Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer.

Ampullary cancer is a rare periampullary cancer currently with no targeted therapeutic agent. It is important to develop a deeper understanding of the carcinogenesis of ampullary cancer. We attempted to explore the characteristics of ampullary cancer in our dataset and a public database, followed by a search for potential drugs. We used a bioinformatics pipeline to analyze complementary (c)DNA microarray data of ampullary cancer and surrounding normal duodenal tissues from five patients. A public database from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) was applied for external validation. Bioinformatics tools used included the Gene Set Enrichment Analysis (GSEA), Database for Annotation, Visualization and Integrated Discovery (DAVID), MetaCore, Kyoto Encyclopedia of Genes and Genomes (KEGG), Hallmark, BioCarta, Reactome, and Connectivity Map (CMap). In total, 9097 genes were upregulated in the five ampullary cancer samples compared to normal duodenal tissues. From the MetaCore analysis, genes of peroxisome proliferator-activated receptor alpha (PPARA) and retinoid X receptor (RXR)-regulated lipid metabolism were overexpressed in ampullary cancer tissues. Further a GSEA of the KEGG, Hallmark, Reactome, and Gene Ontology databases revealed that PPARA and lipid metabolism-related genes were enriched in our specimens of ampullary cancer and in the NCBI GSE39409 database. Expressions of PPARA messenger (m)RNA and the PPAR-α protein were higher in clinical samples and cell lines of ampullary cancer. US Food and Drug Administration (FDA)-approved drugs, including alvespimycin, trichostatin A (a histone deacetylase inhibitor), and cytochalasin B, may have novel therapeutic effects in ampullary cancer patients as predicted by the CMap analysis. Trichostatin A was the most potent agent for ampullary cancer with a half maximal inhibitory concentration of < 0.3 µM. According to our results, upregulation of PPARA and lipid metabolism-related genes are potential pathways in the carcinogenesis and development of ampullary cancer. Results from the CMap analysis suggested potential drugs for patients with ampullary cancer.

Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.

INTRODUCTION: Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. METHODS: A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. RESULTS: Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. CONCLUSIONS: Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma.

Prognostic Significance of Nodal Ratio in Patients Undergoing Adjuvant Chemoradiotherapy After Curative Resection for Ampullary Cancer.

OBJECTIVES: To analyze the outcome of patients with ampullary cancer who had undergone curative surgery followed by adjuvant chemoradiotherapy and to identify the prognostic factors for these patients METHODS: : Between January 1991 and August 2006, 71 patients with ampullary cancer underwent curative resection followed by adjuvant radiotherapy. There were 38 males and 33 females, and median age was 56 years (range, 28 to 77 y). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to 40 to 50 Gy at 2 Gy/fraction; 67 patients also received intravenous 5-fluorouracil as a radiosensitizer. Median follow-up duration was 72 months for survivors. RESULTS: There were 5 isolated locoregional recurrences, 20 isolated distant metastases, and 11 combined locoregional and distant relapses. The 5-year locoregional relapse-free and overall survival rates were 76.2% and 64.5%, respectively. On multivariate analysis, nodal ratio and histologic differentiation were significant prognostic factors for overall survival (P=0.0382 and 0.0331, respectively). CONCLUSIONS: Adjuvant chemoradiotherapy after curative resection can achieve a long-term survival rate in patients with ampullary cancer. Nodal ratio and histologic differentiation are independent prognostic factors for these patients.

Effects of chewing gum against postoperative ileus after pancreaticoduodenectomy--a randomized controlled trial.

