Clinical and Pathologic Response to Neoadjuvant Immunotherapy in DNA Mismatch Repair Protein-Deficient Gastroesophageal Cancers.

BACKGROUND: Mismatch repair deficient (dMMR) gastroesophageal cancers (GEC) are a distinct subgroup. Among patients with locally advanced disease, previous trial data suggest a good response to neoadjuvant immune checkpoint inhibitors (nICI). PATIENTS AND METHODS: Since 2019, our institution has routinely performed MMR testing for new GEC cases. Patients diagnosed with GEC (2019-2024) were included in the study. Quantitative data are described as the median and interquartile range (IQR); qualitative data are described as quantities and percentages. RESULTS: A total of 24 patients with dMMR GEC were identified following implementation of routine immunohistochemical testing; 14 were potentially resectable with a median follow-up of 14 months (IQR 8-27). All patients underwent pre-treatment positron emission tomography (PET; median SUV 20.9). Among the 14 potentially resectable patients, 4 underwent immediate surgery, 10 were treated with nICI, and 5 underwent surgical resection to date. All regimens included PD-1 inhibitors, with 70% receiving pembrolizumab. Re-staging PET was performed in five patients; the median post-nICI SUV was 5.1 (range 4.7-6.3). All resected specimens had gross ulceration after nICI, but 60% (N = 3) had a pathologic complete response (pCR) following nICI; one patient had a near-complete response (nCR) and one patient had a partial response (pPR). Reduction in SUV was 75% and 82% in the pCR patients, 25% in the nCR patient, and 43% in the pPR patient. CONCLUSIONS: dMMR GECs are responsive to nICI in this limited experience, mirroring early clinical trial data. Given persistent metabolic activity and visible ulceration despite pCR, studies should continue to optimize tools for estimating post-nICI pCR in these patients.

Intra-operative pyloric BOTOX injection versus pyloric surgery for prevention of delayed gastric emptying after esophagectomy.

BACKGROUND: Delayed gastric emptying (DGE) is a common complication after esophagectomy. BOTOX injections and pyloric surgeries (PS), including pyloroplasty (PP) and pyloromyotomy (PM), are performed intraoperatively as prophylaxis against DGE. This study compares the effects of pyloric BOTOX injection and PS for preventing DGE post-esophagectomy. METHODS: We retrospectively reviewed Moffitt's IRB-approved database of 1364 esophagectomies, identifying 475 patients receiving BOTOX or PS during esophageal resection. PS was further divided into PP and PM. Demographics, clinical characteristics, and postoperative outcomes were compared using Chi-Square, Fisher's exact test, Wilcoxon rank-sum, and ANOVA. Propensity-score matching was performed between BOTOX and PP cohorts. RESULTS: 238 patients received BOTOX, 108 received PP, and 129 received PM. Most BOTOX patients underwent fully minimally invasive robotic Ivor-Lewis esophagectomy (81.1% vs 1.7%) while most PS patients underwent hybrid open/Robotic Ivor-Lewis esophagectomy (95.7% vs 13.0%). Anastomotic leak (p = 0.57) and pneumonia (p = 0.75) were comparable between groups. However, PS experienced lower DGE rates (15.9% vs 9.3%; p = 0.04) while BOTOX patients had less postoperative weight loss (9.7 vs 11.45 kg; p = 0.02). After separating PP from PM, leak (p = 0.72) and pneumonia (p = 0.07) rates remained similar. However, PP patients had the lowest DGE incidence (1.9% vs 15.7% vs 15.9%; p = < 0.001) and the highest bile reflux rates (2.8% vs 0% vs 0.4%; p = 0.04). Between matched cohorts of 91 patients, PP had lower DGE rates (18.7% vs 1.1%; p = < 0.001) and less weight loss (9.8 vs 11.4 kg; p = < 0.001). Other complications were comparable (all p > 0.05). BOTOX was consistently associated with shorter LOS compared to PS (all p = < 0.001). CONCLUSION: PP demonstrates lower rates of DGE in unmatched and matched analyses. Compared to BOTOX, PS is linked to reduced DGE rates. While BOTOX is associated with more favorable LOS, this may be attributable to difference in operative approach. PP improves DGE rates after esophagectomy without improving other postoperative complications.

