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.

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.

Outcomes of robotic lobectomy for non-small cell lung cancer in a National Cancer Institute-Comprehensive Cancer Center vs. National Cancer Database.

Background: There continues to be a rise in the proportion of resectable non-small cell lung cancer (NSCLC) with the recent expansion of criteria for low-dose lung cancer screening. These are increasingly being treated with minimally invasive techniques. Our study aims to compare outcomes of robotic lobectomy (RL) for NSCLC at a National Cancer Institute-designated Comprehensive Cancer Center (NCI-CCC) to those of open lobectomy (OL), video-assisted thoracoscopic lobectomy (VL), or RL as reported in the National Cancer Database (NCDB). Methods: The first 1,021 patients with NSCLC who underwent RL between 2010 and 2020 were matched with peers from the NCDB who had OL, VL, or RL. Matching was performed based on a propensity score calculated by logistic regression using multiple variables. Surgical outcomes included numbers of examined lymph nodes, performance of mediastinal lymphadenectomy, length of stay (LOS), and 30-day mortality. Kaplan-Meier curves and overall survival (OS) were analyzed using log-rank tests. Results: Most common postoperative complications were persistent air leak, atrial fibrillation, and pneumonia. Median LOS was 4 days, and the 30-day mortality rate was 1% (n=10/1,021). Compared to NCDB patients who underwent OL, NCI-CCC patients had a higher mean number of retrieved lymph nodes (P=0.001), higher rate of mediastinal lymphadenectomy (P<0.001), and shorter median LOS (4 vs. 6 days; P<0.001). There was no difference in 30-day mortality (P=0.176). Kaplan-Meier analyses showed no differences in median OS (log-rank P=0.953) or 5-year OS (P=0.774). Compared to NCDB VL, NCI-CCC patients had a higher nodal yield (P<0.001), higher rates of mediastinal lymphadenectomy (P<0.001), and lower conversion rates (4.1% vs. 13.8%, P<0.001). There were no differences in 30-day mortality (P=0.379) or in median LOS (P=0.351). Kaplan-Meier analyses showed no differences in median OS (P=0.720) or 5-year OS (P=0.735). NCI-CCC patients were also matched with NCDB RL patients and had a higher nodal yield (P<0.001), higher rates of mediastinal lymphadenectomy (P<0.001), and lower conversion rates (4.1% vs. 9.5%; P <0.001). There were no differences in 30-day mortality (P=0.899) or in median LOS (P=0.252). Kaplan-Meier analyses showed no differences in median OS (P=0.484) or 5-year OS (P=0.524). Conclusions: RL for NSCLC performed in an NCI-CCC appears to have improved perioperative outcomes with comparable long-term OS compared to national benchmarks in OL and VL.

Induction Fluorouracil-Based Chemotherapy and PET-Adapted Consolidation Chemoradiation with Esophagectomy for High-Risk Gastroesophageal Adenocarcinoma.

Background: Neoadjuvant chemoradiation with esophagectomy is standard management for locally advanced esophageal adenocarcinoma. Induction chemotherapy with a tailored approach to chemoradiation based on metabolic response to therapy on PET was explored as an alternative strategy in the CALGB 80803 trial. We sought to describe real-world institutional experience implementing this approach outside of a clinical trial. Methods: Patients who were treated with induction fluorouracil-leucovorin-oxaliplatin (FOLFOX) or fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) with tailored chemoradiation based on PET response and subsequent esophagectomy were identified from a prospectively maintained database. Primary outcomes were pathologic complete response (pCR) and overall survival (OS) following completion of all therapy. Results: There were 35 patients who completed induction chemotherapy, chemoradiation, and esophagectomy. Thirty-three completed restaging PET following induction chemotherapy with metabolic response seen in 76% (n = 25/33). The pCR rate was 31% (n = 11/35) and the ypN0 rate was 71% (n = 25/35). Among the patients who demonstrated metabolic response to induction FOLFOX/FLOT and subsequently continued fluorouracil-based chemoradiation, the pCR rate was 39% (n = 9/23). The rate of pathologically negative lymph nodes in this group was high (n = 19/23, 83%) with 100% R0 resection rate (n = 23/23). With the median follow-up of 43 months, the median OS was not reached for this group and was significantly longer than the OS for the remainder of the cohort (p = 0.027, p = 0.046 adjusted for clinical stage). Conclusions: Induction FOLFOX/FLOT chemotherapy with evaluation of sensitivity via metabolic response and tailored chemoradiation seems to lead to high pCR and ypN0 rates in high-risk patients with adenocarcinoma of the esophagus and GE junction. This approach in clinical practice seems to recapitulate encouraging results in clinical trials.

