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Given the exponentially aging population and rising life expectancy in the United States, surgeons are facing a challenging frail population who may require surgery but may not qualify based on their general fitness. There is an urgent need for greater awareness of the importance of frailty measurement and the implementation of universal assessment of frail patients into clinical practice. Pairing risk stratification with stringent protocols for prehabilitation and minimally invasive surgery and appropriate enhanced recovery protocols could optimize and condition frail patients before, during, and immediately after surgery to mitigate postoperative complications and consequences on patient function and quality of life. In this paper, highlights from the 2022 Society for Surgery of the Alimentary Tract State-of-the-Art Session on frailty in surgery are presented. This work aims to improve the understanding of the impact of frailty on patients and the methods used to augment the outcomes for frail patients during their surgical experience. [ABSTRACT FROM AUTHOR]

Introduction: Preoperative eGFR has been found to be a reliable predictor of post-operative outcomes in patients with normal creatinine levels who undergo surgery. The aim of our study was to evaluate the impact of preoperative eGFR levels on short-term post-operative outcomes in patients undergoing pancreatectomy. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) pancreatectomy file (2014–2017) was queried for all adult patients (age ≥ 18) who underwent pancreatic resection. Patients were stratified into two groups based on their preoperative eGFR (eGFR < 60 mL/min/1.73m2 and eGFR ≥ 60 mL/min/1.73m2). Outcome measures included post-operative pancreatic fistula, discharge disposition, hospital length of stay, 30-day readmission rate, and 30-day morbidity and mortality. Multivariate logistic regression analysis was performed. Results: A total of 21,148 were included in the study of which 12% (n = 2256) had preoperative eGFR < 60 mL/min/1.73m2. Patients in the eGFR < 60 group had prolonged length of stay, were less likely to be discharged home, had higher minor and major complication rates, and higher rates of mortality. On logistic regression analysis, lower preoperative eGFR (< 60 mL/min/1.73m2) was associated with higher odds of prolonged length of stay [aOR: 1.294 (1.166–1.436)], adverse discharge disposition [aOR: 1.860 (1.644–2.103)], minor [aOR: 1.460 (1.321–1.613)] and major complications [aOR: 1.214 (1.086–1.358)], bleeding requiring transfusion [aOR: 1.861 (1.656–2.091)], and mortality [aOR: 2.064 (1.523–2.797)]. Conclusion: Preoperative decreased renal function measured by eGFR is associated with adverse outcomes in patients undergoing pancreatic resection. The results of this study may be valuable in improving preoperative risk stratification and post-operative expectations. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to assess the impact of frailty on short-term outcomes after hepatectomy for colorectal liver metastasis (CRLM). Methods: Patients were identified using the National Surgical Quality Improvement Program (NSQIP). Patients were divided into 3 categories using the 5-item Modified Frailty Index (mFI). Results: There were 5230 patients included. 52%, 35%, and 13% had mFI scores of 0, 1, and ≥ 2 respectively. Patients with a ≥ 2 mFI score were more likely to experience minor complication (OR 1.34, 95% CI 1.06–1.69), major complication (OR 1.56, 95% CI 1.15–2.12), readmission (OR 1.55, 95% CI 1.12–2.14), unfavorable discharge (OR 2.48, 95% CI 1.62–3.80), 30-day mortality (OR 3.02, 95% CI 1.02–8.95), prolonged length of stay (OR 1.47, 95% CI 1.18–1.83), and bile leak (OR 1.51, 95% CI 1.02–2.24). Conclusion: Frailty is associated with increased post-operative complications. The 5-item mFI can guide risk stratification, optimization, and counseling. [ABSTRACT FROM AUTHOR]

