Controversial benefit of 5-fluorouracil/leucovorin-based adjuvant chemotherapy for ampullary cancer: a propensity score-matched analysis.

BACKGROUND: Although surgery is the primary treatment for ampullary cancer (AC), the benefit of adjuvant chemotherapy (CTx) has not yet been confirmed. METHODS: AC patients who were administered 5-fluorouracil(FU)/leucovorin(LV)-based CTx after curative intent surgery between 2011 and 2019 were included. Prognosis was compared between the observation (OB) and CTx groups after propensity score matching (PSM) using perioperative variables to control differences in patient characteristics. RESULTS: Before PSM, of 475 patients, those in the CTx group (n = 281) had worse 5-year overall survival (OS) (82.1% vs. 78.5%, p = 0.017) and worse 5-year recurrence-free survival (RFS) (54.9% vs. 75.7%, p < 0.001) than those in the OB group (n = 194). In addition, the CTx group had a higher rate of poor prognostic factors such as a high T stage (p < 0.001), node metastasis (p < 0.001), and poor differentiation (p < 0.001). After PSM, perioperative outcomes were comparable. In addition, there were no significant differences in OS (hazard ratio [HR], 1.085; 95% confidence interval [CI], 0.688-1.710; p = 0.726) or RFS (HR, 0.883; 95% CI, 0.613 1.272; p = 0.505) between the CTx (n = 123) and OB (n = 123) groups even after stratification by TNM stage. Intestinal subtype showed better 5-year OS (83.7% vs 33.2%, p = 0.015) and RFS (46.5% vs 24.9%, p = 0.035) rate compared with pancreatobiliary/mixed subtype. CONCLUSION: Patients who received adjuvant chemotherapy based on 5-FU/LV showed comparable oncologic outcomes to patients in the OB group even after stratification by tumor stage. The patients with intestinal subtype showed oncologic benefit for adjuvant 5-FU/LV CTx compared with pancreatobiliary or mixed subtypes.

Oncologic and Perioperative Outcomes Following Selective Application of Laparoscopic Pancreaticoduodenectomy for Periampullary Malignancies.

BACKGROUND: Data are sparse regarding patient selection criteria or evaluating oncologic outcomes following laparoscopic pancreaticoduodenectomy (LPD). Having prospectively limited LPD to patients with resectable disease defined by National Comprehensive Cancer Network (NCCN) criteria, we evaluated perioperative and long-term oncologic outcomes of LPD compared to a similar cohort of open pancreaticoduodenectomy (OPD). METHODS: Consecutive patients (November 2010-February 2014) undergoing pancreaticoduodenectomy (PD) for periampullary adenocarcinoma were reviewed. Patients were excluded from further analysis for benign pathology, conversion to OPD for portal vein resection, and contraindications for LPD not related to their malignancy. Outcomes of patients undergoing LPD were analyzed in an intention-to-treat manner against a cohort of patients undergoing OPD. RESULTS: These selection criteria resulted in offering LPD to 77 % of all cancer patients. Compared to the OPD cohort, LPD was associated with significant reductions in wound infections (16 vs. 34 %; P = 0.038), pancreatic fistula (17 vs. 36 %; P = 0.032), and median hospital stay (9 vs. 12 days; P = 0.025). Overall survival (OS) was not statistically different between patients undergoing LPD vs. OPD for periampullary adenocarcinoma (median OS 27.9 vs. 23.5 months; P = 0.955) or pancreatic adenocarcinoma (N = 28 vs. 22 patients; median OS 20.7 vs. 21.1 months; P = 0.703). CONCLUSIONS: The selective application of LPD for periampullary malignancies results in a high degree of eligibility as well as significant reductions in length of stay, wound infections, and pancreatic fistula. Overall survival after LPD is similar to OPD.

[The Nutritional Care Experience of a Post-Operative Periampullary Cancer Patient With Cachexia].

Cachexia is one of the most widely overlooked of the syndromes that are experienced by cancer patients. This syndrome is especially prevalent among patients with gastroenterology tract cancer. Although the National Comprehensive Cancer Network (NCCN) issued palliative-care practice guidelines for cachexia in 2015, guidelines have yet to be issued for the clinical setting. The authors reviewed the literature and applied their clinical experience to create an approach for identifying the degree of cachexia in a post-operative patient with periampullary cancer. This approach assesses the nutritional status, physical status, laboratory results, and gastrointestinal system functions of the patient using the Cachexia Assessment Scale (CAS) and NCCN Practice Guidelines for Cachexia. The patient improved under nursing care with an increase in nutritional intake and physical activity facilitating their process of post-surgical physical recovery. The authors hope that this experience using the combined CAS-NCCN Practice Guidelines will help clinical caregivers better understand how to apply the relevant guidelines in clinical settings. The developed approach may help nurses assess the comprehensive nutrition status of patients and related factors in order to provide interventions that will decrease the progression of cachexia effectively and promote quality of life.

