Effect of Neoadjuvant Chemotherapy on Tumor-Infiltrating Lymphocytes in Resectable Gastric Cancer: Analysis from a Western Academic Center.

Tumor-infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center. We hypothesized that NAC executes immunostimulatory roles, as evidenced by an increased number of anti-tumor TILs in the tumor microenvironment. We found significantly elevated levels of conventional and memory CD8+ T cells, as well as total TILs (CD4+, CD8+, Treg, B cells), within chemotherapy-treated tumors compared with chemotherapy-naïve specimens. We also revealed important associations between survival and pathologic responses with enhanced TIL infiltration. Taken together, our findings advocate for an immunostimulatory role of chemotherapy and underscore the potential synergistic effect of combining chemotherapy with immunotherapy in resectable gastric cancer.

The Effect of Laparoscopic Gastric Ischemic Preconditioning Prior to Esophagectomy on Anastomotic Stricture Rate and Comparison with Esophagectomy-Alone Controls.

BACKGROUND: Benign anastomotic stricture is a recognized complication following esophagectomy. Laparoscopic gastric ischemic preconditioning (LGIP) prior to esophagectomy has been associated with decreased anastomotic leak rates; however, its effect on stricture and the need for subsequent endoscopic intervention is not well studied. METHODS: This was a case-control study at an academic medical center using consecutive patients undergoing oncologic esophagectomies (July 2012-July 2022). Our institution initiated an LGIP protocol on 1 January 2021. The primary outcome was the occurrence of stricture within 1 year of esophagectomy, while secondary outcomes were stricture severity and frequency of interventions within the 6 months following stricture. Bivariable comparisons were performed using Chi-square, Fisher's exact, or Mann-Whitney U tests. Multivariable regression controlling for confounders was performed to generate risk-adjust odds ratios and to identify the independent effect of LGIP. RESULTS: Of 253 esophagectomies, 42 (16.6%) underwent LGIP prior to esophagectomy. There were 45 (17.7%) anastomotic strictures requiring endoscopic intervention, including three patients who underwent LGIP and 42 who did not. Median time to stricture was 144 days. Those who underwent LGIP were significantly less likely to develop anastomotic stricture (7.1% vs. 19.9%; p = 0.048). After controlling for confounders, this difference was no longer significant (odds ratio 0.46, 95% confidence interval 0.14-1.82; p = 0.29). Of those who developed stricture, there was a trend toward less severe strictures and decreased need for endoscopic dilation in the LGIP group (all p < 0.20). CONCLUSION: LGIP may reduce the rate and severity of symptomatic anastomotic stricture following esophagectomy. A multi-institutional trial evaluating the effect of LGIP on stricture and other anastomotic complications is warranted.

Hazards of surgical smoke from electrocautery: A critical review of the data.

INTRODUCTION: Concerns have been voiced regarding the possibility of health risks to the operating room personnel from exposure to surgical smoke generated from electrocautery. METHODS: Ovid Medline was queried using search terms "surgical smoke", "electrosurgery," "smoke evacuator". The NIOSH Health Hazard Evaluations Database was searched using terms, "hospital", "operating room", "Ames", "mutagen", and "salmonella". RESULTS: Levels of pollutants in the breathable airspace within the operating room have been repeatedly shown to be very low. Absolute counts of particulate matter in the operating room are low when compared to other environments. The possibility for virus transmission with electrocautery in the operating room is unknown. CONCLUSIONS: The risks related to the exposure to electrocautery surgical smoke have been overstated. Rigid mandates requiring smoke evacuators in all situations are not justified at this time.

Immune Landscape of Epstein-Barr Virus-Associated Gastric Cancer: Analysis From a Western Academic Institution.

INTRODUCTION: Epstein-Barr virus-associated gastric cancer (EBVaGC) may be a meaningful biomarker for potential benefit from immunotherapy. Further investigation is needed to characterize the immune landscape of EBVaGC. We assessed our institutional frequency of surgically treated EBVaGC and analyzed the immunologic biomarker profile and tumor-infiltrating lymphocyte (TIL) phenotypes of a series of EBVaGC compared to non-EBVaGC cases. METHODS: Available tissue samples from all patients with biopsy-confirmed gastric adenocarcinoma who underwent resection with curative intent from 2012 to 2020 at our institution were collected. In situ hybridization was used to assess EBV status; multiplex immunohistochemistry was performed to assess mismatch repair status, Programmed Death-Ligand 1 (PD-L1) expression, and phenotypic characterization of TILs. RESULTS: Sixty-eight samples were included in this study. EBVaGC was present in 3/68 (4%) patients. Among all patients, 27/68 (40%) had positive PD-L1 expression; two of three (67%) EBVaGC patients exhibited positive PD-L1 expression. Compared to non-EBVaGC, EBV-positive tumors showed 5-fold to 10-fold higher density of TILs in both tumor and stroma and substantially elevated CD8+ T cell to Tregulatory cell ratio. The memory subtypes of CD8+ and CD4+ T cells were upregulated in EBVaGC tumors and stromal tissue compared to non-EBVaGC. CONCLUSIONS: The incidence of surgically resected EBVaGC at our center was 4%. EBVaGC tumors harbor elevated levels of TILs, including memory subtypes, within both tumor and tumor-related stroma. Robust TIL presence and upregulated PD-L1 positivity in EBVaGC may portend promising responses to immunotherapy agents. Further investigation into routine EBV testing and TIL phenotype of patients with gastric cancer to predict response to immunotherapy may be warranted.

