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Massimo Falconi

Publications and source records attributed to Massimo Falconi.

At least 19 recordsLinked to original sources
PubMed2024

Implications of noncoding regulatory functions in the development of insulinomas.

Insulinomas are rare neuroendocrine tumors arising from pancreatic β cells, characterized by aberrant proliferation and altered insulin secretion, leading to glucose homeostasis failure. With the aim of uncovering the role of noncoding regulatory regions and their aberrations in the development of these tumors, we coupled epigenetic and transcriptome profiling with whole-genome sequencing. As a result, we unraveled somatic mutations associated with changes in regulatory functions. Critically, these regions impact insulin secretion, tumor development, and epigenetic modifying genes, including polycomb complex components. Chromatin remodeling is apparent in insulinoma-selective domains shared across patients, containing a specific set of regulatory sequences dominated by the SOX17 binding motif. Moreover, many of these regions are H3K27me3 repressed in β cells, suggesting that tumoral transition involves derepression of polycomb-targeted domains. Our work provides a compendium of aberrant cis-regulatory elements affecting the function and fate of β cells in their progression to insulinomas and a framework to identify coding and noncoding driver mutations.

Humans↗
PubMed2007

The determinant factors of recurrence following resection for ductal pancreatic cancer.

Long-term survival for patients with pancreatic carcinoma is low, even following resection. Most patients who undergo curative treatment, develop recurrence usually at the same site of resection or in the liver. Failure seals the fate of the patient. Local recurrence occurs frequently; however, it is rarely a direct cause of death. In fact, most patients die from distant metastases. From a clinical point of view, it is important to distinguish recurrence from relapse. In fact, recurrence can be recognized as the reappearance of the disease in the surgical bed, often due to inadequate surgical clearance. On the other hand, the concept of relapse should be much more related to the appearance of the disease in a distant site. Both underestimated staging of the diagnosis and the biological features of the tumor can cause relapse. Up to now, there have only been a few reviews on the incidence and pattern of failure following resection. Detailed knowledge of the recurring sites of pancreatic carcinoma and study of the factors influencing disease-free survival are significant in developing neoadjuvant, surgical and adjuvant treatment. The aim of this review is to point out the major factors most commonly identified as determinants of both recurrence and relapse.

Carcinoma, Pancreatic Ductal↗
PubMed2006

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.

Adenocarcinoma, Mucinous↗
PubMed2006

Branch-duct intraductal papillary mucinous neoplasms of the pancreas: to operate or not to operate?

BACKGROUND: Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas are reported to be less aggressive than the main-duct type. Hence, less aggressive treatment has been proposed for the former. AIM: To evaluate the effectiveness of a follow-up protocol for BD-IPMNs. DESIGN: Prospective study. SETTING: An academic tertiary referral centre. PATIENTS: From 2000 to 2003, 109 patients with BD-IPMNs underwent trans-abdominal ultrasound and magnetic resonance cholangiopancreatography with secretin. Patients who presented malignancy-related parameters (size >3.5 cm, nodules, thick walls, carbohydrate antigen 19.9 level >25 U/l, recent-onset or worsened diabetes) and/or complained of symptoms were submitted to surgery (arm A). All asymptomatic patients without suspicion of malignancy were followed up according to a 6-month clinical-radiological protocol (arm B). MAIN OUTCOME MEASURES: The effectiveness of conservative management of BD-IPMNs. RESULTS: 20 (18.3%) patients underwent surgery (arm A); pathological diagnosis of BD-IPMNs was always confirmed. 89 (81.7%) patients were followed up for a median of 32 months (arm B); of these, 57 (64%) patients had multifocal disease. After a mean follow-up of 18.2 months, 5 (5.6%) patients showed an increase in lesion size and underwent surgery. The pathological diagnosis was branch-duct adenoma in three patients and borderline adenoma in two. CONCLUSIONS: Surgery is indicated in <20% of cases of BD-IPMNs, and, in the absence of malignancy-related parameters, careful non-operative management seems to be safe and effective in asymptomatic patients. Although observation for a longer time is needed to confirm these results, our findings support the guidelines recently recommended by the International Association of Pancreatology.

