A case report of a prostate cancer metastasis in the pancreas exhibiting vascular encasement.

We report a patient who presented with a 4-month history of intermittent epigastric pain. Computed tomography (CT) angiography of the abdomen demonstrated a stenotic celiac trunk but also encasement of the common proper hepatic artery, gastroduodenal artery, and proper hepatic artery by an ill-defined hypoattenuating mass of the pancreatic head. Biopsy confirmed metastatic prostate cancer to the pancreas that occurred 4 years after radiation and androgen deprivation therapy. A follow-up staging study demonstrated an osseous metastasis at the T4 spinous process. This case demonstrates an unusual case of prostate metastasis to the pancreas with the involvement of a main abdominal vessel. With treatment improvements leading to longer survival rates from prostate cancer, radiologists should be aware of atypical metastases that may arise in the long term.

Microscopic/"Backwash" Ileitis and Its Association With Colonic Disease in New Onset Pediatric Ulcerative Colitis.

BACKGROUND: Microscopic ileitis and its association with pancolitis in adults with ulcerative colitis (UC) have been described. The incidence of ileitis and associations with colonic disease in pediatric UC have, however, not been thoroughly investigated. This study was undertaken to examine the prevalence of microscopic ileal inflammation at the time of initial diagnosis in a cohort of children with UC. METHODS: We reviewed colonoscopy and biopsy data at time of diagnosis from 105 children and young adults with treatment naïve UC; ileal and colonic mucosal biopsies were available on all patients. Ileal mucosal biopsies were examined for the presence and severity of ileal inflammation, and other histologic features. Concurrently obtained colonic mucosal biopsies were assessed to define the severity, distribution, and extent of disease; endoscopic and clinical follow-up data were reviewed. RESULTS: A total of 107 ileal mucosal biopsies and 693 corresponding colonic mucosal biopsies were examined. Seventeen of 105 patients (16%) were found to have ileal inflammation (mean age = 10.4 years, 59% girls), 14 (82%) of whom had histologic pancolitis. The presence of ileal inflammation was significantly associated with endoscopic pancolitis (P = 0.02). The association between histologic pancolitis, severity of active inflammation in the cecum, and ascending colon suggested a possible association with ileal inflammation (P = 0.06, 0.07, and 0.08 respectively), but did not reach statistical significance. CONCLUSION: Patients with new onset UC may have microscopic ileal inflammation at time of diagnosis, even if the terminal ileum appears macroscopically normal. The presence of endoscopic pancolitis is associated with the presence of histologic ileitis. In contrast to existing studies in adults, an association between the presence of ileitis and the histologic severity or the histologic extent of colitis was not observed. Children with microscopic ileitis in the context of UC do not need to be reclassified as "indeterminate colitis" or Crohn disease.

International Validation of the Eighth Edition of the American Joint Committee on Cancer (AJCC) TNM Staging System in Patients With Resected Pancreatic Cancer.

Importance: The recently released eighth edition of the American Joint Committee on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic accuracy but lacks international validation. Objective: To validate the eighth edition of the American Joint Committee on Cancer TNM staging system in an international cohort of patients with resected pancreatic ductal adenocarcinoma. Design, Setting, and Participants: This international multicenter cohort study took place in 5 tertiary centers in Europe and the United States from 2000 to 2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic ductal adenocarcinoma were eligible. Data analysis took place from December 2017 to April 2018. Exposures: Patients were retrospectively staged according to the seventh and eighth editions of the TNM staging system. Main Outcomes and Measures: Prognostic accuracy on survival rates, assessed by Kaplan-Meier and multivariate Cox proportional hazards analyses and concordance statistics. Results: A total of 1525 consecutive patients were included (median [IQR] age, 66 (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in 200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in 144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in 598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%) to a higher stage. Median overall survival for the entire cohort was 24.4 months (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in IIB, and 0% in stage III (log-rank P < .001) via classification with the seventh edition to 39.2% for patients in stage IA, 33.9% in IB, 27.6% in IIA, 21.0% in IIB, and 10.8% in stage III (log-rank P < .001) with the eighth edition. For patients who were node negative, the T stage was not associated with prognostication of survival in either edition. In the eighth edition, the N stage was associated with 5-year survival rates of 35.6% in N0, 20.8% in N1, and 10.9% in N2 (log-rank P < .001). The C statistic improved from 0.55 (95% CI, 0.53-0.57) for the seventh edition to 0.57 (95% CI, 0.55-0.60) for the eighth edition. Conclusions and Relevance: The eighth edition of the TNM staging system demonstrated a more equal distribution among stages and a modestly increased prognostic accuracy in patients with resected pancreatic ductal adenocarcinoma compared with the seventh edition. The revised T stage remains poorly associated with survival, whereas the revised N stage is highly prognostic.

