ASO Author Reflections: The Evolution of Surgery for Patients with Stage IV Melanoma.

The role of surgery for patients with stage IV melanoma is rapidly evolving. In the past, limited treatment options were available and surgery was offered to carefully selected patients. Currently, in the era of effective immunotherapy, the role of surgery is still being defined. The present study examines outcomes for patients with stage IV melanoma receiving immunotherapy and surgery. Future studies will help to better identify which patients should receive surgery and when it should be performed in the setting of increasingly available therapeutic modalities for patients with stage IV melanoma.

Surgical Utilization and Outcomes for Patients with Stage IV Melanoma in the Modern Immunotherapy Era.

BACKGROUND: The benefit of surgery for patients with stage IV melanoma in the modern era of effective immunotherapy is unclear. This study aimed to evaluate trends and outcomes after surgical resection of stage IV melanoma in the modern immunotherapy era. METHODS: Patients with stage IV melanoma who received surgery, immunotherapy, or both from 2012 to 2017 were identified from the National Cancer Database (NCDB). Demographics, facility-level characteristics, and use of immunotherapy were compared between patients who received surgery and those who did not. Multivariate Poisson regression modeling, Kaplan-Meier survival analysis, and Cox regression analysis were performed. RESULTS: The study identified 9800 patients with stage IV melanoma, and 2160 of these patients (22 %) underwent surgery. The patients who received surgery were more likely to be younger (P < 0.001), to have private insurance (P < 0.001), to have a higher median income (P = 0.008), and to receive treatment at academic/research programs (P < 0.001), whereas they were less likely to receive immunotherapy (33.7 % vs 36.6 %; P = 0.013). The patients who received immunotherapy had a lower likelihood of undergoing surgery (relative risk [RR], 0.82; 95 % confidence interval [CI[, 0.75-0.88; P < 0.001). The patients who received both surgery and immunotherapy had a better overall survival rate (hazard ratio [HR], 0.41; 95 % CI, 0.36-0.46; P < 0.01) than the patients who received neither immunotherapy nor surgery. CONCLUSIONS: The use of immunotherapy was associated with a lower use of surgery for patients with stage IV melanoma. The patients with stage IV disease who received both surgery and immunotherapy had the highest overall survival rates.

Association of hospital-level factors with utilization of sentinel lymph node biopsy in patients with early-stage vulvar cancer.

OBJECTIVE: To evaluate utilization of sentinel lymph node biopsy (SLNB) for early-stage vulvar cancer at minority-serving hospitals and low-volume facilities. METHODS: Between 2012-2018, individuals with T1b vulvar squamous cell carcinoma were identified using the National Cancer Database. Patient, facility, and disease characteristics were compared between patients undergoing SLNB or inguinofemoral lymph node dissection (IFLD). Multivariable logistic regression, adjusted for patient, facility, and disease characteristics, was used to evaluate factors associated with SLNB. Kaplan-Meier survival analysis using log rank test and Cox regression was performed. RESULTS: Of the 3,532 patients, 2,406 (68.1%) underwent lymph node evaluation, with 1,704 (48.2%) undergoing IFLD and 702 (19.8%) SLNB. In a multivariable analysis, treatment at minority-serving hospitals (OR 0.39, 95% CI 0.19-0.78) and low-volume hospitals (OR 0.44, 95% CI 0.28-0.70) were associated with significantly lower odds of undergoing SLNB compared to receiving care at non-minority-serving and high-volume hospitals, respectively. While SLNB utilization increased over time for the entire cohort and stratified subgroups, use of the procedure did not increase at minority-serving hospitals. After controlling for patient and tumor characteristics, SLNB was not associated with worse OS compared to IFLD in patients with positive (HR 1.02, 95% CI 0.63-1.66) or negative (HR 0.92, 95% CI 0.70-1.21) nodal pathology. CONCLUSIONS: For patients with early-stage vulvar cancer, treatment at minority-serving or low-volume hospitals was associated with significantly decreased odds of undergoing SLNB. Future efforts should be concentrated toward ensuring that all patients have access to advanced surgical techniques regardless of where they receive their care.

Socioeconomic Disparities in Pancreas Cancer Resection and Survival in the Veterans Health Administration.

