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Management of Neuroendocrine Tumors of the Extrahepatic Bile Duct: Case Report and Review of the Literature

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Management of Neuroendocrine Tumors of the Extrahepatic Bile Duct: Case Report and Review of the Literature www.jcimcr.org Journal of Clinical Images and Medical Case Reports ISSN 2766-7820 Case Report Open Access, Volume 2 Management of neuroendocrine tumors of the extrahepatic bile duct: Case report and review of the literature Luca Portigliotti1*; Fabio Maroso1; Andrea Amabile1; Filadelfio Massimiliano Nicolosi1; Fabio Colli1; Fabio Frosio1; Oscar Soresini1; Nicola de’Angelis2; Renzo Luciano Boldorini3; Raffaele Romito1 1General Surgery Department, A.O.U. “Maggiore della Carità” Hospital, Novara, Italy. 2Minimally Invasive and Robotic Digestive Surgery Unit, Regional General Hospital F. Miulli, Acquaviva delle Fonti (Bari), Italy and University Paris Est - UPEC, France. 3Department of Health Science, School of Medicine, University of Eastern Piedmont “Amedeo Avogadro”. Pathology Unit, “Mag- giore della Carità” Hospital. Abstract *Corresponding Authors: Luca Portigliotti General Surgery Department, A.O.U. “Maggiore Neuroendocrine tumors of the extrahepatic bile duct (EBNETs) della Carità” Hospital, Corso Mazzini 18, 28100, are exceedingly rare neoplasms, whose diagnostic and therapeutic Novara, Italy. process can be challenging. We present the case of a 58-year-old EBNET patient successfully treated at our Institution, followed by a Tel +393474474903, Fax: +39 03213733338; systematic review of the literature on the surgical management of Email: [email protected] these rare tumors. Received: July 01, 2021 Keywords: neuroendocrine tumor; biliary neoplasm; carcinoid; bili- Accepted: Aug 09, 2021 ary tract obstruction. Published: Aug 12, 2021 Archived: www.jcimcr.org Copyright: © Portigliotti L (2021). Case presentation NETs are non-functioning neoplasms, these markers may not be produced, secreted and therefore detected. Computed Tomog- Neuroendocrine tumors (NETs) represent a rare, heteroge- raphy (CT) scan and Magnetic Resonance Cholangiopancreatog- neous group of neoplasms with a distinct functional and bio- raphy (MRCP) are the recommended imaging exams to stage EB- logical behavior depending on their anatomic location, tumor NETs and to plan the operative strategy. However, no specific CT size and clinical symptoms [1]. More than 50% of NETs arises in or MRCP findings allowing distinguishing between EBNETs and the gastrointestinal tract, being the appendix, the small bowel other biliary neoplasms have been described so far. More sen- and the rectum the most common locations [2]. NETs located sitive and specific radiological techniques are available. Above within the extrahepatic bile duct (EBNETs) are amongst the rar- all, positron emission tomography (PET) with radioactively la- est primary sites, accounting for 0.2%-2% of all such malignan- beled somatostatin analogues (like Ga68 DOTA-TATE, DOTATOC cies [3,4] . and DOTANOC) can be useful in case of clinical suspicion of EB- Obtaining a preoperative diagnosis of these tumors is diffi- NETs, in both localized and metastatic settings, with a reported cult. Indeed, the majority of cases reported in the literature are sensitivity and specificity of 81% and 90%, respectively [5]. diagnosed only after surgery, on the final pathological examina- The accuracy of endobiliary brush cytology for the preoperative tion of the surgical specimen. Plasmatic Chromogranin A (CgA) diagnosis of biliary disease has been widely discussed [6], but and urinary 5-hidroxyindole acetic acid (5-HIAA) are slightly its sensitivity for biliary tree tumors is limited. This particularly specific markers that can be used in combination to hypothesize applies to EBNETs, considering the submucosal localization of the presence of NETs. Nevertheless, since, the majority of EB- the lesion [7,8]. Finally, fine needle aspiration cytology (FNAC) Citation:Portigliotti L, Maroso F, Amabile A, Nicolosi FM, Colli F, et al. Management of neuroendocrine tumors of the extra- hepatic bile duct: Case report and review of the literature. J Clin Images Med Case Rep. 2021; 2(4): 1263. and biopsy (FNAB) could be an helpful diagnostic tools[8] , how- fields, and Ki-67 labeling index was 5%. A neural invasion, but ever in most cases a surgical exploration is still mandatory, in no vascular invasion, was detected. Lymph nodes examination the suspicion of cholangiocarcinoma. did not detect any metastases. From a surgical standpoint, the resection of the extrahepatic Thus no adjuvant therapy was proposed by our Board. 