Intraobserver and Interobserver Variability in the Assessment of Dysplasia in Ampullary Mucosal Biopsies.

Endoscopic mucosal biopsies of the ampulla of Vater (AmpBx) are obtained to histologically assess for dysplasia or carcinoma. However, biopsy material is often scant and a host of factors can induce histologic changes that pose diagnostic challenges. We sought to investigate observer variability in interpretation of AmpBx and the impact clinical data may have on diagnostic interpretation. Thirty-one cases from institutional archives were selected, including 12 cases of reactive atypia (RA), 8 indefinite for dysplasia (ID), and 11 showing low-grade dysplasia (LGD). Slides were independently reviewed at 3 time points with and without clinical information by 6 pathologists who categorized the biopsies RA, ID, or LGD. Following the reviews, intraobserver and interobserver agreement was assessed. Review of AmpBx without clinical data showed fair (κ, 0.27), poor (κ, 0.07), and good (κ, 0.42) interobserver agreement for diagnoses of RA, ID, and LGD, respectively. Interobserver agreement improved for LGD (κ, 0.66 and 0.73) when clinical information was provided; however, agreement remained fair for RA (κ, 0.4 and 0.42) and poor-to-fair for ID (κ, 0.17 and 0.25). When follow-up data were reviewed, all cases that reached unanimous agreement had that diagnosis substantiated by subsequent endoscopic or histologic findings. The same was true of 13 of 19 cases that reached majority consensus. Given the potential clinical consequences of these diagnoses combined with the significant intraobserver and interobserver variability found in this study, we conclude that better-defined diagnostic criteria and consensus reads on difficult cases would assist in the histologic assessment of these challenging cases.

Pathological Margin Clearance and Survival After Pancreaticoduodenectomy in a US and European Pancreatic Center.

BACKGROUND: The optimal definition of a margin-negative resection and its exact prognostic significance on survival in resected pancreatic adenocarcinoma remains unknown. This study was designed to assess the relationship between pathological margin clearance, margin type, and survival. METHODS: Patients who underwent pancreaticoduodenectomy with curative intent at two academic institutions, in Amsterdam, the Netherlands, and Boston, Massachusetts, between 2000 and 2014 were retrospectively evaluated. Overall survival, recurrence rates, and progression-free survival (PFS) were assessed by Kaplan-Meier estimates and multivariate Cox proportional hazards analysis, according to pathological margin clearance and type of margin involved. RESULTS: Of 531 patients identified, the median PFS was 12.9, 15.4, and 24.1 months, and the median overall survival was 17.4, 22.9, and 27.7 months for margin clearances of 0, < 1, and ≥1 mm, respectively (all log-rank p < 0.001). On multivariate analysis, patients with a margin clearance of ≥1 mm demonstrated a survival advantage relative to those with 0 mm clearance [hazard ratio (HR) 0.71, p < 0.01], whereas survival was comparable for patients with a margin clearance of < 1 mm versus 0 mm (HR: 0.93, p = 0.60). Patients with involvement (0 or < 1 mm margin clearance) of the SMV/PV margin demonstrated prolonged median overall survival (25.7 months) relative to those with SMA involvement (17.5 months). CONCLUSIONS: In patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, a margin clearance of ≥1 mm correlates with improved survival relative to < 1 mm clearance and may be a more accurate predictor of a complete margin-negative resection in pancreatic cancer. The type of margin involved also appears to impact survival.

Mucinous cystic neoplasms of the pancreas: high-resolution cross-sectional imaging features with clinico-pathologic correlation.

