Pneumatosis intestinalis in cancer patients who received immune checkpoint inhibitors.

PURPOSE: Immune checkpoint inhibitor (ICI) therapy may give rise to immune-related adverse events (irAEs). Pneumatosis intestinalis (PI), or gas within the bowel wall, has very rarely been observed following ICI therapy, and its clinical significance is unclear. We described the clinical characteristics and outcomes of PI as a possible irAE in cancer patients. METHODS: We retrospectively identified 12 adult cancer patients with radiologic evidence of PI within 1 year after ICI exposure during January 2010-January 2023. Clinical characteristics, treatment, and outcomes were evaluated. RESULTS: The median age of our sample was 64 years. The most common cancer types were thoracic/head & neck and gastrointestinal. Eleven patients (92%) received anti-PD-1/L1 monotherapy, while 1 patient (8%) received a combination of anti-PD-1/L1 and anti-CTLA-4. PI occurred a median of 7 months after the first ICI dose. Half the patients (50%) were asymptomatic on diagnosis, and the most common presenting symptom was abdominal pain (42%). Six patients experienced complications, namely pneumoperitoneum (n = 6, 50%) and microperforation (n = 1, 8%), identified on imaging. Nine patients were treated with antibiotics and 3 patients were monitored conservatively. Nine patients (75%) resumed cancer treatment after PI. CONCLUSION: PI may develop as an irAE. While half of cases were incidental radiologic findings, management with antibiotics as well as hospitalization for observation may still be appropriate. The decision to restart cancer therapy and possibly resume ICI therapy remains to be elucidated. Further large-scale studies may be warranted to clarify the association between PI and ICI therapy.

Colon Adenoma After Diagnosis of Immune Checkpoint Inhibitor-mediated Colitis.

Purpose: While the occurrence of colitis during immune checkpoint inhibitor (ICI) treatment is recognized as a sign of robust immune activation and correlates with better oncological outcomes, the long-term impact of ICI-mediated colitis on the colonic mucosa has not been studied. We thus aim to describe the colonoscopy and histology findings in patients at a follow-up time of ≥ 6 months post initial colitis event. Methods: This retrospective analysis included adult cancer patients diagnosed with ICI colitis at a tertiary cancer center between October 2013 and June 2020. The study group included patients diagnosed with immune mediated colitis who had also undergone a follow up colonoscopy or flex sigmoidoscopy. The control group was patients exposed to ICI without immune mediated colitis. We reported patients' colitis clinical course, treatment, outcomes, and endoscopic and histologic features at diagnosis and at follow-up time of ≥ 6 months. Results: Total 39 patients met the study criteria, with 82% being male, and 35.8% having melanoma. Most patients received a combination of CTLA-4 and PD-1/L1 inhibitors (82%). On initial endoscopic evaluation, inflammation without ulceration was reported in 76.9% of patients and active inflammation on histologic examination in 79.3% of patients. Most patients (79.4%) received corticosteroids, and 56.4% received add-on selective immunosuppressive therapy. Four patients received fecal microbiota transplantation. On follow-up, new incidence of colonic polyps was reported in 51.2% of patients, including adenomas in 33.3% among the colitis patients with median follow up duration of 12 months. The incidence of adenoma polyps 12 months after the colitis event was significantly higher compared to the control group without colitis based on the time-to-event analysis (p=0.041). Conclusion: At a median follow up of 12 months after their initial colitis diagnosis, 51.2% of the patients had new incidence of colonic polyps, including a third with adenoma, at a significantly higher incidence than the control group without colitis. Studies with larger sample sizes are needed to further define the long-term impact of colitis and its treatments on colon health and to refine recommendations for surveillance of colonic adenomas and colorectal cancer.

Performance and attitudes toward real-time computer-aided polyp detection during colonoscopy in a large tertiary referral center in the United States.

