The efficacy and safety of 5-fluorouracil based adjuvant therapy in resected biliary tract cancer: A systematic review and meta-analysis.

OBJECTIVES: The adjuvant therapy (AT) for biliary tract cancer (BTC) patients after surgery has always been controversial. More therapeutic regimens and high-quality evidence were needed to evaluate AT's survival benefit further. Thus, this study was performed to investigate the efficacy and safety of the 5-fluorouracil (5-FU) regimen in resected BTC patients. METHODS: PubMed, Cochrane Library, Web of Science, and the Embase were systematically searched from inception to Feb.3, 2021, for eligible studies. The pooled analyses were performed using Review Manager, Stata, and SPSS software. RESULTS: A total of 9 trials involving 1339 participants were included in the meta-analysis. Resected BTC patients could significantly benefit from a 5-FU regimen (HR:0.51, 95%CI, 0.38-0.69, P<0.0001), regardless of gallbladder carcinoma (GBC) or cholangiocarcinoma (CCA). Moreover, both adjuvant chemotherapy (HR:0.61, 95%CI, 0.47-0.79, P=0.0003) and chemoradiotherapy (HR:0.35, 95%CI, 0.14-0.83, P=0.02) could significantly improve clinical survival of resected BTC patients than the surgery alone group. In the subgroup analyses, patients with node-positive (P=0.02) or vascular invasion disease (P=0.002) could better benefit from postoperative AT. CONCLUSION: This study provides the latest evidence to support the 5-FU regimen in resected BTC patients regardless of GBC or CCA. Furthermore, high-risk patients are more likely to benefit from it, such as node-positive or vascular invasion disease.

SEOM clinical guidelines for pancreatic and biliary tract cancer (2020).

Pancreatic cancer (PC) and biliary tract cancer (BTC) are both aggressive and highly fatal malignancies. Nowadays we have a profound knowledge about the molecular landscape of these neoplasms and this has allowed new therapeutic options. Surgery is the only potentially curative therapy in both cancers, but disease recurrence is frequent. In PC, adjuvant treatment with mFOLFIRINOX has improved overall survival (OS) and in BTC adjuvant treatment with capecitabine seems to improve OS and relapse-free survival. Concomitant radio-chemotherapy could also be considered following R1 surgery in both neoplasms. Neoadjuvant treatment represents the best option for achieving an R0 resection in borderline PC. Upfront systemic chemotherapy is the treatment of choice in unresectable locally advanced PC and BTC; then locoregional therapy could be considered after an initial period of at least 3-4 months of systemic chemotherapy. In metastatic PC, FOLFIRINOX or Gemcitabine plus nab-paclitaxel have improved OS compared with gemcitabine alone. In metastatic BTC, cisplatin plus gemcitabine constitute the standard treatment. Progress in the knowledge of molecular biology has enabled the identification of new targets for therapy with encouraging results that could in the future improve the survival and quality of life of patients with PC and BTC.

Meta-analysis of randomized clinical trials of adjuvant chemotherapy for resected biliary tract cancers.

BACKGROUND: This meta-analysis was performed by analyzing randomized controlled trials (RCTs) to assess the potential prognostic value of adjuvant chemotherapy (ACT) for patients with resected biliary tract cancers (BTCs). METHODS: PubMed, EMBASE, and the Cochrane Library were searched for relevant articles published. Only RCTs affected by tumors of gallbladder, intrahepatic, perihilar, and distal bile ducts were considered. Data were pooled using a random-effects model. The primary endpoint of the study was overall survival (OS). RESULTS: The study identified 1192 patients who met the inclusion and exclusion criteria. ACT had nearly reached a significant better OS (HR, 0.88; 95% CI, 0.77-1.01; P = 0.07) and achieved a significant better RFS (HR, 0.83; 95% CI, 0.69-0.99; P = 0.04). The effectiveness of ACT for OS was significantly modified by fluorouracil-based ACT (HR, 0.83; 95% CI, 0.70-0.99; P = 0.04), but not by gemcitabine-based ACT (HR, 0.91; 95% CI, 0.74-1.12; P = 0.36). The survival benefit was also not modified by primary disease site, resection margin status, and lymph node status. CONCLUSIONS: ACT is correlated with favorable relapse-free survival compared with non-ACT for resected BTCs patients. Fluorouracil-based ACT could be viewed as a standard practice for resected BTCs patients regardless of the primary cancer site, lymph node or margin status.

