Predictors of residual neoplasia after noncurative (R1) endoscopic submucosal dissection of lesions in the gastrointestinal tract.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a minimally invasive resection technique that enables the en bloc resection of gastrointestinal lesions. Despite en bloc resection, pathological evaluation of lesions can reveal positive vertical or horizontal margins, which is referred to as R1 resection. Not all R1 lesions referred for surgical resection or endoscopic surveillance show evidence of residual tumor. We aimed to identify the predictors of residual neoplasia in patients with an R1 resection following ESD. PATIENTS AND METHODS: All lesions resected via ESD between June 2016 and September 2021 at a tertiary referral center were retrospectively identified. Lesions with an R1 resection and adequate follow-up were eligible for inclusion. Patient, lesion, and procedural characteristics were analyzed to identify predictors of residual neoplasia. RESULTS: Of 614 lesions, 163 (28%) had R1 resection. Of these, 56 lesions in 51 patients had complete follow-up and were included. Thirteen patients (25.5%) underwent surgical resection and the remainder underwent endoscopic surveillance. Seven (12.5%) patients had residual disease. All patients with residual disease had esophageal carcinoma. Positive deep and lateral margins, severe submucosal fibrosis, and moderate/poorly differentiated tumors were identified as significant predictors of residual neoplasia. CONCLUSION: Most R1 lesions (87.5%) resected by ESD did not have residual disease on follow-up. Those without identified risk factors for residual disease, such as esophageal carcinoma, severe submucosal fibrosis, or both histological margin positivity, may benefit from a strategy of close endoscopic surveillance rather than referral for surgical resection.

Practice Changes in Checkpoint Inhibitor-Induced Immune-Related Adverse Event Management at a Tertiary Care Center.

Understanding of immune-related adverse events (irAEs) has evolved rapidly, and management guidelines are continually updated. We explored temporal changes in checkpoint inhibitor-induced irAE management at a tertiary cancer care center to identify areas for improvement. We conducted a single-center retrospective study of patients who developed a gastrointestinal, pulmonary, renal, or cardiac irAE between July and 1 October in 2019 or 2021. We collected patient demographic and clinical information up to 1 year after toxicity. Endoscopic evaluation and specialty follow-up after discharge for patients with gastrointestinal irAEs declined between the 2019 and 2021 periods. Symptom duration and steroid taper attempts also declined. For pulmonary irAEs, rates of specialty consultation, hospital admission and readmission, and mortality improved in 2021 compared with 2019. Follow-up rates after hospital discharge were consistently low (<50%) in both periods. For cardiac irAEs, consultation with a cardiologist was frequent and prompt in both periods. Outpatient treatment and earlier specialty consultation improved outcomes with gastrointestinal irAEs. Our study exploring irAE practice changes over time identified areas to improve management; specifically, timely specialty consultation was associated with better outcomes for gastrointestinal irAEs. These findings can help improve the quality of management algorithms at our institution and may inform policies in other institutions.

Sclerosing mesenteritis following immune checkpoint inhibitor therapy.

PURPOSE: Sclerosing mesenteritis (SM), a fibroinflammatory process of the mesentery, can rarely occur after immune checkpoint inhibitor (ICI) therapy; however, its clinical significance and optimal management are unclear. We aimed to assess the characteristics and disease course of patients who developed SM following ICI therapy at a single tertiary cancer center. METHODS: We retrospectively identified 12 eligible adult cancer patients between 05/2011 and 05/2022. Patients' clinical data were evaluated and summarized. RESULTS: The median patient age was 71.5 years. The most common cancer types were gastrointestinal, hematologic, and skin. Eight patients (67%) received anti-PD-1/L1 monotherapy, 2 (17%) received anti-CTLA-4 monotherapy, and 2 (17%) received combination therapy. SM occurred after a median duration of 8.6 months from the first ICI dose. Most patients (75%) were asymptomatic on diagnosis. Three patients (25%) reported abdominal pain, nausea, and fever and received inpatient care and corticosteroid treatment with symptom resolution. No patients experienced SM recurrence after the completion of corticosteroids. Seven patients (58%) experienced resolution of SM on imaging. Seven patients (58%) resumed ICI therapy after the diagnosis of SM. CONCLUSIONS: SM represents an immune-related adverse event that may occur after initiation of ICI therapy. The clinical significance and optimal management of SM following ICI therapy remains uncertain. While most cases were asymptomatic and did not require active management or ICI termination, medical intervention was needed in select symptomatic cases. Further large-scale studies are needed to clarify the association of SM with ICI therapy.

