Practical guidelines for acute pancreatitis.

INTRODUCTION: The following is a summary of the official guidelines of the Italian Association for the Study of the Pancreas regarding the medical, endoscopic and surgical management of acute pancreatitis. STATEMENTS: Clinical features together with elevation of the plasma concentrations of pancreatic enzymes are the cornerstones of diagnosis (recommendation A). Contrast-enhanced computed tomography (CT) provides good evidence for the presence of pancreatitis (recommendation C) and it should be carried out 48-72 h after the onset of symptoms in patients with predicted severe pancreatitis. Severity assessment is essential for the selection of the proper initial treatment in the management of acute pancreatitis (recommendation A) and should be done using the APACHE II score, serum C-reactive protein and CT assessment (recommendation C). The etiology of acute pancreatitis should be able to be determined in at least 80% of cases (recommendation B). An adequate volume of intravenous fluid should be administered promptly to correct the volume deficit and maintain basal fluid requirements (recommendation A); analgesia is crucial for the correct treatment of the disease (recommendation A). Enteral feeding is indicated in severe necrotizing pancreatitis and it is better than total parenteral nutrition (recommendation A). The use of prophylactic broad-spectrum antibiotics reduces infection rates in CT-proven necrotizing pancreatitis (recommendation A). Infected pancreatic necrosis in patients with clinical signs and symptoms of sepsis is an indication for intervention, including surgery and radiological drainage (recommendation B). CONCLUSIONS: The participants agreed to revise the guidelines every 3 years in order to re-evaluate each question on the management of acute pancreatitis patients according to the most recent literature.

Pancreata from pediatric donors restore insulin independence in adult insulin-dependent diabetes mellitus recipients.

CONTEXT: The use of pediatric donors can increase the number of donors available for pancreas transplantation. AIM: The aim of this study was to verify if pancreas transplantation from pediatric donors is as effective as transplantation from adult donors to restore metabolic control in type 1 diabetic patients. MATERIALS AND METHODS: From 2000 to April 2009 we performed 17 pancreas transplantations from pediatric donors: 9 simultaneous kidney-pancreas (SPK), 6 pancreas transplantation alone (PTA), and 2 pancreas after kidney (PAK). All subjects received whole organs with enteric diversion of exocrine secretions; 11 underwent systemic and 6 underwent portal venous graft drainage. The immunosuppressive therapy was as follows: prednisone, mycophenolate mofetil, anti-thymocyte globulin (ATG), and cyclosporine or tacrolimus. The pediatric donor population had a mean age of 15.3 years (range, 12-17), a mean weight of 60.1 kg (range, 42-75), and a mean body mass index (BMI) of 21 (range, 17.9-23.4). RESULTS: After 9 years the overall patient survival rate was 94.12%, whereas the graft survival rate was 63.35%. Normal glucose and insulin levels were maintained either fasting or during oral glucose tolerance test (OGTT). The group of recipients of pediatric organs was compared with patients receiving organs from adult donors (n = 125); the mean glucose values were lower in the pediatric group, whereas insulin production was higher in the adult patients. Early venous thrombosis was 17.6% in the pediatric group and 20% in adult recipients (Fisher exact test, P = not significant [NS]). CONCLUSION: Pediatric donors restored insulin independence in adult diabetic recipients, representing a valid source of organs for pancreas transplantation.

Randomized clinical trial of laparoscopic versus open left colonic resection.

BACKGROUND: The main aim of this study was to compare short-term results and long-term outcomes of patients undergoing laparoscopic versus open left colonic resection. METHODS: Between February 2000 and December 2004, all adult patients undergoing elective left colonic resection were assessed for eligibility to the study. The protocol for postoperative care was the same in both groups. Cost-benefit analysis was based on hospital costs. Quality of life, long-term morbidity and 5-year survival were also evaluated. RESULTS: Some 268 patients undergoing left colonic resection were assigned randomly to the laparoscopic (n = 134) or open (n = 134) approach. The short-term morbidity rate was 20.1 per cent in the open group and 11.9 per cent in the laparoscopic group (P = 0.094). Hospital stay was longer in the open group (8.7 versus 7.0 days for the laparoscopic approach; P = 0.002). Cost-benefit analysis showed an additional cost of euro66 per patient randomly allocated to the laparoscopic group. Quality of life was significantly improved in the laparoscopic group 6 months after surgery, but no difference was found subsequently. The long-term morbidity rate was 11.9 per cent in the open group and 7.5 per cent in the laparoscopic group (P = 0.413). The 5-year survival rate of patients with cancer was 66 and 72 per cent for open and laparoscopic groups respectively (P = 0.321). CONCLUSION: Laparoscopic left colonic resection resulted in an earlier recovery after surgery. As cost-benefit analysis and long-term follow-up showed similar results, the laparoscopic approach should be preferred to open surgery.

