{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:02:26Z","timestamp":1790827346794,"version":"4.1.0"},"reference-count":107,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Gallbladder cancer (GBC) is the most common biliary tract cancer worldwide and its incidence has significant geographic variation. A unique combination of predisposing factors includes genetic predisposition, geographic distribution, female gender, chronic inflammation, and congenital developmental abnormalities. Today, incidental GBC is the most common presentation of resectable gallbladder cancer, and surgery (minimally invasive or open) remains the only curative treatment available. Encouragingly, there is an important emerging role for systemic treatment for patients who have R1 resection or present with stage III\u2013IV. In this article, we describe the pathogenesis, surgical and systemic treatment, and prognosis.<\/jats:p>","DOI":"10.3390\/cancers14061413","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T11:46:47Z","timestamp":1646912807000},"page":"1413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Treatment of Resectable Gallbladder Cancer"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4643-0634","authenticated-orcid":false,"given":"Eduardo A.","family":"Vega","sequence":"first","affiliation":[{"name":"Department of Surgery, St. Elizabeth\u2019s Medical Center, Boston University School of Medicine, Boston, MA 02135, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Mellado","sequence":"additional","affiliation":[{"name":"Tufts University School of Medicine, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omid","family":"Salehi","sequence":"additional","affiliation":[{"name":"Department of Surgery, St. Elizabeth\u2019s Medical Center, Boston University School of Medicine, Boston, MA 02135, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Surgery, St. Elizabeth\u2019s Medical Center, Boston University School of Medicine, Boston, MA 02135, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudius","family":"Conrad","sequence":"additional","affiliation":[{"name":"Department of Surgery, St. Elizabeth\u2019s Medical Center, Boston University School of Medicine, Boston, MA 02135, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1245\/s10434-009-0538-x","article-title":"Evolving treatment strategies for gallbladder cancer","volume":"16","author":"Hueman","year":"2009","journal-title":"Ann. Surg. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1093\/annonc\/mdn533","article-title":"Epidemiology of biliary tract cancers: An update","volume":"20","author":"Randi","year":"2009","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s11894-005-0051-8","article-title":"Epidemiology and risk factors for gallstone disease: Has the paradigm changed in the 21st century?","volume":"7","author":"Shaffer","year":"2005","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/sj.bjc.6603703","article-title":"Obesity and the risk of gallbladder cancer: A meta-analysis","volume":"96","author":"Larsson","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/00008469-200308000-00005","article-title":"Lifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancer","volume":"12","author":"Pandey","year":"2003","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/nrc1429","article-title":"Gallbladder cancer: Lessons from a rare tumour","volume":"4","author":"Wistuba","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0046-8177(99)90295-2","article-title":"Gallbladder adenomas have molecular abnormalities different from those present in gallbladder carcinomas","volume":"30","author":"Wistuba","year":"1999","journal-title":"Hum. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1002\/1097-0142(19821115)50:10<2226::AID-CNCR2820501043>3.0.CO;2-3","article-title":"Relation of adenoma to carcinoma in the gallbladder","volume":"50","author":"Kozuka","year":"1982","journal-title":"Cancer"},{"key":"ref_9","first-page":"946","article-title":"Risk factor for extrahepatic bile duct cancer in patients with anomalous pancreaticobiliary ductal union","volume":"51","author":"Jung","year":"2004","journal-title":"Hepato-Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s005340200004","article-title":"Recent advances in pancreaticobiliary maljunction","volume":"9","author":"Matsumoto","year":"2002","journal-title":"J. Hepato-Biliary-Pancreat. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1002\/ijc.2910450228","article-title":"Changing trends of gall-bladder cancer in Chile, a high-risk area","volume":"45","author":"Serra","year":"1990","journal-title":"Int. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1002\/1097-0142(19930915)72:6<1878::AID-CNCR2820720615>3.0.CO;2-2","article-title":"Metaplasia and precursor lesions of gallbladder carcinoma. Frequency, distribution, and probability of detection in routine histologic samples","volume":"72","author":"Duarte","year":"1993","journal-title":"Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/ijc.2910460630","article-title":"Increasing gall-bladder cancer mortality rate during the last decade in Chile, a high-risk area","volume":"46","author":"Chianale","year":"1990","journal-title":"Int. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.hpb.2018.12.006","article-title":"Incidental versus non-incidental gallbladder cancer: Index cholecystectomy before oncologic re-resection negatively impacts survival in T2b tumors","volume":"21","author":"Vega","year":"2019","journal-title":"HPB"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1002\/jso.21681","article-title":"Incidental gallbladder cancer: Analysis of surgical findings and survival","volume":"102","author":"Butte","year":"2010","journal-title":"J. Surg. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.3748\/wjg.v21.i4.1315","article-title":"Clinical characteristics of incidental or unsuspected gallbladder cancers diagnosed during or after cholecystectomy: A systematic review and meta-analysis","volume":"21","author":"Choi","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1097\/SLA.0000000000000485","article-title":"Incidental gallbladder cancer at cholecystectomy: When should the surgeon be suspicious?","volume":"260","author":"Pitt","year":"2014","journal-title":"Ann. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1477-2574.2011.00325.x","article-title":"The role of laparoscopic staging in patients with incidental gallbladder cancer","volume":"13","author":"Butte","year":"2011","journal-title":"HPB"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s12094-011-0613-1","article-title":"Gallbladder carcinoma incidentally encountered during laparoscopic cholecystectomy: How to deal with it","volume":"13","author":"Jin","year":"2011","journal-title":"Clin. Transl. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.canlet.2013.08.034","article-title":"Chronic inflammation and gallbladder cancer","volume":"345","author":"Li","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/onc.2012.61","article-title":"The molecular mechanism of microRNA-145 to suppress invasion\u2013metastasis cascade in gastric cancer","volume":"32","author":"Gao","year":"2013","journal-title":"Oncogene"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"G626","DOI":"10.1152\/ajpgi.2001.281.3.G626","article-title":"Nitric oxide in gastrointestinal epithelial cell carcinogenesis: Linking inflammation to oncogenesis","volume":"281","author":"Jaiswal","year":"2001","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMoa1917239","article-title":"KRASG12C inhibition with sotorasib in advanced solid tumors","volume":"383","author":"Hong","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S1470-2045(11)70184-X","article-title":"Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomised, phase 3 study","volume":"12","author":"Zhou","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1111\/1759-7714.12906","article-title":"Afatinib as first-line treatment for advanced lung adenocarcinoma patients harboring HER2 mutation: A case report and review of the literature","volume":"9","author":"Shi","year":"2018","journal-title":"Thorac. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1200\/JCO.2017.35.4_suppl.402","article-title":"Pertuzumab+ trastuzumab for HER2-positive metastatic biliary cancer: Preliminary data from MyPathway","volume":"35","author":"Javle","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"22087","DOI":"10.1038\/s41598-020-77939-6","article-title":"Genomic profiling reveals high frequency of DNA repair genetic aberrations in gallbladder cancer","volume":"10","author":"Yap","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4753","DOI":"10.1038\/s41467-021-25012-9","article-title":"Genomic characterization of co-existing neoplasia and carcinoma lesions reveals distinct evolutionary paths of gallbladder cancer","volume":"12","author":"Lin","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.gassur.2005.11.003","article-title":"Gallbladder cancer: An analysis of a series of 139 patients with invasion restricted to the subserosal layer","volume":"10","author":"Roa","year":"2006","journal-title":"J. Gastrointest. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1002\/jso.21389","article-title":"Early gallbladder cancer: Is further treatment necessary?","volume":"100","author":"Roa","year":"2009","journal-title":"J. Surg. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1245\/s10434-017-5859-6","article-title":"Incidental Gallbladder Cancer: Residual Cancer Discovered at Oncologic Extended Resection Determines Outcome: A Report from High- and Low-Incidence Countries","volume":"24","author":"Vinuela","year":"2017","journal-title":"Ann. Surg. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s11605-017-3507-x","article-title":"Extended Lymphadenectomy Is Required for Incidental Gallbladder Cancer Independent of Cystic Duct Lymph Node Status","volume":"22","author":"Vega","year":"2017","journal-title":"J. Gastrointest. