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The aim of the current study was to implement whole transcriptome massively parallel sequencing (RNASeq) and copy number analysis to investigate the molecular biology of pancreatic ductal adenocarcinoma (PDAC). Samples from 16 patients with PDAC were collected by ultrasound‑guided biopsy or from surgical specimens for DNA and RNA extraction. All samples were analyzed by RNASeq performed at 75x2 base pairs on a HiScanSQ Illumina platform. Single‑nucleotide variants (SNVs) were detected with SNVMix and filtered on dbSNP, 1000 Genomes and Cosmic. Non‑synonymous SNVs were analyzed with SNPs&GO and PROVEAN. A total of 13 samples were analyzed by high resolution copy number analysis on an Affymetrix SNP array 6.0. RNAseq resulted in an average of 264 coding non‑synonymous novel SNVs (ranging from 146‑374) and 16 novel insertions or deletions (In/Dels) (ranging from 6‑24) for each sample, of which a mean of 11.2% were disease‑associated and somatic events, while 34.7% were frameshift somatic In/Dels. From this analysis, alterations in the known oncogenes associated with PDAC were observed, including Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations (93.7%) and inactivation of cyclin‑dependent kinase inhibitor 2A (CDKN2A) (50%), mothers against decapentaplegic homolog 4 (SMAD4) (50%), and tumor protein 53 (TP53) (56%). One case that was negative for KRAS exhibited a G13D neuroblastoma RAS viral oncogene homolog mutation. In addition, gene fusions were detected in 10 samples for a total of 23 different intra‑ or inter‑chromosomal rearrangements, however, a recurrent fusion transcript remains to be identified. SNP arrays identified macroscopic and cryptic cytogenetic alterations in 85% of patients. Gains were observed in the chromosome arms 6p, 12p, 18q and 19q which contain KRAS, GATA binding protein 6, protein kinase B and cyclin D3. Deletions were identified on chromosome arms 1p, 9p, 6p, 18q, 10q, 15q, 17p, 21q and 19q which involve TP53, CDKN2A/B, SMAD4, runt‑related transcription factor 2, AT‑rich interactive domain‑containing protein 1A, phosphatase and tensin homolog and serine/threonine kinase 11. In conclusion, genetic alterations in PDCA were observed to involve numerous pathways including cell migration, transforming growth factor‑β signaling, apoptosis, cell proliferation and DNA damage repair. However, signaling alterations were not observed in all tumors and key mutations appeared to differ between PDAC cases.

BACKGROUND: Data regarding the quality of life in patients undergoing laparoscopic distal pancreatectomy are lacking and no studies have reported a real cost-effectiveness analysis of this surgical procedure. The aim of this study was to evaluate and compare the quality of life and the cost-effectiveness of a laparoscopic distal pancreatectomy with respect to an open distal pancreatectomy. METHODS: Forty-one patients who underwent a laparoscopic distal pancreatectomy and 40 patients who underwent an open distal pancreatectomy were retrospectively studied as regards postoperative results, quality of life and cost-effectiveness analysis. The Italian neutral version of the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C-30, version 3.0, was used to rate the quality of life. RESULTS: Postoperative results were similar in the two groups; the only difference was that the first oral intake took place significantly earlier in the laparoscopic group than in the open group (P

The aim of this study was to evaluate the safety of pancreatic resections in patients 80 years or older.A systematic search of the literature was carried out that compared perioperative outcomes after pancreatic resection in patients 80 years or older with patients younger than 80 years. The primary end points were postoperative mortality and morbidity. The secondary end points were incidence of postoperative pancreatic fistula, delayed gastric emptying, bile leak, pneumonia, postoperative infection, cardiologic complications, reoperation, and length of hospital stay.Nine studies were found to be suitable for the meta-analysis. The postoperative mortality and morbidity were significantly higher in the group 80 years or older (P0.00001 and P = 0.003, respectively) except for patients in whom there were no differences in preoperative comorbidities (P = 0.56 and P = 0.36, respectively). Postoperative cardiac complications were significantly more frequent in patients 80 years or older (P0.0001), and the length of hospital stay was significantly longer in octogenarian patients (P = 0.008).Patients 80 years or older have an increased incidence of postoperative mortality, morbidity, and cardiac complications and a longer length of hospital stay than do younger patients. Thus, pancreatic resection can be recommended only in a selected group of patients 80 years or older.