Background: R0 resection for pancreatic cancer is considered standard of care, but is not always achieved. This study looks at R1/R2 resection outcomes compared with chemotherapy alone. Our hypothesis is that patients with margin-positive disease have better outcomes than those receiving chemotherapy alone.Study Design: Stage II pancreatic cancer patients who underwent R1/R2 surgery with/without neoadjuvant chemotherapy, from the National Cancer Database (NCDB) 2010 to 2017 were identified and compared with similar staged patients who received chemotherapy alone. The surgical group was then analyzed by subset based on receipt of chemotherapy: upfront surgery (+/- adjuvant therapy) and neoadjuvant therapy followed by surgery (+/- adjuvant therapy).Results: There were 11,699 Stage II pancreatic cancer patients included, 9,521 (81.4%) of whom were treated with chemotherapy alone, 15.7% (n = 1,836) had upfront surgery, and 2.9% (n = 342) had neoadjuvant therapy with surgery. R1/R2 neoadjuvant patients had the best overall survival at a mean of 19.75 months (95% CI 17.91, 22.28) compared with the upfront surgery group (17.77 months, 95% CI 15.64, 19.55) and the chemotherapy alone group (10.12 months, 95% CI 8.97, 11.50) (hazard ratio [HR] 0.46 upfront surgery and 0.32 neoadjuvant group, respectively, p < 0.0001). Even with R2 resection, survival was better in surgical patients compared with patients who underwent chemotherapy only (15.76 mo vs 10.22 mo, p = 0.06). Patients with R1/R2 resections had improved survival if they received neoadjuvant/adjuvant chemotherapy, though the survival rates were significantly lower than those with standard R0 resections (n = 16,129).Conclusions: R1 resection has benefit over chemotherapy alone in pancreatic cancer. Pancreatic cancer patients who are left with microscopic R1 disease have better survival than without surgery, particularly in the setting of neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: Previous studies have documented increased complications following pancreaticoduodenectomy in patients who undergo preoperative biliary stenting (PBS). However, in the modern era, the vast majority of patients with jaundice are stented. We hypothesized that there is no difference in short-term postoperative outcomes between PBS and no PBS in patient with obstructive jaundice undergoing pancreaticoduodenectomy. Methods: We performed an analysis using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) participant use file (2014–2017). Patients who received neoadjuvant chemotherapy and required stenting were excluded from the analysis. A propensity-matched analysis was performed to select obstructive jaundice patients who underwent PBS and those who did not with similar characteristics prior to pancreaticoduodenectomy. Short-term postoperative outcome measures included superficial surgical site infection (S-SSI), deep surgical site infection (D-SSI), hospital length of stay (LOS), postoperative pancreatic fistula (POF), hospital readmission, minor morbidity (Clavien-Dindo I–II), major morbidity (Clavien-Dindo III, IV, V), and 30-day mortality. Results: A total of 5851 patients with obstructive jaundice underwent pancreaticoduodenectomy without neoadjuvant chemotherapy. 81.6% underwent PBS. Based on the propensity-matched analysis, 927 patients who received PBS and 927 patients who did not were selected for comparing the outcomes between the two groups. There was no significant difference in outcome measures between the two groups with respect to S-SSI (OR 1.30 , 95% CI = 0.94–1.80, p = 0.12), D-SSI (OR 1.07, 95% CI = 0.81–1.41, p = 0.62), POF (OR 1.11, 95% CI = 0.87–1.42, p = 0.40), hospital readmission (OR 0.99, 95% CI = 0.77–1.27, p = 0.94), minor morbidity (OR 0.91, 95% CI = 0.76–1.11, p = 0.36), major morbidity (OR 0.84, 95% CI = 0.67–1.06, p = 0.14), and 30-day mortality (OR 1.05, 95% CI = 0.57–1.95, p = 0.87). Patients who underwent PBS were more likely to have shorter LOS (RR 0.87, 95% CI = 0.81–0.93, p < 0.0001). Conclusion: Contrary to previously reported studies, there was no increased risk of short-term postoperative outcomes after pancreaticoduodenectomy between PBS and N-PBS in a propensity-matched analysis. Preoperative biliary stenting is safe and does not need to be avoided before surgical intervention in patients who present with obstructive jaundice. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is the third leading cause of cancer related deaths in the US. Although lymph node (LN) metastasis is a prognostic indicator, the extent of LN resection is still debated. Our goal was to use the distribution of the ratio of positive to negative LNs to derive a more adequate number of necessary examined LNs based on the target LN threshold (TLNT).Study Design: Using the National Cancer Database, we performed a retrospective study of surgically resected pancreatic adenocarcinoma (2010 to 2015). We evaluated the number of positive LNs and total LNs examined and the log of the ratio of positive LNs to negative LNs (LODDS). The distribution of LODDS was examined to determine a target LNs examined threshold sufficient to detect N1 disease. Using the LODDS distribution of N1 cases, target LNs examined threshold were calculated to encompass 90 of the N1 group distribution.Results: Of the total 24,038 resected patients included in this study, 26% underwent operation only, 18% received neoadjuvant therapy, and 56% underwent adjuvant therapy. In all, 8,144 (34%) patients had N0 disease and 15,894 (66%) had N1 disease. To capture 90% to 95% of the N1 group, the minimum number of LNs examined would be 18 (LODDS -2.74) to 24 (LODDS -3.04), respectively.Conclusions: Although previous studies have suggested 11 to 17 LNs required for adequate LN sampling in pancreatic cancer, our findings suggest that to capture 90% of cases with N1 disease, 18 LNs is more appropriate. [ABSTRACT FROM AUTHOR]