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.

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.

Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial.

CONTEXT: Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas. OBJECTIVE: To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection. DESIGN, SETTING, AND PATIENTS: The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers. INTERVENTIONS: One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life. RESULTS: Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; χ2 = 1.33; P = .25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald χ2 = 4.53, P = .03). CONCLUSIONS: Among patients with resected periampullary adenocarcinoma, adjuvant chemotherapy, compared with observation, was not associated with a significant survival benefit in the primary analysis; however, multivariable analysis adjusting for prognostic variables demonstrated a statistically significant survival benefit associated with adjuvant chemotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00058201.

Oral preoperative antioxidants in pancreatic surgery: a double-blind, randomized, clinical trial.

OBJECTIVE: Oxidative stress due to ischemia/reperfusion injury increases systemic inflammation and impairs immune defenses. Much interest has developed for the administration of antioxidant substrates in surgical patients. The purpose of this study was to perform a pilot evaluation of the impact of a carbohydrate- containing preconditioning oral nutritional supplement (pONS) enriched with glutamine, antioxidants, and green tea extract on postoperative oxidative stress. METHODS: We performed a double-blind placebo-controlled randomized clinical trial, involving 36 cancer patients undergoing pancreaticoduodenectomy. Patients were randomized to receive either pONS or placebo twice the day before surgery and once 3 hours before surgery. Total endogenous antioxidant capacity (TEAC), plasma levels of vitamin C, vitamin E, selenium, zinc, F2-isoprostanes, and C-reactive protein were measured at baseline and on postoperative day (POD) 1, 3, and 7. RESULTS: At surgery, the mean gastric residual volume (mL) was 54.2 in the pONS group versus 51.3 in the placebo group (P = NS). On POD 1 plasma levels of vitamin C (P = 0.001), selenium (P = 0.07), and zinc (P = 0.06) were higher in the pONS group compared to placebo. TEAC was improved on POD 1, 3, and 7 in the pONS group compared to placebo (P = 0.01). No difference was found in plasma C-reactive protein levels after surgery in both groups. CONCLUSIONS: Perioperative pONS administration positively affected plasma vitamin C levels and improved TEAC shortly after surgery, but did not reduce oxidative stress and systemic inflammation markers.

Successful endoscopic procedures for intraductal papillary neoplasm of the bile duct: a case report.

Attention has recently been focused on biliary papillary tumors as the novel disease entity intraductal papillary neoplasm of the bile duct (IPNB), which consists of papillary proliferation of dysplastic biliary epithelium. As even benign papillary tumors are considered as premalignant, some investigators recommend aggressive surgical therapy for IPNB, although no guidelines are available to manage this disease. Few reports have described long-term follow-up of patients with benign IPNB without radical resection. If patients with IPNB who are treated only with endoscopic procedures are noted, clinical profiles and alternative therapies other than resection may be recommended. We report the case of a patient who experienced repetitive cholangitis for 10 years and was finally diagnosed with IPNB. Radical resection could not be recommended because of the age of the patient, therefore, endoscopic sphincterotomy was performed. Although an endoscopic retrograde biliary drainage catheter was placed several times for repetitive cholangitis, the patient has done well during follow-up. Our case may offer insights into the natural course and management decisions for the novel disease entity of IPNB.

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.

Adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer: a prospective randomized controlled trial.

BACKGROUND: Success of surgical treatment for pancreatic and periampullary cancer is often limited due to locoregional recurrence and/or the development of distant metastases. OBJECTIVE: The survival benefit of celiac axis infusion (CAI) and radiotherapy (RT) versus observation after resection of pancreatic or periampullary cancer was investigated. METHODS: In a randomized controlled trial, 120 consecutive patients with histopathologically proven pancreatic or periampullary cancer received either adjuvant treatment consisting of intra-arterial mitoxantrone, 5-FU, leucovorin, and cisplatinum in combination with 30 x 1.8 Gy radiotherapy (group A) or no adjuvant treatment (group B). Groups were stratified for tumor type (pancreatic vs. periampullary tumors). RESULTS: After surgery, 120 patients were randomized (59 patients in the treatment group, 61 in the observation group). The median follow-up was 17 months. No significant overall survival benefit was seen (median, 19 vs. 18 months resp.). Progressive disease was seen in 86 patients: in 37 patients in the CAI/RT group, and in 49 patients in the observation group (log-rank P < 0.02). Subgroup analysis showed significantly less liver metastases after adjuvant treatment in periampullary tumors (log-rank P < 0.03) without effect on local recurrence. Nonetheless, there was no significant effect on overall survival in these patients (log-rank P = 0.15). In patients with pancreatic cancer, CAI/RT had no significant effect on local recurrence (log-rank P = 0.12) neither on the development of liver metastases (log-rank P = 0.76) and consequently, no effect on overall survival. CONCLUSION: This adjuvant treatment schedule results in a prolonged time to progression. For periampullary tumors, CAI/RT induced a significant reduction in the development of liver metastases, with a possible effect on overall survival. Especially in these tumors, CAI/RT might prove beneficial in larger groups and further research is warranted.

