More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (~30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC's proximal occurrence (70-80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40-60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/ carcinomas (Muir-Torre variant). LS explains only 10-25% of familial CRC. Keywords colorectal cancer; endometrial cancer; hereditary cancer; hereditary nonpolyposis colorectal cancer; immunohistochemistry; Lynch syndrome; microsatellite instability; mismatch repair; mismatch repair genesThe estimated annual worldwide incidence of colorectal cancer (CRC) is 1,023,152 (1). Lynch syndrome (LS), previously called hereditary non-polyposis colorectal cancer or HNPCC, accounts, conservatively, for approximately 3% (2) of this incidence (~30,700 cases), compared with familial adenomatous polyposis (FAP) syndrome which is about one-tenth as common, occurring in only about 1 in 10,000 of the population (3,4). Hampel et al. studied 500 tumors from unselected CRC affected individuals. Among these 500 CRC patients, 18 (3.6%) had LS. When these results were added to data on 1066 previously studied patients, the entire study cohort (N = 1566) showed 44 patients (2.8; 95% confidence interval (CI), 2.1-3.8) manifesting LS. These authors concluded that approximately 1 in every 35 patients who NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript manifested CRC had LS (2). Given the mentioned worldwide incidence figures of CRC, and extrapolating from the findings of Hampel et al. that 2.8% of the CRC cases they investigated were confirmed to be LS, we arrive at a figure of approximately 28,600 cases of LS to be newly diagnosed this year, worldwide. We have only crude estimates of familial CRC, as defined by the presence of two or more first-degree relatives with CRC, but it is thought by some to involve approximately 20% of all cases of CRC (5,6). These statistics are important given that each hereditary case comes from a family that could benefit from genetic counseling, DNA testing, surveillance, and targeted management (7-9). Yet, when a patient's family risk is overlooked, so too are opportunities fo...

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Background. The usual manifestation of familial adenomatous polyposis (FAP) is hundreds or thousands of colonic adenomas. The authors previously described a colon cancer‐prone syndrome characterized by fewer adenomas (1–100), most located in the proximal colon, and upper gastrointestinal lesions, particularly fundic gland polyps and duodenal adenomas. The colonic adenomas are often flat rather than polypoid, a feature emphasized in earlier reports with the term “hereditary flat adenoma syndrome.” The syndrome has an autosomal dominant pattern of inheritance and is linked to the adenomatous polyposis coli [APC] locus at 5q. Methods. This is a descriptive study based on one family that was followed for more than a decade. Total cell RNA was isolated from cultured lymphoblasts, and an in vitro protein synthesis assay was used to detect APC mutations. Sixteen individuals whose APC mutation status was known had sequential endoscopic evaluations. Five patients were given one or more courses of sulindac. Results. There was perfect concordance between clinical affected status and an APC mutation. All affected members generated a 16‐kDa polypeptide from the mutant allele, consistent with a 2‐base pair deletion at the extreme 5′end of the APC gene. Sixteen mutation‐positive individuals underwent upper gastrointestinal endoscopy and colonoscopy; 13 had colonic adenomas, with the number visualized at any one examination ranging from 1 to greater than 50. Upper gastrointestinal examination revealed fundic gland polyps in 15, gastric or duodenal adenomas in 4, and periampullary carcinoma in 1. Conclusion. AFAP is a phenotypically distinctive syndrome, differing from classic FAP by having fewer colonic adenomas that tend to be proximally distributed and flat rather than polypoid. The position of the APC germline mutation appears to allow for the molecular differentiation between FAP and the attenuated variant in that the extreme 5′ APC mutations are associated with the latter.

Cannabis is a common drug of abuse that is associated with various long-term and short-term adverse effects. The nature of its association with vomiting after chronic abuse is obscure and is underrecognised by clinicians. In some patients this vomiting can take on a pattern similar to cyclic vomiting syndrome with a peculiar compulsive hot bathing pattern, which relieves intense feelings of nausea and accompanying symptoms. In this case report, we describe a twentytwo year-old-male with a history of chronic cannabis abuse presenting with recurrent vomiting, intense nausea and abdominal pain. In addition, the patient reported that the hot baths improved his symptoms during these episodes. Abstinence from cannabis led to resolution of the vomiting symptoms and abdominal pain. We conclude that in the setting of chronic cannabis abuse, patients presenting with chronic severe nausea and vomiting that can sometimes be accompanied by abdominal pain and compulsive hot bathing behaviour, in the absence of other obvious causes, a diagnosis of cannabinoid hyperemesis syndrome should be considered.

To examine putative sources of interindividual variation in calcium absorption efficiency, we studied 41 healthy premenopausal women (mean age, 36.4 yr). About half were randomized to pretreatment with supplemental 25-hydroxyvitamin D (25OHD; 20 micrograms/day [corrected] for approximately 34 days) before testing. We measured dietary factors, humoral regulators, intestinal motility, mucosal histology, mucosal vitamin D receptor levels, and calcium absorption efficiency. In winter tests, but not in summer tests, calcium absorption fraction was significantly higher in the pretreated group (mean, 0.465 vs. 0.387). Serum 25OHD, intestinal transit, and urinary calcium to creatinine ratio were all significantly and positively correlated to calcium absorption efficiency. However, neither the level of 1,25-dihydroxyvitamin D receptors in duodenal mucosa nor circulating 1,25-dihydroxyvitamin D was related to calcium absorption efficiency. These findings, which are consistent with other published human data, suggest that 25OHD plays a more prominent role in the regulation of calcium absorption than is generally believed. In a multiple regression model, serum 25OHD, mouth to cecum transit time, and fasting urinary calcium/creatinine ratio explained 44% of the observed variation in calcium absorption efficiency.

The purpose of this study was to determine gastrointestinal (GI) permeability during prolonged treadmill running (60 min at 70 % V.O2max) with and without fluid intake (3 ml/kg body mass/10 min). Twenty runners (11 males, 9 females; age = 22 +/- 3 (SD) yrs; mean V.O2max = 55.7 +/- 5.0 ml/kg/min) completed four experiments: 1) rest, 2) running with no fluid (NF), 3) running with ingestion of a 4 % glucose solution (GLU), and 4) running with ingestion of a water placebo (PLA). To determine GI permeability, subjects also drank a solution containing 5 g sucrose (S), 5 g lactulose (L), and 2 g rhamnose (R) immediately prior to each trial. Gastroduodenal permeability was determined by urinary S excretion, while small intestinal permeability was determined by the L/R excretion ratio. Percent body mass loss (i.e., dehydration) was negligible during rest, GLU and PLA, while NF resulted in a 1.5 % loss of body mass (p < 0.05). Gastroduodenal and intestinal permeability were significantly (p < 0.008) increased in NF compared to rest. There were no other differences in GI permeability. These results indicate that fluid restriction during 1 h of steady-state running increases GI permeability above resting levels.

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