A Prospective Clinical Trial to Evaluate Mesothelin as a Biomarker for the Clinical Management of Patients With Esophageal Adenocarcinoma.

OBJECTIVE: To investigate the utility of serum soluble mesothelin-related peptide (SMRP) and tumor mesothelin expression in the management of esophageal adenocarcinoma (ADC). BACKGROUND: Clinical management of esophageal ADC is limited by a lack of accurate evaluation of tumor burden, treatment response, and disease recurrence. Our retrospective data showed that tumor mesothelin and its serum correlate, SMRP, are overexpressed and associated with poor outcomes in patients with esophageal ADC. METHODS: Serum SMRP and tumoral mesothelin expression from 101 patients with locally advanced esophageal ADC were analyzed before induction chemoradiation (pretreatment) and at the time of resection (posttreatment), as a biomarker for treatment response, disease recurrence, and overall survival (OS). RESULTS: Pre and posttreatment serum SMRP was ≥1 nM in 49% and 53%, and pre and post-treatment tumor mesothelin expression was >25% in 35% and 46% of patients, respectively. Pretreatment serum SMRP was not significantly associated with tumor stage ( P = 0.9), treatment response (radiologic response, P = 0.4; pathologic response, P = 0.7), or recurrence ( P =0.229). Pretreatment tumor mesothelin expression was associated with OS (hazard ratio: 2.08; 95% CI: 1.14-3.79; P = 0.017) but had no statistically significant association with recurrence ( P = 0.9). Three-year OS of patients with pretreatment tumor mesothelin expression of ≤25% was 78% (95% CI: 68%-89%), compared with 49% (95% CI: 35%-70%) among those with >25%. CONCLUSIONS: Pretreatment tumor mesothelin expression is prognostic of OS for patients with locally advanced esophageal ADC, whereas serum SMRP is not a reliable biomarker for monitoring treatment response or recurrence.

Diagnosis of COVID-19 and the bariatric surgery population: a single center experience.

BACKGROUND: While many cases of the coronavirus disease 2019 (COVID-19) are mild, patients with underlying medical conditions such as hypertension (HTN), diabetes mellitus (DM), older age, and morbid obesity are at higher risk of hospitalization and death. These conditions are characteristic of patients eligible for bariatric surgery, many of whom underwent weight loss procedures in the months prior to cessation of elective surgery in March 2020. The effects of the virus on these high-risk patients who had increased healthcare exposure in the early days of the pandemic are currently unknown. OBJECTIVES: To describe the experience of patients who underwent bariatric surgery during the early evolution of the COVID-19 pandemic. METHODS: This is a cross-sectional study including patients from a single center who underwent bariatric surgery from January 1st, 2020 to March 18th, 2020. A database was created to analyze patients' demographics, operative variables, and postoperative outcomes. All patients were contacted and a telephone survey was completed to inquire about COVID-19 exposure, symptoms, and testing 30 days before and after surgery. RESULTS: A total of 190 patients underwent bariatric surgery during the study period. Laparoscopic sleeve gastrectomy was the most common procedure (71.6%). One hundred seventy-eight patients (93.7%) completed the telephone survey. Postoperatively, 19 patients (10.7%) reported COVID-19 compatible symptoms, and six patients (3.4%) went on to test positive for COVID-19. There were no COVID-19-related hospital admissions or mortalities in this population. CONCLUSIONS: Morbidly obese patients are at high risk of severe disease secondary to COVID-19, and those undergoing bariatric surgery during the evolution of the pandemic reported symptoms at a rate of 10.7% 30 days after the surgery. While none of these patients suffered severe COVID-19 disease, the temporal relationship of their symptomatology and increased exposure to the healthcare system as a result of their surgery suggest an increased risk of disease with elective surgery.

"Sip & Share": Building Resilience in Surgery Residency Through Moral Distress Rounds.