Adenocarcinoma, Mucinous↗
PubMed2006

MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior.

PURPOSE: We investigated the global microRNA expression patterns in normal pancreas, pancreatic endocrine tumors and acinar carcinomas to evaluate their involvement in transformation and malignant progression of these tumor types. MicroRNAs are small noncoding RNAs that regulate gene expression by targeting specific mRNAs for degradation or translation inhibition. Recent evidence indicates that microRNAs can contribute to tumor development and progression and may have diagnostic and prognostic value in several human malignancies. MATERIALS AND METHODS: Using a custom microarray, we studied the global microRNA expression in 12 nontumor pancreas and 44 pancreatic primary tumors, including 12 insulinomas, 28 nonfunctioning endocrine tumors, and four acinar carcinomas. RESULTS: Our data showed that a common pattern of microRNA expression distinguishes any tumor type from normal pancreas, suggesting that this set of microRNAs might be involved in pancreatic tumorigenesis; the expression of miR-103 and miR-107, associated with lack of expression of miR-155, discriminates tumors from normal; a set of 10 microRNAs distinguishes endocrine from acinar tumors and is possibly associated with either normal endocrine differentiation or endocrine tumorigenesis; miR-204 is primarily expressed in insulinomas and correlates with immunohistochemical expression of insulin; and the overexpression of miR-21 is strongly associated with both a high Ki67 proliferation index and presence of liver metastasis. CONCLUSION: These results suggest that alteration in microRNA expression is related to endocrine and acinar neoplastic transformation and progression of malignancy, and might prove useful in distinguishing tumors with different clinical behavior.

Carcinoma, Acinar Cell↗
PubMed2006

Duodenal duplication cyst causing severe pancreatitis: imaging findings and pathological correlation.

We here report a case of a 18-year-old man with a history of recurrent abdominal pain and a previous episode of severe acute pancreatitis. Abdominal ultrasonography, contrast enhanced multislice computer tomography, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography and magnetic resonance imaging demonstrated a cystic mass lesion. Only on delayed phase magnetic resonance images after Gadolinium-BOPTA injection, it was possible to demonstrate the lesionos relationship with the biliary tree, differentiating the lesion from intraluminal duodenal diverticulum, and to achieve the diagnosis of duodenal duplication cyst, a recognized rare cause of acute pancreatitis. The diagnosis was confirmed by histology.

Adolescent↗
PubMed2006

Surgical strategy in the treatment of pancreatic neuroendocrine tumors.

Endocrine pancreatic tumors are rare and their surgical treatment is often debated. This review analyzes the management and the different indications in functioning and non-functioning neoplasms. The choice among different procedures is described as well as the role of intra operative ultrasound. Moreover, the different patterns of tumor spread are considered (local, loco-regional and metastatic) along with the indications according to the main controversies relating to cytoreductive surgery, transplantation and multiple endocrine neoplasia type 1 patients.

Cholecystectomy↗
PubMed2006

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.

Adult↗
PubMed2006

International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.

Non-inflammatory cystic lesions of the pancreas are increasingly recognized. Two distinct entities have been defined, i.e., intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). Ovarian-type stroma has been proposed as a requisite to distinguish MCN from IPMN. Some other distinct features to characterize IPMN and MCN have been identified, but there remain ambiguities between the two diseases. In view of the increasing frequency with which these neoplasms are being diagnosed worldwide, it would be helpful for physicians managing patients with cystic neoplasms of the pancreas to have guidelines for the diagnosis and treatment of IPMN and MCN. The proposed guidelines represent a consensus of the working group of the International Association of Pancreatology.

Endocrine Surgical Procedures↗
PubMed2005

Contrast-enhanced ultrasonography better identifies pancreatic tumor vascularization than helical CT.