BACKGROUND: Disparities based on socioeconomic factors such as race, ethnicity, marital status, and insurance status are associated with pancreatic cancer resection, but these disparities are usually not observed for survival after resection. It is unknown if there are disparities when patients undergo their treatment in a non-fee-for-service, equal-access healthcare system such as the Veterans Health Administration (VHA). METHODS: Patients having T1-T3 M0 pancreatic adenocarcinoma diagnosed between 2006 and 2017 were identified from the VHA Corporate Data Warehouse. Socioeconomic, demographic, and tumor variables associated with resection and survival were assessed. RESULTS: In total, 2580 patients with early-stage pancreatic cancer were identified. The resection rate was 36.5%. Surgical resection was independently associated with younger age [odds ratio (OR) 0.94, p < 0.001], White race (OR 1.35, p = 0.028), married status (OR 1.85, p = 0.001), and employment status (retired vs. unemployed, OR 1.41, p = 0.008). There were no independent associations with Hispanic ethnicity, geographic region, or Social Deprivation Index. Resection was associated with significantly improved survival (median 21 vs. 8 months, p = 0.001). Among resected patients, survival was independently associated with younger age (HR 1.019, p = 0.002), geographic region (South vs. Pacific West, HR 0.721, p = 0.005), and employment (employed vs. unemployed, HR 0.752, p = 0.029). Race, Hispanic ethnicity, marital status, and Social Deprivation Index were not independently associated with survival after resection. CONCLUSIONS: Race, marital status, and employment status are independently associated with resection of pancreatic cancer in the VHA, whereas geographic region and employment status are independently associated with survival after resection. Further studies are warranted to determine the basis for these inequities.

Association of Liver Resection and Visiting More Than One Commission on Cancer Hospital for Colorectal Cancer With Liver Metastasis.

INTRODUCTION: Despite the advances in treatment, there are low rates of liver metastasectomy for colorectal cancer with liver metastasis (CRLM) in the United States. The aim of this study was to investigate the association between likelihood of liver metastasectomy for CRLM and seeking care at >1 versus 1 Commission on Cancer (CoC) hospital. METHODS: We performed a retrospective analysis of the National Cancer Database (2011-2017) for patients with CRLM. Patients were grouped based on seeking care at 1 CoC hospital or >1 CoC hospital. An adjusted multivariable Poisson regression interaction analysis was used to evaluate likelihood of liver metastasectomy for CRLM according to race and whether care was sought at >1 CoC hospital. RESULTS: We identified 25,956 patients with CRLM without extra-hepatic disease. 23,088 (89.0%) patients visited 1 CoC hospital and 2868 (11.1%) visited >1 CoC hospital. Black patients were less likely to seek care at >1 CoC hospital (relative risk [RR] 0.68, confidence intervalCI 0.60-0.76, P < 0.001). Undergoing liver metastasectomy was associated with higher likelihood of seeking care at >1 CoC hospital (RR 1.27, CI 1.26-1.52, P < 0.001). Among patients who sought care at >1 CoC hospital, there was no significant difference between White and Black patients undergoing liver metastasectomy (RR 0.86, 95% CI 0.71-1.04, P = 0.11). CONCLUSIONS: Patients with CRLM who sought care at >1 CoC hospital were more likely to undergo a liver metastasectomy. Among White and Black patients who sought care at >1 CoC hospital, there was no difference in likelihood of undergoing a liver metastasectomy.

Racial Disparity in Pancreatoduodenectomy for Borderline Resectable Pancreatic Adenocarcinoma.

