Safety and efficacy of metal stents for malignant colonic obstruction in patients treated with bevacizumab.

BACKGROUND AND AIMS: The aim of this study was to examine clinical outcomes and adverse events (AEs) of self-expandable metal stents (SEMSs) in the management of malignant colonic obstruction (MCO). METHODS: Patients with SEMSs for MCO treated at our institution from 2007 to 2016 were included. Clinical success was defined as successful oral intake after the procedure and technical success as stent deployment across the stricture in the desired location. RESULTS: Of 199 patients, the mean age was 58, 54% were men, and 99% had stage IV cancer. MCO etiology was colorectal cancer in 82% and extrinsic compression in 17%. Technical success was achieved in 99.5% and clinical success in 89%. The SEMSs were palliative in 97% and were a bridge to surgery in 4%. MCO occurred in the left side of the colon in 90%, transverse in 4.5%, and ascending colon in 5.5%. SEMSs were placed in curved segments in 30% and straight segments in 70%. Tandem SEMSs were required in 27 patients. Forty-six patients had 48 AEs (24%), including 2% periprocedure, 15% postprocedure, and 83% after 72 hours. Stent-related AEs (n = 25) included persistent obstruction (n = 14), occlusion (n = 10), and failure of expansion (n = 1). Procedural AEs (n = 23) included minor bleeding (n = 2), perforations (n = 4), abdominal pain (n = 12), stent migration (n = 4), and respiratory insufficiency (n = 1). Repeat procedures were performed in 21 of 46 patients. After SEMSs, 48 patients underwent surgery, including resection with primary anastomosis (n = 8), resection with definitive stoma (n = 18), and diverting stoma without resection (n = 19). Mean time to surgery after SEMS placement was 175 days. Postsurgical AEs occurred in those with resections (leak, 2; infection, 2). Of 104 receiving bevacizumab, 22% had AEs, including 1 perforation compared with 3 in the nonbevacizumab group (P = .549). Mean overall survival was 5.6 months. Extrinsic compression and curved strictures were associated with poor clinical success by univariate analysis and etiology (noncolonic with poor outcome) by multivariate analysis. CONCLUSIONS: SEMSs for MCO has high technical but suboptimal clinical success. Curved strictures and extrinsic compression are associated with poor outcomes. The perforation rate was not higher in the bevacizumab compared with the nonbevacizumab group, although this should be further validated in a larger population.

Safety of endoscopy in cancer patients with thrombocytopenia and neutropenia.

BACKGROUND AND AIMS: Cancer patients are prone to thrombocytopenia and neutropenia, which increase the risk of bleeding and infection. We assessed the safety of endoscopic procedures in cancer patients with thrombocytopenia and/or neutropenia. METHODS: We studied consecutive cancer patients with thrombocytopenia and/or neutropenia who underwent endoscopic procedures from 2010 through 2015. Neutropenia was defined as an absolute neutrophil count (ANC) <1000 cells/µL, and thrombocytopenia as a platelet count <100 × 103/µL. Univariate and multivariate generalized estimating equation models were used to assess factors associated with risk of adverse events (AEs) or death. RESULTS: We identified 588 patients who underwent 783 procedures; 608 procedures were performed in the setting of thrombocytopenia and 675 procedures in the setting of neutropenia. Concurrent neutropenia and thrombocytopenia were recorded in 500 endoscopies. Twenty-four patients (4.1%) experienced infectious AEs, whereas 29 (4.9%) experienced bleeding AEs within 1 week of the procedure. On multivariate analysis, platelet count ≤50 × 103/µL was associated with risk of bleeding AEs. In contrast, poor performance status was associated with increased risk of infection AEs (P < .01). No association was observed between low ANC and infectious AEs. Poor performance status (P < .01) and platelet count ≤100 × 103/µL (P < .05) were associated with increased risk of 30-day mortality. A persistent platelet count <20 × 103/µL after the procedure, with a baseline platelet count of ≤20 × 103/µL before the procedure, was associated with significant risk of bleeding AEs compared with a platelet count >20 × 103/µL after the procedure (P < .01); furthermore, if the platelet count increased to >50 × 103/µL after the procedure, the bleeding risk after the procedure was greatly reduced (P < .01). CONCLUSIONS: Endoscopic procedures are relatively safe in cancer patients with platelet count >50 × 103/µL. Nevertheless, a platelet count of ≥20 × 103/µL could be an appropriate threshold for platelet transfusion if 50 × 103/µL is difficult to achieve. The functional status of the patient, in the absence of the need for urgent or necessary endoscopic interventions, should be considered when deciding whether to perform endoscopy. The risk of procedure and the ANC did not seem to affect the outcomes.

