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A concerning increase in early-onset colorectal cancer led to guideline changes in 2018 by the American Cancer Society to lower the age for initial colorectal cancer screening from 50 to 45 years of age. Although this would be expected to result in increased screening rates and subsequent earlier detection of colorectal cancer, the effect of this guideline change at a national level is not yet fully understood. Using the National Cancer Database, we identified patients newly targeted for screening (age 45–49 years) diagnosed with colon cancer in either 2017 (early cohort) or 2019 (late cohort). The relationship between time period and stage of disease at presentation was examined by univariate analysis and in a multivariable logistic regression model. In total, 5,479 patients met inclusion criteria. The median age at diagnosis did not differ between patients in the late and early cohorts (47 years for both cohorts, P =.41). Patients in the late and early cohorts had equal odds of having stage III-IV disease (odds ratio for late cohort to early cohort, 1.05, 95% confidence interval, 0.94–1.17), and patients in the late cohort showed slightly increased odds of having higher T-stage (pT3 or pT4) disease (odds ratio, 1.20, 95% confidence interval, 1.05–1.35). Despite recommendations of earlier initial colorectal cancer screening, a clinically meaningful earlier shift in colon cancer stage was not observed in patients newly targeted for screening. Further studies will be needed to assess uptake of these recommendations by providers and patients and identify areas of improvement. [ABSTRACT FROM AUTHOR]

Although historic studies of state registries have demonstrated decreased radiation therapy use for patients with breast cancer living further away from radiation facilities, the association between travel distance and breast cancer treatment in a modern national cohort remains unknown. Female patients with estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative pathologic stages I to II breast cancer were identified from the National Cancer Database (2018–2020) and dichotomized by distance ≤20 miles or >20 miles (75th percentile) from the treatment facility. The association between travel distance and type of surgery and treatment administered was analyzed by univariate and multivariate logistic regression and after 1:1 propensity matching. Of the 293,318 patients identified for inclusion, the median age was 63 years, and most patients (n = 190,567, 65%) lived ≤20 miles of the treatment facility. Patients with a travel burden >20 miles were more likely to receive a mastectomy (≤20 miles 30.4% vs >20 miles 34.0%, P <.001; odds ratio 1.14, P =.016), and less likely to receive radiation (≤20 miles 63.3% vs >20% miles 60.1%, P <.001; odds ratio 0.81, P <.001). These findings persisted after propensity score matching (n = 33,544 per cohort), with patients living further being more likely to undergo a mastectomy (≤20 miles 30.3% vs >20 miles 35.3%, P <.001) and less likely to receive radiation (≤ 20 miles 65.4% vs. >20 miles 58.5%, P <.001). Patients with hormone receptor-positive stage I to II breast cancer with a larger travel burden are more likely to receive a mastectomy and less likely to undergo radiation therapy to treat their disease. [ABSTRACT FROM AUTHOR]

Background: Given the results of the recent KEYNOTE-716 trial, the performance of sentinel lymph node (SLN) biopsy for patients with clinical stage IIB/C melanoma has been questioned.Objective: Determine the utility of SLN status in guiding the recommendations for adjuvant therapy.Methods: Patients with clinical stage IIB/C cutaneous melanoma who underwent wide local excision and SLN biopsy between 2004-2011 were identified from the Surveillance, Epidemiology, and End Results database. Two prognostic models, with and without SLN status, were developed predicting risk of Melanoma specific death (MSD). The primary outcome was net benefit at treatment thresholds of 20-40% risk of 5-year MSD RESULTS: For the 4,391 patients included, the 5-year MSD rate was 46%. The model estimating 5-year MSD risk that included SLN status provided greater net benefit at treatment thresholds from 30-78% compared to the model without SLN status. The added net benefit for the SLN biopsy-containing model persisted in subgroup analysis of patients in different age groups and with various T stages.Limitations: Retrospective study.Conclusions: A prognostic model with SLN status estimating patient risk for 5-year MSD provides superior net benefit compared to a model with primary tumor staging factors alone for threshold mortality rates ≥30%. [ABSTRACT FROM AUTHOR]

