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The proportion of colorectal cancer (CRC) cases in persons younger than age 50, referred to as early onset CRC (EOCRC), has increased from 6% to 11% over the past 25 years, whereas the incidence of CRC has decreased in persons age 50 and older, referred to as late-onset CRC (LOCRC) in the United States.1 It is not known if EOCRC is caused by the same factors that cause LOCRC, or whether there are unique causes that alter the clinical features.2 This study was designed to analyze the clinical and genetic characteristics of EOCRC as presented at a community hospital.

The incidence of colorectal cancer (CRC) in persons under the age of 50 years (EOCRC) is increasing even as the incidence of CRC in persons over age 50 is decreasing. This has led to recommendations to lower the age of CRC screening to age 45. It is not clear whether EOCRC is identical to CRCs in older patients or whether there are distinctive features between the two groups. We reviewed the literature on the clinical and genetic aspects of EOCRC. We found that there is an increased likelihood of a strong genetic basis for EOCRC, but that at least 80% of cases do not come from the known high-penetrance cancer syndromes. Early-onset CRCs tend to occur in the distal colon or rectum, are more likely to be detected due to cancer-related symptoms, appear to be increasing in whites more than non-whites on a population-wide analysis, and are more likely to present in an advanced stage of disease. There are some unique genetic features of EOCRC, including an increased proportion of tumors with LINE-1 hypomethylation, and combined chromosomal and microsatellite stability. EOCRC deserves additional attention because of the high number of life years at risk with EOCRC, and the implications for earlier CRC screening. Additional focus is needed on determining whether some cases of EOCRC have a unique mechanistic basis.

Colorectal cancer (CRC) is the most common gastrointestinal malignancy. There is an association between CRC and endometrial cancer (EC). Up to 10% of this linkage may be due to hereditary non-polyposis colorectal cancer but in the majority of patients a genetic disorder is not found. The National Comprehensive Cancer Network (NCCN) guidelines on CRC since 2005 have suggested that women with endometrial or ovarian cancer diagnosed at less than 60 years of age have CRC screening with colonoscopy beginning at age 40 or at time of diagnosis of the gynecologic tumor. We assessed our population of women with EC to determine if women were receiving CRC screening after a diagnosis of EC. Electronic medical records of all women diagnosed at our institution with EC predominantly between 1997 and 2007 were reviewed. We assessed age at diagnosis, tumor type, family history of malignancy, CRC screening, and findings at CRC screening and recorded the information in a database. Patients were evaluated for the Amsterdam and Bethesda criteria. This study was approved by the Institutional Review Board. Two hundred sixty-seven women with EC were evaluated. The median age was 66; 39% were less than age 60 at diagnosis. Family history of CRC was present in 25 (9.4%) of EC patients. Of these women, 125 (46.8%) had CRC screening, with 12 (9.6%) being screened for CRC within 1 year of diagnosis and 33 (26.4%) screened for CRC before diagnosis of endometrial cancer. Of the women, 142 (53.2%) did not have CRC screening reported. Of the women screened, ten had adenomatous polyps with one of those polyps being greater than 1 cm, four had tubulovillous histology, and three had CRC. Colonoscopy was performed in 59.2% of women who underwent CRC screening. One woman met criteria for Amsterdam and Bethesda criteria. Less than half of women with EC received screening for CRC. Women who were screened had significant pathology in 13.6% of cases and 2.4% had colon cancer. The NCCN guidelines should be more aggressively followed by physicians who care for women. A prospective colonoscopy screening study on these women with EC to assess the yield and utility in screening in this population is needed.

