Novel Biomarker Panels Discriminating between Pancreatic Ductal Adenocarcinoma and Extrahepatic Bile Duct Carcinoma.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) and extrahepatic bile duct carcinoma (EBDC) are distinct entities with different clinicopathological implications. Therefore, research to differentiate between the two diseases is compulsory. In this study, four biomarkers were selected (Hippocalcin-like 1 (HPCAL1); annexin A10 (ANXA10); MUC5AC; sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1)) and focus was placed on clarifying the diagnostic performance of each biomarker and pioneering novel-combined biomarker panels to discriminate between PDAC and EBDC. PROCEDURES: An immunohistochemical microarray analysis of HPCAL1, ANXA10, MUC5AC, and ATP1B1 was conducted for surgically resected 55 PDACs and 77 EBDCs. The diagnostic performance discriminating between PDAC and EBDC was evaluated using four biomarkers and the combined biomarker panels. RESULTS: PDACs exhibited more positive expressions for HPCAL1, ANXA10, and MUC5AC, whereas EBDCs exhibited more ATP1B1-positive expressions. The PDAC panel with the best diagnostic performance was the profile of (+ in ≥ 2 among HPCAL1, ANXA10, MUC5AC)/ATP1B1-. The immunophenotype pattern of (- in ≥ 1 among HPCAL1, ANXA10, MUC5AC)/ATP1B1+ is the EBDC panel with the most excellent discriminating power. CONCLUSION: The suggested combined biomarker panels demonstrate the distinguishing diagnostic ability between PDAC and EBDC is better than previous studies. Therefore, for differentiation between PDAC and EBDC, these panels are expected to help unravel the clinicopathological enigma as promising biomarker panels in the future.

Prognostic implications of immune classification using IDO1 expression in extrahepatic bile duct carcinoma.

Indoleamine 2, 3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme that catalyzes the degradation of tryptophan to kynurenine and induces immune tolerance in tumor cells. The effects of IDO1 on extrahepatic bile duct carcinoma (EHBDC) are poorly understood. Therefore, the present study aimed to investigate the expression and prognostic significance of IDO1 in EHBDC. An immunohistochemical microarray analysis of IDO1 expression was performed for 76 surgically resected cases of EHBDC. CD8+ tumor infiltrating lymphocytes (TILs) were also investigated through a combination analysis with IDO1 expression. IDO1 was highly expressed in 25 of 76 (32.9%) cases. High expression of IDO1 was associated with decreased numbers of CD8+ TILs (P=0.008), a higher pN category (P=0.007), an advanced overall stage (P=0.001) and frequent recurrence (P=0.018). When IDO1 expression was further stratified with CD8+ TIL state, the IDO1high/CD8low subgroup was decreased in terms of overall survival (P=0.025) and disease-free survival (P=0.015) compared with IDO1high/CD8high, IDO1low/CD8high and IDO1low/CD8low subgroups. High IDO1 expression was associated with a decreased number of CD8+ TILs and associated with a poor prognosis. As IDO1 may be a new target of immunotherapy applications, IDO1/CD8+ TIL subgrouping can be a useful prognostic and predictive tool in patients with EHBDC.

Predictors of early recurrence following a curative resection in patients with a carcinoma of the ampulla of Vater.

PURPOSE: Ampulla of Vater (AoV) carcinoma has a relatively good prognosis. The 5-year recurrence rate for AoV is still around 40%-50% however, and most recurrences occur in the early period. The aim of this study was to identify predictors of an early recurrence in AoV patients following a curative resection. METHODS: The clinicopathological data for 501 consecutive patients that underwent a resection for AoV in our institute between January 2000 and December 2015 were retrospectively reviewed. The characteristics of any recurrences and early recurrence patients were analyzed accordingly. Early recurrence was defined as occurring within one year of resection. RESULTS: There were 170 diagnosed recurrences in our study population, 57.1% of whom were men, with a mean age of 60.1 years (range, 30-94 years). Almost all of the study patients underwent a pancreaticoduodenectomy, and 9% underwent minimally invasive surgery. Of the 170 recurrent cases, 107 were diagnosed with an early recurrence and had 1-, 3-, and 5-year overall survival rates of 77.7%, 18.4%, 10.5%, respectively. The factors that significantly influenced early recurrences, determined by multivariate analysis, lymphovascular invasion (LVI), lymph node ratio (LNR), and poor differentiation were found to be independent determinants of a recurrence within 1 year. CONCLUSION: An early recurrence in AoV patients is ultimately lethal even though this cancer has a good prognosis. LVI, LNR, and poor differentiation are powerful predictors of an early recurrence in AoV. Hence, intensive surveillance and new therapeutic strategies should be considered for AoV patients with these predictors following a curative resection.

Prognostic factors predicting survival rate over 10 years of patients with intrahepatic cholangiocarcinoma after hepatic resection.