BACKGROUND: Previous studies have found racial disparity in pancreatectomies for resectable pancreatic adenocarcinoma. The aim of this study was to investigate if racial disparities were worse in the performance of pancreaticoduodenectomy for borderline resectable pancreatic adenocarcinoma. METHODS: This study used the National Cancer Database (2004-2016) and included patients with non-metastatic and head of the pancreas borderline resectable pancreatic adenocarcinoma. Multivariable, Poisson regression models with robust standard errors evaluated the relative risk (RR) of undergoing a pancreaticoduodenectomy among non-White patients (Black, Asian, and non-White Hispanic) compared with White patients. A Poisson regression model with hospital fixed effects was performed to evaluate if findings were due to within-hospital or between-hospital variation. Interaction between race and neoadjuvant therapy was also evaluated. RESULTS: There were 15,482 patients (median age 68 years, interquartile range 60-76 years; 48.6% male) with borderline resectable pancreatic adenocarcinoma who were predominantly White (84.3%, n = 13,058; non-White, 15.7%, n = 2424). Overall, 18.4% (n = 2853) had a pancreatic resection. Non-White patients had a significantly lower likelihood of undergoing a pancreatic resection for borderline resectable pancreatic adenocarcinoma when compared with White patients (RR 0.75, 95% confidence interval 0.68-0.83; p < 0.001). These findings persisted in the hospital fixed-effects model. In the interaction analysis, there were no significant differences in the likelihood of pancreatic resection if patients received neoadjuvant therapy. CONCLUSIONS: Non-White patients were 25% less likely to undergo a pancreatic resection for borderline resectable pancreatic adenocarcinoma compared with White patients. This racial disparity was due to variation in care within-hospitals and disappeared if non-White patients were treated with neoadjuvant therapy.

We Asked the Experts: The WHO Surgical Safety Checklist and the COVID-19 Pandemic: Recommendations for Content and Implementation Adaptations.

BACKGROUND: As surgical systems are forced to adapt and respond to new challenges, so should the patient safety tools within those systems. We sought to determine how the WHO SSC might best be adapted during the COVID-19 pandemic. METHODS: 18 Panelists from five continents and multiple clinical specialties participated in a three-round modified Delphi technique to identify potential recommendations, assess agreement with proposed recommendations and address items not meeting consensus. RESULTS: From an initial 29 recommendations identified in the first round, 12 were identified for inclusion in the second round. After discussion of recommendations without consensus for inclusion or exclusion, four additional recommendations were added for an eventual 16 recommendations. Nine of these recommendations were related to checklist content, while seven recommendations were related to implementation. CONCLUSIONS: This multinational panel has identified 16 recommendations for sites looking to use the surgical safety checklist during the COVID-19 pandemic. These recommendations provide an example of how the SSC can adapt to meet urgent and emerging needs of surgical systems by targeting important processes and encouraging critical discussions.

Use of immunotherapy and surgery for stage IV melanoma.

BACKGROUND: Immunotherapy for stage IV melanoma has dramatically changed the overall prognosis and treatment strategies. The aim of this study was to evaluate whether changes in systemic immunotherapy options have significantly altered surgical resection rates for patients with stage IV melanoma. METHODS: The National Cancer Database (2004-2015) was used to perform a difference-in-difference analysis to evaluate whether the rate of surgical resection of metastatic disease for stage IV melanoma differed with the use of immunotherapy in the checkpoint inhibitor era in comparison with the use of immunotherapy in the pre-checkpoint inhibitor era. An adjusted difference-in-difference analysis stratified by facility type was performed. An adjusted Poisson regression analysis evaluated predictors of surgical resection in patients with stage IV melanoma who received immunotherapy. RESULTS: There were 14,433 patients with stage IV melanoma (median age, 66 years [interquartile range, 56-76 years]; female, 31.7%), and of all patients in the checkpoint inhibitor era (n = 7,524), 25% (n = 1,879) received immunotherapy. Patients with stage IV disease who received immunotherapy in the checkpoint inhibitor era were more likely to be younger, be healthier, have private insurance, come from upper income quartiles, and be treated at academic programs. A difference-in-difference analysis revealed similar rates of surgical resection of metastatic disease with the use of immunotherapy in the checkpoint inhibitor era and the pre-checkpoint inhibitor era, regardless of facility type. CONCLUSIONS: The distribution of immunotherapy was unequal among patients with stage IV melanoma. Across all facilities, the rates of surgical resection of metastatic disease for stage IV melanoma did not differ with the use of immunotherapy between the checkpoint inhibitor era and the pre-checkpoint inhibitor era.

Adjuvant Therapy Failure Patterns in the Modern Era of Melanoma Management.

