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Objective: The aim of this study was to verify the prognostic impact of the tumor exposure at the liver transection margin (LTM) in left-sided perihilar cholangiocarcinoma and the impact of middle hepatic vein (MHV) resection on this exposure. Background: In perihilar cholangiocarcinoma, tumors are unexpectedly exposed at the LTM during left hemihepatectomy (LH). Methods: Patients who underwent LH for perihilar cholangiocarcinoma during 2002 to 2018 were retrospectively evaluated. LH was classified into conventional and extended types, which preserved and resected the MHVs, respectively. Positive LTM was defined as the involvement of invasive carcinoma at the liver transection plane and/or the adjacent Glissonean pedicle exposed. The clinicopathologic features and survival outcomes were compared between procedures. Results: Among 236 patients, conventional and extended LHs were performed in 198 and 38 patients, respectively. The LTM was positive in 31 (13%) patients, with an incidence of 14% versus 8% (P = 0.432) and 24% versus 0% in advanced tumors (P = 0.011). Tumor size ≥ 18 mm (P = 0.041), portal vein invasion (P = 0.009), and conventional LH (P = 0.028) independently predicted positive LTM. In patients with negative LTM, the survival was comparable between the two groups: 60.4% versus 59.2% at 3 years (P = 0.206), which surpassed 17.7% for those with positive LTM in the conventional group (P < 0.001). Multivariable analysis demonstrated that LTM status was an independent prognostic factor (P = 0.009) along with ductal margin status (P = 0.030). Conclusions: The LTM status is an important prognostic factor in perihilar cholangiocarcinoma. Extended LH reduced the risk of tumor exposure at the LTM with a subsequent improvement in the survival, particularly in advanced tumors. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to visualize the postoperative clinical course using the comprehensive complication index (CCI) and to propose an early alarming sign for subsequent serious outcomes in perihilar cholangiocarcinoma. Background: Surgery for this disease carries a high risk of morbidity and mortality. The developmental course of the overall morbidity burden and its clinical utility are unknown. Methods: Patients who underwent major hepatectomy for perihilar cholan-giocarcinoma between 2010 and 2019 were reviewed retrospectively. All postoperative complications were evaluated according to the Clavien-Dindo classification (CDC), and the CCI was calculated on a daily basis until postoperative day 14 to construct an accumulating graph as a trajectory. Group-based trajectory modeling was conducted to categorize the trajectory into clinically distinct patterns and the predictive power of early CCI for a subsequent serious course was assessed. Results: A total of 4230 complications occurred in the 484 study patients (CDC grade I, n = 27; II, n = 132; IlIa, n = 290; IIIb, n = 4; IVa, n = 21; IVb, n = 1; and V, n = 9). The trajectory was categorized into 3 patterns: mild (n = 209), moderate (n = 235), and severe (n = 40) morbidity courses. The 90-day mortality rate significantly differed among the courses: 0%, 0.9%, and 17.5%, respectively (P<0.001). The cutoff values of the CCI on postoperative days 1, 4, and 7 for predicting a severe morbidity course were 15.0, 28.5, and 40.6 with areas under the curves of 0.780, 0.924, and 0.984, respectively. Conclusions: The CCI could depict the chronological increase in the overall morbidity burden, categorized into 3 patterns. Early CCI potentially predicted sequential progression to serious outcomes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of complications on long-term survival in patients with perihilar cholangiocarcinoma. Background: Surgical resection for perihilar cholangiocarcinoma is vulnerable to postoperative complications. The prognostic impact of complications in patients with this disease is unknown. Methods: The medical records of patients who underwent curative-intent hepatectomy for perihilar cholangiocarcinoma between 2010 and 2017 were reviewed retrospectively. The comprehensive complication index (CCI) was calculated based on all postoperative complications, which were graded by the Clavien-Dindo classification (CDC). Patients were divided into high and low CCI groups by the median score, and survival was compared between the 2 groups. Results: Excluding 8 patients who died in hospital, 369 patients were analyzed. The CDC grade was I in 20 (5.4%), II in 108 (29.3%), III in 224 (60.7%), and IV in 17 (4.6%) patients. The CCI increased with increasing CDC grade; the median was 42.9 (range, 15.0–98.9). Overall survival differed significantly between the high (n = 187) and low (n = 182) CCI groups (41.2% vs 47.9% at 5 years; P = 0.041). However, multivariable analyses demonstrated that traditional clinicopathological factors were independent predictors of survival and that the dichotomized CCI was not. In addition, the CCI score as a continuous variable was not an independent prognostic factor for overall survival in the multivariable analyses (hazard ratio per 1 CCI score: 1.00, 95% confidence interval: 0.99–1.01, P = 0.775). Conclusions: Cumulative postoperative complications after resection of perihilar cholangiocarcinoma only moderately deteriorate long-term survival, and should not be an argument to deny surgery in this high-risk population. [ABSTRACT FROM AUTHOR]

