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ABSTRACT: BACKGROUND: Information on malignant pancreatic neuroendocrine neoplasms (pNENs) is mostly from retrospective studies in highly selected patients. The aim of this prospective, multicentre study was to assess treatment and outcomes of malignant pNENs in clinical practice. PATIENTS AND METHODS: Consecutive patients with newly diagnosed, histologically-proven pNENs were included and followed-up for 2 years. Tumours were defined as malignant when nodal or distant metastases were present or invasion of extrapancreatic structures/organs was evident. RESULTS: A total of 140 patients with malignant pNENs were included. Ninety-eight patients (70.0%) underwent a surgical resection (76 radical and 22 palliative). Other non-surgical treatments were used in 101 patients (72.1%): somatostatin analogues (n = 63), chemotherapy (n = 30), ablative treatments (n = 15) and peptide-receptor radionuclide therapy (n = 14). No relationship was observed between the 2010 WHO classification and type of treatment. A surgical resection was more often performed in incidentally detected tumours located in the pancreas body tail. Two-year progression-free survival was 63.8%: 82% after a radical resection, 44% after a palliative resection and 41% without a resection. A radical resection and Ki67 proliferative index >5% and >10% were the only significant prognostic determinants in multivariate analysis. CONCLUSIONS: A radical resection is the cornerstone treatment of malignant pNENs and represents, together with Ki67 assessment, the most powerful prognostic factor for 2-year outcomes.
HPB 03/2013; · 1.60 Impact Factor
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Gabriele Capurso,
Stefania Boccia,
Roberto Salvia,
Marco Del Chiaro,
Luca Frulloni,
Paolo Giorgio Arcidiacono, Alessandro Zerbi,
Raffaele Manta,
Carlo Fabbri,
Maurizio Ventrucci,
Ilaria Tarantino,
Matteo Piciucchi,
Antonella Carnuccio,
Ugo Boggi,
Emanuele Leoncini,
Guido Costamagna,
Gianfranco Delle Fave,
Raffaele Pezzilli,
Claudio Bassi,
Alberto Larghi
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ABSTRACT: OBJECTIVES:To investigate environmental, personal, and hereditary risk factors associated with the occurrence of intraductal papillary mucinous neoplasms of the pancreas (IPMNs).METHODS:Multicentre case-control study. Risk factors were identified from a questionnaire collecting data on family and medical history, and environmental factors. Cases were prevalent IPMNs seen at the participating units within an 18-month timeframe. Matched controls were enrolled alongside patients seen at outpatient clinics.RESULTS:Three-hundred and ninety patients with IPMN and 390 matched controls (166 males, mean age 65 in each group) were enrolled. Of the IPMNs, 310 had branch-duct involvement and 80 main-duct involvement. The only cancer with a 1st degree family history significantly higher in IPMN was pancreatic ductal adenocarcinoma (PDAC) (5.4% vs. 1.5%). Previous history of diabetes (13.6% vs. 7.5%), chronic pancreatitis (CP) (3.1% vs. 0.3%), peptic ulcer (7.2% vs. 4.3%), and insulin use (4.9% vs. 1.1%) were all more frequent with IPMNs. Logistic regression multivariate analysis revealed that history of diabetes (odds ratio (OR): 1.79, confidence interval (CI) 95%: 1.08-2.98), CP (OR: 10.10, CI 95%: 1.30-78.32), and family histories of PDAC (OR: 2.94, CI 95%: 1.17-7.39) were all independent risk factors. However, when analysis was restricted to diabetics who had taken insulin, risk of IPMN became stronger (OR: 6.03, CI 95%: 1.74-20.84). The association with all these risk factors seemed stronger for the subgroup with main duct involvement.CONCLUSIONS:A previous history of diabetes, especially with insulin use, CP, and family history of PDAC are all relevant risk factors for the development of IPMN. These results suggest an overlap between certain risk factors for PDAC and IPMN.Am J Gastroenterol advance online publication, 5 March 2013; doi:10.1038/ajg.2013.42.
