Incidence and prevalence of advanced colorectal neoplasia in Lynch syndrome.

BACKGROUND AND AIMS: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Although colonoscopy reduces CRC in LS, the protection is variable. We assessed the prevalence and incidence of neoplasia in LS during surveillance colonoscopy in the United States and factors associated with advanced neoplasia. METHODS: Patients with LS undergoing ≥1 surveillance colonoscopy and with no personal history of invasive CRC or colorectal surgery were included. Prevalent and incident neoplasia was defined as occurring <6 months before and ≥6 months after germline diagnosis of LS, respectively. We assessed advanced adenoma (AA), CRC, and the impact of mismatch repair pathogenic variant (PV) and typical LS cancer history (personal history of EC and/or family history of EC/CRC) on outcome. RESULTS: A total of 132 patients (inclusive of 112 undergoing prevalent and incident surveillance) were included. The median examination interval and duration of prevalent and incident surveillance was .88 and 1.06 years and 3.1 and 4.6 years, respectively. Prevalent and incident AA were detected in 10.7% and 6.1% and invasive CRC in 0% and 2.3% of patients. All incident CRC occurred in MSH2 and MLH1 PV carriers and only 1 (.7%) while under surveillance in our center. AAs were detected in both LS cancer history cohorts and represented in all PVs. CONCLUSIONS: In a U.S. cohort of LS, advanced neoplasia rarely occurred over annual surveillance. CRC was diagnosed only in MSH2/MLH1 PV carriers. AAs occurred regardless of PV or LS cancer history. Prospective studies are warranted to confirm our findings.

Characteristics of Immune Checkpoint Inhibitor-Associated Gastritis: Report from a Major Tertiary Care Center.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have increased our ability to treat an ever-expanding number of cancers. We describe a case series of 25 patients who were diagnosed with gastritis following ICI therapy. MATERIALS AND METHODS: This was a retrospective study involving 1712 patients treated for malignancy with immunotherapy at Cleveland Clinic from January 2011 to June 2019 (IRB 18-1225). We searched electronic medical records using ICD-10 codes for gastritis diagnosis confirmed on endoscopy and histology within 3 months of ICI therapy. Patients with upper gastrointestinal tract malignancy or documented Helicobacter pylori-associated gastritis were excluded. RESULTS: Twenty-five patients were found to meet the criteria for diagnosis of gastritis. Of these 25 patients, most common malignancies were non-small cell lung cancer (52%) and melanoma (24%). Median number of infusions preceding symptoms was 4 (1-30) and time to symptom onset 2 (0.5-12) weeks after last infusion. Symptoms experienced were nausea (80%), vomiting (52%), abdominal pain (72%), and melena (44%). Common endoscopic findings were erythema (88%), edema (52%), and friability (48%). The most common diagnosis of pathology was chronic active gastritis in 24% of patients. Ninety-six percent received acid suppression treatment and 36% of patients also received steroids with an initial median dose of prednisone 75 (20-80) mg. Within 2 months, 64% had documented complete resolution of symptoms and 52% were able to resume immunotherapy. CONCLUSION: Patients presenting with nausea, vomiting, abdominal pain, or melena following immunotherapy should be assessed for gastritis and if other causes are excluded, may require treatment as consideration for complication of immunotherapy.

Appendiceal Fecalith Presenting as a Submucosal Cecal Polyp Removed During Colonoscopy.

Appendiceal fecaliths, also known as stercoliths or coproliths, are rigid masses comprised of fecal material that become lodged within the appendix. They are generally accepted to be a primary etiologic agent of acute appendicitis and appendiceal intussusception in adults. We report a case of an asymptomatic woman undergoing colonoscopy found to have a submucosal appearing mass below the appendiceal orifice. A neoplastic appearing lesion on the orifice of the appendix was resected, after which a fecalith extruded into the colonic lumen. This is the first reported case of appendiceal fecalith discovered and completely removed during colonoscopy in an asymptomatic patient.

Colorectal Cancer Risk and Recommendations for Colorectal Cancer Surveillance in Adult Survivors of Childhood Cancer.