• M.tb adapts to host environments primarily by alterations in its transcriptome. • Remodelling of M.tb cell wall and metabolic pathways was seen in bone TB lesions. • M.tb virulence genes were upregulated in bone lesions and cell line model. • M.tb virulence proteins inhibit osteoblast differentiation, altering bone homeostasis. • Further studies on the role of these proteins in bone TB needed using M.tb mutants. Bone tuberculosis (TB) is the third most common types of extrapulmonary tuberculosis. It is critical to understand mycobacterial adaptive strategies within bone lesions to identify mycobacterial factors that may have role in disease pathogenesis. Whole genome microarray was used to characterize the in-vivo transcriptome of Mycobacterium tuberculosis (M.tb) within bone TB specimens. Mycobacterial virulent proteins were identified by bioinformatic software. An in vitro osteoblast cell line model was used to study the role of these proteins in bone TB pathogenesis. 914 mycobacterial genes were significantly overexpressed and 1688 were repressed in bone TB specimens. Pathway analysis of differentially expressed genes demonstrated a non-replicative and hypometabolic state of M.tb, reinforcement of the mycobacterial cell wall and induction of DNA damage repair responses, suggesting possible survival strategies of M.tb within bone. Bioinformatics mining of microarray data led to identification of five virulence proteins. The genes encoding these proteins were also upregulated in the in vitro MC3T3 osteoblast cell line model of bone TB. Further, exposure of osteoblast cells to two of these virulence proteins (Rv1046c and Rv3663c) significantly inhibited osteoblast differentiation. M.tb alters its transcriptome to establish infection in bone by upregulating certain virulence genes which play a key role in disturbing bone homeostasis. [ABSTRACT FROM AUTHOR]

Sentinel lymph node biopsy is not routinely recommended for T1a cutaneous melanoma due to the overall low risk of positivity. Prognostic factors for positive sentinel lymph node (SLN+) in this population are poorly characterized. To determine factors associated with SLN+ in patients with T1a melanoma. Patients with pathologic T1a (<0.80 mm, nonulcerated) cutaneous melanoma from 5 high-volume melanoma centers from 2001 to 2020 who underwent wide local excision with sentinel lymph node biopsy were included in the study. Patient and tumor characteristics associated with SLN+ were analyzed by univariate and multivariable logistic regression analyses. Age was dichotomized into ≤42 (25% quartile cutoff) and >42 years. Of the 965 patients identified, the overall SLN+ was 4.4% (N = 43). Factors associated with SLN+ were age ≤42 years (7.5% vs 3.7%; odds ratio [OR], 2.14; P =.03), head/neck primary tumor location (9.2% vs 4%; OR, 2.75; P =.04), lymphovascular invasion (21.4% vs 4.2%; OR, 5.64; P =.01), and ≥2 mitoses/mm2 (8.2% vs 3.4%; OR, 2.31; P =.03). Patients <42 years with ≥2 mitoses/mm2 (N = 38) had a SLN+ rate of 18.4%. Retrospective study. SLN+ is low in patients with T1a melanomas, but younger age, lymphovascular invasion, mitogenicity, and head/neck primary site appear to confer a higher risk of SLN+. [ABSTRACT FROM AUTHOR]

Background: Approval of adjuvant anti-programmed cell death protein 1 therapy for pathologic stage IIB/C cutaneous melanoma has led some to question the role of sentinel lymph node (SLN) biopsy in the clinical stage IIB/C disease.Objective: To determine the prognostic significance of SLN staging on disease-specific survival (DSS) for clinical stage IIB/C primary cutaneous melanoma in the preimmunotherapy era.Methods: A retrospective cohort study was performed evaluating patients who underwent excision of clinical stage IIB/C cutaneous melanoma using the Surveillance, Epidemiology, and End Results database (2004-2011). Patients who did and did not undergo SLN biopsy were compared using propensity matching, and among those who underwent SLN biopsy, matched patients were further stratified by SLN status (SLN positive [SLN+] or SLN negative [SLN-]).Results: Of the 8562 patients evaluated, 6021 (70.3%) underwent SLN biopsy. SLN positivity was associated with significantly reduced 5-year DSS among matched patients who underwent SLN biopsy (47.1% SLN+ vs 75.5% SLN-; P < .001). Five-year DSS remained significantly different across matched T-stages: T3b (54.2% SLN+ vs 64.8% SLN-; P = .004), T4a (55.5% SLN+ vs 71.6% SLN-; P = .001), and T4b (38.6% SLN+ vs 60.9% SLN-; P < .001).Limitations: Retrospective study.Conclusion: For patients with clinical stage IIB/C cutaneous melanoma, SLN status provides essential prognostic information. [ABSTRACT FROM AUTHOR]

The American College of Surgeons National Surgical Quality Improvement Program was established to help participating hospitals track and report surgical complications with the goal of improving surgical care. We sought to determine whether this has led to improvements in surgical outcomes for pancreatic malignancies. Patients with pancreatic malignancies who underwent surgical resection were identified from the American College of Surgeons National Surgical Quality Improvement Program database (2006–2019). Thirty-day postoperative major morbidity and mortality were analyzed by year. Major morbidity included organ and deep surgical site infection, venous thromboembolism, cardiac event, pneumonia, acute renal failure, sepsis, and respiratory failure. Of the 28,888 patients identified, 51% were male, the median age was 68, 74.3% underwent a pancreaticoduodenectomy, and 25.7% underwent a distal pancreatectomy. Among patients who underwent a pancreaticoduodenectomy, there was a significant increase in major morbidity (annual percent change 0.77, P =.012) driven by increases in organ space surgical site infection (annual percent change 3.52, P <.001) and venous thromboembolism (annual percent change 4.72, P =.005). However, there was a decrease in postoperative mortality (annual percent change -4.58, P =.001). For distal pancreatectomy patients, there was no change in rates of overall major morbidity (annual percent change -1.35, P =.08) or mortality (annual percent change -3.21, P =.25). Although major morbidity and mortality have not significantly changed for distal pancreatectomy patients, mortality has steadily decreased for patients undergoing pancreaticoduodenectomy, despite an increase in major morbidity. Whether this trend reflects a change in patient selection, an increase in detection of postoperative morbidities and/or an improvement in mitigation of these morbidities warrants further study. [ABSTRACT FROM AUTHOR]