The American Journal of Gastroenterology 03/2013; · 7.28 Impact Factor
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ABSTRACT: OBJECTIVE:: To evaluate the role of an absorbable fibrin sealant patch (TachoSil) in reducing postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). BACKGROUND:: POPF remains the main complication after DP. METHODS:: This was a prospective, open, randomized, study in which patients undergoing elective DP were randomized to standard surgical suturing or stapling with or without TachoSil. The primary end point was the incidence of POPF according to International Study Group on Pancreatic Fistula criteria. Amylase level in drainage fluid, number of days until removal of drain, and duration of hospital stay were secondary end points. RESULTS:: A total of 275 patients were enrolled at 19 centers over a 2-year period (TachoSil, n = 145; standard, n = 130). Twenty percent of procedures were laparoscopic and 21% were spleen-preserving resections. The incidence of POPF was not significantly different between groups (TachoSil, 62%; standard 68%; P = 0.267). Grade A fistula rate was similar in both groups (TachoSil 54%; standard 55%), whereas the grade B + C fistula rate was 8% with TachoSil versus 14% without (P = 0.139). Amylase drainage level on postoperative day 1 was significantly reduced with TachoSil (P = 0.025). Median number of days until drainage removal and length of hospital stay were similar in both groups (7 and 10 days, respectively). CONCLUSIONS:: The POPF rate was higher than expected when International Study Group on Pancreatic Fistula criteria were strictly applied, although the majority were biochemical fistulas. TachoSil had no significant effect on the rate of POPF, although there was a significant reduction of amylase level in drainage fluid on postoperative day 1.
Annals of surgery 11/2012; 256(5):853-860. · 7.90 Impact Factor
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ABSTRACT: To analyze the characteristics and outcomes following enucleation and pancreatic resections of insulinomas.
Retrospective cohort study; prospective database.
Academic, tertiary, and referral centers.
Consecutive patients with insulinomas (symptoms of hyperinsulinism and positive fasting glucose test) who underwent surgical treatment between January 1990 and December 2009.
Operative morbidity, tumor recurrence, and survival after treatment.
A total of 198 patients (58.5% women; median age, 48 years) were identified. There were 175 (88%) neuroendocrine tumors grade G1 and 23 (12%) neuroendocrine tumors grade G2. Malignant insulinomas defined by lymph node/liver metastases were found in 7 patients (3.5%). Multiple insulinomas were found in 8% of patients, and 5.5% of patients had multiple endocrine neoplasia type 1. Surgical procedures included 106 enucleations (54%) and 92 pancreatic resections (46%). Mortality was nil. Rate of clinically significant pancreatic fistula was 18%. Enucleations had a higher reoperation rate compared with pancreatic resections (8.5% vs 1%; P = .02). Multiple endocrine neoplasia type 1 was significantly associated with younger age at onset (P < .005) and higher rates of malignancies and multiple lesions. Median follow-up was 65 months. Six patients (3%; 5 patients had neuroendocrine tumors grade G2) developed tumor recurrence. Four patients (2%) died of disease. New exocrine (1.5%) and endocrine (4%) insufficiencies were associated only with pancreatic resections.
Outcomes following surgical resection of insulinomas are satisfactory, with no mortality and good functional results. Recurrence is uncommon (3%), and it is more likely associated with neuroendocrine tumors grade G2. Insulinomas in multiple endocrine neoplasia type 1 are at higher risk for being malignant and multifocal, requiring pancreatic resections.
Archives of surgery (Chicago, Ill.: 1960) 03/2012; 147(3):261-6. · 4.32 Impact Factor
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ABSTRACT: PancPRO is a computer program that estimates the risk of pancreatic cancer for asymptomatic individuals based on a genetic model of susceptibility and the familial incidence of cancer.
To evaluate the distribution of the familial risk in a series of incident cases of pancreatic adenocarcinoma.
The lifetime risk of pancreatic cancer was calculated by PancPro for a hypothetical 40-year-old son of 570 consecutive probands with pancreatic cancer.
