Time trends in the treatment and prognosis of resectable pancreatic cancer in a large tertiary referral centre.

OBJECTIVES: Mortality in pancreatic cancer has remained unchanged over the last 20-30 years. The aim of the present study was to analyse survival trends in a selected population of patients submitted to resection for pancreatic cancer at a single institution. METHODS: Included were 544 patients who underwent pancreatectomy for pancreatic cancer between 1990 and 2009. Patients were categorized into two subgroups according to the decade in which resection was performed (1990-1999 and 2000-2009). Predictors of survival were analysed using univariate and multivariate analyses. RESULTS: Totals of 114 (21%) and 430 (79%) resections were carried out during the periods 1990-1999 and 2000-2009, respectively (P < 0.0001). Hospital length of stay (16 days versus 10 days; P < 0.001) and postoperative mortality (3% versus 1%; P = 0.160) decreased over time. Median disease-specific survival significantly increased from 16 months in the first period to 29 months in the second period (P < 0.001). Following multivariate analysis, poorly differentiated tumour [hazard ratio (HR) 3.1, P < 0.001], lymph node metastases (HR = 1.9, P < 0.001), macroscopically positive margin (R2) resection (HR = 3.2, P < 0.0001), no adjuvant therapy (HR = 1.6, P < 0.001) and resection performed in the period 1990-1999 (HR = 2.18, P < 0.001) were significant independent predictors of a poor outcome. CONCLUSIONS: Longterm survival after surgery for pancreatic cancer significantly improved over the period under study. Better patient selection and the routine use of adjuvant therapy may account for this improvement.

Does mediastinal extension of the goiter increase morbidity of total thyroidectomy? A multicenter study of 19,662 patients.

PURPOSE: To compare the outcome in patients with cervical goiters and cervicomediastinal goiters (CMGs) undergoing total thyroidectomy using the cervical or extracervical approach. METHODS: This was a retrospective study conducted at six academic departments of general surgery and one endocrine-surgical unit in Italy. The study population consisted of 19,662 patients undergoing total thyroidectomy between 1999 and 2008, of whom 18,607 had cervical goiter (group A) and 1055 had CMG treated using a cervical approach (group B, n = 986) or manubriotomy (group C, n = 69). The main parameters of interest were symptoms, gender, age, operative time, duration of drain, length of hospital stay, malignancy and outcome. RESULTS: A split-sternal approach was required in 6.5% of cases of CMG. Malignancy was significantly more frequent in group B (22.4%) and group C (36.2%) versus group A (10.4%; both P < .001), and in group C versus group B (P = .009). Overall morbidity was significantly higher in groups B + C (35%), B (34.4%) and C (53.5%) versus group A (23.7%; P < .001). Statistically significant increases for group B + C versus group A were observed for transient hypocalcemia, permanent hypocalcemia, transient recurrent laryngeal nerve (RLN) palsies, permanent RLN palsies, phrenic nerve palsy, seroma/hematoma, and complications classified as other. With the exception of transient bilateral RLN palsy, all of these significant differences between group B + C versus group A were also observed for group B versus group A. CONCLUSIONS: Symptoms, malignancy, overall morbidity, hypoparathyroidism, RLN palsy and hematoma are increased in cases of substernal goiter.

Treatment trends in metastatic pancreatic cancer patients: Is it time to change?

BACKGROUND: Since gemcitabine became the standard treatment for metastatic pancreatic adenocarcinoma, combination chemotherapy obtained conflicting impact on survival (OS). AIMS: To evaluate Italian treatment trends in metastatic pancreatic cancer. METHODS: Data on treatment outcome of 943 chemo-naive patients with pathological diagnosis of stage IV pancreatic adenocarcinoma treated between 1997 and 2007 in Italian centres were analysed. RESULTS: Four treatment groups could be identified: (1) single agent gemcitabine (N=529); (2) gemcitabine-platinating agent doublets (N=105); (3) gemcitabine-free three-drug intraarterial combination (N=75); (4) four-drug gemcitabine-cisplatin-fluoropyrimidine based combinations (N=170). Median and actuarial 1 y OS of the whole population were 6.2 months and 20%, respectively. Gemcitabine (median OS 5.1 months) appeared significantly inferior to gemcitabine-free triplets (median OS 6.0 months; p=.04), gemcitabine-platinating agent doublets (median OS 7.4 months; p=.00001), or gemcitabine-based four drug combinations (median OS 9.1 months; p<.00001). CONCLUSION: These data mirror the Italian clinical practice in the therapeutic management of pancreatic cancer and suggest that four-drug combination chemotherapy may be included amongst the candidate regimens for phase III testing.

