Cronkhite-Canada syndrome: treatment responses and improved overall survival.

BACKGROUND: Cronkhite-Canada syndrome (CCS) is considered a relentlessly progressive disease with high mortality rates. Although disease understanding and treatment options have greatly improved, the prognosis from these advancements has not been well documented. This study aimed to evaluate treatment outcomes and overall survival of CCS. METHODS: Seventeen patients who were diagnosed and treated over a 20-year period at Mayo Clinic (Rochester, Minnesota) were included. Data were abstracted, which included clinical and endoscopic manifestations, treatment course, and survival outcomes. RESULTS: The median (interquartile range) duration of follow-up was 8.3 (3.7-15.8) years. All patients received an initial prednisone dose equivalence of 30-80 mg daily, and five patients required steroids at the time of the last follow-up. Twelve patients trialed thiopurine therapy, and ten patients continued with a thiopurine until the last follow-up. Fifteen patients achieved clinical complete remission, and eleven patients achieved endoscopic complete remission after pharmacotherapy initiation. Seven patients required gastrointestinal surgeries during their disease course. The 5-year overall survival was 93.3% (95% confidence interval (CI): 81.5-100%), and the 3-year relapse-free survival was 82.4% (95% CI: 66.1-100%). CONCLUSION: The prognosis and overall survival of patients with CCS have markedly improved with advancement in disease understanding and therapies. Pharmacotherapy, including corticosteroids and immunomodulators, is effective in inducing and maintaining remission, and gastrointestinal surgery is commonly needed as an adjunct for managing CCS disease complications.

SMAD4 mutation and the combined juvenile polyposis and hereditary hemorrhage telangiectasia syndrome: a single center experience.

PURPOSE: Mutations of the SMAD4 gene can result in a distinct syndrome with combined clinical features of both juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT). Even though it is known that patients with the overlap syndrome are at increased risk for colorectal malignancies and bleeding, the outcomes of this patient population have not been extensively studied. METHODS: Retrospective study aiming to describe the phenotype and clinical outcomes of patients with genetically confirmed JP-HHT combined syndrome in a single large tertiary center in North America. RESULTS: A total of 22 patients were identified, the majority females (59%) with a median age diagnosis at 24 years. Polyps were more commonly seen in the lower gastrointestinal (GI) tract, and tubular adenomas were seen in 50%. Epistaxis and pulmonary arteriovenous malformations (AVM) were the most common manifestations of HHT, with a median Curacao score of 3 [1-4]. Hospitalization for gastrointestinal bleeding and cerebrovascular events occurred at a rate of 28% and 4%, respectively. Two patients had GI malignancies, one rectal and one small bowel adenocarcinoma. Overall mortality was 14%. CONCLUSIONS: Patients with the combined JP-HHT syndrome remain at risk for life-threatening vascular complications and gastrointestinal malignancies; close follow-up is necessary to minimize morbidity and mortality in this patient population.

Colonic Manifestations and Complications Are Relatively Under-Reported in Systemic Sclerosis: A Systematic Review.

OBJECTIVES: Although systemic sclerosis (SSc) is known to affect the gastrointestinal (GI) tract, most of the literature focuses on esophageal, small intestinal, or anorectal manifestations. There have been no reviews focused on large bowel SSc complications in over 30 years. The aim of this study is to perform a systematic review of colonic manifestations and complications of SSc. METHODS: An experienced librarian conducted a search of databases, including English and Spanish articles. The search used keywords including "systemic sclerosis," "scleroderma," and "colon." A systematic review was performed using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Case reports/series were screened for validity by adapting from criteria published elsewhere. RESULTS: Of 1,890 articles, 74 met selection criteria. Fifty-nine of the 77 articles were case reports/series. The most common article topics on colonic SSc complications were constipation/dysmotility (15), colonic volvulus (8), inflammatory bowel disease (7), microscopic colitis (6), megacolon (6), and telangiectasia (6). Colonic manifestations constituted 24% of articles on GI complications of SSc. There were a total of 85 cases (84% women, with a median age of onset of colon complication of 52 years). Limited cutaneous SSc phenotype (65.6%) was more common than diffuse (26.2%). Patients frequently had poor outcomes with high mortality related to colonic complications (27%). Recent studies explore contemporary topics such as the microbiome in SSc and prucalopride for chronic constipation in SSc. DISCUSSION: Colonic complications comprise a large proportion of the published reports on GI symptoms afflicting patients with SSc and require raised diagnostic suspicion and deliberate action to avoid potentially serious complications including death.

Role of Diagnostic Preoperative Upper Gastrointestinal Endoscopy in Radiologically Confirmed Gastric Volvulus.

