Peter P. Stanich

Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer.

Importance Hereditary cancer syndromes infer high cancer risks and require intensive cancer surveillance, yet the prevalence and spectrum of these conditions among unselected patients with early-onset colorectal cancer (CRC) is largely undetermined. Objective To determine the frequency and spectrum of cancer susceptibility gene mutations among patients with early-onset CRC. Design, Setting, and Participants Overall, 450 patients diagnosed with colorectal cancer younger than 50 years were prospectively accrued from 51 hospitals into the Ohio Colorectal Cancer Prevention Initiative from January 1, 2013, to June 20, 2016. Mismatch repair (MMR) deficiency was determined by microsatellite instability and/or immunohistochemistry. Germline DNA was tested for mutations in 25 cancer susceptibility genes using next-generation sequencing. Main Outcomes and Measures Mutation prevalence and spectrum in patients with early-onset CRC was determined. Clinical characteristics were assessed by mutation status. Results In total 450 patients younger than 50 years were included in the study, and 75 gene mutations were found in 72 patients (16%). Forty-eight patients (10.7%) had MMR-deficient tumors, and 40 patients (83.3%) had at least 1 gene mutation: 37 had Lynch syndrome (13, MLH1 [including one with constitutional MLH1 methylation]; 16, MSH2; 1, MSH2/monoallelic MUTYH; 2, MSH6; 5, PMS2); 1 patient had the APC c.3920T>A, p.I1307K mutation and a PMS2 variant; 9 patients (18.8%) had double somatic MMR mutations (including 2 with germline biallelic MUTYH mutations); and 1 patient had somatic MLH1 methylation. Four hundred two patients (89.3%) had MMR-proficient tumors, and 32 patients (8%) had at least 1 gene mutation: 9 had mutations in high-penetrance CRC genes (5, APC; 1, APC/PMS2; 2, biallelic MUTYH; 1, SMAD4); 13 patients had mutations in high- or moderate-penetrance genes not traditionally associated with CRC (3, ATM; 1, ATM/CHEK2; 2, BRCA1; 4, BRCA2; 1, CDKN2A; 2, PALB2); 10 patients had mutations in low-penetrance CRC genes (3, APC c.3920T>A, p.I1307K; 7, monoallelic MUTYH). Importantly, 24 of 72 patients (33.3%) who were mutation positive did not meet established genetic testing criteria for the gene(s) in which they had a mutation. Conclusions and Relevance Of 450 patients with early-onset CRC, 72 (16%) had gene mutations. Given the high frequency and wide spectrum of mutations, genetic counseling and testing with a multigene panel could be considered for all patients with early-onset CRC.

Morbid Obesity Is Associated With Adverse Clinical Outcomes in Acute Pancreatitis: A Propensity-Matched Study.

OBJECTIVES:Morbid obesity may adversely affect the clinical course of acute pancreatitis (AP); however, there are no inpatient, population-based studies assessing the impact of morbid obesity on AP-related outcomes. We sought to evaluate the impact of morbid obesity on AP-related clinical outcomes and health-care utilization.METHODS:The Nationwide Inpatient Sample (2007–2011) was reviewed to identify all adult inpatients (≥18 years) with a principal diagnosis of AP. The primary clinical outcomes (mortality, renal failure, and respiratory failure) and secondary resource outcomes (length of stay and hospital charges) were analyzed using univariate and multivariate comparisons. Propensity score-matched analysis was performed to compare the outcomes in patients with and without morbid obesity.RESULTS:Morbid obesity was associated with 3.9% (52,297/1,330,302) of all AP admissions. Whereas the mortality rate decreased overall (0.97%0.83%, P<0.001), it remained unchanged in those with morbid obesity (1.02%1.07%, P=1.0). Multivariate analysis revealed that morbid obesity was associated with increased mortality (odds ratio (OR) 1.6; 95% confidence interval (CI) 1.3, 1.9), prolonged hospitalization (0.4 days; P<0.001), and higher hospitalization charges (

Colesevelam and colestipol: novel medication resins in the gastrointestinal tract.

5,067; P<0.001). A propensity score-matched cohort analysis demonstrated that the primary outcomes, acute kidney failure (10.8 vs. 8.2%; P<0.001), respiratory failure (7.9 vs. 6.4%; P<0.001), and mortality (OR 1.6, 95% CI 1.2, 2.1) were more frequent in morbid obesity.CONCLUSIONS:Morbid obesity negatively influences inpatient hospitalization and is associated with adverse clinical outcomes, including mortality, organ failure, and health-care resource utilization. These observations and the increasing global prevalence of obesity justify ongoing efforts to understand the role of obesity-induced inflammation in the pathogenesis and management of AP.