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.soc.2018.11.001","article-title":"Minimally invasive surgery for gallbladder cancer","volume":"28","author":"Vega","year":"2019","journal-title":"Surg. Oncol. Clin."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/jso.21141","article-title":"Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC)","volume":"98","author":"Duffy","year":"2008","journal-title":"J. Surg. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1007\/s11605-007-0309-6","article-title":"Incidence of finding residual disease for incidental gallbladder carcinoma: Implications for re-resection","volume":"11","author":"Pawlik","year":"2007","journal-title":"J. Gastrointest. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.ejso.2019.01.013","article-title":"Positive cystic duct margin at index cholecystectomy in incidental gallbladder cancer is an important negative prognosticator","volume":"45","author":"Vega","year":"2019","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/jso.25617","article-title":"Intraoperative bile spillage is associated with worse survival in gallbladder adenocarcinoma","volume":"120","author":"Blakely","year":"2019","journal-title":"J. Surg. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/SLA.0000000000003325","article-title":"Adverse outcomes after bile spillage in incidental gallbladder cancers: A population-based study","volume":"273","author":"Horkoff","year":"2021","journal-title":"Ann. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"287","DOI":"10.35687\/s2452-45492020004575","article-title":"C\u00e1ncer de ves\u00edcula biliar\u00bf La contaminaci\u00f3n por bilis afecta el pron\u00f3stico?","volume":"72","author":"Aretxabala","year":"2020","journal-title":"Revista Cirug\u00eda"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1097\/SLA.0000000000000728","article-title":"Tumor location is a strong predictor of tumor progression and survival in T2 gallbladder cancer: An international multicenter study","volume":"261","author":"Shindoh","year":"2015","journal-title":"Ann. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S1091-255X(01)00014-2","article-title":"Should suspected early gallbladder cancer be treated laparoscopically?","volume":"6","author":"Weiland","year":"2002","journal-title":"J. Gastrointest. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"537","DOI":"10.21037\/hbsn.2019.07.22","article-title":"Biliary spillage a new prognostic factor in gallbladder cancer?","volume":"8","year":"2019","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1097\/SLA.0b013e31806beec2","article-title":"Gallbladder cancer: The role of laparoscopy and radical resection","volume":"245","author":"Shih","year":"2007","journal-title":"Ann. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00423-012-0950-8","article-title":"Outcomes and prognostic factors in gallbladder cancer: A single-centre experience","volume":"397","author":"Cziupka","year":"2012","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1177\/000313481708300721","article-title":"Pathologic and Prognostic Implications of Incidental versus Nonincidental Gallbladder Cancer: A 10-Institution Study from the United States Extrahepatic Biliary Malignancy Consortium","volume":"83","author":"Ethun","year":"2017","journal-title":"Am. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1097\/00000658-200010000-00011","article-title":"Gallbladder cancer: Comparison of patients presenting initially for definitive operation with those presenting after prior noncurative intervention","volume":"232","author":"Fong","year":"2000","journal-title":"Ann. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/hpb.12444","article-title":"Gallbladder cancer: Expert consensus statement","volume":"17","author":"Aloia","year":"2015","journal-title":"HPB"},{"key":"ref_48","first-page":"197","article-title":"Is frozen section effective for diagnosis of unsuspected gallbladder cancer during laparoscopic cholecystectomy?","volume":"16","author":"Aoki","year":"2002","journal-title":"Surg. Endosc. Other Interv. Tech."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/S1499-3872(15)60375-7","article-title":"Histological examination of frozen sections for patients with acute cholecystitis during cholecystectomy","volume":"14","author":"You","year":"2015","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"v28","DOI":"10.1093\/annonc\/mdw324","article-title":"Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"27","author":"Valle","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"350","DOI":"10.6004\/jnccn.2009.0027","article-title":"NCCN clinical practice guidelines in oncology: Hepatobiliary cancers","volume":"7","author":"Benson","year":"2009","journal-title":"J. Natl. Compr. Cancer Netw. JNCCN"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.jamcollsurg.2014.01.069","article-title":"Residual disease predicts outcomes after definitive resection for incidental gallbladder cancer","volume":"219","author":"Butte","year":"2014","journal-title":"J. Am. Coll. Surg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ciresp.2013.11.010","article-title":"Radical surgery for incidental gallbladder cancer: The value of a deferred pathological finding of residual disease","volume":"92","author":"Gil","year":"2014","journal-title":"Cir. Esp."