An Italian study on treatment trends and outcomes of patients with stage III pancreatic adenocarcinoma in the gemcitabine era: is it time to change?

A series of 650 patients treated between 1997 and 2007 at 10 Italian centers was analyzed to assess treatment trends and efficacy in stage III pancreatic adenocarcinoma. Data on patient characteristics, treatment and outcomes were collected. The inclusion criteria were pathological diagnosis of stage III pancreatic adenocarcinoma; age more than 18 years, Eastern Cooperative Oncology Group performance status less than 3, and no past therapy. Most patients (95%) received up-front chemotherapy, which mainly consisted of gemcitabine alone (N=323), gemcitabine-based four-drug combinations (N=107), gemcitabine-platinum compound doublets (N=87), or intra-arterial gemcitabine-free triplets (N=57). The use of gemcitabine-platinum compound doublets increased over time (1997-2001: 2%; 2002-2007: 21%) whereas an inverse trend was observed for gemcitabine (71-61%). No overall survival (OS) difference was observed between patients enrolled in clinical trials and those not enrolled. The median and 1-year OS were 9.5 months and 35.5% for patients treated with gemcitabine; 8.9 months and 36.8% for those treated with gemcitabine-free intra-arterial triplets; 13.3 months and 55.8% for those treated with gemcitabine-platinating agent doublets; and 16.2 months and 62.6% for those treated with gemcitabine-based four-drug combinations. Moreover, the median and 1-year OS were 12.7 months and 51.4% in patients who underwent planned consolidation chemoradiation, and 8.4 months and 30.4% in patients who did not. The use of a strategy consisting of a gemcitabine-platinating agent containing chemotherapy followed by consolidation chemoradiation has been increasing over time and may represent a suitable choice in the therapeutic management of stage III pancreatic adenocarcinoma.

Resectable pancreatic cancer: who really benefits from resection?

BACKGROUND: The 1-year disease-related mortality after resection for pancreatic cancer is approximately 30%. This study examined potential preoperative parameters that would help avoid unnecessary surgery. METHODS: Among the patients resected at our institution from 1997 to 2006, a total of 228 underwent pancreatic resection for ductal adenocarcinoma. By means of a survival cutoff of 12 months, two groups were created: early death (ED) and long survivors. A logistic regression analysis was performed to identify perioperative predictors of ED. RESULTS: Among 228 resected patients, postoperative mortality occurred in four cases (1.8%) that were excluded from the study. In the remaining 224 patients, 43 (19.2%) died of disease within 12 months from surgery (ED), and the remaining 181 (80.8%) had a longer survival. Multivariate analysis selected duration of preoperative symptoms > 40 days, CA 19-9 > 200 U/mL, pathological grading G3-G4, and R2 resection as independent predictors of ED. CONCLUSIONS: Duration of symptoms, CA 19-9 serum level, and pathological grading possibly retrieved by endoscopic ultrasound-guided biopsy can be preoperatively used to identify patients with disease that is not suitable for up-front surgery, even if deemed resectable by high-quality imaging.

Smoking cessation at the clinical onset of chronic pancreatitis and risk of pancreatic calcifications.

