<fpage>361</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1016/j.jamcollsurg.2004.04.016</pub-id><pub-id pub-id-type="pmid">15325604</pub-id></mixed-citation></ref>
<ref id="r90"><label>90</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mente&#x015F;</surname><given-names>BB</given-names></name><name><surname>Ege</surname><given-names>B</given-names></name><name><surname>Leventoglu</surname><given-names>S</given-names></name><name><surname>Oguz</surname><given-names>M</given-names></name><name><surname>Karadag</surname><given-names>A</given-names></name></person-group>. <article-title>Extent of Lateral Internal Sphincterotomy: Up to the Dentate Line or Up to the Fissure Apex?</article-title> <source>Dis Colon Rectum</source>. <year>2005</year>;<volume>48</volume>(<issue>2</issue>):<fpage>365</fpage>&#x2013;<lpage>70</lpage>. <pub-id pub-id-type="doi">10.1007/s10350-004-0812-8</pub-id><pub-id pub-id-type="pmid">15711861</pub-id></mixed-citation></ref>
<ref id="r91"><label>91</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Elsebae</surname><given-names>MMA</given-names></name></person-group>. <article-title>A Study of Fecal Incontinence in Patients with Chronic Anal Fissure: Prospective, Randomized, Controlled Trial of the Extent of Internal Anal Sphincter Division During Lateral Sphincterotomy.</article-title> <source>World J Surg</source>. <year>2007</year>;<volume>31</volume>(<issue>10</issue>):<fpage>2052</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1007/s00268-007-9177-1</pub-id><pub-id pub-id-type="pmid">17665247</pub-id></mixed-citation></ref>
<ref id="r92"><label>92</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ho</surname><given-names>KS</given-names></name><name><surname>Ho</surname><given-names>YH</given-names></name></person-group>. <article-title>Randomized clinical trial comparing oral nifedipine with lateral anal sphincterotomy and tailored sphincterotomy in the treatment of chronic anal fissure.</article-title> <source>Br J Surg</source>. <year>2005</year>;<volume>92</volume>(<issue>4</issue>):<fpage>403</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1002/bjs.4882</pub-id><pub-id pub-id-type="pmid">15739214</pub-id></mixed-citation></ref>
<ref id="r93"><label>93</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schornagel</surname><given-names>IL</given-names></name><name><surname>Witvliet</surname><given-names>M</given-names></name><name><surname>Engel</surname><given-names>AF</given-names></name></person-group>. <article-title>Five-year results of fissurectomy for chronic anal fissure: low recurrence rate and minimal effect on continence.</article-title> <source>Colorectal Dis</source>. <year>2012</year>;<volume>14</volume>(<issue>8</issue>):<fpage>997</fpage>&#x2013;<lpage>1000</lpage>. <pub-id pub-id-type="doi">10.1111/j.1463-1318.2011.02840.x</pub-id><pub-id pub-id-type="pmid">21955514</pub-id></mixed-citation></ref>
<ref id="r94"><label>94</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vershenya</surname><given-names>S</given-names></name><name><surname>Klotz</surname><given-names>J</given-names></name><name><surname>Joos</surname><given-names>A</given-names></name><name><surname>Bussen</surname><given-names>D</given-names></name><name><surname>Herold</surname><given-names>A</given-names></name></person-group>. <article-title>Combined approach in the treatment of chronic anal fissures.</article-title> <source>Updates Surg</source>. <year>2015</year>;<volume>67</volume>(<issue>1</issue>):<fpage>83</fpage>&#x2013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1007/s13304-015-0290-7</pub-id><pub-id pub-id-type="pmid">25895570</pub-id></mixed-citation></ref>
<ref id="r95"><label>95</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zeitoun</surname><given-names>JD</given-names></name><name><surname>Blanchard</surname><given-names>P</given-names></name><name><surname>Fathallah</surname><given-names>N</given-names></name><name><surname>Benfredj</surname><given-names>P</given-names></name><name><surname>Lemarchand</surname><given-names>N</given-names></name><name><surname>de Parades</surname><given-names>V</given-names></name></person-group>. <article-title>Long-term Outcome of a Fissurectomy: A Prospective Single-Arm Study of 50 Operations out of 349 Initial Patients.</article-title> <source>Ann Coloproctol</source>. <year>2018</year>;<volume>34</volume>(<issue>2</issue>):<fpage>83</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.3393/ac.2017.06.12</pub-id><pub-id pub-id-type="pmid">29742858</pub-id></mixed-citation></ref>