The somatic mutation landscape of premalignant colorectal adenoma.

OBJECTIVE: There are few studies which characterised the molecular alterations in premalignant colorectal adenomas. Our major goal was to establish colorectal adenoma genome atlas and identify molecular markers of progression from colorectal adenoma to adenocarcinoma. DESIGN: Whole-exome sequencing and targeted sequencing were carried out in 149 adenoma samples and paired blood from patients with conventional adenoma or sessile serrated adenoma to characterise the somatic mutation landscape for premalignant colorectal lesions. The identified somatic mutations were compared with those in colorectal cancer (CRC) samples from The Cancer Genome Atlas. A supervised random forest model was employed to identify gene panels differentiating adenoma from CRC. RESULTS: Similar somatic mutation frequencies, but distinctive driver mutations, were observed in sessile serrated adenomas and conventional adenomas. The final model included 20 genes and was able to separate the somatic mutation profile of colorectal adenoma and adenocarcinoma with an area under the curve of 0.941. CONCLUSION: The findings of this project hold potential to better identify patients with adenoma who may be candidates for targeted surveillance programmes and preventive interventions to reduce the incidence of CRC.

Loss of the transforming growth factor-ß effector ß2-Spectrin promotes genomic instability.

Exposure to genotoxins such as ethanol-derived acetaldehyde leads to DNA damage and liver injury and promotes the development of cancer. We report here a major role for the transforming growth factor ß/mothers against decapentaplegic homolog 3 adaptor ß2-Spectrin (ß2SP, gene Sptbn1) in maintaining genomic stability following alcohol-induced DNA damage. ß2SP supports DNA repair through ß2SP-dependent activation of Fanconi anemia complementation group D2 (Fancd2), a core component of the Fanconi anemia complex. Loss of ß2SP leads to decreased Fancd2 levels and sensitizes ß2SP mutants to DNA damage by ethanol treatment, leading to phenotypes that closely resemble those observed in animals lacking both aldehyde dehydrogenase 2 and Fancd2 and resemble human fetal alcohol syndrome. Sptbn1-deficient cells are hypersensitive to DNA crosslinking agents and have defective DNA double-strand break repair that is rescued by ectopic Fancd2 expression. Moreover, Fancd2 transcription in response to DNA damage/transforming growth factor ß stimulation is regulated by the ß2SP/mothers against decapentaplegic homolog 3 complex. CONCLUSION: Dysfunctional transforming growth factor ß/ß2SP signaling impacts the processing of genotoxic metabolites by altering the Fanconi anemia DNA repair pathway. (Hepatology 2017;65:678-693).

Outcome of EMR as an alternative to surgery in patients with complex colon polyps.