While many organizations have published guidance on the approach to colorectal cancer (CRC) screening in average-risk and certain high-risk groups, adult survivors of childhood cancer (ASCC) who have a heightened risk of CRC are rarely included as a target group for enhanced CRC surveillance. The population of ASCC continues to grow due to increasingly effective cancer therapies and improved survival. With this increased survival comes an increased risk for subsequent malignant neoplasms, including CRC. Since there is little published guidance for CRC surveillance in ASCC and limited awareness of increased CRC risk among both physicians and patients, the objectives of our paper are to review the incidence of and risk factors for colorectal neoplasia in ASCC, describe the clinical phenotypes of colorectal neoplasia in ASCC, review published surveillance strategies based on consensus-based survivorship guidelines, and outline areas for future research to optimize surveillance strategies.

Prevalence and risk factors of barrett's esophagus in lynch syndrome.

Lynch syndrome (LS), the most common hereditary cause of colorectal cancer, predisposes to upper gastrointestinal neoplasia. The prevalence of Barrett's esophagus (BE) is elevated in some hereditary gastrointestinal cancer syndromes but has not been systematically evaluated in LS. We assessed the prevalence of BE, BE-related dysplasia, esophageal adenocarcinoma (EAC), and factors associated with BE in LS. Asymptomatic patients with a germline pathogenic variant (PV) in the DNA mismatch repair (MMR) genes undergoing EGD for LS surveillance were identified from a hereditary colorectal cancer registry. We assessed the prevalence of BE and compared demographic, clinical, and endoscopic factors in LS patients with and without BE by logistic regression analysis. 323 patients were included. 21 patients (6.5%) were diagnosed with BE including 38% of females and 33% without gastroesophageal reflux disease (GERD). Dysplasia was diagnosed in two patients (9.5%) and EAC in one (4.8%) patient. Factors associated with BE included male gender (OR 3.00, 1.21-7.46), age at last LS EGD (OR 1.04, 1.01-1.08), presence of hiatal hernia (OR 20.09, 4.57-88.23), hiatal hernia > 3 cm (OR 11.25, 2.41-51.94), and GERD (OR 3.39, 1.32-8.67). No MMR PV was associated with BE. BE was diagnosed in 1 of 15 patients undergoing EGD surveillance for LS and nearly 10% had dysplasia including one EAC. Risk factors associated with BE in LS are similar to those established for BE in the general population. More studies are needed to evaluate if an association between BE and LS exists.

The Approach to Performance of Quality Upper Endoscopy in Lynch Syndrome (QUELS): An International Expert Statement.

Strong evidence demonstrates the protective benefit of frequent colonoscopy surveillance for colorectal cancer prevention in Lynch Syndrome (LS) and is endorsed by many guidelines. Until recently, the evidence supporting the utility of upper endoscopy [esophagogastroduodenoscopy (EGD)] for upper gastrointestinal (UGI) cancer surveillance was limited. Over the last 3 years, multiple studies have demonstrated that EGD surveillance in LS is associated with the detection of both precancerous lesions and early-stage UGI cancers. On the basis of the emerging favorable evidence derived from EGD surveillance programs, the 2022 National Comprehensive Cancer Network (NCCN) Guidelines for LS recommend UGI surveillance with EGD starting between age 30 and 40 years with repeat EGDs every 2 to 4 years, preferably in conjunction with colonoscopy, in all patients with a germline pathogenic variant (PV) in MLH1, MSH2, EPCAM, and MSH6 and, because of the lack of data, consideration in PMS2. Standardization of the approach to performing EGD surveillance in LS and reporting clinically actionable findings is requisite for both improving quality and understanding the cost efficiency and outcomes of patients undergoing EGD as a surveillance tool. Accordingly, the primary objective of this Quality of Upper Endoscopy in Lynch Syndrome (QUELS) statement is to articulate a framework for standardizing the approach to performing and reporting EGD findings in patients with LS by introducing emerging quality metrics. The recommendations presented herein were developed from available evidence and consensus-based expert opinion and provide a practical approach for clinicians applying EGD surveillance in accordance with the most recent and existing LS guidelines.

Hepatic Epstein-Barr Virus-Associated Smooth Muscle Tumor in a Heart and Liver Transplant Recipient.

Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMT) have been described in immunosuppressed states, including in post-transplant patients. Here, we discuss a heart-liver transplant recipient who was found to have multifocal hepatic EBV-SMT. His immunosuppression was initially transitioned from tacrolimus to sirolimus because of the proposed benefits of the mechanistic target of rapamycin inhibitors on EBV-SMT. Unfortunately, he suffered acute rejection of his liver allograft while on sirolimus therapy, which ultimately led to consideration of retransplantation.

Risk of hernia-related complications after transjugular intrahepatic portosystemic shunt creation in patients with pre-existing ventral abdominal hernias: 15-year experience at a quaternary medical center.

OBJECTIVE: Transjugular intrahepatic portosystemic shunt (TIPS) placement is used to treat the sequelae of portal hypertension, including refractory variceal bleeding, ascites and hepatic hydrothorax. However, hernia-related complications such as incarceration and small bowel obstruction can occur after TIPS placement in patients with pre-existing hernias. The aim of this study was to determine the incidence of hernia complications in the first year after TIPS placement and to identify patient characteristics leading to an increased risk of these complications. DESIGN: This retrospective analysis included patients with pre-existing abdominal hernias who underwent primary TIPS placement with covered stents at our institution between 2004 and 2018. The 1-year hernia complication rate and the average time to complications were documented. Using a Wilcoxon rank-sum test, the characteristics of patients who developed hernia-related complications versus the characteristics of those without complications were compared. RESULTS: A total of 167 patients with pre-existing asymptomatic abdominal hernias were included in the analysis. The most common reason for TIPS placement was refractory ascites (80.6%). A total of 36 patients (21.6%) developed hernia-related complications after TIPS placement, including 20 patients with acute complications and 16 with non-acute complications. The mean time to presentation of hernia-related complications was 66 days. Patients who developed hernia-related complications were more likely than those without complications to have liver cirrhosis secondary to alcohol consumption (p=0.049), although this association was no longer significant after multivariate analysis. CONCLUSION: Within 1 year after TIPS placement, approximately 20% of patients with pre-existing hernias develop hernia-related complications, typically within the first 2 months after the procedure. Patients with pre-existing hernia undergoing TIPS placement should be educated regarding the signs and symptoms of hernia-related complications, including incarceration and small bowel obstruction.

Upper Gastrointestinal Cancer Surveillance in Lynch Syndrome.

Lynch syndrome is a common hereditary cancer predisposition syndrome associated with increased digestive cancer risk including colorectal, gastric, and duodenal cancers. While colorectal cancer surveillance is widely accepted to be an important part of a comprehensive Lynch syndrome risk management plan, the use of upper gastrointestinal cancer surveillance in Lynch syndrome remains more controversial. Currently, upper gastrointestinal cancer surveillance guidelines for Lynch syndrome vary widely, and there is no consensus on who should undergo upper gastrointestinal cancer surveillance, how surveillance should be performed, the age at which to initiate surveillance, or how often individuals with Lynch syndrome should undergo upper gastrointestinal cancer surveillance. Fortunately, research groups around the world have been focusing on upper gastrointestinal cancer surveillance in Lynch syndrome, and recent evidence in this field has demonstrated that upper gastrointestinal cancer surveillance can be performed with identification of precancerous lesions as well as early-stage upper gastrointestinal cancers. In this manuscript, we review the upper gastrointestinal cancer risks in Lynch syndrome, differing guideline recommendations for surveillance, outcomes of upper gastrointestinal cancer surveillance, and controversies in the field, and we provide a framework based on our collective experience with which to incorporate upper gastrointestinal cancer surveillance into a risk management program for individuals with Lynch syndrome.

Immune checkpoint inhibitor induced colitis: A nationwide population-based study.