<ref id="r96"><label>96</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hancke</surname><given-names>E</given-names></name><name><surname>Suchan</surname><given-names>K</given-names></name><name><surname>Voelke</surname><given-names>K</given-names></name></person-group>. <article-title>Anocutaneous advancement flap provides a quicker cure than fissurectomy in surgical treatment for chronic anal fissure &#x2013; a retrospective, observational study.</article-title> <source>Langenbecks Arch Surg</source>. <year>2021</year>;<volume>406</volume>(<issue>8</issue>):<fpage>2861</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1007/s00423-021-02227-4</pub-id><pub-id pub-id-type="pmid">34159437</pub-id></mixed-citation></ref>
<ref id="r97"><label>97</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Patti</surname><given-names>R</given-names></name><name><surname>Fam&#x00E0;</surname><given-names>F</given-names></name><name><surname>Barrera</surname><given-names>T</given-names></name><name><surname>Migliore</surname><given-names>G</given-names></name><name><surname>Di Vita</surname><given-names>G</given-names></name></person-group>. <article-title>Fissurectomy and anal advancement flap for anterior chronic anal fissure without hypertonia of the internal anal sphincter in females.</article-title> <source>Colorectal Dis</source>. <year>2010</year>;<volume>12</volume>(<issue>11</issue>):<fpage>1127</fpage>&#x2013;<lpage>30</lpage>. <pub-id pub-id-type="doi">10.1111/j.1463-1318.2009.02068.x</pub-id><pub-id pub-id-type="pmid">19843117</pub-id></mixed-citation></ref>
<ref id="r98"><label>98</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nyam</surname><given-names>DCNK</given-names></name><name><surname>Wilson</surname><given-names>RG</given-names></name><name><surname>Stewart</surname><given-names>KJ</given-names></name><name><surname>Farouk</surname><given-names>R</given-names></name><name><surname>Bartolo</surname><given-names>DCC</given-names></name></person-group>. <article-title>Island advancement flaps in the management of anal fissures.</article-title> <source>Br J Surg</source>. <year>1995</year>;<volume>82</volume>(<issue>3</issue>):<fpage>326</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1002/bjs.1800820315</pub-id><pub-id pub-id-type="pmid">7795999</pub-id></mixed-citation></ref>
<ref id="r99"><label>99</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Patel</surname><given-names>SD</given-names></name><name><surname>Oxenham</surname><given-names>T</given-names></name><name><surname>Praveen</surname><given-names>BV</given-names></name></person-group>. <article-title>Medium-term results of anal advancement flap compared with lateral sphincterotomy for the treatment of anal fissure.</article-title> <source>Int J Colorectal Dis</source>. <year>2011</year>;<volume>26</volume>(<issue>9</issue>):<fpage>1211</fpage>&#x2013;<lpage>4</lpage>. <pub-id pub-id-type="doi">10.1007/s00384-011-1234-4</pub-id><pub-id pub-id-type="pmid">21562745</pub-id></mixed-citation></ref>
<ref id="r100"><label>100</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cross</surname><given-names>KLR</given-names></name><name><surname>Massey</surname><given-names>EJD</given-names></name><name><surname>Fowler</surname><given-names>AL</given-names></name><name><surname>Monson</surname><given-names>JRT</given-names></name></person-group>. <article-title>The Management of Anal Fissure: ACPGBI Position Statement.</article-title> <source>Colorectal Dis</source>. <year>2008</year>;<volume>10</volume>:<fpage>1</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1111/j.1463-1318.2008.01681.x</pub-id><pub-id pub-id-type="pmid">18954306</pub-id></mixed-citation></ref>
<ref id="r101"><label>101</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>D&#x2019;Ugo</surname><given-names>S</given-names></name><name><surname>Stasi</surname><given-names>E</given-names></name><name><surname>Gaspari</surname><given-names>AL</given-names></name><name><surname>Sileri</surname><given-names>P</given-names></name></person-group>. <article-title>Hemorrhoids and anal fissures in inflammatory bowel disease.</article-title> <source>Minerva Gastroenterol Dietol</source>. <year>2015</year>;<volume>61</volume>(<issue>4</issue>):<fpage>223</fpage>&#x2013;<lpage>33</lpage>.<pub-id pub-id-type="pmid">26446683</pub-id></mixed-citation></ref>