Adjuvant systemic therapy is selectively considered for high-risk stage II colon cancer, but which patients benefit most from adjuvant systemic therapy is unclear. Patients who underwent resection of stage II colon cancer were identified from the National Cancer Database (2010–2016). Risk-factors for decreased overall survival on multivariable analysis were used to establish a predictive risk-score model for all-cause mortality. After propensity matching within each risk group, 5-year overall survival was estimated based on receipt of adjuvant systemic therapy. Of the 15,241 patients evaluated, 2,857 (18.8%) received adjuvant systemic therapy. Risk factors for decreased overall survival included age >75 (hazard ratio 3.3, P <.001), male sex (hazard ratio 1.2, P <.001), White/Black race (hazard ratio 1.4, P =.020), preoperative carcinoembryonic antigen >3.5 ng/mL (hazard ratio 1.6, P <.001), T4a T-stage (hazard ratio 2.0, P <.001), T4b T-stage (hazard ratio 2.4, P <.001), lymphovascular invasion (hazard ratio 1.2, P =.003), perineural invasion (hazard ratio 1.3, P =.003), and non-R0 proximal/distal resection margins (hazard ratio 1.7, P <.001). An internally validated risk-score model using these factors was developed composed of low-risk (n = 8,489), moderate-risk (n = 4,623), and high-risk (n = 2,129) groups; within each group, 19.9%, 15.7%, and 20.8% of patients, respectively, received adjuvant systemic therapy. After propensity matching, adjuvant systemic therapy was not associated with improved 5-year overall survival for low-risk patients (89.8% vs 88.3%, P =.280), but was for moderate-risk (80.5% vs 70.8%, P <.001), and high-risk (65.2% vs 45.7%, P <.001) patients. A predictive risk-score model incorporating patient and tumor factors identifies a high-risk cohort of stage II colon cancer patients who may benefit from adjuvant systemic therapy, although the minority of these patients appear to be receiving treatment. [ABSTRACT FROM AUTHOR]

Patients who did not receive CRS-HIPEC had the lowest average life expectancy of 2.11 years overall survival. Keywords: Cytoreductive surgery; HIPEC; Malignant peritoneal mesothelioma; Time to treatment; Markov EN Cytoreductive surgery HIPEC Malignant peritoneal mesothelioma Time to treatment Markov 995 997 3 04/28/23 20230501 NES 230501 Presented as a Quick Shot presentation at the 63rd Annual Meeting of the Society for Surgery of the Alimentary Tract, May 21-24, 2022, San Diego, CA. [Extracted from the article]

Extremity soft tissue sarcoma is managed by oncological trained general or orthopedic surgeons, but limited data exist comparing patient characteristics and outcomes between the 2 specialties. Patients were identified from the 2008 to 2017 National Surgical Quality Improvement Program who underwent limb-sparing resection of extremity soft tissue sarcoma by either general surgeons or orthopedic surgeons. Multivariable logistic regression analysis identified factors associated with general surgeons compared with OS. Length of stay was assessed using Poisson regression. Procedure annual percent change was analyzed using Joinpoint Regression. The majority of extremity soft tissue sarcoma cases were performed by general surgeons (N = 304, 69.4%), but general surgeons' resections significantly decreased (35.2%) over the study period (annual percent change –5.8, P <.0001). General surgeons' patients were less likely to receive neoadjuvant chemotherapy (2.0% vs 3.7%, P <.01), and more likely to receive neoadjuvant radiation (9.9% vs 5.2%, P <.01) and have normal preoperative white blood cell counts (77.0% vs. 66.4%, P =.02). Orthopedic surgeons' cases were more often performed under regional anesthesia (9.7% vs. 2.3%, P =.01), and orthopedic patients were more likely to receive postoperative transfusions (5.2% vs 0.3%, P <.01) and had a longer median length of stay (2 vs 1 days, P <.01). Thirty-day overall morbidity (7.2% general surgeon vs 9.7% orthopedic surgeon, P =.38) and all-cause mortality (0.3% general surgeon vs 0% orthopedic surgeon, P =.51) did not differ by specialty. Although postoperative outcomes for extremity soft tissue sarcoma are comparable between general and orthopedic surgeons, treatment and perioperative management differences exist. Future investigation focused on understanding these differences in perioperative management across specialties may help identify areas for quality improvement in care of patients with extremity soft tissue sarcoma. [ABSTRACT FROM AUTHOR]

