Technique, safety, and feasibility of EUS-guided radiofrequency ablation in unresectable pancreatic cancer.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) is a well-recognized local ablative technique applied in the treatment of different solid tumors. Intraoperative RFA has been used for non-metastatic unresectable pancreatic ductal adenocarcinoma (PDAC), showing increased overall survival in retrospective studies. A novel RFA probe has recently been developed, allowing RFA under endoscopic ultrasound (EUS) guidance. Aim of the present study was to assess the feasibility and safety of EUS-guided RFA for unresectable PDACs. METHODS: Patients with unresectable non-metastatic PDAC were included in the study following neoadjuvant chemotherapy. EUS-guided RFA was performed using a novel monopolar 18-gauge electrode with a sharp conical 1 cm tip for energy delivery. Pre- and post-procedural clinical and radiological data were prospectively collected. RESULTS: Ten consecutive patients with unresectable PDAC were enrolled. The procedure was successful in all cases and no major adverse events were observed. A delineated hypodense ablated area within the tumor was observed at the 30-day CT scan in all cases. CONCLUSIONS: EUS-guided RFA is a feasible and safe minimally invasive procedure for patients with unresectable PDAC. Further studies are warranted to demonstrate the impact of EUS-guided RFA on disease progression and overall survival.

Digital Subtraction of Magnetic Resonance Images Improves Detection and Characterization of Pancreatic Neuroendocrine Neoplasms.

OBJECTIVE: The aim of this study was to evaluate the usefulness of digital image subtraction of contrast-enhanced magnetic resonance (MR) images for detection and characterization of pancreatic neuroendocrine neoplasms (PanNENs). METHODS: Magnetic resonance examinations of 50 histologically verified PanNENs were retrospectively evaluated by 2 radiologists; 50 ductal adenocarcinomas were included as a control group. Late arterial phase images and correspondent subtracted images were analyzed. Tumor detectability on a subjective 3-point scale and contrast-to-noise ratios were compared across sequences using paired Student t tests. Tumor signal intensity was compared between sequences using χ or Fisher exact tests. RESULTS: Subjective conspicuity and contrast-to-noise ratios of PanNENs were significantly higher on subtracted images compared with correspondent late arterial phase images (P < 0.001 and P = 0.002). The rate of clearly hyperenhancing PanNENs was higher on subtracted images compared with arterial phase images (76% vs 36%). CONCLUSIONS: Digital image subtraction improves tumor conspicuity and allows better characterization of PanNENs compared with late arterial phase images.

Pancreatic Neuroendocrine Neoplasms: Clinical Value of Diffusion-Weighted Imaging.

BACKGROUND/AIMS: Diffusion-weighted imaging (DWI) can depict random motions of water molecules in biological tissues during magnetic resonance (MR) examinations. Few papers have tested its application to pancreatic neuroendocrine neoplasms (PanNENs). The aim of this paper is to assess the clinical value of DWI regarding the identification and characterization of PanNENs and diagnosis of liver metastases. METHODS: Preoperative MR examinations of 30 PanNEN patients were retrospectively reviewed; 30 patients with pathologically proven pancreatic ductal adenocarcinoma (PDAC) were included to compare the imaging features. Qualitative and quantitative MR features were compared between histotypes. A blinded-reader comparison of diagnostic confidence for PanNENs and liver metastases was conducted on randomized image sets. All results were compared with pathological data. RESULTS: PanNEN conspicuity was higher on DW images compared to conventional MR sequences. DWI had higher detection rates for PanNENs than had conventional sequences (93.3 vs. 71.1%). Sharp margins and absence of main pancreatic duct/common bile duct dilation and chronic pancreatitis were more common among PanNENs as compared to PDACs. Arterial iso- or hyperenhancement and portal hyperenhancement were more frequent within PanNENs as compared to PDACs. No differences between histotypes were found for quantitative features. Arterial-phase images had the highest interobserver agreement for the diagnosis of PanNEN (Cohen's κ = 0.667). DWI provided the highest detection rate for liver metastases as well as excellent interobserver agreement for the diagnosis of liver metastases (κ = 0.932), with good accuracy (AUC = 0.879-0.869). CONCLUSION: DWI has clinical value regarding the identification of PanNENs and the diagnosis of liver metastases, while conventional MR sequences are fundamental for their characterization.