BACKGROUND: Postoperative ileus is common after surgery. One non-pharmacological intervention that has shown promising results in reducing the duration of postoperative ileus is chewing gum after surgery. However, this has not been investigated in upper gastrointestinal surgery such as pancreatic surgery. Hence the aim of this study was to investigate the effects of chewing gum treatment on patients undergoing pancreaticoduodenectomy ad modum whipple due to pancreatic or periampullary cancer. METHODS: This study was conducted as a phase III trial that was terminated early. Patients diagnosed with pancreatic tumours scheduled for pancreaticoduodenectomy ad modum whipple were included. The treatment group received chewing gum postoperatively and standard care. Controls received glucose solution and standard care. Chewing gum and glucose were used four times a day during the whole hospital stay. Time to first flatus and stool was defined as the primary outcome. The secondary outcome was start with clear liquids, start with liquid diet and length of hospital stay. RESULTS: No statistically significant differences could be observed between the chewing gum intervention group and the control group. However, a numerical difference in mean time was observed in first flatus, first stool, start of clear fluids, and start of liquid diet and length of hospital stay in favour of the intervention group. CONCLUSIONS: Although this study did not find statistically significant differences favouring the use of chewing gum for postoperative ileus, a positive trend was observed of a reduction of the impact of postoperative ileus among patients after pancreatic surgery. It also contributes valuable methodological experience that is important for future studies of chewing gum interventions during recovery after pancreatic surgery. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02319512 , publication date 2014-12-17.

Prognostic score for recurrence after Whipple's pancreaticoduodenectomy for ampullary carcinomas; results of an AGEO retrospective multicenter cohort.

BACKGROUND: Ampullary carcinoma (AC) is a relatively rare entity often managed as a biliopancreatic carcinoma. AC has a better prognosis than peri ampullary tumors after resection, but more than a third of patients relapse. Factors predictive of recurrence are controversial, mainly because the relevant studies are very small or also included non AC tumors. There are no guidelines on the use of adjuvant or neoadjuvant chemotherapy. The aim of this study was to identify prognostic factors for recurrence after AC resection in a large multicentric cohort, and to establish a simple, practical, predictive score for recurrence in order to guide multidisciplinary decisions. METHODS: We included 152 consecutive patients who underwent Whipple's pancreaticoduodenectomy for ampullary carcinoma from January 2000 to December 2010 in 10 gastrointestinal oncology departments. RESULTS: The estimated overall 5-year disease-free survival rate (DFS) was 47.1%. In multivariate analysis, age≥ 75 years at diagnosis (p < 0.0001), poor general condition (p = 0.01), poorly (p = 0.005) or moderately differentiated tumors (p = 0.01) and TNM stage IIb or III (p = 0.05) were associated with poor DFS. Based on this multivariate analysis, we developed a prognostic score with three levels of risk: DFS at 5 years was 73.5% in the low-risk group and 20.1% in the high-risk group. CONCLUSION: This simple score based on age, general condition, tumor differentiation and TNM stage can classify patients into subgroups with different risks of recurrence and could help with therapeutic decisionmaking.

Adenocarcinoma of the ampulla of Vater: what treatment options are available?

The scientific literature on adenocarcinoma of the ampulla (papilla) of Vater suggests that it either represents a distinct entity or is more closely related to small bowel adenocarcinoma than to the biliary malignancies. The ambiguity surrounding this rare cancer has kindled research exploring its immunohistochemistry aspects and gene expression profiling. While the basis of management for resectable disease remains surgical intervention, the role of adjuvant chemotherapy is not clear. A recent large phase 3 clinical trial conducted in patients with resected ampulla of Vater adenocarcinoma favored adjuvant chemotherapy over observation alone. The standards of therapy for the advanced small bowel adenocarcinoma and biliary cancer are fluoropyrimidine derivatives and gemcitabine-based combinations, respectively. In addition, new biologic and targeted agents may enhance clinical results seen in this cancer type. Therefore, diligently designed clinical trials are necessary to establish its optimal treatment strategies. We describe herein a patient with ampulla of Vater adenocarcinoma who had an exceptional response to fluoropyrimidine-based chemotherapy. We further include a discussion reviewing the clinicopathologic aspects of this neoplasm as well as focus on currently available and future therapeutic options.

