Efficacy and cost-effectiveness of immediate surgery versus a wait-and-see strategy for sporadic nonfunctioning T1 pancreatic endocrine neoplasms.

BACKGROUND: Whether patients with small (<2 cm), sporadic nonfunctioning pancreatic endocrine tumors (NF-PETs) should directly undergo pancreatic surgery or should be followed longitudinally to detect growth and malignancy still has to be defined. 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 <2 cm represents a reasonable approach in patients over 65 years of age; otherwise, immediate surgery is preferable.

Portal/Superior Mesenteric Vein Reconstruction during Pancreatic Resection Using a Cryopreserved Arterial Homograft.

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.

Laparoscopic distal pancreatectomy: what factors are related to the learning curve?

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.

Are there preoperative factors related to a "soft pancreas" and are they predictive of pancreatic fistulas after pancreatic resection?

PURPOSE: 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. METHODS: 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. RESULTS: Data from 208 patients were recorded. The risk factors predictive of a soft pancreatic remnant were BMI >24 kg/m(2) (P = 0.011), a Wirsung duct size ≤3 mm (P < 0.001), and coexisting periampullary diseases (P < 0.001). 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. CONCLUSIONS: Body mass index >24 kg/m(2), a Wirsung duct size <3 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.

WHO 2010 classification of pancreatic endocrine tumors. is the new always better than the old?

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 <5% and tumors with a Ki index ≥5 and <20%, partially modifying the new classification. In this model, the modified classification showed a superiority with respect to the European Neuroendocrine tumor Society-Tumor-Node-Metastasis staging system in stratifying patients for recurrence, with a relative risk of 19 (P < 0.001). CONCLUSION: The new G2 category seems too large because it includes both benign, low and high grade malignant tumors.

Interventional radiology procedures after pancreatic resections for pancreatic and periampullary diseases.

CONTEXT: The use of interventional radiology has increased as the first-line management of complications after pancreatic resections. METHODS: Patients in whom interventional radiology was performed were compared with those in whom interventional radiology was not performed as regards type of pancreatic resection, diagnosis, postoperative mortality and morbidity, postoperative pancreatic fistula postpancreatectomy haemorrhage, bile leakage, reoperation rate and length of hospital stay. Our aim was to evaluate the usefulness of interventional radiology in the treatment of complications after pancreatic resection. RESULTS: One hundred and eighty-two (62.8%) out of 290 patients experienced postoperative complications. Interventional radiology procedures were performed in 37 cases (20.3%): percutaneous drainage in 28, transhepatic biliary drainage in 8 and arterial embolisation in 3 cases. Technical success was obtained in all cases and clinical success in 75.7%. Reoperation was avoided in 86.5%. In patients with major complications, clinically relevant postoperative pancreatic fistula and bile leaks as well as those with late postpancreatectomy haemorrhage (P=0.030) and patients with postpancreatectomy haemorrhage grade C (P=0.029), interventional radiology was used (P<0.001, P<0.001 and P=0.009, respectively) significantly more frequently than in the remaining patients. The reoperation and mortality rates were similar in the two groups (P=0.885 and P=0.100, respectively) while patients treated with interventional radiology procedures had a significant longer length of hospital stay than those in the non-interventional radiology group (37.5 ± 23.4 vs. 18.7 ± 11.7 days; P<0.001). CONCLUSIONS: Interventional radiology procedures were useful, especially for patients with postoperative pancreatic fistulas and bile leaks in whom reoperation was very often avoided.

The usefulness of a multidisciplinary team approach in decision making for pancreatic serous cystic neoplasms.

CONTEXT: Serous cystic neoplasms of the pancreas are regarded as benign entities with rare malignant potential and are frequently resected. OBJECTIVE: The purpose of the study was to evaluate the usefulness of a multidisciplinary team (MDT) approach in decision making regarding the diagnosis and management of pancreatic serous cystic neoplasms. METHODS: A retrospective study of a prospective database involving 43 patients with serous cystic neoplasms was carried out. Patients who underwent multidisciplinary team evaluation (Group 1) were compared with patients who did not (Group 2) as regards demographic, clinical, radiological, surgical and pathological data. Uni-multivariate analyses were carried out. RESULTS: Uni-multivariate analysis showed that a multidisciplinary team approach was significantly related to the type of management, suggesting that MDT evaluation independently reduced the odds of surgery (odds ratio (OR) 0.1; 95% confidence interval (CI) 0.02-0.8; P=0.027). Age, second level imaging techniques, latero-lateral diameter, cranio-caudal diameter and Wirsung duct size differed between the two groups; however, the differences were not statistically significant. CONCLUSIONS: A multidisciplinary team approach seems to be useful in proper decision making regarding the diagnosis and management of pancreatic serous cystic neoplasms.