PURPOSE: Hepatic resection is considered as the optimal treatment for intrahepatic cholangiocarcinoma (IHCC); however, the survival rate after resection is low and the analysis of long-term (≥10 years) survivors is rare. This study aims to analyze the clinicopathological factors affecting the long-term survival of patients with IHCC. METHODS: Between January 2003 and December 2012, a single-institution cohort of 429 patients who underwent hepatic resection for IHCC were reviewed retrospectively. Surgical results, recurrence, and survival rates were investigated, and multivariate analyses were performed to identify prognostic factors. RESULTS: The overall 1- , 3- , 5- and 10-year survival rates of patients were 76.5%, 44.1%, 33.3%, and 25.1%, respectively. Multivariate analysis showed that the serum CA 19-9 level (≥38 U/mL) (P < 0.001), lymph node (LN) metastasis (P = 0.001), and lymphovascular invasion (LVI) (P = 0.012) were independent factors associated with overall survival. In particular, CA 19-9 level and histologic type were determined to be independent factors affecting survival for more than 10 years. CONCLUSION: CA 19-9 (≥38 U/mL), LN metastasis, and LVI were identified as independent risk factors for survival after resection of IHCC. CA 19-9 (<38 U/mL) and histologic type were independent factors predicting survival for more than 10 years.

Clinicopathologic Characteristics and Optimal Surgical Treatment of Duodenal Gastrointestinal Stromal Tumor.

BACKGROUND: The clinicopathologic characteristics of duodenal gastrointestinal stromal tumor (GIST) were unclear and the optimal surgical procedure for duodenal GIST remains poorly defined. We aimed to analyze clinicopathological characteristics, survival outcomes based on the surgical procedure, and recommend optimal surgical treatment for duodenal GIST. METHODS: From July 2000 to April 2017, 118 patients with localized duodenal GIST underwent curative surgical resection at a single institution. We retrospectively reviewed the clinicopathological characteristics and survival outcomes. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 94.9 and 79.2%, respectively. On multivariate analysis, the mitotic count was a statistically significant prognostic factor for DFS. Limited resection (LR) was performed in 20 patients with GIST in the first or fourth portion of the duodenum. Both LR and pancreaticoduodenectomy (PD) were performed in 98 patients with GIST in second or third portion of the duodenum. The patients in the LR group had less late complications than in the PD group and no postoperative newly developed diabetes mellitus. The minimally invasive LR (MI-LR) group had a shorter duration of surgery and shorter length of postoperative hospital stay. CONCLUSION: LR is a feasible and effective surgical treatment for patients with small-sized and antimesenteric-sided duodenal GIST in terms of late complications and postoperative diabetic complications. MI-LR has better perioperative outcomes than open LR. Therefore, we should consider MI-LR as an optimal surgical treatment for selected patients with duodenal GIST.

Transduodenal ampullectomy for ampullary tumors - single center experience of consecutive 26 patients.

PURPOSE: Transduodenal ampullectomy (TDA) has been reported in a limited number of cases and in a small number of case series. The aim of this study was to analyze perioperative and long-term oncological outcomes of patients with ampullary tumors who underwent TDA in a single large-volume center. METHODS: Through a retrospective review of data from 2004 to 2016, we identified 26 patients who underwent TDA at Asan Medical Center. RESULTS: Eleven of 26 patients underwent TDA for T1 and carcinoma in situ (high-grade dysplasia) cancer; these patients are still alive without recurrence. A major in-hospital complication (3.8%) occurred in 1 case, but there was no case of 90-day mortality. In addition, none of the patients was diagnosed as having newly developed diabetes mellitus after TDA. No significant differences were found between open and laparoscopic-TDA in terms of operation time, painkiller use, and hospital stay. CONCLUSION: TDA is a feasible and effective surgical procedure for the treatment of selected patients with ampullary tumors. It is an alternative treatment option in cases of ampullary tumors not amenable to endoscopic papillectomy or pancreaticoduodenectomy.

Laparoscopic primary repair with omentopexy for duodenal ulcer perforation: a single institution experience of 21 cases.

PURPOSE: Despite the great advances in laparoscopic techniques, most active general surgeons do not apply laparoscopic surgery in the treatment of duodenal ulcer perforation when facing a real-life emergency. Therefore, our study was designed to evaluate the feasibility of laparoscopic surgery in duodenal ulcer perforation, and provide a step-by-step protocol with tips and recommendations for less experienced surgeons. MATERIALS AND METHODS: Between March, 2011 and May, 2012, 21 patients presenting with duodenal ulcer perforation underwent laparoscopic primary repair with omentopexy. There were no contraindications to perform laparoscopic surgery, and the choice of primary repair was decided according to the size of the perforation. The procedure for laparoscopic primary repair with omentopexy consisted of peritoneal lavage, primary suture, and omentopexy using a knot pusher. RESULTS: During the operation, no conversion to open surgery or intra-operative events occurred. The median operation time was 45.0 minutes (20~80 minutes). Median day of commencement of a soft diet was day 6 (4~17 days). After surgery, the median hospital stay was 8.0 days (5~27 days). Postoperative complications occurred in one patient, which included a minor leakage. This complication was resolved by conservative management. CONCLUSIONS: Although our study was carried out on a small number of patients at a single institution, we conclude that laparoscopic primary repair can be an effective surgical method in the treatment of duodenal ulcer perforation. We believe that the detailed explanation of our procedure will help beginners to perform laparoscopic primary repair more easily.