[Show abstract][Hide abstract] ABSTRACT: 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. ResultsTotals 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.
[Show abstract][Hide abstract] ABSTRACT: To compare the outcome in patients with cervical goiters and cervicomediastinal goiters (CMGs) undergoing total thyroidectomy using the cervical or extracervical approach.
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.
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.
Symptoms, malignancy, overall morbidity, hypoparathyroidism, RLN palsy and hematoma are increased in cases of substernal goiter.
[Show abstract][Hide abstract] ABSTRACT: Since gemcitabine became the standard treatment for metastatic pancreatic adenocarcinoma, combination chemotherapy obtained conflicting impact on survival (OS).
To evaluate Italian treatment trends in metastatic pancreatic cancer.
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.
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).
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Chronic pancreatitis (CP) is characterised by the progressive destruction of the pancreatic parenchyma with coincident replacement
by fi brous tissue (Di Magno et al. 1993; Kloeppel and Maillet 1993). As the disease evolves, clinical manifestations and anatomic changes progress forcing an evolving therapeutic approach,
be it surgical or interventional, to these comlex patients (Cavallini et al. 1998). In recent years, the level of sophistication of our knowledge of the epidemiology, etiological factors, and concurrent
increasing availability of new therapeutic options has significantly altered our approach. The following chapter will attempt
to reassess the role of surgery for patients with CP.
[Show abstract][Hide abstract] ABSTRACT: The development of complications in inflammatory pancreopathies is often the main factor responsible for the presence and
severity of the clinical syndrome. A comprehensive short evaluation of clinical features and their significance is difficult
since various manifestations, clinical developments, treatments and prognoses differ wildly.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
Smoking cessation in the first years from the clinical onset of CP reduces the risk of developing pancreatic calcifications.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
The data suggest that genetic susceptibility to pancreatic cancer may be attributable, in addition to BRCA2, to moderate- to low-penetrance gene(s).
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of Gastrointestinal Surgery 05/2006; 10(4):504-10. DOI:10.1016/j.gassur.2005.09.011 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the results of pancreaticogastrostomy versus pancreaticojejunostomy following pancreaticoduodenectomy in a prospective and randomized setting.
While several techniques have been proposed for reconstructing pancreatico-digestive continuity, only a limited number of randomized studies have been carried out.
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).
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.
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.
Annals of Surgery 01/2006; 242(6):767-71, discussion 771-3. DOI:10.1097/01.sla.0000189124.47589.6d · 8.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intraductal papillary mucinous neoplasms (IPMNs) may present with clinical and radiological pictures resembling those of chronic pancreatitis (CP).
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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
The American Journal of Surgery 05/2004; 187(4):564-6. DOI:10.1016/j.amjsurg.2003.12.043 · 2.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cystic tumors of the pancreas are less frequent than other tumors in neoplastic pancreatic pathology, but in recent years the literature has reported an increasing number. After the first report by Becourt in 1830, cystic tumors were classified into 2 different types by Compagno and Oertel in 1978: benign tumors with glycogen-rich cells and mucinous cystic neoplasms with overt and latent malignancy. The WHO classification of exocrine tumors of the pancreas, published in 1996, is based on the histopathological features of the epithelial wall, which are the main factor in differential diagnosis with cystic lesions of the pancreas. Thanks to the knowledge acquired up to now, a surgical procedure is not always required because the therapeutic choice is conditioned by the correct classification of this heterogeneous group of tumors. Clinical signs are not really useful in the clinical work up, most patients have no symptoms and when clinical signs are present, they may help us to pinpoint the organ of origin but never to identify the type of pathology. In the last few years, the great improvement in imaging has enabled us not only to discriminate cystic from solid lesions, but also to identify the features of the lesions and label them preoperatively. More invasive diagnostic procedures such as fine needle aspiration and intracystic fluid tumor marker level are not really useful because they are not sensitive and the cystic wall can show different degrees of dysplasia and de-epithelialization. These are the reasons for sending the entire specimen to pathology. Good cooperation between surgeons, pathologists, radiologists and gastroenterologists is mandatory to increase the chances of making a proper diagnosis. Therefore, we must analyze all the information we have, such as age, sex, clinical history, location of the tumor and radiological features, in order to avoid the mistake of treating a cystic neoplasm as a benign lesion or as a pseudocyst, as described in the literature. Except for inoperable cases due to the critical condition of the patient or non-resectable lesions, surgical treatment differs with the diagnosis. Cystic tumors of the pancreas, therefore, are a heterogeneous group of tumors, with a real problem regarding differential diagnosis between neoplastic and inflammatory lesions. Even with a proper work up, some perplexity may remain about the nature of the lesion and in these cases the surgical procedure has a therapeutic value as well as playing a diagnostic role. The role of surgery is central in the treatment of these tumors because it could be curative when complete resection is possible. In this way, the lack of good therapeutic results with chemotherapy and radiotherapy force the surgeon to go ahead with the procedure. Intraductal papillary mucinous neoplasms represent a new and, from the epidemiological point of view, important chapter in the world of cystic tumors. The margin of resection is important and the surgeon has to be aware that in order to have a curative resection, total pancreatectomy is sometimes required. In the last few years the therapeutic approach has changed thanks to new knowledge of the biological behavior of these tumors. In fact, from a surgical approach in all cases, we are now discussing the possibility of a follow-up not only for asymptomatic serous cystadenomas but also for the little branch side intraductal papillary mucinous neoplasms (IPMNs) in critical patients. A follow-up could be planned even for solid pseudopapillary tumors but it seems risky to leave untreated big tumors in young patients without a certain diagnosis and with so few studies reported in the literature.