Lethal cardiotoxicity, steatohepatitis, chronic pancreatitis, and acute enteritis induced by capecitabine and oxaliplatin in a 36-year-old woman.

A 36-year-old female was hospitalized with symptoms suggesting intestinal occlusion. She was diagnosed with adenocarcinoma of the ampulla of Vater (pT4N0 stage) and underwent cephalic duodenopancreatectomy 8 months ago. Five cycles of postoperative chemotherapy were administrated using capecitabine and oxaliplatin (CAPOX or XELOX), the last one being completed 1 month ago. During the present hospitalization, because of normal computed tomography and ultrasound abdominal examination, rehydration and antibiotherapy were administrated. However, 4 days after hospital admission, the patient died. At autopsy and histological examination, we found a severe myocardial sclerosis with large scarring areas, severe steatohepatitis, chronic pancreatitis with large fibrotic areas, and acute enteritis. Alcohol consumption was denied. The patient died due to associated heart, liver and pancreatic failure. This multiorgan toxicity and death following CAPOX regimen had not yet been reported in the literature. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6472150549833105.

Prognostic significance of tumour location after adjuvant chemoradiotherapy for periampullary adenocarcinoma.

PURPOSE: To analyse the outcome of adjuvant chemoradiotherapy for periampullary adenocarcinoma and the impact of tumour location as a prognosticator. METHODS AND MATERIALS: Between January 1991 and December 2002, 147 patients with periampullary cancer underwent adjuvant chemoradiotherapy after pancreaticoduodenectomy. Postoperative radiotherapy was delivered to tumour bed and regional lymph nodes up to 40 Gy at 2 Gy/fraction with a two-week planned rest. Intravenous 5-fluorouracil (500 mg/m(2)/day) was given on days 1-3 of each split course. The median follow-up period was 82 months in survivors. RESULTS: Tumour >2 cm and margin-positivity were more common in patients with pancreatic cancer than nonpancreatic periampullary cancers (p<0.0001 and 0.0780, respectively). According to the tumour location, 5-year overall survival rates of ampulla of Vater, distal common bile duct, duodenal and pancreatic head cancers were 53.0%, 50.3%, 37.5%, and 13.0%, respectively (p<0.0001). On multivariate analysis, pancreatic location (p<0.0001) and nodal involvement (p=0.0123) were associated with inferior overall survival. CONCLUSION: Regardless of its advanced histologic features, pancreatic location itself was an adverse prognostic factor affecting overall survival.

The influence of prognostic factors and adjuvant chemoradiation on survival after pancreaticoduodenectomy for ampullary carcinoma.

INTRODUCTION: The prognosis after pancreaticoduodenectomy (PD) for ampullary carcinoma (AC) is superior to that of pancreatic cancer. Decisions regarding adjuvant therapy are influenced by factors such as nodal status, stage, and grade, but the influence of these individual variables on survival is unclear. METHODS: A prospective tumor registry database was queried to identify patients who underwent PD for AC at Thomas Jefferson University between Jan 1997 and Apr 2009. The study was conducted with the approval of the institutional review board. Data were collected through review of hospital and departmental charts. Overall survival (OS) was analyzed using univariate and multivariate Cox proportional hazard models. The proportional hazard assumption was verified for the overall model and individual covariates. RESULTS: A total of 61 patients underwent PD for AC at our institution. There were five perioperative deaths (8.2%). Mean age was 70 years (62% male). Median survival time (MST) was 50 months for all patients. Only primary tumor stage, T1/T2 versus T3/T4 (American Joint Committee on Cancer Staging, version 6), was associated with OS in univariate analyses (p = 0.003). The association of nodal status with OS was borderline-significant (p = 0.08), with the MST being 84 months for node-negative and 17 months for node-positive patients. The remaining covariates were not predictors of OS. In the multivariate analysis, only primary tumor stage (HR, 5.1; p < 0.001) and age (HR, 1.04; p = 0.06), but not nodal status or adjuvant therapy, were associated with overall survival. CONCLUSIONS: Advanced primary tumor stage and age were associated with inferior OS after PD for AC. Adjuvant therapy did not impact survival. Patients with advanced tumor stage should be considered for clinical trials of adjuvant therapy after PD with novel compounds and optimized radiation therapy strategies.