Objective: Given the frequent adverse events with multidrug chemotherapy, not only the survival benefit but also the feasibility of using neoadjuvant chemotherapy to treat pancreatic cancer need to be clarified. Summary of Background Data: Although the development of multidrug chemotherapy regimens has improved the survival outcomes of patients with unresectable pancreatic cancer, the benefits of these treatments in the neo-adjuvant setting remain controversial. Methods: Patients with borderline-resectable pancreatic cancer were enrolled and randomly assigned to receive neoadjuvant chemotherapy with either FOLFIRINOX or gemcitabine with nab-paclitaxel (GEM/nab-PTX). After the completion of chemotherapy, patients underwent surgical resection when feasible. This study (NUPAT-01) was a randomized phase II trial, and the primary endpoint was the R0 resection rate. Results: Fifty-one patients were enrolled in this study [FOLFIRINOX (n = 26) and GEM/nab-PTX (n = 25)]. A total of 84.3% (n = 43/51) of the patients eventually underwent surgery, and R0 resection was achieved in 67.4% (n = 33/ 51) of the patients. Adverse events (grade >3) due to neoadjuvant treatment were observed in 45.1% of the patients (n = 23/51), and major surgical complications occurred in 30.0% (n = 13/43), with no mortality noted. The intention-to-treat analysis showed that the 3-year overall survival rate was 54.7%, with a median survival time of 39.4 months, and a significant difference in overall survival was not observed between the FOLFIRINOX and GEM/nab-PTX groups. Conclusions: These results indicate that neoadjuvant chemotherapy with FOLFIRINOX or GEM/nab-PTX is feasible and well tolerated, achieving an R0 resection rate of 67.4%. The survival of patients was even found to be favorable in the intention-to-treat analysis. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objective: To evaluate the efficacy and safety of combined vascular resection (VR) in advanced perihilar cholangiocarcinoma (PHC). Summary of Background Data: Hepatectomy combined with portal vein resection (PVR) and/or hepatic artery resection (HAR) is technically demanding but an option only for tumor eradication against PHC involving the hilar hepatic inflow vessels; however, its efficacy and safety have not been well evaluated. Methods: Patients diagnosed with PHC during 2001–2018 were included. Patients who underwent resection were divided according to combined VR. Patients undergoing VR were subdivided according to type of VR. Postoperative outcomes and OS were compared between patient groups. Results: Among the 1055 consecutive patients, 787 (75%) underwent resection (without VR: n = 484, PVR: n = 157, HAR: n = 146). The incidences of postoperative complications and mortality were 49% (without VR vs with VR, 48% vs 50%; P = 0.715) and 2.1% (without VR vs with VR, 1.2% vs 3.6%; P = 0.040), respectively. The OS of patients who underwent resection with VR (median, 30 months) was shorter than that of those who underwent resection without VR (median, 61 months; P < 0.0001); however, it was longer than that of those who did not undergo resection (median, 10 months; P < 0.0001). OS was not significantly different between those who underwent PVR and those who underwent HAR (median, 29 months vs 34 months; P = 0.517). Conclusion: VR salvages a large number of patients from having locally advanced PHC that is otherwise unresectable and is recommended if the hilar hepatic inflow vessels are reconstructable, providing acceptable surgical outcomes and substantial survival benefits. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objective: To investigate radial margin (RM) status in resected perihilar cholangiocarcinoma (PHCC) and to evaluate the incidence of positive RM and its effect on survival. Background: Although numerous studies have reported on ductal margin (DM) status in resected PHCC, no studies have addressed RM status. Methods: Patients who underwent hepatectomy for PHCC between 2001 and 2014 were retrospectively reviewed. After formalin fixation, resected specimens were serially sectioned at 5-mm intervals. All serial sections were color-copied, and RMs and DMs were identified and indicated on the color copies. Results: Among 478 patients, 85 (17.8%) had positive surgical margins (R1 resection); of the 85 patients, 37 had positive RM alone, 33 had positive DM alone, and the remaining 15 had both positive RM and positive DM. Overall, 52 (61.2%) patients had positive RM. The sites of positive RM included the liver transection plane (n = 20) and the dissection plane in the hepatoduodenal ligament (n = 32). RM positivity on the liver transection plane was higher in left hepatectomy than in other hepatectomies (9.2% vs 1.9%, P < 0.001). RM positivity in the hepatoduodenal ligament was higher in left-sided hepatectomy than in right-sided hepatectomy (8.7% vs 3.6%, P = 0.031). The survival of the patients with positive RM was poorer than that of R0 patients (MST 2.1 vs 4.9 yrs, P < 0.001) and was similar to that of patients with positive DM. Multivariate analysis identified positive RM as one of the independent prognostic factors. Conclusions: Positive RM was the most common cause of R1 resection of PHCC and had similarly negative effects on survival as positive DM. Meticulous handling of the resected specimen is important to accurately evaluate RM status together with DM status. [ABSTRACT FROM AUTHOR]

Objective: To reappraise whether preoperative autologous blood donation reduces post-hepatectomy liver failure (PHLF) in major hepatectomy for perihilar malignancy., Summary Background Data: Autologous blood storage and transfusion are carried out to reduce the use of allogeneic blood transfusion during hepatectomy and prevent postoperative complications. However, the clinical benefit in major hepatectomy has been controversial., Methods: This randomized clinical trial included patients who underwent major hepatectomy with extrahepatic bile duct resection for perihilar malignancy. Eligible patients were randomly assigned (1:1) to undergo surgery with or without the use of autologous blood transfusion. The primary outcome was the incidence of clinically relevant PHLF (grade B/C according to the International Study Group of Liver Surgery definition)., Results: Between February 6, 2019, and May 12, 2023, 138 consecutive patients were enrolled in the study (blood storage group n=68, non-storage group n=70). Twenty-five patients who did not undergo resection were excluded; the remaining 113 patients were investigated as the full analysis set (blood storage group n=60, non-storage group n=53). Surgical procedures, operative time, and blood loss were not significantly different between the two groups. The incidence of PHLF was comparable (blood storage group n=10 [17%], non-storage group n=10 [19%]; P=0.760). There were also no between-group differences in other postoperative outcomes, including the incidence of Clavien-Dindo Grade Ⅲ or higher (72% vs. 72%, P=0.997) and median duration of hospital stay (25 vs. 29 d, P=0.277)., Conclusions: Autologous blood storage did not contribute to reducing the incidence of PHLF in patients undergoing major hepatectomy., Competing Interests: Disclosure of potential conflicts of interest: The authors declare no potential conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine the goal of intraoperative blood loss in hepatectomy for perihilar cholangiocarcinoma., Background: Although massive bleeding can negatively affect the postoperative course, the target value of intraoperative bleeding to reduce its adverse impact is unknown., Methods: Patients who underwent major hepatectomy for perihilar cholangiocarcinoma between 2010 and 2019 were included. Intraoperative blood loss was adjusted for body weight [adjusted blood loss (aBL)], and the overall postoperative complications were evaluated by the comprehensive complication index (CCI). The impact of aBL on CCI was assessed by the restricted cubic spline regression., Results: A total of 425 patients were included. The median aBL was 17.8 (interquartile range, 11.8-26.3) mL/kg, and the CCI was 40.6 (33.7-49.5). Sixty-three (14.8%) patients had an aBL<10 mL/kg, nearly half (45.4%) of the patients were in the range of 10 ≤aBL<20 mL/kg, and 37 (8.7%) patients had an aBL >40 mL/kg. The spline regression analysis showed a nonlinear incremental association between aBL and CCI; CCI remained flat with an aBL under 10 mL/kg; increased significantly with an aBL ranging from 10 to 20 mL/kg; grew gradually with an aBL over 20 mL/kg. These inflection points of ~10 and 20 mL/kg were almost consistent with the cutoff values identified by the recursive partitioning technique. After adjusting for other risk factors for the postoperative course, the spline regression identified a similar model., Conclusions: aBL had a nonlinear aggravating effect on CCI after hepatectomy for perihilar cholangiocarcinoma. The primary goal of aBL should be <10 mL/kg to minimize CCI., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities., Background: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures., Methods: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient., Results: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months., Conclusion: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Competing Interests: The authors report no conflicts of interest.