Effectiveness of omega-3 fatty acid administration on completion rate of adjuvant chemotherapy for biliary tract cancer: study protocol for a single-centre, open-label, single-arm, historically controlled study.

INTRODUCTION: Multimodal treatment prolongs the survival of patients with biliary tract cancer (BTC). However, the chemotherapy choices for this disease are few, and completing each chemotherapy session is important. Adjuvant chemotherapy has been attempted for BTC, but has only had a 75% completion rate. Body weight loss and cholangitis are reasons for the interruption of chemotherapy. Previous reports suggested that nutritional intervention with omega-3 fatty acids maintained body weight and improved the completion rate for chemotherapy. Moreover, omega-3 fatty acids have an anti-inflammatory effect. Therefore, we theorised that omega-3 fatty acids would improve the completion rate of adjuvant chemotherapy in patients with BTC. The aim of this study is thus to evaluate the effectiveness of omega-3 fatty acids for patients planning adjuvant chemotherapy for BTC. METHOD AND ANALYSIS: This study is a single-centre, open-label, single-arm, historically controlled study with a planned enrolment of 55 participants. Protocol treatment consists of four courses of S-1 adjuvant chemotherapy and an oral omega-3 fatty acid pharmaceutic adjuvant (LOTRIGA 2 g (Takeda Pharmaceutical Co.)), which includes 2 g of omega-3 fatty acids from day 1 until day 168 of the treatment period. The primary endpoint is the completion rate of four total courses of S-1. Secondary endpoints are postoperative cholangitis, time to recurrence or distant metastasis, changes in nutritional index, changes in the lymphocyte blast transformation test induced by phytohaemagglutinin, and concanavalin A and diamine oxidase serum activity during adjuvant chemotherapy. All adverse events will be evaluated. ETHICS AND DISSEMINATION: This protocol was approved by the Institutional Review Board of Kobe University Hospital. The findings from this study will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000031247.

Clinical Benefit of Preoperative Exercise and Nutritional Therapy for Patients Undergoing Hepato-Pancreato-Biliary Surgeries for Malignancy.

BACKGROUND: The impact of prehabilitation on physical fitness and postoperative course after hepato-pancreato-biliary (HPB) surgeries for malignancy is unknown. The current study aimed to investigate the effect of preoperative exercise and nutritional therapies on nutritional status, physical fitness, and postoperative outcomes of patients undergoing an invasive HPB surgery for malignancy. METHODS: Patients who underwent open abdominal surgeries for HPB malignancies (major hepatectomy, pancreatoduodenectomy, or hepato-pancreatoduodenectomy) between 2016 and 2017 were subjected to prehabilitation. Patients before the introduction of prehabilitation were included as historical control subjects for 1:1 propensity score-matching (no-prehabilitation group). The preoperative nutritional status and postoperative course were compared between the two groups. RESULTS: The prehabilitation group consisted of 76 patients scheduled to undergo HPB surgeries for malignancy. An identical number of patients were selected as the no-prehabilitation group after propensity score-matching. During the waiting period, serum albumin levels were significantly deteriorated in the no-prehabilitation group, whereas this index did not deteriorate or even improved in the prehabilitation group. By performing prehabilitation, a 6-min walk distance and total muscle/fat ratio were significantly increased during the waiting period. Although the overall incidence of postoperative complications did not differ between the two groups, the postoperative hospital stay was shorter in the prehabilitation group than in the no-prehabilitation group (median, 23 vs 30 days; p = 0.045). CONCLUSION: The introduction of prehabilitation prevented nutritional deterioration, improved physical fitness before surgery, and shortened the postoperative hospital stay for the patients undergoing HPB surgeries for malignancy.

Comparison between autologous and homologous blood transfusions in liver resection for biliary tract cancer: a propensity score matching analysis.

