PubMed Health⌕ Search

Biomedical subjects

Massimo Falconi

Publications and source records attributed to Massimo Falconi.

At least 37 records · Page 2Linked to original sources

Allelotype of ampulla of Vater cancer: highly frequent involvement of chromosome 11.

PURPOSE: To determine the genetic differences/similarities in ampulla of Vater cancers (AVC) with respect to other pancreatic tumor types. METHODS: We analyzed eight cases of primary AVC by genome-wide allelotyping on DNA obtained from frozen tissue. A total of 372 microsatellite loci were used for each case, for a total of 2,976 microsatellites analyzed. RESULTS: Of the 2,159 informative markers, 400 were allelic losses and 1,759 markers were retained for an average fractional allelic loss of 0.19. Seven cases showed LOH on at least two markers on chromosomal arm 11p, while six cases showed allelic losses on 11q. The high frequency of LOH on chromosome 11 was also confirmed by analysis of an additional 17 paraffin-embedded AVC. Frequent LOH (50% or greater) was also found on chromosome arms 5q, 6q, 9p, 13, 16p, 17p, and 18p. CONCLUSIONS: It can be inferred that the targets of inactivation on chromosomes 5q, 9p, and 17p appear to be APC, p16, and p53, respectively, while the critical target(s) of inactivation at the other frequently lost loci remain to be characterized. The resulting allelotype reveals that distinctive chromosomal alterations are present in these neoplasms, indicating that it is a tumor entity distinct from pancreatic adenocarcinoma.

Adult↗

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.

Aged↗

Maldi-TOF analysis of portal sera of pancreatic cancer patients: identification of diabetogenic and antidiabetogenic peptides.

BACKGROUND: Pancreatic cancer (PC) associated diabetes mellitus (DM) might be consequent to the diabetogenic effects of tumour products, possibly acting via nitric oxide (NO). Our aims were: (1) to verify whether PC associated DM determines an increased hepatic NO and (2) using MALDI-TOF analysis, to evaluate the peptide composition of PC cell conditioned media (CM) and of portal sera from patients with PC with (n=7) or without (n=4) DM. METHODS: In liver tissue homogenates of 23 patients with PC (n=17) or chronic pancreatitis (n=6) GAPDH mRNA and activity, glucose, lactate, nitrite and nitrate were assayed. MALDI-TOF analysis was performed in three PC cell lines CM, and in portal sera from patients with PC. RESULTS: Higher GAPDH mRNA and nitrite were found in patients with than in patients without DM. In PC cell CM, only 9 among a total of 75 fragments identified, were tumour specific. One hundred seventy-three fragments were identified in the portal sera of patients: one was positively and six fragments were negatively correlated with DM. CONCLUSIONS: Unlike liver GAPDH, NO appears to be involved in PC associated DM. In portal sera, the absence, rather than the presence, of specific fragments, appears to be correlated with the development of DM.

Aged↗

Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection.

OBJECTIVE: To describe clinical characteristics and outcomes of a large cohort of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas affecting the main pancreatic duct. SUMMARY BACKGROUND DATA: IPMNs are being diagnosed with increasing frequency. Preoperative determination of malignancy remains problematic, and reported results of long-term survival following resection are conflicting. METHODS: The combined databases from the Massachusetts General Hospital and the Pancreatic Unit of the University of Verona were analyzed. To avoid confusing overlap with mucinous cystic neoplasms, only patients with tumors of the main pancreatic duct (with or without side branch involvement) were included. A total of 140 tumors consecutively resected between 1990 and 2002 were classified as either benign (adenoma and borderline tumors) or malignant (carcinoma in situ or invasive cancer) to compare their characteristics and survival. RESULTS: Men and women were equally affected (mean age 65 years). Seven patients (12%) had adenomas, 40 (28%) borderline tumors, 25 (18%) carcinoma in situ, and 58 (42%) invasive carcinoma. The median age of patients with benign IPMN was 6.4 years younger than those with malignant tumors (P = 0.04). The principal symptoms were abdominal pain (65%), weight loss (44%), acute pancreatitis (23%), jaundice (17%), and onset or worsening of diabetes (12%); 27% of patients were asymptomatic. Jaundice and diabetes were significantly associated with malignant tumors. Five- and 10-year cancer-specific survival for patients with noninvasive tumors was 100%, and comparable survival of the 58 patients with invasive carcinoma was 60% and 50%. CONCLUSIONS: Cancer is found in 60% of patients with main-duct IPMNs. Patients with malignant tumors are 6 years older than their benign counterparts and have a higher likelihood of presenting with jaundice or new onset diabetes. No patients with benign tumors or carcinoma in situ died of their disease following resection, and those with invasive cancer had a markedly better survival (60% at 5 years) than pancreatic ductal adenocarcinoma. These findings support both the concept of progression of benign IPMNs to invasive cancer and an aggressive policy of resection at diagnosis.

