- Email: [email protected]
Mo1444 Clinico-Pathological Features and Survival of Resected Pancreatic Neuroendocrine Tumors Associated With Von Hippel Lindau Disease and Multiple Endocrine Neoplasia Type 1
islet TP-IAT with a mean (±standard deviation, SD) follow-up of 29.5 ± 21.9 months. The average (±SD) patient age was 41.5 ± 4.9 years, and BMI was 26.2 ± 7.0. 47% of the patients were female. The etiology of the CP was most commonly idiopathic (n=29, 48.3%). Specific etiologies included genetic/familial (n=12, 20%), alcohol related CP (n=10, 16.7%), sphincter of Oddi dysfunction (n=3, 5%), pancreatic divisum (n=2, 3.3%) and hypertriglyceridemia (n=1, 1.7%). Daily narcotic use was noted in 81.7% of the patients with the average (± SD) morphine equivalents being 198.8 ± 467.4, and duration of pain 103.2 ± 93.6 months. Mean (± SD) depression, anxiety and pain disability index were 14.2 ± 11.7, 8.3 ± 7.8 and 41.9 ± 16.1, respectively. 22% of the patients qualified for a diagnosis of opioid disorder. Central pain block results were available for 30 patients; 29 of these patients were noted to have had pain relief with block and only 4 (13%) were noted to have a central pain component. Male gender, older age, and patients with higher pain disability score as well as higher pain score as noted in the numeric rating scale had better improvement in pain than patients without (all P values <0.05). Central pain component did not differentiate pain change after surgery in our series. At an average of 29.5 months follow-up, 25 (41.7%) patients were noted to be narcotic independent. Analysis for predictors of complete independence from narcotic use did not identify any significant predictor. Conclusion: Patients with significant preoperative pain and disability, as well as high pain rating have the best improvement in pain after TP-IAT for CP. While in our series results of central pain block do not appear to predict either a change in pain or pain relief, we have tailored our use of TP-IAT for patients with limited central pain component with a normal psychological assessment, thus the importance of routine pain block and psychological evaluation in all patients considered candidates for surgery.
Mo1442 Risk Factors of the Recurrence After Surgical Resection for Intraductal Papillary Mucinous Neoplasm of the Pancreas Seiko Hirono, Manabu Kawai, Ken-ichi Okada, Motoki Miyazawa, Atsushi Shimizu, Yuji Kitahata, Hiroki Yamaue Introduction: There has been little evidence about appropriate surveillance following surgical resection for intraductal papillary mucinous neoplasm (IPMN). We evaluate the risk factors of recurrence to establish the postoperative surveillance strategy for IPMN. Methods: This study enrolled 257 IPMN patients undergoing surgical resection at a single institution. We analyzed the frequencies, patterns, time-to-event, and risk factors of the postoperative recurrence for IPMN. Results: Fifty-five IPMN patients (21.4%) developed recurrence after surgery, including remnant pancreatic recurrence (n=14) and extra-pancreatic recurrence (n=41). The remnant pancreatic recurrence had no influence on the overall survival (OS), however, the OS of the patients with extra-pancreatic recurrence was significantly worse than those without (P<0.001). Five (35.7%) of 14 patients with remnant pancreatic recurrence developed it more than 5 years after surgery, and the OS of 8 patients undergoing the second resection tended to be better than 6 patients without. All extra-pancreatic recurrences occurred within 5 years, and especially, 85.4% of them occurred within 2 years from the surgery. We found that positive pancreatic transected margin was only independent risk factor of remnant pancreatic recurrence (P<0.001), and the risk factors of extra-pancreatic recurrence were invasive IPMN (P<0.001), mixed type (P=0.027), tumor size >30 mm (P=0.045), elevated serum CA19-9 (P=0.011), and intraoperative transfusion (P=0.010). Conclusion: Our data suggest that continuous surveillance in more than 5 years are needed after surgery for all IPMN patients to evaluate the remnant pancreatic recurrence, and strict surveillance within 5 years for IPMN patients with risk factors of extra-pancreatic recurrence.
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Decrease of CC-Family Chemokines Levels in the Heart Tissue of Aged Rats Following Severe Acute Pancreatitis: A New Mechanism of Heart Protection During Systemic Inflammation Rizia C. Amaral, Denise F. Barbeiro, Marcia K. Koike, Fabiano P. Silva, Marcel C. Machado
Mo1443 Impaired Mitochondrial Redox Sinalling Leads to Aberrant Epigenetic Regulation in Occult Hepatitis B & C Infections Kewal K. Maudar
Introduction/Background Severe acute pancreatitis (AP) in the elderly is followed by an increased mortality and morbidity rates putting in evidence that the severity of the systemic response is more intense in this population Sustained inflammatory response in distant organs like the heart,may be implicated in this age related vulnerability . CC chemokines are the largest subfamily of chemokines, which are important components of the innate immune system. Chemokines trigger leukocyte trafficking and are implicated in cardiovascular disease pathophysiology.The aim of the present study was to investigate if the cardiac inflammatory response and chemokines expression could be more exacerbated in the elderly, during severe pancreatic injury Methods: AP was induced in male Wistar rats by an intraductal 2.5 % taurocholate injection and divided into 2 experimental groups(20 rats each group) G-1 young (3 month old rats) and G-2 older (18 month old rats) Eleven hours after AP heart tissue was collected for evaluation of gene expression of chemokines and cytokines Results :It was observed an increased expression of chemokines CCL-1, CCL-11 and CKCL1 in the heart of control aged rats when compared to young animals. However we observed a decreased of chemokines expression 11 h after AP induction in old animals without changed in chemokines expression in young rats. Lower levels of I L-10 and IL-6 gene expression was also observed in the heart of old rats with AP Conclusion These unexpected results suggest that in old rats decreased expression of heart chemokines after AP may represent a protective mechanism from further heart damage during systemic inflammatory processes such as severe pancreatic injury.