BACKGROUND AND AIMS: Computer-aided detection (CADe) has been shown to improve polyp detection in clinical trials. Limited data exist on the impact, utilization, and attitudes toward artificial intelligence (AI)-assisted colonoscopy in daily clinical practice. We aimed to evaluate the effectiveness of the first U.S. Food and Drug Administration-approved CADe device for polyp detection in the United States and the attitudes toward its implementation. METHODS: We performed a retrospective analysis of a prospectively maintained database of patients undergoing colonoscopy at a tertiary center in the United States before and after a real-time CADe system was made available. The decision to activate the CADe system was at the discretion of the endoscopist. An anonymous survey was circulated among endoscopy physicians and staff at the beginning and conclusion of the study period regarding their attitudes toward AI-assisted colonoscopy. RESULTS: CADe was activated in 52.1% of cases. Compared with historical control subjects, there was no statistically significant difference in adenomas detected per colonoscopy (1.08 vs 1.04, P = .65), even after excluding diagnostic and therapeutic indications and cases where CADe was not activated (1.27 vs 1.17, P = .45). In addition, there was no statistically significant difference in adenoma detection rate (ADR), median procedure, and withdrawal times. Survey results demonstrated mixed attitudes toward AI-assisted colonoscopy, of which main concerns were high number of false-positive signals (82.4%), high level of distraction (58.8%), and impression it prolonged procedure time (47.1%). CONCLUSIONS: CADe did not improve adenoma detection in daily practice among endoscopists with high baseline ADRs. Despite its availability, AI-assisted colonoscopy was only activated in half of the cases, and multiple concerns were raised by staff and endoscopists. Future studies will help elucidate the patients and endoscopists that would benefit most from AI-assisted colonoscopy.

Continuing Medical Education Questions: December 2022.

Article Title: Use of Benzodiazepines and Z-Drugs in Inflammatory Bowel Disease.

Continuing Medical Education Questions: February 2021.

Article Title: Hypercontractile Esophagus From Pathophysiology to Management: Proceedings of the PISA Symposium.

Continuing Medical Education Questions: August 2021.

Article Title: Antispasmodics for Chronic Abdominal Pain: Analysis of North American Treatment Options.

Patients with non-colorectal cancers may be at elevated risk of colorectal neoplasia.

Background: Screening for colonic neoplasia has decreased the incidence of colorectal cancer in the United States in the past two decades. Whether personal history of noncolorectal cancer is a risk factor for colonic neoplasia has not been well studied. We assessed the risk of colorectal neoplasia in noncolorectal cancer survivors. Methods: We conducted a retrospective study of patients who had undergone colonoscopy for any indication between 2009 and 2018. Colonic adenoma detection rate and multivariate logistic regression were conducted to assess for the primary outcomes of the study. Results: The study included 9408 cancer patients and 3295 control patients. Colonic adenomas were detected in 4503 cancer patients (48%) and 950 cancer-free patients (29%). Histologic examination of these adenomas revealed tubulovillous features in 620 patients (5%) and villous in 153 (1%). High-grade dysplasia was detected in 1611 patients (13%). Invasive colorectal adenocarcinoma was detected in 455 patients (12%); this rate was highest in patients with multiple myeloma (14%). Multivariate analysis revealed that a personal history of noncolorectal cancer was associated with increased risk of adenoma (Odd ratio, 2.04; 95% CI, 1.84-2.26; P<0.001). The adenoma detection rate was 30% in patients younger than 40 years (n=1211), 32% in patients between 41 and 50 years (n=812), 47% in patients between 51 and 60 years (n=2892), and 55% in patients older than 60 years (n=4493). Conclusions: The adenoma detection rate in patients with a personal history of noncolorectal cancer is higher than the reported rate of the general population and our control group.

Chronic Spontaneous Pneumoperitoneum with Pneumatosis Cystoides Intestinalis of the Small and Large Intestine.

Pneumoperitoneum can be an alarming radiological finding and a manifestation of a surgical emergency that warrant urgent intervention, or it can be a manifestation of chronic benign condition that can be managed conservatively. The sequela of misdiagnosing pneumoperitoneum due to surgical abdomen as a chronic benign pneumoperitoneum can be life-threatening and misdiagnosing chronic spontaneous pneumoperitoneum due to chronic condition as surgical emergency will lead to unnecessary surgical interventions. Diagnosis of chronic spontaneous pneumoperitoneum can be challenging to the unwary healthcare-providers. We present a case of chronic pneumoperitoneum secondary to pneumatosis cystoides intestinalis that has been managed conservatively.