Advanced ductal pancreatic carcinoma (PC) remains a challenge for current surgical and medical approaches. It has recently been claimed that radiofrequency ablation (RFA) may be beneficial for patients with locally advanced or metastatic PC. Using the MEDLINE database, we found seven studies involving 106 patients in which PC was treated using RFA. The PC was mainly located in the pancreatic head (66.9%) with a median size of 4.6 cm. RFA was carried out in 85 patients (80.1%) with locally advanced PC and in 21 (19.9%) with metastatic disease. Palliative surgical procedures were carried out in 41.5% of the patients. The average temperature used was 90 °C (with a temperature range of 30-105 °C) and the ratio between the number of passes of the probe and the size of the tumor in centimeters was 0.5 (range of 0.36-1). The median postoperative morbidity and mortality were 28.3% and 7.5%, respectively; the median survival was 6.5 months (range of 1-33 months). In conclusion, RFA is a feasible technique: however, its safety and long-term results are disappointing; Thus, the RFA procedure should not be recommended in clinical practice for a PC patient.

Objective: To evaluate Peng’s binding pancreaticojejunostomy as a safe technique which avoids anastomotic leakage after a pancreaticoduodenectomy. Methods: Prospective, observational, dual-institutional study, of patients who underwent a Peng’s binding pancreaticojejunostomy was conducted. It was compared with an historical control group of patients who underwent duct to mucosa pancreaticojejunostomy. Overall postoperative mortality, morbidity, postoperative pancreatic fistulas, postpancreatectomy hemorrhage, reoperation, length and costs of hospital stay were collected. Factors related with pancreatic fistula were: sex, age, comorbidities, body mass index, American Society of Anesthesiologists score, type of resection, extension of resection, characteristics of the pancreatic remnant, pathological diagnosis and surgeons. Univariate and multivariate analyzes were carried out. Results: Sixty-nine patients who underwent binding pancreaticojejunostomy were reported. The control group consisted of 52 patients. The mean length of hospital stay was significantly shorter in the control group than in binding group (p ¼ 0.003). Multivariate analyzes showed that soft pancreatic remnant was significantly related to an increasing rate of postoperative pancreatic fistula (OR 3.7-CI 1.1e12.8- P ¼ 0.034) while the type of pancreatic anastomosis was not significantly related with the occurrence of postoperative pancreatic fistula. Conclusions: In the European population, the binding pancreaticojejunostomy according to Peng did not preclude or reduce the postoperative pancreatic fistula rate.

Objective The objective of the study is to evaluate the usefulness of neoadjuvant chemoradiotherapy in resectable pancreatic cancer. Methods A single-center RCT of patients affected by resectable pancr eatic adenocarcinoma which included arm A (surgery alone) and arm B (neoadjuvant chemoradiation and surgery). The primary endpoint was R0 resection; the secondary endpoints were toxicity; number of patients who completed the neoadjuvant therapy; radiological and pathological response after chemoradiation; and pTNM stage, postoperative morbidity, mortality, and overall and disease-free survival. A sample size of 32 patients was required for each group. Results The study was terminated early, and 38 patients were randomized: 20 in arm A and 18 in arm B. There was no significant difference regarding R0 resection rate in the two groups (intention-to-treat, OR=1.91, P =0.489). Neoadjuvant chemoradiother- apy was completed in 14 out of 18 cases (77.8 %) and the radiological and pathological response was efficacious in 72.3 and 90.9 % of cases, respectively. Conclusions Neoadjuvant chemoradiation was feasible, safe, and efficacious, although non-significant results were obtained as a result of the underpowered data due to the difficulty in recruiting patients. Additional multicenter RCTs are needed in the future