INTRODUCTIONOccult viral hepatitis is often associated with increased risk of hepatocellular carcinoma (HCC). Epigenetic deregulation and mitochondrial dysfunction lead to genomic and epigenomic damage.Present study was aimed to establish a molecular link between virusinduced mitochondrial oxidative stress and redox mediated epigenetic regulation among occult hepatitis patients.METHODSThe study was carried out on patients with occult HBV & HCV,chronic HBV & HCV patients and age and gender matched controls (n=10 each).The cells were fixed, permeabilized and incubated with antiH3K9me1, anti-H4K20me3, anti-phospho-H3, anti-ubiquitinated H2A/H2B and anti-phospho-H2AX for different histone modifications.Quantification was done through flow cytometric analysis.Fluorescence tagged immune-stained cells were analyzed for 10000 total events.RESULTS In occult HBV patients, HBV DNA was positive in plasma and peripheral lymphocytes,viral load ranged from 20 to 80 IU/mL. Occult HCV patients were reported to be anti-HCV positive, serum HCV RNA negative, but positive for HCV RNA in peripheral lymphocytes with viral load ranging from 30 to 60 IU/ml. The chronic HBV patients were positive for HBsAg, anti-HBc and HBV DNA and their viral load ranged from 500 to 1000 IU/mL. Chronic HCV patients were positive for anti-HCV and had serum HCV RNA levels ranging from 800 to 1500 IU/ml. The results suggested that desspite low viral load,occult hepatitis B & C infections lead to impaired mitochondrial redox signaling and perturbed epigenetic machinery. Higher levels of 8-oxo-dG and reduced mtDNA copy number suggested functional disruption of mitochondrial assembly among occult HBV/HCV infected patients. While epigenetic perturbations in occult hepatitis patients were indicated by distorted histone patterns. Depending on the specific site and degree of methylation within histone sequence, histone lysine methylation correlates with gene expression leading to repression or activation. We observed a dispersed lysine methylation pattern of monomethylated H4K20 and H3K9 histones, widely known to distinctly mark silent chromatin regions within the mammalian epigenome. CONCLUSION The results suggested that in comparison to control cell population the expression pattern of all four core histones altered distinctly in occult patients. Taken together, present study provides novel insights of deregulated ‘histone code' dynamics in occult hepatitis B/C patients that might play an intermediate step for development and progression of HCC among these patients. The virus induced mitochondrial stress and epigenomic imbalance may provide a breakthrough for prevention and novel therapeutic targets for HCC in occult HBV and HCV infections.
Mo1441 Lymph Node Ratio and Para-Aortic Node Involvement Are Not Independent Predictors of Survival After Resection for Pancreatic Cancer Valentina Beltrame, Mario Gruppo, Michele Valmasoni, Stefano Merigliano, Cosimo Sperti Objectives. Lymph node involvement is an important prognostic factors for pancreatic cancer, and metastases to para-aortic nodes are considered a contraindication to radical surgery. Aim of this study was to analyze the importance of lymph node status in a series of patients who underwent pancreaticoduodenectomy in a single Institution. Methods Between January 2000 and December 2012, 144 patients underwent pancreaticoduodenectomy (PD) with para-aortic nodes dissection for pancreatic adenocarcinoma. Pathologic factors, including stage, nodal status, number of positive nodes and lymph node ratio, invasion of paraaortic nodes, tumor's grading, and radicality of resection were studied by univariate and multivariate analysis. Survival curves were constructed with Kaplan-Meier method and compared with Log-rank test: significance was considered as p<0.05. Results A total of 107 patients (74%) had nodal metastases. Mean and median number of pathologically assessed lymph nodes were 28 and 26, respectively (range 14-63). Twenty-two patients (15%) had para-aortic lymph node involvement. Thirty-three patients (23%) underwent R1 pancreatic resection. One-hundred thirty-two patients recurred and died, two are alive with recurrence, and 10 are alive and free of disease. Overall survival was significantly influenced by grading (p= 0.0001), radicality of resection (p=0.001), stage (p=0.03), lymph node status (p=0.04), paraaortic nodes metastases (p=0.02). Multivariate analysis showed that only grading was an independent prognostic factor for overall survival (p=0.0001), while grading (p=0.0001) and radicality of resection (p=0.01) were prognostic parameters for disease-free survival. Number of metastatic nodes, node ratio, and para-aortic nodes involvement were not independent predictors of disease-free and overall survival. Conclusion In this experience the number of positive lymph nodes did not have prognostic implication in patients with node positive pancreatic cancer. Although lymph node status and para-aortic node metastases were associated with poor survival at univariate analysis, they were not independent prognostic index. So, the decision to perform pancreatic resection should not be taken on the basis of lymph node status only.