BACKGROUND: Contrast-enhanced ultrasonography (CEUS) is a recently introduced field of ultrasonography (US). To assess the ability of CEUS to identify the vascularization of solid pancreatic tumors in comparison to helical CT. METHODS: Forty-two resected pancreatic tumors, found at US, were studied with CEUS and helical CT. The tumor enhancement at CEUS was scored in comparison to the baseline aspect of the lesion and/or the extralesional pancreatic parenchyma together with the adjacent vessels during the dynamic study. All the lesions underwent pathological examination using H&E stains and CD34 markers with an evaluation of the microvessel density (MVD). The correlation of CEUS and helical CT with the MVD of the lesions was established with Spearman's test. RESULTS: The correlation of CEUS with the MVD of the lesions was significantly superior (Rs = 0.914; p < 0.0001) to that of helical CT (Rs = 0.635; p < 0.0001). CONCLUSIONS: CEUS is better than helical CT in the identification of the vascularization of solid pancreatic tumors. CEUS, when the pancreatic gland is optimally visualized, should be therefore considered a complementary imaging modality in the characterization of pancreatic tumors. CEUS can be a valid onco-imaging modality for quantifying tumoral vascularization in a noninvasive and accurate way.

Adenocarcinoma↗
PubMed2005

Mucinous cystic carcinoma of the pancreas: a unique cell line and xenograft model of a preinvasive lesion.

Pancreatic mucinous cystic tumors (MCT) are proliferations of mucin-producing epithelia supported by an ovarian-like stroma. They are classified into adenomas (MCA), borderline (MCB) and noninvasive or invasive carcinomas (MCC). The molecular mechanisms underlying their clinical behavior are poorly understood, partly due to the lack of cellular models. We report the establishment of MCC1, the first cell line from a pancreatic MCT, deriving from the highly dysplastic cell component of a noninvasive MCC. MCC1 has mutations in codon 12 of K-RAS (GGT>GAT), codon 58 of P16 (CGA>TGA) and codon 132 of P53 (AAG>AGG). The FHIT and DPC4 genes are unaltered. Immunohistochemistry shows abnormal expression of MUC1 and p53, loss of p16 and retention of Fhit and Dpc4 in both the cell line and the highly dysplastic cells of the primary lesion. The morphological and molecular features of MCC1 and its corresponding primary tumor are consistent with a model for non-invasive MCC, where K-RAS, P16, P53 and MUC1 alterations are pre-invasive changes associated with progression of malignancy of MCT from adenoma to carcinoma. MCC1 is sensitive to 5-fluorouracil, representing the first assessment of drug sensitivity for MCC. Finally, MCC1 is a suitable model for preclinical studies, as it grows in immunodeficient mice.

Aged↗
PubMed2005

Intraductal papillary mucinous tumors of the pancreas. Surgical treatment: at what point should we stop?

The intraoperative management of the margins of intraductal papillary mucinous tumors (IPMNs) undergoing pancreatic resection is crucial. The surgeon must discontinue the resection whenever the pancreatic margin is negative and, of course, when a total pancreatectomy is indicated.Nevertheless, a wide gray area exists. The real surgical problems are represented by i) IPMNs involving only a segment of the pancreatic gland, thus necessitating intraoperative histological examination of the resection and the decision as to "when to stop the resection"; ii) the intraoperative management of those margins which are neither clearly negative nor clearly positive; iii) the actual indications either for surgery or for follow-up in those patients affected by peripheral IPMNs. In the literature, negative resection margins have a range of between 49 to 81% with a pancreatic recurrence rate of from 0 to 25% in follow-ups ranging from 6 months to 11 years after the first operation. In general, in this disease which mainly involves the head and uncinate process of the gland, decisions are a "balance" between the patient and the disease. In fact, on the one hand, there is the usual elderly patient with possible comorbidities, symptoms and the presence of diabetes; on the other hand, the disease, which usually involves the head and the uncinate process of the gland, tends to grow along the duct and be potentially malignant if carcinoma is not already present.

Adenocarcinoma, Mucinous↗
PubMed2005

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.

Analysis of Variance↗
PubMed2005

Prognostic factors and survival in endocrine tumor patients: comparison between gastrointestinal and pancreatic localization.