OBJECTIVE: Cigarette smoking is associated with a higher risk of developing chronic pancreatitis (CP) and increases the likelihood of developing pancreatic calcifications. The aim of this study was to know whether smoking cessation modifies the course of the disease. METHODS: Patients with CP who had been followed up for more than 6 years from clinical onset and who had not developed calcifications after 5 years were analyzed. We studied smokers, never-smokers, and patients who had given up smoking within 5 years. For actuarial analysis, the sixth year was considered as time 0. RESULTS: Of the 360 patients, there were 43 women and 317 men (88.1%) with a mean age of 38.7 years. The median follow-up was 19.0 years. Chronic pancreatitis was alcohol-associated in 255 patients, hereditary in 10, obstructive in 54, and idiopathic in 41. There were 317 smokers (88.1%) and 259 alcohol drinkers (71.9%). At the end of the follow-up, 212 patients (59.8%) developed calcifications. Concerning the risk of calcifications, never-smokers and ex-smokers had similar actuarial curves, and these were significantly different from the curve for smokers (P < 0.003). Considering never-smokers as the reference class, ex-smokers had an odds ratio (OR) of 0.56 (95.0% confidence interval [CI], 0.2-1.4; P = not significant), patients smoking 1 to 10 cigarettes per day had an OR of 1.95 (95.0% CI, 1.1-3.4; P < 0.019), patients smoking 11 to 20 cigarettes per day had an OR of 1.76 (95.0% CI, 1.1-2.8; P < 0.0018), and those smoking more than 20 cigarettes per day had an OR of 1.79 (95.0% CI, 1.1-2.9; P < 0.019). Alcohol cessation seems to have no influence. CONCLUSIONS: Smoking cessation in the first years from the clinical onset of CP reduces the risk of developing pancreatic calcifications.

Cancer risk among the relatives of patients with pancreatic ductal adenocarcinoma.

BACKGROUND/AIMS: Pancreatic cancer is a leading cause of cancer-related death; the most consistently identified risk factors are smoking and family history. Our aims were to examine familial aggregations of pancreas and other cancers, and to determine the relative risk of the family members. METHODS: We prospectively collected data on the families of patients presenting with pancreatic ductal adenocarcinoma. Smoking habits and alcohol consumption of the probands were compared with the available statistics on the Italian population. Mortality from cancer was investigated in first-degree relatives, and age-dependent risks of dying from pancreatic cancer and other tumors were compared with background population levels. RESULTS: Data for 570 families were collected, including 9,204 relatives. Probands were 3- to 5-fold more often heavy smokers than the general population, and 9.3% of them reported a positive family history of pancreatic cancer. In first-degree relatives, only mortality from pancreatic cancer was significantly increased (relative risk at age 85 years = 2.7). Lifetime risk of dying of pancreas cancer was 4.1% for the relatives of all probands, and was 7.2% for the relatives of probands who developed disease before 60 years of age. CONCLUSIONS: The data suggest that genetic susceptibility to pancreatic cancer may be attributable, in addition to BRCA2, to moderate- to low-penetrance gene(s).

Intraductal papillary mucinous neoplasms and chronic pancreatitis.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) may present with clinical and radiological pictures resembling those of chronic pancreatitis (CP). AIMS: To compare the clinical and epidemiological characteristics of patients suffering from CP with those of patients suffering from IPMN. To assess whether CP is associated with an increased risk of developing IPMN. METHODS: In our departments, from 1981 to 1998, we prospectively followed 473 patients suffering from CP, including 93 cases of chronic obstructive pancreatitis (COP), and 45 patients with a histologically confirmed diagnosis of IPMN. Another 6 patients had an initial diagnosis of CP and a subsequent diagnosis of IPMN. RESULTS: Patients with IPMN were more often female (females 53 vs. 15%; p < 0.001), were older (mean age 63.1 vs. 42.8 years; p < 0.001), drank less alcohol (19 vs. 107 g/day; p < 0.001) and smoked fewer cigarettes (mean 8 vs. 21 cigarettes/day) than CP patients. These results were also confirmed when considering only patients with COP. The 6 patients with a subsequent diagnosis of IPMN were males (p n.s.) with a mean age of 51.4 years (p < 0.05). Only 1 patient was a drinker (p < 0.05) and 4 were smokers (p n.s.). Comparing CP and IPMN, logistic regression analysis selected sex, age, alcohol and smoking, whereas only sex and age were selected when comparing COP vs. IPMN. CONCLUSIONS: In general patients with IPMN present different epidemiological characteristics than those with CP and the subgroup with COP. The clinical and pathological features suggest that in most cases IPMN is the cause of CP and not vice versa.