BACKGROUND: ICIs are used in the management of several malignancies. However, they can result in immune-related adverse events, such as colitis. The aim of this study is to obtain an epidemiological survey of patients who develop immune checkpoint inhibitor (ICI)-induced colitis and identify underlying risk factors. METHODS: A cohort study was performed using Explorys, a US-based population database. Our cohort included all patients in a five-year interval on an ICI. We further identified those who developed colitis after initiating an ICI. Demographic data and possible risk factors were assessed. Odds ratios were calculated and multivariable statistical analysis was performed. RESULTS: 3.6% of patients developed ICI-induced colitis. Women [OR: 1.2; 95% CI 1.224-1.231, p <0.001], Caucasians [OR: 2.3; 2.284 - 2.299], individuals older than 65 years [OR: 1.3; 1.319 - 1.326], obese patients [OR: 3.3; 3.273 - 3.302], and those with a history of alcohol abuse [OR: 2.5; 2.485 - 2.523] were more likely to develop colitis. Patients who received Nivolumab [OR: 2.8; 2.563 - 3.022], Ipilimumab [OR: 4.9; 3.937 - 6.061], Pembrolizumab [OR 2.7; 2.463 - 2.868], and Atezolizumab [OR 2.9; 2.430 - 3.388] had an increased odds of developing colitis. The majority of cases were diagnosed in the first 6 months of therapy. CONCLUSIONS: This is the largest study to describe the epidemiology of ICI-induced colitis and it is the first to identify underlying risk factors. Ipilimumab poses the greatest risk for ICI-induced colitis. The risk of colitis should be discussed with all patients prior to initiating an ICI, as it may be a factor in choosing among ICIs.

Clinically actionable findings on surveillance EGD in asymptomatic patients with Lynch syndrome.

BACKGROUND AND AIMS: Lynch syndrome (LS) predisposes patients to multiple cancers including of the gastric and small bowel. Data supporting EGD surveillance in LS are limited. Our aim is to describe upper GI (UGI) findings in asymptomatic LS patients undergoing EGD surveillance within a hereditary colorectal cancer registry. METHODS: Asymptomatic patients with LS who underwent ≥1 surveillance EGD were included. Demographics, genotype, and EGD findings were reviewed. The frequency of clinically actionable findings including neoplasia (cancer, adenomas), Barrett's esophagus (BE), Helicobacter pylori, and hyperplastic polyps >5 mm were assessed. RESULTS: Three hundred twenty-three patients underwent 717 EGDs starting at a median age of 49.5 years. On average, each patient had 2 EGDs with an interval of 2.3 years between examinations. Clinically actionable findings were identified in 57 patients (17.6%). On baseline EGD 27.7% of findings were identified, with the remainder on surveillance EGD over an average of 3.5 years. Five asymptomatic patients (1.5%) had an UGI cancer detected during surveillance, all at early stage, including 1 patient each with BE-related esophageal adenocarcinoma, gastric neuroendocrine tumor, and gastric adenocarcinoma and 2 patients with duodenal adenocarcinoma. Two cancers were found on baseline EGD and 3 on follow-up EGD. CONCLUSIONS: Clinically actionable findings were found in approximately 1 in 6 asymptomatic patients with LS undergoing EGD surveillance. Five patients (1.5%) were diagnosed with cancer, all detected at an early stage. These data suggest that both baseline and follow-up EGD surveillance are effective in detecting early-stage UGI cancers in asymptomatic patients with LS.

Using Immunohistochemistry to Expand the Spectrum of Lynch Syndrome-Related Tumors.

The most common genetic and molecular process leading to sporadic colorectal cancer is chromosomal instability. By contrast, mismatch repair deficiency, which results in high levels of microsatellite instability or lack of mismatch repair (MMR) protein expression on immunohistochemistry (IHC), is the predominant cancer pathway in patients with Lynch syndrome (LS). Importantly, patients with LS may still develop sporadic tumors through chromosomal instability. Testing tumors with IHC staining helps expand the spectrum of LS-related tumors. In this series, we describe 4 cancers in patients with LS that are not typical of the syndrome. Lack of MMR protein expression on IHC staining confirmed that 2 cancers are related to LS, expanding the spectrum of LS-related tumors, and the presence of MMR protein expression on IHC in the other 2 cases confirmed that they were sporadic and not related to mismatch repair deficiency and, thus, not related to LS.

Outpatient Evaluation of Knee Pain.

Knee pain is present in up to 20% of the adult general population and can be significantly debilitating to patients. A thorough history and physical examination can help localize the source of inflammation or injury to further determine if imaging, physical therapy, specialty referral, or surgery is necessary. By following a systematic approach to evaluating knee pain, primary care physicians can make the correct diagnosis and formulate an appropriate therapeutic strategy for patients.