<ref id="r102"><label>102</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wolkomir</surname><given-names>AF</given-names></name><name><surname>Luchtefeld</surname><given-names>MA</given-names></name></person-group>. <article-title>Surgery for symptomatic hemorrhoids and anal fissures in Crohn&#x2019;s disease.</article-title> <source>Dis Colon Rectum</source>. <year>1993</year>;<volume>36</volume>(<issue>6</issue>):<fpage>545</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1007/BF02049859</pub-id><pub-id pub-id-type="pmid">8500370</pub-id></mixed-citation></ref>
<ref id="r103"><label>103</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sweeney</surname><given-names>JL</given-names></name><name><surname>Ritchie</surname><given-names>JK</given-names></name><name><surname>Nicholls</surname><given-names>RJ</given-names></name></person-group>. <article-title>Anal fissure in Crohn&#x2019;s disease.</article-title> <source>Br J Surg</source>. <year>1988</year>;<volume>75</volume>(<issue>1</issue>):<fpage>56</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1002/bjs.1800750120</pub-id><pub-id pub-id-type="pmid">3337953</pub-id></mixed-citation></ref>
<ref id="r104"><label>104</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Madoff</surname><given-names>RD</given-names></name><name><surname>Fleshman</surname><given-names>JW</given-names></name></person-group>. <article-title>AGA technical review on the diagnosis and care of patients with anal fissure.</article-title> <source>Gastroenterology</source>. <year>2003</year>;<volume>124</volume>(<issue>1</issue>):<fpage>235</fpage>&#x2013;<lpage>45</lpage>. <pub-id pub-id-type="doi">10.1053/gast.2003.50005</pub-id><pub-id pub-id-type="pmid">12512046</pub-id></mixed-citation></ref>
<ref id="r105"><label>105</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bove</surname><given-names>A</given-names></name><name><surname>Balzano</surname><given-names>A</given-names></name><name><surname>Perrotti</surname><given-names>P</given-names></name><name><surname>Antropoli</surname><given-names>C</given-names></name><name><surname>Lombardi</surname><given-names>G</given-names></name><name><surname>Pucciani</surname><given-names>F</given-names></name></person-group>. <article-title>Different anal pressure profiles in patients with anal fissure.</article-title> <source>Tech Coloproctol</source>. <year>2004</year>;<volume>8</volume>(<issue>3</issue>):<fpage>151</fpage>&#x2013;<lpage>6</lpage>. <pub-id pub-id-type="doi">10.1007/s10151-004-0079-z</pub-id><pub-id pub-id-type="pmid">15654521</pub-id></mixed-citation></ref>
<ref id="r106"><label>106</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Corby</surname><given-names>H</given-names></name><name><surname>Donnelly</surname><given-names>VS</given-names></name><name><surname>O&#x2019;Herlihy</surname><given-names>C</given-names></name><name><surname>O&#x2019;Connell</surname><given-names>PR</given-names></name></person-group>. <article-title>Anal canal pressures are low in women with postpartum anal fissure.</article-title> <source>Br J Surg</source>. <year>1997</year>;<volume>84</volume>(<issue>1</issue>):<fpage>86</fpage>&#x2013;<lpage>8</lpage>.<pub-id pub-id-type="pmid">9043464</pub-id></mixed-citation></ref>
<ref id="r107"><label>107</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stelzner</surname><given-names>F</given-names></name><name><surname>Staubesand</surname><given-names>J</given-names></name><name><surname>Machleidt</surname><given-names>H</given-names></name></person-group>. <article-title>The corpus cavernosum recti--basis of internal hemorrhoids.</article-title> <source>Langenbecks Arch Klin Chir Ver Dtsch Z Chir.</source> <year>1962</year>;<volume>299</volume>:<fpage>302</fpage>&#x2013;<lpage>12</lpage>.<pub-id pub-id-type="pmid">13916799</pub-id></mixed-citation></ref>
<ref id="r108"><label>108</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Loder</surname><given-names>PB</given-names></name><name><surname>Kamm</surname><given-names>MA</given-names></name><name><surname>Nicholls</surname><given-names>RJ</given-names></name><name><surname>Phillips</surname><given-names>RKS</given-names></name></person-group>. <article-title>Haemorrhoids: Pathology, pathophysiology and aetiology.</article-title> <source>Br J Surg</source>. <year>1994</year>;<volume>81</volume>(<issue>7</issue>):<fpage>946</fpage>&#x2013;<lpage>54</lpage>. <pub-id pub-id-type="doi">10.1002/bjs.1800810707</pub-id><pub-id pub-id-type="pmid">7922085</pub-id></mixed-citation></ref>