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Mo1444 Clinico-Pathological Features and Survival of Resected Pancreatic Neuroendocrine Tumors Associated With Von Hippel Lindau Disease and Multiple Endocrine Neoplasia Type 1 Ilaria Pergolini, Othon Iliopoulos, Cristina R. Ferrone, Vikram Deshpande, Keith D. Lillemoe, Carlos Fernandez-del Castillo Patients with von Hippel Lindau disease (VHL) and multiple endocrine neoplasia 1 (MEN1) are at a risk of developing pancreatic neuroendocrine tumors (PNETs), which may behave in a malignant fashion. We retrospectively evaluated a 15-year experience with resected PNETs associated with these genetic syndromes. Between January 2001 and November 2015, 334 patients underwent resection for a PNET at a single institution. 10 of these had VHL (3%) and 24 MEN1 (7%). 1 patient in each group was found to have distant metastases at the time of diagnosis. Age at diagnosis of PNET in patients with VHL was 17 years younger than in MEN1 (30.5 vs 47.5 years, p=0.1), although the age at the diagnosis of the inherited syndrome was similar (27 vs 27.5 years). Median time of observation between diagnosis and surgical resection was 14 months (2-153) in VHL cases and 1.5 months (0-96) in MEN1 patients (p=0.002). PNETs led to the diagnosis of the genetic syndrome in only one (10%) patient with VHL and in 9 (37.5%) patients with MEN1; 7 of these were functioning tumors. Family history was positive in 90% of VHL patients and in 71% of those with MEN1; the median size of the largest tumor was 2.4 cm (1.8-4.2) and 2.8 cm (0.7-9.0), respectively
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(p=0.353). PNETs were frequently multifocal, particularly in MEN1 (54% vs 30%, p=0.270). In VHL, PNET was more frequently associated with multifocal cystic lesions (60% vs 4%, p=0,001). Distal pancreatectomy was the most frequent procedure (50% in VHL and 59% in MEN1). Invasive lesions represented almost 60% of cases in both groups. Lymph nodes were positive in 30% and 25% of patients, respectively. There were no post-operative deaths, but morbidity occurred in 5 patients with VHL (50%) and in 21% of MEN1 patients. Median follow-up was 25 months (1-126) for VHL patients and 73.5 months (2-169) in the MEN1 group (p=0.259); during follow-up, 1 (10%) and 6 (25%) patients, respectively, experienced recurrence, and 1 patient in each group died of the disease. No correlation between size of the tumor and recurrence was found. Median disease free survival was 25 (1-126) and 56.5 (2-146) months, respectively. Conclusions. 10% of resected PNETs are associated with either VHL or MEN1. Both require careful management due to their malignant potential, young age of diagnosis, frequent multifocal presentation and risk of recurrence.
Mo1447 Graded Morbidity Profiles for Duodenum Preserving Pancreatic Head Resection Are Equivalent To Those For Pancreaticoduodenectomy In HeadDominant Chronic Pancreatitis Olga Kantor, Jeffrey B. Matthews, Mark S. Talamonti, Waseem Lutfi, Marshall Baker Background: European randomized trials have compared duodenum preserving pancreatic head resection (DPPHR) to pancreaticoduodenectomy (PD) for management of head-dominant chronic pancreatitis (HDCP). These consistently demonstrate the improvements in pancreatitic pain and quality of life in DPPHR to be comparable to those following PD. Few studies from American centers have compared perioperative outcomes and no studies have graded the severity of postoperative complications following these procedures. Methods: Medical records for patients undergoing either DPPHR or PD for HDCP between 2006 and 2014 were reviewed to capture all complications, postoperative interventions and 90-day readmission events. Clavien-Dindo grade IIIb, IV and V complications were classified as severe adverse postoperative outcomes (SAPO). Grade I, II, and IIIa complications requiring either prolonged length of stay (LOS) including readmissions (>3 standard deviations beyond the mean for patients without complications) or >1 interventional procedure were also classified as SAPO. All others were considered minor adverse outcomes (MAPO). Results: 27 patients underwent DPPHR (3 Beger, 8 Berne, and 16 Frey procedures) and 20 underwent PD (12 standard, 8 pylorus-preserving). Patients undergoing DPPHR were less likely to have had significant weight loss prior to surgery than those undergoing PD (15% vs 50%, p= 0.01). There were no other significant differences between surgical cohorts with regard to preoperative patient demographics, comorbidities including pre-existing diabetes and pancreatic exocrine insufficiency, alcohol history, or previous pancreatic surgery. There were no significant differences in rates of transfusion (7% vs 15%, p=0.64), postoperative complication (70% vs 60%, p=0.54), 90-day readmission (22% vs 20%, p=0.55), total LOS including readmissions (10.8 ± 5.4 vs 12.1 ± 6.8, p=0.43) or 90-day mortality (4% vs 0%, p=0.58) between groups. Patients undergoing DPPHR were less likely to suffer a postoperative pneumonia than those undergoing PD (0% vs 25%, p=0.01). Postoperative pancreatic fistula was infrequent in both groups (0% for DPPHR vs 10% for PD, p=0.18). There was a trend towards fewer SAPO among patients undergoing DPPHR although this did not reach significance (33% vs 50%, p=0.11). Multivariate regression adjusting for demographics, comorbidities, presenting symptoms, intraoperative blood loss, and procedure performed found no significant independent predictors of SAPO. Conclusions: Although there is a trend towards a lower severity complication profile among patients undergoing DPPHR, graded 90-day perioperative outcomes of DPPHR are equivalent to those of PD. DPPHR procedures are performed seldomly in the United States. At experienced centers, these procedures are safe and provide complication profiles similar to more traditional surgical approaches to HDCP.