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Introduction: Reports on outcomes after double-staple technique (DST) for total and proximal gastrectomy are limited, originating mostly from Asian centers. Our objective was to examine anastomotic leak and stricture with DST for esophagoenteric anastomosis in gastric cancer patients.Methods: A single institution review was performed for patients who underwent total/proximal gastrectomy with DST between 2006 and 2015. DST was performed using transoral anvil delivery (OrVil) with end-to-end anastomosis. Clinical characteristics and outcomes, including anastomotic leak and stricture, were recorded.Results: Overall, DST was performed in 60 patients [total gastrectomy (81.7%, n = 49/60), proximal gastrectomy (10.0%, n = 6/60), and completion gastrectomy (8.3%, n = 5/60)]. Neoadjuvant chemotherapy was administered to 21 patients (35.0%), and 6 patients (10.0%) received external beam radiation therapy prior to completion gastrectomy. Operative approach was open (51.7%, n = 31/60), laparoscopic (43.3%, n = 26/60), or robotic (5.0%, n = 3/60). Anastomotic leak occurred in 6.7% (n = 4/60), while stricture independent of leak was identified in 19.0% (n = 11/58) of patients. Complications occurred in 38.3% (n = 23/60) of patients, of which 52% were classified as Clavien-Dindo grades III-V complications.Conclusion: In the largest Western series of DST for esophagoenteric anastomoses in gastric cancer surgery, our experience demonstrates that DST is safe and effective with low rates of leak and stricture. [ABSTRACT FROM AUTHOR]

BACKGROUND: The treatment for a contralateral breast cancer (CBC) presents a growing dilemma given the expanding number of long-term survivors. We hypothesize that there will be specific surgical treatment trends with demographic differences between the treatment groups. METHODS: The Surveillance, Epidemiology, and End Results (SEER) cancer database was queried to identify CBC patients from 1998 to 2010. Relevant data were compared among the surgical treatment groups of lumpectomy, mastectomy, and mastectomy/reconstruction. RESULTS: Of 1,534 patients, 31% underwent lumpectomy and 69% underwent mastectomy [201 (21%) mastectomy/reconstruction; 748 (69%) mastectomy alone]. Older patients (age >80 years) were more likely to undergo lumpectomy; those with larger tumors (T4) or node-positive disease more often underwent mastectomy. Overall survival was significantly higher in the mastectomy/reconstruction group (P = .05). CONCLUSIONS: Younger age, larger tumor size, and positive nodal disease were independently associated with mastectomy. As the number of long-term breast cancer survivors increases, factors contributing to CBC treatments must be studied to maximize survival potential. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sentinel lymph node biopsy (SLNB) has become the preferred method for axillary nodal staging. The authors examined SLNB utilization in urban versus rural settings as this procedure was adopted and hypothesized that SLNB rates among urban populations increased faster, while the technology shift and acceptance of SLNB were slower at rural centers. METHODS: The Surveillance, Epidemiology and End Results database was used to identify patients with invasive node-negative ductal or lobular breast cancer diagnosed from 1998 to 2008. Exclusion criteria were distant metastatic disease, T4 tumors, or incomplete data. Residential setting was divided into groups on the basis of population density. RESULTS: The overall rate of SLNB increased with time (from 10% in 1998 to 73% in 2008). The adoption of SLNB was slower in rural settings than among urban populations (P, .001). By 2003, only urban areas were using SLNB in .50% of cases. Overall, there was a 2-year lag between the increases in SLNB utilization rates in these groups. There was a significant difference in SLNB rates according to tumor size. CONCLUSION: The overall rate of SLNB remained near 50% and was lower in rural locations in 2004. By 2008, the SLNB rate for T1 and T2 tumors had increased to .50% in all population categories. SLNB utilization was lower in all population categories as tumor size increased. There was an overall 2-year lag in the adoption of SLNB in less populated areas. Although this may represent a more conservative approach, the difference may be attributable to a shortage of experienced surgeons, lack of training, or lack of technological support at smaller institutions. [ABSTRACT FROM AUTHOR]

