International Surgery Intrahepatic Biliary Intraductal Papillary Mucinous Neoplasm With Intermittent Jaundice: Case Report
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1 International Surgery Intrahepatic Biliary Intraductal Papillary Mucinous Neoplasm With Intermittent Jaundice: Case Report --Manuscript Draft-- Manuscript Number: Full Title: Article Type: Keywords: Corresponding Author: INTSURG-D R1 Intrahepatic Biliary Intraductal Papillary Mucinous Neoplasm With Intermittent Jaundice: Case Report Case Report Liver, Intraductal papillary mucinous neoplasm, jaundice, biliary tract Ahmet Bulent Dogrul, Assist. Prof. of General Surgery Hacettepe Universitesi Ankara, TURKEY Corresponding Author Secondary Information: Corresponding Author's Institution: Hacettepe Universitesi Corresponding Author's Secondary Institution: First Author: Omer Cennet, Resident in General Surgery, MD First Author Secondary Information: Order of Authors: Omer Cennet, Resident in General Surgery, MD Ahmet Bulent Dogrul, Assist. Prof. of General Surgery Mehmet Bulent Tırnaksz, Associate Prof. of General Surgery Halit Uner, Resident in Pathology, MD Aytekin Akyol, Associate Prof. in Pathology Musturay Karcaaltincaba, Prof. of Radiology Osman Abbasoglu, Prof. of General Surgery Order of Authors Secondary Information: Abstract: Intraductal papillary mucinous neoplasms (IPMNs) represent a relatively new clinical entity. IPMNs have malignant potential which exhibit a broad histological spectrum, ranging from adenoma to invasive carcinoma. Although IPMNs are commonly seen within pancreas, they may develop anywhere within the biliary ductal system and produce mucin which may cause intermittent jaundice. This report details the case of 50 year-old woman presenting with intermittent jaundice who was diagnosed as hepatic IPMN. Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation
2 Title Page Click here to download Title Page: title page ipmn.docx Tittle of the manuscript : Intrahepatic Biliary Intraductal Papillary Mucinous Neoplasm With Intermittent Jaundice: Case Report Ömer Cennet, MD, Research Assistant of General Surgery, Hacettepe University Faculty of Medicine, Department of General Surgery Ahmet Bülent Doğrul, MD, Assistant Prof. of General Surgery, Hacettepe University Faculty of Medicine, Department of General Surgery Mehmet Bülent Tırnaksız Associate Prof. of General Surgery, Hacettepe University Faculty of Medicine, Department of General Surgery Halit Üner, MD, Research Assistant of Pathology, Hacettepe University Faculty of Medicine, Department of Pathology Aytekin Akyol, MD, Associate Prof. of Pathology, Hacettepe University Faculty of Medicine, Department of Pathology Muşturay Karçaaltıncaba, MD, Prof. of Radiology, Hacettepe University Faculty of Medicine, Department of Radiology Osman Abbasoğlu, MD, Prof. of General Surgery, Hacettepe University Faculty of Medicine, Department of General Surgery Corresponding Author: Ahmet Bülent Doğrul Hacettepe Universtiy Faculty of Medicine Department of General Surgery Sıhhiye/Ankara/TÜRKİYE Phone: cell phone: Fax: adogrul@hacettepe.edu.tr There is no financial support or conflict of interest for this study. Key words: Liver, Intraductal papillary mucinous neoplasm, jaundice, biliary tract Running tittle: Intrahepatic Intraductal Papillary Mucinous Neoplasm
3 Manuscript Click here to download Manuscript: MANUSCRIPT REVISION HIGHLIGHTED.doc Introduction Hepatic cystic lesions are rare entities but increasingly found coincidentally on abdominal imaging modalities. These lesions represent challenging cluster with regard to diagnostic procedures and therapeutic options. Although majority of these lesions are benign and asymptomatic, it is important to assess carefully in terms of differentiation of benign vs neoplastic lesions. Thus it is a challenging condition surgeons encounter. Intraductal mucinous papillary neoplasms (IPMNs) are relatively new entities that are recognized with increasing frequency. Although IPMNs arise from pancreatic ductal system, recently cases of IPMNs of intrahepatic and extrahepatic biliary ductal systems have been introduced to surgical literature. IPMNs have the potential for malignancy. IPMN of pancreas is defined as mucin producing cystic neoplasms with intraductal papillary projections of tall columnar epithelium(1, 2). On the other hand, the term IPMN of intra/extrahepatic bile duct was introduced and it has a more favorable prognosis compared with conventional cholangiocarcinoma.these tumors ( IPMN of pancreas and IPMN of biliary tract) share many, but not all, clinical, histopathological and genetic features(3, 4). Biliary mucin-producing tumors has been classified into various entities(5). Biliary mucinous cystic neoplasms (MCN) are mucin producing neoplasm that the cystic tumor doesn't communicate with bile ducts and presence of ovarian like stroma is necessary to diagnose biliary MCN. On the other hand, intraductal papillary neoplasm (IPMN) in the bile duct, which is characterized by its homology with intraductal