PURPOSE: To describe the high-resolution cross-sectional (MDCT/MRI) features of mucinous cystic neoplasms (MCN) of the pancreas with clinico-pathologic correlation; to identify imaging predictors of high-grade dysplasia/carcinoma; and to estimate MCN growth rate. MATERIALS AND METHODS: Thirty-two women (mean age: 46; range, 25-79 years) with resected MCN who underwent preoperative MDCT (n = 20) or MRI (n = 12) examinations over a 14-year period were included. Two radiologists examined retrospectively in consensus the following MDCT/MRI features: MCN location, size/volume, presence of capsule and thickness of the capsule, and presence of mural nodules, enhancing septations, calcifications, chronic pancreatitis, and main pancreatic duct dilation. Imaging features were correlated with clinical symptoms, biochemistry results, and histopathologic features. A univariate model was analyzed for the prediction of high-grade dysplasia/carcinoma. Preoperative MCN growth rate was assessed using a subset of patients with more than one imaging study available (n = 6). RESULTS: Twenty-five (78%) patients presented with symptoms and 8 (25%) patients had abnormal serum biochemical values. Mean MCN maximum dimensions were 48 × 45 × 45 mm with a mean volume of 169 mL. MCN were located in the tail (n = 18), body (n = 10), neck (n = 2), and (head = 2); 30 (93.5%) MCN were encapsulated, 3 (9%) had calcifications, 4 (12%) showed enhancing nodules, 9 (28%) had enhancing septations, and 5 (15%) had main pancreatic duct dilation. Associated chronic pancreatitis was observed in 4 (12%) patients. The only predictors for high-grade dysplasia/carcinoma were MCN size and volume. Using a cut-off size greater than 8.5 cm, the specificity and sensitivity for high-grade dysplasia/carcinoma were 97 and 60%, respectively (p = 0.003; OR 81, 95% CI 3.9-1655.8). Mean MCN growth rate was estimated at 4.2 mm/year with a doubling time of 8.23 years. CONCLUSION: MCN size (> 8.5 cm) and volume are the only features on MDCT/MR imaging that correlate with high-grade dysplasia/carcinoma. The average growth rate for MCNs is slow at approximately 4 mm per year.

Surgical Management of Gallbladder Cancer: Simple Versus Extended Cholecystectomy and the Role of Adjuvant Therapy.

OBJECTIVE: To assess if simple cholecystectomy with adjuvant therapy could provide outcomes comparable to extended cholecystectomy. BACKGROUND: Current guidelines recommend extended/radical cholecystectomy for T2/T3 gallbladder cancer; however, many tumors are discovered incidentally at laparoscopic cholecystectomy. METHODS: The national Cancer Data Base 2004 to 2014 was queried for patients with pT2/T3 gallbladder adenocarcinoma who underwent resection. Adjuvant therapy was defined as chemotherapy, with or without radiotherapy, within 90 days of surgery. Baseline characteristics and overall survival were compared by χ and Kaplan-Meier method, respectively. One-to-one propensity score matching for receipt of adjuvant therapy was used to account for potential selection bias. RESULTS: A total of 6825 patients were identified. Diagnosis was made predominantly (78.9%) at the time of surgery or on pathology; 31.8% (2168) received adjuvant therapy. The majority, 88.8% (6060), had a simple cholecystectomy. Patients who received adjuvant therapy versus surgery alone were more likely to: be younger, privately insured, have no comorbidities, pT3 disease, positive lymph nodes, positive resection margins, and extended cholecystectomy. After matching, median survival was significantly longer for extended cholecystectomy with adjuvant therapy (23.3 months) than cholecystectomy with adjuvant therapy (16.4 months), which was significantly longer than either simple (12.4 months) or extended (10.7 months) cholecystectomy alone (all log-rank P<0.001). CONCLUSIONS: Adjuvant therapy prolongs survival after resection of T2/T3 tumors. Simple cholecystectomy with adjuvant therapy appears to be superior to extended resection alone in the short term and may serve as a potential alternative to re-resection in select high-risk individuals.

Serum I-FABP Detects Gluten Responsiveness in Adult Celiac Disease Patients on a Short-Term Gluten Challenge.

OBJECTIVES: Response to gluten challenge (GC) is a key feature in diagnostic algorithms and research trials in celiac disease (CD). Currently, autoantibody titers, late responders to GC, and invasive duodenal biopsies are used to evaluate gluten responsiveness. This study investigated the accuracy of serum intestinal-fatty acid binding protein (I-FABP), a marker for intestinal epithelial damage, to predict intestinal damage during GC in patients with CD. METHODS: Twenty adult CD patients in remission underwent a two-week GC with 3 or 7.5 g of gluten daily. Study visits occurred at day -14, 0, 3, 7, 14, and 28. Serum I-FABP, antibodies to tissue transglutaminase (tTG-IgA), deamidated gliadin peptides (IgA-DGP), and anti-actin (AAA-IgA) were assessed at each visit. Villous-height to crypt-depth ratio (Vh:Cd) and intraepithelial lymphocyte (IEL) count were evaluated at day -14, 3, and 14. Forty-three CD-serology negative individuals were included to compare serum I-FABP levels in CD patients on a gluten-free diet (GFD) with those in healthy subjects. RESULTS: Serum I-FABP levels increased significantly during a two-week GC. In contrast, the most pronounced autoantibody increase was found at day 28, when patients had already returned to a GFD for two weeks. IgA-AAA titers were only significantly elevated at day 28. I-FABP levels and IEL count correlated at baseline (r=0.458, P=0.042) and at day 14 (r=0.654, P=0.002) of GC. Neither gluten dose nor time on a GFD influenced I-FABP change during GC. CONCLUSIONS: Serum I-FABP levels increased significantly during a two-week GC in adult CD patients and correlated with IEL count. The data suggest that serum I-FABP is an early marker of gluten-induced enteropathy in celiac patients and may be of use in both clinical and research settings.

