Giorgio Talamini

Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis, and relationship to other mucinous cystic tumors

The clinicopathological features of 56 patients with mucinous cystic tumors (MCTs) of the pancreas were studied. Particular attention was paid to the prognosis of MCTs and the relationship to their ovarian, hepatic, and retroperitoneal counterparts. To distinguish MCTs from pancreatic intraductal papillary-mucinous tumors, MCTs were defined as tumors lacking communication with the duct system and containing mucin-producing epithelium, usually supported by ovarian-like stroma. All 56 tumors occurred in women (mean age 48.2 years) and were preferentially (93%) located in the body and tail of the pancreas. In accordance with the WHO classification, MCTs were divided into adenomas (n = 22), borderline tumors (n= 12), and noninvasive and invasive carcinomas (n = 22). Survival analysis revealed the extent of invasion to be the most significant prognostic factor (p<0.0001). Malignancy correlated with multilocularity and presence of papillary projections or mural nodules, loss of ovarian-like stroma, and p53 immunoreactivity. Stromal luteinization with expression of tyrosine hydroxylase, calretinin, or alpha inhibin was found in 66% of the cases. We conclude that the biologic behavior of MCTs is predictable on the basis of the extent of invasion. The similarities (i.e. gender, morphology, stromal luteinization) between pancreatic MCT and its ovarian, hepatobiliary, and retroperitoneal counterparts suggest a common pathway for their development.

Waist-to-Height Ratio, a Useful Index to Identify High Metabolic Risk in Overweight Children

OBJECTIVE To determine whether using a combination of body mass index (BMI) and waist circumference (WC) or waist-to-height ratio (W/Hr) is clinically helpful in identifying children with high metabolic and cardiovascular risks. STUDY DESIGN Caucasian children (M/F: 740/739; n = 1479; ages 5 to 15 years) were studied. Anthropometry, blood pressure, and venous fasting blood samples tested for triacylglycerol, HDL cholesterol, and glucose were measured. RESULTS Overweight children with a large waist (>90(th) percentile) or high W/Hr (>0.5) but not obese or normal-weight children had significantly greater chances of being at high metabolic and cardiovascular risk than normal-weight children (OR: 7; 95% CI: 3.63-13.48; P < .001, OR: 8.16; 95% CI: 3.87-17.23; P < .001, respectively) with a low waist measurement (</=90(th) percentile) or W/Hr (</=0.5). Interestingly, waist and W/Hr cutoffs (90(th) percentile and 0.5, respectively) were both able to identify children with the highest metabolic and cardiovascular risks among those who were overweight. However, contrary to waist circumference, W/Hr has the advantage of not requiring population specific reference tables as well as age and sex specific cutoffs. CONCLUSIONS Waist circumference and W/Hr are helpful in detecting, among overweight children, those with a higher likelihood of having metabolic and cardiovascular risks.

Early Versus Late Drain Removal After Standard Pancreatic Resections Results of a Prospective Randomized Trial

Summary of Background Data:The role of surgically placed intra-abdominal drainages after pancreatic resections has not been clearly established. In particular, their effect on morbidity rates and the optimal timing for their removal remains controversial. Methods:A total of 114 eligible patients who underwent standard pancreatic resections and at low risk of postoperative pancreatic fistula according to our institutional protocol (amylase value in drains ≤5000 U/L on postoperative day [POD] 1) were randomized on POD 3 to receive either early (POD 3) or standard drain removal (POD 5 or beyond). The primary end point of the study was the incidence of pancreatic fistula. Secondary endpoints included abdominal complications, pulmonary complications, in-hospital stay, and perioperative mortality. Cost-analysis between the 2 groups was also made. Results:Early drain removal was associated with a decreased rate of pancreatic fistula (P = 0.0001), abdominal complications (P = 0.002), and pulmonary complications (P = 0.007). Median in-hospital stay was shorter (P = 0.018), and hospital costs decreased (P = 0.02). Mortality was nil. A significant association with pancreatic fistula was found for timing of drain removal (P < 0.001), unintentional weight decrease before surgery (P = 0.022), type of pancreas texture (P = 0.015), serum amylase levels on POD 1 (P = 0.001), and albumin levels on POD 1 (P = 0.039). Multivariate analysis showed that timing of drain removal (P = 0.0003) and unintentional weight decrease before surgery (P = 0.02) were independent risk factors of pancreatic fistula. Conclusions:In patients at low risk of pancreatic fistula, intra-abdominal drains can be safely removed on POD 3 after standard pancreatic resections. A prolonged period of drain insertion is associated with a higher rate of postoperative complications with increased hospital stay and costs. The manuscript is a randomized trial, registered in the NLM database as NCT00931554.