Is duodenal invasion a relevant prognosticator in patients undergoing adjuvant chemoradiotherapy for distal common bile duct cancer?

PURPOSE: To analyze the outcome of adjuvant chemoradiotherapy for patients with distal common bile duct (CBD) cancer who underwent curative surgery, and to identify the prognostic factors for these patients. METHODS AND MATERIALS: Between January 1991 and December 2002, 38 patients with adenocarcinoma of the distal CBD underwent curative resection followed by adjuvant chemoradiotherapy. There were 27 men and 11 women, and the median age was 60 years (range, 34-73). Adjuvant radiotherapy was delivered to the tumor bed and regional lymph nodes up to 40 Gy at 2 Gy/fraction with a 2-week planned rest. Intravenous 5-fluorouracil (500 mg/m(2)/day) was given on day 1 to day 3 of each split course. The median follow-up period was 39 months. RESULTS: The 5-year overall survival rate of all patients was 49.1%. On univariate analysis, only histologic differentiation (p = 0.0005) was associated with overall survival. Tumor size (< or =2 cm vs. >2 cm) had a marginally significant impact on the treatment outcome (p = 0.0624). However, there was no difference in overall survival rates between T3 and T4 tumors (p = 0.6189), for which the main determinants were pancreatic and duodenal invasion, respectively. On multivariate analysis, histologic differentiation (p = 0.0092) and tumor size (p = 0.0046) were independent risk factors for overall survival. CONCLUSIONS: Long-term survival can be expected in patients with distal CBD cancer undergoing curative surgery and adjuvant chemoradiotherapy. Histologic differentiation and tumor size were significant prognostic factors predicting overall survival, whereas duodenal invasion was not. This finding suggests the need for further refinement in tumor staging.

Role of adjuvant chemoradiotherapy for ampulla of Vater cancer.

PURPOSE: To evaluate the role of adjuvant chemoradiotherapy for ampulla of Vater cancer. METHODS AND MATERIALS: Between January 1991 and December 2002, 118 patients with ampulla of Vater cancer underwent en bloc resection. Forty-one patients received adjuvant chemoradiotherapy [RT(+) group], and 77 did not [RT(-) group]. Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes, for a total dose of up to 40 Gy delivered in 2-Gy fractions, with a planned 2-week rest period halfway through the treatment period. Intravenous 5-fluorouracil (500 mg/m(2)/day) was given on Days 1 to 3 of each split course. The median follow-up was 65 months. RESULTS: The 5-year overall survival rate in the RT(-) and RT(+) groups was 66.9% and 52.8%, respectively (p = 0.2225). The 5-year locoregional relapse-free survival rate in the RT(-) and RT(+) groups was 79.9% and 80.2%, respectively (p = 0.9582). When age, type of operation, T stage, N stage, histologic differentiation, and the use of adjuvant chemoradiotherapy were incorporated into the Cox proportional hazard model, there was an improvement in the locoregional relapse-free survival rate (p = 0.0050) and a trend toward a longer overall survival (p = 0.0762) associated with the use of adjuvant chemoradiotherapy. Improved overall survival (p = 0.0235) and locoregional relapse-free survival (p = 0.0095) were also evident in patients with nodal metastasis. In contrast, enhanced locoregional control (p = 0.0319) did not result in longer survival in patients with locally advanced disease (p = 0.4544). CONCLUSIONS: Adjuvant chemoradiotherapy may enhance locoregional control and overall survival in patients with ampulla of Vater cancer after curative resection, especially in those with nodal involvement.

Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891.

BACKGROUND: The role of adjuvant chemoradiation in pancreatic cancer remains unclear. This report presents the long-term follow-up results of EORTC trial 40891, which assessed the role of chemoradiation in resectable pancreatic cancer. METHODS: Two hundred eighteen patients were randomized after resection of the primary tumor. Eligible patients had T1-2 N0-N1a M0 pancreatic cancer or T1-3 N0-N1a M0 periampullary cancers, all histologic proven. Patients in the treatment group (n = 110) underwent postoperative chemoradiation (40 Gy plus 5-FU). Patients in the control group (n = 108) had no further adjuvant treatment. FINDINGS: After a median follow-up of 11.7 years, 173 deaths (79%) have been reported. The overall survival did not differ between the 2 treatment groups (Chemoradiation treatment vs. CONTROLS: death rate ratio 0.91, 95% CI: 0.68-1.23, P value 0.54). The 10-year overall survival was 18% in the whole population of patients (8% in the pancreatic head cancer group and 29% in the periampullary cancer group). INTERPRETATION: These results confirm the previous short-term analysis, indicating no benefit of adjuvant chemoradiation over observation in patients with resected pancreatic cancer or periampullary cancer. Patients with pancreatic cancer may survive more than 10 years. Only 1 of 31 cases recurred after year 7.

Liver perfusion chemotherapy for selected patients at a high-risk of liver metastasis after resection of duodenal and ampullary cancers.

OBJECTIVE: To evaluate the prognostic benefit of postoperative liver perfusion chemotherapy (LPC) in patients who undergo curative resection of duodenal and ampullary cancers. SUMMARY BACKGROUND DATA: Both nodal involvement and pancreatic invasion are poor prognostic indicators after curative resection of ampullary or duodenal cancers due to high incidences of liver metastasis. Therefore, we have performed postoperative LPC on a number of such "high-risk" patients. METHODS: During the period of 1990 to 2005, 72 consecutive patients successfully underwent curative (R0) resection of duodenal or ampullary carcinomas at our institution, The Osaka Medical Center for Cancer and Cardiovascular Diseases. Of these 72 patients, 38 were found to have positive nodal involvement and/or pancreatic invasion based on an intraoperative inspection, and of these, 28 were deemed to be suitable candidates for intraoperative catheterization: 1 catheter was placed into the gastroduodenal artery; another into the portal vein (group A). Postoperatively, they received an infusion of 5-fluorouracil (5-FU: 125 mg/d) via each of the 2 catheters for a period of 28 continuous days. The remaining 44 patients (group B) did not receive any other adjuvant therapy. The survival rates and patterns of disease failure were compared between these 2 groups and their subgroups. RESULTS: All 72 patients survived the operation, and all 28 patients in group A completed their courses of LPC without showing any significant adverse signs. Postoperative histopathology was later performed to get a more accurate picture regarding the degree of nodal involvement and/or pancreatic invasion: In group A, 21 patients (group A1) proved positive for nodal and/or pancreatic invasion whereas 7 patients (group A2) proved negative; and in group B, 16 patients proved positive (group B1) whereas 28 proved negative (group B2). Although group A displayed higher incidences of nodal involvement and pancreatic invasion, the 5-year survival rates for the 2 groups varied only slightly. The 5-year survival rate was 70% in group A1, 85% in group A2, 35% in group B1, and 92% in group B2, respectively. The difference between B1 and B2 and the difference between A1 and B1 were statistically significant, and these differences were conclusively found to be attributable to the different incidences of liver metastasis. CONCLUSION: Through this research, both nodal involvement and pancreatic invasion were confirmed to be reliable predictors of liver metastasis after curative resection of ampullary and duodenal cancers. Since LPC was proven to be effective in preventing the postoperative development of liver metastasis, it should be more actively performed for patients with a high-risk of liver metastasis.