National trends in technique use for esophagectomy: Does primary surgeon specialty matter?

BACKGROUND: Cardiothoracic surgeons and general surgeons (including surgical oncologists) perform most esophagectomies. The purpose of this study was to explore whether specialty-driven differences in surgical techniques and the use of minimally invasive surgical approaches exist and are associated with postoperative outcomes after esophagectomy. METHODS: This was a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program esophagectomy-targeted participant user file (2016-2018). Patients who underwent esophagectomy were sorted into cardiothoracic and general surgeon cohorts based on surgeon specialty. Perioperative characteristics and postoperative outcomes were compared using the χ2 analysis or independent t test. Multivariable logistic regression controlling for perioperative variables was performed to generate risk-adjusted rates of postoperative outcomes compared by surgical specialty. RESULTS: Of 3,247 patients included, 1,792 (55.2%) underwent esophagectomy by cardiothoracic surgeons and 1,455 (44.5%) by general surgeons as the primary surgeon. Cardiothoracic surgeons were more likely to use traditional minimally invasive surgical (P = .0004) or open approaches (P < .0001) and less likely to use robotic (P = .04) or a hybrid robotic and traditional approaches (P < .0001). Cardiothoracic surgeons performed more Ivor Lewis esophagectomies and fewer transhiatal and McKeown esophagectomies (P < .0001). After risk adjustment, there were no differences in rates of postesophagectomy complications, such as anastomotic leaks or positive margins, between cardiothoracic surgeons and general surgeons (all P > .05). However, cardiothoracic surgeons were more likely than general surgeons to treat anastomotic leaks with surgery rather than procedural interventions (odds ratio = 1.76; 95% confidence interval, 1.24-2.52). CONCLUSION: Cardiothoracic surgeons and general surgeons use minimally invasive surgical subtypes differently when performing esophagectomy. However, there were no risk-adjusted differences in postoperative complications when compared by surgical subspecialty. Esophagectomy is being performed safely by surgeons with different specialties and training pathways.

Unconscious bias in speaker introductions at a national vascular surgery meeting: The impact of rank, race and gender.

OBJECTIVES: Unconscious bias can impact manner of speaker introductions in formal academic settings. We examined speaker introductions at the Society of Vascular Surgeons Annual Meeting to determine factors associated with non-professional address. METHODS: We examined speaker introductions from the 2019 SVS Vascular Annual Meeting. Professional title with either full name or last name was considered professional address. Speaker and moderator demographics were collected. Univariate and multivariate logistic regression analyses were performed to identify associations between introduction and speaker and moderator characteristics. RESULTS: 336 talks met inclusion criteria. Both speakers and moderators were more likely to be white (63.4 â€‹% and 65.8 â€‹%,p â€‹= â€‹0.92), man (75.6 â€‹% and 74.4 â€‹%,p â€‹= â€‹0.82) and full professor rank (34.5 â€‹% and 42.3 â€‹%, p â€‹< â€‹0.001). On multivariable regression, non-professional address was associated with speaker rank of trainee (OR 3.13, p â€‹= â€‹0.05) and when moderator was white (OR 2.42, p â€‹= â€‹0.03). CONCLUSIONS: This study emphasizes the potential negative impact of unconscious bias at a national meeting for vascular surgeons and the need to mitigate this effect at the organization level.

Common Components of General Surgery Robotic Educational Programs.