Alcohol and Smoking as Risk Factors in Chronic Pancreatitis and Pancreatic Cancer

The aim of this study was to compare alcohol andsmoking as risk factors in the development of chronicpancreatitis and pancreatic cancer. We considered onlymale subjects: (1) 630 patients with chronic pancreatitis who developed 12 pancreatic and 47extrapancreatic cancers; (2) 69 patients withhistologically well documented pancreatic cancer and noclinical history of chronic pancreatitis; and (3) 700 random controls taken from the Verona pollinglist and submitted to a complete medical check-up.Chronic pancreatitis subjects drink more than controlsubjects and more than subjects with pancreatic cancer without chronic pancreatitis (P < 0.001).The percentage of smokers in the group with chronicpancreatitis is significantly higher than that in thecontrol group [odds ratio (OR) 17.3; 95% CI 12.6-23.8; P < 0.001] and in the group with pancreaticcarcinomas but with no history of chronic pancreatitis(OR 5.3; 95% CI 3.0-9.4; P < 0.001). In conclusion,our study shows that: (1) the risk of chronic pancreatitis correlates both with alcoholintake and with cigarette smoking with a trendindicating that the risk increases with increasedalcohol intake and cigarette consumption; (2) alcoholand smoking are statistically independent risk factors forchronic pancreatitis; and (3) the risk of pancreaticcancer correlates positively with cigarette smoking butnot with drinking.

Controlled clinical trial of pefloxacin versus imipenem in severe acute pancreatitis

BACKGROUND & AIMS Antibiotic prophylaxis in severe pancreatitis has recently yielded promising clinical results, with imipenem significantly reducing the incidence of infected necrosis compared with an untreated control group. On the bases of pefloxacins spectrum of action and pancreatic penetration, we investigated whether such drugs represent a valid alternative to imipenem. METHODS In a multicenter study, 60 patients with severe acute pancreatitis with necrosis affecting at least 50% of the pancreas were randomly allocated to receive intravenous treatment for 2 weeks with pefloxacin, 400 mg twice daily (30 patients), or imipenem, 500 mg three times daily (30 patients), within 120 hours of onset of symptoms. Age, sex, body weight, Ranson and Apache II scores, C-reactive protein, etiology, and time from onset of symptoms to treatment were well matched in the two groups. RESULTS The incidences of infected necrosis and extrapancreatic infections were 34% and 44%, respectively, in the pefloxacin group and 10% and 20% in the imipenem group. Imipenem proved significantly more effective in prevention of pancreatic infections (P </= 0.05). Mortality was not significantly different in the two groups. CONCLUSIONS Despite its theoretical potential, pefloxacin is inferior to imipenem in the prevention of infections associated with severe pancreatitis.

Amylase Value in Drains After Pancreatic Resection as Predictive Factor of Postoperative Pancreatic Fistula: Results of a Prospective Study in 137 Patients

Background:The correlation of the amylase value in drains (AVD) with the development of pancreatic fistula (PF) is still unclear. Aim:The purpose of this study was to identify within the first postoperative day (POD1) the predictive role of different risks factors, including AVD, in the development of PF. Patients and Methods:We prospectively investigated 137 patients who underwent major pancreatic resections. PF was defined and graded in accordance with the International Study Group on PF. Results:We considered 101 pancreaticoduodenectomies and 36 distal resections. The overall incidence of PF (A, B, and C grades) was 19.7% and it was 14.8% after pancreaticoduodenectomy and 33.3% after distal resection. All PF occurred in “soft” remnant pancreas. The PF developed in patients with a POD1 median AVD of 10,000 U/L, whereas patients without PF had a median AVD of 1222 U/L (P < 0.001). We established a cut-off of 5000 U/L POD1 AVD for univariate and multivariate analysis. The area under the receiver operating characteristic (ROC) curve was 0.922 (P < 0.001). The predicting risk factors selected in the univariate setting were “soft” pancreas (P = 0.005; odds ratio [OR]: 1.54; 95% CI: 1.32–1.79) and AVD (P < 0.001; OR: 5.66; 95% CI: 3.6–8.7; positive predictive value 59%; negative predictive value 98%), whereas in multivariate analysis the predicting risk factor was the POD1 AVD (P < 0.001; OR: 68.4; 95% CI: 14.8–315). Only 2 PFs were detected with AVD <5000 U/L and both were in pancreatogastric anastomosis (P = 0.053). Conclusions:AVD in POD1 ≥5000 U/L is the only significant predictive factor of PF development.

Incidence of cancer in the course of chronic pancreatitis

Objective:Chronic pancreatitis patients appear to present an increased incidence of pancreatic cancer. The aim of the study was to compare the incidence of cancer, whether pancreatic or extrapancreatic, in our chronic pancreatitis cases with that in the population of our region.Methods:We analyzed 715 cases of chronic pancreatitis with a median follow-up of 10 yr (7287 person-years); during this observation period they developed 61 neoplasms, 14 of which were pancreatic cancers. The cancer incidence rates were compared, after correction for age and gender, with those of a tumour registry.Results:We documented a significant increase in incidence of both extrapancreatic (Standardized Incidence Ratio [SIR], 1.5; 95% confidence interval [CI], 1.1–2.0; p <0.003) and pancreatic cancer (SIR, 18.5; 95% CI, 10–30; p < 0.0001) in chronic pancreatitis patients. Even when excluding from the analysis the four cases of pancreatic cancer that occurred within 4 yr of clinical onset of chronic pancreatitis, the SIR is 13.3 (95% CI, 6.4–24.5; p < 0.0001). If we exclude these early-onset cancers, there would appear to be no increased risk of pancreatic cancer in nonsmokers, whereas in smokers this risk increases 15.6-fold.Conclusions:The risks of pancreatic and nonpancreatic cancers are increased in the course of chronic pancreatitis, the former being significantly higher than the latter. The very high incidence of pancreatic cancer in smokers probably suggests that, in addition to cigarette smoking, some other factor linked to chronic inflammation of the pancreas may be responsible for the increased risk.