none 7 no PURPOSE: The factors related to the learning curve for laparoscopic distal pancreatectomy have rarely been evaluated. METHODS: A retrospective study of 32 patients who underwent a laparoscopic distal pancreatectomy performed at a high-volume center by a single pancreatic surgeon experienced with laparoscopic surgery was conducted. Pre-, intra- and postoperative data were collected. The primary endpoint was the length of the operation. The secondary endpoints were the conversion and reoperation rates, overall postoperative morbidity and mortality rates, the length of hospital stay and rate of unplanned splenectomy. RESULTS: The length of the operation and the cumulative sum of the procedures presented a logarithmic correlation (P = 0.048). The learning curve appeared to have been completed after 17 procedures (P = 0.040). The multivariate analysis confirmed that the completion of the learning curve (CLC) reduced the length of the operation by 18 % (P = 0.009), but extended resection increased the length of the operation (P = 0.023). The conversion and reoperation rates, overall postoperative morbidity and mortality rates and length of the hospital stay were not related to the CLC. Unplanned splenectomy was more frequently performed during the first 17 procedures. CONCLUSIONS: The length of the operation seems to be the main factor related to the CLC for laparoscopic distal pancreatectomy. The learning curve could be considered to be completed after about 17 procedures if performed by surgeons experienced with laparoscopic techniques at high-volume centers. Ricci, Claudio; Casadei, Riccardo; Buscemi, Salvatore; Taffurelli, Giovanni; D'Ambra, Marielda; Pacilio, Carlo A.lberto; Minni, Francesco Ricci, Claudio; Casadei, Riccardo; Buscemi, Salvatore; Taffurelli, Giovanni; D'Ambra, Marielda; Pacilio, Carlo A.lberto; Minni, Francesco

BACKGROUND: Laparoscopic distal pancreatectomy was proposed as an oncologically safe approach for pancreatic ductal adenocarcinoma. METHODS: A systematic review of the studies comparing laparoscopic and open distal pancreatectomy was conducted. The primary endpoint was an R0 resection rate. The secondary endpoints were intra- and postoperative results, tumour size, mean harvested lymph node, number of patients eligible for adjuvant therapy and overall survival. RESULTS: Five comparative case control studies involving 261 patients (30.7% laparoscopic and 69.3% open) who underwent a distal pancreatectomy were included. The R0 resection rate was similar between the two groups (P = 0.53). The laparoscopic group had longer operative times (P = 0.04), lesser blood loss (P = 0.01), a shorter hospital stay (P

Background: Whether patients with small (Study Design: Based on the pertinent literature of the past decade, a Markov model was developed to investigate this issue. In the wait-and-see strategy arm, surgery was performed if the tumor attained a size ≥2 cm or surpassed 20% of the initial size. In a Monte Carlo probabilistic analysis, 100 hypothetical patients undergoing a wait-and-see strategy were compared to 100 patients directly undergoing surgery, with the aim of investigating the efficacy and cost-effectiveness of the two strategies. Results: During the postdiagnostic lifetime, 63 NF-PETs in the wait-and-see group showed significant growth and underwent surgery: 38 were stage I, 10 were stage II, 15 were stage III and none were stage IV. In the base-case scenario, the mean life expectancy and quality-adjusted life expectancy were found to be superior after immediate surgery [26.1 years and 11.8 quality-adjusted life years (QALYs)] than with the wait-and-see strategy (22.1 years and 8.3 QALYs) as the consequence of ageing during the wait-and-see follow-up which increased mortality due to surgery, when surgery was needed. The model was sensitive to starting age and length of follow-up; in particular, for patients >65 years of age, the two strategies provided similar results but the wait-and-see strategy was more cost-effective. Conclusions: The wait-and-see strategy for NF-PETs

RFA is a feasible procedure, but its safety still remains under debate. However, the complication rate seems high without a clear benefit of survival. In our opinion, the RFA procedure is not recommended as palliative therapy in clinical practice for patients with unresectable pancreatic adenocarcinoma.

Background: Portal-superior mesenteric vein (PV/SMV) resection during pancreatic resection has been widely applied in clinical practice. Methods: From a prospective data base of pancreatic resections, patients undergoing PV/SMV resection and reconstruction with a cryopreserved arterial homograft were extracted with the aim of evaluating the safety, feasibility and reproducibility of the procedure. Data regarding patient demographics, preoperative staging, surgery, histopathology and postoperative outcomes were analyzed. Results: Five patients were extracted in the last year. Indications for this technique were type IV-V degree of vein involvement and a 3.5 cm median length of vein infiltration. Median operative and clamping times were satisfactory (385 and 27 min, respectively), postoperative outcomes were good and there was no graft infection, thrombosis or stenosis occurred postoperatively and during the follow-up period. Conclusion: The use of a cryopreserved arterial homograft for PV/SMV reconstruction after pancreatic resection seems to be a feasible, safe and easily reproducible surgical technique in high-volume specialized centers and can be added to the pool of surgical solutions in selected patients.