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

PURPOSE: The role and timing of chemotherapy and radiation for treating stage III pancreatic adenocarcinoma remains controversial. METHODS: Treatment-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 6 months followed by radiotherapy (50-60 Gy) with concurrent F or X or G. RESULTS: Ninety-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 16.2 months. Median progression-free survival was 9.9 months. Pattern of failure consisted of isolated local failure (N = 26, 35%); both local and systemic failure (N = 14, 19%); isolated systemic failure (N = 35, 47%). CONCLUSION: Combination chemotherapy with four-drug regimens followed by chemoradiation was a feasible strategy showing relevant results in stage III pancreatic adenocarcinoma.

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

BACKGROUND: No data on chronic pancreatitis in Italy are available yet. AIM: To evaluate demographic, clinical, diagnostic and therapeutic aspects in patients suffering from chronic pancreatitis. PATIENTS AND METHODS: Eligible 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. RESULTS: 893 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%). CONCLUSIONS: An unexpected low frequency of alcohol abuse and new emerging associated risk factors for chronic pancreatitis were observed in Italy.

Fast-track recovery programme after pancreatico- duodenectomy reduces delayed gastric emptying.

BACKGROUND: Data on enhanced recovery programmes after pancreatic surgery are sparse. This retrospective cohort study, using historical controls, aimed to evaluate the impact of a fast-track programme after pancreaticoduodenectomy (PD). METHODS: Between 2004 and 2007, 252 patients undergoing PD were treated by a fast-track programme that included earlier postoperative feeding and mobilization. The patients were compared with an equally sized control group that received a traditional programme from 2000 to 2004. Outcome measures were morbidity, length of stay and readmission rate. RESULTS: The rates of pancreatic fistula and other intra-abdominal complications were similar in the two groups. Delayed gastric emptying (DGE) was significantly reduced in the fast-track group (13.9 versus 24.6 per cent; P = 0.004). The independent effect of the fast-track protocol in reducing DGE was confirmed by the multiple regression analysis (adjusted odds ratio 0.477, P = 0.005). Length of stay was reduced with the fast-track protocol (median 13 versus 15 days; P < 0.001), without increasing the readmission rate (7.1 versus 6.3 per cent; P = 0.865). CONCLUSION: A fast-track programme after PD improves gastric emptying and reduces postoperative stay.

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.

PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) regimen as second-line therapy in patients with progressive or recurrent pancreatic cancer after gemcitabine-containing chemotherapy.

OBJECTIVE: The therapeutic arsenal for salvage therapy in pancreatic cancer is limited. PEFG (cisplatin, epirubicin, 5-fluorouracil [FU], gemcitabine) regimen is an effective upfront treatment in advanced pancreatic cancer. The activity and safety of this combination regimen were assessed by means of an observational study in a population of patients with progressive or recurrent pancreatic adenocarcinoma after gemcitabine-containing chemotherapy. METHODS: Patients with age <76 years, Karnofsky performance status >50 were treated with either classic PEFG (until April 2004: cisplatin and epirubicin 40 mg/m day 1, gemcitabine 600 mg/m day 1 and 8, FU 200 mg/m/d continuous infusion day 1-28) or dose-intense PEFG (since May 2004: cisplatin and epirubicin 30 mg/m, gemcitabine 800 mg/m every 14 days; FU 200 mg/m/d continuous infusion day 1-28) until progressive disease or a maximum of 6 cycles of 28 days. RESULTS: Forty-six patients (37 metastatic) received 69 cycles of classic PEFG (18 patients) or 104 cycles of dose-intense PEFG (28 patients) as second-line therapy. Prior treatment consisted of single agent gemcitabine (N = 17), gemcitabine-based chemotherapy (N = 4), or PEFG regimen (N = 25). Median previous progression-free survival was 7.6 months. Dose intensity (mg/m/wk) with classic PEFG was cisplatin and epirubicin 8.5; gemcitabine 230; FU 1035 and with dose-intense PEFG was cisplatin and epirubicin 11.5 (+36%); gemcitabine 259 (+13%); FU 1046 (+1%). Main grade >2 toxicity consisted of neutropenia in 26 patients (56%), thrombocytopenia in 10 (22%), anemia in 11 (24%), fatigue and stomatitis in 4 (9%), vomiting, diarrhea and hand-foot syndrome in 2 (4%). Partial response was observed in 11 patients (24%) (5 classic PEFG 28% + 6 dose-intense PEFG 21%). Median and 1-year survival was 8.3 months (8.0 vs. 9.0 months) and 26% (17% vs. 32%). Median and 6-months progression-free survival was 5.0 months (4.5 vs. 5.0 months) and 34% (33% vs. 38%). CONCLUSIONS: PEFG regimen in gemcitabine refractory pancreatic cancer had an acceptable toxicity profile and interesting activity, and may constitute a treatment option in this setting.

