The Use of Noninvasive Scores in Predicting NAFLD Progression After Bariatric Surgery.

BACKGROUND: Bariatric surgery has been postulated to impact liver function resulting in favorable effects on nonalcoholic fatty liver disease (NAFLD). We aimed to analyze the long-term impact of bariatric surgery on noninvasive scores predicting the progression of liver fibrosis in a bariatric population. METHODS: We retrospectively reviewed the records of patients without pre-existing liver disease who underwent sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) at our center between 2010 and 2018. Four predictive scores for liver fibrosis (AST/ALT, APRI, Fib-4, and BARD) were calculated preoperatively, 6 months post-operatively, and annually up to 5 years. Correlations were analyzed with Pearson R. Subgroup and sensitivity analyses were performed to identify populations at increased risk. RESULTS: A total of 2769 patients were included. The mean age was 40 years, and the majority was females (88.5%) and of Hispanic ethnicity (59.2%). There was a steady post-operative increase in the percentage of patients at increased risk of progression of liver fibrosis. The Fib-4 score showed the largest increase in the population at risk for liver fibrosis (11.3% preoperatively to 28.9% at 5 years). Patients with diabetes and those who underwent a sleeve gastrectomy continued to display a higher risk for liver fibrosis than did patients without diabetes and those who underwent RYGB, respectively. CONCLUSION: There was an overall trend to increased liver fibrosis scores over the 5-year post-operative follow-up, but this increase remained lower than that reported in previous literature. Bariatric surgery offers NAFLD risk reduction in a high-risk population.

Weight Loss Outcomes following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in an Ethnically Diverse Bariatric Population: Which Is More Effective?

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) have comparable weight loss outcomes in a general bariatric population. OBJECTIVES: This study aimed to investigate whether similar outcomes can be observed in Hispanic and African American population. Settings. Community Hospital in New York, New York, United States. METHODS: The 5-year prospective data of patients who underwent LRYGB and LSG at a single center were retrospectively reviewed. The long-term weight loss outcomes between patients who had LRYGB and LSG were compared after adjusting for age, sex, race, diabetes mellitus, and hypertension with the linear mixed-effects or logistic regression model. RESULTS: Most patients were Hispanic (59.2%) and African American (22.7%). The mean% total weight loss (%TWL) values of patients with BMI <45 kg/m2 who underwent LRYGB and LSG were 73% and 62% after 1 year, 69% and 56% after 2 years, and 71% and 54% after 5 years, respectively. In patients with a BMI of 45-50 kg/m2 who underwent LRYGB and LSG, the mean %TWL values were 69% and 56% after 1 year, 75% and 58% after 2 years, and 57% and 45% after 5 years, respectively. Meanwhile, the %TWL values of patients with BMI >50 kg/m2 who had LRYGB and LSG were 53% and 42% after 1 year, 53% and 45% after 2 years, and 49% and 36% after 5 years, respectively. All results were statistically significant (p < 0.0001) and remained valid after adjusting for cofactors. CONCLUSION: Thus, LRYGB had consistent and sustained long-term weight loss outcomes compared with LSG in a predominantly ethnically diverse patient population with different BMI. Our study had several limitations in that it is retrospective in nature and some patients were lost to follow-up during the study period.

Bariatric Surgery Improves Renal Function: a Large Inner-City Population Outcome Study.

BACKGROUND: Bariatric surgery is associated with improved renal dysfunction in general population studies. The study examined the effects of bariatric surgery on renal function in a predominantly Hispanic and African American population at a community hospital in New York, USA. METHODS: This retrospective study analyzed prospectively collected bariatric surgical data from 2247 patients (89% female) who underwent bariatric surgery at a single center. Changes in glomerular filtration rate (eGFR), urine albumin-creatinine ratio (UACR), micro- and macroalbuminuria, and hyperfiltration, which were measured preoperatively and then yearly for 3 years postoperatively, were evaluated with t tests and logistic regression analysis, after adjusting for confounding variables. The mean age of the patients at surgery was 37.1 years; the mean preoperative body mass index was 45 ± 7 kg/m2. RESULTS: The results obtained 3 years postoperatively showed the following significant improvements compared with the preoperative values: mean UACR decreased from 40.3 to 11.1 mg/g, mean eGFR improved from 79.4 to 87.3 mL/min, the prevalence of microalbuminuria decreased from 13.7 to 6.2%, the prevalence of macroalbuminuria decreased from 2.5 to 0%, and the prevalence of hyperfiltration decreased from 4.4 to 2.7% (all P < .0001). In adjusted multivariate regression analysis, these results remained significant after adjusting for age, sex, race, type of surgery, and presence of diabetes mellitus or hypertension. CONCLUSION: In this large study at an inner-city hospital, bariatric surgery was associated with significant improvements in renal dysfunction parameters. These results could assist with informed decisions regarding indications for bariatric surgery.