BACKGROUND: It remains unclear whether preoperative blood donation is truly beneficial in liver surgery. The aim of this study was to compare surgical outcomes between patients receiving autologous and homologous transfusions during liver resection for biliary tract cancer (BTC). METHODS: Patients who underwent hepatectomy for BTC were retrospectively reviewed (2006-2017). Patients who deposited autologous blood and underwent resection without homologous blood transfusion intraoperatively (Autologous group) were compared with non-depositing patients who required homologous transfusion during hepatectomy (Homologous group). Propensity score matching analyses were performed to adjust the data for the baseline characteristics of both groups. RESULTS: During the study period, 359 patients were included in the Autologous group, and 105 patients were in the Homologous group. The postoperative maximum total bilirubin (T-Bil) levels and the incidence of postoperative liver failure were significantly higher in the Homologous group than in the Autologous group. After propensity score matching, postoperative maximum T-Bil levels were significantly higher in the Homologous group, whereas the incidence of postoperative liver failure was comparable between the two groups; between-group differences were not observed for the remaining major complications, hospital stays and mortality. CONCLUSION: Although autologous blood transfusion may minimize postoperative hyperbilirubinemia, it may not decrease the risk for mortality or morbidities following hepatectomy for BTC.

Efficacy of a sequential treatment strategy with GEMOX-based followed by FOLFIRI-based chemotherapy in advanced biliary tract cancers.

BACKGROUND: Gemcitabine (GEM)-platinum chemotherapy stands as first-line therapy for patients with recurrent/advanced biliary tract cancer (BTC), yielding progression-free survival (PFS) of 3.4-6.4 months. No standard second-line chemotherapy after GEM-platinum failure exists and data on survival benefit remain limited. MATERIAL AND METHODS: We retrospectively reviewed patients with recurrent/advanced BTC who received gemcitabine-oxaliplatin (GEMOX)-based chemotherapy followed by 5-fluorouracil-irinotecan (FOLFIRI)-based chemotherapy to evaluate the efficacy of the sequential treatment strategy. Overall survival (OS) and PFS were calculated by Kaplan-Meier method. RESULTS: Fifty-two patients were analyzed, 21 (40%) had intrahepatic, 14 (27%) had hilar/extrahepatic, and 17 (33%) had gallbladder cancer. Median age was 64 years (range 38-79 years). Prior curative intent resection of the primary tumor was performed in 23 (44.2%) patients and GEMOX adjuvant chemotherapy was given in 12 (23.1%) patients. After a median follow-up of 36.3 months, 47 (90.4%) patients completed the treatment strategy. First-sequence GEMOX and second sequence FOLFIRI achieved 4.8 months and 3.2 months median PFS, respectively. The global OS for the sequential chemotherapy was 21.9 months. The sequence of FOLFIRI resulted in a median OS of 8.4 months. CONCLUSION: The sequence of GEMOX-FOLFIRI is a potential treatment strategy for patients with recurrent/advanced BTC.

Prognostic factors and adjuvant treatments for surgically treated cancers of the biliary tract: a multicentre study of the Anatolian Society of Medical Oncology (ASMO).

BACKGROUND: Biliary tract cancers are rare, and surgical resection is the standard treatment at early stages. However, reports on the benefits of adjuvant treatment following surgical resection are conflicting. This study aimed to evaluate the factors affecting survival and adjuvant treatments in patients with surgically treated biliary tract cancers. MATERIALS AND METHODS: Patient clinical features, adjuvant treatments, and efficacy and prognostic factor data were evaluated. Survival analyses were performed using SPSS 15.0. RESULTS: The median overall survival was 30.7 months (95% confidence interval [CI], 18.4-42.9 months). Median survival was 19 months (95% CI, 6-33) for patients treated with fluorouracil based chemotherapy and 53 months (95% CI, 33.2-78.8) with gemcitabine based chemotherapy (p=0.033). On univariate analysis, poor prognostic factors for survival were galbladder localization, perineural invasion, hepatic invasion, a lack of adjuvant chemoradiotherapy treatment, and a lack of lymph node dissection. On multivariate analysis, perineural invasion was a poor prognostic factor (p=0.008). CONCLUSIONS: Biliary tract cancers generally have poor prognoses. The main factors affecting survival are tumour localization, perineural invasion, hepatic invasion, adjuvant chemoradiotherapy, and lymph node dissection. Gemcitabine-based adjuvant chemotherapy is more effective than 5-fluorouracil-based chemotherapy.