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1007\/s00268-011-1134-3","article-title":"Incidental gallbladder cancer by the AFC-GBC-2009 Study Group","volume":"35","author":"Fuks","year":"2011","journal-title":"World J. Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1245\/s10434-017-5773-y","article-title":"Effective Laparoscopic Management Lymph Node Dissection for Gallbladder Cancer","volume":"24","author":"Vega","year":"2017","journal-title":"Ann. Surg. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1245\/s10434-016-5436-4","article-title":"Laparoscopic Management of Gallbladder Cancer: A Stepwise Approach","volume":"23","author":"Yamashita","year":"2016","journal-title":"Ann. Surg. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"S336","DOI":"10.1245\/s10434-015-4650-9","article-title":"Totally Laparoscopic Hepatic Bisegmentectomy (s4b+s5) and Hilar Lymphadenectomy for Incidental Gallbladder Cancer","volume":"22","author":"Machado","year":"2015","journal-title":"Ann. Surg. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1007\/s00464-010-1102-2","article-title":"Laparoscopic completion radical cholecystectomy for T2 gallbladder cancer","volume":"24","author":"Gumbs","year":"2010","journal-title":"Surg. Endosc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1007\/s00534-012-0584-9","article-title":"Gallbladder bed resection or hepatectomy of segments 4a and 5 for pT2 gallbladder carcinoma: Analysis of Japanese registration cases by the study group for biliary surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery","volume":"20","author":"Horiguchi","year":"2013","journal-title":"J. Hepato-Biliary-Pancreat. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1007\/s00464-010-0914-4","article-title":"Adequate extent in radical re-resection of incidental gallbladder carcinoma: Analysis of the German Registry","volume":"24","author":"Goetze","year":"2010","journal-title":"Surg. Endosc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/bjs.11379","article-title":"Comparison of oncological outcomes after open and laparoscopic re-resection of incidental gallbladder cancer","volume":"107","author":"Vega","year":"2020","journal-title":"Br. J. Surg."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1007\/s00464-012-2330-4","article-title":"Radical resection of gallbladder cancer: Could it be robotic?","volume":"26","author":"Shen","year":"2012","journal-title":"Surg. Endosc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.jamcollsurg.2015.07.010","article-title":"Is Laparoscopy Contraindicated for Gallbladder Cancer? A 10-Year Prospective Cohort Study","volume":"221","author":"Yoon","year":"2015","journal-title":"J. Am. Coll. Surg."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1007\/s00464-010-0925-1","article-title":"Gallbladder cancer: Role of laparoscopy in the management of potentially resectable tumors","volume":"24","author":"Leon","year":"2010","journal-title":"Surg. Endosc."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/s00464-012-2489-8","article-title":"Minimally invasive approaches to extrapancreatic cholangiocarcinoma","volume":"27","author":"Gumbs","year":"2013","journal-title":"Surg. Endosc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1111\/hpb.12406","article-title":"Minimally invasive versus the conventional open surgical approach of a radical cholecystectomy for gallbladder cancer: A retrospective comparative study","volume":"17","author":"Agarwal","year":"2015","journal-title":"HPB"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1007\/s00464-014-3932-9","article-title":"Laparoscopic radical cholecystectomy with lymph node dissection for gallbladder carcinoma","volume":"29","author":"Shirobe","year":"2015","journal-title":"Surg. Endosc."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1001\/archsurg.2009.261","article-title":"Laparoscopic approach for suspected early-stage gallbladder carcinoma","volume":"145","author":"Cho","year":"2010","journal-title":"Arch. Surg."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1007\/s00464-015-4495-0","article-title":"Laparoscopic radical cholecystectomy for suspected early gall bladder carcinoma: Thinking beyond convention","volume":"30","author":"Palanisamy","year":"2016","journal-title":"Surg. Endosc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3600","DOI":"10.1007\/s00464-015-4116-y","article-title":"Novel strategy for laparoscopic treatment of pT2 gallbladder carcinoma","volume":"29","author":"Itano","year":"2015","journal-title":"Surg. Endosc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1002\/jhbp.717","article-title":"Early outcomes of robotic extended cholecystectomy for the treatment of gallbladder cancer","volume":"27","author":"Byun","year":"2020","journal-title":"J. Hepatobiliary Pancreat. