Adrian N. Holm

Constipation and a Low-Fiber Diet Are Not Associated With Diverticulosis

BACKGROUND & AIMS Asymptomatic diverticulosis is commonly attributed to constipation caused by a low-fiber diet, although evidence for this mechanism is limited. We examined the associations between constipation and low dietary fiber intake with risk of asymptomatic diverticulosis. METHODS We performed a cross-sectional study that analyzed data from 539 individuals with diverticulosis and 1569 without (controls). Participants underwent colonoscopy and assessment of diet, physical activity, and bowel habits. Our analysis was limited to participants with no knowledge of their diverticular disease to reduce the risk of biased responses. RESULTS Constipation was not associated with an increased risk of diverticulosis. Participants with less frequent bowel movements (<7/wk) had reduced odds of diverticulosis compared with those with regular bowel movements (7/wk) (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.40-0.80). Those reporting hard stools also had reduced odds (OR, 0.75; 95% CI, 0.55-1.02). There was no association between diverticulosis and straining (OR, 0.85; 95% CI, 0.59-1.22) or incomplete bowel movement (OR, 0.85; 95% CI, 0.61-1.20). We found no association between dietary fiber intake and diverticulosis (OR, 0.96; 95% CI, 0.71-1.30) in comparing the highest quartile with the lowest (mean intake, 25 vs 8 g/day). CONCLUSIONS In our cross-sectional, colonoscopy-based study, neither constipation nor a low-fiber diet was associated with an increased risk of diverticulosis.

Intestinal Helminths Regulate Lethal Acute Graft-versus-Host Disease and Preserve the Graft-versus-Tumor Effect in Mice

Donor T lymphocyte transfer with hematopoietic stem cells suppresses residual tumor growth (graft-versus-tumor [GVT]) in cancer patients undergoing bone marrow transplantation (BMT). However, donor T cell reactivity to host organs causes severe and potentially lethal inflammation called graft-versus-host disease (GVHD). High-dose steroids or other immunosuppressive drugs are used to treat GVHD that have limited ability to control the inflammation while incurring long-term toxicity. Novel strategies are needed to modulate GVHD, preserve GVT, and improve the outcome of BMT. Regulatory T cells (Tregs) control alloantigen-sensitized inflammation of GVHD, sustain GVT, and prevent mortality in BMT. Helminths colonizing the alimentary tract dramatically increase the Treg activity, thereby modulating intestinal or systemic inflammatory responses. These observations led us to hypothesize that helminths can regulate GVHD and maintain GVT in mice. Acute GVHD was induced in helminth (Heligmosomoides polygyrus)–infected or uninfected BALB/c recipients of C57BL/6 donor grafts. Helminth infection suppressed donor T cell inflammatory cytokine generation and reduced GVHD-related mortality, but maintained GVT. H. polygyrus colonization promoted the survival of TGF-β–generating recipient Tregs after a conditioning regimen with total body irradiation and led to a TGF-β–dependent in vivo expansion/maturation of donor Tregs after BMT. Helminths did not control GVHD when T cells unresponsive to TGF-β–mediated immune regulation were used as donor T lymphocytes. These results suggest that helminths suppress acute GVHD using Tregs and TGF-β–dependent pathways in mice. Helminthic regulation of GVHD and GVT through intestinal immune conditioning may improve the outcome of BMT.

Endoscopic Cyanoacrylate Glue Injection in Management of Gastric Variceal Bleeding: US Tertiary Care Center Experience

Background/Aims Although endoscopic cyanoacrylate glue injection (ECGI) is recommended as first-line treatment for bleeding gastric varices (GV) there is still limited experience with this method in the US. Our aim was to analyze our 10-year experience of ECGI for treatment and prophylaxis of gastric variceal bleeding. Methods Records of patients undergoing ECGI of GV at our US tertiary care center between 6/2005 and 5/2015 were reviewed. Assessed outcomes were primary hemostasis, early rebleeding during hospitalization, recurrent bleeding during follow-up, eradication and recurrence of GV. Results Prophylactic ECGI was performed in 16 patients with large GV. Eradication was achieved in 15 (94%). During the median follow-up of 27 (IQR 7-47) months, 4 patients (26.6%) had variceal bleeding; all were treated successfully with ECGI. Fifty-seven patients underwent ECGI for GV bleeding. Primary hemostasis was achieved in all. Early rebleeding occurred in 2 (3.5%) and durable hemostasis could not be achieved. Follow-up beyond initial hospitalization was available in 41 patients. Bleeding recurred in 8 (19.5%) patients during a median follow-up of 12 (IQR, 3-51) months. Eradication of GV was achieved in 92% of patients but recurrent varices were found in 44% during a median follow up period of 33 months. Conclusion ECGI is effective in achieving hemostasis of bleeding GV and their eradication. Recurrent bleeding and recurrence of varices after complete obliteration however are not infrequent and continued surveillance is advisable.

Curative Intent Treatment for Colorectal Cancer with Isolated Brain Metastases: A Case Report

Introduction: Brain metastases (BM) are a rare complication of colorectal cancer (CRC), typically presenting late in the course of the disease and are associated with other systemic metastases. Management of solitary brain metastases in colorectal cancer is still not well established. Case presentation: We describe the case of a 65 year-old man presenting with a solitary brain metastasis as the first sign of colon cancer. The treatment approach included surgical resection of the brain lesion followed by resection of the primary tumor, systemic chemotherapy and local radiation therapy to the BM. Conclusion: This curative intent approach has resulted in dramatically prolonged patient’s survival compared to the average reported in the literature, now nearly 2.5 years after presentation. Our case describes the feasibility of a multidisciplinary curative intent approach to solitary BM in CRC.

Increased Nuclear Localization of Interleukin 33 in Eosinophilic Esophagitis

Aim: Investigate the intensity and distribution of IL-33 staining in patients with EoE compared to healthy controls and patients with GERD. Methods: A retrospective study and reviewed pathology specimens from 20 patients with EoE and 20 patients with GERD and 20 healthy subjects. We performed immunohistochemical staining for IL-33 on these samples. The staining distribution was compared with respect to intranuclear or intracytoplasmic IL-33 intensity and the depth of staining intensity in the biopsies. Results: There was increased intensity of nuclear IL-33 staining in biopsies from patients with EoE as compared to healthy subjects patients with GERD (P<0.001), and no difference in cytoplasmic staining, or IL-33 distribution within biopsies thickness among the groups (P=0.42). Conclusion: This study describes enhanced nuclear expression of IL-33 in EoE, a disorder characterized by a predominantly Th2 response and esophageal hypereosinophilia in the absence of GERD. Our observations may have implications for improved understanding of the pathophysiology, diagnosis and treatment of EoE.