OBJECTIVE: Resident moral distress rounds were instituted during the COVID-19 pandemic to provide a safe zone for discussion, reflection, and the identification of the ethical challenges contributing to moral distress. The sessions, entitled "Sip & Share," also served to foster connectedness and build resilience. DESIGN: A baseline needs assessment was performed and only 36% of general surgery residents in the program were satisfied with the current non-technical skills curriculum. Only 62% were comfortable with navigating ethical issues in surgery. About 72% were comfortable with leading a goals-of-care discussion, and 63% of residents were comfortable with offering surgical palliative care options. Case-based discussions over video conferencing were organized monthly. Each session was structured based on the eight-step methodology described by Morley and Shashidhara. Participation was voluntary. The sessions explored moral distress, and the ethical tensions between patient autonomy and beneficence, and beneficence and non-maleficence. SETTING: Large general surgery residency in an urban tertiary medical center. PARTICIPANTS: General surgery residents. RESULTS: A post-intervention survey was performed with improvement in the satisfaction with the non-technical skills curriculum (70% from 36%). The proportion of residents feeling comfortable with navigating ethical issues in surgery increased from 62% to 72%. A survey was performed to assess the efficacy of the moral distress rounds after eight Sip & Share sessions over ten months. All thirteen respondents agreed that the discussions provided them with the vocabulary to discuss ethical dilemmas and define the ethical principles contributing to their moral distress. 93% were able to apply the templates learned to their practice, 77% felt that the discussions helped mitigate stress. All respondents recommended attending the sessions to other residents. CONCLUSIONS: Moral distress rounds provide a structured safe zone for residents to share and process morally distressing experiences. These gatherings mitigate isolation, promote a sense of community, and provide a support network within the residency. In addition, residents are equipped with the vocabulary to identify the ethical principles being challenged and are provided practical take-aways to avoid similar conflicts in the future.

Postoperative pneumonia after bariatric surgery during the COVID-19 pandemic: a National Surgical Quality Improvement Program study.

BACKGROUND: During the COVID-19 pandemic, surgical centers had to weigh the benefits and risks of conducting bariatric surgery. Obesity increases the risk of developing severe COVID-19 infections, and therefore, bariatric surgery is beneficial. In contrast, surgical patients who test positive for COVID-19 have higher mortality rates. OBJECTIVE: This study investigates the national prevalence of postoperative pneumonia during the COVID-19 pandemic in the bariatric surgery population. SETTING: The American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) database. METHODS: This is a cross-sectional study using the ACS-NSQIP database. The population of concern included patients who underwent sleeve gastrectomy and Roux-en-Y gastric bypass procedures. Information was extracted on rate of postoperative pneumonia and other 30-day complications between 2018 and 2020. RESULTS: All baseline characteristics were similar among patients who underwent bariatric surgery between 2018 and 2020. However, there was a 156% increase in postoperative pneumonia in 2020 compared with the previous year. Furthermore, despite the similar postoperative complication rates across the years, there was a statistically significant increase in all-cause mortality in 2020. The multivariate analysis showed that having surgery in 2020 was a statistically significant risk factor for pneumonia development postoperatively. CONCLUSIONS: This study showed a statistically significant increase in the prevalence of postoperative pneumonia during the COVID-19 pandemic among bariatric surgery patients. Surgical centers must continuously evaluate the risks associated with healthcare-associated exposure to COVID-19 and weigh the benefits of bariatric surgery.

Safety and efficacy of roux-en-y gastric bypass in older aged patients.

INTRODUCTION: laparoscopic Roux-en-Y Gastric Bypass (LRYGB) has been a revolutionary intervention for weight loss with reduction of up to 60-70% of excess body weight. However, these outcomes are not as well validated at the extremes of age, where the safety of the intervention still has some caveats. The aim of this study is to assess the efficacy and safety of primary LRYGB among different age groups. METHODS: the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried for patients who underwent primary LRYGB from January 2014 to December 2017 at a single institution. Four groups were created and compared by dividing our sample by age quartiles. The primary outcome was percent excess weight loss (%EWL) at 1 year. Additional operative outcomes and complications were also compared across groups. RESULTS: a total of 1013 patients underwent non-revisional LRYGB during the study period. Mean %EWL at one year was 55%. When compared between quartiles, there was a statistically significant difference in %EWL: 1st 62%, 2nd 57%, 3rd 54% and 4th 47% (p=0.010). The differences in the secondary outcomes between age groups did not demonstrate statistical significance. CONCLUSIONS: though patients in the fourth age quartile (range) did not demonstrate a statistically significant increase in adverse outcomes, they did lose less weight compared to other cohorts. The %EWL at one year after RYGB varied by age in our cohort. Goals after bariatric surgery should be individualized as weight loss is less robust with aging.