4 papillary mucinous neoplasm of pancreas, is different from biliary MCN. It communicates with biliary tree and doesn't contain ovarian like stroma. IPMN of bile may produce large amount of viscous mucin cause intermittent abdominal pain and obstructive jaundice (6, 7). In this article we report a case of 50 years-old woman who had been diagnosed as intrahepatic IPMN and treated by left liver lobe and common bile duct resection. Case report A 50 years-old woman was admitted to our hospital complaining of vague right subcostal and epigastric pain and nausea for nearly five years. She denied weight loss. She had constipation and mild itching intermittently. She was admitted to epicentral with these complaints. She was diagnosed as hemangioma and followed up. The patient was given proton pump inhibitors and ursadeoxycholic acid therapy but showed no remarkable improvement. When she was admitted to our hospital liver function tests demonstrated mildly increased serum liver enzymes levels: ALT:83 U/L ALP: 133 U/L GGT: 120 U/L with normal serum bilirubin levels. Ca19.9 was slightly increased (51.5 U/ml). Starvation serum blood glucose was 443 mg/dl and HbA1c 10.9%. So she has been diagnosed as diabetes mellitus and triple insulin therapy was started. She had a history of appendectomy and hemoroidectomy. On radiologic evaluation, MRCP imaging revealed an enhancing mass within the left hepatic duct protruding into choledoch consistent with intraductal papillary mucinous tumor (Fig. 1).With these findings we decided to perform laparotomy. On exploration, left hepatic duct was dilated and filled with creamy like substance and it was
5 protruding into common bile duct and choledoch and also choledoch was dilated almost reaching 3 cm in diameter. But the distal portion of choledoch was normal in gross appearance. Based suspected malignancy, concomitant left hemihepatectomy and resection of extra hepatic bile ducts was performed. Frozen section performed from distal choledoch and right hepatic duct margin. The second one was positive for dysplasia on surgical margin. Then we resected main right hepatic duct and reached secondary biliary ducts inside right liver lobe parenchyma. On second frozen section surgical margin was negative. And we have performed double hepaticojejunostomy to restore biliary tract. Grossly, the tumor was fragile, creamy colored, cystic and protruding to hepatic duct. Microscopically, H&E stained sections demonstrated frond like papillary epithelium with columnar cells and contained eosinophilic cytoplasm and hyperchromatic nucleus. Histopathological subtype of neoplasm was oncocytic in morphology. The fibrous intratumoral interstitium was lacked any ovarian like stroma (Fig. 2). The patient recovered without incident and was alive and well at last follow up, 12 months post resection, with no evidence of recurrent disease. Discussion Cystic liver lesions are heterogeneous group of disorders. As a result of increasing utilization of abdominal imaging techniques especially US, evaluation and treatment of these cystic liver lesions in the differential diagnosis becomes more necessary than
6 ever. The prevalence of liver cysts thought to be in the range of 5 %. Although most of these lesions are asymptomatic and benign in course, a careful assessment is important. Accurate diagnosis in the early stage means specific treatment modality for each case. Specifically these rare entities require accurate diagnoses and treatment, as they can pose a malignant potential. IPMNs are relatively rare cystic neoplasms which are characterized by papillary projections of duct epithelium, mucin production and dilatation of ductal system, with association risk of malignant transformation(2). Although most IPMNs arise from pancreas, a subset of IPMN, biliary tract IPMN, has been introduced as unique type of biliary neoplasm. As the name implies, biliary tract IPMN share some common radiological and clinical features with pancreatic IPMN, but with its own separate identity(7, 8). IPMN of biliary tract occurs equally in both sexes, with a mean age of 58 years-old(9). IPMNs are defined histologically papillary cystic lesions of pancreatic ductal system and produce mucin. IPMNs may develop anywhere within pancreatic ductal system. On the other hand, IPMN of biliary system is analogous to IPMN of pancreas regarding histopathological and the production of large amount of mucin. IPMN of biliary tract occurs equally in both sexes, with a mean age of 58 years of age. Clinicopathological characteristics of IPMN of pancreas and biliary tract show 4 types of tumor cells: pancreaticobiliary type, intestinal type, gastric type and oncocytic type(4). In IPMN of pancreas, gastric and intestinal subtypes are more common. On the other hand, in IPMN of biliary tract, pancreaticobiliary subtype is seen commonly.
