A. Zerbi

Effect of hospital volume on outcome of pancreaticoduodenectomy in Italy

An inverse relationship between hospital volume and death following pancreatico duodenectomy (PD) has been reported from several countries. The aim of this study was to assess the volume–outcome effect of PD in Italy.

Chronic pancreatitis: report from a multicenter Italian survey (PanCroInfAISP) on 893 patients.

BACKGROUNDnNo data on chronic pancreatitis in Italy are available yet.nnnAIMnTo evaluate demographic, clinical, diagnostic and therapeutic aspects in patients suffering from chronic pancreatitis.nnnPATIENTS AND METHODSnEligible patients were prospectively enrolled from 2000 to 2005. Information concerning demographic data, lifestyle risk factors, family and clinical history, associated factors (alcohol, autoimmunity, cystic dystrophy of the duodenal wall, obstruction, genetic mutations) concomitant diseases, diagnostic findings, and pharmacological, endoscopic and surgical therapy were gathered.nnnRESULTSn893 patients (74% males, mean age 53.7+/-15.2 years) were evaluated. 519/859 patients (60%) were drinkers and 555/840 (66%) were smokers. A strong positive correlation between drinking and cigarette consumption (R=0.53; p<0.0001) was found. Heavy alcohol consumption (>80g of alcohol/day for more than 5 years) was considered the most important risk factor in 300 patients (34%), obstruction in 238 (27%), alcohol and obstruction in 82 (9%), autoimmunity in 34 (4%), cystic dystrophy of the duodenal wall/groove pancreatitis in 55 (6%), gene mutations in 36 (4%), and none (idiopathic) in 148 (17%). Bile stones were diagnosed in 287 patients (33%) and cholecystectomy was performed in 329 patients (38%). Pancreatic calcifications were diagnosed in 547/879 patients (62%). Pancreatic surgery was performed in 273 patients (31%). Endoscopic sphincterotomy was performed in 371 patients (42%). Exocrine and endocrine insufficiency were found, respectively, in 373/834 (45%) and 275/885 patients (31%).nnnCONCLUSIONSnAn unexpected low frequency of alcohol abuse and new emerging associated risk factors for chronic pancreatitis were observed in Italy.

Definitive Results of a Phase II Trial of Cisplatin, Epirubicin, Continuous-Infusion Fluorouracil, and Gemcitabine in Stage IV Pancreatic Adenocarcinoma

PURPOSEnTo evaluate the efficacy and toxicity of a cisplatin, epirubicin, gemcitabine, and fluorouracil (PEF-G) schedule on stage IV pancreatic adenocarcinoma.nnnPATIENTS AND METHODSnPatients < or = 70 years, with no prior chemotherapy and with bidimensionally measurable stage IV pancreatic adenocarcinoma, Eastern Cooperative Oncology Group performance status < or = 2, and adequate bone marrow, kidney, and liver function were eligible for this trial. Eligibility criteria for clinical benefit assessment were pain with at least a daily analgesic consumption of two nonsteroidal anti-inflammatory drugs or Karnofsky performance status between 50 and 70. Treatment consisted of 40 mg/m2 each of cisplatin and epirubicin day 1, gemcitabine 600 mg/m2 on days 1 and 8 every 4 weeks, and fluorouracil 200 mg/m2/d as a protracted venous infusion.nnnRESULTSnBetween April 1997 and April 1999, 49 patients from a single institution were eligible for the study. Altogether, 203 cycles (median, four cycles) of PEF-G were delivered. The objective response rate was 58% in 43 assessable patients and 51% in the intent-to-treat population. Fourteen patients had stable disease. Grade 3 or 4 World Health Organization neutropenia occurred in 51% of cycles, thrombocytopenia in 28%, anemia in 7%, stomatitis in 5%, and diarrhea, and nausea, and vomiting in 2%. The median duration of response was 8.5 months. The median time to tumor progression was 7.5 months. The median survival was 11 months in the assessable population and 10 months in the intent-to-treat population. Clinical benefit was achieved in 22 (78%) of 28 assessable patients.nnnCONCLUSIONnPEF-G is a well-tolerated and safe regimen; it obtained a very high rate of durable responses and deserves further evaluation in a phase III trial.

