BACKGROUND AND AIMS Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates. METHODS A literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate. RESULTS The overall prevalence of CRC in any UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2–4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years. The worldwide cancer incidence rates varied geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd in Scandinavia and other countries. Over time the cancer risk has increased since 1955 but this finding was not significant (p=0.8). CONCLUSIONS Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.

https://gut.bmj.com/content/gutjnl/48/4/526.full.pdf

The risk of colorectal cancer in ulcerative colitis: a meta-analysis

The cell biology of caveolae is a rapidly growing area of biomedical research. Caveolae are known primarily for their ability to transport molecules across endothelial cells, but modern cellular techniques have dramatically extended our view of caveolae. They form a unique endocytic and exocytic compartment at the surface of most cells and are capable of importing molecules and delivering them to specific locations within the cell, exporting molecules to extracellular space, and compartmentalizing a variety of signaling activities. They are not simply an endocytic device with a peculiar membrane shape but constitute an entire membrane system with multiple functions essential for the cell. Specific diseases attack this system: Pathogens have been identified that use it as a means of gaining entrance to the cell. Trying to understand the full range of functions of caveolae challenges our basic instincts about the cell.

The Caveolae Membrane System

http://www.klinikcity.ru/wp-content/uploads/2012/03/Guidelines/Gastroenterology/Ulceral_Colitis_ACG_2010.pdf

Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee.

Background The risk of colorectal cancer is increased among patients with ulcerative colitis. The magnitude of this increase in risk and the effects of the length of follow-up, the extent of disease at diagnosis, and age at diagnosis vary substantially in different studies. Methods To provide accurate estimates of the risk of colorectal cancer among patients with ulcerative colitis, we studied a population-based cohort of 3117 patients given a diagnosis of ulcerative colitis from 1922 through 1983 who were followed up through 1984. Results Ninety-two cases of colorectal cancer occurred in 91 patients. As compared with the expected incidence, the incidence of colorectal cancer in the cohort was increased (standardized incidence ratio [ratio of observed to expected cases] = 5.7; 95 percent confidence interval, 4.6 to 7.0). Less extensive disease at diagnosis was associated with a lower risk; for patients with ulcerative proctitis, the standardized incidence ratio was 1.7 (95 percent confidence interval, 0.8 to 3.2); for those with left-sided colitis, 2.8 (95 percent confidence interval, 1.6 to 4.4); and for those with pancolitis (extensive colitis, or inflammation of the entire colon), 14.8 (95 percent confidence interval, 11.4 to 18.9). Age at diagnosis and the extent of disease at diagnosis were strong and independent risk factors for colorectal cancer. For each increase in age group at diagnosis (less than 15 years, 15 to 29 years, 30 to 39 years, 40 to 49 years, 50 to 59 years, and greater than or equal to 60 years), the relative risk of colorectal cancer, adjusted for the extent of disease at diagnosis, decreased by about half (adjusted standardized incidence ratio = 0.51; 95 percent confidence interval, 0.46 to 0.56). The absolute risk of colorectal cancer 35 years after diagnosis was 30 percent for patients with pancolitis at diagnosis and 40 percent for those given this diagnosis at less than 15 years of age. Conclusions Close surveillance and perhaps even prophylactic proctocolectomy should be recommended for patients given a diagnosis of pancolitis, especially those who are less than 15 years of age at diagnosis.

https://www.nejm.org/doi/pdf/10.1056/NEJM199011013231802

Ulcerative colitis and colorectal cancer. A population-based study.