Background: There is ongoing debate whether extended lymphadenectomy improves survival in gastric cancer patients who undergo surgical resection. We previously observed that Korean-American patients had the highest overall survival in Los Angeles County. Our objective was to assess lymph node (LN) number and its impact on survival for Korean-American gastric cancer patients. Methods: We utilized the National Cancer Institute's Surveillance, Epidemiology, and End Results registry to identify Korean-Americans with gastric adenocarcinoma treated with curative-intent gastrectomy between 1988 and 2008. We grouped patients according to examined LN number (1-15 and 16+) and compared characteristics. We performed similar analysis for white patients. Results: Out of 982 Korean-American patients with gastric adenocarcinoma, most patients had 1-15 examined LNs (60 %). When we compared LN groups, we observed higher overall survival in the 1-15 group than the 16+ group (5-year survival, 59 % vs 52 %, respectively; p = 0.04). However, LN number was not prognostic of overall survival on stepwise Cox proportional hazards analysis. In contrast, LN number was prognostic for white patients. Conclusions: Although examined LN number may impact survival for white patients, outcomes of Korean-American gastric cancer patients were independent of LN number. Our data suggest that survival of Korean-American gastric cancer patients are comparable with outcomes from East Asian hospitals and may be independent of surgical technique. [ABSTRACT FROM AUTHOR]

Abstract: Background: Oncolytic adenoviruses provide a promising alternative for cancer treatment. Recently, adjuvant interferon (IFN)-alfa has shown significant survival benefits for pancreatic cancer, yet was impeded by systemic toxicity. To circumvent these problems adenovirus with high-level targeted IFN-alfa expression can be generated. Methods: Conditionally replicative adenoviruses (CRAds) with improved virulence and selectivity for pancreatic cancer were generated. The vectors were tested in vitro, in vivo, and in human pancreatic cancer and normal tissue specimens. Results: Adenoviral death protein and fiber modifications significantly improved oncolysis. CRAds selectively replicated in vitro, in vivo and showed persistent spread in cancer xenografts. They showed high-level replication in human pancreatic cancer specimens, but not in normal tissues. Improved IFN-CRAd oncolytic efficiency was shown. Conclusions: Optimized cyclooxygenase-2 CRAds show highly favorable effects in vitro and in vivo. We report a pancreatic cancer–specific, highly virulent, IFN-expressing CRAd, and we believe that adenovirus-based IFN therapy offers a new treatment opportunity for pancreatic cancer patients. [Copyright &y& Elsevier]

Introduction: ERBB2 is overexpressed in 15-25% of upper gastrointestinal adenocarcinomas. We use a stable lentiviral shRNA model to demonstrate that ERBB2 suppression in upper gastrointestinal adenocarcinomas with documented ERBB2 amplification effectively decreases ERBB2 protein levels and decreases cell viability. Further, we evaluate tumor growth of cells treated with the ERBB2 shRNA.Methods: Three upper gastrointestinal adenocarcinoma cells lines with varying ERBB2 levels were treated with one of three separate lentiviral green fluorescent protein (GFP)-labeled ERBB2 shRNA vectors or a nonsilencing control shRNA vector for 6 h. Protein levels on day 6 and cell viability was evaluated on days 3-10. A xenograft in vivo experiment was performed using OE19 cells pretransduced with ERBB2 shRNA to evaluate tumor growth.Results: ERBB2 protein levels decreased by 80%. ERBB2 knockdown significantly decreased cell viability in cell lines with high ERBB2 levels. In vivo tumor growth was suppressed in ERBB2-shRNA-treated groups.Conclusion: ERBB2 suppression based on a stable lentiviral shRNA transfection system effectively decreases cell viability in cell lines with amplification of ERBB2 as compared to cell lines without overexpression. ERBB2 knockdown significantly decreases tumor growth in vivo. ERBB2-directed therapy may be of benefit in the subset of patients with gastrointestinal adenocarcinomas exhibiting overamplification of ERBB2. [ABSTRACT FROM AUTHOR]

Background: Although the incidence of adenocarcinoma of the esophageal and gastroesophageal junction has increased at an alarming rate in the past 30 years, little improvement has been made in treatment strategies. Previous studies have demonstrated that many upper gastrointestinal (GI) adenocarcinomas exhibit ERBB2 amplification. In cancers proven to have similar amplification, such as breast, ERBB2–targeted therapies have dramatically improved overall survival and disease-free rates of survival. This study uses siRNA to knockdown ERBB2 in GI adenocarcinoma cell lines to evaluate cell viability, apoptosis, and changes in cell cycle. Methods: A cell line with a baseline amount of ERBB2 (Seg-1) and 2 upper GI adenocarcinoma cell lines with known amplification of ERBB2 (esophageal [OE19] and gastric [MKN45]) were treated with 120 pmol of 1 of 2 independent ERBB2 siRNAs or control siRNA for 6 hours. Results: We demonstrate that knockdown of ERBB2 in esophageal and gastric cancer cell lines with known ERBB2 amplification effectively decreases ERBB2 protein levels and decreases cell viability mainly via apoptotic pathways. Conclusion: ERBB–directed therapy may be of benefit in the subset of patients with GI adenocarcinomas exhibiting amplification of ERBB2. [Copyright &y& Elsevier]