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Goel, M., Kurunkar, S.R., Kanetkar, A., and Patkar, S. (2019). Outcome of robot-assisted radical cholecystectomy in a high-volume tertiary cancer center in India. Videoscopy, 29.","DOI":"10.1089\/vor.2018.0539"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e2312","DOI":"10.1002\/rcs.2312","article-title":"Robotic-assisted completion cholecystectomy: A safe and effective approach to a challenging surgical scenario\u2013A single center retrospective cohort study","volume":"17","author":"Tschuor","year":"2021","journal-title":"Int. J. Med. Robot. Comput. Assist. Surg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1007\/s00464-020-07554-z","article-title":"Robotic extended cholecystectomy in gallbladder cancer","volume":"34","author":"Byun","year":"2020","journal-title":"Surg. Endosc."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1016\/j.hpb.2019.03.053","article-title":"Robotic radical cholecystectomy for gallbladder cancer at a high-volume minimally invasive center","volume":"21","author":"Pickens","year":"2019","journal-title":"HPB"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/jso.24591","article-title":"Routine port-site excision in incidentally discovered gallbladder cancer is not associated with improved survival: A multi-institution analysis from the US Extrahepatic Biliary Malignancy Consortium","volume":"115","author":"Ethun","year":"2017","journal-title":"J. Surg. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1245\/s10434-011-1850-9","article-title":"Is port site resection necessary in the surgical management of gallbladder cancer?","volume":"19","author":"Maker","year":"2012","journal-title":"Ann. Surg. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.surg.2016.08.007","article-title":"Trends in port-site metastasis after laparoscopic resection of incidental gallbladder cancer: A systematic review","volume":"161","author":"Chesney","year":"2017","journal-title":"Surgery"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.hpb.2016.05.016","article-title":"Rates and patterns of recurrence after curative intent resection for gallbladder cancer: A multi-institution analysis from the US Extra-hepatic Biliary Malignancy Consortium","volume":"18","author":"Margonis","year":"2016","journal-title":"HPB"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1245\/s10434-021-09626-3","article-title":"Conditional recurrence-free survival after oncologic extended resection for gallbladder cancer: An international multicenter analysis","volume":"28","author":"Vega","year":"2021","journal-title":"Ann. Surg. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1111\/j.1477-2574.2012.00498.x","article-title":"Relevance of residual disease after liver resection for incidental gallbladder cancer","volume":"14","author":"Lendoire","year":"2012","journal-title":"HPB"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1245\/s10434-016-5637-x","article-title":"A Novel Pathology-Based Preoperative Risk Score to Predict Locoregional Residual and Distant Disease and Survival for Incidental Gallbladder Cancer: A 10-Institution Study from the U.S. Extrahepatic Biliary Malignancy Consortium","volume":"24","author":"Ethun","year":"2017","journal-title":"Ann. Surg. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1056\/NEJMoa0908721","article-title":"Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer","volume":"362","author":"Valle","year":"2010","journal-title":"New Engl. J. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1002\/cncr.10831","article-title":"Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma","volume":"95","author":"Takada","year":"2002","journal-title":"Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1200\/JCO.2014.60.2219","article-title":"SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma","volume":"33","author":"Guthrie","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1200\/JCO.2011.40.5381","article-title":"Adjuvant therapy in the treatment of biliary tract cancer: A systematic review and meta-analysis","volume":"30","author":"Horgan","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1200\/JCO.2017.35.4_suppl.225","article-title":"Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial","volume":"35","author":"Edeline","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4006","DOI":"10.1200\/JCO.2017.35.15_suppl.4006","article-title":"Adjuvant capecitabine for biliary tract cancer: The BILCAP randomized study","volume":"35","author":"Primrose","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/s11605-021-05143-6","article-title":"Prospective Randomized Controlled Trial Comparing Adjuvant Chemotherapy vs. No Chemotherapy for Patients with Carcinoma of Gallbladder Undergoing Curative Resection","volume":"26","author":"Saluja","year":"2021","journal-title":"J. Gastrointest. Surg."