Surgery for Pancreatic Neuroendocrine Tumor G3 and Carcinoma G3 Should be Considered Separately.

BACKGROUND: The role of surgery in pancreatic neuroendocrine neoplasm grade 3 (pNEN-G3) treatment remains unclear. We aimed to clarify the role of surgery for pNEN-G3, which has recently been reclassified as pancreatic neuroendocrine tumor-G3 (pNET-G3) and pancreatic neuroendocrine carcinoma-G3 (pNEC-G3), with and without metastases, respectively. METHODS: We analyzed a subgroup of patients from the Japanese pancreatic NEC study, a Japanese multicenter case-series study of pNEN-G3. Pathologists subclassified 67 patients as having pNET-G3 or pNEC-G3 based on morphological features. We compared the overall survival (OS) rates among patients who were grouped according to whether they had undergone tumor-targeted surgery for tumors without (SwoM) or with (SwM) metastases, or non-surgical procedures (NS). RESULTS: Data from 21 patients with pNET-G3 (SwoM, n = 6; SwM, n = 5; NS, n = 10) and 46 patients with pNEC-G3 (SwoM, n = 8; SwM, n = 5; NS, n = 33) were analyzed. OS of patients with pNET-G3 was significantly longer after SwoM and SwM than with NS (p = 0.018 and p = 0.022). In contrast, OS did not significantly differ between either SwoM or SwM and NS (p = 0.093 and p = 0.489) among patients with pNEC-G3. CONCLUSION: The role of surgery should be considered separately for pNET-G3 and pNEC-G3. Although SwoM and SwM can be considered for pNET-G3, caution is advised before considering SwM and SwoM for pNEC-G3.

SLCO1B1 Polymorphism Is a Drug Response Predictive Marker for Advanced Pancreatic Cancer Patients Treated With Gemcitabine, S-1, or Gemcitabine Plus S-1.

OBJECTIVES: The aim of this study was to evaluate the effects of single-nucleotide polymorphisms (SNPs) on advanced pancreatic cancer risk and overall survival (OS) in a candidate-gene approach. METHODS: Overall, 5438 SNPs in 219 candidate genes encoding several drug-metabolizing enzymes or transporters were analyzed. In the screening study, 3 SNPs were found associated with OS (P ≤ 0.0005). We validated these SNPs as part of the randomized phase 3 study (GEST study). The associations between OS and SNPs were investigated using log-rank test and Cox proportional hazards model. RESULTS: From the GEST study, the SNP rs4149086 in the 3' UTR of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene showed significant interaction with treatment (P = 0.02). In the gemcitabine group, the SNP was associated with short OS (hazard ratio [HR], 3.75; 95% confidence interval [CI], 1.30-10.8; P = 0.008) even after multiple-comparisons adjustment. In contrast, the SNP was not associated with OS in S-1 (HR, 0.77; 95% CI, 0.33-1.81; P = 0.55) or gemcitabine plus S-1 groups (HR, 1.18; 95% CI, 0.46-3.00; P = 0.72). CONCLUSIONS: Patients with advanced pancreatic cancer with the rs4149086 AG or GG genotype may obtain good clinical results when treated with S-1-containing regimens.

Rb Loss and KRAS Mutation Are Predictors of the Response to Platinum-Based Chemotherapy in Pancreatic Neuroendocrine Neoplasm with Grade 3: A Japanese Multicenter Pancreatic NEN-G3 Study.

Purpose: Patients with pancreatic neuroendocrine neoplasm grade-3 (PanNEN-G3) show variable responses to platinum-based chemotherapy. Recent studies indicated that PanNEN-G3 includes well-differentiated neuroendocrine tumor with G3 (NET-G3). Here, we examined the clinicopathologic and molecular features of PanNEN-G3 and assessed the responsiveness to chemotherapy and survival.Experimental Design: A total of 100 patients with PanNEN-G3 were collected from 31 institutions, and after central review characteristics of each histologic subtype [NET-G3 vs. pancreatic neuroendocrine carcinoma (NEC-G3)] were analyzed, including clinical, radiological, and molecular features. Factors that correlate with response to chemotherapy and survival were assessed.Results: Seventy patients analyzed included 21 NETs-G3 (30%) and 49 NECs-G3 (70%). NET-G3 showed lower Ki67-labeling index (LI; median 28.5%), no abnormal Rb expression (0%), and no mutated KRAS (0%), whereas NEC-G3 showed higher Ki67-LI (median 80.0%), Rb loss (54.5%), and KRAS mutations (48.7%). Chemotherapy response rate (RR), platinum-based chemotherapy RR, and prognosis differed significantly between NET-G3 and NEC-G3. Chemotherapeutic outcomes were worse in NET-G3 (P < 0.001). When we stratified PanNEN-G3 with Rb and KRAS, PanNENs-G3 with Rb loss and those with mutated KRAS showed significantly higher RRs to platinum-based chemotherapy than those without (Rb loss, 80% vs. normal Rb, 24%, P = 0.006; mutated KRAS, 77% versus wild type, 23%, P = 0.023). Rb was a predictive marker of response to platinum-based chemotherapy even in NEC-G3 (P = 0.035).Conclusions: NET-G3 and NEC-G3 showed distinct clinicopathologic characteristics. Notably, NET-G3 does not respond to platinum-based chemotherapy. Rb and KRAS are promising predictors of response to platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G3. Clin Cancer Res; 23(16); 4625-32. ©2017 AACR.