Aged↗

Pancreatic fistula rate after pancreatic resection. The importance of definitions.

BACKGROUND: Pancreatic fistula (PF) is still regarded as a serious complication both in terms of frequency and sequelae. The incidence varies greatly in different reports because of the different definitions used. The aim of this study was to compare several definitions of PF encountered in the current literature and to demonstrate that the PF rate in the same group of patients treated in a high volume center is dependent upon the definition applied. METHODS: A Medline search of the last 10 years was performed as regards the definition of PF. A score was assigned to the reproducible definitions based upon two basic parameters: daily output (cm3) and duration of the fistula represented by the number of days between the postoperative day of onset and the duration of the complication. Four definitions were formulated and were then applied to a group of 242 patients that underwent pancreatic head or intermediate resections with pancreatico-jejunal anastomosis in our Pancreatic Unit between November 1996 and December 2000. Statistical analysis was carried out using the Yates correct chi2 test with statistical significance set at p < 0.05. RESULTS: Among 26 different definitions identified, 14 were found suitable for the applied score. We formulated four final definitions summarizing the current concepts of PF. The incidence of PF ranged between 9.9 and 28.5% according to the different definitions applied with highly statistical differences between them. CONCLUSIONS: The PF rate after pancreatic resections is strictly dependent upon the definition used. An overall general agreement for an internationally accepted definition is urgently needed to correctly compare different experiences.

Anastomosis, Surgical↗

Management of 100 consecutive cases of pancreatic serous cystadenoma: wait for symptoms and see at imaging or vice versa?

Pancreatic serous cystadenomas have a low malignancy rate. When nonsymptomatic, in selected patients, they can be managed without surgery; however, a high degree of diagnostic reliability is crucial. We admitted 100 consecutive cases (87 women with a median age of 51.86 years). Of these, 44 were symptomatic and 56 were diagnosed incidentally. Ultrasound correctly diagnosed 53% of the cases, incorrectly 31%, and was nondiagnostic in 16%. Computed tomography scan had similar rates (54%, 34% and 12%, respectively), while magnetic resonance imaging improved diagnostic accuracy to 74% and reduced incorrect diagnoses to 26%. In 21 cases, exploratory needle aspiration of the cyst was carried out; only 8 samples (38%) resulted in a diagnosis; in 12 patients (57%) insufficient material was acquired to allow for diagnosis, one case demonstrated epithelial dysplasia. In 1 patient an exploratory puncture resulted in a very serious bleeding. Sixty-eight patients were treated surgically, the 44 symptomatic cases and another 24 patients with ill-defined oligocystic lesions that could not be differentiated as serous or mucinous in the preoperative period. Two patients underwent resection because of frank tumor growth. In the two time periods analyzed (the first 7 years and the subsequent 6.5 years) the relationship between cases observed/operated on did not significantly change. Twenty-one (30.8%) distal pancreatectomies, 14 (20.5%) intermediate resections, 10 (14.7%) pancreaticoduodenectomies 4 (5.8%) enucleations, and 1 (1.4%) duodenum-preserving pancreatic head resection were carried out. Nine patients (13.2%), underwent exploratory laparotomy with a diagnostic biopsy. Another 9 underwent decompressive interventions with cystojejunostomies. The morbidity was 27.9%, with a reoperation rate of 7.3% and zero mortality. In general the patient's pain resolved in the postoperative period. Median follow-up was 43 months (range, 4-191 months). One patient died from other causes, and all others are currently alive. In the group of 32 patients who did not undergo operation, the median follow-up is 69 months (range, 8-164 months). Until more sophisticated technologies can be developed, the current diagnostic work-up will not result in increased preoperative diagnosis of serous-cystic tumors of the pancreas. This is mainly relevant to the oligocystic forms, which account for about one fourth of all serous tumors observed.