Objective: To evaluate the optimal duration of antimicrobial prophylaxis in patients undergoing "complicated"' major hepatectomy with extrahepatic bile duct resection., Background: To date, 4 randomized controlled trials (RCTs) have assessed the duration of antimicrobial prophylaxis after hepatectomy. However, all of these previous studies involved only "simple" hepatectomy without extrahepatic bile duct resection., Methods: Patients with suspected hilar obstruction scheduled to undergo complicated hepatectomy after biliary drainage were randomized to 2-day (antibiotic treatment on days 1 and 2) or 4-day (on days 1 to 4) groups. Antibiotics were selected based on preoperative bile culture. The primary endpoint was the incidence of postoperative infectious complications., Results: In total, 86 patients were included (43 patients in each arm) without between-group differences in baseline characteristics. Bile culture positivity was similar between the 2 groups. No significant between-group differences were observed in surgical variables. The incidence of any infectious complications was similar between the 2 groups (30.2% in the 2-day group and 32.6% in the 4-day group). The positive rate of systemic inflammatory response syndrome and the incidence of additional antibiotic use were almost identical between the 2 groups. According to Clavien-Dindo classification, grade 3a or higher complications occurred in 23 patients (53.5%) in the 2-day group and 29 patients (67.4%) in the 4-day group (P = 0.186). Postoperative hospital stay was not different between the 2 groups., Conclusions: Two-day administration of antimicrobial prophylaxis is sufficient for patients undergoing hepatectomy with extrahepatic bile duct resection [Registration number: ID 000009800 (University Hospital Medical Information Network, http://www.umin.ac.jp)].

Objectives: The aim of this study was to compare the perioperative clinical characteristics between patients with distal cholangiocarcinoma (DCC) and pancreatic head carcinoma (PHC) with biliary obstruction., Methods: This study included patients who underwent pancreatoduodenectomy and were diagnosed with DCC (n = 85) or PHC (n = 90) by final pathological examination. Perioperative clinical characteristics were compared for patients with DCC versus PHC with biliary obstruction., Results: Median coronal thickness of the pancreatic neck was significantly greater, whereas the main pancreatic duct diameter was significantly smaller in patients with DCC than patients with PHC. Most patients with DCC (95%) had a soft pancreas, whereas only 29% of patients with PHC had. The incidence rates of overall morbidity, infectious complications, and pancreatic fistula were significantly higher in patients with DCC than those in patients with PHC. Eleven DCC patients (12%) were preoperatively misdiagnosed with PHC. Among them, intraductal ultrasonography of the bile duct was performed in 7 patients, and the presence of PHC was suspected in 3 of these patients because intraductal ultrasonography detected a small intrapancreatic mass., Conclusions: This study clearly showed different perioperative characteristics between patients with DCC and PHC. It is not uncommon to misdiagnose PHC as DCC. Intraductal ultrasonography may be helpful in differentiating DCC and PHC.

Objective: The aim of the study was to evaluate whether carcinoma in situ (CIS) residue at the ductal stump affects the survival of patients undergoing resection for extrahepatic cholangiocarcinoma., Background: Positive ductal margin with CIS has been treated as a tumor-free margin from a prognostic viewpoint because several studies have reported that residual CIS foci at the ductal stump do not affect survival after resection., Methods: Patients who underwent resection for extrahepatic cholangiocarcinoma were retrospectively reviewed. The surgical margin status was histologically divided into negative (R0), positive with CIS (R1cis), and positive with invasive cancer (R1inv). The survival and incidence of local recurrence were compared among the groups., Results: Of 684 consecutive resected patients, 172 patients with early-stage (pTis-2N0M0) cholangiocarcinoma (perihilar, n = 144; distal, n = 28) were analyzed. The cumulative incidence of local recurrence in R1cis patients was higher than R0 patients (32.8% vs 4.4% at 5 years, P < 0.001) and lower than R1inv patients (50.0% at 2 years, P = 0.012). The disease-specific survival for R1cis patients was worse than for R0 patients (35.1% vs 78.7% at 5 years, P = 0.005) and better than for R1inv patients (40.0% at 2 years, P = 0.002). The uni- and multivariate analyses identified the surgical margin status as an independent prognostic factor (R1cis vs R0, relative risk 2.39, P = 0.026; R1inv vs R0, RR 10.28, P < 0.001)., Conclusion: R1cis increases the incidence of local recurrence and shortens postoperative survival in patients with early-stage cholangiocarcinoma, although this prognostic effect was less severe compared with R1inv. R1cis should be avoided as much as possible in surgery for early-stage cancer, although it may be allowed in advanced tumors.

Objective: To review our experiences with surgery for recurrent biliary tract cancer (BTC)., Background: Few studies have reported on surgical procedures for recurrent BTC; therefore, it is unclear whether this surgery has survival benefit., Methods: Between 1991 and 2010, 606 patients had recurrences after resection of BTC (gallbladder cancer, n = 135; cholangiocarcinoma, n = 471); 74 patients underwent resection for recurrence, whereas the remaining 532 did not. The medical records were retrospectively reviewed., Results: Compared with the 532 patients without surgery for recurrence, the 74 patients with surgery had less advanced cancer, and their time to recurrence was significantly longer (1.4 vs 0.8 years; P < 0.001). A total of 89 surgical procedures for recurrence were performed in the 74 patients (1 time in 63 and ≥2 times in 11). Survival after recurrence was significantly better in the 74 patients with surgery than in the 532 without (32% vs 3% at 3 years; P < 0.001). Survival after surgery for recurrence was (1) similar between gallbladder cancer and cholangiocarcinoma; (2) significantly better in patients with initial disease-free interval of 2 or more years; (3) significantly worse in patients with chest or abdominal wall recurrences; and (4) significantly better in patients with pN0 disease in their primary cancer. Nodal status of the primary tumor and the site of initial recurrence were identified as independent prognostic factors after surgery for recurrence., Conclusions: Surgical resection for recurrent BTC can be performed safely and offers a better chance of long-term survival in selected patients.

