Riccardo Casadei

Nonfunctioning Pancreatic Endocrine Tumors: A Multicenter Clinical Study

OBJECTIVES:Nonfunctioning pancreatic endocrine tumors (NFPTs) are rare neoplasms that have been the object of few studies that have involved only small numbers of patients. This study was carried out to obtain a comprehensive and up-to-date clinical picture of these tumors.METHODS:A total of 184 patients with NFPT admitted to three Italian hospitals in the last 15 yr were studied. The diagnosis of NFPT was confirmed histologically using conventional and immunohistochemical techniques. Data were obtained from the medical charts or directly from the patients.RESULTS:There were 85 men (46.2%) and 99 women (53.8%). The mean age at diagnosis was 55.2 yr (range 17–82 yr). The percentage of smokers and alcohol drinkers was similar to that in the general population. Seven patients (3.9%) had a family history of exocrine pancreatic carcinoma. In 120 cases (65.2%), the diagnosis was made after workup for pain or other symptoms, in the remaining 64 cases (34.8%), the tumor was discovered incidentally by ultrasound; in this group survival was significantly greater than it was for the symptomatic patients (p = 0.0043). Survival was also found to be improved by tumor resection (p < 0.0001), absence of metastases (p < 0.0001), and small tumor size (≤3 cm) (p < 0.0007).CONCLUSIONS:NFPTs were slightly more frequent in women and were diagnosed most often in middle-aged individuals. No risk factors other than a family history of exocrine pancreatic carcinoma were found. Tumor discovery while patients were still asymptomatic, tumor resection, absence of metastases, and tumor size ≤3 cm significantly prolonged survival.

Tumor M2-Pyruvate Kinase, a New Metabolic Marker for Pancreatic Cancer

An isoenzyme of pyruvate kinase (Tu M2-PK) is overexpressed by tumor cells and can be measured in blood by a specific immunoenzymatic assay. Our objective was to investigate the diagnostic value of Tu M2-PK in comparison with that of CA 19-9 in pancreatic cancer. We studied 265 subjects: 60 with histologically confirmed pancreatic cancer, 43 with benign pancreatic diseases (acute and chronic pancreatitis), 5 with benign cystic neoplasms of the pancreas, 9 with neuroendocrine tumors, 77 with other abdominal malignancies, 47 with benign digestive diseases, and 24 healthy controls. Levels of plasma Tu M2-PK and serum CA 19-9 were determined by commercially available specific immunoassays. The diagnostic sensitivity and specificity of Tu M2-PK for pancreatic cancer were 85 and 41%, respectively, while those of CA 19-9 were 75 and 81%. The combination of the two tests significantly increased sensitivity (97%) but lowered specificity (38%). In discriminating between pancreatic cancer and acute or chronic pancreatitis, Tu M2-PK turned out to be less accurate than CA 19-9. In patients without pancreatic tumor, cholestasis appeared not to affect the values of Tu M2-PK, while CA 19-9 was found to be significantly higher. Tu M2-PK was also abnormally high in the majority of patients with other digestive malignancies or neuroendocrine tumors. The results demonstrate that Tu M2-PK has a satisfactory sensitivity but a poor specificity in the diagnosis of pancreatic cancer. Used together with CA 19-9, the sensitivity increases considerably.

Do early symptoms of pancreatic cancer exist that can allow an earlier diagnosis

Diagnosis of pancreatic cancer is made late, and prognosis remains extremely poor. This study was carried out to investigate whether symptoms exist before pain or jaundice that could suggest pancreatic cancer and favor earlier diagnosis. The study involved 305 patients with confirmed pancreatic cancer and 305 controls. All subjects were interviewed personally at least twice about their clinical history; pancreatic cancer patients were asked about any disturbances before abdominal pain or jaundice. Of the 305 pancreatic cancer patients, 151 (49.5%) had some prior disturbances, 108 (35.4%) 6 months or less before pain or jaundice and 43 (14.1%) more than 6 months before. Among the latter, 14 (4.6% of all patients) had had anorexia and/or early satiety and/or asthenia (7–20 months before pain or jaundice), 11 (3.6%) had disgust for coffee and/or smoking and/or wine (7–20 months before), 14 (4.6%) had diabetes (7–24 months before), and four (1.3%) had acute pancreatitis (8–26 months before). Among the controls, the only reports of these symptoms were two (0.7%) cases of asthenia (4 and 6 years earlier), 22 (7.2%) cases of diabetes (of which only two [0.7%] were diagnosed 7–24 months before the interview), and one (0.33%) case of acute pancreatitis (10 years earlier). Apart from acute pancreatitis, all the other differences between patients and controls were statistically significant. In approximately 15% of patients, disturbances existed more than 6 months before pain or jaundice, which, although not specific, could raise suspicion of the possibility of pancreatic cancer. These disturbances could represent the one current opportunity for an earlier diagnosis in a significant minority of pancreatic cancer patients.

Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms.

This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.

Pancreatic Endocrine Tumors Less Than 4 cm in Diameter Resect or Enucleate? A Single-Center Experience

Objective: Pancreatic endocrine tumors (PETs) are usually small, benign or low-grade malignant, and surgery should preserve the pancreatic parenchyma as much as possible. The aim of the study was to evaluate the postoperative and long-term survival of patients undergoing enucleation in small PETs. Methods: Of 82 patients having PETs, 46 with tumor less than 4 cm in diameter, without distant metastases and with R0 resection by final pathologic examination, were included in this study. Enucleation was performed when the tumor did not involve the main pancreatic duct and in the absence of peripancreatic lymphadenopathy (group A); a typical resection was carried out in all other cases (group B). The 2 groups were compared regarding postoperative mortality and morbidity, pancreatic fistula, postoperative hospital stay, reoperation, World Health Organization classification, TNM stage, recurrence, and long-term survival. Results: There were 15 patients (32.6%) in group A and 31 (67.4%) in group B. Postoperative and long-term results were similar in the 2 groups, whereas World Health Organization classification was significantly different; enucleation was performed more frequently than typical R0 resection in benign tumors (P = 0.009). Conclusions: Enucleation should be reserved for patients having benign PETs less than 4 cm in diameter and far from the main pancreatic duct.

Endocrine Tumors of the Ileum: Factors Correlated with Survival

Aim: To evaluate the most important factors correlated with survival in patients with endocrine tumors of the ileum, both at the time of diagnosis and during the follow-up period. Methods: Fifty-nine patients with ileal endocrine tumors diagnosed in our institution between 1990 and 2004 were studied. Results: The study included 36 men (61%) and 23 women (39%). The median age of the patients at the time of diagnosis was 61.4 (range 18–83) years. The median follow-up period was 71.9 (range 5–287) months. Forty patients (67.8%) were still alive at the end of the study; the median survival time was 172 months, and the 5-year survival rate was 78.9%. By univariate analysis, the survival rate was significantly related to female sex (p = 0.024) and flushing alone (p = 0.028) and associated with diarrhea at diagnosis (p = 0.015), weight loss at diagnosis (p = 0.038), Ki-67 level (p = 0.025), stage of disease at diagnosis (p = 0.012), presence of liver metastases at follow-up (p = 0.005), presence of diffuse metastases at diagnosis (p = 0.005) and at follow-up (p = 0.007), and type of surgical approach (overall: p = 0.018; not operated vs. radical surgery: p = 0.008; not operated vs. palliative surgery: p = 0.045). Using multivariate analysis, only female gender (p = 0.012) and the presence of liver metastases at follow-up (p = 0.004) were significantly related to survival. Conclusion: In the present study, female gender and the appearance of liver metastases at follow-up seem to be the main conditions which determine the poor prognosis of patients with ileal endocrine tumors.

The role of ultrasound in the differential diagnosis of serous and mucinous cystic tumours of the pancreas

Objective: To evaluate the usefulness of a series of ultrasound parameters in the differential diagnosis between serous and mucinous forms of cystic tumours of the pancreas. Setting: Retrospective comparative study between the histological analysis of surgical specimens from cystic tumours of the pancreas (4 serous cystadenomas, 6 mucinous cystadenomas and 11 mucinous cystadenocarcinomas) and ultrasound evaluation. Methods: The ultrasound images of the 21 tumours were analysed by an operator who did not know the result of the histological diagnosis and were divided according to Johnsons criteria (number of cysts >6 and diameter <2 cm for serous tumours; number of cysts <6 and diameter >2cm for mucinous tumours) and according to other anatomicopathological parameters such as the presence of septae, endocystic projections, central scar, central calcification and/or in the tumour wall. Results: The ultrasound study gave a correct diagnosis in two out of the four (50%) serous cystic tumours. A central scar and internal calcification was present in one of them. Fifteen (88.2%) of the 17 mucinous tumours were correctly diagnosed; one presented peripheral calcifications and three endocystic projections. Conclusion: Ultrasound has a high degree of sensitivity in the differential diagnosis of serous and mucinous cystic tumours of the pancreas if the ultrasound aspects corresponding to the anatomicopathological structure of the neoplasms are correctly evaluated.