Adenomas of the rectosigmoid colon are considered markers of risk for advanced adenomas of the proximal colon. However, studies report a wide variation in risk. This study was designed to determine the risk for advanced adenomas in the proximal colon in patients from a large, homogeneous population with an advanced or nonadvanced adenoma of the distal colon. We designed a prospective study of 7157 patients who were evaluated for neoplasia by flexible sigmoidoscopy and, when adenomas were found, by colonoscopy. Adenomas were considered advanced if they wereor =10 mm in size or had villous or dysplastic features. Ninety-seven patients had an advanced adenoma of the distal colon (Group A) and were compared with 183 patients who had a nonadvanced adenoma (Group B). Seven patients (7.2%) in Group A had an advanced adenoma of the proximal colon, compared with four patients (2.2%) in Group B (P0.05, relative risk = 3.3). When patients with adenomas of the distal colon5 mm (Group C) were compared to patients with adenomasor =5 mm (Group D), the prevalence of advanced adenomas of the proximal colon remained at 7% (10/143) for Group C but fell to 0.73% (1/137) for Group D (P = 0.011, relative risk = 9.6). By expanding the criteria for risk from adenomas of the distal colon to include all adenomas5 mm, the relative risk for advanced adenoma of the proximal colon was increased threefold.

Multiple studies link the use of nonsteroidal antiinflammatory drugs (NSAIDs) with severe upper gastrointestinal bleeding (UGIB); the incidence of such bleeding is 2-4%. One common regimen to assure patency after intracoronary stent placement requires an anticoagulant (warfarin) combined with aspirin as an antiplatelet agent. However, a 13-fold increase in the risk of UGIB occurs with long-term use of oral anticoagulants and NSAIDs. We retrospectively assessed the rate of UGIB in 138 patients who had received coronary stents (group I, receiving heparin followed by warfarin in combination with aspirin) and 109 angioplasty patients without stents (group II, receiving aspirin alone) between 1990 and 1994. UGIB was identified by hematemesis or melena, which led to gastrointestinal consultation. Patients were analyzed for multiple risk factors. UGIB occurred in 28 of 138 group I patients (20%; 95% CI 13.3-26.7%) and 0 of 109 group II patients (P < 0.0001). Esophagogastroduodenoscopy (EGD) findings on the 28 patients with UGIB included 13 patients with esophagitis or gastritis, 7 patients with gastric or duodenal ulcers, and 8 patients with no identifiable source of bleeding. UGIB occurred within a mean of 2.5 days of initiation of combination therapy. Of patients with UGIB, 10 required blood transfusion (mean number of units = 5.3). Previous history of peptic ulcer disease, smoking, and use of antiulcer medication did not significantly differ between the two groups. The concurrent use of anticoagulant and aspirin in patients with coronary stents creates a significant potential for UGIB and should be used only with extreme caution.

The role of alcohol in causing chronic pancreatitis is well-known, but the role of abstinence remains controversial and not well-understood. In this article, I examine the literature dealing with the effect of abstinence on chronic pain and the long-term outcome of chronic pancreatitis. A series of 50 patients with alcoholic chronic pancreatitis from my practice supplements the data. Alcohol consumption > 70 g/day for 7 or more years is characteristic. Moderate to severe abdominal pain is the dominant symptom. When patients stop drinking, abdominal pain disappears in the majority, pancreatic function deteriorates more slowly, the death rate diminishes, and a normal life is often possible. If abdominal pain continues after abstinence and the pancreatic duct remains dilated, a lateral pancreatojejunostomy helps most patients. In many patients not suitable for surgery, pain resolves with time.

A family history of colorectal cancer is considered an independent risk factor for advanced neoplasia at colonoscopy. The expected outcome for screening colonoscopy in patients with a family history is not well established in all populations. We designed a large, prospective study of an unselected population in San Diego, California to assess the impact of a family history of colorectal cancer on the prevalence of advanced neoplasia on screening colonoscopy. We evaluated 6,905 consecutive patients referred for colonoscopy between January 2005 and December 2006. Of the 4,967 who met the inclusion criteria, the mean age was 58.8 and consisted of 58.6% women. Overall 930 (18.7%) had neoplasia and 249 (5%) had advanced neoplasia, eight (0.16%) of which were cancer. The 4,967 patients were divided into 643 with and 4,324 without a family history of colorectal cancer. Of the 643 patients with a family history, 38 (5.9%) had advanced neoplasia, one of which was cancer. Of the 4,324 patients without a family history, 211 (4.9%) had advanced neoplasia including seven cancers. The relative risk for finding advanced neoplasia in patients with a single affected first degree relative was 1.21 (95% CI, 0.87–1.69; P = 0.31). A family history of one first-degree relative with colorectal cancer did not predict a significantly higher prevalence of advanced neoplasia at screening colonoscopy in this Southwestern cohort.