[Show abstract][Hide abstract] ABSTRACT: Although studies on the use of the somatostatin analogues in the elective pancreatic surgery are mostly prospective, double blind and randomised, the results are contradictory and not univocally interpretable. Through the examination of all randomised perspective works published on this subject, a critical interpretation is attempted which may give relevant suggestions for further studies. A new clinical, randomised, double blind and multicentric prospective trial should take into proper consideration even the changes which have occurred in the care of the patients. Over the years a significant decrease of postoperative hospital stay and a deeper awareness of the medical expenses have been observed. Moreover, since the drug has a potential advantage on specific pancreatic complications, only these must be considered among the end points of the study and the population studied will be limited exclusively to patients who underwent resection of the pancreatic head or of the periampullar region because of neoplastic disease. Finally, the selection of the centres that enrol the patients must be considered, since the expertise of each operator or of the team, affects, as an independent variable, both morbidity and mortality.
[Show abstract][Hide abstract] ABSTRACT: About 90% of patients suffering from pancreatic carcinoma are diagnosed with disease that is not amenable to surgical intervention due to local infiltration or the presence of hepatic metastases. Palliative intra-arterial chemotherapy was developed to improve the response in these patients by increasing the antiblastic dose and minimizing the side effects. The aim of this study is to evaluate the efficacy of this treatment comparison to a control group. From December 1994 to February 1997, 135 patients with ductal carcinoma, in whom 68 were stage III and 67 stage IV, with a median age of 63.3 years (range 38.4-79), were enrolled in an open study. Sixty four patients were subjected to a median of 3.5 cycles, according to intra-arterial FLEC protocol. Four patients had a partial response (6.3%), 27 enjoyed a stabilization of their disease (42.2%) and 13 showed disease progression (20.3%). The toxicity was mild. The overall survival was 8.3 months, better in the treated group (9.6 months) in respect to the control one (7.1 months), although this was not statistically significant. The treatment reported here, therefore, does not seem to change the prognosis of patients affected by no resectable pancreatic carcinoma, but it may demonstrate good tolerability and minimal toxicity.
[Show abstract][Hide abstract] ABSTRACT: To date, gabexate mesilate, a synthetic protease inhibitor, has been used in the prophylaxis and treatment of acute pancreatitis, but has yet to be tested in preventing the postoperative complications of pancreatic surgery. For this purpose we planned a pilot study based on two treatment groups, each numbering 25 patients, submitted to high-risk pancreatic resection. In the first group, all patients received a continuous infusion of gabexate mesilate 1 g/day up to postoperative day 4; the second group of patients received the same treatment plus octreotide 0.1 mg every 8 hours for 5 days after surgery. All patients were followed until discharge with clinical and instrumental investigations to detect the onset of postoperative complications. The overall incidences of an uneventful course were 40% (10/25) and 32% (8/25), respectively. We found 12 complications closely related to pancreatic surgery in the former and 8 in the latter group. In the combined treatment group therefore we observe a 33% reduction in the incidence of related abdominal complications (12 vs 8). This favourable trend, however, needs to be confirmed in a larger multicentre trial.
[Show abstract][Hide abstract] ABSTRACT: Because of advances in knowledge over recent years there is reason to believe that surgical attitudes towards patients with chronic pancreatitis may have changed.
Some 547 patients were treated surgically for chronic pancreatitis from 1971 to June 1998. Anastomoses were performed in 80 per cent (438 patients) and resections in 20 per cent (109 patients). Indications and type of operation were analysed, as were mortality and morbidity rates and long-term follow-up results, in patients undergoing resection both over the period as a whole and after dividing the series into two subperiods of 14 years.
In the second 14-year period, there was a significant reduction in the percentage of resections compared with anastomoses (28 per cent (69 of 244 patients) versus 13 per cent (40 of 303); P < 0.0001), and a significant change in the type of resection with a substantial increase in resections of the head compared with those of the body and tail. Statistically significant reductions occurred in operating times, number of units of blood transfused (mean(s.d.) 4.7(3.6) versus 1.2(1.6) units; P = 0.0001) and mean hospital stay (18 versus 14 days for pylorus-preserving and 12 versus 8 days for left pancreatectomy with splenectomy; P < 0. 01); mortality and morbidity rates also tended to decrease, but not significantly.
A different pattern has emerged over the years as regards both the type and number of resections performed.
British Journal of Surgery 04/2000; 87(4):428-33. DOI:10.1046/j.1365-2168.2000.01391.x · 5.54 Impact Factor