Tumor and Tumor-Associated Macrophage Programmed Death-Ligand 1 Expression Is Associated With Adjuvant Chemotherapy Benefit in Lung Adenocarcinoma.

INTRODUCTION: Patients with stage II to III lung adenocarcinomas are treated with adjuvant chemotherapy (ACT) to target the premetastatic niche that persists after curative-intent resection. We hypothesized that the premetastatic niche is a scion of resected lung tumor microenvironment and that analysis of tumor microenvironment can stratify survival benefit from ACT. METHODS: Using tumor and tumoral stroma from 475 treatment-naive patients with stage II to III lung adenocarcinomas, we constructed a tissue microarray and performed multiplex immunofluorescent staining for immune markers (programmed death-ligand 1 [PD-L1], tumor-associated macrophages [TAMs], and myeloid-derived suppressor cells) and derived myeloid-lymphoid ratio. The association between immune markers and survival was evaluated using Cox models adjusted for pathologic stage. RESULTS: Patients with high PD-L1 expression on TAMs or tumor cells in resected tumors had improved survival with ACT (TAMs: hazard ratio [HR] = 1.79, 95% confidence interval [CI]: 1.12-2.85; tumor cells: HR = 3.02, 95% CI: 1.69-5.40). Among patients with high PD-L1 expression on TAMs alone or TAMs and tumor cells, ACT survival benefit is pronounced with high myeloid-lymphoid ratio (TAMs: HR = 3.87, 95% CI: 1.79-8.37; TAMs and tumor cells: HR = 2.19, 95% CI: 1.02-4.71) or with high stromal myeloid-derived suppressor cell ratio (TAMs: HR = 2.53, 95% CI: 1.29-4.96; TAMs and tumor cells: HR = 3.21, 95% CI: 1.23-8.35). Patients with low or no PD-L1 expression on TAMs or tumor cells had no survival benefit from ACT. CONCLUSIONS: Our observation that PD-L1 expression on TAMs or tumor cells is associated with improved survival with ACT provides rationale for prospective investigation and developing chemoimmunotherapy strategies for patients with lung adenocarcinoma.

The COVID-19 Pandemic Did Not Affect Target Weight Loss 1 Year Post Bariatric Surgery.

BACKGROUND: Bariatric surgery is one of the most effective treatments for patients with severe and complex obesity. Lifestyle modifications in diet and exercise habits have long been important adjunct to the long-term success after bariatric surgery. The effect of the COVID-19 pandemic on the postoperative bariatric patient is not well understood. We sought to evaluate the impact the COVID-19 pandemic on postoperative weight loss at 1 year in a bariatric cohort. METHODS: All patients who underwent bariatric surgery from January 1, 2020, to March 12, 2020, were included. Patients who underwent bariatric surgery during the same period of the two preceding years (2018 and 2019) were included as control groups. Primary end point was %EBMIL at 1 year. A telephone survey was administered to all patients from 2020 to assess for their perception on the effects of the COVID-19 pandemic on weight loss. RESULTS: A total of 596 patients were included: 181 from 2020, 199 from 2019, and 216 from 2018. The response rate was 97% and 53.4% of patients reported that the lockdown affected their ability to lose weight. The %EBMIL at 1 year was 64.1%, 63.7%, and 68.1% for 2020, 2019, and 2018, respectively. There was no difference in weight loss at 1 year (p = 0.77) despite a decrease in exercise activity in those who had surgery just before the pandemic. CONCLUSION: There was no difference in target weight loss at 1 year in a cohort who underwent bariatric surgery before the pandemic.

A prospective trial of intraoperative tissue oxygenation measurement and its association with anastomotic leak rate after Ivor Lewis esophagectomy.