BACKGROUND AND AIMS: Patients with complex colon polyps were traditionally referred for surgery to avoid adverse events associated with endoscopic resection. Recent advances in endoscopic imaging as well as endoscopic hemostasis and clip closure allow for the use of EMR as an alternative to surgery for such lesions. To determine the outcome of treatment of complex colon polyps with EMR as an alternative to surgery, we conducted a retrospective observational study. METHODS: Two hundred three patients with complex colon polyps were referred to an EMR center as an alternative to surgery. Patients underwent a protocol-driven EMR. The primary endpoint was the complete resection rate. Secondary endpoints were safety, residual adenoma rate, and incidence of missed synchronous polyps. RESULTS: EMR was performed in 155 patients and was deferred in 48 patients who were referred to surgery. EMR specimens revealed benign polyps in 149 and cancer in 6 patients. EMR adverse events occurred in 7 patients, requiring hospitalization in 5 of them. None of the patients died as a result of their adverse events. Surveillance colonoscopy at 4 to 6 months after resection of a benign lesion in 137 patients revealed residual adenoma at the scar site in 6 patients and additional synchronous precancerous lesions in 117 patients that were not removed by the referring endoscopist. None underwent surgery for failure of EMR. The overall precancerous lesion burden was 2.83 per patient, the adenoma burden was 2.13 per patient, and the serrated polyp burden was .69 per patient. CONCLUSIONS: EMR can be used instead of surgery for complex colon polyps in 75% of patients with few adverse events and few residual adenomas at resection sites. In addition, careful repeat examination of the entire colon for synchronous lesions overlooked by the referring endoscopist is required for most patients. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01827241.).

Natural language processing as an alternative to manual reporting of colonoscopy quality metrics.

BACKGROUND AND AIMS: The adenoma detection rate (ADR) is a quality metric tied to interval colon cancer occurrence. However, manual extraction of data to calculate and track the ADR in clinical practice is labor-intensive. To overcome this difficulty, we developed a natural language processing (NLP) method to identify adenomas and sessile serrated adenomas (SSAs) in patients undergoing their first screening colonoscopy. We compared the NLP-generated results with that of manual data extraction to test the accuracy of NLP and report on colonoscopy quality metrics using NLP. METHODS: Identification of screening colonoscopies using NLP was compared with that using the manual method for 12,748 patients who underwent colonoscopies from July 2010 to February 2013. Also, identification of adenomas and SSAs using NLP was compared with that using the manual method with 2259 matched patient records. Colonoscopy ADRs using these methods were generated for each physician. RESULTS: NLP correctly identified 91.3% of the screening examinations, whereas the manual method identified 87.8% of them. Both the manual method and NLP correctly identified examinations of patients with adenomas and SSAs in the matched records almost perfectly. Both NLP and the manual method produced comparable values for ADRs for each endoscopist and for the group as a whole. CONCLUSIONS: NLP can correctly identify screening colonoscopies, accurately identify adenomas and SSAs in a pathology database, and provide real-time quality metrics for colonoscopy.

Genetic and intermediate phenotypic susceptibility markers of gastric cancer in Hispanic Americans: a case-control study.

BACKGROUND: Hispanics are the largest nonwhite ethnic group in the US population, and they have higher incidence and mortality rates for gastric cancer (GC) than whites and Asians. Studies have identified several genetic susceptibility loci and intermediate phenotypic biomarkers for GC in whites and Asians. No studies have evaluated genetic susceptibility and intermediate phenotypic biomarkers in Hispanics. METHODS: In a case-control study of 132 Hispanic patients with GC (cases) and a control group of 125 Hispanics (controls), the authors evaluated the association of 5 single nucleotide polymorphisms (SNPs) that predispose whites and/or Asians to GC and of 2 intermediate phenotypic markers in peripheral blood leukocytes, ie, telomere length and mitochondrial DNA (mtDNA) copy number, with the GC risk. RESULTS: The variant C allele of the reference SNP rs2294008 in the PSCA gene was associated with a significantly reduced risk of GC (per allele-adjusted odds ratio [aOR], 0.51; 95% confidence interval [CI], 0.33-0.77; P = .002). Leukocyte mtDNA copy numbers were significantly lower in GC cases (mean ± standard deviation, 0.91 ± 0.28) than in controls (1.29 ± 0.42; P < .001). When individuals were dichotomized into high and low mtDNA copy number groups based on the median mtDNA copy number value in the controls, those who had a low mtDNA copy number had a significantly increased risk of GC (aOR, 11.00; 95% CI, 4.79-25.23; P < .001) compared with those who had a high mtDNA copy number. Telomere length was not associated significantly with the risk of GC (aOR, 1.21; 95% CI, 0.65-2.27; P = .551). CONCLUSIONS: Hispanics share certain genetic susceptibility loci and intermediate phenotypic GC biomarkers with whites and Asians and may also have distinct genetic susceptibility factors.