Colonic manifestations of PTEN hamartoma tumor syndrome: Case series and systematic review

We report the morphologic description of the bile acid sequestrants (BAS) colesevelam and colestipol, as well as the largest series of cholestyramine. Histologically similar medication resins from 4 institutions were prospectively collected over 1 year (26 specimens, 15 patients). Comorbidities included hyperlipidemia (4/15), hypertension (4/15), inflammatory bowel disease (4/15), coronary artery disease (3/15), diarrhea (7/15), hypothyroidism (2/15), and ischemic bowel (1/15). Sites of involvement included the esophagus (1/26), stomach (1/26), small intestine (1/26), ileocecal valve (1/26), and colorectum (22/26). Associated histologic diagnoses included normal (8/26), chronic mucosal injury (11/26), acute inflammation (9/26), erosion/ulceration (6/26), and cytomegalovirus (2/26). The BAS resins were histologically indistinguishable from each other; they were all eosinophilic on hematoxylin and eosin (H&E) and lacked internal “fish-scales.” To validate these observations, respective medications were submitted for histologic processing; the processed medications were identical to those in the patient specimens. Rare, irregular “fracture” lines presented diagnostic pitfalls by mimicking the true “fish-scales” of Kayexalate and sevelamer. Clues to the correct identification of BAS include recognition that the “fracture” lines were subtle, irregular, and restricted to large fragments or thick sections, likely representing a processing artifact. Moreover, Kayexalate is violet on H&E and black on acid fast bacillus, and sevelamer characteristically displays a 2-tone color on H&E and is magenta on acid fast bacillus. An association with inflammatory injury was seen (15/26). We believe that the BAS are innocent bystanders in complicated patients, although we cannot exclude their ability to cause mucosal injury in specific settings.

Video capsule endoscopy is successful and effective in outpatients with implantable cardiac devices

AIM To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten (PTEN) hamartoma tumor syndrome (PHTS) and to perform a systematic literature review regarding the same. METHODS This study was approved by the appropriate institutional review board prior to initiation. A clinical genetics database was searched for patients with PHTS or a component syndrome that received gastrointestinal endoscopy or pathology interpretation at our center. These patients records were retrospectively reviewed for clinical characteristics (including family history and genetic testing), endoscopy results and pathology findings. We also performed a systematic review of the literature for case series of PHTS or component syndromes that reported gastrointestinal manifestations and investigations published after consensus diagnostic criteria were established in 1996. These results were compiled and reported. RESULTS Eight patients from our institution met initial inclusion criteria. Of these, 5 patients underwent 4.2 colonoscopies at mean age 45.8 ± 10.8 years. All were found to have colon polyps during their clinical course and polyp histology included adenoma, hyperplastic, ganglioneuroma and juvenile. No malignant lesions were identified. Two had multiple histologic types. One patient underwent colectomy due to innumerable polyps and concern for future malignant potential. Systematic literature review of PHTS patients undergoing endoscopy revealed 107 patients receiving colonoscopy at mean age 37.4 years. Colon polyps were noted in 92.5% and multiple colon polyp histologies were reported in 53.6%. Common polyp histologies included hyperplastic (43.6%), adenoma (40.4%), hamartoma (38.3%), ganglioneuroma (33%) and inflammatory (24.5%) polyps. Twelve (11.2%) patients had colorectal cancer at mean age 46.7 years (range 35-62). Clinical outcomes secondary to colon polyposis and malignancy were not commonly reported. CONCLUSION PHTS has a high prevalence of colon polyposis with multiple histologic types. It should be considered a mixed polyposis syndrome. Systematic review found an increased prevalence of colorectal cancer and we recommend initiating colonoscopy for colorectal cancer surveillance at age 35 years.

Video capsule endoscopy after bariatric and gastric surgery: oral ingestion is associated with satisfactory completion rate.

Implantable cardiac devices are a relative contraindication to video capsule endoscopy (VCE) because of concerns regarding interference. As a result of a lack of alternatives, some centers have adopted protocols to allow for VCE in these patients. There are minimal published descriptions of the gastrointestinal outcomes of these procedures. We investigated the completion rate and diagnostic yield of VCE carried out in outpatients with implantable cardiac devices.

Video capsule endoscopy completion and total transit times are similar with oral or endoscopic delivery

Goals: To investigate the outcomes of video capsule endoscopy (VCE) performed on patients after bariatric and gastric surgery with a focus on delivery method (oral ingestion or endoscopic placement). Background: There is minimal published data regarding the use of VCE in patients after bariatric and gastric surgery and the optimal delivery method is unknown. Methods: Retrospective case series of patients with bariatric or gastric surgery undergoing VCE in a tertiary care center over 3 years. Outcomes of interest were completion of the procedure and bowel transit times. Results: Twenty-three patients met study criteria. They underwent 24 VCE in the study period, with 13/16 (81.3%; 95% CI, 54%-96%) completed to the colon after oral ingestion and 5/8 (62.5%; 95% CI, 24%-91%) completed after endoscopic deployment. The median gastric transit time after oral ingestion was <1 minute (IQR, <1 to 99). Median total transit time after oral ingestion was 291 minutes (IQR, 213 to 434) and after endoscopic deployment was 364 minutes (IQR, 233 to >440) (P=0.48). There were no instances of capsule retention. Conclusions: Oral ingestion of VCE resulted in a satisfactory completion rate with rapid gastric transit after bariatric and gastric surgery. There were no capsule retention events. Given this and the favorable risk and cost profile, oral ingestion should be favored over endoscopic placement in this patient population.