Male breast cancer: 6-year experience.

AIM: Breast cancer in men is a very rare neoplasm accounting 1% of all breast cancer with an incidence ratio of 1:100 of men to women and about 1% of all malignancies in men. On the basis of the literature review the authors tried to determine the main characteristics of this rare neoplasm in terms of epidemiology, diagnosis, prognosis, treatment and survival. METHODS: The authors report the experience of the Breast Unit of the San Giovanni Addolorata Hospital in Rome, where 4 cases of male breast cancer were observed and treated over 784 breast cancers. RESULTS: All tumours were ductal carcinomas. The extent of disease was as follows: 3 cases with stage I and 1 case with Stage IIIB; in two cases estrogen and progesterone receptors expression was 100% and in the other two cases it was 20-80%. Median follow up was 57.5 months. At present, after 6-year follow up the three patients with stage I are in good conditions; the patient with stage III died after 27 months with metastatic disease. CONCLUSIONS: Surgical treatment remains the gold standard in male breast cancer. The prognosis for males with breast cancer is similar to female patients on equal terms of stage of disease. Adjuvant therapy is based on retrospective studies of male breast cancer conducted over the past 20 years using the guidelines for breast cancer in women.

Effect of hospital volume on outcome of pancreaticoduodenectomy in Italy.

BACKGROUND: 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. METHODS: The study group comprised 1576 patients who underwent PD in 2003. Hospitals were allocated to four volume groups: low volume, five PDs or fewer; medium volume, six to 13 PDs; high volume, 14 to 51 PDs; and very high volume, two hospitals that performed 89 and 104 PDs. RESULTS: Some 221 hospitals performed at least one PD in 2003; hospital volume was low in 74.7 per cent, medium in 17.6 per cent, high in 6.8 per cent and very high in 0.9 per cent. The overall mortality rate was 8.1 per cent. Increasing hospital volume was associated with a significantly reduced mortality rate: 12.4 per cent (adjusted odds ratio (OR) 1.000) for low-volume, 7.8 per cent (OR 0.611) for medium-volume, 5.9 per cent (OR 0.466) for high-volume and 2.6 per cent (OR 0.208) for very high-volume hospitals. Length of postoperative stay was reduced in very high-volume hospitals (P < 0.001). CONCLUSION: The outcome of PD in Italy is dependent on hospital volume and a policy of centralization may therefore be appropriate.

Arterial vs pancreatic phase: which is the best choice in the evaluation of pancreatic endocrine tumours with multidetector computed tomography (MDCT)?

PURPOSE: The aim of this study was to assess whether the pancreatic phase may replace the arterial phase in the evaluation of endocrine pancreatic tumours. MATERIALS AND METHODS: Twenty-nine endocrine pancreatic lesions with definitive morphological and immunohistochemical characterisation after surgical treatment (n=24) or fine-needle-aspiration cytology under endoscopic ultrasonography guidance (n=5) were retrospectively evaluated. All lesions were studied with triple-phase 16-row multidetector computed tomography (MDCT). Images obtained during each phase were separately interpreted by two senior radiologists experienced in pancreatic pathology and who were blinded to surgical results. Endocrine tumour and normal pancreas attenuation and the mean absolute tumour-to-gland attenuation difference were measured in each phase, and data were analysed with Student's t test. Visualisation of arterial vascular abnormalities and hypervascular liver metastases in the arterial and pancreatic phases and the diagnostic contribution of the two phases were compared. RESULTS: For both radiologists, the mean absolute tumour-to-gland attenuation difference was significantly higher (p<0.05) in the pancreatic phase (40+/-53 HU and 34+/-56 HU) than in the arterial phase (31+/-38 HU and 26+/-43 HU). There were no differences in the detection of arterial vascular abnormalities or hypervascular liver metastases in the two phases. The diagnostic contribution was higher in the pancreatic phase. CONCLUSIONS: In our experience, the pancreatic phase can replace the arterial phase in the evaluation of pancreatic endocrine tumours.