Objective: To review our 34-year experience with 574 consecutive resections for perihilar cholangiocarcinoma and to evaluate the progress made in surgical treatment of this disease., Background: Few studies have reported improved surgical outcomes for perihilar cholangiocarcinoma; therefore, it is still unclear whether surgical treatment of this intractable disease has progressed., Methods: Between April 1977 and December 2010, a total of 754 consecutive patients with perihilar cholangiocarcinoma were treated, of whom 574 (76.1%) underwent resection. The medical records of these resected patients were retrospectively reviewed., Results: The incidence of major hepatectomies has increased, and limited resections, including central hepatectomies and bile duct resections, were rarely performed. Combined vascular resection was being used more often. Operative time has become shorter, and intraoperative blood loss has also decreased significantly. Because of refinements in surgical techniques and perioperative management, morbidity decreased significantly but was still high, with a rate of 43.1% in the last 5 years. Mortality rate has also decreased significantly (P < 0.001) from 11.1% (8/72) before 1990 to 1.4% (3/218) in the last 5 years. The ratio of advanced disease defined as pStage IVA and IVB has increased significantly from 49.4% before 2000 to 61.4% after 2001. The disease-specific survival for the 574 study patients (including all deaths) was 44.3% at year 3, 32.5% at year 5, and 19.9% at year 10. The survival was significantly better in the later period of 2001 to 2010 than in the earlier period of 1977 to 2000 (38.1% vs 23.1% at year 5, P < 0.001). For pM0, R0, and pN0 patients (n = 243), the survival in the later period was good with 67.1% at year 5, which was significantly better than that of the earlier period (P < 0.001). For pM0, R0, and pN1 patients (n = 142), however, the survival in the later period was similar to that of the earlier period (22.1% vs 14.6% at year 5, P = 0.647). Multivariate analysis revealed that lymph node metastasis was the strongest prognostic indicator., Conclusions: Surgical treatment of perihilar cholangiocarcinoma has been evolving steadily, with expanded surgical indication, decreased mortality, and increased survival. Survival for R0 and pN0 patients was satisfactory, whereas survival for pN1 patients was still poor, suggesting that establishment of effective adjuvant chemotherapy is needed.

Objective: To analyze lymph node status in resected perihilar cholangiocarcinoma, to clarify which index (ie, location, number, or ratio of involved nodes) is better for staging, and to determine the minimum requirements for node examination., Background: In the TNM classification for perihilar cholangiocarcinoma, the number or ratio of involved nodes is not considered for nodal staging. The minimum requirement for histologic examination of lymph nodes is arbitrary., Methods: This study involved 320 patients with perihilar cholangiocarcinoma who underwent resection from January 2000 to December 2009 at Nagoya University Hospital. The relationship between lymph node status and patient survival was retrospectively analyzed., Results: Total lymph node counts (TLNCs), ie, the number of lymph nodes examined histologically, averaged 12.9 ± 8.3 (range: 1-59). Lymph node metastasis was found in 146 (45.6%) patients and was an independent, powerful prognostic factor. The survival rates were not significantly different between patients with regional node metastasis alone and those with distant node metastasis (19.2% vs 11.5% at 5 years, P = 0.058). The survival for patients with multiple node metastases was significantly worse than that for patients with single metastasis (12.1% vs 27.6% at 5 years, P = 0.002), regardless of the presence or absence of distant lymph node metastasis. The survival for patients with lymph node ratios (LNRs) of 0.2 or less was significantly better than that for patients with LNRs greater than 0.2 (21.4% vs 13.5% at 5 years, P = 0.032). Upon multivariate analysis of the 146 patients with lymph node metastasis, the number of involved nodes (single vs multiple) was identified as an independent prognostic factor (RR of 1.61, P = 0.045), whereas the locations (regional alone vs distant) and ratios (LNR ≤ 0.2 vs LNR > 0.2) of involved nodes were not. When the 148 pN0-R0 patients were divided into 3 groups (ie, those with TLNC ≥ 8, with TLNC = 5, 6, or 7, and with TLNC ≤ 4), survivals were identical between the first and second groups, whereas they were largely different between the former two and the third., Conclusions: Lymph node metastasis is a powerful, independent prognostic factor in perihilar cholangiocarcinoma and is better classified based not on location but on the number of involved nodes. To adequately assess nodal status, histologic examination of 5 or more nodes is recommended.

Objective: To assess the clinical benefits of preoperative endoscopic nasobiliary drainage (ENBD) in patients with perihilar cholangiocarcinoma., Background: The advantages of ENBD have been previously reported. However, no studies to date have examined a large number of patients, including those with Bismuth-Corlette (B-C) type III to IV tumors. In addition, sufficient data on the risk factors associated with ENBD complications are not available., Methods: This study involved 164 consecutive patients with suspected perihilar cholangiocarcinoma (128 patients with B-C type III-IV tumors) who had undergone unilateral ENBD between January 2007 and December 2010. The success and efficacy of this procedure and the risk factors for post-ENBD cholangitis and pancreatitis were retrospectively evaluated., Results: The ENBD procedure was successful in 153 (93.3%) of the 164 patients. Of these 164 patients, 65 had serum total bilirubin (TB) levels of 2.0 mg/dL or more before the drainage. The first unilateral ENBD was successfully performed in 60 of the 65 patients, and the TB level decreased to less than 2.0 mg/dL after ENBD in 50 of these 60 patients (83.3%). The significant predictive factors for ENBD efficacy included the pre-ENBD TB level (P = 0.032; 95% confidence interval [CI], 1.01-1.23) and post-ENBD cholangitis (P = 0.012; 95% CI, 1.61-43.2). Post-ENBD cholangitis occurred in 47 (28.8%) of the 163 patients, and a previous endoscopic sphincterotomy (EST) was found to be a significant risk factor for post-ENBD cholangitis (P = 0.008; 95% CI, 1.30-5.46). Post-ENBD pancreatitis occurred in 33 (20.1%) of the 164 patients (26 grade 1 patients, 4 grade 2 patients, and 3 grade 3 patients). The significant risk factors included undergoing pancreatography (P < 0.001; 95% CI, 2.44-31.1) and the absence of previous EBS or ENBD (P < 0.001; 95% CI, 3.03-29.2)., Conclusions: Unilateral ENBD of the future remnant lobe(s) exhibited a high success rate, suggesting that it is an effective and suitable preoperative drainage method for perihilar cholangiocarcinoma even in patients with B-C type III to IV tumors. To reduce the postprocedural complications, ENBD should be performed without EST or pancreatography.