Systematic review with network meta-analysis: adjuvant therapy for resected biliary tract cancer.

BACKGROUND: Major adjuvant therapies for biliary tract cancer (BTC) include fluorouracil, gemcitabine and chemoradiation (CRT), but the optimum regimen remains inconclusive. AIM: To compare these therapies in terms of patient survival rates after resection and toxic effects. METHODS: We searched PubMed for controlled trials comparing the above three therapies with each other or observation alone until 31 January 2014. We estimated the hazard ratios (HRs) for death and odds ratios (ORs) for toxic effects among different therapies. Subgroup analyses based on positive lymph node or resection margin were also performed. RESULTS: Twelve eligible articles were included. Gemcitabine improved 5-year survival (HR 2.12, 95% CI, confidence interval 1.23-4.02, P = 0.01), whereas fluorouracil (HR 1.61, 95% CI 0.74-3.67) and CRT (HR 1.55, 95% CI 0.82-3.32) provided a poorer survival outcome compared with gemcitabine after 1 year. Similarly, for 5-year survival rates, although differing, CRT did not provide a significant improvement in survival (HR 0.46, 95% CI 0.20-0.97) compared with gemcitabine. Fluorouracil did not appear to provide benefit over gemcitabine (HR 1.56, 95% CI 0.77-3.35). CRT was ranked highest for toxic effects including haematological (OR 5.45, 95% CI 0.01-483.85) and nonhaematological (OR 5.77, 95% CI 0.01-3807.40). CONCLUSIONS: Chemotherapy with gemcitabine is the optimum adjuvant treatment with a balanced benefit-toxicity ratio for resected biliary tract cancer. Chemoradiation was more likely to cause toxic effects.

Safety and optimal management of hepatic arterial infusion chemotherapy after pancreatectomy for pancreatobiliary cancer.

OBJECTIVE: The purpose of this study was to assess the safety of hepatic arterial infusion (HAI) chemotherapy after pancreatectomy for pancreatobiliary cancer. MATERIALS AND METHODS: The study subjects comprised 51 patients treated with HAI chemotherapy after pancreatectomy: 31 patients had undergone pancreaticoduodenectomy or total pancreatectomy and 20 patients had undergone distal pancreatectomy. HAI chemotherapy was performed for the prevention of liver metastasis in 42 patients and for the treatment of metastases in nine patients. HAI chemotherapy consisted of 5-fluorouracil administered at 1000 mg/m(2)/wk. After each cycle of chemotherapy, the patency of the hepatic artery and complications were evaluated using digital subtraction angiography and CT arteriography via the catheter-port system. RESULTS: Placement of the catheter-port system was successful in all patients. Hepatic arterial occlusion and severe asymptomatic hepatic artery stenosis were observed in one patient (2%) and 10 patients (19.6%), respectively. The hepatic arterial patency rate tended to be lower in the group who underwent pancreaticoduodenectomy or total pancreatectomy (71%) than in the group who underwent distal pancreatectomy (90%), although the difference was not significant (p = 0.107). Four asymptomatic patients with hepatic artery stenosis restarted HAI chemotherapy after a 4-week withdrawal of treatment. In three patients (5.9%), all of whom had undergone pancreaticoduodenectomy, liver abscess or biloma developed synchronously with asymptomatic hepatic artery stenosis. All three cases were cured by percutaneous abscess drainage or conservative management. The tumor response rate in the treatment of liver metastases was 44.4%. The hepatic recurrence rate with adjuvant therapy was 7.1%. CONCLUSION: Our findings suggest that HAI chemotherapy after pancreatectomy is feasible and tolerable, although caution is required particularly after pancreaticoduodenectomy or after total pancreatectomy.

Role of chemotherapy in treatments for biliary tract cancer.