Dose-intense PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) in advanced pancreatic adenocarcinoma: a dose-finding study.

The aim of this study was to assess the maximum tolerated dose (MTD) of an intensified PEFG regimen administered every 14 days to patients with Stage III or metastatic pancreatic adenocarcinoma. Twenty-nine patients received fixed doses of both epirubicin (30 mg/m2) and 5-fluorouracil (200 mg/m2/day on Days 1-14) and of escalating doses of cisplatin and gemcitabine. The MTD was cisplatin 30 mg/m2 and gemcitabine 800 mg/m2. With respect to classical PEFG, intensified regimen potentially improved the dose-intensity of both cisplatin and epirubicin by 50 percent and of gemcitabine by 33 percent, reduced Grade 3-4 haematological toxicity and the number of outpatient accesses.

Diagnostic assessment and outcome of acute pancreatitis in Italy: results of a prospective multicentre study. ProInf-AISP: Progetto informatizzato pancreatite acuta, Associazione Italiana Studio Pancreas, phase II.

BACKGROUND AND AIM: Up till now, only one study providing practically complete information on acute pancreatitis in Italy has been published. The aim of this prospective study was to evaluate the clinical characteristics, in terms of diagnostic assessment and outcome, of a large series of patients affected by acute pancreatitis in Italy. MATERIALS AND METHODS: The study involved 56 Italian centres, homogeneously distributed throughout the entire national territory. Each participating centre was furnished with an ad hoc software including 530 items along with subsequent collection, tabulation and quality control of the data. RESULTS: One thousand five hundred and forty case report forms of patients affected by acute pancreatitis were collected but 367 of them (24%) were subsequently eliminated from the final analysis. Therefore, 1173 patients (581 females and 592 males) were recruited. Mean age of patients was 62.0+/-18.2 years (95% confidence interval, 60.9-63.0). On the basis of Atlanta classification, 1006 patients (85.8%) were defined as mild and 167 (14.2%) as severe pancreatitis. Biliary forms represented the most frequent aetiological category (813 cases, 69.3%) while alcoholic forms only 6.6% (77 cases); the remaining aetiologies accounted for 7.1% (83 cases) while 200 cases (17.1%) remained without a definite aetiological factor. Complete recovery was achieved in 1016 patients (86.6%) whereas morphological sequelae were found in 121 patients (10.3%) and mortality in 36 patients (3.1%; 0.4% in mild and 19.2% in severe acute pancreatitis). Ultrasonography was largely utilised as a first line diagnostic tool in all patients, with valuable visualisation of the pancreas in 85% of patients. Computer tomography scan was also widely used, with 66.7% of exams in mild and 33.3% in severe pancreatitis. Patients affected by biliary pancreatitis presented more severe (p=0.004) and necrotizing forms (p=0.021). Mortality was significantly related (p<0.001) with the extension of pancreatic necrosis and with an age of over 70 years. Body mass index presented significantly greater values in severe than in mild forms (p<0.001). CONCLUSIONS: Association of creatinine serum level over 2mg/dl with an abnormal chest X-ray showed a high significant correlation with a more severe outcome in terms of morphological sequelae and mortality (p=0.0001). Acute pancreatitis in Italy more commonly presents biliary aetiology and favourable outcome with low rate of complications and mortality. From a cost-effectiveness standpoint, diagnostic approach to this disease needs to be better standardised.

A prospective multicentre survey on the treatment of acute pancreatitis in Italy.