Efficiency of cell-free and cell-associated virus in mucosal transmission of human immunodeficiency virus type 1 and simian immunodeficiency virus.

Effective strategies are needed to block mucosal transmission of human immunodeficiency virus type 1 (HIV-1). Here, we address a crucial question in HIV-1 pathogenesis: whether infected donor mononuclear cells or cell-free virus plays the more important role in initiating mucosal infection by HIV-1. This distinction is critical, as effective strategies for blocking cell-free and cell-associated virus transmission may be different. We describe a novel ex vivo model system that utilizes sealed human colonic mucosa explants and demonstrate in both the ex vivo model and in vivo using the rectal challenge model in rhesus monkeys that HIV-1-infected lymphocytes can transmit infection across the mucosa more efficiently than cell-free virus. These findings may have significant implications for our understanding of the pathogenesis of mucosal transmission of HIV-1 and for the development of strategies to prevent HIV-1 transmission.

Anti-melanin-concentrating hormone treatment attenuates chronic experimental colitis and fibrosis.

Fibrosis represents a major complication of several chronic diseases, including inflammatory bowel disease (IBD). Treatment of IBD remains a clinical challenge despite several recent therapeutic advances. Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide shown to regulate appetite and energy balance. However, accumulating evidence suggests that MCH has additional biological effects, including modulation of inflammation. In the present study, we examined the efficacy of an MCH-blocking antibody in treating established, dextran sodium sulfate-induced experimental colitis. Histological and molecular analysis of mouse tissues revealed that mice receiving anti-MCH had accelerated mucosal restitution and lower colonic expression of several proinflammatory cytokines, as well as fibrogenic genes, including COL1A1. In parallel, they spared collagen deposits seen in the untreated mice, suggesting attenuated fibrosis. These findings raised the possibility of perhaps direct effects of MCH on myofibroblasts. Indeed, in biopsies from patients with IBD, we demonstrate expression of the MCH receptor MCHR1 in α-smooth muscle actin(+) subepithelial cells. CCD-18Co cells, a primary human colonic myofibroblast cell line, were also positive for MCHR1. In these cells, MCH acted as a profibrotic modulator by potentiating the effects of IGF-1 and TGF-ß on proliferation and collagen production. Thus, by virtue of combined anti-inflammatory and anti-fibrotic effects, blocking MCH might represent a compelling approach for treating IBD.

Prognostic implications of the magnetic resonance imaging appearance in papillary renal cell carcinoma.

OBJECTIVE: To evaluate the prognostic implications of the MRI appearance and pathological features of papillary renal cell carcinoma (pRCC). METHODS: A total of 128 pRCC in 115 patients who underwent preoperative MRI were characterised in terms of pathological type (type 1 vs. type 2), MRI appearance (focal vs. infiltrative) and additional MRI features. Patients were classified on the basis of the presence or absence of metastatic disease. RESULTS: There were 65 focal type 1, 54 focal type 2 and 9 infiltrative pRCC. All infiltrative pRCC were of histopathological type 2. Renal vein thrombus was present in 89 % of infiltrative pRCC and no cases of focal pRCC. Metastatic disease was observed in 3.7 % of focal type 1, 7.5 % of focal type 2 and 75.0 % of infiltrative type 2 pRCC. Infiltrative MRI appearance was a significant predictor of metastatic disease, independent of pathological type, size and T stage (P ≤ 0.020). Among focal pRCC on MRI, pathological type 2 was not a significant predictor of metastatic disease (P = 0.648). No combination of features achieved significantly greater accuracy for predicting metastatic disease than renal vein thrombus alone (P > 0.5). CONCLUSION: Infiltrative MRI appearance and renal vein thrombus identify a subset of pathological type 2 pRCC at a significantly increased risk of metastatic disease.