Mo1445 Impact of Fellow vs. Resident Assistance on Outcomes Following Pancreaticoduodenectomy Christian Schmidt, Andrea Jester, Catherine Chung, Alexandra M. Roch, Rosalie Carr, E M. Kilbane, Michael G. House, Nicholas J. Zyromski, Attila Nakeeb, C. Max Schmidt, Eugene P. Ceppa Purpose: Participation by residents and fellows in procedures of higher complexity is key to their development as future practicing surgeons. The impact of experience on outcomes of pancreaticoduodenectomy (PD) has been clearly shown in a number of studies. The impact of surgical fellows vs. general surgery resident assistance in outcomes in PD has not been studied. The purpose of this study was to determine if there were significant differences in patient outcomes following pancreaticoduodenectomy as a function of hepatopancreatobiliary surgery fellow vs. general surgery resident intraoperative assistance. Methods: Consecutive cases of PD (n=220) were reviewed at a single high-volume institution over an 18month period (July 2013-December 2014). Inclusion criteria consisted of any patient who underwent a PD with involvement of a surgical trainee. Thirty-day outcomes were monitored through the American College of Surgeon's National Surgical Quality Improvement Program (NSQIP); all PD are tracked using NSQIP. Quality In-Training Initiative (QITI) is a novel component of NSQIP with a variable that included documenting the PGY level of the trainee assisting in the case. As a result, we are able to distinguish the exact PGY level per case. Each faculty member performing PD is beyond the learning curve of 60 cases. Two-way statistical analyses were used to compare categories. Results: The hepatopancreatobiliary surgery fellows and general surgery residents participated in n=98 and n=122, PD respectively. There were no statistical differences in demographics, BMI, ASA score, or any other preoperative variable between groups. Intraoperative variables were nearly identical: median operative time (275 + 10 vs. 285 + 10 minutes), rate of transfusion (25% vs. 25%), and mean units of blood transfused (4.1 + 0.3 vs. 5.1 + 0.65 units) for fellows vs. residents respectively. Post-operative outcomes were similar and are listed in the table. Conclusions: These results suggest that in the training environment that either dedicated hepatopancreatobiliary surgery fellows or general surgery residents are of comparable safety as assistants to performing pancreaticoduodenectomy. Table
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Background: The association between postoperative inflammatory markers and risk of complications after pancreaticoduodenectomy (PD) is controversial. We sought to assess the diagnostic value of perioperative C-reactive protein (CRP) and procalcitonin (PCT) levels in the early identification of patients at risk for complications after pancreaticoduodenectomy (PD). Method: In 2014, 84 patients undergoing elective PD were enrolled in a prospective database. Clinicopathological characteristics, CRP and PCT, as well as short-term outcomes, such as complications and pancreatic fistula, were analyzed. Complications and pancreatic fistula were defined based on the Clavien-Dindo classification and the International Study Group on Pancreatic Fistula (ISGPF) classification, respectively. High CRP and PCT were classified using cut-off values based on ROC curve analysis. Results: The majority (73.8%) of patients had pancreatic adenocarcinoma. CRP and PCT levels over the first 5 post-operative days (POD) were higher among patients who experienced a complication versus those who did not (p<0.001). Postoperative CRP and PCT levels were also higher among patients who developed a grade B or C pancreatic fistula (p<0.05). A CRP concentration >84 mg/l on POD 1 (AUC 0.77) and >127 mg/l on POD 3 (AUC 0.79) was associated with the highest risk of overall complications (OR 6.86 and 9.0, respectively; both p<0.001). Similarly patients with PCT > 0.7 mg/dl on POD 1 (AUC 0.67) were at higher risk to develop a postoperative complication (OR 3.33; p=0.024). On POD 1 a CRP > 92 mg/l (AUC 0.72) and a PCT > 0.4 mg/dl (AUC 0.70) were associated with the highest risk of pancreatic fistula (OR 5.63 and 5.62 respectively; both p<0.05). Conclusion: CRP and PCT concentration were associated with an increased risk to develop complications and clinical relevant pancreatic fistula after PD. Use of these biomarkers may help identify those patients at highest risk for perioperative morbidity and help guide postoperative management of patients undergoing PD.
Mo1446 Prospective Randomized Study Comparing Outcome of Duodenum Preserving Pancreatic Head Coring With Duodenum Preserving Pancreatic Head and Body Coring in Chronic Pancreatitis Vikash Moond, Rajesh Gupta, Surinder S. Rana, Ritambhra Nada, Mandeep Kang, Rajinder Singh, Deepak K. Bhasin Introduction:- Chronic pancreatitis is a progressive inflammatory disease with uncertain course. There is no single effective surgery for the variable structural abnormalities associated with this disease. The aim of this study is to ascertain whether more extensive pancreatic resection would lead to better outcome in terms of post-op pain control, exocrine and endocrine deficiency, morbidity and mortality. Methodology:- 20 patients of chronic pancreatitis undergoing surgery were randomly allocated into 2 groups to undergo head coring or head and body coring and were followed post-operatively at 1, 3 and 6 months. Pain score, exocrine and endocrine function and quality of life were assessed for the 2 groups. Results:A total of 20 patients were divided in two groups. Four females and six males were included in each study group. Duration of surgery (p=1.0), intra-operative blood loss (p=1.0), postop bleeding (p=1.0) and anastomotic leak (p=1.0) were not significantly different between the two groups. There were 2 postoperative deaths in the group undergoing head and body coring and 1 death in the group, which underwent head coring (p=1). Post-operative pain control was comparable in the two groups (p=0.478). Exocrine (p=1.0) and endocrine (p= 1.0) functions were also comparable between the two groups at 6 months follow up. Quality of life analysis will be presented during meeting. Conclusion:- More extensive pancreatic resection does not lead to increased operative mortality and increased morbidity in the immediate post operative period. Long term follow up will be required to assess the effect of extensive pancreatic coring on pain control, exocrine and endocrine deficiency which were not different at 6-month follow up.