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Rizzo, A., Ricci, A.D., and Brandi, G. (2021). PD-L1, TMB, MSI, and other predictors of response to immune checkpoint inhibitors in biliary tract cancer. Cancers, 13.","DOI":"10.3390\/cancers13030558"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"DiPeri, T.P., Javle, M.M., and Meric-Bernstam, F. (2021). Next Generation Sequencing for Biliary Tract Cancers, Taylor & Francis.","DOI":"10.1080\/17474124.2021.1896967"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Canale, M., Monti, M., Rapposelli, I.G., Ulivi, P., Sullo, F.G., Bartolini, G., Tiberi, E., and Frassineti, G.L. (2021). Molecular Targets and Emerging Therapies for Advanced Gallbladder Cancer. Cancers, 13.","DOI":"10.3390\/cancers13225671"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Kuipers, H., de Bitter, T.J., Boer, M.T.d., Post, R.S., Nijkamp, M.W., Reuver, P.R.d., Fehrmann, R.S., and Hoogwater, F.J. (2021). Gallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications. Cancers, 13.","DOI":"10.3390\/cancers13215257"},{"key":"ref_94","first-page":"42","article-title":"Overexpression of the HER2\/neu gene: A new therapeutic possibility for patients with advanced gallbladder cancer","volume":"7","author":"Roa","year":"2014","journal-title":"Gastrointest. Cancer Res. GCR"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Jeong, H., Jeong, J.H., Kim, K.-P., Lee, S.S., Oh, D.W., Park, D.H., Song, T.J., Park, Y., Hong, S.-M., and Ryoo, B.-Y. (2021). Feasibility of HER2-targeted therapy in advanced biliary tract cancer: A prospective pilot study of trastuzumab biosimilar in combination with gemcitabine plus cisplatin. Cancers, 13.","DOI":"10.3390\/cancers13020161"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/S1470-2045(21)00336-3","article-title":"Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): A multicentre, open-label, phase 2a, multiple basket study","volume":"22","author":"Javle","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.humpath.2013.11.001","article-title":"Molecular characterization of gallbladder cancer using somatic mutation profiling","volume":"45","author":"Javle","year":"2014","journal-title":"Hum. Pathol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"S112","DOI":"10.1016\/S0959-8049(16)30326-4","article-title":"525 Safety and efficacy of pembrolizumab (MK-3475) in patients (pts) with advanced biliary tract cancer: Interim results of KEYNOTE-028","volume":"3","author":"Bang","year":"2015","journal-title":"Eur. J. Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-2776(06)90001-7","article-title":"Cancer immunosurveillance and immunoediting: The roles of immunity in suppressing tumor development and shaping tumor immunogenicity","volume":"90","author":"Smyth","year":"2006","journal-title":"Adv. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1038\/sj.bjc.6601331","article-title":"Clinical significance of immune cell infiltration within gallbladder cancer","volume":"89","author":"Nakakubo","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1038\/bjc.2013.610","article-title":"Prognostic impact of tumour-infiltrating immune cells on biliary tract cancer","volume":"109","author":"Goeppert","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.humpath.2004.03.016","article-title":"Dendritic cells, T-cell infiltration, and Grp94 expression in cholangiocellular carcinoma","volume":"35","author":"Takagi","year":"2004","journal-title":"Hum. Pathol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/jso.10321","article-title":"Prognostic value of intratumoral CD8+ T lymphocyte in extrahepatic bile duct carcinoma as essential immune response","volume":"84","author":"Oshikiri","year":"2003","journal-title":"J. Surg. Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1126\/science.1251102","article-title":"Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer","volume":"344","author":"Tran","year":"2014","journal-title":"Science"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1200\/jco.2015.33.3_suppl.285","article-title":"Tumor profiling of biliary tract carcinomas to reveal distinct molecular alterations and potential therapeutic targets","volume":"33","author":"Holcombe","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Albrecht, T., Brinkmann, F., Albrecht, M., Lonsdorf, A.S., Mehrabi, A., Hoffmann, K., Kulu, Y., Charbel, A., Vogel, M.N., and Rupp, C. (2021). Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer. Cancers, 13.","DOI":"10.3390\/cancers13071682"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1001\/jamaoncol.2020.0930","article-title":"A phase 2 multi-institutional study of nivolumab for patients with advanced refractory biliary tract cancer","volume":"6","author":"Kim","year":"2020","journal-title":"JAMA Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/6\/1413\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:34:13Z","timestamp":1760135653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/6\/1413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,10]]},"references-count":107,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["cancers14061413"],"URL":"https:\/\/doi.org\/10.3390\/cancers14061413","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,10]]}}}