BACKGROUND AND AIMS: Gastric volvulus (GV) is a life-threatening condition that warrants prompt diagnosis and treatment. GV is a radiologic diagnosis. The role of preoperative upper gastrointestinal endoscopy (UGIE) for individuals with radiologically confirmed GV is poorly defined. Our objective was to assess the diagnostic yield of UGIE in the preoperative evaluation of patients presenting with radiologically confirmed GV. METHODS: Retrospective review of all adult patients undergoing surgery for GV between July 1996 and August 2016 has been carried out. We performed analyses evaluating diagnostic yield of preoperative UGIE and compared outcomes in patients who did and did not undergo preoperative UGIE. Outcomes were diagnostic yield of preoperative UGIE, length of hospital stay, postoperative complications, and mortality at 30 days and 1 year. RESULTS: In the preoperative UGIE group, the diagnostic yield was 34.6% (27/78). The most common endoscopic findings were erosive esophagitis (13/27) and clean based gastric or duodenal ulcers (5/27). There were no cases of esophago-gastric malignancy. Three patients had ulcers with stigmata of recent bleeding, and three patients had features suggestive of gastric ischemia. Endoscopic findings did not influence surgical management. There was no statistically significant difference in mortality between patients who did and did not undergo preoperative UGIE, both at 30 days (0 vs. 2.5%) and 1 year (3.8 vs. 7.5%). CONCLUSION: Among patients with radiologically confirmed GV, preoperative UGIE rarely demonstrates clinically significant findings and can potentially delay definitive surgical intervention.

Multitarget stool DNA test: clinical performance and impact on yield and quality of colonoscopy for colorectal cancer screening.

BACKGROUND AND AIMS: Multitarget stool DNA (MT-sDNA) testing is now approved by the U.S. Food and Drug Administration for average-risk colorectal cancer screening. Trials leading to its approval used blinded colonoscopy as the reference standard. In the postapproval screen setting, the clinical performance and impact of MT-sDNA testing on unblinded colonoscopy has not been described. We measured the impact that knowledge of a positive MT-sDNA test result has on colonoscopy yield and quality. METHODS: The unblinded group comprised all patients with positive MT-sDNA results on screening from September 1, 2014 to September 30, 2015 at a single tertiary center. Off-label test patients were excluded. The blinded group included all MT-sDNA-positive participants in a preapproval screening study from the same center. Detailed colonoscopy findings and withdrawal times were recorded. RESULTS: There were 172 MT-sDNA-positive patients in the unblinded group and 72 in the blinded group. More total adenomatous/sessile serrated polyps (70% vs 53%, P = .013) and advanced neoplasms (28% vs 21%, P = .27) were detected in unblinded than in blinded groups. Median numbers of polyps detected were 2 (IQR, 1-4) and 1 (IQR, 0-2) in unblinded and blinded groups, respectively (P = .0007). Among polyps detected, flat or slightly raised lesions in the right side of the colon were proportionately more frequent with unblinded (40%) than with blinded examinations (9%) (P = .0017). Median withdrawal time was 19 minutes (IQR, 13-29) in the unblinded group compared with 13 minutes (IQR, 10-20) in the blinded group (P = .0001). CONCLUSIONS: Knowledge of a positive MT-sDNA result appears to have a beneficial impact on the diagnostic yield and quality of subsequent colonoscopy.

Sessile Serrated Polyps are Precursors of Colon Carcinomas With Deficient DNA Mismatch Repair.

We investigated whether sessile serrated adenomas/polyps (SSA/Ps) are direct precursors of colorectal carcinomas. We identified colon carcinomas that arose from SSA/Ps among 2646 colorectal cancers included in the surgical pathology database at the Mayo Clinic (2006-2012). Molecular features of the serrated neoplasia pathway were analyzed in these tumors by immunohistochemical analyses of mutant BRAF (V600E) and MLH1 proteins. Among the 33 identified SSA/P-associated colonic adenocarcinomas (median patient age, 75 y), 24 developed in women (73%), 31 were located in the proximal colon (94%), and 23 (69%) were TNM stage I or II. Thirty-one of the tumors (94%) expressed mutant BRAF; of these, 26 also had loss of MLH1 (79%), indicating deficient DNA mismatch repair of sporadic origin. Twenty-two of the tumors (67%) were interval cancers that were more common in women and did not differ significantly in TNM stage, BRAF mutation, or loss of MLH1. By histopathology, SSA/Ps that were associated with colon carcinomas contained frequent dysplasia (48%). Most cancers that arose from SSA/Ps were located on the right side of the colon and had mutant BRAF and loss of MLH1. These findings indicate that SSA/Ps are precursors of most sporadic colon carcinomas with deficient DNA mismatch repair.

Endoscopic overestimation of colorectal polyp size.