The 570 risk values were included between 1% and 13%. The distribution was bimodal, with the antimode located at risk=7.5%. Considering a 10-fold risk over the general population as a threshold for including a subject in a surveillance program, 19 families (3.3%) would be selected, totalling 92 first-degree relatives with age >40 years.
PancPro is a valid instrument to rank families based on risk of pancreatic cancer.
Digestive and Liver Disease 01/2012; 44(7):585-8. · 3.05 Impact Factor
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Michele Reni,
Gianpaolo Balzano,
Giuseppe Aprile,
Stefano Cereda,
Paolo Passoni, Alessandro Zerbi,
Maria Chiara Tronconi,
Carlo Milandri,
Piercarlo Saletti,
Alessia Rognone,
Clara Fugazza,
Alessandro Magli,
Nadia Di Muzio,
Valerio Di Carlo,
Eugenio Villa
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ABSTRACT: Information from randomized trials on the role of combination chemotherapy in the adjuvant treatment of pancreatic adenocarcinoma is limited. This randomized phase II trial aimed to identify the most promising regimen warranting phase III evaluation.
Therapy-naive patients, age 18-75 years, Karnofsky Performance Status (KPS)>60, gross total resection of stage IB-III pancreatic adenocarcinoma, stratified for center and surgical margins, were randomly assigned to receive either gemcitabine 1 g/m2 weekly on days 1, 8, and 15 (arm A) or the PEFG regimen (cisplatin and epirubicin 40 mg/m2, day 1; gemcitabine 600 mg/m2, days 1, 8; 5-fluorouracil 200 mg/m2 daily, days 1-28) (arm B). Chemotherapy was administered every 4 weeks for 3 months and followed by irradiation concurrent to continuous infusion of 5-fluorouracil 250 mg/m2 daily. Primary endpoint was the probability of being disease-free at 1 year from surgery. Assuming P0=35% and P1=55%, α=.05 and β=.10, the study was to enroll 51 patients per arm.
A total of 102 patients were randomized; 100 were eligible (arm A: 51; arm B: 49). Baseline characteristic (A/B) were: Median age was 61/60 years; 75% had KPS>80 75/76%; 36% grade 3 tumor 29/43%, 79% stage IIB/III 75/84%, 31% R1 resection 35/29%. Survival figures (A/B) were: Median disease-free survival was 11.7 and 15.2 months; 1-year disease-free survival 49.0% (95% confidence interval [95% CI] 35-63%) and 69.4% (95% CI 56-83%); median survival 24.8 and 28.9 months. Combination chemotherapy produced more hematological toxicity without relevant differences in nonhematological toxicities.
The 4-drug regimen deserves further assessment in resectable pancreatic cancer.
Annals of Surgical Oncology 01/2012; 19(7):2256-63. · 4.17 Impact Factor
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Luigi Laghi,
Stefania Beghelli,
Antonino Spinelli,
Paolo Bianchi,
Gianluca Basso,
Giuseppe Di Caro,
Anna Brecht,
Giuseppe Celesti,
Giona Turri,
Samantha Bersani,
Guido Schumacher,
Christoph Röcken,
Ilona Gräntzdörffer,
Massimo Roncalli, Alessandro Zerbi,
Peter Neuhaus,
Claudio Bassi,
Marco Montorsi,
Aldo Scarpa,
Alberto Malesci
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ABSTRACT: Pancreatic cancer risk is increased in Lynch syndrome (LS) patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI). However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI in surgically resected pancreatic cancers in a multicentric, retrospective study, and to assess the occurrence of pancreatic cancer in LS.
MS-status was screened by a panel of 5 mononucleotide repeats (Bat26, Bat25, NR-21, NR-24 and NR-27) in 338 consecutive pancreatic ductal adenocarcinoma (PDAC), resected at two Italian and one German referral centres. The personal history of pancreatic cancer was assessed in an independent set of 58 probands with LS and in 138 first degree relatives who had cancers.