Endoscopic Intrapyloric Botulinum Toxin Injection with Pyloric Balloon Dilation for Symptoms of Delayed Gastric Emptying after Distal Esophagectomy for Esophageal Cancer: A 10-Year Experience.

Patients with esophageal cancer undergoing esophagectomy have an improved survival over time, however adverse events associated with the use of a gastric conduit are increasingly being reported. Delayed gastric emptying (DGE) is an esophagectomy-related complication which can decreased quality of life by causing debilitating gastrointestinal symptoms and malnutrition. The aim of our study was to evaluate the effect of endoscopic intrapyloric botulinum (BT) injection in combination with pyloric balloon dilation in patients with DGE following distal esophagectomy at our tertiary cancer center. Patients with a prior history of distal esophagectomy who had also undergone endoscopic BT injection with pyloric balloon dilation by a single endoscopist between 2007 and 2017 were included in the study. One hundred units of BT were injected endoscopically into the pylorus in four quadrants using an injection needle. Following BT injection, a standard through-the-scope balloon was passed to the pylorus and inflated to a maximum diameter of 12−20 mm. For patients who underwent repeat procedures, the symptomatic outcomes were assessed and documented by the endoscopist; for the other patients, the electronic medical records were reviewed. A total of 21 patients undergoing 44 endoscopic intrapyloric botox injections combined with balloon dilatations were identified. The patients underwent the procedures at a median of 22 months (range, 1−108 months) after esophagectomy. The procedures were performed only once in 43% of the patients; 43% patients underwent the procedure twice, while 14% had it multiple times (>2). Overall, intrapyloric BT injection coupled with balloon dilation was a safe procedure, without any major immediate or delayed (1 month) procedure-related adverse events. Eighteen patients (85%) reported a significant overall improvement in symptoms from the initial presentation. One patient (5%) showed no improvement, whereas in two (10%) patients responses were not available. In our particular cohort of patients, the interventions of endoscopic intrapyloric BT injection with pyloric balloon dilation proved to be very beneficial, leading to significant symptomatic improvement. The balloon dilation after BT injection might have resulted in better diffusion of the BT into the pyloric sphincter complex, possibly increasing its therapeutic effects. Further prospective studies are needed to validate these results.

Incidental finding of focal FDG uptake in the bowel during PET/CT: CT features and correlation with histopathologic results.

OBJECTIVE: The purpose of this study was to identify and characterize the clinically significant lesions associated with incidental detection of focal uptake of (18)F-FDG in the bowel at PET/CT. MATERIALS AND METHODS: Among 2,250 consecutively registered patients with various nongastrointestinal malignant diseases who underwent FDG PET/CT as part of their care, patients with the incidental finding of focal bowel uptake of FDG were included in the study. All patients underwent an endoscopic or surgical procedure for characterization of the lesions. The location, intensity of uptake, and appearance of the lesions on PET/CT images were recorded and compared with the endoscopic and surgical pathologic results. RESULTS: Twenty-one of 25 foci of intense uptake in the bowel were associated with endoscopic or surgical abnormalities (positive predictive value, 84%). Seven lesions were malignant (two primary, five secondary); 13 were premalignant (nine tubovillous adenoma, four tubular adenoma); and one lesion was benign (hyperplastic polyp). Eleven lesions detected with endoscopy were not FDG avid, and all 11 were smaller than 1 cm in diameter. There was no statistically significant difference in the maximum standardized uptake values of the benign and malignant lesions. CONCLUSION: The incidental finding of focal FDG uptake in the bowel justifies further investigation of these foci and should not be dismissed as physiologic uptake. Premalignant lesions, such as adenoma, are often found, and early treatment may prevent the development of carcinoma.

Quality of life impact of EUS in patients at risk for developing pancreatic cancer.