Improvement in glycated hemoglobin A1C after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy in an ethnically diverse population with diabetes.

BACKGROUND: Obesity is a well-known risk factor for the development of type 2 diabetes. The efficacy of bariatric surgery in reducing weight with resulting improvement in type 2 diabetes has been reliably demonstrated. OBJECTIVES: We investigated and compared the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) on glycated hemoglobin (HbA1C) levels in a predominantly Hispanic and black population. SETTINGS: Community Hospital in New York, New York, United States. METHODS: This is a retrospective review of a 5-year data from a single center where patients with diabetes who underwent LRYGB or LSG were included. HbA1C levels and body mass index were analyzed preoperatively and then annually postoperatively for up to 5 years. Improvements in HbA1C were compared between the 2 groups after adjusting for age, sex, race, and hypertension with linear mixed-effects or logistic regression models. RESULTS: Of the 676 included patients, 84.8% were females and the mean age was 47 years. HbA1C levels decreased significantly (P < .05) in the entire group at 1 (21%), 2 (20%), 3 (20%), 4 (18%), and 5 (14%) years. Compared with LSG, LRYGB patients displayed greater improvement in HbA1C levels at 1 year (25% versus 17%, P = .001). The differences in the reduction of HbA1C between LRYGB and LSG for the other time intervals were not significant (P > .05), 24% versus 17% (2 yr), 22% versus 16% (3 yr), 22% versus 13% (4 yr), and 17% versus 10% (5 yr). Changes in body mass index were not correlated to changes in HbA1C at various study points. CONCLUSION: Both LRYGB and LSG resulted in significant decreases in HbA1C levels and are correlated with changes in body mass index. LRYGB had the greatest effect at 1 year postoperatively. There was no significant difference in HbA1C reduction for LRYGB and LSG after 1 year postoperatively in this predominantly Hispanic and black cohort.

Thyroid Lobectomy for T1b-T2 Papillary Thyroid Cancer with High-Risk Features.

BACKGROUND: Thyroid lobectomy (TL) has been proposed as definitive surgical treatment for papillary thyroid cancers (PTC) up to 4 cm. This study evaluates the use and appropriateness of TL for T1b and T2 PTC. STUDY DESIGN: The National Cancer Database was interrogated for adult patients having TL for T1b-T2 PTC between 2004 and 2014. Patients who should have undergone total thyroidectomy (TT) instead of lobectomy based on high-risk tumor features were identified. The 2 groups were compared for clinical and demographic characteristics, and overall survival. RESULTS: Of 8,083 patients undergoing lobectomy, 1,552 patients had high-risk features and should have undergone TT. These included 194 with cN1, 571 with pN1, 307 with lymphovascular invasion (LVI), 645 with extra thyroidal extension (ETE), 567 with positive margins, 42 with poorly differentiated PTC, and 25 with M1 disease. At 10 years of follow-up, 92.4% of appropriate lobectomy (aTL) patients were alive compared with 88.5% of inappropriate lobectomy (iTL) patients (p < 0.001). On univariate and multivariable Cox survival analysis, age greater than 45 years, male sex, comorbidities, government or no insurance, low income, and tumor size >2 cm were associated with poorer survival (all p < 0.05). Thyroid lobectomy patients with high-risk features had significantly higher mortality on unadjusted (hazard ratio [HR] 1.98, 95% CI 1.52 to 2.59, p < 0.001) and adjusted survival analysis (HR 1.97, 95% CI 1.51 to 2.58, p < 0.001). Total thyroidectomy with radioiodine treatment had improved overall survival in comparison to iTL (HR 0.65, 95% CI 0.51 to 0.83, p < 0.001). CONCLUSIONS: A substantial number of patients (19.2%) with tumor size >1 cm and high-risk features undergo thyroid lobectomy for PTC. Exclusion of high-risk features is important when adopting lobectomy as the definitive surgical therapy for T1b and T2 PTC because they have a potential adverse effect on long-term survival.