The purpose of chemotherapy in patients with advanced solid cancers, including biliary tract cancer, is generally to improve the survival and quality of life of the patients. Also, adjuvant chemotherapy is expected to increase the curability of surgery in patients scheduled to undergo surgery. Most patients with unresectable biliary tract cancer develop obstructive jaundice, and biliary drainage is needed before any of the aforementioned treatments. Once jaundice is resolved by stenting of the bile duct or bilio-intestinal bypass, cholangitis often develops, leading to rapid deterioration of the patient's general condition. Therefore, the beneficial effect of chemotherapy in such patients remains controversial. A few randomized controlled trials have demonstrated the survival benefit of chemotherapy as compared with supportive care. In one of these trials, improvement of the quality of life was also confirmed. Recently, since the survival benefit of combined gemcitabine plus cisplatin therapy over gemcitabine alone has been demonstrated in randomized controlled clinical trials, this combined regimen has been recognized as a standard therapy for unresectable biliary tract cancer. A second-line regimen is now expected to be established for patients with gemcitabine-refractory biliary tract cancer, although the significance of second-line therapy remains unclear. One of the next issues in relation to chemotherapy for biliary tract cancer is the development of molecular-targeted agents; however, few large clinical trials of such agents have been conducted for biliary tract cancer. Various issues in chemotherapy for biliary tract cancer remain to be investigated, and global cooperation is necessary to conduct large clinical trials.

Adjuvant chemotherapy for resectable biliary tract cancer: current status and future direction.

The prognosis of patients with biliary tract cancer remains unsatisfactory even with surgery owing to the high recurrence rate. Therefore, an effective adjuvant chemotherapy is required to prolong survival. A few randomized controlled trials in patients with limited biliary tract cancer have been reported, but the efficacy of adjuvant chemotherapy could not be clarified. To date, effective adjuvant chemotherapy with evidence has not been established, and the standard therapy for patients with resectable biliary tract cancer has only been surgical treatment. Recently, a number of newer toxic agents have been shown to induce response in patients with advanced biliary tract cancer. Moreover, the morbi-mortality rate of operation for this cancer has been decreasing owing to advances in operative techniques and perioperative management. Given this background, a number of adjuvant chemotherapy trials have been started using gemcitabine, capecitabine, S-1, and combination chemotherapy with platinum. The results of these trials will be reported in the near future. Overall, the important aspects of adjuvant chemotherapy for biliary tract cancer are to establish well-organized and active clinical trial study groups, to conduct well-designed multicenter randomized controlled trials, and to continue such trials without interruption in the future.

Treatment of borderline cases for curative resection of biliary tract cancer.

BACKGROUND AND AIM: To dissect the high rate of non-curative resection associated with biliary tract cancer, we compared the outcome of non-curative resection with that of inoperable cancer in patients referred for surgery. METHODS: We retrospectively analyzed 447 patients with biliary tract cancer who were referred to our hospital between 1970 and 2008. We compared the background and overall survival (OS) rates accordingly to surgery (curative resection, non-curative resection, or no surgery "inoperable") and alternative therapies (chemotherapy and/or radiotherapy). RESULTS: The 3-year OS rate was 19% for the non-curative resection group (n=72) and 2% for the inoperable group (n=135, P<0.0001). Among the inoperable cases, the 3-year OS rate for patient who received chemotherapy, including gemcitabine (GEM), was 18% (n=18), which was similar to that of patients of the non-curative resection who were treated with GEM (P=0.7379). There were no significant differences in survival between non-curative resection without GEM and inoperable cases with GEM-based chemotherapy. CONCLUSION: Our results indicate that the prognosis of patients who undergo non-curative surgery is better than those with inoperable cancer, but similar to those who receive chemotherapy including GEM.

Complementary and alternative medicine use among general surgery, hepatobiliary surgery and surgical oncology patients.

BACKGROUND: The use of complementary and alternative medicine (CAM) is becoming more common, particularly among cancer patients. We sought to define the frequency of CAM use among general surgery, hepatobiliary and surgical oncology patients and to define some of the determinants of CAM use in patients with benign and malignant disease. METHODS: We asked all patients attending the clinics of 3 hepatobiliary/surgical oncology surgeons from 2002 to 2005 to voluntarily respond on first and subsequent visits to a questionnaire related to the use of CAM. We randomly selected patients for review. RESULTS: We reviewed a total of 490 surveys from 357 patients. Overall CAM use was 27%. There was significantly more CAM use among cancer (34%) versus noncancer patients (21%; p = 0.008), and the use of CAM was more common in patients with unresectable cancer (51%) than resectable cancer (22%; p < 0.001). There was no significant difference in use between men and women. There did not appear to be a change in CAM use with progression of cancer. The most common CAM was herbs or supplements (58% of all users), which were most frequently used by patients with malignant disease. Among the 27 herbs reported to be ingested, 10 are associated with bleeding and hepatotoxicity, as described in the literature. CONCLUSION: Prospective studies evaluating surgical outcomes related to CAM use are needed.