BACKGROUND: The Italian Association for the Study of the Pancreas released a diagnostic and therapeutic algorithm for acute pancreatitis in 1999. AIM: This study focused on the analysis of the therapeutic approach for the treatment of acute pancreatitis in Italy. PATIENTS: One thousand, one hundred and seventy-three patients were recruited: 1006 patients (85.8%) had mild acute pancreatitis (MAP) and 167 (14.2%) had the severe acute pancreatitis (SAP); 161 patients showed pancreatic necrosis at computed tomography; 121 patients (10.3%) had sequelae and 36 (3.1%) died. RESULTS: Non-steroidal anti-inflammatory drugs and tramadol were used more frequently in patients with the MAP whereas opioids and the association schedules were used more frequently in patients with the SAP (P<0.001). Gabexate mesilate was utilised in 831 out of 1173 patients (70.8%); in particular, gabexate mesilate was used in 70.6% patients with MAP and in 73.1% of those with SAP (P=0.521). The duration of the drug administration was significantly shorter in those having MAP than in those having the SAP (P<0.001). The antibiotics most frequently used for the prophylaxis against infection from pancreatic necrosis (43.1%) were carbapenems. Only a small number of patients received enteral nutrition (4.7%). Endoscopic retrograde cholangiopancreatography was carried out in 344 of the 1173 patients (29.3%). Surgery was performed in 48 with SAP (19 had elective biliary surgery and 29 had pancreatic surgery). CONCLUSIONS: The results of this survey indicate a lack of compliance with the guidelines which regard the indications mainly for interventional endoscopy and surgery.

A preclinical evaluation of pemetrexed and irinotecan combination as second-line chemotherapy in pancreatic cancer.

Gemcitabine (GEM)-based chemotherapy is regarded as the standard treatment of pancreatic adenocarcinoma, but yields a very limited disease control. Very few studies have investigated salvage chemotherapy after failure of GEM or GEM-containing chemotherapy and preclinical studies attempting to widen the therapeutic armamentarium, not including GEM, are warranted. MIA PaCa2, CFPAC-1 and Capan-1 pancreatic cancer cell lines were treated with GEM, fluouracil (5-FU), docetaxel (DCT), oxaliplatin (OXP), irinotecan (CPT-11), pemetrexed (PMX) and raltitrexed (RTX) as single agent. Pemetrexed, inducing apoptosis with IC50s under the Cmax in the three lines tested, appeared the most effective drug as single agent. Based on these results, schedule- and concentration-dependent drug interactions (assessed using the combination index) of PMX/GEM, PMX/DCT and PMX-CPT-11 were evaluated. The combinatory study clearly indicated the PMX and CPT-11 combination as the most active against pancreatic cancer. To confirm the efficacy of PMX-CPT-11 combination, we extended the study to a panel of 10 pancreatic cancer cell lines using clinically relevant concentrations (PMX 10 microM; CPT-11 1 microm). In eight of 10 lines, the PMX-CPT-11 treatment significantly reduced cell recovery and increased both the subG1 and caspase 3/7 fraction. After a 5-day wash out period, an increased fraction of subG1 and caspase3/7 persisted in PMX-CPT-11-pretreated cell lines and a significant reduction in the clonogenicity capacity was evident. Finally, in vivo, the PMX/CPT-11 combination showed the ability to inhibit xenograft tumours growth as second-line therapy after GEM treatment. The PMX and CPT-11 combination displays a strong schedule-independent synergistic cytotoxic activity against pancreatic cancer, providing experimental basis for its clinical testing as salvage chemotherapy in pancreatic cancer patients.

Dose-intense PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) in advanced pancreatic adenocarcinoma.

BACKGROUND: PEFG regimen (cisplatin and epirubicin 40 mg/m2 day 1, gemcitabine 600 mg/m2 days 1 and 8, 5-fluorouracil (FU) 200 mg/m2/day continuous infusion) significantly improved the outcome of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine in a previous phase III trial. This regimen was subsequently modified in a dose-finding study by increasing dose intensity of cisplatin and epirubicin (both at 30 mg/m2 every 14 days) and of gemcitabine (at 800 mg/m2 every 14 days). Results of a consecutive series treated by dose-intense PEFG regimen are herewith reported. MATERIAL AND METHODS: Dose-intense PEFG was administered to chemotherapy-naive patients with stages III-IV PA, < 75 years, performance status (PS) > 50, till progressive disease or for a maximum of 6 months. RESULTS: Between January 2004 and June 2005, 49 (31 or 63% metastatic) patients, median age 62 years, median PS 80, were treated with dose-intense PEFG. Partial response and stable disease was observed in 24 (49%) and 16 (33%) patients, respectively; 31 patients were progression-free at 6 months (PFS-6 = 63%). Median survival was 10.5 months and 1-year overall survival (OS) was 48% (95% confidence interval: 33-61%). Main grade 3-4 toxicity was: neutropenia in 26% of patients, stomatitis and fatigue in 8%, anaemia, diarrhoea, nausea/vomit in 6%, febrile neutropenia and thrombocytopaenia in 4%, hand-foot syndrome in 2%. CONCLUSION: When compared with 84 patients treated by classical PEFG at the same institution, dose-intense PEFG was not inferior in terms of PFS-6 (63 versus 57%), 1-year OS (48 versus 42%) and response rate (49 versus 49%); it allowed to increase dose intensity for gemcitabine by 32%, for cisplatin and epirubicin by 36% (FU reduced by 3%), to significantly reduce grade 3-4 hematological toxicity (neutropenia: 26 versus 86%; P < 0.00001; thrombocytopaenia: 4 versus 58%; P < 0.00001) and to reduce by one-third the number of outpatient accesses. The new PEFG schedule appears more suitable for clinical use and should be preferred as a basis for further development of therapeutic strategies against pancreatic cancer.