Total gastrectomy for gastric cancer is associated with significant 30-day mortality, but this endpoint may underestimate the short-term mortality of the procedure. Retrospective analysis was performed using the National Cancer Database (2004−2015). Patients who underwent total gastrectomy for stage I to III gastric adenocarcinoma were identified and divided into cohorts based on 90-day mortality. Predictors of mortality were analyzed using multivariable logistic regression, and annual trends in mortality rates were calculated by Joinpoint Regression. Of the 5,484 patients who underwent total gastrectomy, 90-day and 30-day mortality rates were 9.1% and 4.7%, respectively. Factors associated with 90-day mortality included increasing age (odds ratio 1.0, P <.001), income below the median (odds ratio 1.2, P =.039), Charlson-Deyo score ≥2 (odds ratio 1.4, P =.039), treatment at low-volume facilities (odds ratio 1.5, P <.001), N1 (odds ratio 2.0, P <.001), N2 (odds ratio 2.0, P <.001), or N3 (odds ratio 2.7, P <.001) stage disease, having <16 lymph nodes harvested (odds ratio 1.5, P <.001), and lack of treatment with chemotherapy (3.7, P <.001). Lack of health insurance (odds ratio 4.1, P =.080), and positive microscopic margins (odds ratio 1.3, P =.080) were correlated, but not significantly associated, with 90-day mortality. The 90-day mortality rate significantly declined from 14.3% in 2004 to 7.9% in 2015 (P =.006), and the 30-day mortality rate significantly declined from 7.7% in 2004 to 4.8% in 2015 (P =.009). Nearly half of the deaths within 90 days after total gastrectomy for cancer occur beyond 30 days postoperative. Ninety-day mortality has improved over time, but rates remain high, suggesting the need for improved out-of-hospital postoperative care beyond 30 days. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 outbreak has spread worldwide and has resulted in hospital restrictions. The perceived impact of these practices on patients undergoing essential surgeries is less understood. Adult (≥18 years) patients who underwent medically necessary surgical procedures spanning multiple surgical specialties from March 23, 2020, to April 24, 2020, during the coronavirus disease 2019 pandemic were identified as eligible for a phone survey. Survey responses were analyzed using a mixed-methods approach involving descriptive statistics and thematic analysis of coded and annotated survey results. Of the 212 patients who underwent medically necessary surgical procedures during the coronavirus disease 2019 pandemic, the majority of these patients were male (61.3%), White (83.5%), married or with a domestic partner (68.9%), and underwent oncologic procedures (69.3%). Of the 46 patients (21.7%) who completed the survey, the majority of these patients indicated that coronavirus disease 2019 pandemic restrictions had no impact on their inpatient hospital stay and were satisfied with their decision to proceed with surgery. Severity of patient condition (44.4%), the risk/benefit discussion with the surgeon (24.4%), and coronavirus disease 2019 education and testing (19.5%) were the most important factors in proceeding with surgery during the pandemic; 34.4% of patients said their inpatient postoperative course was negatively affected by the lack of visitors. Medically necessary, time-sensitive surgical procedures, as determined by the surgeon, can be performed during a pandemic with good patient satisfaction provided there is an appropriate discussion between the surgeon and patient about the risks and benefits. [ABSTRACT FROM AUTHOR]

Background: The Affordable Care Act's Medicaid expansion is associated with earlier diagnosis and improved care among lower socioeconomic status populations with cancer, but its impact on melanoma is undefined.Objective: To determine the association of Medicaid expansion with stage of diagnosis and use of sentinel lymph node biopsy in nonelderly adult patients with newly diagnosed clinically localized melanoma.Methods: Quasi-experimental, difference-in-differences retrospective cohort analysis using data from the National Cancer Database from 2010 to 2017. Patients from expansion versus nonexpansion states and diagnosed before (2010-2013) versus after (2014-2017) expansion were identified.Results: Of 83,322 patients, 46.6% were female, and the median age was 55 years (interquartile range, 49-60). After risk adjustment, Medicaid expansion was associated with a decrease in the diagnosis of T1b stage or higher melanoma (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.88-0.98; P = .011) and decrease in uninsured status (OR, 0.61; 95% CI, 0.52-0.72; P < .001) but was not associated with a difference in sentinel lymph node biopsy performance when indicated (OR, 1.06; 95% CI, 0.95-1.20; P = .29).Limitations: Retrospective study using a national database.Conclusion: In this study of patients with clinically localized melanoma, Medicaid expansion was associated with a decrease in the diagnosis of later T-stage tumors. [ABSTRACT FROM AUTHOR]