<ref id="r109"><label>109</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thomson</surname><given-names>WHF</given-names></name></person-group>. <article-title>The nature of haemorrhoids.</article-title> <source>Br J Surg</source>. <year>1975</year>;<volume>62</volume>(<issue>7</issue>):<fpage>542</fpage>&#x2013;<lpage>52</lpage>. <pub-id pub-id-type="doi">10.1002/bjs.1800620710</pub-id><pub-id pub-id-type="pmid">1174785</pub-id></mixed-citation></ref>
<ref id="r110"><label>110</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Banov</surname><given-names>L</given-names></name><name><surname>Knoepp</surname><given-names>LF</given-names></name><name><surname>Erdman</surname><given-names>LH</given-names></name><name><surname>Alia</surname><given-names>RT</given-names></name></person-group>. <article-title>Management of hemorrhoidal disease.</article-title> <source>J S C Med Assoc</source>. <year>1985</year>;<volume>81</volume>(<issue>7</issue>):<fpage>398</fpage>&#x2013;<lpage>401</lpage>.<pub-id pub-id-type="pmid">3861909</pub-id></mixed-citation></ref>
<ref id="r111"><label>111</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Siminoff</surname><given-names>LA</given-names></name><name><surname>Rogers</surname><given-names>HL</given-names></name><name><surname>Harris-Haywood</surname><given-names>S</given-names></name></person-group>. <article-title>Missed Opportunities for the Diagnosis of Colorectal Cancer.</article-title> <source>BioMed Res Int</source>. <year>2015</year>;<volume>2015</volume>:<elocation-id>285096</elocation-id>. <pub-id pub-id-type="doi">10.1155/2015/285096</pub-id><pub-id pub-id-type="pmid">26504796</pub-id></mixed-citation></ref>
<ref id="r112"><label>112</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rex</surname><given-names>DK</given-names></name><name><surname>Boland</surname><given-names>RC</given-names></name><name><surname>Dominitz</surname><given-names>JA</given-names></name><name><surname>Giardiello</surname><given-names>FM</given-names></name><name><surname>Johnson</surname><given-names>DA</given-names></name><name><surname>Kaltenbach</surname><given-names>T</given-names></name><etal/></person-group> <article-title>Colorectal Cancer Screening: Recommendations for Physicians and Patients from the U.S. Multi-Society Task Force on Colorectal Cancer.</article-title> <source>Am J Gastroenterol</source>. <year>2017</year>;<volume>112</volume>(<issue>7</issue>):<fpage>1016</fpage>&#x2013;<lpage>30</lpage>. <pub-id pub-id-type="doi">10.1038/ajg.2017.174</pub-id><pub-id pub-id-type="pmid">28555630</pub-id></mixed-citation></ref>
<ref id="r113"><label>113</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McGill</surname><given-names>CR</given-names></name><name><surname>Devareddy</surname><given-names>L</given-names></name></person-group>.<article-title> Ten-Year Trends in Fiber and Whole Grain Intakes and Food Sources for the United States Population: National Health and Nutrition Examination Survey 2001&#x2013;2010.</article-title> <source>Nutrients</source>. <year>2015</year>;<volume>7</volume>(<issue>2</issue>):<fpage>1119</fpage>&#x2013;<lpage>30</lpage>. <pub-id pub-id-type="doi">10.3390/nu7021119</pub-id><pub-id pub-id-type="pmid">25671414</pub-id></mixed-citation></ref>
<ref id="r114"><label>114</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alonso-Coello</surname><given-names>P</given-names></name><name><surname>Mills</surname><given-names>E</given-names></name><name><surname>Heels-Ansdell</surname><given-names>D</given-names></name><name><surname>Lopez-Yarto</surname><given-names>M</given-names></name><name><surname>Zhou</surname><given-names>Q</given-names></name><name><surname>Johanson</surname><given-names>JF</given-names></name><etal/></person-group> <article-title>Fiber for the Treatment of Hemorrhoids Complications: A Systematic Review and Meta-Analysis.</article-title> <source>Am J Gastroenterol</source>. <year>2006</year>;<volume>101</volume>(<issue>1</issue>):<fpage>181</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1111/j.1572-0241.2005.00359.x</pub-id><pub-id pub-id-type="pmid">16405552</pub-id></mixed-citation></ref>