BACKGROUND AND OBJECTIVES: The current knowledge about the psychological impact of pancreatic cancer (PC) screening is limited. We aimed to assess the changes in quality of life (QOL) and level of distress after undergoing EUS in individuals with pancreatic cystic lesions (PCLs) and in patients at high risk for PC based on genetic and familial factors. METHODS: Eighty patients with PCL and/or increased genetic or familial risk for PC who had undergone EUS were contacted. Fifty percent of those patients successfully completed the brief profile of mood states (POMS) and the linear analog scale assessment (LASA) QOL questionnaires to evaluate their pre/post-EUS overall QOL. The effect size (ES) method was used to assess clinically meaningful changes in the scores. RESULTS: There was a significant difference in patients' overall QOL scores before and after the EUS procedure (LASA, mean difference 0.73, standard deviation (SD) 1.76, ES 0.58, P < 0.01; brief POMS, mean difference -5.46, SD -6.72, ES 0.81, P < 0.01). CONCLUSIONS: QOL of patients with PCL or increased risk factors for PC is significantly improved after a EUS/EUS-guided fine-needle aspiration (FNA) negative for malignancy.

Cap-fitted endoscopic mucosal resection of ≥ 20 mm colon flat lesions followed by argon plasma coagulation results in a low adenoma recurrence rate.

Background and study aims Endoscopic mucosal resection (EMR) is increasingly used for the treatment of large colonic polyps (≥ 20 mm). A drawback of EMR is local adenoma recurrence. Therefore, we studied the impact of argon plasma coagulation (APC) of the EMR edge on local adenoma recurrence. Patients and methods This was a retrospective study of patients with laterally spreading tumors (LST) ≥ 20 mm, who underwent EMR from January 2009 to August 2018 and follow-up endoscopic assessment. A cap-fitted endoscope was used to assess completeness of resection by systematically inspecting the EMR defect for any macroscopic disease. This was followed by forced APC of the resection edge followed by clip closure of the defect. Surveillance colonoscopy was performed at 6 months after resection to detect recurrence. Results Two hundred forty-six patients met the inclusion criteria. Most were female (53 %) and white (80 %), with a Median age of 64 years. Median polyp size was 35 mm (interquartile range, 30-45 mm). Most polyps were located in the right colon (77 %) and were removed by piecemeal EMR (70 %). Eleven patients (5 %) had residual tumor at the resection site. Conclusions We observed low adenoma recurrence after argon plasma coagulation of the EMR edge with a cap fitted colonoscope in patients with LST ≥ 20 mm of the colon, which requires further validation in a randomized controlled study.

Recurrent Clostridium difficile infection is associated with treatment failure and prolonged illness in cancer patients.

BACKGROUND: Cancer patients are susceptible to recurrent Clostridium difficile infection (CDI) that is increasing globally, necessitating new approaches to prevent fatal consequences. We examined the clinical characteristics of cancer patients with recurrent CDI (RCDI). PATIENTS AND METHODS: A retrospective review of cancer patients with C. difficile-positive test between January 2015 and May 2017 was carried out. CDI was defined as diarrhea and toxigenic C. difficile detection in the stool by nucleic acid amplification test and enzyme immunoassay. Patients having two CDI episodes were categorized as single recurrent CDI (SRCDI), and those having three or more CDI episodes were categorized as multiple recurrent CDI (MRCDI). Treatment failure was defined as the requirement of antimicrobial alteration or repetition. RESULTS: We included 170 patients having 270 CDI episodes; 85 patients had non-RCDI, and 85 had RCDI; 14 of them had MRCDI. Previous hospitalization and immunosuppressant use were more frequent in MRCDI group than in SRCDI group (P=0.009 and 0.002, respectively). Physicians treated more SRCDI episodes than MRCDI episodes with metronidazole alone (P=0.017), whereas, more MRCDI episodes needed combination antimicrobials (P=0.072). The mean duration of CDI treatment was longer in the MRCDI group than in the SRCDI group (P=0.030). MRCDI was associated with treatment failure more than SRCDI (P=0.021). The risk for a recurrent episode of CDI was increased in patients who had the following features of the first CDI episode: previous use of antibiotic, NSAID, immunosuppressant, chemotherapy, comorbidities, CDI treatment failure, and severe CDI (P<0.05). CONCLUSION: Risk factors for RCDI in cancer patients are similar to those without cancer, with the exception of chemotherapy that is only given to cancer patients. Long CDI treatment and CDI treatment failure are associated with MRCDI.