Only one PDAC (0.3%) showed MSI. This was a medullary type cancer, with hMLH1-deficiency, and no identified germ-line mutation but methylation of hMLH1. Pancreatic cancer occurred in 5 (2.5%) LS patients. Histological sampling was available for 2 cases, revealing PDAC in one case and an ampullary cancer in the other one.
MSI prevalence is negligible in sporadic, resected PDAC. Differently, the prevalence of pancreatic cancer is 2.5% in LS patients, and cancers other than PDAC may be encountered in this setting. Surveillance for pancreatic cancer should be advised in LS mutation carriers at referral centers.
PLoS ONE 01/2012; 7(9):e46002. · 4.09 Impact Factor
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ABSTRACT: Despite the close relationship between hospital volume and mortality after pancreaticoduodenectomy (PD), the role of surgeon volume still remains an open issue. Retrospective multi-institutional reviews considered only in-hospital mortality, whereas no data about major complications are available so far. The aim of this study is to assess the independent impact of surgeon volume on outcome after PD in a single high-volume institution.
Demographics and clinical and surgical variables were prospectively collected on 610 patients who underwent PD from August 2001 to August 2009. The cutoff value to categorize high- and low-volume surgeons (HVS and LVS, respectively) was 12 PD/year. The primary endpoint was operative mortality (death within 30-day post-discharge). Secondary endpoints were morbidity, pancreatic fistula (PF), and length of hospital stay (LOS).
In the whole series, mortality was 4.1%, overall morbidity was 61.3%, and PF rate was 27.5%. Two HVS performed 358 PD (58.6%), while six LVS performed 252 PD (41.4%). Mortality was 3.9% for HVS and 4.3% for LVS (p=0.84). The major complication rate was similar for HVS and LVS (14.5% vs. 16.2%). The PF rate was higher for LVS (32.4% vs. 24.1%, p=0.03). The mean LOS was 15.5 days for HVS vs. 16.9 days for LVS (p=0.11). At multivariate analysis, risk factors for PF occurrence were LVS, soft pancreatic stump, small duct diameter, and longer operative time.
Low-volume surgeons had a higher PF rate. However, this did not increase mortality and major morbidity rates probably because of the protective effect of high-volume hospital in improving patient rescue from life-threatening complications.
Journal of Gastrointestinal Surgery 11/2011; 16(3):518-23. · 2.83 Impact Factor
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ABSTRACT: The introduction of contrast-enhanced ultrasound has been a major innovation in liver and pancreatic imaging. Previous studies have validated its intraoperative use during liver surgery, while there is a lack of data regarding its use during pancreatic surgery. The purpose of the present study was to prospectively evaluate the possible role of contrast-enhanced intraoperative ultrasound (CEIOUS) during resective pancreatic surgery for primary lesion characterization and intraoperative staging.
Thirty-four patients (70% males, mean age 67.9 years) were selected for pancreatic surgery between October 2006 and July 2009. All patients underwent intraoperative ultrasound with intravenous injection of 4.8 mL sulfur-hexafluoride microbubbles. Location of the primary tumor, relation to the main vessels, contrast medium uptake modalities, presence of liver metastases, and multifocal pancreatic involvement were evaluated. The majority of operations were pancreatoduodenectomies (70.6%) performed for pancreatic ductal adenocarcinoma (64.7%).
Additional lesions were detected by ultrasound in six patients (17.6%: liver metastases in four patients, a hemangioma in one patient, and a further pancreatic lesion in one patient). In five of these patients (5/34, 14.7%) surgical management was modified by these findings. All these new findings were diagnosed before injection of contrast medium, except for a metastasis from a neuroendocrine tumor; the characterization of the hemangioma was possible only after contrast injection. Intraoperative findings regarding location of primary tumor, relation to the main vessels, and lesion characterization did not differ from those obtained with preoperative imaging.
In our experience intraoperative ultrasound is a valid technique for intraoperative staging prior to pancreatic resection; it is unclear whether, in pancreatic surgery, the addition of contrast enhancement adds any benefit to traditional intraoperative ultrasound.