BACKGROUND: The management of patients with resected stage 3 melanoma has changed significantly due to adoption of the Multicenter Selective Lymphadenectomy Trial (MSLT)-2 guidelines and to the survival benefit of adjuvant anti-PD-1 immunotherapy and BRAF/MEK-inhibitor (BRAF/MEKi) therapy. Data are scarce regarding recurrence patterns, adjuvant therapy responses, and therapy-associated adverse events (AEs) in the modern era. METHODS: This single-institution, retrospective study analyzed surgically resected stage 3 and oligometastatic stage 4 patients who received anti-PD-1, BRAF/MEKi, or surgery with active surveillance only. The primary end point of the study was recurrence-free survival (RFS). The secondary end points were the location and clinical characteristics of recurrence and therapy-associated AEs. RESULTS: From a cohort of 137 patients, the study enrolled 102 patients treated with adjuvant anti-PD-1 (n = 46), adjuvant BRAF/MEKi (n = 3), or surgery alone (n = 26). During a mean follow-up period of 17 months, 20% of the ani-PD-1 patients, 13% of the BRAF/MEKi patients, and 42% of the surgery-only patients experienced recurrence. Log-rank testing showed a significantly longer RFS for the patients treated with anti-PD-1 [15.3 months; interquartile range (IQR), 8.2-23.2 months; p = 0.04] or BRAF/MEKi (17.9 months; IQR, 12.5-23 months; p = 0.01) than for those treated with surgery alone (11.9 months; IQR, 7.0-17.6 months). In the anti-PD-1 group, AEs occurred less frequently than in the BRAF/MEKi group (54% vs 80%; p = 0.03). CONCLUSIONS: Adjuvant anti-PD-1 and BRAF/MEKi were associated with significantly improved RFS for the patients with resected stage 3 or 4 melanoma. The BRAF/MEKi group had significantly more AEs than the anti-PD-1 group. This is the first study to characterize real-world recurrence in the modern era of adjuvant therapy for melanoma.

Neoadjuvant Therapy is Associated with Improved Survival in Borderline-Resectable Pancreatic Cancer.

BACKGROUND: Neoadjuvant therapy has shown value in various cancer types. The role of neoadjuvant therapy in pancreatic ductal adenocarcinoma (PDAC), however, remains unknown. The aim of the present work is to evaluate the effect of neoadjuvant therapy on the survival of patients with borderline-resectable PDAC. PATIENTS AND METHODS: Between 2004 and 2015, 7730 patients with resectable PDAC and 1980 patients with borderline-resectable PDAC were identified from the National Cancer Database (NCDB). Survival was compared between resectable and borderline-resectable patients. Survival and pathologic characteristics were also compared within borderline-resectable patients who received neoadjuvant therapy and those who received adjuvant therapy alone. Kaplan-Meier method and Cox proportional-hazard models were used for analysis. RESULTS: Median overall survival (mOS) of all patients with resectable PDAC was similar to that of patients with borderline-resectable disease treated with neoadjuvant therapy (26.5 versus 25.7 months, p = 0.78). Patients with borderline-resectable disease treated with neoadjuvant therapy had improved mOS compared with borderline-resectable patients treated with adjuvant therapy alone (25.7 versus 19.6 months, p < 0.0001). When comparing patients with borderline-resectable disease who received neoadjuvant therapy versus those who received adjuvant therapy alone, the former less often had node-positive pancreatic cancer (40.6% versus 76.3%, p < 0.001) and margin-positive resections (17.8% versus 44.4%, p < 0.001). CONCLUSION: Neoadjuvant therapy is associated with enhanced survival in patients with borderline-resectable pancreatic cancer, which may be attributed to tumor downstaging.

Diagnosis of Depression is Associated with Readmission Following Elective Pancreatectomy.