Observational study of the incidence of pancreatic and extrapancreatic malignancies during surveillance of patients with branch-duct intraductal papillary mucinous neoplasm.

OBJECTIVE: This observational analysis assessed the incidence of pancreatic and extrapancreatic malignancies in BD-IPMN patients. BACKGROUND: Previous studies showed that progression to malignancy of pancreatic branch-duct (BD) intraductal papillary mucinous neoplasm (IPMN) is infrequent and that extrapancreatic malignancies (EPMs) occur with unusual frequency in IPMN patients. METHODS: Patients observed from 2000 to 2012 and enrolled in a surveillance protocol according to the current guidelines were considered eligible for the study. Only patients with follow-up of more than 12 months were evaluated. The incidence of EPM was calculated only in patients who were free of them at the time of IPMN diagnosis. Data were compared with Italian cancer statistics. The standardized incidence ratios (SIRs) and the 5- and 10-year incidence rates were estimated. RESULTS: The study population consisted of 569 patients. At a median follow-up of 56 months, 9 patients developed a pancreatic malignancy. Of these, 5 were unresectable. The SIR was 9.21 [95% confidence interval (CI), 1.85-26.91] in males, and 11.94 (95% CI, 4.36-26.0) in females, with a 5-year cumulative incidence of 1.4%. The EPM incidence analysis was performed in 456 patients. Thirty EPMs developed during the follow-up. The SIR was 1.40 (95% CI, 0.72-2.45) in males and 1.37 (95% CI, 0.81-2.16) in females. The 5-year rate of developing any EPM was 5.7%. CONCLUSIONS: BD-IPMN patients are at risk of pancreatic carcinogenesis. Although the 5-year incidence rate was as low as 1.4%, the surveillance protocol based on the current guidelines failed to identify a small subset of patients who progressed to advanced disease. Patients with BD-IPMN are not at risk of extrapancreatic carcinogenesis.

Uncommon presentations of common pancreatic neoplasms: a pictorial essay.

Pancreatic neoplasms are a wide group of solid and cystic lesions with different and often characteristic imaging features, clinical presentations, and management. Among solid tumors, ductal adenocarcinoma is the most common: it arises from exocrine pancreas, comprises about 90% of all pancreatic neoplasms, and generally has a bad prognosis; its therapeutic management must be multidisciplinary, involving surgeons, oncologists, gastroenterologists, radiologists, and radiotherapists. The second most common solid pancreatic neoplasms are neuroendocrine tumors: they can be divided into functioning or non-functioning and present different degrees of malignancy. Cystic pancreatic neoplasms comprise serous neoplasms, which are almost always benign, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms, which can vary from benign to frankly malignant lesions, and solid pseudopapillary tumors. Other pancreatic neoplasms, such as lymphoma, metastases, or pancreatoblastoma, are rarely seen in clinical practice and have different and sometimes controversial managements. Rare clinical presentations and imaging appearance of the most common pancreatic neoplasms, both solid and cystic, are more frequently seen and clinically relevant than rare pancreatic tumors; their pathologic and radiologic appearances must be known to improve their management. The purpose of this paper is to present some rare or uncommon clinical and radiological presentations of common pancreatic neoplasms providing examples of multi-modality imaging approach with pathologic correlations, thus describing the histopathological bases that can explain the peculiar imaging features, in order to avoid relevant misdiagnosis and to improve lesion management.

Triple approach strategy for patients with locally advanced pancreatic carcinoma.

BACKGROUND: Radiofrequency ablation (RFA) is a relatively new technique, applied to metastatic solid tumours which, in recent studies, has been shown to be feasible and safe on locally advanced pancreatic carcinoma (LAPC). RFA can be combined with radio-chemotherapy (RCT) and intra-arterial plus systemic chemotherapy (IASC). The aim of this study was to investigate the impact on the prognosis of a multimodal approach to LAPC and define the best timing of RFA. METHODS: This is a retrospective observational study of patients who have consecutively undergone RFA associated with multiple adjuvant approaches. RESULTS: Between February 2007 and December 2011, 168 consecutive patients were treated by RFA, of which 107 were eligible for at least 18 months of follow-up. Forty-seven patients (group 1) underwent RFA as an up-front treatment and 60 patients as second treatment (group 2) depending on clinician choice. The median overall survival (OS) of the whole series was 25.6 months: 14.7 months in the group 1 and 25.6 months in the group 2 (P = 0.004). Those patients who received the multimodal treatment (RFA, RCT and IASC-triple approach strategy) had an OS of 34.0 months. CONCLUSIONS: The multimodal approach seems to be feasible and associated with an improved longer survival rate.