World Journal of Surgery 09/2011; 35(11):2521-7. · 2.36 Impact Factor
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ABSTRACT: The objective of the study was to evaluate clinical features and quality of life (QoL) in a 2-year follow-up study in subjects who underwent pancreatic head resection (PHR).
One hundred ninety-seven patients with benign and malignant diseases who underwent PHR were studied. A dedicated clinical form and the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire C-30 were administered at evaluation times (immediately before surgery and 6, 12, 18, and 24 months after discharge). A sample of 197 sex- and age-matched norms was also included into the study as reference group.
Of the 197 patients studied, 164 (83.2%) had malignant disease, and 33 had benign disease (16.8%). At initial evaluation, global health was significantly lower (P = 0.001) in the study population as compared with the norms. At the end of the study, the QoL was not significantly different from the norms, although the QoL of the 30 patients with benign disease was significantly better than that of the 72 patients with malignant disease.
The QoL before PHR was impaired in study patients before resection as compared with the normative population, whereas in patients who survived resection, it significantly improved in the 24 months after surgery.
Pancreas 05/2011; 40(6):938-45. · 2.39 Impact Factor
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ABSTRACT: Information on the treatment of pancreatic endocrine tumours (PETs) comes mostly from small, retrospective, uncontrolled studies.
Newly diagnosed, histologically proven PETs, observed from June 2004 to March 2007 in 24 Italian centres, were included in a specific dataset.
Three-hundred and ten patients (mean age 57.6 years, females 46.6%) were analysed. At the time of recruitment, 262 (84.5%) underwent surgery. The percentage of operated patients was 91.9% and 62.0% in surgical and non-surgical centres, respectively. A curative resection was carried out in 83.6% (n = 219) of cases, a palliative resection (debulking) in 10.7% (n = 28), an exploratory laparotomy in 4.6% (n = 12), and a bypass procedure in 1.1% (n = 3). Laparoscopy was performed in 8.0% (n = 21) of cases. Resection consisted of a pancreatoduodenectomy in 46 cases (21.0%), a distal pancreatectomy in 95 (43.4%), an enucleation in 50 (22.8%), a middle pancreatectomy in 16 (7.3%) and a total pancreatectomy in 12 (5.5%). Liver resection was associated with pancreatic resection in 26 cases (9.9%). Post-operative mortality was 1.5% and morbidity 39.7%, respectively. A curative resection was performed more frequently in asymptomatic, small, non-metastatic, benign and at uncertain behaviour tumours, with low Ki67 values.
This study strongly indicates the fact that surgical resection represents the cornerstone treatment of PETs.
Langenbeck s Archives of Surgery 03/2011; 396(3):313-21. · 1.81 Impact Factor
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ABSTRACT: This study aimed to evaluate the surgical treatment of acute pancreatitis in Italy and to assess compliance with international guidelines.
A series of 1173 patients in 56 hospitals were prospectively enrolled and their data analysed.
Twenty-nine patients with severe pancreatitis underwent surgical intervention. Necrosectomy was performed in 26 patients, associated with postoperative lavage in 70% of cases. A feeding jejunostomy was added in 37% of cases. Mortality was 21%. Of the patients with mild pancreatitis, 714 patients with a biliary aetiology were evaluated. Prophylactic treatment of relapses was carried out in 212 patients (36%) by cholecystectomy and in 161 using a laparoscopic approach. Preoperative endoscopic retrograde cholangiopancreatography was associated with cholecystectomy in 83 patients (39%). Forty-seven patients (22%) were treated at a second admission, with a median delay of 31 days from the onset of pancreatitis. Eighteen patients with severe pancreatitis underwent cholecystectomy 37.9 days after the first admission. There were no deaths.
The results indicate poor compliance with published guidelines. In severe pancreatitis, early surgical intervention is frequently performed and enteral feeding is seldom used. Only a small number of patients with mild biliary pancreatitis undergo definitive treatment (i.e. cholecystectomy) within 4 weeks of the onset of pancreatitis.