Adjuvant therapy for ampullary carcinomas: the Mayo Clinic experience.

PURPOSE: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. METHODS AND MATERIALS: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. RESULTS: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p=0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p=0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. CONCLUSIONS: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed.

Adjuvant chemo-radiotherapy in ampullary cancers.

PURPOSE: Patterns of failure following surgical treatment of ampullary cancers indicate that up to 45% of patients develop loco-regional recurrence. The effect of adjuvant chemo-radiotherapy on survival and loco-regional control is not yet established in this malignancy. PATIENTS AND METHODS: From January 1989 to December 2000, 113 patients underwent pancreatico-duodenectomy for ampullary cancer. One hundred and four patients who survived the operation were available for analysis to study the effect of adjuvant chemo-radiotherapy on survival and loco-regional control. Forty-nine patients received adjuvant chemo-radiotherapy (median dose 50.4 Gy with concurrent 5-Flurouracil) and long-term outcome in these patients was compared with those 55 who did not receive adjuvant therapy. RESULTS: The overall median survival was 30.1 (range 1.6-140.0) months with actuarial 1, 3 and 5-year survival rates of 79, 43 and 33%, respectively. No significant difference in median survival (34.6 vs 24.5 months; P=0.3) and actuarial 5-year survival rates (38 vs 28%) was seen between those who received and those who did not receive adjuvant therapy. Adjuvant chemo-radiotherapy did not influence the survival in high-risk patients (P=0.84), in various T and N stages and had no impact on loco-regional recurrence (P=0.6). CONCLUSIONS: Adjuvant chemo-radiotherapy did not improve the long-term survival or decrease recurrence rates in patients with ampullary cancers who had undergone pancreatico-duodenectomy.

Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma.

BACKGROUND: To the authors' knowledge, the significance of postoperative adjuvant chemotherapy in pancreaticobiliary carcinoma has not yet been clarified. A randomized controlled study evaluated the effect of postoperative adjuvant therapy with mitomycin C (MMC) and 5-fluorouracil (5-FU) (MF arm) versus surgery alone (control arm) on survival and disease-free survival (DFS) for each specific disease comprising resected pancreaticobiliary carcinoma (pancreatic, gallbladder, bile duct, or ampulla of Vater carcinoma) separately. METHODS: Between April 1986 and June 1992, a total of 508 patients with resected pancreatic (n = 173), bile duct (n = 139), gallbladder (n = 140), or ampulla of Vater (n = 56) carcinomas were allocated randomly to either the MF group or the control group. The MF group received MMC (6 mg/m(2) intravenously [i.v.]) at the time of surgery and 5-FU (310 mg/m(2) i.v.) in 2 courses of treatment for 5 consecutive days during postoperative Weeks 1 and 3, followed by 5-FU (100 mg/m(2)orally) daily from postoperative Week 5 until disease recurrence. All patients were followed for 5 years. RESULTS: After ineligible patients were excluded, 158 patients with pancreatic carcinoma (81 in the MF group and 77 in the control group), 118 patients with bile duct carcinoma (58 in the MF group and 60 in the control group), 112 patients with gallbladder carcinoma (69 in the MF group and 43 in the control group), and 48 patients with carcinoma of the ampulla of Vater (24 in the MF group and 24 in the control group) were evaluated. Good compliance (> 80%) was achieved with MF treatment. The 5-year survival rate in gallbladder carcinoma patients was significantly better in the MF group (26.0%) compared with the control group (14.4%) (P = 0.0367). Similarly, the 5-year DFS rate of patients with gallbladder carcinoma was 20.3% in the MF group, which was significantly higher than the 11.6% DFS rate reported in the control group (P = 0.0210). Significant improvement in body weight compared with the control was observed only in patients with gallbladder carcinoma. There were no apparent differences in 5-year survival and 5-year DFS rates between patients with pancreatic, bile duct, or ampulla of Vater carcinomas. Multivariate analyses demonstrated a tendency for the MF group to have a lower risk of mortality (risk ratio of 0.654; P = 0.0825) and recurrence (risk ratio of 0.626; P = 0.0589). The most commonly reported adverse drug reactions were anorexia, nausea/emesis, stomatitis, and leukopenia, none of which were noted to be serious. CONCLUSIONS: The results of the current study indicate that gallbladder carcinoma patients who undergo noncurative resections may derive some benefit from systemic chemotherapy. However, alternative modalities must be developed for patients with carcinomas of the pancreas, bile duct, or ampulla of Vater.