Time trends in the treatment and prognosis of resectable pancreatic cancer in a large tertiary referral centre.

OBJECTIVES: Mortality in pancreatic cancer has remained unchanged over the last 20-30 years. The aim of the present study was to analyse survival trends in a selected population of patients submitted to resection for pancreatic cancer at a single institution. METHODS: Included were 544 patients who underwent pancreatectomy for pancreatic cancer between 1990 and 2009. Patients were categorized into two subgroups according to the decade in which resection was performed (1990-1999 and 2000-2009). Predictors of survival were analysed using univariate and multivariate analyses. RESULTS: Totals of 114 (21%) and 430 (79%) resections were carried out during the periods 1990-1999 and 2000-2009, respectively (P < 0.0001). Hospital length of stay (16 days versus 10 days; P < 0.001) and postoperative mortality (3% versus 1%; P = 0.160) decreased over time. Median disease-specific survival significantly increased from 16 months in the first period to 29 months in the second period (P < 0.001). Following multivariate analysis, poorly differentiated tumour [hazard ratio (HR) 3.1, P < 0.001], lymph node metastases (HR = 1.9, P < 0.001), macroscopically positive margin (R2) resection (HR = 3.2, P < 0.0001), no adjuvant therapy (HR = 1.6, P < 0.001) and resection performed in the period 1990-1999 (HR = 2.18, P < 0.001) were significant independent predictors of a poor outcome. CONCLUSIONS: Longterm survival after surgery for pancreatic cancer significantly improved over the period under study. Better patient selection and the routine use of adjuvant therapy may account for this improvement.

Growth pattern of serous cystic neoplasms of the pancreas: observational study with long-term magnetic resonance surveillance and recommendations for treatment.

BACKGROUND AND AIMS: The natural history and growth pattern of pancreatic serous cystic neoplasms (SCNs) are not well understood. This study was designed in order to get insight into the growth rate of SCNs and to suggest recommendations for their management. METHODS: Patients with well-documented incidentally discovered or minimally symptomatic SCNs who underwent yearly surveillance MRI were analysed using a linear mixed model. The growth rate and the effects of different fixed factors (sex, personal history of other non-pancreatic malignancies, radiological pattern, clinical presentation, tumour site) and random factors (age and tumour diameter at the time of diagnosis) on tumour growth were investigated. RESULTS: Study population consisted of 145 patients. Estimated overall mean growth rate was 0.28 cm/year, but the growth curve analysis showed a different trend between the first 7 years after the baseline evaluation (growth rate of 0.1 cm/year) and the subsequent period (years 7 to 10, growth rate of 0.6 cm/year, p<0.0001). Tests for fixed effects demonstrated that an oligocystic/macrocystic pattern and a personal history of other tumours are significant predictors of a more rapid mean tumour growth (p<0.0001 and 0.022, growth rates of 0.34 cm/year). Furthermore, tumour growth significantly increased with age (p = 0.0001). CONCLUSION: Overall, SCNs grow slowly, and an initial non-operative approach is feasible in all the asymptomatic or minimally symptomatic patients. The oligocystic/macrocystic variant, a history of other non-pancreatic malignancies and patients' age impact on tumour growth. In any case, a significant growth is unlikely to occur before 7 years from the baseline evaluation. Tumour size at the time of diagnosis should not be used for decisional purposes.

Perioperative and long-term results of laparoscopic spleen-preserving distal pancreatectomy with or without splenic vessels conservation: a retrospective analysis.