Natural history of branch-duct intraductal papillary mucinous neoplasms of the pancreas: a case report.

CONTEXT: The natural history of incidental branch-duct intraductal papillary mucinous neoplasm of the pancreas is still unknown. CASE REPORT: The case of a 74-year-old man who had been diagnosed 14 years previously with an incidental branch-duct intraductal papillary mucinous neoplasm of the pancreatic head, 30 mm in size, without mural nodules and dilatation of the main pancreatic duct is herein reported. After an exploratory laparotomy at the time of diagnosis (when he was 60 year-old), the patient was enrolled in a surveillance program. Fourteen years after the diagnosis, the cystic lesion showed an increase in size, Wirsung duct dilatation and the presence of several mural nodules. A total pancreatectomy was performed and a diagnosis of mixed-intraductal papillary mucinous neoplasm diffused throughout the entire pancreas with high grade dysplasia, and a micro-invasive carcinoma (<1 mm) of the pancreatic head was reached. CONCLUSION: The present case confirmed that the natural history of branch-duct intraductal papillary mucinous neoplasms is unpredictable. Thus, an appropriate surveillance program is required for prompt identification of the signs predictive of a malignant transformation of branch-duct intraductal papillary mucinous neoplasms. In high-volume centers, surgery should seriously be considered in young patients who are fit for surgery.

Laparoscopic distal pancreatectomy in Italy: a systematic review and meta-analysis.

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<0.001). The most frequent lesions operated on in HVCs were cystic tumors (62.1%, P<0.001) while, in LVCs, solid neoplasms (76.7%, P<0.001). In HVCs, malignant neoplasms were treated with LDP less frequently than in LVCs (17.9% vs 50.0%, P<0.001). Splenectomy was performed for non-oncologic reason frequenter in HVCs than in LVCs (70.2% vs 25.0%, P=0.004). The length of stay was shorter in HVCs than in LVCs (7.5 vs 11.3, P<0.001). No differences were found regarding age, gender, ductal adenocarcinoma treated, operative time, conversion, morbidity, postoperative pancreatic fistula, reoperation and margin status. CONCLUSIONS: LDPs were frequently performed in Italy. The "HVC approach" is characterized by a careful selection of patients undergoing LDP. The "LVC approach" is based on the hypothesis that LDPs are equivalent both in short-term and long-term results to laparotomic approach. These data are not conclusive and they point out the need for a national register of laparoscopic pancreatectomy.

The role of lymph node ratio in recurrence after curative surgery for pancreatic endocrine tumours.

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.

Peng's binding pancreaticojejunostomy after pancreaticoduodenectomy. An Italian, prospective, dual-institution study.

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, co-morbidities, 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 = 0.003). Multivariate analyzes showed that soft pancreatic remnant was significantly related to an increasing rate of postoperative pancreatic fistula (OR 3.7-CI 1.1-12.8-P = 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.

Pancreatic mucinous cystic neoplasm in a male patient.

CONTEXT: Mucinous cystic neoplasm (MCN) of the pancreas usually affects female patients and is characterized by an ovarian-type stroma. From literature review, only 9 cases of MCNs have been reported in male patients. CASE REPORT: We describe the 10th case of a MCN in a 65-year-old male patient who underwent a distal pancreatectomy with spleen resection and standard lymphadenectomy. CONCLUSIONS: MCN may rarely regard male patients, probably for embryological abnormalities.

Assessment of complications according to the Clavien-Dindo classification after distal pancreatectomy.