Reduced intestinal tumorigenesis in APCmin mice lacking melanin-concentrating hormone.

BACKGROUND: Melanin-concentrating hormone (MCH) is an evolutionary conserved hypothalamic neuropeptide that in mammals primarily regulates appetite and energy balance. We have recently identified a novel role for MCH in intestinal inflammation by demonstrating attenuated experimental colitis in MCH deficient mice or wild type mice treated with an anti-MCH antibody. Therefore, targeting MCH has been proposed for the treatment of inflammatory bowel disease. Given the link between chronic intestinal inflammation and colorectal cancer, in the present study we sought to investigate whether blocking MCH might have effects on intestinal tumorigenesis that are independent of inflammation. METHODOLOGY: Tumor development was evaluated in MCH-deficient mice crossed to the APCmin mice which develop spontaneously intestinal adenomas. A different cohort of MCH-/- and MCH+/+ mice in the APCmin background was treated with dextran sodium sulphate (DSS) to induce inflammation-dependent colorectal tumors. In Caco2 human colorectal adenocarcinoma cells, the role of MCH on cell survival, proliferation and apoptosis was investigated. RESULTS: APCmin mice lacking MCH developed fewer, smaller and less dysplastic tumors in the intestine and colon which at the molecular level are characterized by attenuated activation of the wnt/beta-catenin signaling pathway and increased apoptotic indices. Form a mechanistic point of view, MCH increased the survival of colonic adenocarcinoma Caco2 cells via inhibiting apoptosis, consistent with the mouse studies. CONCLUSION: In addition to modulating inflammation, MCH was found to promote intestinal tumorigenesis at least in part by inhibiting epithelial cell apoptosis. Thereby, blocking MCH as a therapeutic approach is expected to decrease the risk for colorectal cancer.

Barrett's esophagus: progression to adenocarcinoma and markers.

The following on progression to adenocarcinoma and markers of Barrett's esophagus includes commentariess on the expression of claudin 4 in Barrett's adenocarcinoma; the role of acid and bile salts; the role of insulin-like growth factor; the value of reactive oxygen species; the importance of abnormal methylation; genetic alterations in stromal cells and genomic changes in the epithelial cells; the value of confocal laser endomicroscopy for the subsurface analysis of the mucosa; indications for statins as adjuvant chemotherapeutic agent; the sequence of molecular events in malignant progression in Barrett's mucosa; and the value of the macroscopic markers and of p53 mutations.

Small intestinal release mesalamine for the treatment of refractory celiac disease type I.

GOAL: The goal of this study is to evaluate the safety and efficacy of Small intestinal release mesalamine (SIRM) for symptom relief in refractory celiac disease (RCD). BACKGROUND: Therapeutic options for the RCD are inadequate and treatment with corticosteroids and immunosuppressants is limited by side effects. SIRM has been shown to have local antiinflammatory action and excellent tolerability. STUDY: We reviewed records of the RCD patients who received SIRM in an open-label therapeutic trial. Data included demographics, disease characteristics, dose and duration of SIRM therapy, and response. Response was categorized as complete if there was complete resolution of symptoms, partial if there was at least 50% improvement, and nonresponsive if there was less than 50% improvement. RESULTS: Four patients were treated with SIRM alone and 6 received SIRM and oral budesonide. Within 4 weeks, 50% had complete response and an additional 10% had partial response. Two of the 6 patients were able to discontinue budesonide. One patient discontinued SIRM owing to headaches. CONCLUSION: SIRM seems to be a safe and efficacious treatment option in patients with RCD. Larger, controlled trials of this agent are warranted.

Perspective: Uses and misuses of thresholds in diagnostic decision making.

The concept of thresholds plays a vital role in decisions involving the initiation, continuation, and completion of diagnostic testing. Much research has focused on the development of explicit thresholds, in the form of practice guidelines and decision analyses. However, these tools are used infrequently; most medical decisions are made at the bedside, using implicit thresholds. Study of these thresholds can lead to a deeper understanding of clinical decision making. The authors examine some factors constituting individual clinicians' implicit thresholds. They propose a model for static thresholds using the concept of situational gravity to explain why some thresholds are high, and some low. Next, they consider the hypothetical effects of incorrect placement of thresholds (miscalibration) and changes to thresholds during diagnosis (manipulation). They demonstrate these concepts using common clinical scenarios. Through analysis of miscalibration of thresholds, the authors demonstrate some common maladaptive clinical behaviors, which are nevertheless internally consistent. They then explain how manipulation of thresholds gives rise to common cognitive heuristics including premature closure and anchoring. They also discuss the case where no threshold has been exceeded despite exhaustive collection of data, which commonly leads to application of the availability or representativeness heuristics. Awareness of implicit thresholds allows for a more effective understanding of the processes of medical decision making and, possibly, to the avoidance of detrimental heuristics and their associated medical errors. Research toward accurately defining these thresholds for individual physicians and toward determining their dynamic properties during the diagnostic process may yield valuable insights.