Role of adjuvant chemoradiation therapy in adenocarcinomas of the ampulla of vater.

PURPOSE: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. METHODS AND MATERIALS: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). RESULTS: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). CONCLUSIONS: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.

Adjuvant concurrent chemoradiation for adenocarcinoma of the distal common bile duct.

PURPOSE: To examine the effect of adjuvant chemoradiation for adenocarcinoma of the distal common bile duct (DCBD) after pancreaticoduodenectomy (PD) on local control and survival. METHODS AND MATERIALS: A total of 34 cases of adenocarcinoma of the DCBD were treated with PD and adjuvant chemoradiation at Johns Hopkins Hospital between 1994 and 2003. Median radiation dose was 5,040 cGy (range, 4,000-5,400 cGy). Concurrent 5-fluorouracil-based chemotherapy was given with radiation therapy, followed by maintenance chemotherapy. RESULTS: The median follow-up of patients alive at the time of analysis was 41 months. Death occurred in 21 of 34 patients (62%) during the follow-up period, all from progressive, distant metastatic disease. Median overall survival was 36.9 months, with a 5-year survival of 35%. On multivariate analysis, only nodal status significantly predicted survival (p < 0.02). For patients with negative and positive lymph nodes, 5-year survival was 100% and 24%, respectively. Actuarial 5-year local control was 70%. Compared with historical controls who underwent PD alone, patients who underwent surgery and adjuvant chemoradiation had significantly longer survival (36.9 months vs. 22 months; p < 0.05). Overall survival was significantly longer for both lymph node negative and lymph node positive patients (p < 0.05). CONCLUSIONS: Adjuvant chemoradiation after PD for adenocarcinoma of the DCBD may improve local control and overall survival. The predominant mode of failure is distant metastatic disease, highlighting the need for improved systemic therapy.

Missing effect of glutamine supplementation on the surgical outcome after pancreaticoduodenectomy for periampullary tumors: a prospective, randomized, double-blind, controlled clinical trial.

BACKGROUND: The effect of glutamine (Gln) supplementation in patients undergoing a major operation has not been conclusively established. This study was designed to elucidate the effect of Gln supplementation on the surgical outcome after a pancreaticoduodenectomy (PD) for periampullary tumors. METHODS: A prospective, randomized, double-blind, and controlled clinical trial was undertaken for patients who underwent a classical PD or a pylorus-preserving PD for periampullary tumors. The Gln and control groups received isonitrogenous amino acid, with a 0.2 g/kg per day Gln regimen administered to the Gln group. The surgical outcome was compared in light of length of postoperative hospital stay, nutritional and chemical profiles, and complication rate between the Gln and control groups. RESULTS: Sixty of the consecutive 143 patients who were admitted to undergo operation for periampullary tumors were enrolled in our study; 32 were in the Gln group and 28 in the control group. The two groups were comparable prior to and during the operation. The median length of the postoperative hospital stay and the postoperative nutritional and chemical profiles were not different between two groups. The overall and PD-related complication rates of the Gln group (37.5% and 25.0%) and the control group (28.6% and 14.3%) were not statistically different. CONCLUSIONS: No significant beneficial effect of Gln supplementation with a low-dose parenteral regimen was demonstrated on the surgical outcome after a PD for periampullary tumors. Therefore, we should be prudent in using Gln as a routine pharmacologic supplement to the standard nutrition in patients who undergo major operations.

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.

Outcome of surgical treatment of pancreatic, peri-ampullary and ampullary cancer diagnosed in the south of The Netherlands: a cancer registry based study.