Mo1449 How Can We Measure Learning Curves in Complex Laparoscopic Pancreas Resections? Uwe A. Wittel, Simon Küsters, Frank Makowiec, Tobias Keck, Ulrich T. Hopt Background: Laparoscopic pancreas resections however, greatly vary in their technical difficulty. This implies that surgeons have to wisely select appropriate patients according to their technical skill while they pass through their individual learning curve. With our analyses we try to identify parameters that are indicators of success during the personal learning curve using 2 independent learning curves with 30 hybrid laparoscopically assisted pancreatoduodenectomies for each surgeon. Material and Methods: Between 2010 and 2015 106 laparoscopic hybrid pancreatoduodenectomies with open reconstruction were performed at the Clinic of General and Visceral Surgery, University of Freiburg. These operations were performed by two surgeons independently responsible for patient selection and operative
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C-Reactive Protein and Procalcitonin As Predictors of Postoperative Inflammatory Complications After Pancreatic Surgery Giardino Alessandro, Gaya Spolverato, Paolo Regi, Isabella Frigerio, Filippo Scopelliti, Roberto Girelli, Timothy M. Pawlik, Paolo Pederzoli, Giovanni Butturini
Mo1442 Risk Factors of the Recurrence After Surgical Resection for Intraductal Papillary Mucinous Neoplasm of the Pancreas Seiko Hirono, Manabu Kawai, Ken-ichi Okada, Motoki Miyazawa, Atsushi Shimizu, Yuji Kitahata, Hiroki Yamaue Introduction: There has been little evidence about appropriate surveillance following surgical resection for intraductal papillary mucinous neoplasm (IPMN). We evaluate the risk factors of recurrence to establish the postoperative surveillance strategy for IPMN. Methods: This study enrolled 257 IPMN patients undergoing surgical resection at a single institution. We analyzed the frequencies, patterns, time-to-event, and risk factors of the postoperative recurrence for IPMN. Results: Fifty-five IPMN patients (21.4%) developed recurrence after surgery, including remnant pancreatic recurrence (n=14) and extra-pancreatic recurrence (n=41). The remnant pancreatic recurrence had no influence on the overall survival (OS), however, the OS of the patients with extra-pancreatic recurrence was significantly worse than those without (P<0.001). Five (35.7%) of 14 patients with remnant pancreatic recurrence developed it more than 5 years after surgery, and the OS of 8 patients undergoing the second resection tended to be better than 6 patients without. All extra-pancreatic recurrences occurred within 5 years, and especially, 85.4% of them occurred within 2 years from the surgery. We found that positive pancreatic transected margin was only independent risk factor of remnant pancreatic recurrence (P<0.001), and the risk factors of extra-pancreatic recurrence were invasive IPMN (P<0.001), mixed type (P=0.027), tumor size >30 mm (P=0.045), elevated serum CA19-9 (P=0.011), and intraoperative transfusion (P=0.010). Conclusion: Our data suggest that continuous surveillance in more than 5 years are needed after surgery for all IPMN patients to evaluate the remnant pancreatic recurrence, and strict surveillance within 5 years for IPMN patients with risk factors of extra-pancreatic recurrence.
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Decrease of CC-Family Chemokines Levels in the Heart Tissue of Aged Rats Following Severe Acute Pancreatitis: A New Mechanism of Heart Protection During Systemic Inflammation Rizia C. Amaral, Denise F. Barbeiro, Marcia K. Koike, Fabiano P. Silva, Marcel C. Machado
Mo1443 Impaired Mitochondrial Redox Sinalling Leads to Aberrant Epigenetic Regulation in Occult Hepatitis B & C Infections Kewal K. Maudar
Introduction/Background Severe acute pancreatitis (AP) in the elderly is followed by an increased mortality and morbidity rates putting in evidence that the severity of the systemic response is more intense in this population Sustained inflammatory response in distant organs like the heart,may be implicated in this age related vulnerability . CC chemokines are the largest subfamily of chemokines, which are important components of the innate immune system. Chemokines trigger leukocyte trafficking and are implicated in cardiovascular disease pathophysiology.The aim of the present study was to investigate if the cardiac inflammatory response and chemokines expression could be more exacerbated in the elderly, during severe pancreatic injury Methods: AP was induced in male Wistar rats by an intraductal 2.5 % taurocholate injection and divided into 2 experimental groups(20 rats each group) G-1 young (3 month old rats) and G-2 older (18 month old rats) Eleven hours after AP heart tissue was collected for evaluation of gene expression of chemokines and cytokines Results :It was observed an increased expression of chemokines CCL-1, CCL-11 and CKCL1 in the heart of control aged rats when compared to young animals. However we observed a decreased of chemokines expression 11 h after AP induction in old animals without changed in chemokines expression in young rats. Lower levels of I L-10 and IL-6 gene expression was also observed in the heart of old rats with AP Conclusion These unexpected results suggest that in old rats decreased expression of heart chemokines after AP may represent a protective mechanism from further heart damage during systemic inflammatory processes such as severe pancreatic injury.