The role of ciprofloxacin in prolonging polyethylene biliary stent patency: a multicenter, double-blinded effectiveness study.

Plastic stents are the mainstay of the palliation of malignant jaundice but are complicated by recurrent obstruction. Previous trials have failed to demonstrate any improvement in patency with the use of antibiotics. Patients with malignant jaundice were randomized in a double-blind fashion, after polyethylene stent insertion, to receive ciprofloxacin or placebo. After successful stent decompression, there were 50 patients in the treatment arm and 44 in the placebo. There were 14 (33%) episodes of stent occlusion in the ciprofloxacin group versus 23 (49%) in placebo (chi(2) test, P=0.115). There was no significant difference in patency (log-rank test, P=0.17). There were significantly fewer episodes of cholangitis with ciprofloxacin: 10 (23%) versus 21 (42%) in the placebo (P=0.047). The ciprofloxacin group also demonstrated a significant improvement in the Social Function domain of the SF-36 Quality of Life Survey at 1 month (paired T test, P=0.03). The other domains of the SF-36 were not different, nor was survival (log rank, P=0.80). There is insufficient evidence to show that prophylactic ciprofloxacin can prolong plastic biliary stent patency. The observed trends suggest that ciprofloxacin significantly decreases the incidence of cholangitis and results in improvements in certain aspects of quality of life.

One hundred consecutive hepatobiliary resections for biliary hilar malignancy: preoperative blood donation, blood loss, transfusion, and outcome.

BACKGROUND: Many reports on blood loss and transfusion requirements during hepatectomy for metastatic liver cancer or hepatocellular carcinoma have been published; however, there are no reports on these issues in hepatectomy for biliary hilar malignancy. The aim of this study was to review our experience with blood loss and perioperative blood requirements in 100 consecutive hepatectomies for biliary hilar malignancy. METHODS: One hundred consecutive hepatectomies with en bloc resection of the caudate lobe and extrahepatic bile duct for hilar malignancies were performed, including 81 perihilar cholangiocarcinomas and 19 advanced gallbladder carcinomas involving the hepatic hilus. Fifty-eight hilar resections were combined with other organ and/or vascular resection. Data on preoperative blood donation, intraoperative blood loss, and perioperative transfusion were collected and analyzed. RESULTS: Preoperative autologous blood donation was possible in 73 patients (3.4 +/- 1.2 U). Intraoperative blood loss was 1850 +/- 1000 mL (range, 677-5900 mL), and it was < 2000 mL in 62 patients. Intraoperatively, only 7 of the 73 patients (10%) who donated blood received transfusion of unheated, homologous blood products (packed red blood cells or fresh frozen plasma), whereas 18 the 23 patients (67%) without donation received homologous transfusions. Only 16 patients received transfusion postoperatively, and overall, 35 patients received unheated homologous blood products. Total serum bilirubin concentrations after hepatectomy in patients receiving autologous blood transfusion only was similar to those in patients who did not receive transfusion. The incidence of postoperative complications was higher in the 35 patients who received perioperative homologous transfusion than in 65 patients who did not (94% vs 52%; P <.0001). The mortality rate (including all deaths) was 3% (myocardial infarction, intra-abdominal bleeding, and liver failure, 1 patient each). CONCLUSIONS: Despite the technical difficulties arising from hepatectomy for biliary hilar malignancy, approximately two thirds of hepatectomies can be performed in an experienced center without perioperative homologous blood transfusion using preoperative blood donation.

[Adjuvant arterial infusion chemotherapy for patients with biliary cancer].