Leveraging real-world data to predict cancer cachexia stage, quality of life, and survival in a racially and ethnically diverse multi-institutional cohort of treatment-naïve patients with pancreatic ductal adenocarcinoma.

Introduction: Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management. Objectives: The main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS). Materials and methods: A population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations. Results: CC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS. Conclusions: Using clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey.

Totally minimally invasive laparoscopic robot-assisted Ivor Lewis esophagectomy: improved technique and outcomes over 200 cases.

Background: Surgical resection of esophageal and gastroesophageal junction cancers is a very complex procedure with step learning curve. New technologies have made minimally invasive surgery possible, but challenges still remain for wide spread adoption of these techniques. This article aims to describe the outcomes and salient technical points of a totally minimally invasive, laparoscopic, robot-assisted Ivor Lewis esophagectomy (LRAMIE). Methods: Retrospective observational cohort study performed at a specialty cancer center using a prospectively maintained institutional database. Patients undergoing LRAMIE (laparoscopic abdomen, robotic chest) from 2014-2023 were included. Patients undergoing transhiatal and three-field esophagectomy were excluded. Operative and postoperative outcomes were compared over the study period to identify potential associations between outcomes over time. Results: Two-hundred patients were identified who underwent LRAMIE. Median age was 65 years and most were male (87.5%). The open conversion rate was 1% (n=2), which occurred within the first 30 cases. Operative time and blood loss were improved at the 60-case mark (P<0.001). Anastomotic stricture rate improved after 50 cases, and leak rate improved after 80 cases. Postoperative length of stay improved at both 50 and 100 cases with a median LOS of 6 days after 100 cases. Rate of postoperative pneumonia, 30- and 90-day mortality were reduced after 100 cases, although not statistically significant for mortality due to too few events. Conclusions: Totally minimally invasive Ivor Lewis esophagectomy at a high-volume center is a safe procedure. Operative outcomes improved significantly after 50-80 cases, followed by improvement in anastomotic results and postoperative outcomes, with corresponding excellent oncologic outcomes.

Initial Experience Using Laparoscopic HIPEC for Gastric Cancer with Peritoneal Metastasis: Safety and Outcomes.

BACKGROUND: Peritoneal metastases (PM) develop in approximately 20% of patients with gastric cancer (GC). For selected patients, treatment of PM with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results. This report aims to describe the safety and perioperative outcomes of laparoscopic HIPEC for GC/PM. METHODS: This retrospective cohort study evaluated patients who had GC and PM treated with laparoscopic HIPEC (2018-2022). The HIPEC involved cisplatin and mitomycin C (MMC) or MMC alone. The primary end point was perioperative safety. RESULTS: The 22 patients in this study underwent 27 procedures. The mean age was 58 ± 13 years. All the patients were Eastern Cooperative Oncology Group (ECOG) 0 or 1 (55 and 45%, respectively). Five patients underwent a second laparoscopic HIPEC, with a median of 126 days (interquartile range [IQR], 117-166 days) between procedures. The median peritoneal carcinomatosis index (PCI) was 4 (IQR, 2-9), and the median hospital stay was 2 days (IQR, 1-3 days). No 30-day readmissions or complications occurred. Eight patients (36%) underwent gastrectomy (CRS ± HIPEC). After an average follow-up period of 11 months, 7 (32%) of the 22 patients were alive. The median overall survival was 11 months (IQR, 195-739 days) from the initial procedure and 19.3 months (IQR, 431-1204 days) from the diagnosis. CONCLUSIONS: Laparoscopic HIPEC appears to be safe with minimal perioperative complications. Approximately one third of the patients undergoing initial laparoscopic HIPEC ultimately proceeded to cytoreduction and gastrectomy. Preliminary survival data from this highly selected cohort suggest that the addition of laparoscopic HIPEC to systemic chemotherapy does not compromise other treatment options. These initial results suggest that laparoscopic HIPEC may offer benefit to patients with GC and PM and aid in the selection of patients who may benefit from curative-intent resection.