Association between the Preoperative Standard Uptake Value (SUV) and Survival Outcomes after Robotic-Assisted Segmentectomy for Resectable Non-Small Cell Lung Cancer (NSCLC).

BACKGROUND: Lung-sparing procedures, specifically segmentectomies and wedge resections, have increased over the years to treat early-stage non-small cell lung cancer (NSCLC). We investigate here the perioperative and long-term outcomes of patients who underwent robotic-assisted segmentectomy (RAS) at an NCI-designated cancer center and aim to show associations between the preoperative standard update value (SUV) to tumor stage, recurrence patterns, and overall survival. METHODS: A retrospective analysis was performed on 166 consecutive patients who underwent RAS at a single institution from 2010 to 2021. Of this number, 121 robotic-assisted segmentectomies were performed for primary NSCLC, and a total of 101 patients were evaluated with a PET-CT scan. The SUV from the primary tumor was determined from the PET-CT. The clinical, surgical, and pathologic profiles and perioperative outcomes were summarized via descriptive statistics. Numerical variables were described as the median and interquartile range because all numerical variables were not normally distributed as assessed by the Shapiro-Wilk test of normality. Categorical variables were described as the count and proportion. Chi-square or Fisher's exact test was used for association. The main outcomes were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier (KM) curves were constructed to visualize the OS and RFS, which were also stratified according to tumor histology, the pathologic stage, and standard uptake value. A log-rank test for the equality of survival curves was performed to determine significant differences between groups. RESULTS: The most common postoperative complications were atrial fibrillation (8.8%, 9/102), persistent air leak (7.84%, 8/102), and pneumonia (4.9%, 5/102). The median operative duration was 168.5 min (IQR 59), while the median estimated blood loss was 50 mL (IQR 125). The conversion rate to thoracotomy in this cohort was 3.9% (4/102). Intraoperative complications occurred in 2.9% (3/102). The median hospital length of stay was 3 days (IQR 3). The median chest tube duration was 3 days (IQR 2), but 4.9% (5/102) of patients were sent home with a chest tube. The recurrence for this cohort was 28.4% (29/102). The time to recurrence was 353 days (IQR 504), while the time to mortality was 505 days (IQR 761). The NSCLC patients were divided into the following two groups: low SUV (<5, n = 55) and high SUV (≥5, n = 47). Statistically significant associations were noted between SUV and the tumor histology (p = 0.019), tumor grade (p = 0.002), lymph-vascular invasion (p = 0.029), viscera-pleural invasion (p = 0.008), recurrence (p < 0.001) and the site of recurrence (p = 0.047). KM survival analysis showed significant differences in the curves for OS (log-rank p-value 0.0204) and RFS (log-rank p-value 0.0034) between the SUV groups. CONCLUSION: Robotic-assisted segmentectomy for NSCLC has reasonable perioperative and oncologic outcomes. Furthermore, we demonstrate here the prognostic implication of preoperative SUV to pathologic outcomes, recurrence-free survival, and overall survival.

Changes in Perioperative Outcomes after Robotic-Assisted Pulmonary Lobectomy during the COVID-19 Era.

Background: The COVID-19 pandemic presented patients with barriers to receiving healthcare. We sought to determine whether changes in healthcare access and practice during the pandemic affected perioperative outcomes after robotic-assisted pulmonary lobectomy (RAPL). Methods: We retrospectively analyzed 721 consecutive patients who underwent RAPL. With March 1st, 2020, defining the start of the COVID-19 pandemic, we grouped 638 patients as "PreCOVID-19" and 83 patients as "COVID-19-Era" based on surgical date. Demographics, comorbidities, tumor characteristics, intraoperative complications, morbidity, and mortality were analyzed. Variables were compared utilizing Student's t-test, Wilcoxon rank-sum test, and Chi-square (or Fisher's exact) test, with significance at p ≤ 0.05 . Multivariable generalized linear regression was used to investigate predictors of postoperative complication. Results: COVID-19-Era patients had significantly higher preoperative FEV1%, lower cumulative smoking history and higher incidences of preoperative atrial fibrillation, peripheral vascular disease (PVD), and bleeding disorders compared to PreCOVID-19 patients. COVID-19-Era patients had lower intraoperative estimated blood loss (EBL), reduced incidence of new-onset postoperative atrial fibrillation (POAF), but higher incidence of effusion or empyema postoperatively. Overall postoperative complication rates between the groups were similar. Older age, increased EBL, lower preoperative FEV1%, and preoperative COPD are all predictive of an increased risk for postoperative complication. Conclusions: COVID-19-Era patients having lower EBL and less new-onset POAF, despite greater incidences of multiple preoperative comorbidities, demonstrates that RAPL is safe during the COVID-19 era. Risk factors for development of postoperative effusion should be determined to minimize risk of empyema in COVID-19-Era patients. Age, preoperative FEV1%, COPD, and EBL should all be considered when planning for complication risk.