Results Of 114,957 patients who met inclusion criteria, 2071 (1.8%) patients had mMetS, and 1392 (1.2%), 422 (0.4%), and 257 (0.2%) patients had class I, II, and III obesity, respectively (Table 1). Keywords: Obesity; Metabolic syndrome; Surgery and obesity; Surgical outcomes; Hernia repair EN Obesity Metabolic syndrome Surgery and obesity Surgical outcomes Hernia repair 1565 1568 4 06/16/21 20210601 NES 210601 Introduction Central obesity is a nationwide epidemic with an age-adjusted prevalence of 42.4%.[1] Metabolic syndrome (MetS) defines a cluster of diagnostic criteria, including central obesity, insulin resistance, hypertension, and elevated triglycerides, that indicate an increased risk for cardiovascular disease, mortality, and surgical complications and readmission.[2]-[5] Researchers have defined modified metabolic syndrome (mMetS) to analyze outcomes within validated surgical databases as BMI >= 30 kg/m SP 2 sp , hypertension, and diagnosis of diabetes mellitus.[5],[6] Prior studies suggest that MetS may more reliably predict postoperative morbidity compared to its individual components.[5],[6] The purpose this study was to evaluate the impact of mMetS on perioperative outcomes in patients undergoing elective open inguinal hernia repair. [Extracted from the article]

Background: Transfusion guidelines have been established for severe anemia, but limited data is available regarding the utility of preoperative transfusion. This study evaluates the predictive factors and relative value of preoperative transfusion in oncologic patients with moderate anemia undergoing abdominal surgery.Methods: Using the American College of Surgeons National Surgical Quality Improvement Program database, adult patients with moderate anemia (hematocrit 21-27%) who underwent non-emergent abdominal oncologic resection from 2005 to 2017 were identified. Preoperative transfusion and non-transfused patients were propensity score matched based on baseline covariates. Outcomes were compared using univariate and Poisson regression analysis.Results: Of 6222 patients, preoperative transfused (N = 1000, 16.1%) patients were more likely to have bleeding disorders (12.1% vs 6.7%, p < 0.0001) and baseline thrombocytopenia (12% vs 7.3%, p < 0.0001) and had shorter operative length (< 180 min: 69.4% vs 59.8%, p < 0.0001). After matching (N = 987/group), preoperative transfusion was associated with higher rates of intraoperative/postoperative transfusion (odds ratio 1.24, p 0.017) and surgical site infections (odds ratio 1.67, p 0.004) and longer length of stay (incidence rate ratio 1.06, p < 0.0001).Conclusions: Preoperative transfusion is associated with increased surgical site infections and longer hospital stay and should be carefully considered in oncologic patients given the absence of improvement in outcomes. [ABSTRACT FROM AUTHOR]

Conclusion In this study of patients with CD who underwent surgical resection of clinical stage I-III SBA, LNH >= 8 nodes was prognostic for improved OS across all stages of disease, as well as among stage I/II patients, but not for stage III patients, likely representing a stage migration effect. Most stage III patients ( I n i = 122 [71.8%]) received aST, while the minority of stage II patients ( I n i = 82, 39.2%) did. Keywords: Crohn's disease; Small bowel adenocarcinoma; Surgery; Lymph node; Survival; outcomes EN Crohn's disease Small bowel adenocarcinoma Surgery Lymph node Survival outcomes 1311 1313 3 06/15/22 20220601 NES 220601 This manuscript was presented as an oral presentation at the 2021 Pennsylvania Society of Colon & Rectal Surgeons Resident Research Meeting: Meeting date: April 8, 2021. [Extracted from the article]

Although tumor size and mitotic rate are established prognostic factors for worse survival in patients undergoing surgical resection for gastric gastrointestinal stromal tumors, the impact of microscopic margins, or R1 resection, is not completely established. Patients who received no neoadjuvant therapy and underwent surgical resection for stage I to III gastric gastrointestinal stromal tumors were identified from the 2010 to 2013 National Cancer Database and divided into 2 cohorts, R0 and R1 resections. Cox proportional hazards ratio and Kaplan Meier survival estimates were utilized to analyze 5-y overall survival. Of 2,084 patients, those with R1 resection (57, 2.7%) were more likely to have tumors >10 cm (28.1% vs 11.9%, odds ratio 3.51, P =.017) and stage III disease (26.3% vs 11.2%, odds ratio 2.26, P =.047). Although margin status was associated with higher risk tumors, it was not associated with receipt of adjuvant therapy. After multivariate Cox regression, R1 and R0 patients did not have a difference in 5-y overall survival (82.5% vs 88.6%, hazards ratio 1.26, P =.49). When stratified by stage of disease, there remained no difference in survival across all stages when comparing R1 and R0 patients. Positive microscopic margins are uncommon but do not appear to impact survival outcomes in patients with resected localized gastric gastrointestinal stromal tumors. [ABSTRACT FROM AUTHOR]