Most studies reporting polyp size use visual estimates. Determining the prevalence of advanced histology based on direct measurement of polyp size may help guide the management of polyps found at optical colonoscopy (OC) and CT colonography (CTC). We designed a large, prospective study to assess the prevalence of advanced adenomas based on direct measurement of polyp size by a certified pathologists’ assistant as reported in the pathology report. Patients between 40 and 89 years of age who presented for screening colonoscopy were included in our study. Advanced adenomas were defined as ≥10 mm or ≥25% villous features, high grade dysplasia or cancer. Polyps were divided by size into three groups: diminutive (≤5 mm), small (6–9 mm) and large (≥10 mm). If more than one adenoma was present, the most advanced was used for analysis. We evaluated 6,905 consecutive patients referred for colonoscopy between January 2005 and December 2006. Of the 4,967 who met the inclusion criteria, the mean age was 58.8 and consisted of 59% women. Overall, 930 (18.7%) had an adenoma; 248 (5%) were advanced adenomas including 8 (0.16%) cancers. Of 89 polyps ≥10 mm, 76 (85%) had advanced histology; of 247 polyps 6–9 mm, 67 (27%) were advanced; of 1,025 polyps ≤5 mm, 105 (10%) were advanced. Thus, 172 of 248 (69%) patients with advanced adenomas had small or diminutive adenomas. Our data indicate the majority (69%) of advanced adenomas are

Gastrojejunal bypass surgery may be complicated by nutritional deficiencies, including trace elements. Copper, which is absorbed in the duodenum and proximal jejunum, is poorly absorbed when a significant portion of the proximal small intestine is bypassed. However, despite this theoretical risk of hypocupremia in the gastrojejunal bypass patient, reports of symptomatic copper deficiency are very rare, and even then the deficiency is often potentiated by an accelerant, such as concomitant zinc ingestion. We report a case of hypocupremia resulting in hematologic abnormalities and myeloneuropathy after gastrojejunal bypass surgery for morbid obesity. It stresses the importance of recognizing nutritional deficiencies, particularly copper deficiency, because of the possible and serious sequelae of bone marrow suppression and myeloneuropathy. The early recognition and treatment of the symptoms of hypocupremia is emphasized to avoid these long-term sequelae. With the rapidly growing number of patients undergoing gastrojejunal bypass surgery for morbid obesity, the index of suspicion for hypocupremia must be heightened.

Failures of diagnosis of colorectal cancer by colonoscopy, barium enema, and flexible sigmoidoscopy have been demonstrated using various techniques. A relative assessment of these diagnostic tests for patients with colorectal cancer has not been reported. This study was designed to determine relative rates of failures for these tests when applied to diagnosis of colorectal cancer. We created a database of patients with colorectal cancer diagnosed between 2000 and 2005. Records were reviewed for the results of colonoscopy, barium enema, and flexible sigmoidoscopy in the 3 years prior to diagnosis. An examination that was negative for cancer with no immediate follow-up was defined as a failure of diagnosis, either from inaccurate observation, failure to examine the entire colon, or failure of timely follow-up. The failure rates were compared. Three hundred seventy-nine patients, who had 421 examinations, were analyzed. The diagnosis of colorectal cancer failed in 60 of 379 patients (16%). These 60 patients had 71 examinations that failed to make the diagnosis: 25 of 282 colonoscopies (9%), 16 of 79 barium enemas (20%), and 30 of 60 flexible sigmoidoscopies (50%). These differences were statistically significant. Failure rates for colonoscopy, barium enema, and flexible sigmoidoscopy were 9%, 20%, and 50%.