Can Immune Checkpoint Inhibitors Induce Microscopic Colitis or a Brand New Entity?

Background: Microscopic colitis (MC) has been described as 1 pattern of injury in immune checkpoint inhibitor (ICPI)-induced colitis. The main objective of this study was to characterize ICPI-induced MC by exploring the differences in risk factors, colitis treatments, endoscopic features, and clinical outcomes between cancer and noncancer patients with MC with and without exposure to ICPIs. Methods: A retrospective chart review was conducted among patients diagnosed with MC from our institutional pathology database from January 2012 to January 2018. Patients were categorized into MC in cancer patients with or without ICPI exposure and in noncancer patients. Risk factors (use of tobacco and certain medications), colitis treatments (antidiarrheals and immunosuppressants), endoscopic features (with or without mucosal abnormality), and clinical outcomes (diarrhea recurrence, hospitalization, mortality) were collected and compared among the 3 groups. Results: Of the 65 eligible patients with MC, 15 cancer patients had exposure to ICPI, 39 cancer patients had no exposure to ICPI, and 11 had no cancer diagnosis. Among the risk factors, proton pump inhibitor was more frequently used in the ICPI-induced MC cohort (P = 0.040). Furthermore, in this population, mucosal abnormality was the most common endoscopic feature compared with normal findings in the non-ICPI-induced MC groups (P = 0.106). Patients with ICPI-induced MC required more treatments with oral and intravenous steroids and nonsteroidal immunosuppressive agents (all P < 0.001) and had a higher rate of hospitalization (P < 0.001). Conclusion: This study suggests that despite some similarities between MC with and without exposure to ICPIs, ICPI-induced MC has a more aggressive disease course that requires more potent immunosuppressive treatment regimens and greater need for hospitalization. 10.1093/ibd/izy240_video1izy240.video15828223597001.

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.

Author Correction: Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.

In the version of this article originally published, an author was missing from the author list. Alexander J. Lazar should have been included between Jorge M. Blando and James P. Allison. The author has been added to the list, and the author contributions section has been updated to include Alexander J. Lazar's contribution to the study. The error has been corrected in the print, PDF and HTML versions of the manuscript.

Context-dependent functions of KLF4 in cancers: Could alternative splicing isoforms be the key?

Krüppel-like factor 4 (KLF4) is an important transcription factor that is expressed in a variety of tissues and regulates many critical physiologic and cellular processes, including cell proliferation, differentiation, stem cell reprogramming, maintenance of genomic stability, and normal tissue homeostasis. KLF4 has both tumor suppressive and oncogenic functions in gastrointestinal and other cancers. These functions are thought to be context dependent, but how KLF4 exerts these differential functions and the molecular mechanisms behind them remain poorly understood. Recent studies have shown that the KLF4 gene undergoes alternative splicing, and the protein products of certain transcripts antagonize wild-type KLF4 function, suggesting an additional layer of regulation of KLF4 function. Therefore, detailed study of KLF4 alternative splicing may not only provide new insights into the complexity of KLF4 functions but also lead to rational targeting of KLF4 for cancer prevention and therapy.

Immune-checkpoint inhibitor-induced diarrhea and colitis in patients with advanced malignancies: retrospective review at MD Anderson.