[MR imaging of pancreatic lesions with Mn-DPDP. A histopathologic correlation]. / MRT von Läsionen des Pankreas mittels Mn-DPDP - Eine histopathologische Korrelation.

PURPOSE: To examine the diagnostic accuracy of pancreatic lesions using mangafodipir-trisodium (Mn-DPDP) enhanced MR imaging. The imaging results were correlated with the histopathological results. MATERIAL AND METHODS: 40 patients with suspicion of pancreatic carcinoma were examined with MRI before and after i. v. administration of Mn-DPDP (Philips Gyroscan ACS NT 1.5 T, phased array body-coil: TSE T 2 with and without SPIR, TR 2000 ms, TE 120ms; FFE T 1 breathhold, TR 115 ms, TE 4.6 ms; MRCP, TR 6000 ms, TE 1200 ms; Teslascan i. v. 5 micromol Mn/kg; FFE T 1 breathhold SPIR, TR 140 ms, TE 4,6 ms). Two observers evaluated in consensus the number and characteristics of focal pancreatic lesions. The MR findings were correlated with histopathological findings retrospectively. RESULTS: The following lesions were found: adenocarcinoma (19), pancreatitis (8), adenocarcinoma within pancreatitis (3), insulinoma (2), hematoma (1), papillitis stenosans (1), signet ring cell carcinoma (1), metastasis of rectal carcinoma (1), papillary mesothelioma (1). In three patients there was no pathological finding. Mn-DPDP enhanced MRI showed a sensitivity of 100 % and a specificity of 56 %. CONCLUSION: Mn-DPDP enhanced MRI in conjunction with MRCP showed a high sensitivity for the detection of pancreatic lesions. However, the specificity is low, thus recommending Mn-DPDP enhanced MRI only as a complementary imaging method.

Adenocarcinoma of the distal bile duct. A clinicopathologic outcome analysis after curative resection.

BACKGROUND/AIMS: Primary distal bile duct adenocarcinomas (DBDAs) are unusual neoplasms, necessitating pancreaticoduodenectomy for cure. The aims of this study were to evaluate the prognostic importance of lymphatic and perineural invasion, long-term outcome of patients after resection, and differences in outcome with hilar cholangiocarcinoma and pancreatic carcinoma. METHODS: The medical records and histopathological slides of 15 patients (8 men and 7 women) with documented DBDA after curative pancreaticoduodenectomy were reviewed. RESULTS: Nine standard and 6 pylorus-preserving pancreaticoduodenectomies were performed. TNM staging included 1, 3, 2, 8, and 1 patient in stages I, II, III, and IVA and IVB, respectively. Lymphatic and perineural invasion was present in 4 (27%) and 9 (60%) patients, respectively. With multivariate analysis only serum bilirubin was a significant prognostic factor. Median survival was 21 months, and 2- and 5-year actuarial survivals were 40 and 20%, respectively. Median survival with adjuvant therapy (n = 6) was 21 months, with 5-year survival of 33%. Five-year actuarial survivals when lymphatic or perineural invasion was present were 0 and 11%, respectively. CONCLUSION: DBDA is aggressive, but entails a better prognosis than pancreatic ductal or more proximal bile duct carcinoma. Lymphatic and/or perineural invasion worsen survival.