<ref id="r115"><label>115</label><mixed-citation publication-type="book">Corman ML. Haemorrhoids. U: Colon and rectal surgery. 5th Edition. Philadelphia: Lippincott Williams and Wilkins; 2004.</mixed-citation></ref>
<ref id="r116"><label>116</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alonso-Coello</surname><given-names>P</given-names></name><name><surname>Zhou</surname><given-names>Q</given-names></name><name><surname>Martinez-Zapata</surname><given-names>MJ</given-names></name><name><surname>Mills</surname><given-names>E</given-names></name><name><surname>Heels-Ansdell</surname><given-names>D</given-names></name><name><surname>Johanson</surname><given-names>JF</given-names></name><etal/></person-group> <article-title>Meta-analysis of flavonoids for the treatment of haemorrhoids.</article-title> <source>Br J Surg</source>. <year>2006</year>;<volume>93</volume>(<issue>8</issue>):<fpage>909</fpage>&#x2013;<lpage>20</lpage>. <pub-id pub-id-type="doi">10.1002/bjs.5378</pub-id><pub-id pub-id-type="pmid">16736537</pub-id></mixed-citation></ref>
<ref id="r117"><label>117</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>MacRae</surname><given-names>HM</given-names></name><name><surname>McLeod</surname><given-names>RS</given-names></name></person-group>. <article-title>Comparison of hemorrhoidal treatments: a meta-analysis.</article-title> <source>Can J Surg</source>. <year>1997</year>;<volume>40</volume>(<issue>1</issue>):<fpage>14</fpage>&#x2013;<lpage>7</lpage>.<pub-id pub-id-type="pmid">9030078</pub-id></mixed-citation></ref>
<ref id="r118"><label>118</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Iyer</surname><given-names>VS</given-names></name><name><surname>Shrier</surname><given-names>I</given-names></name><name><surname>Gordon</surname><given-names>PH</given-names></name></person-group>. <article-title>Long-Term Outcome of Rubber Band Ligation for Symptomatic Primary and Recurrent Internal Hemorrhoids.</article-title> <source>Dis Colon Rectum</source>. <year>2004</year>;<volume>47</volume>(<issue>8</issue>):<fpage>1364</fpage>&#x2013;<lpage>70</lpage>. <pub-id pub-id-type="doi">10.1007/s10350-004-0591-2</pub-id><pub-id pub-id-type="pmid">15484351</pub-id></mixed-citation></ref>
<ref id="r119"><label>119</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ahmad</surname><given-names>A</given-names></name><name><surname>Kant</surname><given-names>R</given-names></name><name><surname>Gupta</surname><given-names>A</given-names></name></person-group>. <article-title>Comparative Analysis of Doppler Guided Hemorrhoidal Artery Ligation (DG-HAL) &amp; Infrared Coagulation (IRC) in Management of Hemorrhoids.</article-title> <source>Indian J Surg</source>. <year>2013</year>;<volume>75</volume>(<issue>4</issue>):<fpage>274</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1007/s12262-012-0444-5</pub-id><pub-id pub-id-type="pmid">24426452</pub-id></mixed-citation></ref>
<ref id="r120"><label>120</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moser</surname><given-names>KH</given-names></name><name><surname>Mosch</surname><given-names>C</given-names></name><name><surname>Walgenbach</surname><given-names>M</given-names></name><name><surname>Bussen</surname><given-names>DG</given-names></name><name><surname>Kirsch</surname><given-names>J</given-names></name><name><surname>Joos</surname><given-names>AK</given-names></name><etal/></person-group> <article-title>Efficacy and safety of sclerotherapy with polidocanol foam in comparison with fluid sclerosant in the treatment of first-grade haemorrhoidal disease: a randomised, controlled, single-blind, multicentre trial.</article-title> <source>Int J Colorectal Dis</source>. <year>2013</year>;<volume>28</volume>(<issue>10</issue>):<fpage>1439</fpage>&#x2013;<lpage>47</lpage>. <pub-id pub-id-type="doi">10.1007/s00384-013-1729-2</pub-id><pub-id pub-id-type="pmid">23775099</pub-id></mixed-citation></ref>