HPB 11/2010; 12(9):597-604. · 1.60 Impact Factor
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ABSTRACT: In Italy, pancreatic cancer is the fifth leading cause of tumor related death with about 7000 new cases per year and a mortality rate of 95%. In a recent prospective epidemiological study on the Italian population, a family history was found in about 10% of patients suffering from a ductal adenocarcinoma of the pancreas (PDAC). A position paper from the Italian Registry for Familial Pancreatic Cancer was made to manage these high-risk individuals. Even though in the majority of high-risk individuals a genetic test to identify familial predisposition is not available, a screening protocol seems to be reasonable for subjects who have a >10-fold greater risk for the development of PDAC. However this kind of screening should be included in clinical trials, performed in centers with high expertise in pancreatic disease, using the least aggressive diagnostic modalities.
Digestive and Liver Disease 09/2010; 42(9):597-605. · 3.05 Impact Factor
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ABSTRACT: To evaluate the data from a survey carried out in Italy regarding the endoscopic approach to acute pancreatitis in order to obtain a picture of what takes place after the release of an educational project on acute pancreatitis sponsored by the Italian Association for the Study of the Pancreas.
Of the 1 173 patients enrolled in our survey, the most frequent etiological category was biliary forms (69.3%) and most patients had mild pancreatitis (85.8%).
344/1 173 (29.3%) underwent endoscopic retrograde cholangiopancreatography (ERCP). The mean interval between the onset of symptoms and ERCP was 6.7 ± 5.0 d; only 89 examinations (25.9%) were performed within 72 h from the onset of symptoms. The main indications for ERCP were suspicion of common bile duct stones (90.3%), jaundice (44.5%), clinical worsening of acute pancreatitis (14.2%) and cholangitis (6.1%). Biliary and pancreatic ducts were visualized in 305 patients (88.7%) and in 93 patients (27.0%) respectively. The success rate in obtaining a cholangiogram was statistically higher (P = 0.003) in patients with mild acute pancreatitis (90.6%) than in patients with severe disease (72.2%). Biliary endoscopic sphincterotomy was performed in 295 of the 305 patients (96.7%) with no difference between mild and severe disease (P = 0.985). ERCP morbidity was 6.1% and mortality was 1.7%; the mortality was due to the complications of acute pancreatitis and not the endoscopic procedure.
The results of this survey, as with those carried out in other countries, indicate a lack of compliance with the guidelines for the indications for interventional endoscopy.
World journal of gastrointestinal endoscopy. 09/2010; 2(9):308-13.
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ABSTRACT: Pancreatic metastases, although uncommon, have been observed with increasing frequency recently, especially by high-volume pancreatic surgery centers. They are often asymptomatic and detected incidentally or during follow-up investigations even several years after the removal of the primary tumor. Renal cell cancer represents the most common primary tumor by far, followed by colorectal cancer, melanoma, sarcoma and lung cancer. Pancreatic metastasectomy is indicated for an isolated and resectable metastasis in a patient fit to tolerate pancreatectomy. Both standard and atypical pancreatic resection can be performed: a resection strategy providing adequate resection margins and maximal tissue preservation of the pancreas should be pursued. The effectiveness of resection for pancreatic metastases is mainly dependent on the tumor biology of the primary cancer; renal cell cancer is associated with the best outcome with a 5-year survival rate greater than 70%.
World journal of gastrointestinal surgery. 08/2010; 2(8):255-9.
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ABSTRACT: Information on pancreatic endocrine tumors (PETs) comes mostly from small, retrospective, uncontrolled studies conducted on highly selected patients. The aim of the study was to describe the clinical and pathological features of PETs in a prospective, multicenter study.
Newly diagnosed, histologically proven, sporadic PETs observed from June 2004 to March 2007 in 24 Italian centers were included in a specific data set.