BACKGROUND: Anastomotic leak following Ivor Lewis esophagectomy is associated with increased morbidity/mortality and decreased survival. Tissue oxygenation at the anastomotic site may influence anastomotic leak. Methods for establishing tissue oxygenation at the anastomotic site are lacking. METHODS: Over a 2-year study period, 185 Ivor Lewis esophagectomies were performed. Study participants underwent measurement of gastric conduit tissue oxygenation at the planned anastomotic site using the wireless pulse oximetry device. Associations between anastomotic leaks or strictures and tissue oxygenation levels were analyzed using Wilcoxon rank sum test or Fisher's exact test. RESULTS: Among study participants (n=114), median gastric conduit tissue oxygenation level was 92% (range, 62-100%). There were 8 (7.0%) anastomotic leaks and 3 (2.6%) strictures. Analysis of tissue oxygenation as a continuous variable showed no difference in median tissue oxygenation in patients with and without leaks (98% and 92%; P=0.2) and stricture formation (89% and 92%; P=0.6). Analysis of tissue oxygenation as a dichotomous variable found no difference in anastomotic leak rates [7.5% (n=93) in >80% vs. 0% (n=20) in ≤80%; P=0.3]. There were no significant differences in leak rates in concurrent study nonparticipants. CONCLUSIONS: No significant association was observed between intraoperative tissue oxygenation at the anastomotic site and subsequent anastomotic leak or stricture formation among patients undergoing Ivor Lewis esophagectomy.

Combination Immunotherapy with CAR T Cells and Checkpoint Blockade for the Treatment of Solid Tumors.

Checkpoint blockade (CPB) therapy can elicit durable clinical responses by reactivating an exhausted immune response. However, response rates remain limited, likely secondary to a lack of a tumor-reactive immune infiltrate. Chimeric antigen receptor (CAR) T cells may provide the necessary tumor-targeting immune infiltrate and a highly specific antitumor immune response. This can be further amplified by the addition of CPB agents, which serve to counteract the immune inhibitory environment undermining optimal CAR T cell efficacy. Herein, we review preclinical and clinical combination therapy with CAR T cells and CPB agents, with a focus on solid tumor malignancies.

Safety and efficacy of roux-en-y gastric bypass in older aged patients / Segurança e eficácia do bypas gástrico em Y de Roux em pacientes idosos

ABSTRACT Introduction: laparoscopic Roux-en-Y Gastric Bypass (LRYGB) has been a revolutionary intervention for weight loss with reduction of up to 60-70% of excess body weight. However, these outcomes are not as well validated at the extremes of age, where the safety of the intervention still has some caveats. The aim of this study is to assess the efficacy and safety of primary LRYGB among different age groups. Methods: the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried for patients who underwent primary LRYGB from January 2014 to December 2017 at a single institution. Four groups were created and compared by dividing our sample by age quartiles. The primary outcome was percent excess weight loss (%EWL) at 1 year. Additional operative outcomes and complications were also compared across groups. Results: a total of 1013 patients underwent non-revisional LRYGB during the study period. Mean %EWL at one year was 55%. When compared between quartiles, there was a statistically significant difference in %EWL: 1st 62%, 2nd 57%, 3rd 54% and 4th 47% (p=0.010). The differences in the secondary outcomes between age groups did not demonstrate statistical significance. Conclusions: though patients in the fourth age quartile (range) did not demonstrate a statistically significant increase in adverse outcomes, they did lose less weight compared to other cohorts. The %EWL at one year after RYGB varied by age in our cohort. Goals after bariatric surgery should be individualized as weight loss is less robust with aging.

RESUMO Introdução: o Bypass Gástrico Laparoscópico em Y de Roux (LRYGB) tem sido uma intervenção revolucionária para perda de peso com redução de até 60-70% do excesso de peso corporal. No entanto, esses resultados não são tão bem validados nos extremos de idade, onde a segurança da intervenção ainda possui algumas ressalvas. O objetivo deste estudo é avaliar a eficácia e segurança do LRYGB entre diferentes faixas etárias. Métodos: O banco de dados do Programa de Acreditação e Melhoria da Qualidade da Cirurgia Metabólica e Bariátrica (MBSAQIP) foi consultado para pacientes submetidos a LRYGB de janeiro de 2014 a dezembro de 2017 em uma única instituição. Quatro grupos foram criados e comparados dividindo a amostra por quartis de idade. O desfecho primário foi perda percentual de excesso de peso (%EWL) em 1 ano. Resultados: 1013 pacientes foram submetidos a LRYGB durante o período do estudo. A média de %EWL em um ano foi de 55%. Quando comparados entre os quartis, houve diferença significante no %EWL: 1º 62%, 2º 57%, 3º 54%, e 4º 47% (p=0,010). As diferenças nos desfechos secundários entre as faixas etárias não demonstraram significância estatística. Conclusões: embora os pacientes no quarto quartil de idade não tenham demonstrado um aumento estatisticamente significativo nos resultados adversos, eles perderam menos peso em comparação com outras coortes. O %EWL um ano após RYGB variou de acordo com a idade em nossa coorte. Os objetivos após a cirurgia bariátrica devem ser individualizados, pois a perda de peso é menos robusta com o envelhecimento.