CONTEXT: The absence of a definition and a widely accepted ranking system to classify surgical complications has hampered proper interpretation of the surgical outcome. PATIENTS: Sixty-one patients undergoing distal pancreatectomy. MAIN OUTCOME MEASURES: The complications were classified according to the Clavien-Dindo classification; each grade was evaluated regarding the length of the postoperative stay and was compared to the most important complications. RESULTS: Thirty (49.2%) patients had no complications; out of the thirty-one (50.8%) patients with complications, 9 (14.5%) had grade I, 15 (24.6%) had grade II, 6 (9.8%) had grade III, and 1 (1.6%) had grade IV. There were no postoperative deaths (grade V). A progressive increase in the length of hospitalization from patients with no complications to those having grade IV (P < 0.001) was noted. Postoperative pancreatic fistula and postpancreatectomy hemorrhage rates did not significantly increase from Clavien-Dindo grade I to grade IV (P = 0.118 and P = 0.226, respectively). The severity of a postpancreatectomy hemorrhage, instead, was positively related to the grade of the Clavien-Dindo classification (P = 0.049) while postoperative pancreatic fistula resulted near the significant value (P = 0.058). CONCLUSIONS: The Clavien-Dindo classification is a simple way of reporting all complications following distal pancreatectomy. It allows us to distinguish a normal postoperative course from any deviation and the severity of complications and it may be useful for comparing postoperative morbidity between different pancreatic centers.

Are there prognostic factors related to recurrence in pancreatic endocrine tumors?

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.

Managing unsuspected tumour invasion of the superior mesenteric-portal vein during surgery for pancreatic head cancer. A case report.

CONTEXT: 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. CASE REPORT: 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. CONCLUSIONS: 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.

Laparoscopic versus open distal pancreatectomy for ductal adenocarcinoma: a systematic review and meta-analysis.

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 < 0.001) and smaller tumour size (P = 0.04) as compared with the laparotomic group. Overall morbidity, postoperative pancreatic fistula, reoperation, mortality and number of patients eligible for adjuvant therapy were similar. The mean harvested lymph nodes were comparable in the two groups (P = 0.33). The laparoscopic approach did not affect the overall survival rate (P = 0.32). CONCLUSION: Even if the number of patients compared is underpowered, the laparoscopic approach in the treatment of PDAC seems to be safe and efficacious. However, additional prospective, randomised, multicentric trials are needed to correctly evaluate the laparoscopic approach in PDAC.

Neoadjuvant Chemoradiotherapy and Surgery Versus Surgery Alone in Resectable Pancreatic Cancer: A Single-Center Prospective, Randomized, Controlled Trial Which Failed to Achieve Accrual Targets.

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 pancreatic 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 chemoradiotherapy 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.

Laparoscopic Distal Pancreatectomy in Benign or Premalignant Pancreatic Lesions: Is It Really More Cost-Effective than Open Approach?

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 < 0.001). Regarding quality of life, the laparoscopic approach was able to ameliorate physical functioning (P = 0.049), role functioning (P = 0.044) and cognitive functioning (P = 0.030) and reduce the sleep disturbance scale (P = 0.050). The cost-effectiveness analysis showed that the acceptability curve for a laparoscopic distal pancreatectomy had a higher probability of being more cost-effective than an open distal pancreatectomy when a willingness to pay above 5400 Euros/quality-adjusted life years (QALY) was accepted. CONCLUSION: Despite the limitations of the study, laparoscopic distal pancreatectomy can be considered not only safe and feasible but also permits a better quality of life and is acceptable in terms of cost-effectiveness to Italian and European health care services.

Characterization of pancreatic ductal adenocarcinoma using whole transcriptome sequencing and copy number analysis by single-nucleotide polymorphism array.

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 ultrasound­guided 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. Single­nucleotide variants (SNVs) were detected with SNVMix and filtered on dbSNP, 1000 Genomes and Cosmic. Non­synonymous 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 non­synonymous novel SNVs (ranging from 146­374) and 16 novel insertions or deletions (In/Dels) (ranging from 6­24) for each sample, of which a mean of 11.2% were disease­associated 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 cyclin­dependent 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 inter­chromosomal 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, runt­related transcription factor 2, AT­rich interactive domain­containing 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 factor­ß 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.

Pancreatic resection in patients 80 years or older: a meta-analysis and systematic review.

OBJECTIVE: The aim of this study was to evaluate the safety of pancreatic resections in patients 80 years or older. METHODS: 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. RESULTS: 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 (P < 0.00001 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 (P < 0.0001), and the length of hospital stay was significantly longer in octogenarian patients (P = 0.008). CONCLUSIONS: 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.