BACKGROUND AND AIMS: Polyp size ≥ 1 cm triggers more frequent colonoscopic surveillance, yet size is typically based on subjective endoscopic estimates. We sought to compare contemporary assessments of polyp size by endoscopic estimation and pathology measurement. METHODS: Colonoscopy and pathology reports were reviewed from the 2012 medical records at a large institution. Only polyps resected in toto with both endoscopic estimates and pathology measurements were included. Pathology measurements were considered the criterion standard. Factors affecting endoscopic miscall rates were assessed by multivariate analyses. RESULTS: From 6067 polyps resected, both endoscopic and pathology sizes were available on 1528. Distribution of polyp size appraised by endoscopy but not by pathology revealed modal clustering, particularly around 1 cm. Among 99 polyps endoscopically called 1 cm, 72% were <1 cm on pathology. Of all 222 polyps estimated as ≥ 1 cm on endoscopy, 46% were <1 cm on pathology; of 1306 polyps estimated as <1 cm, 3.9% were ≥ 1 cm on pathology. By histology, 39% of adenomatous, 59% of sessile serrated, and 73% of hyperplastic polyps were overcalled; P = .008. By configuration, 34% of pedunculated, 49% of sessile, and 61% of flat polyps were overcalled; P = .014. Endoscopic overestimation was more common in women (54%) than in men (40%) (P = .03) and with proximal (56%) than distal (40%) sites; P = .02. Miscall rates were unaffected by endoscopist covariates. CONCLUSIONS: Substantial discordance exists between endoscopic and pathology-based assessments of polyp size. Almost half of polyps called advanced on endoscopic estimates of size ≥ 1 cm fell below this threshold on actual pathology measurements.

Multi-Target Stool DNA Test: Is the Future Here?

Colorectal cancer (CRC) screening reduces CRC incidence and mortality and is widely recommended. However, despite these demonstrated benefits, a large percentage of the population remains unscreened. The multi-target stool DNA (MT-sDNA) test is a new, non-invasive option for CRC screening that has a high accuracy rate in detection of colorectal neoplasia and offers great opportunity to enhance screening uptake. This review provides the current state of the art knowledge about the use of MT-sDNA in CRC screening.

A population-based study of incidence, risk factors, clinical spectrum, and outcomes of ischemic colitis.

BACKGROUND & AIMS: Little is known about progression of ischemic colitis (IC) among unselected patients. We aimed to estimate the incidence, risk factors, and natural history of IC in a population-based cohort in Olmsted County, Minnesota. METHODS: We performed a retrospective population-based cohort and nested case-control study of IC. Each IC case was matched to 2 controls from the same population on the basis of sex, age, and closest registration number. Conditional logistic regression, the Kaplan-Meier method, and proportional hazards regression were used to assess comorbidities, estimate survival, and identify characteristics associated with survival, respectively. RESULTS: Four hundred forty-five county residents (median age, 71.6 years; 67% female) were diagnosed with IC from 1976 through 2009 and were matched with 890 controls. The age-adjusted and sex-adjusted incidence rates of IC nearly quadrupled from 6.1 cases/100,000 person-years in 1976-1980 to 22.9/100,000 in 2005-2009. The odds for IC were significantly higher among subjects with atherosclerotic diseases; odds ratios ranged from 2.6 for individuals with coronary disease to 7.9 for individuals with peripheral vascular disease. Of IC cases, 59% survived for 5 years (95% confidence interval, 54%-64%), compared with 90% of controls (95% confidence interval, 88%-92%). Age >40 years, male sex, right-sided colon involvement, concomitant small bowel involvement, and chronic obstructive pulmonary disease were all independently associated with mortality (P < .05). CONCLUSIONS: The incidence of IC increased during the past 3 decades in a population-based cohort in Minnesota. IC typically presents in older patients with multiple comorbidities and is associated with high in-hospital mortality (11.5%) and rates of surgery (17%).

Esophagitis Dissecans Superficialis: Clinical, Endoscopic, and Histologic Features.

BACKGROUND: Esophagitis dissecans superficialis (EDS) is a desquamative disorder of the esophagus, but there is a paucity of the literature regarding this condition. AIM: We examined our institution's experience to further characterize clinical outcomes, and endoscopic and histopathologic features. METHODS: Endoscopy and pathology databases were retrospectively reviewed from 2000 to 2013 at Mayo Clinic Rochester to identify potential cases of EDS. Medical records and endoscopic images were reviewed to identify cases, and original pathologic specimens were also reviewed. Clinical, endoscopic, and histologic characteristics of EDS were defined. RESULTS: Forty-one subjects were identified with a median age at diagnosis of 65.0 years (IQR 52.8-76.1) and a female preponderance (63.4 %). Many patients were taking a psychoactive agent (73.1 %) or acid-suppressive therapy (58.5 %) preceding the index endoscopy. Strips of sloughed membranes had a predilection for the distal and/or middle esophagus and resolved in 85.7 % of subjects at endoscopic follow-up. Parakeratosis and intraepithelial splitting were histologic features seen in all patients, while splitting of the connective tissue and intraepithelial bullae were seen in 46.2 and 11.1 %, respectively. There were no disease-related complications at a median follow-up of 10.4 months (IQR 1.2-17.2). CONCLUSIONS: EDS is likely under-recognized. A distinct endoscopic feature of EDS is "sloughing" strips of mucosa with parakeratosis and intraepithelial splitting being sine qua non histologic findings. The use of psychoactive agents (particularly a SSRI or SNRI) was prevalent at endoscopic diagnosis, although the clinical relevance of this is uncertain. EDS appears to be a benign, incidental finding without complications.