BACKGROUND: In 2010, the World Health Organization released a new classification system for endocrine pancreatic tumors. The new categories replaced those in the old classification. METHODS: To test the safety and accuracy of the new classification in stratifying patients, we retrospectively evaluated 64 consecutive patients, surgically R0 resected for pancreatic endocrine tumors. RESULTS: In our experience, only 19/31 (61.3%) patients classified as having well-differentiated tumors were included in the new neuroendocrine tumor G1 category while the remaining 12 (38.7%) shifted into the G2 category. Moreover, 10/33 (30.3%) patients classified as affected by a malignant endocrine neoplasm in the old system were considered as G1 tumors in the new one. These differences were statistically significant (P < 0.001) and changed the risk category in 22 (33.3%) patients with well-differentiated pancreatic endocrine tumors. Multiple multivariate models were produced and the poor stratification of the new system was found to be in the G2 category which presents too wide a range of the Ki 67 index (2 to 20%). We built a model in which the G2 category was divided into two subcategories: tumors with a Ki 67 index ≥2 and

Soft pancreatic parenchyma is the most widely recognized risk factor for pancreatic fistula. We conducted this study to clarify if there are preoperative factors related to a soft pancreatic remnant and to establish if they are useful for predicting pancreatic fistula.This was a retrospective study of patients who underwent pancreatic resections at the Department of Surgical Sciences of the S. Orsola-Malpighi Hospital, Bologna, Italy. The factors considered were sex, age, co-morbidities, body mass index, American Society of Anesthesiologists score, characteristics of the pancreatic remnant, and preoperative diagnosis.Data from 208 patients were recorded. The risk factors predictive of a soft pancreatic remnant were BMI24 kg/m(2) (P = 0.011), a Wirsung duct size ≤3 mm (P0.001), and coexisting periampullary diseases (P0.001). Using these factors, we developed a risk score model that was validated by considering the pancreatic fistula rate. The overall and clinically relevant pancreatic fistula rate increased with increasing score values (P = 0.002 and P = 0.028, respectively). Using a score cut-off value of six points, patients with a score ≥6 were considered to be at high risk.Body mass index24 kg/m(2), a Wirsung duct size3 mm, and preoperative diagnosis represented the preoperative factors related to a soft pancreas. These factors proved useful in the building of a risk score model to predict the incidence of pancreatic fistula.

Background The prognostic role of lymph nodes metastasis in pancreatic neuroendocrine tumours is unclear. Methods Retrospective study of 53 patients who underwent a curative standard resection for pancreatic neuroendocrine tumours. The endpoint was to define the role of the lymph nodes ratio in recurrence after curative surgery. The following data were considered as possible factors for predicting the risk of recurrence: gender, age, presence of symptoms, hormonal status, site of tumours, type of resection, size of the tumours, radical resection, pathological T, N and M stage, the Ki67 index, the number of lymph nodes harvested, the number of metastatic lymph nodes and the lymph node ratio. Recurrence rate and time of recurrence were evaluated. Results Twelve (26.4%) patients developed a recurrence with a median time of 42.8 (1–305) months. At multivariate analysis, the only factors related to recurrence were: size of lesions (HR 1.1, C.I. 95% 1.0–1.1, P = 0.011), Ki67 ≥ 5% (HR 3.6, C.I. 95% 1.3–10, P = 0.014) and LNR > 0.07 (HR 5.2, C.I. 95% 1.1–25, P = 0.045). Conclusions Our study confirmed that the lymph nodes ratio played an important role in the recurrence rate and suggested that a low number of metastatic lymph nodes reduced the disease free survival.