BACKGROUND AND OBJECTIVES: Laparoscopic spleen-preserving distal pancreatectomy can be performed with or without splenic vessels conservation. The formation of perigastric varices is the main long-term complication and represents the area of major concern among surgeons. Aim of this paper was to evaluate the outcomes of patients who underwent spleen-preserving distal pancreatectomy (with or without splenic vessels conservation) at our institution. METHODS: Retrospective search of an electronic database from 1999 through 2007. Standard statistical methods were used. RESULTS: 43 individuals were analyzed. Postoperative morbidity was 56%. Patients managed by splenic vessels conservation were 36; in the remaining seven splenic vessels resection was performed. Pathologic details and the rate postoperative complications were not different between the two groups. Two splenectomies were necessary for postoperative splenic infarction (one in each group). 28 patients accepted the follow-up protocol. At 12 months, the rate of perigastric varices was 60.0% after splenic vessels resection and 21.7% after splenic vessels conservation (P = 0.123). No gastrointestinal bleeding occurred at a median follow-up of 69 months (37-139). CONCLUSION: Laparoscopic spleen-preserving distal pancreatectomy is feasible. A moderate risk of postoperative splenic infarction has to be taken into account, and the formation of perigastric varices may be interpreted as a paraphysiologic phenomenon, especially after splenic vessels resection.

Circulating autoantibodies to phosphorylated α-enolase are a hallmark of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and no diagnostic markers have, as of yet, been defined. In PDAC patients, α-enolase (ENOA) is up-regulated and elicits the production of autoantibodies. Here, we analyzed the autoantibody response to post-translational modifications of ENOA in PDAC patients. ENOA isolated from PDAC tissues and cell lines was characterized by two-dimensional electrophoresis (2-DE) Western blot (WB), revealing the expression of six different isoforms (named ENOA1,2,3,4,5,6) whereas only 4 isoforms (ENOA3,4,5,6) were detectable in normal tissues. As assessed by 2-DE WB, 62% of PDAC patients produced autoantibodies to the two more acidic isoforms (ENOA1,2) as opposed to only 4% of controls. Mass spectrometry showed that ENOA1,2 isoforms were phosphorylated on serine 419. ROC analysis demonstrated that autoantibodies to ENOA1,2 usefully complement the diagnostic performance of serum CA19.9 levels, achieving approximately 95% diagnostic accuracy in both advanced and resectable PDAC. Moreover, the presence of autoantibodies against ENOA1,2 correlated with a significantly better clinical outcome in advanced patients treated with standard chemotherapy. In conclusion, our results demonstrate that ENOA phosphorylation is associated with PDAC and induces specific autoantibody production in PDAC patients that may have diagnostic value.

Splenic artery invasion in pancreatic adenocarcinoma of the body and tail: a novel prognostic parameter for patient selection.

BACKGROUND: The value of splenic vessels invasion (which identified T3 tumors) in prognosis after resection for pancreatic ductal adenocarcinoma (PDA) of the body and tail has not been extensively investigated. The goal of this study was to evaluate prognostic factors in PDA of the body/tail, emphasizing the role of splenic vessels infiltration. METHODS: Between 1990 and 2008, 87 patients who underwent distal pancreatectomy (DP) for histologically proven PDA of the body and tail were analyzed. Clinicopathological prognostic factors for survival were evaluated. Univariate and multivariable analyses were performed. RESULTS: Postoperative morbidity was 31% with no mortality. The 1-, 3-, and 5-year overall survival rates were 77%, 48%, and 24.5%, respectively. Invasion of the splenic artery (SA) was observed in 19 patients (22%). Patients with SA invasion had a significantly poorer prognosis compared with those without SA invasion (median survival: 15 vs. 39 months, P = 0.014). On multivariable analysis, adjuvant therapy, poor differentiation (G3/G4), R2 resection, the presence of lymph node metastases, and SA invasion were independent predictors of survival. CONCLUSIONS: Along with other well-known prognostic factors, invasion of SA is an independent predictor of poor survival in PDA of the body/tail. In case of the presence of SA infiltration, neoadjuvant treatment should be considered. SA infiltration might be reclassified from a T3 to T4 tumor.

Laparoscopic pancreatectomy for solid pseudo-papillary tumors of the pancreas is a suitable technique; our experience with long-term follow-up and review of the literature.