Preoperative versus intraoperative diagnosis of hiatal hernia in bariatric population.

BACKGROUND: Hiatal hernia is frequently encountered intraoperatively during bariatric surgery. There is scarce research pertaining to the diagnostic accuracy of a preoperative diagnostic modality in comparison to intraoperative diagnosis, along with patient characteristics and related factors contributing to hiatal hernia. OBJECTIVE: To identify the prevalence and associations of hiatal hernia in the bariatric patient population, we compared the diagnostic accuracy of upper gastrointestinal series and esophagogastroduodenoscopy with the intraoperative findings across various patient characteristics. SETTING: Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program, Teaching Hospital, New York, USA. METHODS: Retrospective study of patients from 2015 to 2018 who met National Institutes of Health criteria for bariatric surgery. RESULTS: There were 1094 patients included (135 males, 959 females), with an age range of 18 to 74 years. The diagnostic accuracy was determined by a sensitivity of 64.71% (95% confidence interval [CI] .55-.70), specificity of 74.38% (95% CI .71-.70), positive predictive value of 29.86% (95% CI .24-.30), negative predictive value of 92.59% (95%CI .89-90), likelihood ratio of 2.526, and P value < .0001 for esophagogastroduodenoscopy; a sensitivity of 14.02% (95% CI .08-0), specificity of 98.23% (95% CI .96-.90), positive predictive value of 71.43% (95% CI .50-.80), negative predictive value of 78.35% (95% CI .74-.80), likelihood ratio 7.921, and P value < .0001 were used for upper gastrointestinal series. Hiatal hernia with age <60 years was 17.09% versus 48.44% at >60 years (P < .0001). Hiatal hernia incidence was 17% in Hispanics, 22.5% in Caucasians, and 23.10% in blacks. CONCLUSION: The prevalence of hiatal hernia is 18.92%. There is strong association between hiatal hernia and age and ethnicity and no association based on sex and body mass index. The diagnostic accuracy of upper gastrointestinal series is very low compared with that of esophagogastroduodenoscopy for hiatal hernia. Preoperative diagnosis of hiatal hernia in the bariatric population is not required based on our study. Not only does it lessen the economic burden, patient wait time, and discomfort of an additional study, but preoperative diagnosis does not change, alter, or aid in the intraoperative management of hiatal hernia considering the suboptimal accuracy of preoperative diagnostics, thus deeming them unwarranted.

ReShape Intragastric Balloon Complicated by Gastric Perforation and Peritonitis.

BACKGROUND: Obesity is a growing global epidemic with tremendous financial burden and health care costs worldwide. Restrictive surgery has emerged as the definitive treatment option to combat morbid obesity and its associated comorbidities. The advent of endoscopy has new grounds in obesity with the introduction of inflatable balloon placed in the stomach that decreases satiety by volume restriction. MATERIALS AND METHODS: We report a first case of gastric perforation with peritonitis after ReShape intragastric balloon placement that needed emergent surgical intervention. Decision was made to proceed with exploratory laparotomy, device deflation, and removal with subsequent gastric defect repair. RESULTS: Postoperative period was uneventful, drain was removed on postoperative day 2, and patient tolerated diet and was discharged home subsequently. Biopsy of the perforation site demonstrated mild non-specific chronic gastritis. CONCLUSION: In the modern era of minimal invasiveness, any new approach would roar popularity among patients and hence is of utmost importance for clinicians to be constantly educated on scientific research and innovations in their field.

CONCORDANCE OF PRE-OPERATIVE CLINICAL STAGE WITH PATHOLOGIC STAGE IN PATIENTS ≥45 YEARS OLD WITH WELL-DIFFERENTIATED THYROID CANCER.