<ref id="r121"><label>121</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>El Nakeeb</surname><given-names>AM</given-names></name><name><surname>Fikry</surname><given-names>AA</given-names></name><name><surname>Omar</surname><given-names>WH</given-names></name><name><surname>Fouda</surname><given-names>EM</given-names></name><name><surname>El Metwally</surname><given-names>TA</given-names></name><name><surname>Ghazy</surname><given-names>HE</given-names></name><etal/></person-group> <article-title>Rubber band ligation for 750 cases of symptomatic hemorrhoids out of 2200 cases.</article-title> <source>World J Gastroenterol</source>. <year>2008</year>;<volume>14</volume>(<issue>42</issue>):<fpage>6525</fpage>. <pub-id pub-id-type="doi">10.3748/wjg.14.6525</pub-id><pub-id pub-id-type="pmid">19030206</pub-id></mixed-citation></ref>
<ref id="r122"><label>122</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wechter</surname><given-names>DG</given-names></name><name><surname>Luna</surname><given-names>GK</given-names></name></person-group>. <article-title>An unusual complication of rubber band ligation of hemorrhoids.</article-title> <source>Dis Colon Rectum</source>. <year>1987</year>;<volume>30</volume>(<issue>2</issue>):<fpage>137</fpage>&#x2013;<lpage>40</lpage>. <pub-id pub-id-type="doi">10.1007/BF02554954</pub-id><pub-id pub-id-type="pmid">3803121</pub-id></mixed-citation></ref>
<ref id="r123"><label>123</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Guy</surname><given-names>RJ</given-names></name><name><surname>Seow-Choen</surname><given-names>F</given-names></name></person-group>. <article-title>Septic complications after treatment of haemorrhoids.</article-title> <source>Br J Surg</source>. <year>2003</year>;<volume>90</volume>(<issue>2</issue>):<fpage>147</fpage>&#x2013;<lpage>56</lpage>. <pub-id pub-id-type="doi">10.1002/bjs.4008</pub-id><pub-id pub-id-type="pmid">12555289</pub-id></mixed-citation></ref>
<ref id="r124"><label>124</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Adami</surname><given-names>B</given-names></name><name><surname>Eckardt</surname><given-names>VF</given-names></name><name><surname>Suermann</surname><given-names>BR</given-names></name><name><surname>Karbach</surname><given-names>U</given-names></name><name><surname>Ewe</surname><given-names>K</given-names></name></person-group>. <article-title>Bacteremia after proctoscopy and hemorrhoidal injection sclerotherapy.</article-title> <source>Dis Colon Rectum</source>. <year>1981</year>;<volume>24</volume>(<issue>5</issue>):<fpage>373</fpage>&#x2013;<lpage>4</lpage>. <pub-id pub-id-type="doi">10.1007/BF02603422</pub-id><pub-id pub-id-type="pmid">7261821</pub-id></mixed-citation></ref>
<ref id="r125"><label>125</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Albuquerque</surname><given-names>A</given-names></name></person-group>. <article-title>Rubber band ligation of hemorrhoids: A guide for complications.</article-title> <source>World J Gastrointest Surg</source>. <year>2016</year>;<volume>8</volume>(<issue>9</issue>):<fpage>614</fpage>. <pub-id pub-id-type="doi">10.4240/wjgs.v8.i9.614</pub-id><pub-id pub-id-type="pmid">27721924</pub-id></mixed-citation></ref>
<ref id="r126"><label>126</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McCloud</surname><given-names>JM</given-names></name><name><surname>Jameson</surname><given-names>JS</given-names></name><name><surname>Scott</surname><given-names>AND</given-names></name></person-group>. <article-title>Life-threatening sepsis following treatment for haemorrhoids: a systematic review.</article-title> <source>Colorectal Dis</source>. <year>2006</year>;<volume>8</volume>(<issue>9</issue>):<fpage>748</fpage>&#x2013;<lpage>55</lpage>. <pub-id pub-id-type="doi">10.1111/j.1463-1318.2006.01028.x</pub-id><pub-id pub-id-type="pmid">17032319</pub-id></mixed-citation></ref>
<ref id="r127"><label>127</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chau</surname><given-names>NG</given-names></name><name><surname>Bhatia</surname><given-names>S</given-names></name><name><surname>Raman</surname><given-names>M</given-names></name></person-group>. <article-title>Pylephlebitis and Pyogenic Liver Abscesses: A Complication of Hemorrhoidal Banding.</article-title> <source>Can J Gastroenterol</source>. <year>2007</year>;<volume>21</volume>(<issue>9</issue>):<fpage>601</fpage>&#x2013;<lpage>3</lpage>. <pub-id pub-id-type="doi">10.1155/2007/106946</pub-id><pub-id pub-id-type="pmid">17853956</pub-id></mixed-citation></ref>