BACKGROUND: Solid pseudopapillary tumors (SPTs) are rare pancreatic neoplasms of low malignant potential that occur mainly in young women. Only 17 cases of SPT treated laparoscopically have been published in the literature and long-term follow-up data are still lacking. METHODS: Retrospective analysis of ten patients (8 women, 2 men; mean age, 25.4 years) (DS: 12.1; minimum 11, maximum 51) who underwent laparoscopic distal pancreatectomy with a definitive histological diagnosis of SPT. Long-term follow-up data were collected. RESULTS: The average tumor size was 43.8 mm (minimum 20, maximum 65 mm). The mean operative time was 177.5 minutes (DS: 53.7; minimum 120, maximum 255). In all, five patients underwent distal splenopancreatectomy; five patients underwent spleen-preserving distal pancreatectomy of whom three with splenic vessel preservation and two with the Warshaw technique. The conversion rate was nil and no case of perioperative mortality was recorded. The mean hospital stay was 7 days (DS: 2.7; minimum 4, maximum 12). Six patients had an uneventful postoperative course and four had postoperative complications. Two of them underwent reoperation, and the other two had nonsurgical complications. After a median follow-up of 47 (range, 5-98) months, all patients were alive and disease-free. CONCLUSIONS: Laparoscopic pancreatic resection is a safe and feasible procedure that could become the treatment of choice for patients affected by pancreatic SPT. Distal pancreatectomy should be performed, if possible, with spleen-preserving technique, especially in young patients. To avoid metastatic spread, laparoscopic or laparotomic biopsy should not be performed in patients affected by SPT.

Surgical treatment of pancreatic tumors in childhood and adolescence: uncommon neoplasms with favorable outcome.

BACKGROUND/AIMS: Pancreatic tumors in children and adolescents are uncommon. The aim of the present paper was to analyze short- and long-term outcomes after surgical treatment of primary pancreatic neoplasms in children and adolescents at a single high-volume center for pancreatic diseases. METHODS: Retrospective review of medical records and pathology reports of patients younger than 18 years who underwent surgery at Verona University Hospital from 1990 through 2010. RESULTS: The study population consisted of 20 patients. Abdominal pain and palpable mass were the most common presenting symptoms. No patient had a locally advanced, unresectable or metastatic disease. Complete resection (R0) was achieved in 19 patients. There was no postoperative mortality, but postoperative complications occurred in 5 cases (25%). Histological examination showed 12 solid pseudopapillary tumors, 5 neuroendocrine tumors, 2 cystadenomas and 1 epithelial malignant tumor. At a median follow-up of 49.5 months (range: 7-234), there was no tumor recurrence. Postoperative diabetes was diagnosed in 1 patient and 4 other patients developed pancreatic exocrine insufficiency. CONCLUSION: In the setting of a high-volume surgical center, radical resection of pancreatic tumors in children and adolescents is associated with acceptable postoperative morbidity and favorable long-term outcome.

Endoscopic transmural drainage of pseudocysts associated with pancreatic resections or pancreatitis: a comparative study.

BACKGROUND: Endoscopy has been regarded as an effective modality for draining pancreatic collections, pseudocysts, and abscesses. This study analyzes our experience with endoscopic transmural drainage of pancreatic pseudocysts and compares the outcomes in patients with postsurgical and pancreatitis-associated ones. METHODS: Patients who underwent endoscopic drainage of a pancreatic pseudocyst from January 1999 through June 2008 were included in this retrospective analysis. The specific indication for attempting the procedure was the presence of direct contact between the pseudocyst and the gastric wall. All the drainages were carried out via a transgastric approach, and one or two straight plastic stents (10 or 11.5 French) were positioned. A comparative analysis of short- and long-term results was made between patients with postoperative pseudocysts (group A) and patients with pancreatitis-associated pseudocysts (group B). RESULTS: Fifty-five patients were included in the study, 25 in group A and 30 in group B. Overall, a single stent was inserted in 84.0% of patients, while two stents were needed in the remaining 16.0%. The technical success rate was 78.2%, whereas procedure-related complications were 16.4%. Complications included pseudocyst superinfection and major bleeding and were managed mainly by surgery. Mortality rate was 1.8% (1 patient). There were no significant differences in the technical success rate and procedure-related complications between the two groups (p=0.532 and 0.159, respectively) Recurrences were 13.9% and significantly more common in group B (p=0.021). In such cases, a second endoscopic drainage was successfully performed. CONCLUSION: Transmural endoscopic treatment of pancreatic pseudocysts is feasible and has a technical success rate of 78.2%, without differences related to the pseudocyst etiology. Recurrences, on the other hand, are more common in patients with pancreatitis. Given the severe complications that may occur after the procedure, we recommend that endoscopic drainage be performed in a tertiary-care center with specific expertise in pancreatic surgery.