Introduction: The long-term results of pancreatic tumors resections are disappointing. In order to increase postoperative survival after resections by surgical control of liver metastasis and peritoneal dissemination no-touch techniques of PD were proposed. Methods: We investigated the results of no-touch PD for malignant periampullary tumors in 31 patients, treated in our clinic in the period of November 20082011 years. In 14 patients tumors of papilla of Vater (PV) were diagnosed, in 12 tumors of the pancreas, 1neuroendocrine tumor, in 3 patientstumors of bile ducts (BD), 1 – gastrointestinal stromal tumor (GIST) of the duodenum. In 19 patients pylorus-preserving PD were done, in 12standard PD. In 3 patients additional resections of the affected portal or superior mesenteric vein were done. Results: Duration of the operation was 440,4 +77,4 minutes (from 340 to 745). Mean blood loss was 575,0 + 320,1 ml (from minimal to 1800). Morbidity was 22,6% (7 patients). Mortality was zero. Median survival in the group of BD cancer patients was 21,5 month. 1and 2year survival in pancreatic cancer patients was 63,5%, maximal follow-up26 months. 1and 2year survival for PV cancer patients was 100%, 3year survival85,7%, disease free 3-year survival57,1%. Patient with GIST is alive 34 months after procedure with metastatic disease from second postoperative year. Patient with neuroendocrine tumor is alive without metastatic disease 26 months after operation. Conclusion: No-touch PD is safe procedure. Further investigations should be done to evaluate potential benefit of the procedure.

Introduction: The long-term results of pancreatic tumors resections are disappointing. In order to increase postoperative survival after resections by surgical control of liver metastasis and peritoneal dissemination no-touch techniques of PD were proposed. Methods: We investigated the results of no-touch PD for malignant periampullary tumors in 31 patients, treated in our clinic in the period of November 20082011 years. In 14 patients tumors of papilla of Vater (PV) were diagnosed, in 12 tumors of the pancreas, 1neuroendocrine tumor, in 3 patientstumors of bile ducts (BD), 1 – gastrointestinal stromal tumor (GIST) of the duodenum. In 19 patients pylorus-preserving PD were done, in 12standard PD. In 3 patients additional resections of the affected portal or superior mesenteric vein were done. Results: Duration of the operation was 440,4 +77,4 minutes (from 340 to 745). Mean blood loss was 575,0 + 320,1 ml (from minimal to 1800). Morbidity was 22,6% (7 patients). Mortality was zero. Median survival in the group of BD cancer patients was 21,5 month. 1and 2year survival in pancreatic cancer patients was 63,5%, maximal follow-up26 months. 1and 2year survival for PV cancer patients was 100%, 3year survival85,7%, disease free 3-year survival57,1%. Patient with GIST is alive 34 months after procedure with metastatic disease from second postoperative year. Patient with neuroendocrine tumor is alive without metastatic disease 26 months after operation. Conclusion: No-touch PD is safe procedure. Further investigations should be done to evaluate potential benefit of the procedure.

Background Pancreatic metastases from renal cell carcinoma are uncommon. Methods Retrospective study of 8 patients with a diagnosis of pancreatic metastasis from renal cell carcinoma observed in our Institute. Results Patients were 6 (75%) males and 2 (25%) females. Mean age was 65.3 years. In 5 patients (57.1%), symptoms were present. The median interval of onset from nephrectomy was 10 years. No cases of synchronous pancreatic metastases were observed. Surgical resection was performed in 7 (87.5%) patients. At pathological examination, solitary metastases were identified in 5 patients (71.4%). No post-operative mortality was observed; the morbidity rate was 42.8%. In the group of patients who underwent pancreatic resection, median overall survival was 43.0 months (range 12.9–74.5), median disease-free survival was 23.6 months (range 9.9–74.5). Conclusions Pancreatic metastasis from renal cell carcinoma typically occurs after a long period from the initial nephrectomy, and seems to be related to a good prognosis.

The aim of this study was to test the usefulness of the Clavien-Dindo classification after pancreatic resection. In 183 patients who underwent pancreatic resections, complications were classified according to Clavien-Dindo classification and each grade was evaluated regarding the length of the postoperative stay and was compared to the most important complications. Sixty-four (35.0%) patients had no complications; out of the 119 (65.0%) patients with complications, grade I, was 9.3%; grade II, 35.5%; grade III, 9.3%; grade IV, 7.7% and grade V, 3.3%. The postoperative pancreatic fistula rate was 29.1%, postpancreatectomy hemorrhage, 35% and delayed gastric emptying, 11.5%. There was a progressive increase in the length of hospitalization from patients with no complications to those having grade IV (P < 0.001). Postoperative pancreatic fistula, postpancreatectomy hemorrhage and delayed gastric empty rates significantly increased from Clavien-Dindo grade I to grade IV; only postoperative pancreatic fistula and postpancreatectomy hemorrhage severity significantly increased from grade I to grade IV (both P < 0.001). The Clavien-Dindo classification is an objective, simple, and reliable way of reporting all complications following pancreatic resections and it allows to recognize appropriately all the most important complications after pancreatic resection, and the severity of postoperative pancreatic fistula and postpancreatectomy hemorrhage.