OBJECTIVE: Robotically assisted surgery has become more common in general surgery, but there is limited guidance from the Accreditation Council for Graduate Medical Education (ACGME) regarding this type of training. We sought to determine common elements and differences in the robotic educational curricula developed by general surgery residency programs. DESIGN: Robotic educational curricula were obtained from the 7 individuals who presented at the workshop, "Robotic Education in General Surgery" at the 2023 Association of Program Directors in Surgery annual meeting. RESULTS: All 7 general surgery programs had training beginning intern year, required online robotic modules, had at least 1 dedicated simulation training console not used for clinical purposes, and ran dry and wet (tissue) robotic labs at least annually. All programs had bedside and console surgeon case minimums and had administrative support to run the educational programs. Differences existed regarding how training intern year was executed, the simulations required, clinical practice minimum requirements, how progress was monitored over time, and how case numbers were tracked. Some programs had salary support for a director of robotic education. CONCLUSIONS: There are several common elements to robotic educational curricula in general surgery, however significant variation does exist between programs. Given the frequency of robotic use in general surgery and current lack of standardization, formal guidance from the ACGME specifically regarding robotic education in general surgery residency is warranted.

Prospective Evaluation of a Universally Applied Laparoscopic Gastric Ischemic Preconditioning Protocol Prior to Esophagectomy with Comparison with Historical Controls.

BACKGROUND: Anastomotic leak after esophagectomy is associated with significant morbidity and mortality. Our institution began performing laparoscopic gastric ischemic preconditioning (LGIP) with ligation of the left gastric and short gastric vessels prior to esophagectomy in all patients presenting with resectable esophageal cancer. We hypothesized that LGIP may decrease the incidence and severity of anastomotic leak. METHODS: Patients were prospectively evaluated following the universal application of LGIP prior to esophagectomy protocol in January 2021 until August 2022. Outcomes were compared with patients who underwent esophagectomy without LGIP from a prospectively maintained database from 2010 to 2020. RESULTS: We compared 42 patients who underwent LGIP followed by esophagectomy with 222 who underwent esophagectomy without LGIP. Age, sex, comorbidities, and clinical stage were similar between groups. Outpatient LGIP was generally well tolerated, with one patient experiencing prolonged gastroparesis. Median time from LGIP to esophagectomy was 31 days. Mean operative time and blood loss were not significantly different between groups. Patients who underwent LGIP were significantly less likely to develop an anastomotic leak following esophagectomy (7.1% vs. 20.7%, p = 0.038). This finding persisted on multivariate analysis [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.03-0.42, p = 0.029]. The occurrence of any post-esophagectomy complication was similar between groups (40.5% vs. 46.0%, p = 0.514), but patients who underwent LGIP had shorter length of stay [10 (9-11) vs. 12 (9-15), p = 0.020]. CONCLUSIONS: LGIP prior to esophagectomy is associated with a decreased risk of anastomotic leak and length of hospital stay. Further, multi-institutional studies are warranted to confirm these findings.

Social vulnerability is associated with increased postoperative morbidity following esophagectomy.

OBJECTIVES: The effect of a patient's Social Vulnerability Index (SVI) on complication rates after esophagectomy remains unstudied. The purpose of this study was to determine how social vulnerability influences morbidity following esophagectomy. METHODS: This was a retrospective review of a prospectively collected esophagectomy database at one academic institution, 2016 to 2022. Patients were grouped into low-SVI (<75%ile) and high-SVI (>75%ile) cohorts. The primary outcome was overall postoperative complication rate; secondary outcomes were rates of individual complications. Perioperative patient variables and postoperative complication rates were compared between the 2 groups. Multivariable logistic regression was used to control for covariates. RESULTS: Of 149 patients identified who underwent esophagectomy, 27 (18.1%) were in the high-SVI group. Patients with high SVI were more likely to be of Hispanic ethnicity (18.5% vs 4.9%, P = .029), but there were no other differences in perioperative characteristics between groups. Patients with high SVI were significantly more likely to develop a postoperative complication (66.7% vs 36.9%, P = .005) and had greater rates of postoperative pneumonia (25.9% vs 6.6%, P = .007), jejunal feeding-tube complications (14.8% vs 3.3%, P = .036), and unplanned intensive care unit readmission (29.6% vs 12.3%, P = .037). In addition, patients with high SVI had a longer postoperative hospital length of stay (13 vs 10 days, P = .017). There were no differences in mortality rates. These findings persisted on multivariable analysis. CONCLUSIONS: Patients with high SVI have greater rates of postoperative morbidity following esophagectomy. The effect of SVI on esophagectomy outcomes warrants further investigation and may prove useful in identifying populations that benefit from interventions to mitigate these complications.

Cannabis use and post-operative complications in patients undergoing pancreatic resection.