[Laparoscopic-assisted versus open surgery for colorectal cancer: postoperative morbidity in a single center randomized trial]. / Laparoscopia vs approccio aperto in chirurgia colorettale: morbidità postoperatoria in un trial randomizzato monocentrico.

AIM: The primary objective of the study was to compare the effect of laparoscopic-assisted (LPS) versus open surgery (LPT) for colorectal cancer on postoperative morbidity. The secondary objectives were to evaluate immune response and intestinal wall oxygen perfusion. METHODS: A total of 610 patients with colorectal cancer were randomly assigned to receive colon resection by either LPS (n=306) or LPT (n=304). Four surgical staff members not involved in the study recorded postoperative complications up to 30 days after the operation. Immune response was evaluated by measuring lymphocytic proliferation after challenge with Candida albicans and phytohemoagglutinin before, at 3 and 15 days after the operation. Intestinal wall oxygen perfusion was continuously monitored using a probe. RESULTS: The conversion rate was 4.6% in the LPS group. Morbidity was 18.6% in the LPS group and 34.5% in the LPT group (P<0.0005). Infections developed in 9.1% of LPS-treated patients and in 20.2% of LPT-treated patients (P<0.0005). The mean length of stay was 9.7+/-2.6 days in the LPS group and 12.2+/-4.2 days in the LPT group (P<0.0001). In both groups lymphocytic proliferation was low at 3 days postoperative but returned to normal range at 15 days only in the LPS group. Interoperative intestinal oxygen perfusion values were higher in the LPS group. CONCLUSIONS: Laparoscopic colorectal surgery reduced both postoperative morbidity and length of stay. Lymphocytic proliferation and intestinal wall oxygen perfusion were higher in patients who underwent laparoscopic-assisted surgery.

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 >or=50, with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-containing chemotherapy, and progression-free survival (PFS) <12 months received a combination of raltitrexed (3 mg m(-2)) and oxaliplatin (130 mg m(-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.

Cardiovascular benefits of simultaneous pancreas-kidney transplant versus kidney alone transplant in diabetic patients.

UNLABELLED: The aim of our study was to demonstrate the cardiovascular benefits of simultaneous pancreas-kidney transplantation when compared to kidney-alone transplants in diabetic recipients. PATIENTS AND METHODS: A total of 386 renal transplants were performed from 1985 to 2004, including 262 (68%) in diabetic recipients and 124 (32%) in nondiabetics. Among the former group, 200 kidneys were transplanted simultaneously to the pancreatic graft (KP group) and 62 were kidney-alone transplants (KA group). The mean time on dialysis was 31 +/- 20 months (range 0-126 months). The duration of diabetes was 24 +/- 7 years (range 5-51 years). Ninety-nine percent of the patients were on renal replacement therapy (79% on hemodialysis and 20% on peritoneal dialysis). RESULTS: Among 262 patients, 28 (11%) died due to a cardiovascular event, which was higher among KA patients compared with the KP group (P = .004). Overall patient survival was significantly higher in the KP group when compared with the KA group (log-rank: P = .0004). Patient survivals were 80% and 70% versus 70% and 40% at 5 and 10 years in the KP and KA groups, respectively. Kidney graft survivals were 81% and 60% versus 63% and 26% at 5 and 10 years in the KP and KA groups, respectively. Pancreas graft survival was 70% and 50% at 5 and 10 years, respectively. CONCLUSIONS: This clinical evaluation, even if retrospective, confirmed that simultaneous pancreas-kidney transplantation has a protective effect against cardiovascular mortality in diabetic recipients affected by end-stage renal disease.