Two hundred ninety-seven patients (mean age 58.6+/-14.7 years, females 51.2%, males 48.8%) were analyzed. In 73 cases (24.6%), the tumor was functioning (F) (53 insulinomas, 15 gastrinomas, 5 other syndromes) and in 232 (75.4%) it was non-functioning (NF); in 115 cases (38.7%), the diagnosis was incidental. The median tumor size was 20 mm (range 2-150). NF-PETs were significantly more represented among carcinomas (P<0.001). Nodal and liver metastases were detected in 84 (28.3%) and 85 (28.6%) cases, respectively. The presence of liver metastases was significantly higher in the NF-PETs than in the F-PETs (32.1% vs. 17.8%; P<0.05), and in the symptomatic than in the asymptomatic patients (34.6% vs. 19.1%; P<0.005). At the time of recruitment, the majority of patients (251, 84.5%) had undergone surgery, with complete resection in 209 cases (83.3%).
This study points out the high number of new cases of PETs observed in Italy, with a high prevalence of NF and incidentally discovered forms. The size of the tumor was smaller and the rate of metastasis was lower than usually reported, suggesting a trend toward an earlier diagnosis.
The American Journal of Gastroenterology 06/2010; 105(6):1421-9. · 7.28 Impact Factor
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ABSTRACT: The pancreatic stump is the major source of morbidity and mortality of pancreatoduodenectomy (PD). Any surgeon experienced
in pancreatic surgery is often dealing with the dramatic consequences of the failure of the technique he or she adopted; thus
we ask ourselves what technical errors we have committed, or whether it would have been better to perform a different reconstruction,
maybe an anastomosis with the stomach, or an interrupted suture instead of a continuous one, or to use a Roux-en-Y limb, or
to close the stump without anastomosis. In these circumstances the questions are many and legitimate, because pancreatic surgery
requires an extremely accurate technique and we need to choose the proper solution based on the pancreas’ characteristics
and on our own experience. However, it is important, first of all, to realize that the main actor in the dramatic consequences
of pancreatic surgery is the pancreas itself, with the destructive potential of its digestive secretions. There is no evidence
that any given technique is able to solve the problems of the pancreatic remnant, and no comparative study has proved one
specific technique to be clearly better than another. Nevertheless, if our aim is to expose our patient who is a candidate
for a PD to the smallest possible risk of death (for that is what is at issue), there is one vital element that is frequently
ignored.
05/2010: pages 297-304;
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ABSTRACT: Parenchyma-preserving resections (PPRs), including enucleation and middle pancreatectomy (MP), are accepted procedures for insulinomas, but their role in the treatment of nonfunctioning pancreatic endocrine tumors (NF-PETs) is debated. The aim of this study was to evaluate perioperative and long-term outcomes after PPRs for NF-PETs.
All patients who underwent PPRs for NF-PETs between 1990 and 2005 were included. Patients with multiple endocrine neoplasia type 1 were excluded.
Overall, 50 patients (23 men, 27 women, median age 59 years) underwent 26 enucleations and 24 MP. A total of 58% of NF-PETs were incidentally discovered. Median size of the tumors was 13.5 mm with no preoperative suspicion of malignancy in all patients. Overall morbidity and pancreatic fistula rates were 58 and 50%, respectively. Reoperation rate was 4%, with no mortality. Postoperative complications were higher in the MP group. At pathology, there were 34 (68%) benign lesions, 13 (26%) neoplasms of uncertain behavior, and 3 (6%) well-differentiated carcinomas. Forty-one patients (82%) had tumors < or =2 cm in size. Only eight patients (16%) had at least one lymph node removed. After a median follow-up of 58 months, no patient died of disease. Overall, four patients (8%) experienced tumor recurrence after a mean of 68 months. The incidence of exocrine/endocrine insufficiency was 8%.
PPRs are generally safe and effective procedures for treating small NF-PETs. However, better selection criteria must be identified, and lymph node sampling should be performed routinely to avoid understaging. Long-term follow-up evaluation (>5 years) is of paramount importance given the possible risk of late recurrence.