7 Our case revealed oncocytic subtype which represents the least common type(10). Table 1 summarizes and comparises some features of pancreatic and biliary tract IPMN. Preoperative assessment of cystic neoplasm is important as IPMN of biliary tract has the potential to spread along bile duct mucosa unlike MCN which is usually a closed cyst (7). So IPMN of bile should be widely resected. In our case, the frozen section revealed positive tumor margin so wider resection is applied to achieve negative tumor margin. An excellent prognosis with 5 years survival rate higher than 80% have been reported after resection of IPMN of biliary tract with negative margins. IPMN of biliary biliary tract shows excellent postoperative prognosis when it is compared with conventional cholangiocarcinoma. 5 years survival rates of patients with non-invasive IPMN of biliary tract, invasive IPMN of biliary tract, cholangiocarcinoma and IPMN of pancreas are 100%, 53%, 0% and 58% respectively(4). 40%-80% of resected IPMNs of biliary tract contain invasive components. Frequency of malignancy is higher in patients with IPMN of biliary tract than in those with IPMN of pancreas(11). Majority of cystic neoplasms are asymptomatic. Vague abdominal pain or discomfort is the most common symptom. Rarely, IPMN of biliary tract can be complicated as fistula, even case of bronchobiliary fistula is reported(12). IPMN of biliary tract produces mucin which may cause intermittent biliary obstruction and other clinical symptoms like pain, fever, jaundice. Intermittent symptoms, as in our patient, are characteristic for IPMN of biliary tract and are unusual for other bile duct tumors. The
8 tumor was symptomatic in our patient, as she complained intermittent upper abdominal pain and itching. Most of biliary tract IPMNs are associated with biliary stones, especially proximal biliary stones. Surgery is the main treatment option for IPMN of biliary tract. Hepatectomy is suggested for tumors located in intrahepatic bile duct, but pancreticoduedonectomy and bile duct resections are preferred for tumors located in the extrahepatic bile duct(8). Diagnosis needs multimodality assessment. Abdominal USG is usually the first tool for suspected liver diseases. USG may show polypoid intraluminal mass. On USG studies mucin is usually anechoic, as seen in bile. Also CT cannot detect mucin, because CT attenuation of mucin same as that of water(13). MRI/MRCP is non-invasive examination that has capability to detect biliary and vascular extensions. However, it is difficult to distinguish bile and mucin as both of them have same signal intensity(6). On the other hand, ERCP depicts mucin as defective filling with contrast medium. This mismatch between ERCP and MRCP states mucin exists in the bile duct. In conclusion, IPMN of biliary tract is a rare disorder which may present with intermittent jaundice and preoperative assessment is very important as it has potential to spread along bile duct in terms of achievement of negative margins.