Adult↗

Sonography versus helical CT in identification and staging of pancreatic ductal adenocarcinoma.

PURPOSE: The aim of this prospective study was to compare sonography with helical CT in the identification and staging of ductal adenocarcinoma of the pancreas. METHODS: Sixty-four patients with histopathologically proven pancreatic ductal adenocarcinoma underwent both sonography and helical CT at our hospital between November 1, 2000, and October 31, 2001. These diagnostic imaging examinations were performed by 2 independent radiologists who were unaware of the findings of any other imaging or histopathologic examination and who assessed each case for the presence of tumor, involvement of peripancreatic vessels, the presence of metastases in the liver, and the resectability of the tumor. In the patients who underwent subsequent laparotomy, imaging-based diagnoses of overall resectability and vascular involvement were compared with surgical findings, which were considered the gold standard. Imaging-based diagnoses for the presence of hepatic metastases were compared with the findings of intraoperative sonography in patients who underwent radical resection and with the surgical findings in the patients who underwent palliative surgery; the operative findings were considered the gold standard. RESULTS: In the identification of pancreatic adenocarcinoma, sonography was more accurate (61 of 64 tumors, 95.3%) than helical CT was (57 of 64 tumors, 89.1%). In the overall prediction of resectability among the 43 patients who underwent laparotomy, sonography (81.4%) was less accurate than CT was (86.0%). In diagnosing involvement of the superior mesenteric artery, sonography (95.3%) was more accurate than CT (88.4%). The 2 methods were equally accurate in diagnosing hepatic metastases (86.0%) and involvement of the celiac trunk (100%) and the superior mesenteric vein (88.4%), but sonography was less accurate than CT for diagnosing involvement of the common hepatic artery (90.7% versus 95.3%, respectively) and portal vein (88.4% versus 93.0%, respectively). CONCLUSIONS: Sonography is more reliable than CT in identifying pancreatic adenocarcinoma, and its accuracy in staging is similar to that of CT.

Adenocarcinoma↗

Duct-to-mucosa versus end-to-side pancreaticojejunostomy reconstruction after pancreaticoduodenectomy: results of a prospective randomized trial.

BACKGROUND: Anastomotic failure is still a significant problem that affects the outcome of pancreaticoduodenectomy. There have been many techniques proposed for the reconstruction of pancreatic digestive continuity, but there have been few prospective and randomized studies that compare their efficacy. METHODS: In the current work, 144 patients who underwent a pancreaticoduodenectomy with soft residual tissue were assigned randomly to receive either a duct-to-mucosa anastomosis (group A) or a 1-layer end-to-side pancreaticojejunostomy (group B). RESULTS: The 2 treatment groups were found not to have any differences in regards to vital statistics, underlying disease, or operative techniques. The postoperative course was complicated in 54% of the 144 patients, with a comprehensive incidence of abdominal complications in 36% (group A, 35%; group B, 38%; P=not significant). The principal complication was pancreatic fistulas, which occurred in 14% of patients (group A, 13%; group B, 15%; P=not significant). Two patients (2%) required reoperation; the postoperative mortality rate was 1%. CONCLUSION: The 2 methods that were studied revealed no significant difference the rate of complications.