Prognostic Factors in Periampullary and Pancreatic Tumor Resection in Elderly Patients

BackgroundMore than half of all patients with pancreatic adenocarcinoma are over 70 years of age. Life expectancy for the elderly population is increasing and currently major pancreatic resection provides the only meaningful chance of cure for periampullary and pancreatic tumors. Controversy over what constitutes the correct treatment of these tumors in elderly patients continues to this day. The aim of our study was to determine whether age alone or age plus some prognostic factors constitute contraindications to major pancreatic resections.MethodsBetween 2000 and 2005, data from 88 consecutive patients who had major pancreatic resection for periampullary or pancreatic tumors were entered into a prospective database. Fifty-three patients under 70 years of age (young patients), and 35 patients 70 years of age or older (elderly patients) were compared with respect to several characteristics and the postoperative course.ResultsPostoperative mortality and morbidity, length of hospital stay, and long-term survival were similar in the two groups. In the elderly group, the mortality rate was significantly higher in patients with chronic obstructive pulmonary disease (COPD), and the morbidity rate was significantly higher in patients with ASA 3 than in patients with ASA 1–2, in whom a pancreaticoduodenectomy or total pancreatectomy had been performed.ConclusionsAge alone is not a contraindication for major pancreatic resection. In elderly patients a careful evaluation of the co-morbidities and of the type of surgical procedure is mandatory in order to allow the proper selection of those patients best suited for surgery in specialized centers.

Total pancreatectomy: indications, operative technique, and results: a single centre experience and review of literature.

The aims of this study were to identify the indications to perform a total pancreatectomy and to evaluate the outcome and quality of life of the patient who underwent this operation. A retrospective analysis of a prospective database, regarding all the patients who underwent total pancreatectomy from January 2006 to June 2009, was carried out. Perioperative and outcome data were analyzed in two different groups: ductal adenocarcinoma (group 1) and non-ductal adenocarcinoma (group 2). Twenty (16.9%) total pancreatectomies out of 118 pancreatic resections were performed. Seven (35.0%) patients were affected by ductal adenocarcinoma (group 1) and the remaining 13 (65.0%) by pancreatic diseases different from ductal adenocarcinoma (group 2) [8 (61.5%) intraductal pancreatic mucinous neoplasms, 2 (15.4%) well-differentiated neuroendocrine carcinomas, 2 (15.4%) pancreatic metastases from renal cell cancer and, finally, 1 (7.7%) chronic pancreatitis]. Eleven patients (55%) underwent primary elective total pancreatectomy; nine (45%) had a completion pancreatectomy previous pancreaticoduodenectomy. Primary elective total pancreatectomy was significantly more frequent in group 2 than in group 1. Early and long-term postoperative results were good without significant difference between the two groups except for the disease-free survival that was significantly better in group 2. The follow-up examinations showed a good control of the apancreatic diabetes and of the exocrine insufficiency without differences between the two groups. In conclusion, currently, total pancreatectomy is a standardized and safe procedure that allows good early and late results. Its indications are increasing because of the more frequent diagnose of pancreatic disease that involved the whole gland as well as intraductal pancreatic mucinous neoplasm, neuroendocrine tumors and pancreatic metastases from renal cell cancer.

Are There Prognostic Factors Related to Recurrence in Pancreatic Endocrine Tumors

Aims: The aim of this study was to evaluate the rate, site, time of recurrence and prognostic factors related to the appearance of recurrences in patients affected by pancreatic endocrine tumors (PETs). Methods: Data from 67 consecutive patients with PETs who underwent R0 resection were analyzed. The prognostic factors considered were: gender, age, type of tumor, presence of symptoms, size of tumor, tumor node metastasis (TNM) stage, WHO classification and adjuvant therapy. Results: The recurrence rate was 24.6%, with a mean time of 7.3 ± 4.5 years. The majority were in the liver (75% of cases) and were rarely local (25%). Univariate analysis of the prognostic factors showed that the risk of recurrences is significantly higher in PETs in MEN-1 syndrome, in tumor size ≧4 cm, in the presence of liver metastases, in TNM stages III–IV and, finally, in PD-Cas and WD-Cas. Multivariate Cox regression analysis showed that only MEN-1 syndrome and the WHO classification were independent predictors of an increased risk of recurrence. Conclusions: Several prognostic factors were related to recurrences in PETs. MEN-1 syndrome and the WHO classification can be considered independent factors of an increased risk of recurrence.