Objective: To outline our experience with hepatopancreatoduodenectomy (HPD) as a treatment for cholangiocarcinoma and to appraise the clinical significance of this challenging procedure., Background: Cholangiocarcinomas often exhibit an extensive ductal spread invading from the hepatic hilus to the lower bile duct, and such tumors can be completely resected only by HPD. Early experiences with HPD were associated with high mortality and morbidity, leading to an underestimation of the survival benefit of HPD., Methods: We retrospectively reviewed the medical records of 85 patients with cholangiocarcinoma who underwent HPD from 1992 to 2011. Major hepatectomy was performed in 79 patients (92.9%), and combined vascular resection was performed in 26 patients (30.6%)., Results: The operating time was 762 ± 141 minutes, and blood loss was 2696 ± 1970 mL. Liver failure was the most common abdominal complication (n = 64), followed by pancreatic fistula (n = 60), wound sepsis (n = 33), intra-abdominal abscess (n = 22), refractory ascites (n = 17), bacteremia (n = 16), bile leakage (n = 13), and delayed gastric emptying (n = 12). Re-laparotomy was necessary in 9 cases (11.1%). Overall, 19 patients (22.4%) exhibited Clavien grade 0 to II complications, 58 (68.2%) exhibited grade III, 6 (7.1%) exhibited grade IV, and 2 (2.4%) exhibited grade V (mortality). The overall survival rate for the 85 patients was 79.7% after 1 year, 48.5% after 3 years, 37.4% after 5 years, and 32.1% after 10 years; 9 (10.5%) patients survived for more than 5 years. The rate of survival for the 53 patients with pM0 disease who underwent R0 resection was the most favorable, with 5- and 10-year survival rates of 54.3% and 46.6%, respectively., Conclusions: HPD is technically demanding and is associated with high morbidity. However, this surgery can be performed with low mortality and offers a better probability of long-term survival in selected patients. As hepatobiliary surgeons, we should consider HPD to be a standard procedure for laterally advanced cholangiocarcinomas that are otherwise unresectable.

Objective: To review our experiences with left-sided hepatectomy for perihilar cholangiocarcinoma, to compare left hepatectomy with left trisectionectomy, and to evaluate the clinical significance of left trisectionectomy from the viewpoint of surgical oncology., Background: Only 4 large case series have been reported on left trisectionectomy, with only a few patients diagnosed with perihilar cholangiocarcinoma. Therefore, the oncologic advantage of left trisectionectomy compared with left hepatectomy for perihilar cholangiocarcinoma is still unclear., Methods: This study involved 201 patients who underwent left-sided hepatectomy for perihilar cholangiocarcinoma (86 trisectionectomies and 115 hepatectomies). Surgical outcome and survival were compared between the 2 types of hepatectomy. The length of the resected right posterior bile duct was also measured., Results: Patients who underwent trisectionectomy had more advanced tumors, thus requiring combined vascular and/or other organ resection. Operative time and blood loss were significantly greater in trisectionectomy than in hepatectomy; therefore, overall morbidity was significantly higher in the former (59.3% vs 33.0%, P < 0.001). Mortality was similar (1.2% vs 0.9%) in both techniques. The length of the resected supraportal right posterior bile duct was significantly longer in trisectionectomy than in hepatectomy (20.7 ± 6.4 vs 13.6 ± 5.2 mm, P < 0.001). However, there was no difference in length of the infraportal type right posterior bile duct. The percentage of negative radial and distal common bile duct margins was similar, but the percentage of negative right posterior bile duct margins was significantly higher in trisectionectomy than in hepatectomy (97.7% vs 89.6%, P = 0.027). Overall, R0 resection was achieved in 84.9% of patients with trisectionectomy and in 70.4% of patients with hepatectomy (P = 0.019). Survival rates were similar between patients with trisectionectomy and those with hepatectomy (36.8% vs 34.0% at 5-year), despite the fact that the former had more advanced disease., Conclusions: Left trisectionectomy for perihilar cholangiocarcinoma, although technically demanding, can be performed with similar mortality rates as left hepatectomy. From an oncologic viewpoint, this operation can increase the number of negative proximal ductal margins, leading to a high proportion of R0 resection, and, in turn, to improved survival rates of patients with advanced left-sided perihilar cholangiocarcinoma.

Objective: To clarify the value of resection of gallbladder cancer involving the extrahepatic bile duct., Background: : Several recent studies have proven that jaundice and extrahepatic biliary involvement are independent predictors of a poor outcome. Only a few authors recommend resection of such advanced disease., Methods: One hundred patients with pT3/4, pN0/1, M0 disease were the subjects of this study. Mortality and long-term outcome were analyzed using a prospectively collected database., Results: The only factor associated with mortality in univariate and multivariate analyses was intraoperative blood loss. The 5-year survival rate and median survival time were 23% and 1.5 years for patients with pathologic extrahepatic biliary invasion (pEBI), and 54% and 15.4 years for patients without pEBI. Twelve patients with pEBI survived beyond 5 years. Multivariate analysis revealed that R1/2 resection and combined resection of adjacent organs other than the liver and extrahepatic bile duct (CRAO) were independent predictors of poor outcome. Five-year survival rate and median survival time after R0 resection without CRAO were 36% and 3.8 years even in patients with pEBI. In contrast, after R0 resection with CRAO 5-year survival and median survival time were 16% and 0.8 years, respectively., Conclusions: Patients with advanced gallbladder cancer with pEBI are candidates for resection when distant metastases are absent and R0 resection is achievable. When CRAO is unnecessary, surgical resection should be aggressively planned.

Background: There is little evidence indicating a causal linkage between bacterial translocation and postoperative infectious complication (POIC) in human studies., Objective: To investigate the correlation between the occurrence of bacterial translocation in the mesenteric lymph node (MLN) and POIC with a sensitive quantitative method using bacterium-specific ribosomal RNA (rRNA)-targeted reverse transcriptase-polymerase chain reaction (RT-qPCR)., Methods: Patients who underwent major hepatectomy for biliary malignancies involving hepatic hilus were included in this study (n = 65). Mesenteric lymph nodes were harvested from the jejunal mesentery 2 times during the operation (MLN-1 harvested at laparotomy and MLN-2 harvested after tumor resection). Microorganisms were detected by a bacterium-specific rRNA-targeted RT-qPCR method. Perioperative factors and POIC were recorded prospectively., Results: Of 65 patients, 51 completed the study. Microorganisms were detected in MLN-1 and MLN-2 in 15 (29.4%) and 19 (37.3%) patients, respectively. The detection of microorganisms in MLN-1 was significantly correlated with the incidence of preoperative cholangitis (P = 0.04), whereas the detection of microorganisms in MLN-2 was significantly correlated with the incidence of POIC (P = 0.002). In multivariate analysis, a positive result for detection of microorganisms in MLN-2 was one of the independent predictive factors of POIC (odds ratio = 26.1)., Conclusions: Intraoperative analysis of MLNs (especially MLN-2) by rRNA-targeted RT-qPCR can strongly predict the occurrence of POIC after hepatectomy for biliary malignancy. This method is more sensitive and faster at detection of microorganisms than the conventional culture method. Therefore, we can obtain the information of bacterial translocation immediately after the surgery and can select the group of patients with high risk for POIC.