Attaining Proficiency in Robotic-Assisted Minimally Invasive Esophagectomy While Maximizing Safety During Procedure Development.

OBJECTIVE: Robotic-assisted minimally invasive esophagectomy (RAMIE) is an emerging complex operation with limited reports detailing morbidity, mortality, and requirements for attaining proficiency. Our objective was to develop a standardized RAMIE technique, evaluate procedure safety, and assess outcomes using a dedicated operative team and 2-surgeon approach. METHODS: We conducted a study of sequential patients undergoing RAMIE from January 25, 2011, to May 5, 2014. Intermedian demographics and perioperative data were compared between sequential halves of the experience using the Wilcoxon rank sum test and the Fischer exact test. Median operative time was tracked over successive 15-patient cohorts. RESULTS: One hundred of 313 esophageal resections performed at our institution underwent RAMIE during the study period. A dedicated team including 2 attending surgeons and uniform anesthesia and OR staff was established. There were no significant differences in age, sex, histology, stage, induction therapy, or risk class between the 2 halves of the study. Estimated blood loss, conversions, operative times, and overall complications significantly decreased. The median resected lymph nodes increased but was not statistically significant. Median operative time decreased to approximately 370 minutes between the 30th and the 45th cases. There were no emergent intraoperative complications, and the anastomotic leak rate was 6% (6/100). The 30-day mortality was 0% (0/100), and the 90-day mortality was 1% (1/100). CONCLUSIONS: Excellent perioperative and short-term patient outcomes with minimal mortality can be achieved using a standardized RAMIE procedure and a dedicated team approach. The structured process described may serve as a model to maximize patients' safety during development and assessment of complex novel procedures.

Pretreatment Dysphagia in Esophageal Cancer Patients May Eliminate the Need for Staging by Endoscopic Ultrasonography.

BACKGROUND: Neoadjuvant therapy is commonly administered to patients with localized disease who have T3-4 esophageal disease as staged by endoscopic ultrasound (EUS). Previously, we noted that patients who present with dysphagia have a higher EUS T stage. We hypothesized that the presence of dysphagia is predictive of EUS T3-4 disease and that staging EUS could be forgone for esophageal cancer patients with dysphagia. METHODS: We performed a prospective, intent-to-treat, single-cohort study in which patients with potentially resectable esophageal cancer completed a standardized four-tier dysphagia score survey. EUS was performed as part of our standard evaluation. To determine whether the presence of dysphagia predicted EUS T3-4 disease, the dysphagia score was compared with EUS T stage. RESULTS: The study enrolled 114 consecutive patients between August 2012 and February 2014: 77% (88 of 114) received neoadjuvant therapy, 18% (20 of 114) did not, and 5% (6 of 114) pursued treatment elsewhere. In total, 70% (80 of 114) underwent esophagectomy; of these, 54% (61 of 114) had dysphagia and 46% (53 of 114) did not. Dysphagia scores were 66% (40 of 61) grade 1, 25% (15 of 61) grade 2, and 10% (6 of 61) grade 3 to 4. Among patients with dysphagia, 89% (54 of 61) had T3-4 disease by EUS; among those without dysphagia, only 53% (28 of 53) had T3-4 disease by EUS (p < 0.001). CONCLUSIONS: The presence of dysphagia in patients with esophageal cancer was highly predictive of T3-4 disease by EUS. On the basis of this finding, approximately 50% of patients currently undergoing staging EUS at our institution could potentially forgo EUS before neoadjuvant therapy. Patients without dysphagia, however, should still undergo EUS.