[Two cases of pancreatic cancer with multiple liver metastases treated with radical treatment after successful treatment with gemcitabine plus S-1 therapy].

UNLABELLED: We report two cases of pancreatic cancer with multiple liver metastases for which successful gemcitabine (GEM) +S-1 therapy facilitated radical resection. Case 1: A 40-year-old man with jaundice was diagnosed with pancreatic head cancer and multiple metastases. Radical treatment was not possible. Therefore, he was administered GEM +S-1 (GEM 1,000 mg/m² on days 1 and 8; S-1, 100mg/day for 14 days). Administration of seven courses of therapy achieved complete remission (CR) of the metastatic lesions. Considering the possibility of residual tumors, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Although pathological examination revealed a residual tumor in the primary lesion, R0 resection was achieved. GEM+S-1 therapy was resumed, and the patient is currently relapse-free. Case 2: A 65-year-old man with obstructive jaundice was diagnosed with pancreatic head cancer and multiple metastases. Radical treatment was not possible. Therefore, GEM +S-1 therapy was initiated. After 11 therapy courses, only one metastatic lesion remained. Radical treatment was then deemed possible, and a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination revealed residual tumors in the primary lesion and the peripancreatic lymph nodes. However, the liver nodules were only fibrotic, and their surgical radicality was R0. GEM +S-1 therapy was resumed, and the patient is currently relapse-free. CONCLUSION: The high response rate of GEM+S-1 therapy suggests its usefulness in facilitating radical resection after treatment with (GEM) +S-1.

Giant hepatic cyst with septal structure: diagnosis and management.

The hepatic cyst is a common benign liver tumor, and no surgical treatment is necessary. However, it is difficult to correctly diagnose the giant hepatic cyst containing the solid septal structures inside, from the malignant cystadenocarcinomas. The various imaging modalities such as computed tomography, magnetic resonance imaging, and ultrasonography, have been developed and are useful for the diagnosis of these liver tumors. Reviewing the other reports in this paper, the combination of more than 2 modalities will help to diagnose these tumors; however, the malignant potential is unable to be excluded if the tumor is huge. Therefore, the surgical resection should be considered for the huge hepatic cysts with septal structures if the correct diagnosis is unable to be made. For example, when the hemorrhages cause the granulation in the septa which often shows neovascularization, the imaging modalities are unable to define this situation from the malignant tissue with hypervascularity. Therefore, with the careful review of other reports, we conclude that if the imaging studies show the possible malignant potential or the sizing-up is marked, the surgical treatment should be considered with the consent from the patients.

[An 84-year-old man with highly advanced gastric cancer showing good response after chemotherapy with docetaxel, cisplatin and S-1 combination therapy].

An 84-year-old man had the wall thickness of his stomach accidentally detected by CT scan, and was diagnosed as type 2 advanced gastric cancer with liver and lung metastasis. Chemotherapy with docetaxel, cisplatin and S-1 combination therapy was adopted. Grade 4 neutropenia was revealed, but the treatment could be continued by G-CSF or by down dosing the anticancer agents. By maintaining CR of the primary lesion and PR of the liver and lung metastases, he has been kept at a PS 0 state and has been receiving regular outpatient treatment for 28 months now since the beginning of treatment.

Portal vein infusion chemotherapy with gemcitabine after surgery for pancreatic cancer.