Adult↗

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 (< or =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 < or =3 cm significantly prolonged survival.

Adenoma, Islet Cell↗

The value of standard serum tumor markers in differentiating mucinous from serous cystic tumors of the pancreas: CEA, Ca 19-9, Ca 125, Ca 15-3.

BACKGROUND: Differentiating between mucinous cystic tumors (MCTs) and serous cystic tumors (SCTs) can be a troubling diagnostic dilemma in pancreatology: when SCTs present in their macro-oligocystic form they must be resected because MCT cannot be ruled out, and some tumors considered benign are actually MCTs, which delays diagnosis and places patients at increased risk. Examination of preoperative serum tumor markers may help improve preoperative diagnosis. MATERIALS AND METHODS: The tumor markers CEA, Ca 19-9, Ca 125, and Ca 15-3 were examined in 157 patients with SCTs or MCTs. RESULTS: Positive CEA marker status is an indicator of an MCT, although sensitivity is low at 17%. Using three serum tumor markers (CEA, Ca 19-9, and Ca 125), 27% of MCTs were found to have two or more markers positive, compared to none for the SCTs. Sensitivity decreases to 13% for differentiating benign MCTs from benign SCTs but specificity remains 100%. CONCLUSIONS: In the differential diagnosis of SCTs vs. MCTs no reliable serum tumor marker exists which can diagnose SCTs and spare some patients unnecessary operations. Nonetheless, positive CEA serum marker status and or the presence of more than two positive serum markers (CEA, Ca 19-9, or Ca 125) indicates the presence of an MCT and can prevent delay in diagnosis.

Adult↗

Absence of mutations in the transforming growth factor-beta inducible early gene 1, TIEG1, in pancreatic cancer.

Pancreatic cancers frequently have defects in components of the transforming growth factor-beta (TGF-beta) signaling pathway. TIEG1 (TGF-beta inducible early gene) is a recently characterized transcription factor regulated by TGF-beta that induces apoptosis when overexpressed in pancreatic adenocarcinoma cell lines. Alterations on chromosome 8q, where TIEG1 is located, are also relatively frequent in pancreatic cancers. To determine if TIEG1 may be involved in the tumorigenesis of pancreatic cancer, we performed mutational screening of this gene in 22 pancreatic cancer cell lines. No sequence alterations were observed. Reverse transcription-polymerase chain reaction analysis was also performed to rule out the possibility that the expression of the gene is altered by genetic events other than mutation. Likewise, no alterations in expression were found. Thus, an essential role of TIEG1 in pancreatic cancer can be excluded.

DNA Mutational Analysis↗

Non-traumatic abdominal emergencies: imaging and intervention in acute pancreatic conditions.

Pancreatic emergency, unrelated to traumatic events, can occur as a consequence of the more significant pancreatic pathologies (acute and chronic pancreatitis, tumors) or of the interventional or surgical treatment carried out as therapy for the above-mentioned lesions. Acute pancreatic conditions are represented by pancreatic infections, the involvement of organs, structures, and adjacent spaces within the pancreatic disease, and, lastly, vascular complications. Acute pancreatic conditions are common in pancreatic diseases and can be catastrophic; even if there is a gamut in the severity of clinical presentation, each can be potentially life threatening. Immediate radiological detection of the lesions together with a correct therapeutic percutaneous radiological approach whenever an interventional procedure is preferable to surgery or, when performed before surgery, whenever it can optimize its results, is of fundamental importance in the management of these patients. This article focuses on the essential role of radiology and the integration of imaging and intervention in acute pancreatic conditions.

Acute Disease↗

Ampulla of vater cancers: T-stage and histological subtype but not Dpc4 expression predict prognosis.