Insights into insulin resistance, lifestyle, and anthropometric measures of patients with prior colorectal cancer compared to controls: A National Health and Nutrition Examination Survey (NHANES) Study

Background and study aims: Video capsule endoscopy (VCE) is limited by incomplete procedures. There are also contraindications to the standard ingestion of the capsule that require endoscopic placement. Our aim was to compare the study completion rate of VCE after oral ingestion and endoscopic deployment. Patients and methods: We performed a review of all VCE from April 2010 through March 2013. Inpatient and outpatient cohorts grouped by the method of capsule delivery were formed and compared. Multivariable logistic regression modeling was utilized adjusting for variables with a P value ≤ 0.1 in group comparisons. Log-rank analysis was used to compare transit times. Results: A total of 687 VCE were performed, including 316 inpatient (36 endoscopic deployment, 280 oral ingestion) and 371 outpatient (20 endoscopic deployment, 351 oral ingestion). For VCE on hospitalized patients, the completion rates were similar after endoscopic deployment and oral ingestion (72 % vs 73 %, P = 0.94). The completion rates were also similar for ambulatory patients (90 % vs 87 %, P = 0.69). There remained no difference after multivariable modeling for inpatients (P = 0.71) and outpatients (P = 0.46). Total transit times were not significantly different. Conclusions: VCE completion rates and total transit times are similar after oral or endoscopic deployment for both hospitalized and ambulatory patients. Endoscopic placement is effective in patients with contraindications to standard oral ingestion, but should otherwise be avoided to limit unnecessary procedural risks and costs.

Crospovidone and Microcrystalline Cellulose: A Novel Description of Pharmaceutical Fillers in the Gastrointestinal Tract.

BACKGROUND Insulin resistance (IR) increases the risk of index colorectal cancer (CRC) development. Limited data exist on IR values, lifestyle, and anthropometric alterations of patients after CRC diagnosis, a population at high risk for CRC recurrence. METHODS This is a retrospective cohort study using the National Health and Nutrition Examination Survey (NHANES), 1999-2010. We identified patients with and without prior CRC above age 50. Our outcomes were lifestyle, anthropometric measures, and IR measured using the triglyceride to high-density lipoprotein ratio and the homeostasis model assessment IR. RESULTS There were 146,841 patients with prior CRC and 26,979,507 without prior cancer (controls) in our cohort. Prior patients with CRC were significantly older than controls (75.8 vs 62.3, P < 0.01), however, there were no significant differences in gender, ethnicity, income, caloric intake, tobacco use or alcohol consumption between both groups. Multivariate analysis revealed no difference between prior patients with CRC and controls in triglyceride to high-density lipoprotein ratio (adjusted percentage change = -2.17; 95% CI: -27.96 to 18.43) or homeostasis model assessment IR (adjusted percentage change = -6.85; 95% CI: -35.74 to 15.90). Despite similar weight at age 25, prior CRC subjects had lower weights compared to controls (at time of NHANES survey, one and 10 years before survey and greatest weight). Furthermore prior CRC subjects gained less weight in the 10 years before survey. CONCLUSION Patients with prior CRC above age 50 have no conclusive evidence of increased IR compared to non-CRC controls. This is possibly due to lesser weight gain in the peri-CRC diagnosis or treatment period. Future efforts should focus on alternate etiologies for the increased CRC recurrence in this high-risk group.

Lymphocytic Gastritis Identified by Abnormal PET Scan

Crospovidone and microcrystalline cellulose (MCC) are pharmaceutical fillers well known in the pulmonary pathology literature. Fillers are inactive substances incorporated into medications to facilitate drug delivery. By examining 545 consecutive gastrointestinal surgical specimens from 302 patients between September 11, 2015 and October 23, 2015, we identified the fillers in 29 specimens from 26 patients. The control group consisted of an equal number of consecutive site-matched specimens collected during this same time. Pertinent clinicopathologic data were analyzed, and 1 case was subject to special stains. To confirm the histologic diagnosis, a variety of fillers and medications common to the patients were processed. The fillers were found in 9% of all patients, and there were no specific clinicopathologic associations. In the gastrointestinal tract, crospovidone is nonbirefringent and has a coral shape with each segment composed of a pink core and purple coat; MCC is brightly birefringent with matchstick shape and clear color. Identical material was seen in the processed crospovidone and MCC powders, as well as oxycodone-acetaminophen and omeprazole tablets. In summary, crospovidone and MCC are common, biologically inert, and they are most often seen in the small bowel. Their presence outside of the luminal bowel may serve as a surrogate marker for perforation. Awareness of their morphology is important to distinguish fillers from parasites, calcifications, and other medications, particularly those linked to mucosal injury. We report the unique histomorphologic profile of these fillers as a helpful diagnostic aide, and caution that the fillers have slightly divergent features when compared with those described in the lung.