<ref id="r128"><label>128</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tejirian</surname><given-names>T</given-names></name><name><surname>Abbas</surname><given-names>MA</given-names></name></person-group>. <article-title>Bacterial Endocarditis Following Rubber Band Ligation in a Patient with a Ventricular Septal Defect: Report of a Case and Guideline Analysis.</article-title> <source>Dis Colon Rectum</source>. <year>2006</year>;<volume>49</volume>(<issue>12</issue>):<fpage>1931</fpage>&#x2013;<lpage>3</lpage>. <pub-id pub-id-type="doi">10.1007/s10350-006-0769-x</pub-id><pub-id pub-id-type="pmid">17080276</pub-id></mixed-citation></ref>
<ref id="r129"><label>129</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Davis</surname><given-names>BR</given-names></name><name><surname>Lee-Kong</surname><given-names>SA</given-names></name><name><surname>Migaly</surname><given-names>J</given-names></name><name><surname>Feingold</surname><given-names>DL</given-names></name><name><surname>Steele</surname><given-names>SR</given-names></name></person-group>. <article-title>The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Hemorrhoids.</article-title> <source>Dis Colon Rectum</source>. <year>2018</year>;<volume>61</volume>(<issue>3</issue>):<fpage>284</fpage>&#x2013;<lpage>92</lpage>. <pub-id pub-id-type="doi">10.1097/DCR.0000000000001030</pub-id><pub-id pub-id-type="pmid">29420423</pub-id></mixed-citation></ref>
<ref id="r130"><label>130</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>You</surname><given-names>SY</given-names></name><name><surname>Kim</surname><given-names>SH</given-names></name><name><surname>Chung</surname><given-names>CS</given-names></name><name><surname>Lee</surname><given-names>DK</given-names></name><name><surname>Open</surname><given-names>VS</given-names></name></person-group>. <article-title>Closed Hemorrhoidectomy.</article-title> <source>Dis Colon Rectum</source>. <year>2005</year>;<volume>48</volume>(<issue>1</issue>):<fpage>108</fpage>&#x2013;<lpage>13</lpage>. <pub-id pub-id-type="doi">10.1007/s10350-004-0794-6</pub-id><pub-id pub-id-type="pmid">15690666</pub-id></mixed-citation></ref>
<ref id="r131"><label>131</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bhatti</surname><given-names>MI</given-names></name><name><surname>Sajid</surname><given-names>MS</given-names></name><name><surname>Baig</surname><given-names>MK</given-names></name></person-group>. <article-title>Milligan&#x2013;Morgan (Open) Versus Ferguson Haemorrhoidectomy (Closed): A Systematic Review and Meta-Analysis of Published Randomized, Controlled Trials.</article-title> <source>World J Surg</source>. <year>2016</year>;<volume>40</volume>(<issue>6</issue>):<fpage>1509</fpage>&#x2013;<lpage>19</lpage>. <pub-id pub-id-type="doi">10.1007/s00268-016-3419-z</pub-id><pub-id pub-id-type="pmid">26813541</pub-id></mixed-citation></ref>
<ref id="r132"><label>132</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gen&#x00E7;osmano&#x011F;lu</surname><given-names>R</given-names></name><name><surname>&#x015E;ad</surname><given-names>O</given-names></name><name><surname>Ko&#x00E7;</surname><given-names>D</given-names></name><name><surname>&#x0130;nceo&#x011F;lu</surname><given-names>R</given-names></name></person-group>. <article-title>Hemorrhoidectomy: Open or Closed Technique?</article-title> <source>Dis Colon Rectum</source>. <year>2002</year>;<volume>45</volume>(<issue>1</issue>):<fpage>70</fpage>&#x2013;<lpage>5</lpage>. <pub-id pub-id-type="doi">10.1007/s10350-004-6116-1</pub-id><pub-id pub-id-type="pmid">11786767</pub-id></mixed-citation></ref>
<ref id="r133"><label>133</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van Tol</surname><given-names>RR</given-names></name><name><surname>Kleijnen</surname><given-names>J</given-names></name><name><surname>Watson</surname><given-names>AJM</given-names></name><name><surname>Jongen</surname><given-names>J</given-names></name><name><surname>Altomare</surname><given-names>DF</given-names></name><name><surname>Qvist</surname><given-names>N</given-names></name><etal/></person-group> <article-title>European Society of ColoProctology: guideline for haemorrhoidal disease.</article-title> <source>Colorectal Dis</source>. <year>2020</year>;<volume>22</volume>(<issue>6</issue>):<fpage>650</fpage>&#x2013;<lpage>62</lpage>. <pub-id pub-id-type="doi">10.1111/codi.14975</pub-id><pub-id pub-id-type="pmid">32067353</pub-id></mixed-citation></ref>