6- and bile ducts with portal lymphadenectomy and Roux-en-Y hepati- 12-month CT scans showed no evidence of local recurrence or cojejunostomy provides radical tumor clearance in most cases. distant metastases. At the 16-month follow-up, the patient is in In very selected patients a more extensive resection may be re- good health, completely asymptomatic and with normal blood quired, with various degrees of hepatic or pancreatic resection chemistry tests. according to the tumor site. Review of the literature In this paper, we present the case of a 58-year-old patient with an EBNET treated at our Institution. Moreover, we per- We aimed at conducting a comprehensive systematic review formed a systematic review of the literature on the surgical and collecting data of all ENNETs cases which have been report- management of these rare neoplasms. ed in the literature. Case report Materials and methods A 58-year-old man with history of type 2 diabetes and The review of the literature was conducted through a sys- polycythaemia vera presented to our Hospital complaining of tematic approach, following the PRISMA statements checklist epigastric pain. Symptoms had started one month earlier. An (Figure 2). The following online databases were consulted: Esophago-Gastro-Duodenoscopy (EGDS) showed mild gastritis MEDLINE (through PubMed), EMBASE, Google Scholar, Co- (negative for Helicobacter pylori). Abdominal US demonstrated chrane and ProQuest Dissertations, and Thesis Database. the presence of a mass (28 x 28 mm) located within the extra- In order to increase the accuracy in identifying relevant ar- hepatic bile duct, causing diffuse dilatation of the intrahepatic ticles, a research equation was formulated for each database, biliary system. Despite the degree of ductal dilation, liver func- using specific keywords and/or MeSH terms (i.e., “neuroendo- tion tests and serum markers of cholestasis were within the crine tumor”, “Carcinoid”, “Bile Duct”). In addition, bibliogra- normal ranges. The levels of alpha-fetoprotein, CA 19-9 and phy from both eligible studies and relevant review articles (not CEA were unremarkable. Endoscopic Ultrasound (EUS) showed included in the systematic review) was crosschecked in order a 28 mm hyperechoic lesion, with arterial and venous contrast to identify additional reports. A grey literature search was also enhancement after injection of SonoVue® contrast-agent; EUS performed using the OpenGrey database. confirmed the dilation of both right and left hepatic ducts, en- compassing the cystic and the common bile duct, and also de- No time restrictions were applied. Relevant articles were tected the presence of two reactive nodes within the hepato- defined as those written in English and reporting at least the duodenal ligament. A Fine Needle Biopsy (FNB) was performed following clinical, radiological and pathological patients’ charac- and pathological analysis reported signet-ring cells adenocarci- teristics: age, gender, tumor location and size, symptoms, pres- noma. Since the patient did not present with jaundice, Endo- ence of metastases, time of diagnosis, treatment, immunohis- scopic Retrograde Cholangiopancreatography (ERCP) was not tochemistry, pathology, and follow-up data. performed. Abdominal CT-scan and MRCP revealed a mass of The studies eligible for inclusion, e.g., case report, case se- 28 x 24 mm in the common bile duct, without any suspicious ries have been all those answering to specific research question nodes nor distant metastases. “How to manage successfully EBNETs patients?” The case was submitted to our Institutional Board and the Reports of tumors involving intra-hepatic biliary ducts, liver patient was considerate candidate for exploratory surgery, fol- parenchyma, gallbladder, and Vater region were excluded. Re- lowed by a bile duct resection, eventually associated with ex- ports of Neuroendocrine Carcinomas (NEC) and mixed tumors, tended pancreatic or liver resection (established through intra- including both NET and adenocarcinoma features, were also operative frozen section assessment of surgical margins). excluded. Two reviewers (LP and FM) independently retrieved, At the laparotomic abdominal exploration, there was no screened and analyzed the selected studies. Conflicts between evidence of carcinomatosis or distant metastases. The extrahe- the two independent reviewers were solved with discussion patic bile duct and the gallbladder were resected, and a radi- with a third one (RR). A quality assessment and risk of bias of cal lymphadenectomy of the liver pedicle was performed. The every study selected has been performed using tool described proximal and distal common bile duct margins were negative by Murad et al. for malignancy on frozen section analysis, so a Roux-en-Y he- Results paticojejunostomy was finally performed. The postoperative course was unremarkable, and the patient was discharged on Studied population the post-operative day 6. After removal of duplicates, the literature search identified The final pathological analysis (Figure 1) demonstrated a G2 a total of 763 articles. Of these, 619 were excluded upon title EBNET of 35 x 30 x 25
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