Objective: To outline our experience with hepatectomy with simultaneous resection of the portal vein and hepatic artery for advanced perihilar cholangiocarcinoma, and to discuss the clinical significance of this challenging hepatectomy., Summary Background Data: Only a few authors reported negative results for this surgery in a very limited number of patients., Methods: We retrospectively reviewed medical records of 50 patients with advanced cholangiocarcinoma who underwent hepatectomy (left trisectionectomy in 26, left hepatectomy in 23, and right hepatectomy in 1) with simultaneous resection and reconstruction of the portal vein and hepatic artery, focusing on surgical outcome and survival., Results: The operative time was 776 +/- 191 minutes, and blood loss was 2593 +/- 1890 mL. Time of vessel resection and reconstruction was 25 +/- 19 minutes for the portal vein and 119 +/- 56 minutes for the hepatic artery. A total of 27 (54.0%) patients developed several kinds of complications, including intra-abdominal abscess (n = 13), wound infection (n = 9), bile leakage from liver stump (n = 9), and liver failure (n = 7). Relaparotomy was necessary in 5 (10.0%) patients. One (2.0%) patient died of a postoperative complication. Microscopic cancer invasion of the resected portal vein was found in 44 (88.0%) patients, while that of the resected hepatic artery was found in 27 (54.0%). The distal bile duct margin, proximal bile duct margin, and radial margin were positive for cancer in 2 (4.0%), 4 (8.0%), and 17 (34.0%) patients, respectively. Consequently, R0 resection was achieved in 33 (66.0%) patients. The 1-, 3-, and 5-year survival rates were 78.9%, 36.3%, and 30.3%, respectively. Survival for 30 patients with pM0 disease who underwent R0 resection was better, being 40.7% at the 3- and 5-year time points., Conclusion: Major hepatectomy with simultaneous resection and reconstruction of the portal vein and hepatic artery is technically demanding. However, this surgery can be performed with acceptable mortality by an experienced surgeon and offers a better chance of long-term survival in selected patients.

Objective: To review our experience with cholangiocarcinoma with superficial spread, to clarify its clinical features, and to discuss treatment strategies., Summary Background Data: Most of the previous reports on cholangiocarcinoma with superficial spread were case reports. Little is known about this type of cholangiocarcinoma., Methods: The medical records of 471 patients with cholangiocarcinoma who underwent resection (351 perihilar and 120 distal cancers) were retrospectively reviewed, focusing on superficial spread, which was defined as noninvasive cancer extension of more than 20 mm., Results: Superficial spread was found in 69 (14.6%) of 471 patients, and its length was 54 +/- 19 mm. Histologically, papillary and well differentiated adenocarcinomas were observed more frequently in cholangiocarcinomas with superficial spread (C(+SS)), compared with those without superficial spread (C(-SS)). Histologic indexes showing tumor aggressiveness, including lymphatic, venous, and perineural invasions, were lower in C(+SS), and all factors of tumor staging (pT, pN, and pM) were less advanced in C(+SS) than in C(-SS). Regarding surgical procedure, a combined hepatectomy and pancreatoduodenectomy was indicated in 26 (37.7%) of the 69 patients with C(+SS), but in only 25 (6.2%) of the 402 patients with C(-SS). Positivity of the proximal ductal margin was higher in C(+SS) than in C(-SS) (18.8% vs. 11.9%), although this was not statistically significant. All positive proximal ductal margins in C(+SS) were because of carcinoma in situ, whereas invasive cancer was the main reason for positivity in C(-SS). Survival (excluding 29 in-hospital deaths) was significantly better in the patients with C(+SS) than in those with C(-SS) (5- and 10-year survival rates; 48.8% and 19.6% vs. 26.8% and 16.6%, P = 0.0009). Survival was comparable between the patients with a negative ductal margin and those with a positive margin with carcinoma in situ. On multivariate analysis, the presence or absence of superficial spread was not identified as a prognostic factor., Conclusions: C(+SS) is associated with less advanced, slower growing tumors and better survival compared with C(-SS). In many cases of C(+SS), the survival does not depend on the complete resection of all the superficial spread but on the stage of the main lesion.

Objective: To clarify the optimal surgical strategy for Bismuth type I and II hilar cholangiocarcinomas., Summary Background Data: Local or hilar resections is often performed for Bismuth type I and II tumors; however, reported outcomes have been unsatisfactory with a high recurrence and low survival rate. To improve survival, some authors have recommended right hepatectomy. However, the clinical value of this approach has not been validated., Methods: Records of 54 consecutive patients who underwent resection of a Bismuth type I or II hilar cholangiocarcinoma were analyzed retrospectively. Through 1996, bile duct resection or the smallest necessary hepatic segmentectomy was performed. Beginning in 1997, choice of resection was based on the cholangiographic tumor type. For nodular or infiltrating tumor, right hepatectomy was indicated; for papillary tumor, bile duct resection with or without limited hepatectomy was chosen., Results: Right hepatectomy was performed in 5 (20.8%) of 24 patients through 1996 and was done in 22 (73.3%) of 30 patients from 1997 (P = 0.0003). In patients without pM1 disease, R0 resection was achieved more frequently in the later period than in the earlier period (23 of 24 = 95.8% vs. 13 of 21 = 61.9%, P = 0.0073), which lead to better survival (5-year survival, 44.3% vs. 25.0%, P = 0.0495). In the 31 patients with nodular or infiltrating tumor, who tolerated surgery and did not have pM1 disease, survival was better in the 18 patients who underwent right hepatectomy than in those who did not (5-year survival, 62.9% vs. 23.1%, P = 0.0030). In cases of papillary tumor, bile duct resection with or without limited hepatectomy was sufficient to improve long-term survival., Conclusions: The surgical approach to Bismuth type I and II hilar cholangiocarcinomas should be determined according to cholangiographic tumor type. For nodular and infiltrating tumors, right hepatectomy is essential; for papillary tumor, bile duct resection with or without limited hepatectomy is adequate.

