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Background and Aim: In patients with hilar cholangiocarcinoma (HC), longitudinal tumor extent is important for curative resection. The purpose of this study was to evaluate the longitudinal extents of HC using transpapillary intraductal ultrasonography (IDUS) for optimal surgical planning. Methods: From July 2006 to April 2010, a total of 42 patients with borderline resectable HC were enrolled at Samsung Medical Center, a tertiary referral hospital in Seoul, Korea. All patients were evaluated using multi-detector computed tomography (MDCT), endoscopic retrograde cholangiopancreatography (ERCP) and IDUS. The new modified Bismuth Type (MBT) classification, in which the traditional Bismuth type IV stage is divided into stages IVa and IVb, was used to determine whether the tumor invaded the left lateral section. Among the subtypes of HC, the periductal infiltrative type (PDI) and intraductal papillary neoplasm of the bile duct (IPN-B) were compared. The accuracies of CT, ERCP, and IDUS were assessed through comparison with the postoperative histology findings. Results: A total of 42 patients were prospectively enrolled, and the tumor extent could be assessed histologically in 30 patients. The accuracies of CT, ERCP, and IDUS were 66.6%, 60%, and 90%, respectively. The accuracy of IDUS was 85.7% in 21 patients with PDI and 100% in nine patients with IPN-B. Conclusions: Hilar cholangiocarcinoma staging based on IDUS findings was highly accurate. We therefore highly recommend using IDUS for optimal surgical planning in patients with borderline resectable HC.

Background and Aim: This study aimed to determine the clinical characteristics of immunoglobulin G4 (IgG4)-associated sclerosing cholangitis (ISC) and provide clinical clues differentiating ISC from primary sclerosing cholangitis (PSC) or hilar cholangiocar- cinoma (CCC). Methods: Sixteen patients with ISC manifesting as hilar/intrahepatic strictures were ana- lyzed for clinical characteristics and compared with patients with PSC and hilar CCC as disease controls for histology and serum IgG4 levels. Results: Distinguished biliary imaging findings of ISC included multifocal biliary tree involvement (n = 14), concentric bile duct thickening with preserved luminal patency (n = 13), and relatively mild proximal dilatation, despite prominent bile duct thickening (n = 11). Serum IgG4 levels were elevated in 12 patients (75%), but not in any of the 25 patients with hilar CCC.Ten patients (63%) had a past or concurrent history of autoimmune pancreatitis (AIP). The significant infiltration of IgG4-positive cells was observed with endobiliary or liver biopsy in 11 of 16 patients (69%) with ISC, but not in any patients with PSC or hilar CCC. Extrabiliary organ involvement, including sialadenitis, inflammatory pseudotumor of the liver and kidney, and retroperitoneal fibrosis, was present in seven patients. Marked improvement of biliary strictures and/or extrabiliary involvement was observed in all ISC patients after steroid therapy. Conclusions: ISC should be considered in the differential diagnosis of hilar/intrahepatic biliary strictures. Past or concurrent AIP or extrabiliary organ involvement strongly sug- gests the possibility of ISC. Significant infiltration of IgG4-positive cells on endobiliary or liver biopsy specimens, and/or elevated serum IgG4 levels, highly support the diagnosis of ISC and provide the rationale for steroid therapy.

Background and Aim: A high prevalence of intrahepatic stones in some areas of East Asia has been believed to be related with Clonorchis sinensis infection. The authors conducted a hospital-based case–control study to evaluate the role of Clonorchis sinensis infection as a risk factor for the development of gallstones in Korea. Methods: The cases of 138 patients with gallstones (intrahepatic 44, gallbladder 67, and extrahepatic 27) and matched controls underwent microscopy for C. sinensis, serological tests for C. sinensis using enzyme-linked immunosorbent assay, radiological examinations, and interviews concerning the history of eating raw freshwater fish. We assessed a relationship of three types of gallstones and variables regarding C. sinensis by using univariate and multivariate statistical analyses. Results: Univariate statistical analyses showed that radiological evidence of C. sinensis and recent history of eating raw freshwater fish were related to an increased risk of intrahepatic stones (P = 0.0002 and 0.0039, respectively). According to multivariate statistical analyses, radiological evidence of C. sinensis was the only risk factor for intrahepatic stones (odds ratio = 7.835; 95% confidence interval = 1.671–36.724). Any evidence regarding C. sinensis was not related to an increased risk of either gallbladder or extrahepatic stones. Conclusion: Radiological evidence of C. sinensis was significantly associated with intrahepatic stones.