BACKGROUND: Many states have legalized medical cannabis with various reported therapeutic benefits. However, there is little data assessing the effects of cannabis on surgical outcomes. We sought to compare post-operative pancreatic resection complications between cannabis users and non-users. METHODS: This is a single-center, retrospective review of patients who underwent Whipple or distal pancreatectomy from 1/2017-12/2020. The primary outcome was any in-hospital complication, using Clavien-Dindo. Multivariable regression analysis was performed. RESULTS: There were 486 patients who underwent Whipple (n=346, 71.2%) or distal pancreatectomy (n=140, 28.8%). Overall, 21.4% (n=104) reported cannabis use, of whom 80.8% were current users. Cannabis users were younger (60 vs. 66 years, p < 0.001), and more likely to have smoked tobacco (p=0.04), but otherwise had similar demographics as non-users. There were 288 (59.3%) patients who developed an in-hospital complication (grade 1-2, 75.3%; grade 3-5, 24.7%). A trend towards increased complications was observed with tobacco smoking (OR 1.33, 95% CI 0.91-1.94, p=0.14), but no association of cannabis use with complications was observed (OR 0.93, 95% CI 0.58-1.47, p=0.74). DISCUSSION: A significant proportion of patients undergoing pancreatic resection report cannabis use. These results suggest that there was no association between cannabis use and post-operative complications, future prospective evaluation is warranted.

Informational Needs of Surgical Oncology Patients: A Cross-Sectional Patient Survey.

INTRODUCTION: Patients newly diagnosed with cancer often seek information prior to being seen by a specialist. Little is known about the type of information desired and the sources used. We asked how patients find information about their new cancer diagnoses to improve information provision. METHODS: An anonymous seven-question survey was provided to new patients in the surgical and medical oncology clinics at a comprehensive cancer center from February 2021 to June 2021. RESULTS: Of 503 consecutive patients, 405 (81%) returned surveys; 49% female, 57% aged 51-75 y, and 71% Caucasian. Many (74%) sought information before their visit. Most (57%) relied on prior medical providers and 77% reported them as a trusted source. Nearly 80% of patients used at least one nonvalidated resource; 21% friends and relatives, 20% nongovernment or hospital resources, and 12% social media. Importantly, 23% found conflicting information. Respondents desired information on cancer treatment (58%), alternative therapies (35%), and nutrition and supplements (31%). CONCLUSIONS: Patients with cancer trust information from medical providers but seek information from a variety of sources that can provide conflicting information. These data support encouraging patients to use validated sources, providing robust organization-based resources, and engaging patients on topics such as alternative therapies and nutrition.

Lipoma and Its Doppelganger: The Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma.

Lipomatous tumors are among the most common soft tissue lesions encountered by the general surgeon. Shared history and clinical presentation make differentiation between benign lipomas and low-grade liposarcomas a diagnostic dilemma. This article reviews the epidemiology, clinical history, diagnostic workup, management, natural history, and surveillance of benign lipomas and atypical lipomatous tumors/well-differentiated liposarcomas. Although it is important that aggressive, potentially malignant atypical lipomatous tumors and liposarcomas be managed in a multidisciplinary, preferably high-volume setting, it is equally as important for the nonspecialist general surgeon to be familiar with lipoma and its doppelganger-the well-differentiated liposarcoma.

Adjuvant Therapy for Stage III Melanoma Without Immediate Completion Lymph Node Dissection.

INTRODUCTION: For patients with stage III melanoma with occult lymph node metastasis, the use of adjuvant therapy is increasing, and completion lymph node dissection (CLND) is decreasing. We sought to evaluate the use of modern adjuvant therapy and outcomes for patients with stage III melanoma who did not undergo CLND. METHODS: Patients with a positive SLNB from 2015 to 2020 who did not undergo CLND were evaluated retrospectively. Nodal recurrence, recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and melanoma-specific survival were evaluated. RESULTS: Among 90 patients, 56 (62%) received adjuvant therapy and 34 (38%) underwent observation alone. Patients who received adjuvant therapy were younger (mean age: 53 vs. 65, p < 0.001) and had higher overall stage (Stage IIIb/c 75% vs. 54%, p = 0.041). Disease recurred in 12 of 34 patients (35%) in the observation group and 11 of 56 patients (20%) in the adjuvant therapy group. The most common first site of recurrence was distant recurrence alone (5/34 patients) in the observation group and nodal recurrence alone (8/90 patients) in the adjuvant therapy group. Despite more adverse nodal features in the adjuvant therapy group, 24-month nodal recurrence rate and RFS were not significantly different between the adjuvant and observation cohorts (nodal recurrence rate: 26% vs. 20%, p = 0.68; RFS: 75% vs. 61%, p = 0.39). Among patients with stage IIIb/c disease, adjuvant therapy was associated with a significantly improved 24-month DMFS (86% vs. 59%, p = 0.04). CONCLUSIONS: In this early report, modern adjuvant therapy in patients who forego CLND is associated with longer DMFS among patients with stage IIIb/c disease.