PURPOSES: Pancreatic cancer still has a poor prognosis even after curative resection because of the high incidence of postoperative liver metastasis. This study prospectively evaluated the feasibility and tolerability of portal vein infusion chemotherapy of gemcitabine (PVIG) as an adjuvant setting after pancreatic resection. METHODS: Thirteen patients enrolled in this study received postoperative chemotherapy with PVIG. The patients received intermittent administration of gemcitabine (800 mg/m(2)) via the portal vein on days 1, 8, and 15 after surgery. The tolerability and the toxicity of PVIG were closely monitored. RESULTS: The PVIG was started on an average of 3.1 days after surgery. Complete doses of chemotherapy (three sessions of portal infusion) were accomplished in 11 of the 13 patients. Grade 3 or 4 leukocytopenia was observed in three patients (23 %), and liver dysfunction was found in one patient (7.7 %). Grade 2 sepsis developed in two cases due to bloodstream infection. Liver metastasis was the first site of recurrence in only two patients. CONCLUSIONS: PVIG can be administered to the liver with acceptable toxicity, but myelosuppression is similar to the systemic use of gemcitabine. Careful observation is required even for locoregional chemotherapy.

[Review of fundus examinations of patients with candidemia from a survey of systemic management physicians].

PURPOSE: To assess, as one part of systemic management, the needs for a fundus examination of patients with candidemia to accommodate the possibility of endogenous fungal endophthalmitis. PATIENTS AND METHODS: We reviewed retrospectively the medical records of in-patients diagnosed with candidemia between January 2003 and September 2009 at Niigata Cancer Center Hospital. Thirty seven patients were found. We attempted to make a survey of the physicians in charge of the patients' candidemia regarding the management of fungal endophthalmitis. RESULTS: Thirteen (24.5%) doctors answered that they had ordered an ophthalmologic consultation for all the patients with candidemia either with or without eye symptoms. However, 31 (58.5%) doctors referred only the patients with eye symptoms to an ophthalmologist. Among the six (16.2%) patients who underwent ophthalmic examination, only one patient had chorioretinitis consistent with early stages of endogenous fungal endophthalmitis, and that completely resolved with systemic treatments. CONCLUSIONS: Not all patients with candidemia need to receive ophthalmologic evaluations routinely wherever adequate antifungal therapies can be performed, although fully dilated optic fundus examination is important for all candidemic patients who have visual symptoms. It is, however, necessary to educate all physicians about endogenous fungal endophthalmitis.

Surgical outcomes of minor hepatectomy for locally advanced gallbladder carcinoma.

BACKGROUND/AIMS: This study aimed to evaluate whether wedge resection or S4bS5 resection was the more beneficial hepatectomy procedure for patients with locally advanced gallbladder carcinoma. METHODOLOGY: A retrospective analysis of 70 patients who underwent either wedge resection (n=58) or S4bS5 resection (n=12) for locally advanced gallbladder carcinoma without clinically evident liver metastases was conducted. Clinicopathological characteristics, histological features of hepatic invasion and surgical outcomes were analyzed. RESULTS: Sixteen patients had tumors with hepatic invasion. Of the 16 patients with hepatic invasion, 6 had direct liver invasion alone and 10 had portal tract invasion featuring intrahepatic stromal invasion (n=5), intrahepatic lymphatic invasion (n=4) and intrahepatic venous invasion (n=l). The hepatectomy procedure was not significantly associated with survival after resection (p=0.518) as patients who underwent wedge resection showed an overall cumulative 3-year survival rate of 74% compared with 60% for patients who underwent S4bS5 resection. The Cox proportional hazard regression analysis revealed that pT classification (p<0.001), pM classification (p=0.001) and resection of the extrahepatic bile duct (p=0.048) were independently significant factors associated with survival after resection. CONCLUSIONS: Hepatectomy procedure may not significantly affect surgical outcomes in patients with gallbladder carcinoma. Partial hepatectomy involving the gallbladder bed is critical due to possible tumor cells.

[A case of advanced gastric cancer showing pathological CR after neoadjuvant chemotherapy with docetaxel, cisplatin and S-1 combination].

A 69-year-old man suffering from heart-burn was referred to our hospital, and diagnosed as type 3 advanced gastric cancer with lymph node metastasis. Neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin and S-1 was attempted. After two courses of chemotherapy were completed, distal gastrectomy with D2 lymphadenectomy was performed. Pathologically, there were no viable cancer cells remaining in the primary lesion and lymph nodes. The pathological response of NAC was judged to be grade 3. The postoperative course was uneventful, and the patient is currently visiting our outpatient clinic for treatment with S-1 as postoperative adjuvant chemotherapy.