Ventral hernias in patients with intra-abdominal metastases may not be addressed owing to other oncologic priorities, but they can affect quality of life and lead to sequelae necessitating an emergency operation. We compared the national trends and perioperative outcomes for elective and nonelective ventral hernia repairs for patients with intra-abdominal metastases. Patients were identified from the National Inpatient Sample (2003−2015). Temporal trends were described using average annual percent change. Perioperative outcomes between elective and nonelective ventral hernia repairs were compared using multivariable regressions. An estimated 947,112 ventral hernia repairs were performed nationally, including 5,602 (0.6%) in patients with intra-abdominal metastases. Among patients with intra-abdominal metastases, 40.1% had a nonelective ventral hernia repair, mean (standard deviation) age was 64 (12) years, and 65.1% were women. Between 2003 and 2015, the total number of ventral hernia repairs performed nationally did not change (average annual percent change 0.062, P =.84). For patients with intra-abdominal metastases, although there was no change in the number of elective ventral hernia repairs (average annual percent change 0.65, P =.59), the number of nonelective ventral hernia repairs increased significantly (average annual percent change 2.7, P =.025). By multivariable analyses, patients with intra-abdominal metastases who underwent a nonelective repair were more likely to experience complications (odds ratio 1.76, P =.001), nonroutine discharge (odds ratio 1.93, P <.001), and mortality (odds ratio 2.27, P =.035). Nonelective ventral hernia repairs was also associated with a 38.5% (P <.001) longer hospital stay and 24.4% (P <.001) higher charges. The number of nonelective ventral hernia repairs, which is associated with substantial perioperative morbidity, has increased significantly among patients with intra-abdominal metastases. Surgeons should consider a nonemergency operation for select patients to mitigate the burden of nonelective ventral hernia repairs. [ABSTRACT FROM AUTHOR]

Complex cancer operations performed at high-volume and teaching hospitals have been associated with better outcomes. The purpose of this study was to determine the national trends in the performance of these operations at large teaching hospitals. Patients who underwent elective esophagectomies, gastrectomies, pancreatectomies, and hepatectomies for cancer (2003–2015) were identified using the National Inpatient Sample. We determined average annual percent change (AAPC) in the proportion of operations at large teaching hospitals, inpatient complications, length of stay (LOS), and inpatient mortality. Between 2003 and 2015, 38,932 esophageal, 104,941 gastric, 96,098 hepatic, and 137,440 pancreatic cancer resections were performed. The proportion at large teaching hospitals increased with an AAPC of 2.5 for esophagectomies (P <. 001), 3.6 for gastrectomies (P <. 001), and 1.5 for pancreatectomies (P =. 039), but did not change for hepatectomies (AAPC 0.48, P =. 50). During the study period, mean LOS and inpatient mortality rates at large teaching hospitals decreased across hospital types. By 2013 to 2015, the operations at large hospitals were associated with decreased mortality only for pancreatectomies (odds ratio, 0.62, 95% confidence interval, 0.43–0.91, P =. 015). Complex cancer operations are performed increasingly at large teaching hospitals, but perioperative outcomes have improved nationally across hospital types. Further studies should identify actionable areas for improvement to ensure accessible quality cancer care. [ABSTRACT FROM AUTHOR]

Clinically relevant postoperative pancreatic fistula and delayed gastric emptying cause substantial morbidity after pancreatoduodenectomy. Per international guidelines, the placement of jejunostomy tubes may be considered for patients at risk for malnutrition, such as those with a high risk for clinically relevant postoperative pancreatic fistula and related complications. This study determined predictors and postoperative outcomes of jejunostomy tube placement. Patients undergoing pancreatoduodenectomy in 2014 to 2015 were identified using the American College of Surgeons National Surgical Quality Improvement Program and Procedure-Targeted Pancreatectomy Participant Use Files. Multivariable logistic regressions were used to identify factors associated with concurrent jejunostomy tube placement and postoperative outcomes. Of 3,600 patients, 8.9% underwent jejunostomy tube placement. Patients given a jejunostomy tube were more likely white (odds ratio 1.46, P =.016), to have low preoperative serum albumin levels (odds ratio 2.13, P <.001), to have received neoadjuvant radiotherapy (odds ratio 2.14, P <.001), and to have received an intraoperative transfusion (odds ratio 1.50, P =.004). We observed no association between jejunostomy tube placement and an increasing number of risk factors for clinically relevant postoperative pancreatic fistula (P =.96) or delayed gastric emptying (P =.54). Overall, jejunostomy tube placement was associated with increased morbidity (odds ratio 1.34, P =.020) and duration of stay (P <.001), but not mortality (P =.12). Among patients with low serum albumin or those who developed clinically relevant postoperative pancreatic fistula or delayed gastric emptying, jejunostomy tube utilization was not associated with morbidity or mortality. Jejunostomy tube placement during pancreatoduodenectomy was not driven by risk factors for clinically relevant postoperative pancreatic fistula or delayed gastric emptying, suggesting that practice patterns play a role. Among patients with at-risk preoperative albumin or who developed these complications, jejunostomy tube placement was not associated with worse outcomes, supporting selective utilization per guideline recommendations. [ABSTRACT FROM AUTHOR]