Data-Driven Respectful Discourse in the Society of Surgical Oncology.

BACKGROUND: We previously reported that professional forms of address in speaker introductions were inconsistently used at the Society of Surgical Oncology (SSO) 2018 and 2019 annual meetings, suggesting unconscious bias in speaker introductions. We sought to better understand how speakers would like to be introduced, and if guidelines could improve consistency in speaker introductions. METHODS: SSO 2021 abstract submitters received a survey regarding demographics and preferred form of address at the meeting. Respectful discourse guidelines were developed and distributed to meeting moderators. Speaker introductions were reviewed for the 2021 SSO annual meeting and were compared with the 2018 and 2019 meetings. RESULTS: The survey response rate was 183/347 (53%) abstract submitters, most of whom (143/183, 78%) indicated preference for a professional form of address (Doctor/Professor) during speaker introductions, which was significantly greater than those who were introduced with a professional form of address during the 2018 and 2019 meetings (351/499, 70%; Chi-square = 4.08, p = 0.043). There was no difference in speaker introduction preference based on gender or race/ethnic identification. Respectful discourse guidelines were developed and distributed to meeting moderators. During the 2021 SSO annual meeting, professional forms of address were used for 104 (84%) speakers, significantly greater than during the 2018 and 2019 meetings (Chi-square = 9.23, p = 0.002). CONCLUSIONS: More survey respondents preferred speaker introductions with a professional form of address than were used in prior meetings. This preference was similar across all demographic groups evaluated. Professional addresses during speaker introductions increased significantly after the distribution of guidelines encouraging consistency to decrease unconscious bias and promote an inclusive environment.

Cholecystectomy in patients with hematologic malignancies.

BACKGROUND: Cholecystectomy in patients with hematologic malignancies remains poorly understood. METHODS: We retrospectively evaluated patients with hematologic malignancies who underwent cholecystectomy at a single institution. RESULTS: Of 313 patients who presented for evaluation of abdominal pain, 64 underwent cholecystectomy for acute cholecystitis (34.4%), gangrenous cholecystitis (21.9%), chronic cholecystitis (23.4%), and cholelithiasis (20%). Most had a history of hematopoietic cell transplantation (62.5%) and/or immunosuppressive medication within 30 days of consultation (82.8%). Ultrasound had a 39% false-negative rate for acute nongangrenous cholecystitis. Operative time was 92 ± 39 min, 7 were performed open, 10 had intraoperative transfusions, and 4 had grade 3+ complications. Intraoperative transfusion was associated with increased postoperative length of stay (p = 0.03). Open procedure, operative time, estimated blood loss, intraoperative transfusion, and complications were not associated with timing of surgery. CONCLUSIONS: Patients with hematologic malignancies can safely undergo cholecystectomy. Length of postoperative stay for inpatients is associated with intraoperative blood transfusion.

A Quantitative Analysis of Surgical Smoke Exposure as an Occupational Hazard.

OBJECTIVE: We hypothesized that OR airborne PM was different in quantity and mutagenic potential than office air and cigarette smoke. SUMMARY OF BACKGROUND DATA: Exposure to surgical smoke has been equated to cigarette smoking and thought to be hazardous to health care workers despite limited data. METHODS: PM was measured during 15 operations in ORs with 24.8 ±â€Š2.0 air changes/h, and in controls (cigarettes, office air with 1.9-2.9 air changes/h). Mutagenic potential was assessed by gamma Histone 2A family member X staining of DNA damage in small airway epithelial cells co-cultured with PM. RESULTS: Average PM concentration during surgery was 0.002 ±â€Š0.002 mg/m3 with maximum values at 1.08 ±â€Š1.30 mg/m3. Greater PM correlated with more diathermy (ρ = 0.69, P = 0.006). Values were most often near zero, resulting in OR average values similar to office air (0.002 ±â€Š0.001 mg/m3) (P = 0.32). Cigarette smoke average PM concentration was significantly higher, 4.8 ±â€Š5.6 mg/m3 (P < 0.001). PM collected from 14 days of OR air caused DNA damage to 1.6% ±â€Š2.7% of cultured cells, significantly less than that from office air (27.7% ±â€Š11.7%, P = 0.02), and cigarette smoke (61.3% ±â€Š14.3%, P < 0.001). CONCLUSIONS: The air we breathe during surgery has negligible quantities of PM and mutagenic potential, likely due to low frequency of diathermy use coupled with high airflow. This suggests that exposure to surgical smoke is associated with minimal occupational risk.