No abstract is available for this article.

e14541 Background: The aim of the study was to determine prognostic factors for recurrence in resected pancreatic cancer. Methods: We analyzed retrospectively 47 patients who underwent pancreatic r...

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

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

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

In some cases, synchronous superior mesenteric-portal vein resection can be performed during pancreatic resection for cancer. The reconstruction technique is usually primary anastomosis; in only a few cases is an autologous vein graft needed.We report a case of reconstruction of the superior mesenteric-portal vein with a splenic vein autograft in a patient affected by pancreatic head adenocarcinoma who underwent a total pancreatectomy.The reconstruction of the superior mesenteric-portal vein with a splenic vein autograft should be performed in selected cases. It allows a reduction of operating time, it is a less invasive approach than reconstruction using an internal jugular vein autograft and it can be an oncologically correct approach.

4048 Background: A deeper knowledge of the pancreatic cancer (PDAC) biology is needed to improve the prognosis of the disease. Methods: 17 PDAC samples were collected by ultrasound-guided biopsy used for DNA and RNA extraction. 14 samples were analyzed by high resolution copy number analysis (CNA) on Affymetrix SNP array 6.0 and with segmentation algorithm against a reference of 270 Ceu HapMap individuals (Partek Genomic Suite). 17 samples were analyzed by whole transcriptome massively parallel sequencing, performed at 75x2 bp on a HiScanSQ Illumina platform. An average of 7, 3x107 reads per sample were generated, with a mean read depth of 50X. Single nucleotide variants (SNVs) were detected with SNVMix2 and compared with genetic variation databases (dbSNP, 1000genomes, Cosmic). Non-synonimous SNVs were analyzed with the predictors SNPs and GO and PROVEAN. Results: CNA results in 9/14 samples exhibited both macroscopic and cryptic cytogenetic alterations, with a mean of 10 CNA per patient. Most frequent gains were observed in 18q11.2 involving GATA6 (3/14) and 19q13 targeting AKT2 (3/14) while hotspot deletions were found on 18q21 (7/14), 17p13 (6/14), 9p21.3 (6/14), 15q (5/14) and 1q35 (4/14). RNAseq showed that samples exhibited a mean of 145 (range: 61-240) non-synonimous SNVs, of which 16 on average are potentially disease-related. Merging copy number and RNAseq data we highlighted the major oncogenic hits of PDAC, confirming the prevalence (14/17) of KRAS mutations, in one case also NRAS (G13D), and the three oncosuppressor CDKN2A (mutated in 3 cases and deleted in 6 cases, in hetero- or homozygosity), SMAD4 (altered by point mutation or gene deletion in 7/14), and TP53 (lost in 6/14 and mutated in 5/17). The signaling pathways affected were: KRAS/MAPK, TGFbeta and integrin signaling, proliferation and apoptosis, DNA damage response, and epithelial to mesenchymal transition. Moreover we found new oncogenic alterations, such as HMGCR, that displayed mutations in 17% of the analyzed patients (3/17). Conclusions: NGS combined with high resolution cytogenetic analysis can improve the understanding of pancreatic carcinogenesis.