Background: There is large variability in the risk of sentinel lymph node (SLN) positivity among patients with intermediate thickness melanoma (ITM), with a subgroup of patients exhibiting a low risk of nodal disease.Objective: To identify a group of patients with ITM for whom the risk of nodal disease is low.Methods: A retrospective cohort of patients with ITM who underwent wide excision and nodal evaluation from 2010 to 2013 was identified by using the National Cancer Database and analyzed for the presence of nodal disease. Classification and regression tree analysis identified the most important factors used in a model to identify groups at low risk of SLN positivity.Results: Of 23,440 patients, 14.7% were found to have nodal metastasis. On classification and regression tree analysis, patients older than 55 years without lymphovascular invasion and with a lesion thickness less than 1.7 mm had an SLN positivity rate of 4.9%. A model using age and thickness in nonulcerated patients identified a low-risk subgroup with a corresponding SLN positivity rate of 4.7%.Limitations: This was a retrospective study, and the model developed requires prospective validation.Conclusions: Patient age is an important factor in estimating risk of SLN in patients with ITM and may help identify patients without ulceration who may be safely spared an SLN biopsy. [ABSTRACT FROM AUTHOR]

Macrophages play a pivotal role in tumor immunity. We report that reprogramming of macrophages to tumor-associated macrophages (TAMs) promotes the secretion of exosomes. Mechanistically, increased exosome secretion is driven by MADD, which is phosphorylated by Akt upon TAM induction and activates Rab27a. TAM exosomes carry high levels of programmed death-ligand 1 (PD-L1) and potently suppress the proliferation and function of CD8+ T cells. Analysis of patient melanoma tissues indicates that TAM exosomes contribute significantly to CD8+ T cell suppression. Single-cell RNA sequencing analysis showed that exosome-related genes are highly expressed in macrophages in melanoma; TAM-specific RAB27A expression inversely correlates with CD8+ T cell infiltration. In a murine melanoma model, lipid nanoparticle delivery of small interfering RNAs (siRNAs) targeting macrophage RAB27A led to better T cell activation and sensitized tumors to anti-programmed cell death protein 1 (PD-1) treatment. Our study demonstrates tumors use TAM exosomes to combat CD8 T cells and suggests targeting TAM exosomes as a potential strategy to improve immunotherapies. [Display omitted] • Tumor-associated macrophages secrete a large amount of PD-L1+ small extracellular vesicles • Akt promotes exosome secretion in TAMs through MADD phosphorylation • TAM-derived exosomes inhibit CD8 T cell proliferation and function • Targeting macrophage RAB27A by LNPs sensitizes tumor to anti-PD-1 antibody Zhong and colleagues report that tumor-associated macrophages secrete a large amount of small extracellular vesicles that carry PD-L1, which actively inhibit the proliferation and function of CD8 T cells. [ABSTRACT FROM AUTHOR]

Background: The immune response to melanoma is manifested locally by tumor-infiltrating lymphocytes (TILs). Men and women are known to have varying patterns of immunity, yet sex-specific prognostic implications of TILs have not been explored.Methods: Patients who had clinically localized primary melanoma with a Breslow thickness of 0.76 mm or more and underwent sentinel lymph node (SLN) biopsy at our institution were identified. The association between TILs (absent, nonbrisk, and brisk) and SLN positivity was evaluated by using logistic regression. Overall survival (OS) was evaluated by TIL status and sex.Results: Among 1367 patients identified, 794 were men. TILs were brisk in 143 lesions, nonbrisk in 903, and absent in 321, which did not vary by sex (P = .71). SLN positivity was associated with TILs among men (brisk, 3.8%; nonbrisk, 16.9%; and absent, 26.6% [P < .001]). In contrast, there was no association between SLN positivity and TILs among women (P = .49). Interaction between brisk TILs and sex on SLN positivity was significant (P = .029). Among men, presence of brisk TILs was associated with prolonged OS (P = .038) but not after adjustment for SLN status (P = .42). There was no association between TIL status and OS among women.Limitations: Findings from this single-institution study have yet to be validated by other research groups.Conclusions: The implications of TILs in predicting SLN positivity appear to be more relevant for men than for women. [ABSTRACT FROM AUTHOR]

Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups. [ABSTRACT FROM AUTHOR]