BACKGROUND: Diagnosis of depression may be associated with adverse outcomes following surgery. The aim of this study is to investigate whether depression is associated with an increased readmission rate following elective pancreatectomy, which is currently unknown. METHODS: The 2014 Nationwide Readmissions Database was used to evaluate whether diagnosis of depression was associated with 30-day readmission following elective pancreatectomy in adult patients. Univariate and multivariate logistic regression models were adjusted for clustering by facility. A secondary analysis was performed to evaluate whether the risk of diagnosis of depression on 30-day readmission rates was modified by length of stay (median 8 days). All multivariate models were adjusted for patient-level characteristics. RESULTS: There were an estimated 11,992 patients who underwent elective pancreatectomy. Mean age was 63 years, and 48.9% were male. Approximately 10.2% (n = 1223) had diagnosis of depression. Depression was associated with higher odds of 30-day readmission following elective pancreatectomy on univariate [odds ratio (OR) 1.26, 95% confidence interval (CI) 1.01-1.59; P = 0.043] and multivariate analyses (OR 1.29, 95% CI 1.01-1.65; P = 0.039). Although length of stay > 8 days was independently associated with higher odds of 30-day readmission (P = 0.005), length of stay did not alter the association between diagnosis of depression and odds of readmission (P = 0.90). CONCLUSIONS: Diagnosis of depression was associated with higher odds of 30-day readmission following pancreatectomy, regardless of length of stay. Enhanced focus on evaluation and optimization of perioperative mental health is warranted to identify patients at high risk for readmission and reduce the burden related to readmission following pancreatic surgery.

Mixed Response to Immunotherapy in Patients with Metastatic Melanoma.

BACKGROUND: Immunotherapy has improved overall survival in metastatic melanoma. Response to therapy can be difficult to evaluate as the traditionally used RECIST 1.1 criteria do not capture heterogeneous responses. Here we describe the clinical characterization of melanoma patients with a clinically defined mixed response to immunotherapy. METHODS: This was a single institution, retrospective analysis of stage IV melanoma patients who received first-line anti-CTLA-4, anti-PD1, or combination anti-CTLA-4/anti-PD1. Therapy response was assessed via clinical definitions, which consisted of cross-sectional imaging combined with clinical exam. Course of disease, clinicopathological characteristics, and management in patients with a mixed clinical response were analyzed. RESULTS: In 292 patients (anti-CTLA4 = 63; anti-PD1 = 148, anti-CTLA4/anti-PD1 = 81), 103 were responders (35%), 64 mixed responders (22%), and 125 patients had progressive disease (43%). Of patients with a mixed response, 56% eventually had response to therapy (mixed response followed by response, MR-R), while 31% progressed on therapy (MR-NR). MR-NR patients had higher median LDH (p < 0.01), 3 or more organ sites with metastases (p < 0.01), and more frequently had M1d disease (p < 0.01). Mixed responders who underwent surgery (n = 20) had a significantly longer mean OS compared to patients who did not undergo surgery (6.9 years, 95% CI 6.2-7.6 vs. 6.0 years, 95% CI 4.6-7.3, p = 0.02). DISCUSSION: Mixed response to immunotherapy in metastatic melanoma was not uncommon in our cohort (22%). Clinical characteristics associated with progression of disease after initial mixed response included higher LDH, brain metastases, and ≥ 3 organ sites with metastases. Surgical treatment for highly selected patients with a mixed response was associated with improved outcomes.

Global Survey of Perceptions of the Surgical Safety Checklist Among Medical Students, Trainees, and Early Career Providers.

BACKGROUND: The Surgical Safety Checklist (SSC) has been shown to reduce perioperative complications across global health systems. We sought to assess perceptions of the SSC and suggestions for its improvement among medical students, trainees, and early career providers. METHODS: From July to September 2019, a survey assessing perceptions of the SSC was disseminated through InciSioN, the International Student Surgical Network comprising medical students, trainees, and early career providers pursuing surgery. Individuals with ≥2 years of independent practice after training were excluded. Respondents were categorized according to any clinical versus solely non-clinical SSC exposure. Logistic regression was used to evaluate associations between clinical/non-clinical exposure and promoting future use of the SSC, adjusting for potential confounders/mediators: training level, human development index, and first perceptions of the SSC. Thematic analysis was conducted on suggestions for SSC improvement. RESULTS: Respondent participation rate was 24%. Three hundred and eighteen respondents were included in final analyses; 215 (67%) reported clinical exposure and 190 (60%) were promoters of future SSC use. Clinical exposure was associated with greater odds of promoting future SSC use (aOR 1.81 95% CI [1.03-3.19], p = 0.039). A greater proportion of promoters reported "Improved Operating Room Communication" as a goal of the SSC (0.21 95% CI [0.15-0.27]-vs.-0.12 [0.06-0.17], p = 0.031), while non-promoters reported the SSC goals were "Not Well Understood" (0.08 95% CI [0.03-0.12]-vs.-0.03 [0.01-0.05], p = 0.032). Suggestions for SSC improvement emphasized context-specific adaptability and earlier formal training. CONCLUSIONS: Clinical exposure to the SSC was associated with promoting its future use. Earlier formal clinical training may improve perceptions and future use among medical students, trainees, and early career providers.