OBJECTIVE: Clinical stage (cStage) in thyroid cancer determines extent of surgical therapy and completeness of resection. Pathologic stage (pStage) is an important determinant of outcome. The rate of discordance between clinical and pathologic stage in thyroid cancer is unknown. METHODS: The National Cancer Data Base was queried to identify 27,473 patients ≥45 years old with cStage I through IV differentiated thyroid cancer undergoing surgery from 2008-2012. RESULTS: There were 16,286 (59.3%) cStage I patients; 4,825 (17.6%) cStage II; 4,329 (15.8%) cStage III; and 2,013 (7.3%) cStage IV patients. The upstage rate was 15.1%, and the downstage rate was 4.6%. For cStage II, there was a 25.5% upstage rate. The change in cStage was a result of inaccurate T-category in 40.8%, N-category in 36.3%, and both in 22.9%. On multivariate analysis, the patients more likely to be upstaged had papillary histology, tumors 2.1 to 4 cm, total thyroidectomy, nodal surgery, positive margins, or multifocal disease. Upstaged patients received radioiodine more frequently (75.3% vs. 48.1%; P<.001). CONCLUSION: Approximately 20% of cStage is discordant to pStage. Certain populations are at risk for inaccurate staging, including cT2 and cN0 patients. Upstaged patients are more likely to receive radioactive iodine therapy. ABBREVIATIONS: CI = confidence interval; cStage = clinical stage; DTC = differentiated thyroid cancer; NCDB = National Cancer Data Base; OR = odds ratio; pStage = pathologic stage; RAI = radioactive iodine.

Preoperative adrenal biopsy does not affect overall survival in adrenocortical carcinoma.

BACKGROUND: The impact of preoperative biopsy on overall survival (OS) in adrenocortical carcinoma (ACC) is unclear. We analyzed the National Cancer Data Base (NCDB) for factors associated with preoperative adrenal biopsy and its effect on OS in ACC. METHODS: The NCDB was queried from 2003 to 2012 for M0 ACC. Patients with or without preoperative biopsy were compared for factors associated with an increased rate of biopsy. Survival analysis was performed after adjusting for patient and tumor-related variables. RESULTS: There were 1782 patients with M0 ACC of whom 332 (19%) had a preoperative biopsy. Treatment outside academic cancer centers (OR 1.36, 95% CI 1.04-1.77, P = 0.023) and male gender (OR 1.45, 95% CI 1.11-1.88, P = 0.006) were associated with an increased rate of biopsy. In patients undergoing adrenalectomy with negative margins, biopsy failed to impact OS (log-rank P = 0.225, HR 1.20, 95% CI 0.84-1.72, P = 0.306). CONCLUSIONS: Preoperative adrenal biopsy continues to be performed for ACC with no added survival benefit. Adrenalectomy offers the best chance of survival in patients with ACC.

Timing of Adjuvant Radioactive Iodine Therapy Does Not Affect Overall Survival in Low- and Intermediate-Risk Papillary Thyroid Carcinoma.

There is no consensus regarding the timing of adjuvant radioactive iodine therapy (RAI) therapy in low- and intermediate-risk papillary thyroid carcinoma (PTC). We analyzed the impact of adjuvant RAI on overall survival (OS) in low- and intermediate-risk PTC. The National Cancer Data Base was queried from 2004 to 2011 for pN0M0 PTC patients having near/subtotal or total thyroidectomy and adjuvant RAI. Tumors ≤1 cm with negative margins were low risk while 1.1- to 4-cm tumors with negative margins or ≤1 cm with microscopic margins were termed intermediate risk. RAI in ≤3 months and between 3 and 12 months was termed as early and delayed, respectively. Survival analysis was performed after adjusting for patient and tumor-related variables. There were 7,306 low-risk and 16,609 intermediate-risk patients. Seventeen per cent low-risk and 15 per cent intermediate-risk patients had delayed RAI. Kaplan-Meier analysis did not show a difference in OS for early versus delayed RAI administration in low- (10-year OS 94.5% vs 94%, P = 0.627) or intermediate-risk (10-year OS 95.3% vs 95.9%, P = 0.944) patients. In adjusted survival analysis, RAI timing did not affect OS in all patients (hazard ratios = 0.98, 95% confidence interval = 0.71-1.34, P = 0.887). In conclusion, the timing of postthyroidectomy adjuvant RAI therapy does not affect OS in low- or intermediate-risk PTC.

TIMING OF RADIOACTIVE IODINE THERAPY DOES NOT IMPACT OVERALL SURVIVAL IN HIGH-RISK PAPILLARY THYROID CARCINOMA.