BACKGROUND The authors performed a Phase II study of combination chemotherapy with gemcitabine and cisplatin in patients with inoperable biliary tract cancer to evaluate efficacy and toxicity of this combination. In addition, the correlation between the CA 19-9 response and clinical outcome was analyzed. METHODS The eligibility criteria for this study were 1) histologically or cytologically confirmed inoperable biliary tract cancer in patients with metastatic or recurrent disease; 2) age between 18 and 70 years; 3) at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria; 4) an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2; 5) a life expectancy of at least 3 mos; and 6) adequate bone marrow, hepatic, and renal function. The patients received gemcitabine (1250 mg/m2, Days 1 and 8) and cisplatin (60 mg/m2, Day 1) every 3 weeks. Tumor response was assessed by RECIST criteria every 2 cycles of chemotherapy. Treatment was continued until progression of disease was documented. RESULTS Twenty-nine patients were enrolled. The median age of these patients was 52 years (range, 37 to 69 yrs), and the median ECOG performance status was 1. No complete response was observed, and 10 of 29 patients had partial responses. The overall response rate was 34.5% (95% confidence interval [CI], 17.9–54.3) for the intent-to-treat analysis. Stable disease was observed in 4 (13.8%) patients and progressive disease in 13 (44.8%) patients. The median follow-up time was 10.0 months (95% CI, 7.2–12.8). The median time to progression (TTP) was 3.0 months (95% CI, 2.12–3.88), and the median overall survival was 11 months (95% CI, 5.49–16.5). Although these results showed a better response rate (57.1 % vs. 27.3%) and survival (12 vs. 10 mos) in patients with a decline in CA 19-9 of at least 25%, these data were statistically not significant. In addition, there was a significant positive correlation between the increment in CA 19-9 values and tumor progression as determined with RECIST criteria (r = 0.96, P < 0.01). However, there was no definite correlation between the CA 19-9 response and the response according to RECIST criteria (P = 0.087). National Cancer Institute (NCI) common toxicity criteria (CTC) Grade 3 or 4 hematologic toxicities included neutropenia in 4 (14%) patients and anemia in 1 (3%) patient. Two of 4 patients with Grade 3 or 4 neutropenia had febrile episodes (7%) and required hospital admissions. NCI-CTC Grade 3 or 4 nonhematologic toxicity included nausea in 1 (3%) patient. There were no treatment-related deaths. CONCLUSION The combination chemotherapy with gemcitabine and cisplatin in inoperable biliary tract cancer was tolerable for most patients and showed modest response rates. The role of CA 19-9 monitoring as a surrogate biomarker in patients with BTC treated with gemcitabine chemotherapy should be further investigated. Cancer 2006. © 2006 American Cancer Society.

Background and Aim: Intraductal papillary mucinous tumor (IPMT) of the pancreas can be divided into three clinically distinct subtypes: main duct type, branch duct type and mixed type. Although it has been reported that the branch duct type IPMT is less invasive than the main duct type IPMT, we experienced a number of branch duct type IPMT having a poor prognosis. In the present study we surveyed the survival and recurrence rates according to the subtypes. Methods: Sixty-seven IPMT cases were studied to investigate clinical behavior according to the duct types. Diagnostic findings and late results of treatment were reviewed in 27 cases of the main duct type IPMT and in 35 cases of the branch duct type IPMT. Results: There was no statistically significant difference in the survival analysis between the main duct type IPMT and the branch duct type IPMT (P = 0.93). Seven patients (25.9%) died among the main duct type IPMT while six patients (17.1%) died among the branch duct type IPMT (P = 0.36). Tumor recurrence was noticed in four patients (18.1%) among 22 operated main duct type IPMT and in two patients (6.9%) among 29 operated branch duct type IPMT (P = 0.35). Conclusion: The long-term follow up result of the branch duct type IPMT is similar to that of the main duct type IPMT. Therefore, it is not safe just to monitor the branch duct type IPMT without operation. Surgery, whenever possible, is clearly the gold standard for treatment of IPMT, regardless of duct type.

Background and Aims: No information is available on the nature of the correlation between cyclooxygenase-2 (COX-2) expression and the clinicopathological features and prognosis of cholangiocarcinoma (CC). The goal of the present study was to determine the possible roles and clinical significance of COX-2 expression in CC. Methods: We investigated the immunohistochemical expression of COX-2 in 102 patients with CC with respect to clinicopathological characteristics, namely evidence of Clonorchis sinensis infection, proliferation index (PI, assessed by Ki-67 expression), apoptotic index (AI, assessed by TUNEL stain), and microvessel density (MVD, assessed by CD34 expression). Evidence of C. sinensis infection was assessed by the microscopic examination of stools for C. sinensis ova, serological testing (ELISA), and the detection of peripheral bile duct dilations by imaging studies. Results: An immunohistochemical investigation demonstrated the immunolabeling of tumor cells, mainly in the cytoplasmic and perinuclear regions, in 53 (52%) of the 102 patients with CC. No significant differences were found in terms of age, sex, tumor differentiation, involvement of the resection margin, presence of lymph nodes or liver metastases, or in pTNM stage between COX-2 positive and COX-2 negative patients. However, evidence of C. sinensis infection was more common in COX-2 positive patients (P