<ref id="r134"><label>134</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Abramowitz</surname><given-names>L</given-names></name><name><surname>Batallan</surname><given-names>A</given-names></name></person-group>. <article-title>&#x00C9;pid&#x00E9;miologie des l&#x00E9;sions anales (fissure et thrombose h&#x00E9;morro&#x00EF;daire externe) pendant la grossesse et le post-partum.</article-title> <source>Gyn&#x00E9;col Obst&#x00E9;t Fertil</source>. <year>2003</year>;<volume>31</volume>(<issue>6</issue>):<fpage>546</fpage>&#x2013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1016/S1297-9589(03)00127-9</pub-id><pub-id pub-id-type="pmid">12865195</pub-id></mixed-citation></ref>
<ref id="r135"><label>135</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shirah</surname><given-names>BH</given-names></name><name><surname>Shirah</surname><given-names>HA</given-names></name><name><surname>Fallata</surname><given-names>AH</given-names></name><name><surname>Alobidy</surname><given-names>SN</given-names></name><name><surname>Al Hawsawi</surname><given-names>MM</given-names></name></person-group>. <article-title>Hemorrhoids during pregnancy: Sitz bath vs. ano-rectal cream: A comparative prospective study of two conservative treatment protocols.</article-title> <source>Women Birth</source>. <year>2018</year>;<volume>31</volume>(<issue>4</issue>):<fpage>e272</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1016/j.wombi.2017.10.003</pub-id><pub-id pub-id-type="pmid">29055673</pub-id></mixed-citation></ref>
<ref id="r136"><label>136</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rao</surname><given-names>SSC</given-names></name><name><surname>Qureshi</surname><given-names>WA</given-names></name><name><surname>Yan</surname><given-names>Y</given-names></name><name><surname>Johnson</surname><given-names>DA</given-names></name></person-group>. <article-title>Constipation, Hemorrhoids, and Anorectal Disorders in Pregnancy.</article-title> <source>Am J Gastroenterol</source>. <year>2022</year>;<volume>117</volume> <supplement>10S</supplement>:<fpage>16</fpage>&#x2013;<lpage>25</lpage>. <pub-id pub-id-type="doi">10.14309/ajg.0000000000001962</pub-id><pub-id pub-id-type="pmid">36194029</pub-id></mixed-citation></ref>
<ref id="r137"><label>137</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Saleeby</surname><given-names>RG</given-names></name><name><surname>Rosen</surname><given-names>L</given-names></name><name><surname>Stasik</surname><given-names>JJ</given-names></name><name><surname>Riether</surname><given-names>RD</given-names></name><name><surname>Sheets</surname><given-names>J</given-names></name><name><surname>Khubchandani</surname><given-names>IT</given-names></name></person-group>. <article-title>Hemorrhoidectomy during pregnancy.</article-title> <source>Dis Colon Rectum</source>. <year>1991</year>;<volume>34</volume>(<issue>3</issue>):<fpage>260</fpage>&#x2013;<lpage>1</lpage>. <pub-id pub-id-type="doi">10.1007/BF02090166</pub-id><pub-id pub-id-type="pmid">1999133</pub-id></mixed-citation></ref>
<ref id="r138"><label>138</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nelson</surname><given-names>RS</given-names></name><name><surname>Thorson</surname><given-names>AG</given-names></name></person-group>. <article-title>Risk of bleeding following hemorrhoidal banding in patients on antithrombotic therapy.</article-title> <source>Gastroenterol Clin Biol</source>. <year>2009</year>;<volume>33</volume>(<issue>6&#x2013;7</issue>):<fpage>463</fpage>&#x2013;<lpage>5</lpage>. <pub-id pub-id-type="doi">10.1016/j.gcb.2009.05.007</pub-id><pub-id pub-id-type="pmid">19524384</pub-id></mixed-citation></ref>
<ref id="r139"><label>139</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Beeckman</surname><given-names>D</given-names></name><name><surname>Verhaeghe</surname><given-names>S</given-names></name><name><surname>Defloor</surname><given-names>T</given-names></name><name><surname>Schoonhoven</surname><given-names>L</given-names></name><name><surname>Vanderwee</surname><given-names>K</given-names></name></person-group>. <article-title>A 3-in-1 perineal care washcloth impregnated with dimethicone 3% versus water and pH neutral soap to prevent and treat incontinence-associated dermatitis: a randomized, controlled clinical trial.</article-title> <source>J Wound Ostomy Continence Nurs</source>. <year>2011</year>;<volume>38</volume>(<issue>6</issue>):<fpage>627</fpage>&#x2013;<lpage>34</lpage>. <pub-id pub-id-type="doi">10.1097/WON.0b013e31822efe52</pub-id><pub-id pub-id-type="pmid">21952346</pub-id></mixed-citation></ref>
</ref-list>
</back>
</article>