The Zygomycetes represent relatively uncommon isolates in the clinical laboratory, reflecting either environmental contaminants or, less commonly, a clinical disease called zygomycosis. There are two orders of Zygomycetes containing organisms that cause human disease, the Mucorales and the Entomophthorales. The majority of human illness is caused by the Mucorales. While disease is most commonly linked to Rhizopus spp., other organisms are also associated with human infection, including Mucor, Rhizomucor, Absidia, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces, and Syncephalastrum spp. Although Mortierella spp. do cause disease in animals, there is no longer sufficient evidence to suggest that they are true human pathogens. The spores from these molds are transmitted by inhalation, via a variety of percutaneous routes, or by ingestion of spores. Human zygomycosis caused by the Mucorales generally occurs in immunocompromised hosts as opportunistic infections. Host risk factors include diabetes mellitus, neutropenia, sustained immunosuppressive therapy, chronic prednisone use, iron chelation therapy, broad-spectrum antibiotic use, severe malnutrition, and primary breakdown in the integrity of the cutaneous barrier such as trauma, surgical wounds, needle sticks, or burns. Zygomycosis occurs only rarely in immunocompetent hosts. The disease manifestations reflect the mode of transmission, with rhinocerebral and pulmonary diseases being the most common manifestations. Cutaneous, gastrointestinal, and allergic diseases are also seen. The Mucorales are associated with angioinvasive disease, often leading to thrombosis, infarction of involved tissues, and tissue destruction mediated by a number of fungal proteases, lipases, and mycotoxins. If the diagnosis is not made early, dissemination often occurs. Therapy, if it is to be effective, must be started early and requires combinations of antifungal drugs, surgical intervention, and reversal of the underlying risk factors. The Entomophthorales are closely related to the Mucorales on the basis of sexual growth by production of zygospores and by the production of coenocytic hyphae. Despite these similarities, the Entomophthorales and Mucorales have dramatically different gross morphologies, asexual reproductive characteristics, and disease manifestations. In comparison to the floccose aerial mycelium of the Mucorales, the Entomophthorales produce a compact, glabrous mycelium. The asexually produced spores of the Entomophthorales may be passively released or actively expelled into the environment. Human disease with these organisms occurs predominantly in tropical regions, with transmission occurring by implantation of spores via minor trauma such as insect bites or by inhalation of spores into the sinuses. Conidiobolus typically infects mucocutaneous sites to produce sinusitis disease, while Basidiobolus infections occur as subcutaneous mycosis of the trunk and extremities. The Entomophthorales are true pathogens, infecting primarily immunocompetent hosts. They generally do not invade blood vessels and rarely disseminate. Occasional cases of disseminated and angioinvasive disease have recently been described, primarily in immunocompromised patients, suggesting a possible emerging role for this organism as an opportunist.

Zygomycetes in Human Disease

Cancer in universal and left-sided ulcerative colitis: factors determining risk.

The changing spectrum of disease, etiology, and diagnosis of mucormycosis

A freeze fracture study of Crohn's disease of the terminal ileum: changes in epithelial tight junction organization.

A series of experiments was devised to determine possible modifying effects of stress, aspirin, and sodium taurocholate on the activity of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in the Buffalo rat stomach. MNNG is a well known, direct-reacting carcinogen, and has been a reliable agent for the experimental production of gastric adenocarcinoma. The authors were able to produce adenocarcinomas in rats, but found a great number of gastric leiomyosarcomas. These occurred only in the groups given MNNG in combination with stress, aspirin, or sodium taurocholate, and did not occur in experimental groups given either MNNG, stress, aspirin, or sodium taurocholate alone, and did not occur in the control group. Cancer 53:1088-1092, 1984.

Experimental models for gastric leiomyosarcoma. The effects of N-methyl-N'-nitro-N-nitrosoguanidine in combination with stress, aspirin, or sodium taurocholate.

The diagnosis of pulmonary nontuberculous mycobacterial (NTM) infection may be difficult to establish unless open-lung biopsy is performed. Mycobacteria were present in resected lung tissues from forty patients at the Mount Sinai Hospital during the period 1969-1980. M. avium-intracellulare was cultured in 24 patients, M. tuberculosis in six, M. gordonae in three, and M. fortuitum in two. In five instances, mycobacteria were seen in smears of lung tissues but failed to grow in culture. Three distinct clinicopathologic groups of patients with NTM were recognized. (1) Eighteen patients had solitary pulmonary nodules resected with the clinical diagnosis of lung cancer. Histologically, they exhibited granulomas with varying degrees of necrosis. Mediastinal lymph nodes had no granulomas, except in one case. (2) Seven patients presented with roentgenologic evidence of bilateral, diffuse interstitial infiltration. M. avium-intracellulare or M. gordonae were isolated from lung tissue which histologically showed interstitial fibrosis and organizing pneumonia. In only one instance a few non-caseating epitheloid cell granulomas were found. Three of these patients had underlying malignancies treated with chemotherapy and one other had arthritis. The other three had no underlying diseases. (3) Three patients had multiple discrete infiltrates on chest roentgenograms. M. avium-intracellulare was isolated from their lung tissues. One of these patients exhibited necrotizing granulomatous vasculitis indistinguishable from Wegener's granulomatosis. It is apparent that classical "tuberculosis-like" granulomatous reaction is the most common histologic pattern but should not be expected in all patients with NTM infections.

Stephen A. Geller

Papers

Cancer in universal and left-sided ulcerative colitis: factors determining risk.

The changing spectrum of disease, etiology, and diagnosis of mucormycosis

A freeze fracture study of Crohn's disease of the terminal ileum: changes in epithelial tight junction organization.

Experimental models for gastric leiomyosarcoma. The effects of N-methyl-N'-nitro-N-nitrosoguanidine in combination with stress, aspirin, or sodium taurocholate.

The Spectrum of Pathology of Nontuberculous Mycobacterial Infections in Open-Lung Biopsy Specimens