The purpose of the present study was to define the differential diagnostic markers of benign and malignant bile duct strictures without demonstrable mass on ultrasonography (US) or computed tomography (CT) using aspects of clinical, laboratory and imaging findings.Between February 1995 and February 2001, 24 patients who underwent surgical resection for dilations of the bile duct (peripheral and hilar) without visible mass lesion on US or CT were included in our study. Hospital records, laboratory results, findings of imaging studies and pathological findings were reviewed retrospectively.For laboratory results, levels of alkaline phosphatase (benign 163.9 +/- 145.1 vs malignant 407.25 +/- 481.7; p0.05) and CA 19-9 (benign 25.0 +/- 41.1 vs malignant 614.6 +/- 818.5; p0.05) levels were significantly elevated in the malignant group compared with that of the benign group. Findings such as thickening of the bile duct wall/= 5 mm (P0.05) on radiological examination, significant regional lymph node enlargement (1 cm, p = 0.01) on CT scan and abrupt cut-off (P0.01), and separation of bile ducts (P0.05) on cholangiogram were differential diagnostic markers between the two groups.Preoperative laboratory data such as alkaline phosphatase and CA 19-9, and imaging findings such as significant wall thickening and regional lymph node enlargement on CT, abrupt cut-off and separation of bile duct on cholangiogram are useful differential diagnostic markers for benign and malignant bile duct strictures without demonstrable mass on US or CT.

Background and Aim: Recently, it has been recognized that both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) produce important endogenous factors of human tumor progression. However, the clinicopathological and biological significance of the expression of COX-2 and iNOS in pancreatic cancer remains unclear. The objective of this study is to find the possible roles and clinical significance of COX-2 and iNOS expression in pancreatic cancer. Methods: Seventy-two pancreatic adenocarcinoma tissue specimens were obtained through surgical resection. We investigated the immunohistochemical expression of COX-2 and iNOS in respect to variable clinicopathological characteristics, proliferation activity (by Ki-67 expression), apoptosis (by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling stain), and microvessel density (by CD34 expression; angiogenesis). Results: Immunohistochemical investigations demonstrated immunolabeling of tumor cells with the primary antibodies, bovine anti-iNOS and anti-COX-2 antibodies. The COX-2 and iNOS positive rates were 41.7 and 66.7%, respectively. There was significant correlation between positive COX-2 and positive iNOS expression (P = 0.043). The proliferation index (Ki-67 labeling index) was higher in COX-2 positive specimens compared to COX-2 negative specimen (P = 0.015). The apoptotic index of positive iNOS expressions was significantly higher than negative expressions (P < 0.001). The expression of COX-2 and iNOS proteins did not correlate with age, sex, serum bilirubin, CA-19–9, location, size, American Joint Committee on Cancer stage, differentiation, distant metastasis, patient survival, or microvessel density. Conclusions: Although the pattern of positive expression was similar in both enzymes, the effect on tumor progression differed; iNOS expression may play a role in apoptosis of tumor cell, while COX-2 expression may contribute to tumor proliferation. However, COX-2 and iNOS expression is not related to prognosis in patients with pancreatic cancer. © 2002 Blackwell Publishing Asia Pty Ltd

Studies in rats have shown that brain death decreases beta-cell function and causes islet cell death during islet isolation and transplantation. Because a direct comparison of human islet cells between living and cadaveric donors has not been reported to date, we studied the effects of brain death on islet cell yield. A total of 36 pancreas specimens from 20 living donors and 16 cadaveric donors were used for analysis. Islets were isolated with a Ricordi chamber, and counted as equivalent islet numbers (EIN). Living donors were predominantly female, and cadaveric donors were mainly male. Although the cold ischemic time, pancreas distensibility and digestion time were not different, islet yield was observed to be higher in living donors compared with cadaveric donors (5800 +/- 3500 vs. 1900 +/- 2000 EIN/g pancreas). Islet isolation success rates (when defined as more than 2000 EIN/g) were 94.1% and 42.9%, respectively. Post-Ficoll islet recovery rates and purity were also better in living donors. However, islet viability and in vitro function of isolated islets showed no significant differences between the groups. These results suggested that brain death negatively affected the processes of islet isolation from the pancreas.