Objective: We present our experiences with infraportal bile duct of the caudate lobe (B1) and discuss surgical implications of this rare variation., Summary Background Data: Although various authors have investigated biliary anatomy at the hepatic hilum, an infraportal B1 (joining the hepatic duct caudally to the transverse portion of the left portal vein) has not been reported., Methods: Between January 1981 and December 2005, 334 patients underwent hepatectomy combined with caudate lobectomy for perihilar cholangiocarcinoma. Four of them (1.2%) had infraportal B1 and were investigated clinicoanatomically., Results: All infraportal B1 were B1l, draining Spiegel's lobe; no infraportal B1r (draining the paracaval portion) or B1c ducts (draining the caudate process) were found. The infraportal B1l joined the common hepatic duct or the left hepatic duct. Three patients underwent right trisectionectomy with caudate lobectomy; for one, in whom preoperative diagnosis was possible, combined portal vein resection and reconstruction were performed before caudate lobectomy to resect the caudate lobe en bloc without division of infraportal B1. For the other 2 patients, the infraportal B1 was divided to preserve the portal vein, and then the caudate lobe was resected en bloc. The fourth patient underwent right hepatectomy with right caudate lobectomy; the cut end of the infraportal B1 showed no cancer by frozen section, so the bile duct was ligated and divided to preserve the left caudate lobe., Conclusion: Infraportal B1 can cause difficulties in performing right-sided hepatectomy with caudate lobectomy or harvesting the left side of the liver with the left caudate lobe for transplantation. Hepatobiliary and transplant surgeons should carefully evaluate biliary anatomy at the hepatic hilum, keeping this variation in mind.

Summary Background Data: Use of synbiotics has been reported to benefit human health, but clinical value in surgical patients remains unclear., Objective: To investigate the effect of perioperative oral administration of synbiotics upon intestinal barrier function, immune responses, systemic inflammatory responses, microflora, and surgical outcome in patients undergoing high-risk hepatobiliary resection., Methods: Patients with biliary cancer involving the hepatic hilus (n = 101) were randomized before hepatectomy, into a group receiving postoperative enteral feeding with synbiotics (group A); or another receiving preoperative plus postoperative synbiotics (group B). Lactulose-mannitol (L/M) ratio, serum diamine oxidase (DAO) activity, natural killer (NK) cell activity, interleukin-6 (IL-6), fecal microflora, and fecal organic acid concentrations were determined before and after hepatectomy. Postoperative infectious complications were recorded., Results: Of 101 patients, 81 completed the trial. Preoperative and postoperative changes in L/M ratio and DAO activity were similar between groups. Preoperatively in group B, NK activity, and lymphocyte counts increased, while IL-6 decreased significantly (P < 0.05). Postoperative serum IL-6, white blood cell counts, and C-reactive protein in group B were significantly lower than in group A (P < 0.05). During the preoperative period, numbers of Bifidobacterium colonies cultured from and total organic acid concentrations measured in feces increased significantly in group B (P < 0.05). Postoperative concentrations of total organic acids and acetic acid in feces were significantly higher in group B than in group A (P < 0.05). Incidence of postoperative infectious complications was 30.0% (12 of 40) in group A and 12.1% (5 of 41) in group B (P < 0.05)., Conclusions: Preoperative oral administration of synbiotics can enhance immune responses, attenuate systemic postoperative inflammatory responses, and improve intestinal microbial environment. These beneficial effects likely reduce postoperative infectious complications after hepatobiliary resection for biliary tract cancer.

Objective: To investigate whether immunohistochemically demonstrated lymph node micrometastasis has a survival impact in patients with advanced gallbladder carcinoma (pT2-4 tumors)., Summary Background Data: The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, few reports have addressed this issue with regard to gallbladder carcinoma., Methods: A total of 1476 lymph nodes from 67 patients with gallbladder carcinoma (pN0, n = 40; pN1, n = 27) who underwent curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were correlated with clinical and pathologic features and with patient survival., Results: Lymph node micrometastases were detected immunohistochemically in 23 (34.3%) of the 67 patients and in 37 (2.5%) of the 1476 nodes examined. Of the 37 nodal micrometastases, 21 (56.8%) were single-cell events, and the remaining 16 were clusters. Five micrometastases were detected in the paraaortic nodes. Clinicopathologic features showed no significant associations with the presence of lymph node micrometastases. Survival was worse in the 27 patients with pN1 disease than in the 40 with pN0 disease (5-year survival; 22.2% vs. 52.6%, P = 0.0038). Similarly, survival was worse in the 23 patients with micrometastasis than in the 44 without micrometastasis (5-year survival; 17.4% vs. 52.7%, P = 0.0027). Twenty-eight patients without any lymph node involvement had the best prognosis, whereas survival for the 11 patients with both types of metastasis was dismal. The grade of micrometastasis (single-cell or cluster) had no effect on survival. The Cox proportional hazard model identified perineural invasion, lymph node micrometastasis, and microscopic venous invasion as significant independent prognostic factors., Conclusions: Lymph node micrometastasis has a significant survival impact in patients with pN0 or pN1 gallbladder carcinoma who underwent macroscopically curative resection. Extensive lymph node sectioning with keratin immunostaining is recommended for accurate prognostic evaluation for patients with gallbladder carcinoma.

Objective: To assess clinical benefit of portal vein embolization (PVE) before extended, complex hepatectomy for biliary cancer., Summary Background Data: Many investigators have addressed clinical utility of PVE before simple hepatectomy for metastatic liver cancer or hepatocellular carcinoma, but few have reported PVE before hepatectomy for biliary cancer due to the limited number of surgical cases., Methods: This study involved 240 consecutive patients with biliary cancer (150 cholangiocarcinomas and 90 gallbladder cancers) who underwent PVE before an extended hepatectomy (right or left trisectionectomy or right hepatectomy). All PVEs were performed by the "ipsilateral approach" 2 to 3 weeks before surgery. Hepatic volume and function changes after PVE were analyzed, and the outcome also was reviewed., Results: There were no procedure-related complications requiring blood transfusion or interventions. Of the 240 patients, 47 (19.6%) did not undergo subsequent hepatectomy. The incidence of unresectability was higher in gallbladder cancer than in cholangiocarcinoma (32.2% versus 12.0%, P < 0.005). The remaining 193 patients (132 cholangiocarcinomas and 61 gallbladder cancers) underwent hepatectomy with resection of the caudate lobe and extrahepatic bile duct (n = 187), pancreatoduodenectomy (n = 42), and/or portal vein resection (n = 63). Seventeen (8.8%) patients died of postoperative complications: mortality was higher in gallbladder cancer than in cholangiocarcinoma (18.0% versus 4.5%, P < 0.05); and it was also higher in patients whose indocyanine green clearance (KICG) of the future liver remnant after PVE was <0.05 than those whose index was >or=0.05 (28.6% versus 5.5%, P < 0.001). The 3- and 5-year survival after hepatectomy was 41.7% and 26.8% in cholangiocarcinoma and 25.3% and 17.1% in gallbladder cancer, respectively (P = 0.011). In 136 other patients with cholangiocarcinoma who underwent a less than 50% resection of the liver without PVE, a mortality of 3.7% and a 5-year survival of 27.6% were observed, which was similar to the 132 patients with cholangiocarcinoma who underwent extended hepatectomy after PVE., Conclusions: PVE has the potential benefit for patients with advanced biliary cancer who are to undergo extended, complex hepatectomy. Along with the use of PVE, further improvements in surgical techniques and refinements in perioperative management are necessary to make difficult hepatobiliary resections safer.