OBJECTIVE: Postthyroidectomy radioiodine (RAI) therapy is indicated for papillary thyroid carcinoma (PTC) with high-risk features. There is variability in the timing of RAI therapy with no consensus. We analyzed the impact of the timing of initial RAI therapy on overall survival (OS) in PTC. METHODS: The National Cancer Data Base (NCDB) was queried from 2003 to 2006 for patients with PTC undergoing near/subtotal or total thyroidectomy and RAI therapy. High-risk patients had tumors >4 cm in size, lymph node involvement, or grossly positive margins. Early RAI was ≤3 months, whereas delayed was between 3 and 12 months after thyroidectomy. Kaplan-Meier (KM) and Cox survival analyses were performed after adjusting for patient and tumor-related variables. A propensity-matched set of high-risk patients after eliminating bias in RAI timing was also analyzed. RESULTS: There were 9,706 patients in the high-risk group. The median survival was 74.7 months. KM analysis showed a survival benefit for early RAI in high-risk patients (P = .025). However, this difference disappeared (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.98-1.62, P = .07) on adjusted Cox multivariable analysis. Timing of RAI therapy failed to affect OS in propensity-matched high-risk patients (HR 1.09, 95% CI 0.75-1.58, P = .662). CONCLUSION: The timing of postthyroidectomy initial RAI therapy does not affect OS in patients with high-risk PTC. ABBREVIATIONS: CI = confidence interval CLNM = cervical lymph node metastasis FVPTC = follicular variant papillary thyroid carcinoma HR = hazard ratio KM = Kaplan-Meier NCDB = National Cancer Data Base OS = overall survival PTC = papillary thyroid carcinoma RAI = radioactive iodine.

Risk factors for central lymph node metastasis in papillary thyroid carcinoma: A National Cancer Data Base (NCDB) study.

BACKGROUND: There is no consensus regarding prophylactic central lymph node dissection (pCLND) in patients with papillary thyroid carcinoma (PTC). Identification of risk factors for central lymph node metastasis (CLNM) in patients with PTC could assist surgeons in determining whether to perform selective pCLND. METHODS: The National Cancer database was queried from 1998 to 2011 for patients with clinical staging T1-4cN0M0 PTC. All patients underwent near, sub-, or total thyroidectomy with or without pCLND. Univariate and multivariable logistic regressions were performed on the following clinical variables: age, sex, race and tumor size as risk factors for pathologic CLNM (pN1a). RESULTS: In 39,562 patients with T1-4cN0M0 PTC, 61% underwent pCLND. Patients with age >45 years, African American race, tumor size ≤ 1 cm, unifocal tumors, follicular variant PTC, no insurance, and treatment at community cancer facilities were less likely to have pCLND (P < .001). In the pCLND group, 15.6% of patients had CLNM. On adjusted multivariable logistic regression, age ≤ 45 years, Asian race, male sex, and larger tumors were statistically significantly associated with CLNM. CONCLUSION: Age ≤ 45 years, Asian race, male sex, and larger tumors are associated with the presence of CLNM, which allows for selective pCLND in PTC.

Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer.

AIM: To develop a panel of blood-based diagnostic biomarkers consisting of circulating microRNAs for the detection of pancreatic cancer at an early stage. METHODS: Blood-based circulating microRNAs were profiled by high throughput screening using microarray analysis, comparing differential expression between early stage pancreatic cancer patients (n = 8) and healthy controls (n = 11). A panel of candidate microRNAs was generated based on the microarray signature profiling, including unsupervised clustering and statistical analysis of differential expression levels, and findings from the published literature. The selected candidate microRNAs were then confirmed using TaqMan real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) to further narrow down to a three-microRNA diagnostic panel. The three-microRNA diagnostic panel was validated with independent experimental procedures and instrumentation of RT-qPCR at an independent venue with a new cohort of cancer patients (n = 11), healthy controls (n = 11), and a group of high risk controls (n = 11). Receiver operating characteristic curve analysis was performed to assess the diagnostic capability of the three-microRNA panel. RESULTS: In the initial high throughput screening, 1220 known human microRNAs were screened for differential expression in pancreatic cancer patients versus controls. A subset of 42 microRNAs was then generated based on this data analysis and current published literature. Eight microRNAs were selected from the list of 42 targets for confirmation study, and three-microRNAs, miR-642b, miR-885-5p, and miR-22, were confirmed to show consistent expression between microarray and RT-qPCR. These three microRNAs were then validated and evaluated as a diagnostic panel with a new cohort of patients and controls and found to yield high sensitivity (91%) and specificity (91%) with an area under the curve of 0.97 (P < 0.001). Compared to the CA19-9 marker at 73%, the three-microRNA panel has higher sensitivity although CA19-9 has higher specificity of 100%. CONCLUSION: The identified panel of three microRNA biomarkers can potentially be used as a diagnostic tool for early stage pancreatic cancer.