Loss of immunohistochemical expression of Dpc4 occurs in about 50% of pancreatic ductal cancers and its loss correlates with DPC4/Smad4 gene inactivation. Dpc4 expression was also lost in 6 of 16 (37%) ampulla of Vater cancers (AVCs) previously analyzed. Furthermore, chromosomal losses involving 18q, where DPC4 is located, have been observed in 34% of AVCs and are associated with decreased survival. To evaluate the possibility that expression of Dpc4 may be correlated with survival, we analyzed 89 AVCs for inactivation of DPC4 by immunohistochemical staining. Thirty-seven cases showed no expression of Dpc4 (41%). Multivariate survival analysis was performed including age, sex, tumor size, histological subtype (intestinal or pancreatobiliary), grade of differentiation, T-stage, lymph-node metastases and Dpc4 status. T-stage and histological subtype were selected as independent prognostic factors, while Dpc4 immunostaining was not significantly associated with any clinicopathological variable, including histological subtype. Although Dpc4 expression is of no clinical relevance, its involvement in AVC gives additional weight to the hypothesis that, among all pancreatic exocrine and endocrine tumors, only AVC and common ductal adenocarcinomas have similar molecular fingerprints. Moreover, comparison of the frequencies of allelic loss on chromosomal arm 18q and the loss of Dpc4 expression (34% and 41%, respectively) is highly suggestive that DPC4 is the major target of these losses.

Adult↗

Sex chromosome anomalies in pancreatic endocrine tumors.

We have investigated the status of sex chromosomes in 40 pancreatic endocrine tumors (PETs) using 2 complementary techniques: microsatellite and interphase FISH analysis. Twenty-five tumors were from female and 15 from male patients and included 31 nonfunctioning and 9 functioning PET (6 insulinomas, 2 glucagonomas and 1 VIPoma). Microsatellite and FISH analysis showed concordant results in all cases. PETs from females showed frequent loss of chromosome X (40%) whereas PETs from males showed relatively frequent loss of chromosome Y (36%) but never loss of the X chromosome. Statistical analysis showed significant association of sex chromosome loss with metastases (Spearman correlation test, r = 0.5, p < 0.001), local invasion (r = 0.33, p < 0.05) and high proliferation rate measured as Ki-67 index with a 5% cut-off (r = 0.42, p < 0.02). The analysis also showed that local invasion and metastases were highly correlated (r = 0.86). Multivariate survival analysis was therefore carried out including local invasion and loss of sex chromosomes. The presence of local invasion increased the risk of death almost 9 times whereas sex chromosome loss was an independent variable associated with a shorter survival period and an increased risk of death of approximately 4-fold.

Adolescent↗

Dpc4 is expressed in virtually all primary and metastatic pancreatic endocrine carcinomas.

DPC4/Smad4 is inactivated in about 50% of pancreatic ductal cancers. It has been recently reported that this gene is also inactivated in neoplasms arising from pancreatic islet cells, a phenomenon suggested to be related to similar progressions of malignancy found in common ductal cancers. To evaluate this possibility, we analysed 20 metastases of pancreatic endocrine carcinomas and their corresponding primary lesion for inactivation of DPC4 using immunohistochemical staining. In fact, immunohistochemical labelling has been shown to correlate with DPC4 gene status with high sensitivity and specificity. The cancers included 18 nonfunctioning tumours, one gastrinoma and one ViPoma all with liver, nodal and/or adrenal metastases. Seventeen were well-differentiated and three poorly differentiated endocrine carcinomas. Dpc4 expression was absent in only one primary well-differentiated endocrine cancer and its liver metastasis, while all the remaining 19 primary tumours and their metastases stained positive for the protein. All positively staining cases showed diffuse cytoplasmic and nuclear staining in virtually all neoplastic cells. Our data suggest that DPC4 is only rarely involved in pancreatic endocrine tumourigenesis and give further weight to the hypothesis that tumours arising from pancreatic exocrine and endocrine epithelia are genetically distinct.

Adult↗