BACKGROUND: The use of laparoscopic distal pancreatectomy (LDP) increased in the past twenty years but the real diffusion of this technique is still unknown as well as the type of centers (high or low volume) in which this procedure is more frequently performed. DATA SOURCE: A systematic review was performed to evaluate the frequency of LDP in Italy and to compare indications and results in high volume centers (HVCs) and in low volume centers (LVCs). RESULTS: From 95 potentially relevant citations identified, only 5 studies were included. A total of 125 subjects were analyzed, of whom 95 (76.0%) were from HVCs and 30 (24.0%) from LVCs. The mean number of LDPs performed per year was 6.5. The mean number of patients who underwent LDP per year was 8.8 in HVCs and 3.0 in LVCs (P

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a 5-year survival rate of 4%. Even if some genetic hits leading to PDAC development are known, a deeper knowledge of the genetic landscape of tumor is necessary to identify druggable targets. Methods: PDAC samples from 14 localized and advanced cases of pancreatic adenocarcinomas were collected by ultrasound-guided biopsy used for DNA and RNA extraction. High resolution copy number analysis was performed on Affymetrix SNP array 6.0 and analyzed with segmentation algorithm against a reference of 270 Ceu HapMap individuals (Partek Genomic Suite). Whole transcriptome massively parallel sequencing was performed at 75x2 bp on a HiScanSQ Illumina platform. An average of 7,3x107 reads per sample were generated, with a mean read depth of 50X. Single nucleotide variants (SNVs) were detected with SNVMix2 and compared with genetic variation databases (dbSNP, 1000genomes, Cosmic). Non-synonimous SNVs were analyzed with SNPs&GO and SIFT to predict disease association. Results: Whole transcriptome sequencing showed that PDAC samples exhibited a mean of 145 (range: 61-240) non-synonimous SNVs, of which 16 on average are potentially disease-related. 9/14 patients exhibited both macroscopic and cryptic cytogenetic alterations, with a mean of 10 copy number alterations per patient, while 5 patients did not show any copy number gain or loss. Most frequent gains were observed in 18q11.2 involving GATA6 (3/14) and 19q13 targeting AKT2 (3/14) while hotspot deleted regions were found on 18q21 (7/14), 17p13 (6/14), 9p21.3 (6/14), 15q (5/14) and 1q35 (4/14). Merging copy number and RNAseq data we highlighted the major oncogenic hits of PDAC, confirming the prevalence (9/14) of KRAS mutations, in one case also NRAS (G13D), and the central role of the three oncosuppressor CDKN2A (mutated in 3 cases and deleted in 6 cases, either in hetero- or homozygosity), SMAD4 (altered by either point mutation or gene deletion in 8/14 cases), and TP53 (lost in 7/14 samples). We identified novel pathogenic single nucleotide variants and frameshift mutations, and inter- and intra-chromosomal translocation events that give rise to chimeric fusion transcripts. Even if the mutation profile was heterogeneous in different patients the signaling pathways affected were shared, and included KRAS/MAPK, TGFbeta and integrin signaling, proliferation and apoptosis, DNA damage response, and epithelial to mesenchymal transition. New oncogenic alterations emerged, as ARID1A that was inactivated by somatic mutation (G91R and P1425fs) or copy number loss in 6 patients, NOTCH2 and HMGCR, that displayed pathogenic mutations in 15-20% of the analyzed patients. Conclusions: Next generation sequencing combined with high resolution cytogenetic analysis can improve the understanding of carcinogenesis and highlight new biomarkers for early diagnosis and potential therapeutic targets in PDAC. Citation Format: Marina Macchini, Annalisa Astolfi, Riccardo Casadei, Valentina Indio, Carla Serra, Silvia Vecchiarelli, Elisa Grassi, Claudio Ricci, Marielda D'Ambra, Giovanni Taffurelli, Donatella Santini, Raffaele Pezzilli, Francesco Minni, Guido Biasco, Mariacristina Di Marco. Whole genome discovery of genetic alterations carried by pancreatic adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 812. doi:10.1158/1538-7445.AM2013-812