INTRODUCTIONOccult viral hepatitis is often associated with increased risk of hepatocellular carcinoma (HCC). Epigenetic deregulation and mitochondrial dysfunction lead to genomic and epigenomic damage.Present study was aimed to establish a molecular link between virusinduced mitochondrial oxidative stress and redox mediated epigenetic regulation among occult hepatitis patients.METHODSThe study was carried out on patients with occult HBV & HCV,chronic HBV & HCV patients and age and gender matched controls (n=10 each).The cells were fixed, permeabilized and incubated with antiH3K9me1, anti-H4K20me3, anti-phospho-H3, anti-ubiquitinated H2A/H2B and anti-phospho-H2AX for different histone modifications.Quantification was done through flow cytometric analysis.Fluorescence tagged immune-stained cells were analyzed for 10000 total events.RESULTS In occult HBV patients, HBV DNA was positive in plasma and peripheral lymphocytes,viral load ranged from 20 to 80 IU/mL. Occult HCV patients were reported to be anti-HCV positive, serum HCV RNA negative, but positive for HCV RNA in peripheral lymphocytes with viral load ranging from 30 to 60 IU/ml. The chronic HBV patients were positive for HBsAg, anti-HBc and HBV DNA and their viral load ranged from 500 to 1000 IU/mL. Chronic HCV patients were positive for anti-HCV and had serum HCV RNA levels ranging from 800 to 1500 IU/ml. The results suggested that desspite low viral load,occult hepatitis B & C infections lead to impaired mitochondrial redox signaling and perturbed epigenetic machinery. Higher levels of 8-oxo-dG and reduced mtDNA copy number suggested functional disruption of mitochondrial assembly among occult HBV/HCV infected patients. While epigenetic perturbations in occult hepatitis patients were indicated by distorted histone patterns. Depending on the specific site and degree of methylation within histone sequence, histone lysine methylation correlates with gene expression leading to repression or activation. We observed a dispersed lysine methylation pattern of monomethylated H4K20 and H3K9 histones, widely known to distinctly mark silent chromatin regions within the mammalian epigenome. CONCLUSION The results suggested that in comparison to control cell population the expression pattern of all four core histones altered distinctly in occult patients. Taken together, present study provides novel insights of deregulated ‘histone code' dynamics in occult hepatitis B/C patients that might play an intermediate step for development and progression of HCC among these patients. The virus induced mitochondrial stress and epigenomic imbalance may provide a breakthrough for prevention and novel therapeutic targets for HCC in occult HBV and HCV infections.
Mo1441 Lymph Node Ratio and Para-Aortic Node Involvement Are Not Independent Predictors of Survival After Resection for Pancreatic Cancer Valentina Beltrame, Mario Gruppo, Michele Valmasoni, Stefano Merigliano, Cosimo Sperti Objectives. Lymph node involvement is an important prognostic factors for pancreatic cancer, and metastases to para-aortic nodes are considered a contraindication to radical surgery. Aim of this study was to analyze the importance of lymph node status in a series of patients who underwent pancreaticoduodenectomy in a single Institution. Methods Between January 2000 and December 2012, 144 patients underwent pancreaticoduodenectomy (PD) with para-aortic nodes dissection for pancreatic adenocarcinoma. Pathologic factors, including stage, nodal status, number of positive nodes and lymph node ratio, invasion of paraaortic nodes, tumor's grading, and radicality of resection were studied by univariate and multivariate analysis. Survival curves were constructed with Kaplan-Meier method and compared with Log-rank test: significance was considered as p<0.05. Results A total of 107 patients (74%) had nodal metastases. Mean and median number of pathologically assessed lymph nodes were 28 and 26, respectively (range 14-63). Twenty-two patients (15%) had para-aortic lymph node involvement. Thirty-three patients (23%) underwent R1 pancreatic resection. One-hundred thirty-two patients recurred and died, two are alive with recurrence, and 10 are alive and free of disease. Overall survival was significantly influenced by grading (p= 0.0001), radicality of resection (p=0.001), stage (p=0.03), lymph node status (p=0.04), paraaortic nodes metastases (p=0.02). Multivariate analysis showed that only grading was an independent prognostic factor for overall survival (p=0.0001), while grading (p=0.0001) and radicality of resection (p=0.01) were prognostic parameters for disease-free survival. Number of metastatic nodes, node ratio, and para-aortic nodes involvement were not independent predictors of disease-free and overall survival. Conclusion In this experience the number of positive lymph nodes did not have prognostic implication in patients with node positive pancreatic cancer. Although lymph node status and para-aortic node metastases were associated with poor survival at univariate analysis, they were not independent prognostic index. So, the decision to perform pancreatic resection should not be taken on the basis of lymph node status only.
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Mo1444 Clinico-Pathological Features and Survival of Resected Pancreatic Neuroendocrine Tumors Associated With Von Hippel Lindau Disease and Multiple Endocrine Neoplasia Type 1 Ilaria Pergolini, Othon Iliopoulos, Cristina R. Ferrone, Vikram Deshpande, Keith D. Lillemoe, Carlos Fernandez-del Castillo Patients with von Hippel Lindau disease (VHL) and multiple endocrine neoplasia 1 (MEN1) are at a risk of developing pancreatic neuroendocrine tumors (PNETs), which may behave in a malignant fashion. We retrospectively evaluated a 15-year experience with resected PNETs associated with these genetic syndromes. Between January 2001 and November 2015, 334 patients underwent resection for a PNET at a single institution. 10 of these had VHL (3%) and 24 MEN1 (7%). 1 patient in each group was found to have distant metastases at the time of diagnosis. Age at diagnosis of PNET in patients with VHL was 17 years younger than in MEN1 (30.5 vs 47.5 years, p=0.1), although the age at the diagnosis of the inherited syndrome was similar (27 vs 27.5 years). Median time of observation between diagnosis and surgical resection was 14 months (2-153) in VHL cases and 1.5 months (0-96) in MEN1 patients (p=0.002). PNETs led to the diagnosis of the genetic syndrome in only one (10%) patient with VHL and in 9 (37.5%) patients with MEN1; 7 of these were functioning tumors. Family history was positive in 90% of VHL patients and in 71% of those with MEN1; the median size of the largest tumor was 2.4 cm (1.8-4.2) and 2.8 cm (0.7-9.0), respectively
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(p=0.353). PNETs were frequently multifocal, particularly in MEN1 (54% vs 30%, p=0.270). In VHL, PNET was more frequently associated with multifocal cystic lesions (60% vs 4%, p=0,001). Distal pancreatectomy was the most frequent procedure (50% in VHL and 59% in MEN1). Invasive lesions represented almost 60% of cases in both groups. Lymph nodes were positive in 30% and 25% of patients, respectively. There were no post-operative deaths, but morbidity occurred in 5 patients with VHL (50%) and in 21% of MEN1 patients. Median follow-up was 25 months (1-126) for VHL patients and 73.5 months (2-169) in the MEN1 group (p=0.259); during follow-up, 1 (10%) and 6 (25%) patients, respectively, experienced recurrence, and 1 patient in each group died of the disease. No correlation between size of the tumor and recurrence was found. Median disease free survival was 25 (1-126) and 56.5 (2-146) months, respectively. Conclusions. 10% of resected PNETs are associated with either VHL or MEN1. Both require careful management due to their malignant potential, young age of diagnosis, frequent multifocal presentation and risk of recurrence.