BACKGROUND: Immune checkpoint inhibitors (ICPIs) are gaining increasing popularity as an efficacious treatment for advanced malignancies. ICPI treatment can be complicated by diarrhea and colitis. Systemic steroids are the first line treatment. Infliximab is reserved for severe refractory cases. We aimed to assess the impact of ICPI-induced diarrhea and colitis and their immunosuppressive treatment on patients' outcomes. METHODS: This retrospective analysis was conducted in 327 cancer patients who received ICPIs between 2011 and 2017. Patients with ICPI-induced toxicities in other organs were excluded. We collected data about patient demographics, clinical variables, and overall survival. We used descriptive analysis to compare different groups based on the occurrence and the treatment of diarrhea and colitis. Kaplan-Meier and log-rank test were used to estimate and compare overall survival durations between groups. RESULTS: Diarrhea was recorded in 117 (36%) patients; 79 (24%) of them required immunosuppressive treatment of either systemic corticosteroid without infliximab (n = 44) or with infliximab (n = 35). Caucasian ethnicity, melanoma, stage 3 cancer, and ipilimumab were predictors of colitis that requires immunosuppression. Patients who required immunosuppressants had better overall survival than those who did not require treatment for colitis or diarrhea (P < 0.001). Immunosuppression for diarrhea or colitis did not affect the overall survival significantly (P = 0.232), nor did the choice of treatment (corticosteroids with vs. without infliximab; P = 0.768). Diarrhea was an independent predictor of a favorable overall survival (P < 0.001), irrespective of treatment need (P = 0.003). We confirmed the same results in a subgroup analysis for patients with stage IV malignancies only. Patients who received long duration of steroid treatment (> 30 days) had numerically higher infection rate than those who received steroid for shorter duration (40.4 vs. 25.8%, P = 0.160). Likewise, long duration of steroid without infliximab was associated with increased risk of infection compared to short duration of steroid with infliximab (42.9% vs. 14.3%, P = 0.089). CONCLUSIONS: Patients with ICPI-induced diarrhea or colitis have improved survival outcomes. Diarrhea is an independent predictor of an improved survival regardless of treatment requirement. Immunosuppressive treatment for diarrhea did not significantly affect overall survival, however, infection rates were numerically higher among patients who received steroids for a long duration. Therefore, early non-steroid immunosuppressive therapy may ensure a more favorable overall outcome.

Endoscopic and Histologic Features of Immune Checkpoint Inhibitor-Related Colitis.

Background: Diarrhea and colitis are the second most common immune checkpoint inhibitor (ICPI)-induced adverse events. However, a comprehensive characterization of the endoscopic and histologic features of ICPI-induced diarrhea and colitis is lacking. Therefore, we aimed to describe endoscopic and histologic features of ICPI-induced gastrointestinal toxicities and to assess their association with patients' clinical characteristics and outcomes. Methods: We retrospectively reviewed records of 53 patients with ICPI-related diarrhea/colitis between 2011 and 2017. We collected data on demographics, diarrhea/colitis grade, treatment, and endoscopic and histologic findings. Long-term follow-up included repeat endoscopy findings, diarrhea recurrence, and overall survival. We compared groups by treatment, endoscopic and histologic findings, and constructed Kaplan-Meier survival curves. Results: Most patients had grade 2 or higher diarrhea (87%) and colitis (60%). Thirty-one patients were successfully treated with corticosteroids, and 22 additionally required infliximab. On endoscopy, 21 (40%) patients had ulcerations and 22 (42%) had nonulcerative inflammation. Patients with ulcerations had more steroid-refractory disease (P = 0.044) and high-grade diarrhea (P = 0.033). Histology showed mostly acute (23%) or chronic (60%) inflammation. During mean follow-up duration of 18.9 months, 19 (36%) developed recurrent diarrhea. Most patients had persistent endoscopic (8/13, 62%) and histologic (9/11, 82%) inflammation. Patients with higher-grade adverse events had improved survival. Higher-grade colitis was associated with endoscopic inflammation (P = 0.039), but grade of diarrhea was not associated with endoscopic inflammation or grade of colitis. Conclusion: 10.1093/ibd/izy104_video1izy104.video15808053084001.

Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.

We report the first case series of immune checkpoint inhibitors (ICI)-associated colitis successfully treated with fecal microbiota transplantation, with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T-cells within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.