Depth of invasion determines the postresectional prognosis for patients with T1 extrahepatic cholangiocarcinoma.

BACKGROUND: We tested the hypothesis that in patients with T1 extrahepatic cholangiocarcinoma (EHC), prognosis postresection is significantly different for those with tumors that are limited to the mucosa than for those with tumors that have invaded (but not penetrated) the fibromuscular layer. METHODS: A retrospective analysis was conducted of 33 consecutive patients with pathologic T1 (pT1) EHC tumors. According to the depth of invasion, the pT1 tumors were divided into 2 groups: Group 1, tumors that were limited to the mucosa (mucosal tumors); and Group 2, tumors that had invaded (but not penetrated) the fibromuscular layer (fibromuscular layer-invasive tumors). Long-term outcomes after resection were compared between the 2 groups for a median follow-up time of 175 months. RESULTS: Eighteen patients had mucosal tumors and 15 patients had tumors that had invaded the fibromuscular layer. None of the patients with mucosal tumors had lymphovascular invasion, whereas 3 of the patients with fibromuscular layer-invasive tumors had lymphovascular invasion (P = .083). Overall survival after resection was better in Group 1 than in Group 2 (cumulative 10-year survival rate, 100% vs 52%; P = .024). The rate of disease-free survival after resection was higher in Group 1 than in Group 2 (cumulative disease-free 10-year survival rate, 100% vs 56%; P = .022). CONCLUSIONS: The long-term outcome after resection for EHC is significantly better for patients with mucosal tumors than for patients with fibromuscular layer-invasive tumors. This suggests that the depth of tumor invasion affects the postresection prognosis for patients with pT1 EHC.

Preoperative chemotherapy with S-1 and cisplatin for highly advanced gastric cancer.

UNLABELLED: Feasibility and efficacy of S-1 and cisplatin followed by surgery was evaluated, and factors contributing to survival benefit were analyzed. PATIENTS AND METHODS: In total, 120 consecutive patients with highly advanced gastric cancer were treated with S-1 (80 mg/m(2) for 21 consecutive days) and cisplatin (50 mg/m(2) on day 8). RESULTS: The response rate was 62.5% overall, and 75.7% for these with metastatic lymph nodes. Grade 3/4 adverse events were less than 10%. The median survival time was 41.9 months among 93 patients whose primary lesion was resected. Liver metastasis, R2 resection, poor performance status and lack of response were identified as independent risk factors by a multivariate analysis. CONCLUSION: Preoperative chemotherapy with S-1 and cisplatin was effective. The results show the need for different approaches in the treatment of patients with metastases and these without.

[Evaluation of hepatic resection for synchronous liver metastasis from gastric cancer].

To evaluate the effect of hepatic resection for synchronous liver metastasis from gastric cancer, the clinicopathological factors of gastric cancer, the size and number of liver metastasis and surgical procedures for liver metastasis were studied. Between 1977 and 2006, a total of 49 patients (38 men and 11 women) underwent hepatic resections and gastrectomy. The median age was 70 years old (range 41-81). As for pathological type, intestinal/diffuse was 26/23. T1/T2/T3/T4 was 4/14/23/8. For lymph node metastasis, N0/N1/N2/N3 was 4/15/18/12. The number of liver metastasis: 27 patients had 1 lesion, 9 patients had 2 lesions, and 13 patients had more than 3 lesions. A partial resection was performed for 37 patients. MST was 663 days. The 5-year survival rate was 19.7%. Univariate analysis pointed out several prognostic factors such as histological type of primary lesion, T-factor, lymph node metastasis, the number and size of liver metastasis and the procedures for hepatic resection. Multivariate analysis revealed that two factors of N0 or N1 in lymph node metastasis and partial resection of liver metastasis were favorable independent prognostic factors (p=0.0108 and p=0.0192). In conclusion, N0 and N1 state and partial resection of the liver metastasis would be good candidates for gastrectomy and synchronous resection of liver metastatic lesions.

Prognostic factors for radical resection of middle and distal bile duct cancer.