Annals of Surgical Oncology 02/2010; 17(6):1621-7. · 4.17 Impact Factor
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ABSTRACT: Radiologic assessment of tumor response in pancreatic cancer is complicated by desmoplastic reactions within or around the tumor. The objective of this study was to evaluate the correlation between a decline in carbohydrate antigen 19-9 (CA 19-9) and survival in patients with advanced pancreatic cancer who received upfront chemotherapy.
CA 19-9 serum basal values were measured in 247 patients with advanced pancreatic cancer who were enrolled in 5 consecutive trials between 1997 and 2007. Survival curves were compared among patients who had a predefined CA 19-9 nadir variation (<50%. Group 1; 50% to 89%, Group 2; or >89%, Group 3). To eliminate guarantee-time bias, survival analysis was repeated using the landmark method.
In both univariate and multivariate analysis, the basal CA 19-9 value significantly predicted survival. The median survival was 15.5 months for 34 patients who had normal basal CA 19-9 values, 11.9 months for 108 patients who had basal values between 38 U/mL and 1,167 U/mL, and 8 months for 105 patients who had basal values >1,167 U/mL. At least 1 CA 19-9 follow-up value was available for 204 patients who had baseline values greater than normal. A significant difference in overall survival was observed in univariate and multivariate analyses between Groups 1 and 2, between Groups 1 and 3, and between Groups 2 and 3. The results were confirmed using the landmark method.
In this study, baseline CA 19-9 was confirmed as an independent prognostic factor for survival, and it may be considered as a stratification factor in trials in patients with advanced pancreatic cancer. Biochemical response may be used as a complementary measure to radiologic response to provide a better assessment of chemotherapy activity and to drive treatment decisions in clinical practice.
Cancer 04/2009; 115(12):2630-9. · 4.77 Impact Factor
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Federica Marchesi,
Lorenzo Piemonti,
Giuseppe Fedele,
Annarita Destro,
Massimo Roncalli,
Luca Albarello,
Claudio Doglioni,
Achille Anselmo,
Andrea Doni,
Paolo Bianchi,
Luigi Laghi,
Alberto Malesci,
Luigi Cervo,
Marialuisa Malosio,
Michele Reni, Alessandro Zerbi,
Valerio Di Carlo,
Alberto Mantovani,
Paola Allavena
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ABSTRACT: Tumor perineural dissemination is a hallmark of human pancreatic ductal adenocarcinoma (PDAC) and represents a major source of local tumor recurrence after surgery. In this study, we provide in vitro and in vivo evidence that the chemokine receptor CX3CR1 may be involved in the neurotropism of PDAC cells to local peripheral nerves. Neoplastic cells from PDAC cell lines and surgical specimens express the chemokine receptor CX3CR1, absent in normal pancreatic ducts. Its unique ligand, the transmembrane chemokine CX3CL1, is expressed by neurons and nerve fibers. CX3CR1 + PDAC cell lines migrated in response to human recombinant CX3CL1 and specifically adhered to CX3CL1-expressing cells of neural origin via mechanisms involving activation of G proteins, beta1 integrins, and focal adhesion kinase. In vivo experiments with transplanted PDAC showed that only CX3CR1-transfected tumor cells infiltrated the local peripheral nerves. Immunohistochemistry of CX3CR1 in PDAC specimens revealed that 90% of the samples were positive with a heterogeneous pattern of expression. High receptor score was significantly associated with more prominent tumor perineural infiltration evaluated histologically (P = 0.026). Regression analyses (univariate and multivariate) showed that high CX3CR1 expression and perineural invasion were strongly associated with local and earlier tumor recurrence (P = 0.007). Collectively, this study shows that the CX3CR1 receptor may be involved in PDAC tumor neurotropism and is a relevant and independent risk factor to predict an early local tumor relapse in resected patients. Thus, the CX3CR1-CX3CL1 axis could represent a valuable therapeutic target to prevent tumor perineural dissemination in pancreatic cancer.
Cancer Research 12/2008; 68(21):9060-9. · 7.86 Impact Factor