Cigarette smoking : an independent risk factor in alcoholic pancreatitis

It is not known whether cigarette smoking plays a role as a risk factor in alcoholic pancreatitis. The aim of this study was to compare drinking and smoking habits in three groups of male subjects with an alcohol intake in excess of 40 g/day: (i) 67 patients with acute alcoholic pancreatitis, without other known potential causative agents; (ii) 396 patients with chronic alcoholic pancreatitis; and (iii) 265 control subjects randomly selected from the Verona polling lists and submitted to a complete medical checkup. The variables considered were age at onset of disease, years of drinking and smoking, daily alcohol intake in grams, number of cigarettes smoked daily, and body mass index (BMI). Cases differed from controls in daily grams of alcohol, number of cigarettes smoked and BMI (Mann-Whitney U test, p < 0.00001 for each comparison). Multivariate logistic regression analysis, comparing acute and chronic cases, respectively, versus controls, revealed an increased relative risk of pancreatitis in the two comparisons, associated in both cases with a higher alcohol intake (p < 0.00001) and cigarette smoking (p < 0.00001). No significant interaction between alcohol and smoking was noted, indicating that the two risks are independent. In conclusion, in males a higher number of cigarettes smoked daily seems to be a distinct risk factor in acute and chronic alcoholic pancreatitis.

Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study.

OBJECTIVES:Prospective studies have identified a number of patient- and procedure-related independent risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, with different conclusions, so various questions are still open. The endoscopists expertise, case volume, and case mix can all significantly influence the outcome of ERCP procedures, but have been investigated little to date.METHODS:We identified patient- and procedure-related risk factors for post-ERCP pancreatitis and the impact of the endoscopists experience and the centers case volume, using univariate and multivariate analysis, in a multicenter, prospective study involving low- and high-volume centers, over a 6-month period.RESULTS:A total of 3,635 ERCP procedures were included; 2,838 (78%) ERCPs were performed in the 11 high-volume centers (median 257 each) and 797 in the 10 low-volume centers (median 45 each). Overall, 3,331 ERCPs were carried out by expert operators and 304 by less-skilled operators. There were significantly more grade 3 difficulty procedures in high-volume centers than in low-volume ones (P<0.0001). Post-ERCP pancreatitis occurred in 137 patients (3.8%); the rates did not differ between high- and low-volume centers (3.9% vs. 3.1%) and expert and non-expert operators (3.8% vs. 5.5%). However, in high-volume centers, there were 25% more patients with patient- and procedure-related risk factors, and the pancreatitis rate was one-third higher among non-expert operators. Univariate analysis found a significant association with pancreatitis for history of acute pancreatitis, either non-ERCP- or ERCP-related and recurrent, young age, absence of bile duct stones, and biliary pain among patient-related risk factors, and >10 attempts to cannulate the Vaters papilla, pancreatic duct cannulation, contrast injection of the pancreatic ductal system, pre-cut technique, and pancreatic sphincterotomy, among procedure-related risk factors. Multivariate analysis also showed that a history of post-ERCP pancreatitis, biliary pain, >10 attempts to cannulate the Vaters papilla, main pancreatic duct cannulation, and pre-cut technique were significantly associated with the complication.CONCLUSIONS:A history of pancreatitis among patient-related factors, and multiple attempts at cannulation among procedure-related factors, were associated with the highest rates of post-ERCP pancreatitis. Pre-cut sphincterotomy, although identified as another significant risk factor, appeared safer when done early (fewer than 10 attempts at cannulating), compared with repeated multiple cannulation. The risk of post-ERCP pancreatitis was not associated with the case volume of either the single endoscopist or the center; however, high-volume centers treated a larger proportion of patients at high risk of pancreatitis and did a significantly greater number of difficult procedures.

Reference values for exhaled nitric oxide (reveno) study.

BackgroundDespite the widespread use of fractional exhaled nitric oxide (FENO) as a biomarker of airways inflammation, there are no published papers describing normal FENO values in a large group of healthy adults.ObjectiveThe aim of this study was to establish adult FENO reference values according to the international guidelines.MethodsFENO was measured in 204 healthy, non-smoking adults with normal spirometry values using the on-line single-breath technique, and the results were analysed chemiluminescently.ResultsThe main result of the study was the significant difference in FENO values between men and women, thus indicating that gender-based reference FENO values are necessary. The FENO levels obtained at expiratory flows of 50 ml/s ranged from 2.6 to 28.8 ppb in men, and from 1.6 to 21.5 ppb in women.ConclusionWe propose reference FENO values for healthy adult men and women that could be used for clinical and research purposes.