9 References 1. Kappeli RM, Muller SA, Hummel B, Kruse C, Muller P, Fornaro J, et al. IPMN: surgical treatment. Langenbecks Arch Surg. 2013;398(8): doi: /s PubMed PMID: Sugiyama M, Suzuki Y, Abe N, Mori T, Atomi Y. Management of intraductal papillary mucinous neoplasm of the pancreas. J Gastroenterol. 2008;43(3): doi: /s PubMed PMID: Minagawa N, Sato N, Mori Y, Tamura T, Higure A, Yamaguchi K. A comparison between intraductal papillary neoplasms of the biliary tract (BT-IPMNs) and intraductal papillary mucinous neoplasms of the pancreas (P-IPMNs) reveals distinct clinical manifestations and outcomes. Eur J Surg Oncol. 2013;39(6): doi: /j.ejso PubMed PMID: Nakanuma Y. A novel approach to biliary tract pathology based on similarities to pancreatic counterparts: is the biliary tract an incomplete pancreas? Pathol Int. 2010;60(6): doi: /j x. PubMed PMID: Zen Y, Pedica F, Patcha VR, Capelli P, Zamboni G, Casaril A, et al. Mucinous cystic neoplasms of the liver: a clinicopathological study and comparison with intraductal papillary neoplasms of the bile duct. Mod Pathol. 2011;24(8): doi: /modpathol PubMed PMID: Ohtsuka M, Shimizu H, Kato A, Yoshitomi H, Furukawa K, Tsuyuguchi T, et al. Intraductal papillary neoplasms of the bile duct. Int J Hepatol. 2014;2014: doi: /2014/ PubMed PMID: ; PubMed Central PMCID: PMC Takanami K, Yamada T, Tsuda M, Takase K, Ishida K, Nakamura Y, et al. Intraductal papillary mucininous neoplasm of the bile ducts: multimodality assessment with pathologic correlation. Abdom Imaging. 2011;36(4): doi: /s x. PubMed PMID: Wang X, Cai YQ, Chen YH, Liu XB. Biliary tract intraductal papillary mucinous neoplasm: report of 19 cases. World J Gastroenterol. 2015;21(14): doi: /wjg.v21.i PubMed PMID: ; PubMed Central PMCID: PMC Soares KC, Arnaoutakis DJ, Kamel I, Anders R, Adams RB, Bauer TW, et al. Cystic neoplasms of the liver: biliary cystadenoma and cystadenocarcinoma. J Am Coll Surg. 2014;218(1): doi: /j.jamcollsurg PubMed PMID: ; PubMed Central PMCID: PMC Liszka L, Pajak J, Zielinska-Pajak E, Krzych L, Golka D, Mrowiec S, et al. Intraductal oncocytic papillary neoplasms of the pancreas and bile ducts: a description of five new cases and review based on a systematic survey of the literature. J Hepatobiliary Pancreat Sci. 2010;17(3): doi: /s PubMed PMID: Rocha FG, Lee H, Katabi N, DeMatteo RP, Fong Y, D'Angelica MI, et al. Intraductal papillary neoplasm of the bile duct: a biliary equivalent to intraductal papillary mucinous neoplasm of the pancreas? Hepatology. 2012;56(4): doi: /hep PubMed PMID: Mo A, Brat G, Spolverato G, Pawlik TM. Intraductal papillary mucinous neoplasm of the liver: GI image. J Gastrointest Surg. 2015;19(4): doi: /s PubMed PMID:
10 13. Oki H, Hayashida Y, Namimoto T, Aoki T, Korogi Y, Yamashita Y. Usefulness of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance cholangiography for detecting mucin retention in bile ducts: a rare intraductal papillary mucinous neoplasm of the bile duct. Jpn J Radiol. 2011;29(8): doi: /s PubMed PMID:
11 Figure-1 Click here to download Figure: Figure 1.jpg
12 Figure-2 Click here to download Figure: Figure 2.jpg
13 Figure legend Click here to download Figure: figure legends-ipmn.docx Figure 1: A 50-year old woman with intraductal papillary mucinous tumor. MRCP image (A) shows a mass (arrows) originating from left hepatic duct with extension to choleduct causing biliary dilatation of left liver lobe. Axial T2 (B) and postcontrast T1 (C) weighted images show a papillary tumor (arrow) filling the biliary system and enhancement consistent with a solid lesion. Figure 2: Gross and microscopic findings of resected specimen. A: Macroscopic evaluation of the tumor shows papillary mass protruding to liver and main hepatic duct. B and C: Microscopic finding of specimen. The micrographs at lower (20x) and higher (100x) magnification show papillary structures composed of cuboidal cells with eosinophilic cytoplasm, and hyperchromatic nucleoli (hemotoxylin-eosin).
14 Table Click here to download Table: table IS.docx Table 1:Demographics and clinicopathological features and comparison of pancreatic IPMN and cases of biliary tract IPMN (5,8). IPMN of Pancreas IPMN of Biliary tract cases In Our Case Sex Male>female(2:1) Equal Female Age 6-7th decade 5-6th decade 50 years old Symptoms Mostly asymptomatic Abdominal discomfort, jaundice Intermittent abdominal pain and jaundice Location Head of pancreas(60%) Intrahepatic and hilum(68%) Intrahepatic Pathological subtype Main duct:intestinal Branch duct:gastric type Pancreticobiliary (45%) Oncocytic Communication with ductal System Present (absent in Mucinous cystic neoplasm) Present Present
15 Cover Letter Click here to download Cover Letter: Cover Letter ipmn.docx
16 Copyright Statement Click here to download Copyright Statement: _ jpg
17 Copyright Statement Click here to download Copyright Statement: _ jpg
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