Long-term results of Frey's procedure for chronic pancreatitis: a longitudinal prospective study on 40 patients.

Only limited prospective data are available regarding the long-term outcome of local resection of the pancreatic head in combination with longitudinal pancreaticojejunostomy in patients with chronic pancreatitis. From 1997 to 2001, 40 patients affected by chronic pancreatitis were subjected to the Frey's procedure. Preoperative selection criteria included confirmed diagnosis of chronic pancreatitis, dilation of Wirsung's duct to a diameter greater than 6 mm, and the absence of obstructive chronic pancreatitis secondary to fibrotic stenosis at the pancreatic body or tail. Preoperative pain was present in 38 cases (95%), and follow-up was performed in all patients at least once yearly up to 2003 (median 60 months, inter percentile range 20.1-79.6). Postoperative morbidity occurred in three cases (7.5%). The percentage of pain-free patients was 94.7%, 93.7%, 87.5%, and 90% at 1, 2, 3, and 4/5 years after surgical operation, respectively. After surgery, three patients developed diabetes. Both the body mass index and quality of life showed statistically significant improvements at all follow-up intervals. Whenever surgery is indicated, the short-term and long-term outcomes confirm that Frey's procedure is an appropriate means of management for patients with chronic pancreatitis in the absence of doubts of neoplasia and/or distal ductal obstruction.

Reconstruction by pancreaticojejunostomy versus pancreaticogastrostomy following pancreatectomy: results of a comparative study.

OBJECTIVE: To compare the results of pancreaticogastrostomy versus pancreaticojejunostomy following pancreaticoduodenectomy in a prospective and randomized setting. SUMMARY BACKGROUND DATA: While several techniques have been proposed for reconstructing pancreatico-digestive continuity, only a limited number of randomized studies have been carried out. METHODS: A total of 151 patients undergoing pancreaticoduodenectomy with soft residual tissue were randomized to receive either pancreaticogastrostomy (group PG) or end-to-side pancreaticojejunostomy (group PJ). RESULTS: The 2 treatment groups showed no differences in vital statistics or underlying disease, mean duration of surgery, and need for intraoperative blood transfusion. Overall, the incidence of surgical complications was 34% (29% in PG, 39% in PJ, P = not significant). Patients receiving PG showed a significantly lower rate of multiple surgical complications (P = 0.002). Pancreatic fistula was the most frequent complication, occurring in 14.5% of patients (13% in PG and 16% in PJ, P = not significant). Five patients in each treatment arm required a second surgical intervention; the postoperative mortality rate was 0.6%. PG was favored over PJ due to significant differences in postoperative collections (P = 0.01), delayed gastric emptying (P = 0.03), and biliary fistula (P = 0.01). The mean postoperative hospitalization period stay was comparable in both groups. CONCLUSIONS: When compared with PJ, PG did not show any significant differences in the overall postoperative complication rate or incidence of pancreatic fistula. However, biliary fistula, postoperative collections and delayed gastric emptying are significantly reduced in patients treated by PG. In addition, pancreaticogastrostomy is associated with a significantly lower frequency of multiple surgical complications.

Prophylactic pylorus-preserving gastric transposition in unresectable carcinoma of the pancreatic head.

Patients with unresectable carcinoma of the pancreas head often present with intestinal obstruction during their disease, but the efficacy of a prophylactic gastrointestinal anastomosis is still under debate. Some investigators consider the population of patients who eventually develop this complication too small to justify the prophylactic use of this procedure. When done prophylactically, the gastrointestinal anastomosis tends not to function and close. Other surgeons have proposed supplementing the gastric bypass using technique alternatives. To demonstrate the low morbidity, the feasibility, and the advantages and disadvantages of this procedure, we report our personal experience with transection of the duodenum and re-establishment of the continuity of the alimentary tract with a duodenojejunal anastomosis performed in 34 patients.