AIMS: To gain insight into the quality of pancreatic cancer surgery in 10 low-volume (median sized) hospitals, each serving 150,000-250,000 people, in the Comprehensive Cancer Centre South (CCCS) area and of referred patients to academic centres to determine the need for further regionalization. METHOD: The population-based Eindhoven Cancer Registry was used to select all patients in the CCCS area with pancreatic, peri-ampullary and ampullary cancer diagnosed between January 1, 1995 and April 30, 2000 (N = 1130). Of those, 124 patients (11%) underwent surgical resection (of which 40 were treated in university hospitals outside the region). RESULTS: For all pancreatic carcinoma resections, the 3-month survival rate was 82%, varying from 95% for referred patients to 76% for patients treated within the region (p = 0.014). One- and two-year survival rates showed no difference between both groups (p = 0.36 and p = 0.55, respectively). Surgically treated patients who were referred to university hospitals outside the CCCS area were younger, more often male, more often diagnosed with pTNM stage III, exhibited less comorbidity and had a higher socio-economic status than patients surgically treated within the region. CONCLUSION: Although the results are based on small numbers and patient selection probably influenced these outcomes, these data seem to support further hospital specialisation, to which the surgeons of the CCCS area have committed themselves.

Reoperative pancreaticoduodenectomy for periampullary carcinoma.

BACKGROUND: Potentially resectable periampullary tumours may not be treated appropriately due to lack of local expertise in both assessment of resectability and resection in referring centres. Tata Memorial Hospital is a major referral centre for oncology and these patients are finally referred to this institution. In carefully selected patients, resection can be accomplished. The purpose of the present paper was to determine the perioperative morbidity and mortality for patients undergoing reoperative pancreaticoduodenectomy at a major comprehensive cancer centre. METHODS: Between January 1991 and December 2001 15 patients, who had undergone previous non-resectional surgery for operable periampullary carcinoma, underwent re-exploration. The perioperative morbidity and mortality were analysed and compared with that of the group of patients undergoing primary pancreaticoduodenectomy (143 patients) in the same period. RESULTS: All the 15 patients undergoing re-exploration had a successful resection by pancreaticoduodenectomy. In the reoperative group eight patients (53%) underwent classic pancreaticoduodenectomy and seven patients (46%) had a pylorus-preserving pancreaticoduodenectomy, as compared to 102 (71%) and 41 (29%) patients in the primary surgery group, respectively. Although the mean operative time and the estimated blood loss were higher in the reoperative group, the morbidity and mortality rates were similar in the two groups. The overall 30-day mortality rate was 6.6% and 6.9% in the reoperative and the primary surgery group, respectively. Major morbidity occurred in two of the 15 patients (13.3%), and one patient (6.6%) died following surgery in the reoperative group. CONCLUSION: Reoperative pancreaticoduodenectomy can be performed safely in carefully selected patients with resectable, localized periampullary tumours with similar morbidity and mortality to patients undergoing primary surgery.

Survival after attempted surgical resection and intraoperative radiation therapy for pancreatic and periampullary adenocarcinoma.

PURPOSE: To evaluate a single institution's experience with intraoperative radiation therapy (IORT) in combination with attempted surgical resection for pancreatic and periampullary adenocarcinoma. METHODS AND MATERIALS: From May 1986 until June 2001, 77 patients at LDS Hospital underwent attempted surgical resection and IORT for pancreatic or periampullary adenocarcinoma. A potentially curative resection was defined as surgery with negative or microscopic positive margins. No patients had metastatic disease at the time of surgery and IORT. Forty-four patients with tumors located in the pancreas and 9 patients with periampullary tumors underwent potentially curative surgical resection and IORT. Twenty-four patients had pancreatic tumors deemed unresectable and underwent surgical bypass and IORT. Actuarial survival was calculated from the date of IORT until last follow-up or death by use of the Kaplan-Meier method. RESULTS: Patients undergoing a potentially curative resection and IORT for periampullary adenocarcinoma had a median survival of 167 months and a 56% 5-year actuarial survival, compared with a median survival of 16 months and a 19% 5-year actuarial survival for patients undergoing the same treatment for pancreatic adenocarcinoma (p = 0.03). Patients with unresectable disease who underwent bypass and IORT had a median survival of 11 months and a 0% 3-year survival, significantly worse than patients able to undergo surgical resection and IORT (p = 0.0002). The operative mortality for all patients undergoing potentially curative resection and IORT was 3.7%. CONCLUSIONS: Intraoperative radiation therapy is well tolerated and does not increase the morbidity or mortality of potentially curative surgical resection for pancreatic or periampullary adenocarcinoma. Patients with periampullary adenocarcinoma have a better prognosis than those with pancreatic adenocarcinoma, and patients with unresectable pancreatic disease fared worse.

[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.