Tumor-sequencing studies have revealed the widespread genetic diversity of melanoma. Sequencing of 108 genes previously implicated in melanomagenesis was performed on 462 patient-derived xenografts (PDXs), cell lines, and tumors to identify mutational and copy number aberrations. Samples came from 371 unique individuals: 263 were naive to treatment, and 108 were previously treated with targeted therapy (34), immunotherapy (54), or both (20). Models of all previously reported major melanoma subtypes (BRAF, NRAS, NF1, KIT, and WT/WT/WT) were identified. Multiple minor melanoma subtypes were also recapitulated, including melanomas with multiple activating mutations in the MAPK-signaling pathway and chromatin-remodeling gene mutations. These well-characterized melanoma PDXs and cell lines can be used not only as reagents for a large array of biological studies but also as pre-clinical models to facilitate drug development. [ABSTRACT FROM AUTHOR]

Background As payment shifts toward bundled reimbursement, decreasing unnecessary inpatient care may provide cost savings. This study examines the association between discharge status, hospital duration of stay, and cost for colorectal operation patients without complications and uses risk factors to predict the need for post–acute care. Methods We used the New York Statewide Planning and Research Cooperative System and the California Healthcare Cost and Utilization Project State Inpatient Databases to identify all patients who underwent operative resection for colorectal cancer in 2009–2010 and were discharged to home or post–acute care. Patients with complications were excluded. Duration of stay and inpatient costs were calculated. Risk factors associated with discharge to post–acute care were identified using multivariable logistic regression and were incorporated into a model to predict discharge status. Results A total of 5.4% of 23,942 patients were discharged to a post–acute care facility. Duration of sty was 2 days greater and $3,823 more costly for patients discharged to post–acute care. Significant risk factors included age, number of comorbidities, emergency admission, open operation, admission in the previous year, and a new ostomy. A scoring system using these factors accurately predicted discharge to post–acute care. Conclusion Admissions after colorectal operations were greater and more costly for patients discharged to post–acute care even without operative complications. Risk factors can predict the need for post–acute care early in the postoperative course, thereby potentially facilitating early discharge planning. [ABSTRACT FROM AUTHOR]

Background Obesity is a risk factor for cholelithiasis leading to acute cholecystitis which is treated with cholecystectomy. The purpose of this study was to analyze the associations between body mass index class and the intended operative approach (laparoscopic versus open) for and outcomes of cholecystectomy for acute cholecystitis. Methods We conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program data from 2008–2013. The effects of body mass index class on intended procedure type (laparoscopic versus open), conversion from laparoscopic to open operation, and outcomes after cholecystectomy were examined using multivariable logistic regression. Results Data on 20,979 patients who underwent cholecystectomy for acute cholecystitis showed that 18,228 (87%) had a laparoscopic operation; 639 (4%) of these patients required conversion to an open approach; and 2,751 (13%) underwent intended open cholecystectomy. There was an independent association between super obesity (body mass index 50+) and an intended open operation (odds ratio 1.53, 95% confidence interval 1.14–2.05, P = .01). An intended open procedure (odds ratio 3.10, 95% confidence interval 2.40–4.02, P < .0001) and conversion (odds ratio 3.45, 95% confidence interval 2.16–5.50, P < .0001) were associated with increased risk of death/serious morbidity in a model, even when controlling for all other important factors. In the same model, body mass index class was not associated with increased death/serious morbidity. Outcomes after conversion were not substantially worse than outcomes after intended open cholecystectomy. Conclusion This study supports the possibility that an intended open approach to acute cholecystitis, not body mass index class, is associated with worse outcomes after cholecystectomy. An initial attempt at laparoscopy may benefit patients, even those at the highest end of the body mass index spectrum. [ABSTRACT FROM AUTHOR]

Summary Melanoma patients with oncogenic BRAF V600E mutation have poor prognoses. While the role of BRAF V600E in tumorigenesis is well established, its involvement in metastasis that is clinically observed in melanoma patients remains a topic of debate. Here, we show that BRAF V600E melanoma cells have extensive invasion activity as assayed by the generation of F-actin and cortactin foci that mediate membrane protrusion, and degradation of the extracellular matrix (ECM). Inhibition of BRAF V600E blocks melanoma cell invasion. In a BRAF V600E -driven murine melanoma model or in patients’ tumor biopsies, cortactin foci decrease upon inhibitor treatment. In addition, genome-wide expression analysis shows that a number of invadopodia-related genes are downregulated after BRAF V600E inhibition. Mechanistically, BRAF V600E induces phosphorylation of cortactin and the exocyst subunit Exo70 through ERK, which regulates actin dynamics and matrix metalloprotease secretion, respectively. Our results provide support for the role of BRAF V600E in metastasis and suggest that inhibiting invasion is a potential therapeutic strategy against melanoma. [ABSTRACT FROM AUTHOR]