Clinical significance of colonic intraepithelial lymphocytosis in a pediatric population.

The significance of colonic intraepithelial lymphocytosis has been well described in adults, and is associated with lymphocytic colitis, untreated celiac disease, and medications, among others. Little is known about the meaning of colonic intraepithelial lymphocytosis in the pediatric population; this study examines this finding in a cohort of children. Twenty patients in whom colonic intraepithelial lymphocytosis was a prominent feature were identified from 1999 to 2005. Colonic intraepithelial lymphocytosis was defined as 20 or more intraepithelial lymphocytes per 100 colonocytes present in at least one colonic mucosal biopsy. Each biopsy was examined for numbers of intraepithelial lymphocytes per 100 surface and crypt colonocytes; various architectural, inflammatory, and metaplastic changes were also noted. When available, concurrent duodenal and/or ileal biopsies were examined. Studied clinical parameters included indications for biopsy, clinical follow-up, final diagnosis, comorbidities, autoimmune serologies, and medications. A total of 121 colonic mucosal biopsies were examined in 20 patients who ranged from 1 to 17 years (mean 10.2 years; 40% male). Common indications for endoscopy included diarrhea and abdominal pain. A mean of 29 (+/-22) intraepithelial lymphocytes per 100 enterocytes were seen. Seven patients had colonic intraepithelial lymphocytosis as the only histologic finding. The remaining 13 patients had additional architectural, inflammatory, and metaplastic changes. The mean follow-up period was 14 months (range 1-48 months). Inflammatory bowel disease was diagnosed in 4 of 20 patients and was seen chiefly in biopsies in which colonic intraepithelial lymphocytosis was associated with architectural or inflammatory changes. Common disease associations include celiac disease, lymphocytic colitis, and autoimmune enteropathy. Pediatric colonic intraepithelial lymphocytosis, in the absence of other histologic findings, is associated with various diseases, including celiac disease, lymphocytic colitis, and autoimmune enteropathy. Colonic intraepithelial lymphocytosis in the presence of other inflammatory changes indicates the possibility of idiopathic inflammatory bowel disease. These findings are similar to those seen in adults, with the exception of autoimmune enteropathy.

Metabolic syndrome compared with type 2 diabetes mellitus as a risk factor for stroke: the Framingham Offspring Study.

BACKGROUND: Metabolic syndrome (MetS) has been recognized as a prediabetic constellation of symptoms and an independent risk factor for cardiovascular disease. METHODS: To evaluate the age-adjusted risk of stroke and population-attributable risk associated with MetS and compare with those of overt type 2 diabetes mellitus (hereinafter, "diabetes"), we determined the prevalence of MetS alone, diabetes alone, and both in 2097 subjects in the Framingham Offspring Study, aged 50 to 81 years and free of stroke. Age-adjusted risk ratios, 10-year incidence, and population-attributable risks of stroke were estimated for men and women with MetS alone, diabetes alone, and both. RESULTS: Criteria for MetS were met in 30.3% of men and 24.7% of women. Twenty-four percent of men had MetS alone; 7% had diabetes alone; and 6% had both. Twenty percent of women had MetS alone; 3% had diabetes alone; and 5% had both. Over 14 years of follow-up, 75 men and 55 women developed a first stroke; all but 4 events were ischemic. Relative risk (RR) of stroke in persons with both diabetes and MetS (RR, 3.28; confidence interval [CI], 1.82-5.92) was higher than that for either condition alone (MetS alone: RR, 2.10; CI, 1.37-3.22; diabetes alone: RR, 2.47; CI, 1.31-4.65). The population-attributable risk, owing to its greater prevalence, was greater for MetS alone than for diabetes alone (19% vs 7%), particularly in women (27% vs 5%). CONCLUSIONS: Metabolic syndrome is more prevalent than diabetes and a significant independent risk factor for stroke in people without diabetes. Prevention and control of MetS and its components are likely to reduce stroke incidence.