Mo1447 Graded Morbidity Profiles for Duodenum Preserving Pancreatic Head Resection Are Equivalent To Those For Pancreaticoduodenectomy In HeadDominant Chronic Pancreatitis Olga Kantor, Jeffrey B. Matthews, Mark S. Talamonti, Waseem Lutfi, Marshall Baker Background: European randomized trials have compared duodenum preserving pancreatic head resection (DPPHR) to pancreaticoduodenectomy (PD) for management of head-dominant chronic pancreatitis (HDCP). These consistently demonstrate the improvements in pancreatitic pain and quality of life in DPPHR to be comparable to those following PD. Few studies from American centers have compared perioperative outcomes and no studies have graded the severity of postoperative complications following these procedures. Methods: Medical records for patients undergoing either DPPHR or PD for HDCP between 2006 and 2014 were reviewed to capture all complications, postoperative interventions and 90-day readmission events. Clavien-Dindo grade IIIb, IV and V complications were classified as severe adverse postoperative outcomes (SAPO). Grade I, II, and IIIa complications requiring either prolonged length of stay (LOS) including readmissions (>3 standard deviations beyond the mean for patients without complications) or >1 interventional procedure were also classified as SAPO. All others were considered minor adverse outcomes (MAPO). Results: 27 patients underwent DPPHR (3 Beger, 8 Berne, and 16 Frey procedures) and 20 underwent PD (12 standard, 8 pylorus-preserving). Patients undergoing DPPHR were less likely to have had significant weight loss prior to surgery than those undergoing PD (15% vs 50%, p= 0.01). There were no other significant differences between surgical cohorts with regard to preoperative patient demographics, comorbidities including pre-existing diabetes and pancreatic exocrine insufficiency, alcohol history, or previous pancreatic surgery. There were no significant differences in rates of transfusion (7% vs 15%, p=0.64), postoperative complication (70% vs 60%, p=0.54), 90-day readmission (22% vs 20%, p=0.55), total LOS including readmissions (10.8 ± 5.4 vs 12.1 ± 6.8, p=0.43) or 90-day mortality (4% vs 0%, p=0.58) between groups. Patients undergoing DPPHR were less likely to suffer a postoperative pneumonia than those undergoing PD (0% vs 25%, p=0.01). Postoperative pancreatic fistula was infrequent in both groups (0% for DPPHR vs 10% for PD, p=0.18). There was a trend towards fewer SAPO among patients undergoing DPPHR although this did not reach significance (33% vs 50%, p=0.11). Multivariate regression adjusting for demographics, comorbidities, presenting symptoms, intraoperative blood loss, and procedure performed found no significant independent predictors of SAPO. Conclusions: Although there is a trend towards a lower severity complication profile among patients undergoing DPPHR, graded 90-day perioperative outcomes of DPPHR are equivalent to those of PD. DPPHR procedures are performed seldomly in the United States. At experienced centers, these procedures are safe and provide complication profiles similar to more traditional surgical approaches to HDCP.