Since gastro-entero-pancreatic endocrine tumors are rare and heterogeneous diseases, their prognosis and long-term survival are not well known. This study aimed at identifying prognostic factors and assessing long-term survival in gastro-entero-pancreatic endocrine tumors. A total of 156 patients enrolled. Prognostic factors were determined by univariate/multivariate analysis; survival rates were assessed by the Kaplan-Meier method. The tumors were non-functioning in 59.6% of patients, and originated from the pancreas in 42.9%. At diagnosis, 64.3% of patients had metastases. The tumors were well differentiated in 89.6% of patients. Ki67 was >2% in 39.6% of patients. Primary tumor size was >3 cm in 49.6% of cases studied. For the univariate analysis, the negative prognostic factors were: pancreatic origin (rate ratio 4.64, P = 0.0002), poorly differentiated tumor (rate ratio 7.70, P = 0.0001), primary tumor size >3 cm (rate ratio 4.26, P = 0.0009), presence of distant metastases (liver: rate ratio 5.88, P = 0.01; distant extra-hepatic: rate ratio 13.41, P = 0.0008). The pancreatic site, the poor degree of differentiation and the distant metastases were confirmed as negative prognostic factors at multivariate analysis. Overall 5-year survival rate was 77.5%. Survival rates differed according to: primary tumor site (62% for pancreatic vs 89.9% for gastrointestinal tract, P = 0.0001) and size (65.7% for >3 cm vs 88.8% for < or = 3 cm, P = 0.0003), degree of differentiation (22% for poor vs 86.8% for good, P < 0.0001), Ki67 (53.5% for > 2% vs 90.1% for < or = 2%, P = 0.003), metastases (96.1, 77, 73.3 and 50.1% for absent, local, liver and distant extra-hepatic metastases respectively), age at diagnosis (85.3% for < or = 50 years vs 70.3% for > 50 years, P = 0.03). Although 64.3% of gastro-entero-pancreatic endocrine tumors present metastases at diagnosis, the 5-year survival rate is 77.5%. Pancreatic site, a poor degree of tumor cell differentiation and distant extra-hepatic metastases are the major negative prognostic factors.

Adolescent↗
PubMed2005

Contrast-enhanced ultrasonography of small solid pseudopapillary tumors of the pancreas: enhancement pattern and pathologic correlation of 2 cases.

OBJECTIVE: The purpose of this series is to describe the value of contrast-enhanced ultrasonography (CEUS) in the characterization of small pseudopapillary tumors (SPTs) of the pancreas. METHODS: Two cases of SPTs found on conventional ultrasonography, both located at the pancreatic body, were studied with spiral computed tomography, magnetic resonance imaging, and CEUS. A final diagnosis was obtained with histologic analysis after distal pancreatectomy. Immunohistochemical analysis of the tumors with the CD34 antigen was performed. RESULTS: At CEUS, the 2 SPTs had a slight peripheral rim enhancement in the early dynamic phases. The presence of this enhancement pattern at CEUS, not clear at spiral computed tomography or at magnetic resonance imaging, suggested the diagnosis of SPTs with a peripheral pseudocapsule deriving from the compression of the pancreatic parenchyma. The presence of a perilesional pseudocapsule was proved at immunohistochemical analysis of the tumors with the CD34 antigen. CONCLUSIONS: Contrast-enhanced ultrasonography can improve the characterization of SPTs by showing the typical rim enhancement of these pancreatic tumors.

Adolescent↗
PubMed2004

A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer.

BACKGROUND: The effect of adjuvant treatment on survival in pancreatic cancer is unclear. We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and update the interim results. METHODS: In a multicenter trial using a two-by-two factorial design, we randomly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone (20 Gy over a two-week period plus fluorouracil), 75 patients to chemotherapy alone (fluorouracil), 72 patients to both chemoradiotherapy and chemotherapy, and 69 patients to observation. RESULTS: The analysis was based on 237 deaths among the 289 patients (82 percent) and a median follow-up of 47 months (interquartile range, 33 to 62). The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy (P=0.05). The five-year survival rate was 21 percent among patients who received chemotherapy and 8 percent among patients who did not receive chemotherapy (P=0.009). The benefit of chemotherapy persisted after adjustment for major prognostic factors. CONCLUSIONS: Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.

Aged↗