Effects of preoperative pulmonary function on perioperative outcomes after robotic-assisted pulmonary lobectomy.

INTRODUCTION: Effects of pulmonary function test (PFT) results on perioperative outcomes were investigated after robotic-assisted video-thoracoscopic (RAVT) pulmonary lobectomy. METHODS: We retrospectively analyzed 706 consecutive patients who underwent RAVT lobectomy by one surgeon over 10.8 years. Preoperative (preop) forced expiratory volume in 1 s as a percent of predicted (FEV1%) was used to group patients as having normal FEV1% (≥80%) versus reduced FEV1% (<80%). Demographics, preop comorbidities, intraoperative (intraop) and postoperative (postop) complications, perioperative outcomes, and median survival time (MST) were compared across patients with normal vs. reduced FEV1% using Chi-Square (X2), Fisher's Exact test, Student's t-test, Kruskal-Wallis test, or Kaplan-Meier analysis respectively, with significance at p ≤ 0.05. Multivariable analysis was performed for perioperative outcomes to investigate the differences across patients in the FEV1% groups. RESULTS: There were 470 patients with normal FEV1% and 236 patients with reduced FEV1%. The two FEV1% groups did not differ in intraop or postop complication rates, except for higher postop other arrhythmia requiring intervention (p = 0.004), prolonged air leak >5 days (p = 0.002), mucous plug formation (p = 0.009), hypoxia (p < 0.001), and pneumonia (p = 0.002), and total postop complications (p < 0.001) in reduced-FEV1% patients. Reduced FEV1% correlated with increased intraop estimated blood loss (p < 0.0001) and skin-to-skin operative time (p < 0.0001). Median overall survival in patients with normal FEV1% was 93.20 months (95% CI: 76.5-126.0) versus 58.9 months (95% CI: 50.4-68.4) in patients with reduced FEV1% (p = 0.0004). CONCLUSION: Patients should have PFTs conducted before surgery to determine at-risk patients. However, RAVT pulmonary lobectomy is feasible and safe even in patients with reduced FEV1%.

Surgical Aortic Valve Replacement in the Setting of Anomalous Circumflex Coronary Artery.

BACKGROUND: The anomalous circumflex coronary artery (ACCA) from the right coronary artery or sinus of Valsalva lies in proximity to the aortic valve annulus. This study sought to determine the prevalence of injury to the ACCA during surgical aortic valve replacement (SAVR). METHODS: We queried the databases of the Departments of Cardiovascular Surgery and Cardiovascular Diseases of Mayo Clinic, Rochester, Minnesota for all patients who underwent SAVR in the setting of an ACCA. The study investigators identified 31 patients operated on from September 2002 through December 2018. The end point was myocardial ischemia in the distribution of the ACCA. RESULTS: The patients' mean age was 69 ± 11 years, sex was female in 8 patients (26%), and ejection fraction was 62% (interquartile range, 59% to 68%). No patient underwent exploration of the ACCA, but 5 (16%) had a coronary artery bypass graft to the ACCA. No patient demonstrated myocardial infarction or underwent perioperative intervention on the ACCA; however, discharge echocardiography showed new lateral wall motion abnormality in 5 (16%) patients that was associated with a reduction in ejection fraction of -11% from baseline (P = .007). Coronary artery bypass graft to the ACCA was not protective of new lateral wall motion abnormality (P = .968). Mortality was 34% ± 10% at 10 years and was not associated with new lateral wall motion abnormality (log-rank test P = .183). CONCLUSIONS: Clinically apparent myocardial infarction was not identified after SAVR, but echocardiographic evidence of myocardial ischemia in the distribution of the ACCA was identified in 16% of patients. Protective adjuvant intervention on the ACCA may be indicated. Further study is warranted.