Gastrointestinal Motility Issues in Cancer Patients.

PURPOSE OF REVIEW: This paper seeks to highlight GI motility disorders that are frequently present in patients with a malignancy. GI dysmotility can occur due to the cancer itself or as a consequence of medical and surgical treatments. Often, symptoms are nonspecific and the diagnosis requires a high index of suspicion. The goal of the paper is to review the common motility problems seen in patients with cancer, their clinical manifestations, and options for management. RECENT FINDINGS: Studies show that newer endoscopy techniques such as endoscopic mucosal dissection can cause esophageal dysmotility. Opioid-induced constipation is frequently encountered in patients with cancer. Motility disorders in cancer patient can lead to clinical morbidity, poor quality of life, and malnutrition. Newer diagnostic tests and medical and surgical treatments may be helpful in improving the diagnosis and management of these disorders.

Continuing Medical Education Questions: September 2019.

Article Title: Endoscopic Bariatric Therapy: A Guide to the Intragastric Balloon.

Continuing Medical Education Questions: May 2019.

To receive CME/MOC credit for this activity, please go to: http://acgjournalcme.gi.org/Article Title: Current Status of Endoscopic Resection of Gastric Subepithelial Tumors.

Clinical Features of Rituximab-associated Gastrointestinal Toxicities.

BACKGROUND: Rituximab is effective in treating several cancers. Little is known about gastrointestinal adverse events associated with rituximab. We describe the clinical, endoscopic, and histologic features of rituximab-associated colitis (RC) at a tertiary care cancer center. METHODS: We conducted a retrospective study of cancer patients who had received rituximab and had undergone a colonoscopy between 2000 and 2018. Patients with competing etiologies for colitis were excluded. RESULTS: Of the 13,717 patients who had received rituximab during the study period, 1660 had undergone colonoscopy. Among them, 70 (4%) had RC. Median time from rituximab treatment to RC onset was 181 days. Fifty-three patients had clinical gastrointestinal symptoms: 39 had diarrhea, 19 had abdominal pain, 11 had blood per rectum, and 5 had a concurrent fever. The median duration of symptoms was 21 days. Fifty patients (71%) received treatment for RC: immunosuppressive therapy in 12, antimicrobial agents in 21, antimotility agents in 42, and supportive care in 42. Nine patients had mucosal ulceration on endoscopy, and 52 had features of active inflammation on histology. Thirty-nine patients needed hospital admission, and 2 needed intensive care unit admission. One patient had colonic perforation that required surgical intervention. Patients who had abnormal endoscopic findings needed more frequent hospitalization (P=0.024) and more treatment for RC (P=0.001). CONCLUSIONS: RC is usually a mild disease requiring supportive care only. Nonetheless, on rare occasions, it can be severe enough to lead to colonic perforation and intensive care unit admission. Steroids used with the chemotherapeutic regimen can hamper RC severity.

Quality of endoscopy reporting at index colonoscopy significantly impacts outcome of subsequent EMR in patients with > 20 mm colon polyps.

Background and study aims Endoscopic mucosal resection (EMR) is safe and cost-effective in management of patients with colon polyps. However, very little is known about the actions of the referring endoscopist following identification of these lesions at index colonoscopy, and the impact of those actions on the outcome of subsequent referral for EMR. The aim of this study was to identify practices at index colonoscopy that lead to failure of subsequent EMR. Patients and methods Two hundred and eighty-nine consecutive patients with biopsy-proven non-malignant colon polyps (> 20 mm) referred for EMR were analyzed to identify practices that could be improved from the time of identifying the lesion at index colonoscopy until completion of therapy. Results EMR was abandoned at colonoscopy at the EMR center in 71 of 289 patients (24.6 %). Reasons for abandoning EMR included diagnosis of invasive carcinoma (n = 9; 12.7 %), tethered lesions (n = 21; 29.6 %) from prior endoscopic interventions, and overly large (n = 22; 31 %) and inaccessible lesions (n = 17; 24 %) for complete and safe resection whose details were not recorded in the referring endoscopy report, or polyposis syndromes (n = 2; 2.8 %) that were not recognized. Conclusions In our practice, one in four EMR attempts were abandoned as a result of inadequate diagnosis or management by the referring endoscopist, which could be improved by education on optical diagnosis of polyps, comprehensive documentation of the procedure and avoidance of interventions that preclude resection.