Mo1445 Impact of Fellow vs. Resident Assistance on Outcomes Following Pancreaticoduodenectomy Christian Schmidt, Andrea Jester, Catherine Chung, Alexandra M. Roch, Rosalie Carr, E M. Kilbane, Michael G. House, Nicholas J. Zyromski, Attila Nakeeb, C. Max Schmidt, Eugene P. Ceppa Purpose: Participation by residents and fellows in procedures of higher complexity is key to their development as future practicing surgeons. The impact of experience on outcomes of pancreaticoduodenectomy (PD) has been clearly shown in a number of studies. The impact of surgical fellows vs. general surgery resident assistance in outcomes in PD has not been studied. The purpose of this study was to determine if there were significant differences in patient outcomes following pancreaticoduodenectomy as a function of hepatopancreatobiliary surgery fellow vs. general surgery resident intraoperative assistance. Methods: Consecutive cases of PD (n=220) were reviewed at a single high-volume institution over an 18month period (July 2013-December 2014). Inclusion criteria consisted of any patient who underwent a PD with involvement of a surgical trainee. Thirty-day outcomes were monitored through the American College of Surgeon's National Surgical Quality Improvement Program (NSQIP); all PD are tracked using NSQIP. Quality In-Training Initiative (QITI) is a novel component of NSQIP with a variable that included documenting the PGY level of the trainee assisting in the case. As a result, we are able to distinguish the exact PGY level per case. Each faculty member performing PD is beyond the learning curve of 60 cases. Two-way statistical analyses were used to compare categories. Results: The hepatopancreatobiliary surgery fellows and general surgery residents participated in n=98 and n=122, PD respectively. There were no statistical differences in demographics, BMI, ASA score, or any other preoperative variable between groups. Intraoperative variables were nearly identical: median operative time (275 + 10 vs. 285 + 10 minutes), rate of transfusion (25% vs. 25%), and mean units of blood transfused (4.1 + 0.3 vs. 5.1 + 0.65 units) for fellows vs. residents respectively. Post-operative outcomes were similar and are listed in the table. Conclusions: These results suggest that in the training environment that either dedicated hepatopancreatobiliary surgery fellows or general surgery residents are of comparable safety as assistants to performing pancreaticoduodenectomy. Table
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Background: The association between postoperative inflammatory markers and risk of complications after pancreaticoduodenectomy (PD) is controversial. We sought to assess the diagnostic value of perioperative C-reactive protein (CRP) and procalcitonin (PCT) levels in the early identification of patients at risk for complications after pancreaticoduodenectomy (PD). Method: In 2014, 84 patients undergoing elective PD were enrolled in a prospective database. Clinicopathological characteristics, CRP and PCT, as well as short-term outcomes, such as complications and pancreatic fistula, were analyzed. Complications and pancreatic fistula were defined based on the Clavien-Dindo classification and the International Study Group on Pancreatic Fistula (ISGPF) classification, respectively. High CRP and PCT were classified using cut-off values based on ROC curve analysis. Results: The majority (73.8%) of patients had pancreatic adenocarcinoma. CRP and PCT levels over the first 5 post-operative days (POD) were higher among patients who experienced a complication versus those who did not (p<0.001). Postoperative CRP and PCT levels were also higher among patients who developed a grade B or C pancreatic fistula (p<0.05). A CRP concentration >84 mg/l on POD 1 (AUC 0.77) and >127 mg/l on POD 3 (AUC 0.79) was associated with the highest risk of overall complications (OR 6.86 and 9.0, respectively; both p<0.001). Similarly patients with PCT > 0.7 mg/dl on POD 1 (AUC 0.67) were at higher risk to develop a postoperative complication (OR 3.33; p=0.024). On POD 1 a CRP > 92 mg/l (AUC 0.72) and a PCT > 0.4 mg/dl (AUC 0.70) were associated with the highest risk of pancreatic fistula (OR 5.63 and 5.62 respectively; both p<0.05). Conclusion: CRP and PCT concentration were associated with an increased risk to develop complications and clinical relevant pancreatic fistula after PD. Use of these biomarkers may help identify those patients at highest risk for perioperative morbidity and help guide postoperative management of patients undergoing PD.
Mo1446 Prospective Randomized Study Comparing Outcome of Duodenum Preserving Pancreatic Head Coring With Duodenum Preserving Pancreatic Head and Body Coring in Chronic Pancreatitis Vikash Moond, Rajesh Gupta, Surinder S. Rana, Ritambhra Nada, Mandeep Kang, Rajinder Singh, Deepak K. Bhasin Introduction:- Chronic pancreatitis is a progressive inflammatory disease with uncertain course. There is no single effective surgery for the variable structural abnormalities associated with this disease. The aim of this study is to ascertain whether more extensive pancreatic resection would lead to better outcome in terms of post-op pain control, exocrine and endocrine deficiency, morbidity and mortality. Methodology:- 20 patients of chronic pancreatitis undergoing surgery were randomly allocated into 2 groups to undergo head coring or head and body coring and were followed post-operatively at 1, 3 and 6 months. Pain score, exocrine and endocrine function and quality of life were assessed for the 2 groups. Results:A total of 20 patients were divided in two groups. Four females and six males were included in each study group. Duration of surgery (p=1.0), intra-operative blood loss (p=1.0), postop bleeding (p=1.0) and anastomotic leak (p=1.0) were not significantly different between the two groups. There were 2 postoperative deaths in the group undergoing head and body coring and 1 death in the group, which underwent head coring (p=1). Post-operative pain control was comparable in the two groups (p=0.478). Exocrine (p=1.0) and endocrine (p= 1.0) functions were also comparable between the two groups at 6 months follow up. Quality of life analysis will be presented during meeting. Conclusion:- More extensive pancreatic resection does not lead to increased operative mortality and increased morbidity in the immediate post operative period. Long term follow up will be required to assess the effect of extensive pancreatic coring on pain control, exocrine and endocrine deficiency which were not different at 6-month follow up.
Mo1449 How Can We Measure Learning Curves in Complex Laparoscopic Pancreas Resections? Uwe A. Wittel, Simon Küsters, Frank Makowiec, Tobias Keck, Ulrich T. Hopt Background: Laparoscopic pancreas resections however, greatly vary in their technical difficulty. This implies that surgeons have to wisely select appropriate patients according to their technical skill while they pass through their individual learning curve. With our analyses we try to identify parameters that are indicators of success during the personal learning curve using 2 independent learning curves with 30 hybrid laparoscopically assisted pancreatoduodenectomies for each surgeon. Material and Methods: Between 2010 and 2015 106 laparoscopic hybrid pancreatoduodenectomies with open reconstruction were performed at the Clinic of General and Visceral Surgery, University of Freiburg. These operations were performed by two surgeons independently responsible for patient selection and operative
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SSAT Abstracts
C-Reactive Protein and Procalcitonin As Predictors of Postoperative Inflammatory Complications After Pancreatic Surgery Giardino Alessandro, Gaya Spolverato, Paolo Regi, Isabella Frigerio, Filippo Scopelliti, Roberto Girelli, Timothy M. Pawlik, Paolo Pederzoli, Giovanni Butturini