Raltitrexed–eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer

Limited information on salvage treatment in patients affected by pancreatic cancer is available. At failure, about half of the patients present good performance status (PS) and are candidate for further treatment. Patients >18 years, PS ⩾50, with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-containing chemotherapy, and progression-free survival (PFS) <12 months received a combination of raltitrexed (3u2009mgu2009m−2) and oxaliplatin (130u2009mgu2009m−2) every 3 weeks until progression, toxicity, or a maximum of six cycles. A total of 41 patients received 137 cycles of chemotherapy. Dose intensity for both drugs was 92% of the intended dose. Main grade >2 toxicity was: neutropenia in five patients (12%), thrombocytopenia, liver and vomiting in three (7%), fatigue in two (5%). In total, 10 patients (24%) yielded a partial response, 11 a stable disease. Progression-free survival at 6 months was 14.6%. Median survival was 5.2 months. Survival was significantly longer in patients with previous PFS >6 months and in patients without pancreatic localisation. A clinically relevant improvement of quality of life was observed in numerous domains. Raltitrexed–oxaliplatin regimen may constitute a treatment opportunity in gemcitabine-resistant metastatic pancreatic cancer. Previous PFS interval may allow the identification of patients who are more likely to benefit from salvage treatment.

Surgical Treatment of Benign and Borderline Neoplasms of the Pancreatic Body

Background: Conventional operations for benign and borderline tumors of the pancreatic body are distal pancreatectomy and enucleation. An unusual operation allowing the preservation of the proximal and distal pancreas is median pancreatectomy. Method: A retrospective analysis of prospectively collected data on 67 patients with nonmalignant neoplasms of the pancreatic body was performed. The operations were: 32 median pancreatectomies (22 with duct occlusion of the distal pancreas, 10 with pancreaticojejunostomy), 21 distal pancreatectomies, and 14 enucleations. The operative and long-term outcomes of the different operations were compared. Results: Enucleation had a shorter operative time and less blood loss than the other operations. No mortality was observed. The pancreatic fistula rate was 50% after median pancreatectomy (59% in case of distal duct occlusion, 30% in case of pancreaticojejunostomy), 14% after distal pancreatectomy and 14% after enucleation. Diabetes appeared in 3 patients after distal pancreatectomy and 3 patients after median pancreatectomy with duct occlusion. Conclusions: When indicated, enucleation is the operation of choice for a nonmalignant neoplasm of the pancreatic body. With respect to distal resection, the higher fistula rate of median pancreatectomy with pancreaticojejunostomy could be the price for a better long-term endocrine function; median pancreatectomy with duct occlusion had worse operative results and no long-term advantages.

Value of abdominal sonography and MR imaging at 0.5 T in preoperative detection of pancreatic insulinoma: a comparison with dynamic CT and angiography

Abstract.Background: Abdominal sonography, computed tomography (CT), angiography, and magnetic resonance (MR) imaging are the most widely used modalities for preoperative localization of insulinomas. CT and angiography are generally considered the techniques of reference, and the role of sonography and MR imaging in these patients is controversial. The purpose of this study was to compare these four modalities in a group of patients with pancreatic insulinoma and determine an effective radiological approach to this disease.nn Methods: Twenty-eight patients with clinical and biochemical signs of pancreatic insulinoma underwent abdominal sonography, MR imaging at 0.5 T (spin echo technique), bolus dynamic CT, and digital subtraction angiography. Examinations were evaluated independently for the presence, size, and location of the lesions; preoperative diagnoses were compared with surgical findings based on palpation and intraoperative sonography. Tumoral vascularity was histologically graded. Sensitivities of the four imaging techniques were calculated and compared with the size, location, and vascularity of the tumors. Detection rates of combined techniques were finally determined.nn Results: At surgery, 29 lesions in the 28 patients were found (range = 0.8–4.3 cm, average = 1.65 cm). Sensitivities of abdominal sonography, MR imaging, CT, and angiography were 79.3%, 65.5%, 44.8%, and 69% respectively. Correct localization of tumor was achieved in 96.6% of cases by a combination of sonography and MR imaging and in 72.4% of cases by using CT with angiography.nn Conclusion: In our experience, sonography and MR imaging performed well in the preoperative detection of pancreatic insulinoma. Therefore, we believe that the combination of abdominal sonography and MR imaging may represent the first radiological approach in clinically suspected insulinomas and that CT and angiography should be reserved for negative and/or doubtful cases.n