BACKGROUND/AIMS: Prognostic factors after radical operation for middle and distal bile duct cancer are not fully understood. The aim of this study is to identify prognostic factors for patients undergoing radical operation for middle and distal bile duct cancer. METHODOLOGY: The records of 57 patients with middle (n=22) and distal (n=35) bile duct cancer who had undergone radical surgery were reviewed (pancreaticoduodenectomy in 46 patients, extrahepatic bile duct resection in 6, and major hemihepatectomy in 5). The clinicopathological prognostic factors affecting survival were examined. RESULTS: The 5 years survival rate was 36% (median survival time, 34 months). Significant prognostic factors according to univariate analysis include pT classification, papillary type, number of metastatic lymph node, positive radial margin, pancreatic invasion, lymphatic invasion, venous invasion, common hepatic node metastasis, paraaortic node metastasis, and combined vascular resection. Independent significant prognostic factors according to multivariate analysis include the number of metastatic lymph nodes (5 or more), positive radial margin, and common hepatic node metastasis. CONCLUSIONS: The number of metastatic lymph nodes, common hepatic node metastasis, and positive radial margin are independent prognostic factors for middle and distal bile duct cancer. The surgical treatment of middle and bile duct cancer should achieve a negative radial margin for a favorable outcome.

[Examination of s-1 therapy for adjuvant chemotherapy in patients with advanced gastric cancer].

PURPOSE: In our department, S-1 has been administered for 1 year as postoperative adjuvant chemotherapy for advanced gastric cancer since 2000. It was started by a standard dosage of 4-week administration with 2 weeks rest since 2000(A group). However, since 2002, it was changed with the expectation of the reduction of side effects by 2-week administration with a one-week rest(B group). Treatment continuity, adverse events and efficacy in both A and B groups were examined. SUBJECTS: The subjects were 96 patients with fStage II, III A and III B who were treated with S-1 after curative operation between 2000 and 2006. RESULTS: The percentage of patients who complied with the dosing instructions completely during a 1-year period was 70.2% in the A group and 77.6% in the B group. The incidence of Grade 3 and 4 toxicity was 1 nausea, 2 appetite loss, 1 neutropenia, 1 liver dysfunction in the A group and 1 nausea, 3 neutropenia in the B group, against, 76.6% in the A group and 44.9% in the B group, respectively, in the case of discontinuation, Thus, the trend in significantly high incidence in the A group was recognized. The 3-year survival rates in cases with a case of over 3 years were 88.5% in the A group and 87.5% in the B group, i. e., no difference. CONCLUSION: Though the difference was not recognized in continuation rate, efficacy and adverse events in both A and B groups, there were significantly few withdrawal cases in the B group, and it seemed to be an effective medication method.

Preoperative cholangitis independently increases in-hospital mortality after combined major hepatic and bile duct resection for hilar cholangiocarcinoma.

PURPOSE: This study evaluated the impact of ductal bile bacteria (bactibilia or cholangitis) on the development of surgical site infection (SSI) or in-hospital mortality after resection for hilar cholangiocarcinoma. MATERIALS AND METHODS: A retrospective analysis was conducted on 81 patients who underwent a combined major hepatic (hemihepatectomy or more extensive hepatectomy) and bile duct resection for hilar cholangiocarcinoma. Ductal bile was submitted for bacterial culture before or during the operation. RESULTS: The incidence of SSI was higher in patients with preoperative bactibilia (83%) than in patients without (52%; P = 0.008). Preoperative bactibilia was an independent variable associated with SSI (relative risk 9.003; P = 0.002). The incidence of in-hospital mortality was higher in patients with preoperative cholangitis (33%) than in patients without (6%; P = 0.009). Preoperative cholangitis was the only independent variable associated with in-hospital mortality (relative risk 9.115; P = 0.006). CONCLUSIONS: Preoperative cholangitis independently increases in-hospital mortality after combined major hepatic and bile duct resection for hilar cholangiocarcinoma, whereas preoperative bactibilia independently increases SSI.

Liver perfusion chemotherapy with 5-Fluorouracil followed by systemic gemcitabine administration for resected pancreatic cancer: preliminary results of a prospective phase 2 study.

OBJECTIVES: Liver perfusion chemotherapy (LPC) for pancreatic cancer has been rarely undertaken in a postoperative adjuvant setting. We evaluated the feasibility and antitumor efficacy of LPC with 5-fluorouracil (5-FU) followed by gemcitabine treatment. METHODS: This prospective study enrolled 27 patients who underwent pancreatic resection and subsequent LPC + gemcitabine treatment during a 3-year period. The liver was infused with 5-FU (125 mg/body per day per route) via both routes of hepatic artery and portal vein for more than 21 days. After that, gemcitabine (1000 mg/m) was administered biweekly. RESULTS: Portal vein thrombosis developed in 1 patient, but 89% patients tolerated LPC for more than 21 days with no life-threatening complication. Systemic administration of gemcitabine was accomplished in 93%; however, 1 patient died of serious capillary leak syndrome. No grade 4 toxicity was recorded, except for that patient. Median survival time and disease-free survival were 27.5 and 24.5 months, respectively. Hepatic relapse was observed in 25.9% (n = 7). Survival was in favor of paraaortic node-negative cases (n = 20) with a 2-year survival of 68.7%. CONCLUSIONS: Liver perfusion chemotherapy was feasible with acceptable toxicity. Systemic use of gemcitabine also seems to be safe for the most part. This adjuvant chemotherapy shows promising survival benefit and seems to be indicative to paraaortic node-negative tumors.