Robotic distal pancreatectomy.

BACKGROUND: A robotic-assisted minimal invasive approach has the potential to overcome the limitations of conventional laparoscopic pancreatectomies. We analyzed the outcomes of robotic-assisted distal pancreatectomies (RDPs) to demonstrate the safety and feasibility of robotic distal pancreas resection, including spleen preservation. METHODS: We performed a descriptive retrospective analysis of 40 RDPs. Statistical comparisons were performed between two groups of patients undergoing robotic-assisted spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (SDP). Survival analysis was performed using the Kaplan-Meier method. RESULTS: Of 49 attempted RDPs, 40 were completed with robotic assistance, with a conversion rate of 18.4%. Compared with the published reports of laparoscopic distal pancreatotomy (DP) and robotic DP, the spleen preservation rate (30%), operating time (203 minutes), major complications rate (5%), fistula rate (20%), and length of hospital stay (5 days) were similar in our RDP patients. Also, the perioperative outcomes of the SPDP and SDP groups did not differ significantly. The median survival was 12.5 months for the patients undergoing RDP for pancreatic ductal adenocarcinoma. CONCLUSIONS: Robotic-assisted distal pancreatectomy, with or without splenic preservation, can be safely performed for lesions of the distal pancreas, with appropriate indications.

The use of angiogenic-antimicrobial agents in experimental wounds in animals: problems and solutions.

A topical combination (silvathymosin) of natural proangiogeneic protein thymosin ß4 (Tß4) and antimicrobial silver sulfadiazine was hypothesized to promote the healing of large, full-thickness, clean or infected wounds in rats. Silvathymosin showed the fastest wound healing (85%) followed by silver sulfadiazine (84%) and Tß4 (72%). In the infected groups, the healing pattern was different, as Tß4 and silvathymosin groups did not show similar wound healing. Wound histopathology and VEGF and KI67 immunohistochemical assessment of angiogenesis was consistent and correlated well with the tempo of healing of the acute wounds. These preliminary data demonstrate the more rapid acute wound healing properties of the combination formulation of thymosin ß4 and silver sulfadiazine as compared to these agents alone. This novel agent could prove an effective treatment modality for debilitating chronic wounds and decubitus ulcers.

RAGE gene deletion inhibits the development and progression of ductal neoplasia and prolongs survival in a murine model of pancreatic cancer.

BACKGROUND: The receptor for advanced glycation end-products (RAGE) is implicated in pancreatic tumorigenesis. Activating Kras mutations and p16 inactivation are genetic abnormalities most commonly detected as pancreatic ductal epithelium progresses from intraepithelial neoplasia (PanIN) to adenocarcinoma (PDAC). OBJECTIVE: The aim of this study was to evaluate the effect of RAGE (or AGER) deletion on the development of PanIN and PDAC in conditional Kras ( G12D ) mice. MATERIALS AND METHODS: Pdx1-Cre; LSL-Kras ( G12D/+) mice were crossed with RAGE (-/-) mice to generate Pdx1-Cre; LSL-Kras ( G12D/+) ; RAGE (-/-) mice. Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-) mice were crossed with RAGE (-/-) mice to generate Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (-/-) mice. Pancreatic ducts were scored and compared to the relevant RAGE (+/+) controls. RESULTS: At 16 weeks of age, Pdx1-Cre; LSL-Kras ( G12D/+); RAGE (-/-) mice had significantly fewer high-grade PanIN lesions than Pdx1-Cre; LSL-Kras ( G12D/+); RAGE (+/+) controls. At 12 weeks of age, none of the Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (-/-) mice had PDAC compared to a 45.5% incidence of PDAC in Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (+/+) controls. Finally, Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (-/-) mice also displayed markedly longer median survival. CONCLUSION: Loss of RAGE function inhibited the development of PanIN and progression to PDAC and significantly prolonged survival in these mouse models. Further work is needed to target the ligand-RAGE axis for possible early intervention and prophylaxis in patients at risk for developing pancreatic cancer.