Diagnosis and treatment of acute pancreatitis: the position statement of the Italian Association for the study of the pancreas.

This medical position statement has been developed by the board of ProInf AISP (Computerized Project on Acute Pancreatitis) Study Group. The evidence and key recommendations were discussed at a dedicated meeting held in Milan on September 2007 and during this meeting the main clinical and therapeutic medical topics were extensively discussed. Each of the proposed recommendations was discussed and an initial consensus was reached. Acute pancreatitis in Italy is a disease of increasing annual incidence. The diagnosis of the disease should be established within 48hours of admission. Early identification of patients at risk of developing a severe attack of acute pancreatitis is of great importance because rapid therapeutic interventions improve outcome. The endoscopic approach seems to be most beneficial measure in patients with acute pancreatitis with jaundice and in those with cholangitis. The development of infected necrosis should be assessed using fine-needle aspiration and the sample should be cultured for germ isolation and characterization. The role of early ERCP in all patients with severe acute pancreatitis of biliary origin is still controversial. The data supporting the efficacy of antibiotic prophylaxis to prevent infection of necrosis are conflicting. The refeeding is a crucial topic in patients who have recovered from an acute episode of mild acute pancreatitis, but there are very few studies on this issue.

Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma: a phase I and II trial.

Background: This study evaluates the maximum tolerated dose (MTD) and activity of mitomycin, docetaxel, and irinotecan (MDI) regimen on metastatic pancreatic adenocarcinoma, previously treated with gemcitabine-containing chemotherapy. Patients and Methods: Patients with less than 76 years, Karnofsky performance status ≥ 60, and adequate bone marrow, kidney, and liver function were eligible for this trial. Treatment consisted of mitomycin 6 mg/m2 day 1, docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks. Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m2; level 3:30 and 85 mg/m2; and level 4:35 and 85 mg/m2. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia > 7 days, febrile neutropenia, grade 4 thrombocytopenia, nausea and vomiting, or diarrhea, grade ≥ 3 nonhematological toxicity, or failure to recover to grade ≤ 1 toxicity by day 43, occurring during the first cycle of chemotherapy. Results: Between September 2001 and October 2002, 15 eligible patients, three of whom had been previously treated with two lines of chemotherapy, received 33 cycles of MDI. Toxicity consisted of grade 3 to 4 neutropenia in 23% of cycles, fatigue, diarrhea, and vomiting in 10% of cycles, and one toxic death. DLT was observed in 2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3 level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen patients were assessable for response. No objective response was observed among patients treated with MTD or higher doses. Three patients had stable disease; all other patients had progressive disease. The median time to tumor progression and median survival was 1.7 and 6.1 months, respectively. Conclusion: The MTD was mitomycin 6 mg/m2 day one, and docetaxel 30 and irinotecan 85 mg/m2 days 2 and 8. This regimen is inactive in metastatic pancreatic cancer.