Perioperative and long-term results after left pancreatectomy: a single-institution, non-randomized, comparative study between open and laparoscopic approach.

BACKGROUND: Laparoscopic left pancreatic resections are being increasingly performed. In this study, we provide a nonrandomized comparison between laparoscopic and open left pancreatectomy (OLP) for benign and borderline tumors, focusing on both perioperative and long-term results. METHODS: Demographic, pathologic, and perioperative details from patients who underwent laparoscopic and OLP between 1999 and 2006 were retrieved from our database and analyzed. Long-term results, including resume to full-time work, occurrence of incisional hernias, and incidence of exocrine and endocrine insufficiency also were evaluated. RESULTS: A total of 116 patients were included in the analysis; 43 (37.1%) were managed laparoscopically and 73 (62.9%) underwent the open procedure. There were no significant differences regarding clinical and pathological data. All of the resections attempted laparoscopically were completed. The rate of splenic preservation was significantly higher in the laparoscopic group (P = 0.0001). Postoperative outcomes were similar between the two groups. Longitudinal comparison between two time periods (1999-June 2004 vs. July 2004-2006) showed that pancreatic fistula and hospital stay significantly diminished over time in the laparoscopic group (P = 0.04 and P = 0.004, respectively). Median follow-up was 53 months. The incidence of exocrine insufficiency and incisional hernias was significantly higher after open resections (both P = 0.05). After hospital discharge, median time to resume full-time work was 6 weeks in the open group and 3 weeks after laparoscopic resections (P < 0.0001). Laparoscopy also resulted as an independent factor for an early resume to full-time activities in the multivariate analysis (P < 0.0001). CONCLUSIONS: Laparoscopic left pancreatectomy is a safe procedure for benign and borderline tumors, with similar perioperative outcomes compared with the open procedure. In the long term, the laparoscopic approach is likely to be superior thanks to a more rapid resume of full-time activities and to the lower incidence of incisional hernias and exocrine insufficiency. Clearly, these results have yet to be confirmed in large, randomized trials.

A grading system can predict clinical and economic outcomes of pancreatic fistula after pancreaticoduodenectomy: results in 755 consecutive patients.

AIM: Postoperative pancreatic fistula (POPF) has a wide range of clinical and economical implications due to the difference of the associated complications and management. The aim of this study is to verify the applicability of the International Study Group of Pancreatic Fistula (ISGPF) definition and its capability to predict hospital costs. METHODS: This is a retrospective study based on prospectively collected data of 755 patients who underwent pancreaticoduodenectomy in our institution between November 1996 and October 2006. A number of 147 patients (19.5%) have developed a POPF according to ISGPF definition. RESULTS: Grade A fistula, which has no clinical impact, occurred in 19% of all cases. Grade B occurred in 70.7% and was successfully managed with conservative therapy or mini-invasive procedures. Grade C (8.8%) was associated to severe clinical complications and required invasive therapy. Pulmonary complications were statistically higher in the groups B and C rather than the group A POPFs (p < 0.005; OR 8). Patients with carcinoma of the ampullary region had a higher incidence of POPF compared to ductal cancer, with a predominance of grade A (p = 0.036). Increasing fistula grades have higher hospital costs (€11,654, €25,698, and €59,492 for grades A, B, and C, respectively; p < 0.001). CONCLUSIONS: The development of a POPF does not always determine a substantial change of the postoperative management. Clinically relevant fistulas can be treated conservatively in most cases. Higher fistula severity corresponds to increased costs. The grading system proposed by the ISGPF allows a correct stratification of the complicated patients based on the real clinical and economic impact of the POPF.

Pancreaticoduodenectomy for pancreatic cancer: the Verona experience.

Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related mortality in the Western world. The current treatment is multimodal, and in resectable patients radical surgery represents the key-step toward long-term survival. Pancreaticoduodenectomy (PD) is the most widely performed operation, because the majority of ductal carcinomas arise in the head of the pancreas. Once considered extremely hazardous, PD has evolved into a safe procedure, with mortality below 5% and morbidity rates in the range from 20% to 60% at high-volume centers. Verona is regarded as one of the most prominent institutions for pancreatic surgery in Europe. More than 5500 patients with pancreatic diseases have been managed, and the surgical case load has increased substantially, with more than 1350 PDs performed. This review discusses this center's experience in surgical treatment of pancreatic head cancer. Furthermore, the preliminary results of radiofrequency thermal ablation of locally advanced ductal cancer are presented.

DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association.

Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs.

Early versus late drain removal after standard pancreatic resections: results of a prospective randomized trial.

SUMMARY OF BACKGROUND DATA: The role of surgically placed intra-abdominal drainages after pancreatic resections has not been clearly established. In particular, their effect on morbidity rates and the optimal timing for their removal remains controversial. METHODS: A total of 114 eligible patients who underwent standard pancreatic resections and at low risk of postoperative pancreatic fistula according to our institutional protocol (amylase value in drains < or =5000 U/L on postoperative day [POD] 1) were randomized on POD 3 to receive either early (POD 3) or standard drain removal (POD 5 or beyond). The primary end point of the study was the incidence of pancreatic fistula. Secondary endpoints included abdominal complications, pulmonary complications, in-hospital stay, and perioperative mortality. Cost-analysis between the 2 groups was also made. RESULTS: Early drain removal was associated with a decreased rate of pancreatic fistula (P = 0.0001), abdominal complications (P = 0.002), and pulmonary complications (P = 0.007). Median in-hospital stay was shorter (P = 0.018), and hospital costs decreased (P = 0.02). Mortality was nil. A significant association with pancreatic fistula was found for timing of drain removal (P < 0.001), unintentional weight decrease before surgery (P = 0.022), type of pancreas texture (P = 0.015), serum amylase levels on POD 1 (P = 0.001), and albumin levels on POD 1 (P = 0.039). Multivariate analysis showed that timing of drain removal (P = 0.0003) and unintentional weight decrease before surgery (P = 0.02) were independent risk factors of pancreatic fistula. CONCLUSIONS: In patients at low risk of pancreatic fistula, intra-abdominal drains can be safely removed on POD 3 after standard pancreatic resections. A prolonged period of drain insertion is associated with a higher rate of postoperative complications with increased hospital stay and costs. The manuscript is a randomized trial, registered in the NLM database as NCT00931554.

Invasive intraductal papillary mucinous carcinomas of the pancreas: predictors of survival and the role of lymph node ratio.

INTRODUCTION: Intraductal papillary mucinous neoplasms (IPMNs) are being increasingly recognized, and often harbor cancer. Lymph node metastases are an important prognostic factor for patients with invasive intraductal papillary carcinoma (I-IPMC), but the role of lymph node ratio (LNR) in predicting survival after surgery for I-IPMC is unknown. METHODS: The combined databases from the Surgical Department of Massachusetts General Hospital of Boston and the University of Verona were queried. We retrospectively reviewed clinical and pathologic data of all patients with resected, pathologically confirmed, I-IPMC between 1990 and 2007. Univariate and multivariate analysis were performed. RESULTS: I-IPMCs were diagnosed in 104 patients (55 males and 49 females), median age was 69 years. Recurrent disease was identified in 49 patients (47.1%) and the median 5-year disease specific survival (DSS) was 60.1%. The median number of resected/evaluated nodes was 15 (range, 5-60). There were 60 (57.7%) patients who had negative lymph nodes (N0), whereas 44 (42.3%) had lymph node metastases (N1). Patients with lymph node metastases had a shorter 5-year DSS (28.9%) compared with patients with negative lymph nodes (80.3%; P < 0.05) As the LNR increased, 5-year DSS decreased (LNR = 0, 86.5%; LNR >0 to 0.2, 34.4%; LNR >0.2, 11.1%; P < 0.05). On multivariate analysis, LNR, the presence of a family history of pancreatic cancer and a preoperative value of Ca 19.9 > 37 U/L were significant predictors of survival (P < 0.05). CONCLUSIONS: Lymph node ratio is a strong predictor of survival after resection for invasive intraductal papillary mucinous carcinoma.