Although surgery is the only potentially curative treatment for biliary cancer, patients frequently develop liver metastasis, local recurrence, and peritoneal metastasis after complete resection. Liver metastasis is a common mode of progression for biliary cancer, and the prognosis is extremely poor when it occurs. Between January 2000 and December 2003, 18 out of 37 patients received adjuvant arterial infusion chemotherapy after curative resection of biliary cancer. Nine of these 18 patients had bile duct cancer, seven had gallbladder cancer, and two had cancer of the papilla of Vater. A catheter was placed using Seldinger's technique, with the tip being advanced into the common hepatic artery via the femoral artery. Then 1,000 mg/body of 5-FU was administered as a 24-hour continuous infusion on days 1-3 and 5-7. Two cycles of this chemotherapy were delivered through an angiography catheter without using a reservoir port. This treatment caused no severe systemic or abdominal complications. The two groups were well balanced with respect to prognostic factors. The 1-year survival rate was 76.2% in the adjuvant chemotherapy group versus 52.7% in the non-adjuvant chemotherapy group, while the 3-year survival rates were 47.6% and 39.5%, respectively (Wilcoxon test, p=0.048). Median overall survival was superior in the adjuvant chemotherapy group and the difference was significant. High-dose arterial infusion of 5-FU seems to be a safe, tolerable, and effective regimen for preventing the postoperative recurrence of biliary cancer.

Percutaneous portal vein embolisation in preparation for extended hepatic resection of primary nonresectable liver tumours.

BACKGROUND: In patients with malignant primary and secondary liver tumours or proximal bile duct carcinoma radical surgery is superior to all other therapeutic modalities in terms of survival and quality of life. Radical resection, however, often requires the removal of a large amount of liver parenchyma, resulting in a marked reduction of functional liver tissue with the risk of liver failure. AIM: Preoperative partial portal vein embolisation induces hypertrophy of the controlateral liver and thereby increases the safety of extended liver resections. PATIENTS AND METHODS: Between January 1997 and February 2001 we applied this strategy in 19 patients with primary and secondary nonresectable hepatobiliary malignancies, in whom the estimated amount of the remnant liver was < or =25% of the liver volume. RESULTS: The increase in volume ranged between 7 and 245%. Radical extended liver resection was performed in 13 patients (68%) without mortality. After a mean observation time of 22 months patient survival was 19 months with six tumour-related deaths during the second year after surgery. The remaining seven patients are alive and well with tumour recurrence in one. CONCLUSION: Preoperative partial portal vein embolisation allows more patients with previously unresectable liver tumours to benefit from a potentially curative resection.

Regional chemotherapy in biliary tract cancers--a single institution experience.

BACKGROUND/AIMS: The prognosis of biliary tract cancers is poor. The aim of the present report was to analyze retrospectively the effectiveness of regional chemotherapy in patients with biliary tract cancers treated at a single institution. METHODOLOGY: Thirty-two patients with biliary tract cancers, 17 patients with cholangiocarcinoma and 15 patients with gallbladder carcinoma, were treated by regional administration of the chemotherapy, usually the combination of 5-fluorouracil, cisplatin and folinic acid. Eighteen patients with inoperable tumors received no surgical treatment, 10 patients were treated by palliative resection (cohort B), and 4 patients received radical surgery (cohort C). RESULTS: The median survival of the patients is (mean +/- standard deviation) 14 +/- 17+ (median 7+) months for cohort A patients, 22 +/- 17+ (median 17+) months for cohort B patients, and 32 +/- 4+ (median 33+) months for cohort C patients. One-year survival was 38% (6 out of 16 patients) for cohort A, 80% (8 out of 10 patients) for cohort B, and 100% (4 out of 4 patients for cohort C). Two-year survival was 15% (2 out of 13) for cohort A, 30% (3 out of 10) for cohort B, and 100% (4 out of 4) for cohort C. One out of 12 patients (8%) in cohort A and 1 out of 10 patients (10%) in cohort B survived more than 5 years. After intraarterial chemotherapy, a significant increase was observed in the absolute numbers of CD3+, CD3+CD8+ and CD8+CD28+ lymphocytes, as well as an increase in CD3+CD4+ and natural killer lymphocytes. CONCLUSIONS: Regional chemotherapy is active in controlling the disease, and seems to result in prolongation of survival in patients with biliary tract cancer. Administration of regional chemotherapy is also associated with a rise of circulating lymphocyte numbers.