Prevalence and risk factors of extrapancreatic malignancies in a large cohort of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas

BACKGROUNDnThe objectives of this study are to estimate prevalence and incidence of extrapancreatic malignancies (EPMs) among intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to identify risk factors for their occurrence.nnnPATIENTS AND METHODSnWe conducted multicentric cohort study in Italy from January 2010 to January 2011 including 390 IPMN cases. EPMs were grouped as previous, synchronous (both prevalent) and metachronous (incident). We calculated the observed/expected (O/E) ratio of prevalent EPMs, and compared the distribution of demographic, medical history and lifestyle habits.nnnRESULTSnNinety-seven EPMs were diagnosed in 92 patients (23.6%), among them 78 (80.4%) were previous, 14 (14.4%) were synchronous and 5 (5.2%) were metachronous. O/E ratios for prevalent EPMs were significantly increased for colorectal carcinoma (2.26; CI 95% 1.17-3.96), renal cell carcinoma (6.00; CI 95% 2.74-11.39) and thyroid carcinoma (5.56; CI 95% 1.80-12.96). Increased age, heavy cigarette smoking, alcohol consumption and first-degree family history of gastric cancer are significant risk factors for EPMs, while first-degree family history of colorectal carcinoma was borderline.nnnCONCLUSIONnWe report an increased prevalence of EPMs in Italian patients with IPMN, especially for colorectal carcinoma, renal cell and thyroid cancers. A systematic surveillance of IPMN cases for such cancer types would be advised.BACKGROUNDnThe objectives of this study are to estimate prevalence and incidence of extrapancreatic malignancies (EPMs) among intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to identify risk factors for their occurrence.nnnPATIENTS AND METHODSnWe conducted multicentric cohort study in Italy from January 2010 to January 2011 including 390 IPMN cases. EPMs were grouped as previous, synchronous (both prevalent) and metachronous (incident). We calculated the observed/expected (O/E) ratio of prevalent EPMs, and compared the distribution of demographic, medical history and lifestyle habits.nnnRESULTSnNinety-seven EPMs were diagnosed in 92 patients (23.6%), among them 78 (80.4%) were previous, 14 (14.4%) were synchronous and 5 (5.2%) were metachronous. O/E ratios for prevalent EPMs were significantly increased for colorectal carcinoma (2.26; CI 95% 1.17-3.96), renal cell carcinoma (6.00; CI 95% 2.74-11.39) and thyroid carcinoma (5.56; CI 95% 1.80-12.96). Increased age, heavy cigarette smoking, alcohol consumption and first-degree family history of gastric cancer are significant risk factors for EPMs, while first-degree family history of colorectal carcinoma was borderline.nnnCONCLUSIONnWe report an increased prevalence of EPMs in Italian patients with IPMN, especially for colorectal carcinoma, renal cell and thyroid cancers. A systematic surveillance of IPMN cases for such cancer types would be advised.

Outcome of upfront combination chemotherapy followed by chemoradiation for locally advanced pancreatic adenocarcinoma.

PurposeThe role and timing of chemotherapy and radiation for treating stage III pancreatic adenocarcinoma remains controversial.MethodsTreatment-naive patients with stage III non-resectable pancreatic adenocarcinoma were treated with PEFG/PEXG (cisplatin, epirubicin, 5-fluorouracil (F)/capecitabine (X), gemcitabine) or PDXG (docetaxel substituting epirubicin) regimen for 6xa0months followed by radiotherapy (50–60xa0Gy) with concurrent F or X or G.ResultsNinety-one patients were registered between April 1997 and December 2007. Forty-three patients (47%) had a partial remission and 38 (42%) had a stable disease. Thirteen patients (14%) were radically resected yielding one pathologic complete remission. Median survival (OS) was 16.2xa0months. Median progression-free survival was 9.9xa0months. Pattern of failure consisted of isolated local failure (Nxa0=xa026, 35%); both local and systemic failure (Nxa0=xa014, 19%); isolated systemic failure (Nxa0=xa035, 47%).ConclusionCombination chemotherapy with four-drug regimens followed by chemoradiation was a feasible strategy showing relevant results in stage III pancreatic adenocarcinoma.