Correction to: Global Survey of Perceptions of the Surgical Safety Checklist Among Medical Students, Trainees, and Early Career Providers.

In the original version of the article, Dominique Vervoort's last name was misspelled. It is correct as reflected here. The original article has been updated.

Pudendal nerve terminal motor latency testing does not provide useful information in guiding therapy for fecal incontinence.

PURPOSE: Pudendal nerve terminal motor latency (PNTML) testing is a standard recommendation for the evaluation of fecal incontinence. Its role in guiding therapy for fecal incontinence has been previously questioned. The aim of this study was to evaluate the relationship between PNTML testing and anorectal dysfunction. METHODS: This was a retrospective analysis of data collected prospectively from patients who presented to a pelvic floor disorder center from 2007 to 2015. The relationship between PNTML (normal versus delayed) and anorectal manometry, fecal incontinence severity, and fecal incontinence-related quality of life scores was assessed using the Wilcoxon-Mann-Whitney test. RESULTS: Two hundred sixty-nine patients underwent PNTML testing, and 91.1% were female (N = 245) (median age 62.2 years). Normal PNTML was seen in 234 (87.0%) patients. Among 268 patients who underwent anorectal manometry, delayed PNTML was only significantly associated with median maximum anal squeeze pressure (P = 0.04). Delayed PNTML was not associated with a decrease in median fecal incontinence severity or fecal incontinence-related quality of life scores (N = 99). CONCLUSIONS: PNTML was only associated with median maximum anal squeeze pressure, and it was not associated with patient-reported severity of symptoms of fecal incontinence, changes in quality of life attributable to fecal incontinence, median mean resting anal pressure, or median maximum resting anal pressure. PNTML testing may not be relevant to current therapeutic algorithms for fecal incontinence and its routine use should be questioned.

Perception of Safety of Surgical Practice Among Operating Room Personnel From Survey Data Is Associated With All-cause 30-day Postoperative Death Rate in South Carolina.

OBJECTIVE: To evaluate whether the perception of safety of surgical practice among operating room (OR) personnel is associated with hospital-level 30-day postoperative death. BACKGROUND: The relationship between improvements in the safety of surgical practice and benefits to postoperative outcomes has not been demonstrated empirically. METHODS: As part of the Safe Surgery 2015: South Carolina initiative, a baseline survey measuring the perception of safety of surgical practice among OR personnel was completed. We evaluated the relationship between hospital-level mean item survey scores and rates of all-cause 30-day postoperative death using binomial regression. Models were controlled for multiple patient, hospital, and procedure covariates using supervised principal components regression. RESULTS: The overall survey response rate was 38.1% (1793/4707) among 31 hospitals. For every 1 point increase in the hospital-level mean score for respect [adjusted relative risk (aRR) 0.78, 95% CI 0.65-0.93, P = 0.0059], clinical leadership (aRR 0.86, 95% CI 0.74-0.9932, P = 0.0401), and assertiveness (aRR 0.71, 95% CI 0.54-0.93, P = 0.01) among all survey respondents, there were associated decreases in the hospital-level 30-day postoperative death rate after inpatient surgery ranging from 14% to 29%. Higher hospital-level mean scores for the statement, "I would feel safe being treated here as a patient," were associated with significantly lower hospital-level 30-day postoperative death rates (aRR 0.83, 95% CI 0.70-0.97, P = 0.02). Although most findings seen among all OR personnel were seen among nurses, they were often absent among surgeons. CONCLUSIONS: Perception of OR safety of surgical practice was associated with hospital-level 30-day postoperative death rates.