Dysphagia: An Unusual Presentation of Metastatic Uterine Cervical Carcinoma.

Worldwide, cervical cancer is the third most common cancer among women and the fourth leading cause of death from cancer. The most common sites of metastasis are the pelvic lymph nodes, vagina, and the pelvic sidewalls. Distant metastases are uncommon but can involve the bone, lung, and liver. Characteristics associated with increased rate of distant metastasis include bulky tumor, endometrial extension, lymph node involvement, and advanced disease. We report the case of a woman with stage II cervical carcinoma, who presented with dysphagia due to cervical cancer metastases to the mediastinum.

Impact of Hepatitis B Core Antibody Seropositivity on the Outcome of Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma.

Hepatitis B core antibody (HBcAb) seropositivity has been associated with a higher rate of hepatitis B virus (HBV) reactivation after chemotherapy, even in patients who are hepatitis B surface antigen (HBsAg) negative. However, little is known about the risk of HBV reactivation after autologous hematopoietic stem cell transplantation (auto-HCT). We evaluated the incidence of HBV reactivation, liver toxicity, and survival in patients with multiple myeloma (MM) who received auto-HCT at our institution. We retrospectively identified 107 MM patients with resolved HBV infection (HBcAb positive, HBsAg negative) and 125 patients with negative HBV serology (control subjects) who were matched for age, timing of auto-HCT from diagnosis, cytogenetics, disease status at transplant, induction therapy, and preparative regimen. All patients underwent auto-HCT between 1991 and 2013. Primary endpoints were HBV reactivation, defined as HBsAg positivity or ≥10-fold increase in HBV DNA, and hepatotoxicity, as defined in the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. In the resolved HBV infection group, 52 patients (49%) were HBsAb positive and 24 (22%) had detectable HBV DNA before auto-HCT. Only 1 patient with resolved HBV infection received pre-emptive antiviral therapy with lamivudine, whereas 4 patients received lamivudine (n = 3) or tenofovir (n = 1) at reactivation after auto-HCT for a median duration of 12 months. HBV reactivation occurred in 7 of 107 patients (6.5%) in the resolved HBV group. Median time to HBV reactivation from auto-HCT was 16 months. The cumulative incidence of grade 2 or greater hepatotoxicity was 30% in the resolved HBV infection group and 22% in the control group (hazard ratio, 1.3; 95% confidence interval, .7 to 2.3; P = .4). Nonrelapse mortality for the 2 groups was not statistically different at 2 years (P = .06), although it trended higher in the control group than in the resolved HBV infection group (8% versus 1%). The median progression-free survival (PFS) and overall survival (OS) durations in the resolved HBV infection and control groups were 21 versus 18 months (P = .5) and 53 versus 67 months (P = .2), respectively. Our data suggest that resolved HBV infection in patients undergoing auto-HCT for MM is associated with a low risk of HBV reactivation and hepatotoxicity; these complications were reversible and did not adversely affect the PFS or OS.

Mutational Profiles Reveal an Aberrant TGF-ß-CEA Regulated Pathway in Colon Adenomas.

Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-ß pathway and CEA-associated genes in 4 out of 11 adenomas, overlapping with the Wnt pathway. Immunohistochemical labeling reveals a nearly 5-fold increase in CEA levels in 23% of adenoma samples with a concomitant loss of TGF-ß signaling. We also define a functional role by which the CEA B3 domain interacts with TGFBR1, potentially inactivating the tumor suppressor function of TGF-ß signaling. Our study uncovers diverse mutational processes underlying the transition from early adenoma to cancer. This has broad implications for biomarker-driven targeting of CEA/TGF-ß in high-risk adenomas and may lead to early detection of aggressive adenoma to CRC progression.