Diarrhea and colitis related to immune checkpoint inhibitor and BRAF/MEK inhibitor therapy.

Background: Immune checkpoint inhibitor (ICI) therapy can be complicated by gastrointestinal adverse events (AEs). Similarly, gastrointestinal AEs have been reported with the use of serine/threonine-protein kinase B-Raf (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitor therapy. We investigated the characteristics and management of gastrointestinal AEs related to sequential ICI and BRAF/MEK inhibitor therapy. Methods: We identified 255 adult cancer patients who received both BRAF/MEK inhibitor therapy and ICI therapy between 2014 and 2021. Thirty-two eligible patients had gastrointestinal AEs after receiving both therapies and were categorized based on the order of their administration. Their clinical characteristics, evaluation, treatment and outcomes were compared. Results: Of the 32 eligible patients, 18 (56.3%) received ICI therapy followed by BRAF/MEK inhibitors (early ICI group), and 14 (44.8%) received BRAF/MEK inhibitor therapy followed by ICI (early BRAF/MEK inhibitor group). Compared with the early BRAF/MEK inhibitor group, the early ICI group had higher rates of grade 3-4 diarrhea (50.0% vs. 14.3%, P=0.047) and grade 3-4 colitis (38.9% vs. 0%, P=0.010). The early ICI group had a later onset of colitis (347.5 vs. 84.5 days, P=0.011) and a higher rate of hospitalization at initial colitis presentation (100% vs. 71.4%, P=0.028). Patients in the early ICI group were more likely to have diarrhea or colitis recurrence (69.2% vs. 9.1%, P=0.019) and re-hospitalization for colitis (38.9% vs. 0%, P=0.010). Conclusion: The sequential exposure of BRAF/MEK therapy after ICI may contribute to a more aggressive clinical profile of gastrointestinal toxicities that may warrant a more aggressive management strategy.

Both acute and chronic inflammation are associated with less perineural invasion in men with prostate cancer on repeat biopsy.

OBJECTIVES: To evaluate the association between acute and chronic inflammation with the presence of perineural invasion (PNI) in prostate biopsies positive for prostate cancer (PCa). MATERIAL AND METHODS: We conducted a retrospective analysis of 1 399 prostate biopsies positive for PCa in the Reduction by Dutasteride of PCa Events (REDUCE) study. PCa, acute and chronic prostate inflammation and PNI were assessed by central pathology review. The association between acute and chronic inflammation with PNI was evaluated using chi-squared and Kruskal-Wallis tests, and logistic regression adjusting for clinicopathological and biochemical variables. RESULTS: The presence of PNI was identified in 133 biopsies (9.5%). In all, 267 biopsies (19.1%) had acute inflammation, 1 038 (74.2%) had chronic inflammation, and 255 (18.2%) had both. The presence of both acute and chronic inflammation had a mutual association (P < 0.001). Chronic inflammation was associated with a lower Gleason score (P = 0.009) and lower tumour volume (P < 0.001), while acute inflammation was associated with lower Gleason score (P = 0.04), lower tumour volume (P = 0.004) and higher prostate-specific antigen levels (P = 0.05). In both univariable and multivariable analyses, chronic prostate inflammation was significantly associated with less PNI (univariable odds ratio [OR] 0.54, 95% confidence interval [CI] 0.37-0.79, P = 0.001; multivariable OR 0.65, 95% CI 0.43-0.99, P = 0.045). Acute prostate inflammation was associated with less PNI only in univariable analysis (univariable OR 0.51, 95% CI 0.29-0.89, P = 0.018; multivariable OR 0.63, 95% CI 0.35-1.13, P = 0.12). CONCLUSION: Acute and chronic prostate inflammation were both associated with a lower prevalence of PNI in prostate biopsies positive for PCa. If confirmed, this suggests that inflammation and immunomodulation can serve as areas of potential therapeutic design to mitigate PNI in patients with PCa.