Context Patients with locally advanced pancreatic cancer are usually treated with chemoradiotherapy and rarely they became resectable. Herein, we present the case of a patient with locally advanced pancreatic cancer. Case report A 56-year-old man was observed in October 2011 because of high blood levels of CA 19.9 (>230 U/mL) and the presence of a pancreatic mass of the uncinate process (diameter 3.8x3.5 cm) revealed by US and CT scan. An US-guided biopsy allowed the diagnosis of well differentiated pancreatic adenocarcinoma, biliopancreatic type. CT scan showed a vascular involvement of both superior mesenteric vein and artery. The disease was defined as locally advanced unresectable pancreatic cancer. The patient started chemotherapy with gemcitabine and oxaliplatin. Five months later, CT scan re-evaluation of the disease showed a stable disease. Thus, a protocol of radio-chemotherapy was suggested. Eight months later from diagnosis, the mass was still unresectable. Other eight cycles of gemcitabine and oxaliplatin were performed. In February 2013 a further CT scan evaluation demonstrated a smaller lesion (3.5x2.2 cm) and also the vascular involvement was decreased, still without a normal fat plane between the tumor and the vessels. Another cycle of gemcitabine and oxaliplatin was completed. At the end of May 2013, the 18FDG-PET was negative; CT scan demonstrated a further decreased of the mass (maximum diameter: 2.5 cm) while the mesenteric vessels involvement still remained. Moreover, the genomic characteristics of the patient DNA were different from other the pancreatic cancer. Because of the long-term survival of the young patient, the partial regression of the disease and the genomic characteristics of the tumor, a surgical approach was indicated. The patient underwent to a total pancreatectomy with splenectomy plus segmental resection of portal mesenteric trunk. Pathological diagnosis confirmed a well-differentiated ductal pancreatic carcinoma, biliopancreatic type (T4), with R0 resection. Conclusion Our case suggests that there are locally advanced pancreatic cancers in which chemoradiotherapy can allow surgical pancreatic resection probably because they have particular genomic characteristics., JOP. Journal of the Pancreas, Vol 14, N° 5S (2013): September (Suppl.) - p. 528-602

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a 5-year survival rate of 4%. Even if some genetic hits leading to PDAC development are known, a deeper knowledge of the genetic landscape of tumor is necessary to identify druggable targets. Methods: PDAC samples from 14 localized and advanced cases of pancreatic adenocarcinomas were collected by ultrasound-guided biopsy used for DNA and RNA extraction. High resolution copy number analysis was performed on Affymetrix SNP array 6.0 and analyzed with segmentation algorithm against a reference of 270 Ceu HapMap individuals (Partek Genomic Suite). Whole transcriptome massively parallel sequencing was performed at 75x2 bp on a HiScanSQ Illumina platform. An average of 7,3x107 reads per sample were generated, with a mean read depth of 50X. Single nucleotide variants (SNVs) were detected with SNVMix2 and compared with genetic variation databases (dbSNP, 1000genomes, Cosmic). Non-synonimous SNVs were analyzed with SNPs&GO and SIFT to predict disease association. Results: Whole transcriptome sequencing showed that PDAC samples exhibited a mean of 145 (range: 61-240) non-synonimous SNVs, of which 16 on average are potentially disease-related. 9/14 patients exhibited both macroscopic and cryptic cytogenetic alterations, with a mean of 10 copy number alterations per patient, while 5 patients did not show any copy number gain or loss. Most frequent gains were observed in 18q11.2 involving GATA6 (3/14) and 19q13 targeting AKT2 (3/14) while hotspot deleted regions were found on 18q21 (7/14), 17p13 (6/14), 9p21.3 (6/14), 15q (5/14) and 1q35 (4/14). Merging copy number and RNAseq data we highlighted the major oncogenic hits of PDAC, confirming the prevalence (9/14) of KRAS mutations, in one case also NRAS (G13D), and the central role of the three oncosuppressor CDKN2A (mutated in 3 cases and deleted in 6 cases, either in hetero- or homozygosity), SMAD4 (altered by either point mutation or gene deletion in 8/14 cases), and TP53 (lost in 7/14 samples). We identified novel pathogenic single nucleotide variants and frameshift mutations, and inter- and intra-chromosomal translocation events that give rise to chimeric fusion transcripts. Even if the mutation profile was heterogeneous in different patients the signaling pathways affected were shared, and included KRAS/MAPK, TGFbeta and integrin signaling, proliferation and apoptosis, DNA damage response, and epithelial to mesenchymal transition. New oncogenic alterations emerged, as ARID1A that was inactivated by somatic mutation (G91R and P1425fs) or copy number loss in 6 patients, NOTCH2 and HMGCR, that displayed pathogenic mutations in 15-20% of the analyzed patients. Conclusions: Next generation sequencing combined with high resolution cytogenetic analysis can improve the understanding of carcinogenesis and highlight new biomarkers for early diagnosis and potential therapeutic targets in PDAC.