Objectives Although the National Lung Screening Trial (NLST) lauds the efficacy of low-dose computed tomography (LDCT) at reducing lung cancer mortality, it has not been widely used for population-based screening. By examining the availability of U.S. LDCT screening centers, and underlying rates of lung cancer incidence, mortality, and smoking prevalence, the need for additional centers may be determined. Materials and methods Locations of 203 LDCT screening centers from the Lung Cancer Alliance Screening Centers of Excellence database, a list of active NLST and International Early Lung and Cardiac Action Program (I-ELCAP) screening centers, and an independently conducted survey of Society of Thoracic Radiology members were geocoded and mapped. County-level rates of lung cancer incidence, mortality, and smoking prevalence were also mapped and overlaid with the locations of the 203 LDCT screening centers. Results and conclusions Results showed the majority of LDCT screening centers were located in the counties with the highest quartiles of lung cancer incidence and mortality in the Northeast and East North Central states, but several high-risk states had no or few identified screening centers including Oklahoma, Nevada, Mississippi, and Arkansas. As guidelines are implemented and reimbursement for LDCT screening follows, equitable access to LDCT screening centers will become increasingly important, particularly in regions with high rates of lung cancer incidence and smoking prevalence. [ABSTRACT FROM AUTHOR]

Background: Orthotopic liver transplantation (OLT) is the gold standard treatment for patients with early hepatocellular carcinoma (HCC). There are concerns about the efficacy of OLT for HCC in older patients, who we hypothesized might have poorer outcomes. Therefore, we sought to examine advanced age and its impact on OLT outcomes. Study Design: The United Network for Organ Sharing database was queried for patients who underwent OLT for HCC from 1987 to 2009. Patients were divided into 3 age groups: 35 to 49 years old, 50 to 64 years old, and 65 years or older, and patient characteristics were compared. Univariate and multivariate analyses were performed to assess the impact of age on OLT outcomes. Results: Of 10,238 patients with OLT for HCC, 16.5% (n = 1,688) of patients were 35 to 49 years old, 67.8% (n = 6,937) were 35 to 49 years old, and 15.8% (n = 1,613) were 65 years and older. By Kaplan-Meier method, the 50- to 64-year-old age group had the highest overall survival, despite having one of the highest rates of hepatitis C positivity (70%), but this group also had the lowest rate of diabetes mellitus (8.7%). The lowest overall survival was observed in the 65-year or older age group (p < 0.001). Finally, there was no difference in disease-specific survival among the age groups (p = 0.858), and patients aged 65 years and older had the highest rate of death from nonhepatic causes (17.5%). Conclusions: Although OS was prolonged in younger patients who underwent OLT for HCC, there was no observed difference in disease-specific survival among the age groups. Our results suggest that carefully selected patients 65 years of age and older can derive equal benefit from OLT for HCC when compared with their younger counterparts. [Copyright &y& Elsevier]

Background: In May 2005 the Organ Procurement Transplant Network (OPTN) and United Network for Organ Sharing (UNOS) implemented the donor lung allocation score (LAS) system to prioritize organ allocation among prospective transplant recipients. The purpose of our study was to determine the impact of LAS implementation on 90-day survival, early complications and incidence of severe primary graft dysfunction (PGD) after the transplant procedure. Methods: Early outcomes among 78 patients receiving transplants after the initiation of the scoring system were compared with those of the 78 previous patients. Survival rates at 90 days and 1 year were the primary end-points of the study. Arterial blood-gas measurements were collected for all patients at the time of ICU arrival and at 12, 24 and 48 hours after surgery to determine the distribution of International Society of Heart and Lung Transplant (ISHLT) PGD grade. Major complications within 30 days post-transplant were recorded. Results: We found a small but significant 1-year survival advantage among post–LAS implementation patients, which was largely due to decreased early mortality in comparison to the control cohort. The incidence of ISHLT Grade 3 PGD measured within the first 24 hours after transplant did not differ between groups, nor was there an increase in the rate of major post-operative complications. Conclusions: Implementation of the LAS system has not been associated with an increase in early mortality, immediate PGD or major complications. [Copyright &y& Elsevier]