[Three cases of complete response after treatment with UFT and leucovorin for recurrent colorectal cancer].

We report three cases of complete response (CR) after treatment with UFT/LV for recurrent colorectal cancer. Case 1: A 44-year-old man was diagnosed with multiple liver metastases after resection of cecal cancer. UFT (500 mg/day)/Leucovorin (75 mg/day) was administered. Metastatic lesions of the liver completely disappeared on computed tomography(CT)one month after chemotherapy. Grade 2 hyperbilirubinemia and grade 1 diarrhea, pigmentation and rash were recognized. No signs of recurrence were observed for 35 months. Case 2: A 66-year-old man who underwent left colectomy and partial hepatectomy for transverse colon cancer and descending colon cancer with liver metastasis was determined to have multiple lung metastases. UFT/LV therapy was started. The lung lesions became only scars 7 months later. Adverse events were not seen. No other recurrence was found over 20 months. Case 3: A 66- year-old woman was detected with a lymph node recurrence after surgery for rectal cancer. CT revealed the disappearance of the tumor after 7 courses of UFT/LV therapy. Grade 2 hyperbilirubinemia appeared. Recurrence was not observed for 22 months, and the treatment has been discontinued.

[A case of advanced gastric cancer responding to neoadjuvant S-1/CDDP therapy].

A 77-year-old male had complaints of epigastralgia. Gastrointestinal endoscopic examination revealed type 2 advanced gastric cancer. Computed tomography revealed metastatic Bulkey group 2 lymph nodes. The diagnosis was sStage IIIB gastric cancer (sT3 sN2sH0 sP0 CY0) at staging laparoscopy. S-1 (100 mg/body/day) was orally administered for 3 weeks followed by a drug-free 2 weeks, and CDDP (74 mg/body/day) was given intravenously on day 8. After 3 courses of chemotherapy, the primary lesion and the regional lymph nodes were significantly reduced in size. He was judged as clinical PR, followed by total gastrectomy, splenectomy and lymph node dissection. The pathological findings showed that there were very few cancer cells in the primary lesion, and lymph nodes had become scarred and fibrous. The final diagnosis was T2N0 H0 P0, fStageIB and curability A.

Combined major hepatectomy and pancreaticoduodenectomy for locally advanced biliary carcinoma: long-term results.

BACKGROUND: This study aimed to define the role of combined major hepatectomy and pancreaticoduodenectomy in the surgical management of biliary carcinoma and to identify potential candidates for this aggressive procedure. METHODS: A retrospective analysis was conducted on 28 patients who underwent a combined major hepatectomy and pancreaticoduodenectomy for extrahepatic cholangiocarcinoma (n = 17) or gallbladder carcinoma (n = 11). Major hepatectomy was defined as hemihepatectomy or more extensive hepatectomy. Altogether, 11 patients underwent a Whipple procedure, and 17 had a pylorus-preserving pancreaticoduodenectomy. The median follow-up time was 169 months. RESULTS: Morbidity and in-hospital mortality were 82% and 21%, respectively. Overall cumulative survival rates after resection were 32% at 2 years and 11% at 5 years (median survival time 9 months). The median survival time was 6 months with a 2-year survival rate of 0% in 11 patients with residual tumor, whereas the median survival time was 26 months with a 5-year survival rate of 18% in 17 patients with no residual tumor (P = 0.0012). Residual tumor status was the only independent prognostic factor of significance (relative risk 4.65; P = 0.003). There were three 5-year survivors (two with diffuse cholangiocarcinoma and one with gallbladder carcinoma with no bile duct involvement) among the patients with no residual tumor. CONCLUSIONS: Combined major hepatectomy and pancreaticoduodenectomy provides survival benefit for some patients with locally advanced biliary carcinoma only if potentially curative (R0) resection is feasible. Patients with diffuse cholangiocarcinoma and gallbladder carcinoma with no bile duct involvement are potential candidates for this aggressive procedure.