Background: The techniques of right hepatic trisectionectomy are now standardized in patients with hepatocellular or metastatic carcinoma, but not in those with hilar cholangiocarcinoma., Methods: Under preoperative diagnosis of hilar cholangiocarcinoma, 8 patients underwent "anatomic" right hepatic trisectionectomy with en bloc resection of the caudate lobe and the extrahepatic bile duct, in which the bile ducts of the left lateral section were divided at the left side of the umbilical fissure following complete dissection of the umbilical plate., Results: Liver resection was successfully performed, and all patients were discharged from the hospital in good condition, giving a mortality of 0%. All patients were histologically diagnosed as having cholangiocarcinoma. The proximal resection margins were cancer-negative in 7 patients and cancer-positive in 1 patient. Four patients with multiple lymph node metastases died of cancer recurrence within 3 years after hepatectomy. One patient died of liver failure without recurrence 42 months after hepatectomy. The remaining 3 patients without lymph node metastasis are now alive after more than 5 years., Conclusions: Anatomic right hepatic trisectionectomy with caudate lobectomy can produce a longer proximal resection margin and can offer a better chance of long-term survival in some selected patients with advanced hilar cholangiocarcinoma.

Although fluorine-18 deoxyglucose-positron emission tomography (FDG-PET) is a sensitive diagnostic modality in detecting malignant tumors, differential diagnosis of malignant tumors from inflammatory lesion is challenging. We experienced a case of acute degenerative necrosis superimposed on chronic pancreatitis, which was difficult to distinguish from pancreatic cancer. The patient was a 66-year-old man with a complaint of upper abdominal pain. Abdominal computed tomography revealed low-density masses in the head and body of the pancreas. FDG-PET revealed intense accumulations at the head and body of the pancreas (mean standard uptake value for the head and body pancreatic tumors was 4.1 and 6.7, respectively) corresponding to the 2 tumors detected by computed tomography. Because of a possible malignant pancreatic tumor, the patient underwent pylorus-preserving pancreatoduodenectomy. Histologic examination of the resected specimen revealed a characteristic of chronic pancreatitis in a nontumorous area. Two tumors detected by FDG-PET consisted of degenerative necrosis surrounded by granulation tissue. The amount of granulation tissue was correlated to the levels of standard uptake value. No malignant tumors were observed. This case suggests a limitation of FDG-PET in distinguishing malignant neoplastic lesions in the pancreas, especially from acute degenerative changes in chronic pancreatitis. Repetitive PET examination is recommended for the accurate diagnosis.

Objective: To better determine the role of portal vein resection and its effect on survival, as well as to appreciate the impact of portal vein invasion on prognosis in hilar cholangiocarcinoma., Summary Background Data: Hepatectomy with portal vein resection is sometimes performed for locally advanced hilar cholangiocarcinoma. However, the significance of microscopic invasion of the portal vein has not been determined., Methods: Medical records of 160 patients with hilar cholangiocarcinoma who underwent macroscopically curative hepatectomy with (n = 52) or without portal vein resection (n = 108) were reviewed. Invasion of the portal vein was assessed histologically on the surgical specimen, and results were correlated with clinicopathologic features and survival., Results: Surgical mortality, including all hospital deaths, was similar in patients who did and did not undergo portal vein resection (9.6% vs. 9.3%), but the primary tumor was more advanced in patients who underwent portal vein resection. Histologically, no invasion was found in 16 (30.8%) of resected portal veins. However, dense fibrosis adjacent to the portal vein was common, and the mean distance between the leading edge of cancer cells and the adventitia of the portal vein was 437 +/- 431 mum. The prognosis was worse in patients with than without portal vein resection (5-year survival, 9.9% vs. 36.8%; P < 0.0001). The presence or absence of microscopic invasion of the resected portal vein did not influence survival (16.6 months in patients with microscopic invasion vs. 19.4 months in those without; P = 0.1506). Multivariate analysis identified histologic differentiation, lymph node metastasis, and macroscopic portal vein invasion as independent prognostic factors., Conclusions: Microscopic invasion of the portal vein may be misdiagnosed clinically in patients with hilar cholangiocarcinoma. However, the distance between tumor and adventitia is so narrow that curative resection without portal vein resection is unlikely to be possible. Gross portal vein invasion has a negative impact on survival, and hepatectomy with portal vein resection can offer long-term survival in some patients with advanced hilar cholangiocarcinoma.

Objective: To investigate whether immunohistochemically demonstrated lymph node micrometastasis has prognostic significance in patients with histologically node-negative (pN0) hilar cholangiocarcinoma., Summary Background Data: The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, no reports have addressed this issue with regard to hilar cholangiocarcinoma., Methods: A total of 954 lymph nodes from surgical specimens of 45 patients with histologically node-negative hilar cholangiocarcinoma who underwent macroscopically curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were examined for relationships with clinical and pathologic features and with patient survival., Results: Lymph node micrometastases were detected immunohistochemically in 11 (24.4%) of the 45 patients, being found in 13 (1.4%) of 954 lymph nodes examined. Of the 13 nodal micrometastases, 11 (84.6%) were found in the N2 regional lymph node group rather than N1. Clinicopathologic features showed no associations with lymph node micrometastases. Survival curves were essentially similar between patients with and without micrometastasis. In addition, the grade of micrometastasis showed no effect on survival. The Cox proportional hazard model identified microscopic venous invasion, microscopic resection margin status, and histologic differentiation as significant prognostic factors in patients with pN0 disease., Conclusions: Lymph node micrometastasis has no survival impact in patients with otherwise node-negative hilar cholangiocarcinoma. The authors do not recommend extensive lymph node sectioning with keratin immunostaining for prognostic evaluation.