Flexible sigmoidoscopy is advised as a screening test for colorectal cancer for persons with a family history of late-onset colorectal cancer. The expected outcome for this approach is not well established. We designed a large, prospective study of an unselected population to assess the impact of a family history of one first-degree relative with colorectal cancer on the prevalence of advanced adenomas at screening flexible sigmoidoscopy. We evaluated 8121 patients referred for flexible sigmoidoscopy between 1997 and 1999 and 3147 patients met the inclusion criteria. The 3147 patients were divided into 210 with a family history of colorectal cancer and 2937 without a family history and analyzed for differences in the prevalence of advanced adenomas. Of the 210 with a family history, 3 had an advanced adenoma of the rectosigmoid colon (1.4%) Of the 2937 without a family history, 52 had an advanced adenoma of the rectosigmoid colon (1.8%), including 2 cancers. These differences were not significant. In conclusion, a family history of colorectal cancer had no impact on the prevalence of advanced adenomas in asymptomatic patients at screening flexible sigmoidoscopy. The prevalence rates for advanced adenomas and carcinomas of the rectosigmoid colon were low.

Background: Among the risk factors for colorectal cancer (CRC) is a family history of colorectal cancer. Reliable evidence is needed regarding the clinical characteristics of cancer in patients with this history to determine if a change in the diagnostic approach is needed. Aim of the Study: This study set out to determine specific clinical outcomes in patients with CRC with a family history of one first-degree relative with sporadic colorectal cancer compared to control patients with colorectal cancer but without the family history. Methods: We designed a case-control study of colorectal cancer registry data between 1988 and 1999. Patients with a family history of one first-degree relative with colorectal cancer were compared to those without the history with regard to four characteristics: age at cancer diagnosis, anatomic location of the cancer, presence of distal adenomas with proximal cancer, and stage of disease at diagnosis. Results: Nine hundred and twenty-one patients met the inclusion criteria. Family history was positive in 124 patients. The demography of the populations was similar, except for mean age, which was 65 yr for men with a family history and proximal cancer compared to 70 yr for their counterparts without the family history (p=0.03). The anatomic location of the cancer, presence of distal benign neoplasia when the cancer was proximal, and disease stage at diagnosis were not different between the groups. Conclusions: Men with a family history of sporadic colorectal cancer and proximal colon cancer were younger than men without the family history and proximal colon cancer. The overall results do not indicate that a change in the diagnostic approach is needed.

Flexible sigmoidoscopy is recommended for persons at average risk for colorectal cancer. A follow-up is advised in 3 to 5 years, although the outcomes are not well established. We designed a large, prospective study of an unselected population to measure the incidence of advanced adenomas at flexible sigmoidoscopy 3 and 5 years after an initial negative examination. Adenomas were considered advanced if they were villous, tubulovillous, high-grade dysplasia, adenocarcinoma, oror = 10 mm in size. We evaluated 8121 patients referred for flexible sigmoidoscopy and 4010 met the inclusion criteria. Group 1 had flexible sigmoidoscopy between 3 and 4 years and Group 2 between 5 and 6 years after a negative examination. Group 1 included 1300 patients with an incidence rate for advanced adenomas of 0.9% (12/1300) and Group 2 included 2710 patients with an incidence rate for advanced adenomas of 1.1% (30/2710). When the two group were subdivided by the presence or absence of a family history of a first-degree relative with sporadic colorectal cancer, the incidence rates for advanced adenomas between the populations were not different. Our data indicate incidence rates of 0.9 and 1.1% for advanced adenomas at flexible sigmoidoscopy 3 and 5 years, respectively, after a negative flexible sigmoidoscopy, with no impact from a family history.

Prognosis in gastric adenocarcinoma (GAC) and esophageal cancer (EC) is intimately related to cancer stage, and a simple method of predicting GAC and EC stage without invasive testing would be of great utility. We previously reported a study using a cancer registry database to derive a formula for a “staging score” (SS), using various clinical factors to predict GAC and EC stage. The gastric SS formula is (Hemoglobin x Total Protein x Albumin x Body Mass Index) / Age. A score of 50 years of age, the SS was correct in identifying stage in 29/37 of cases (78.4%). There were 17 EC cases of which 6 and 11 cases were early and late EC, respectively. The SS identified 5/6 cases (83.3%) of early EC and 9/11 cases (81.8%) of late EC. Overall, the SS correctly identified stage in 14/17 cases (82.4%) of EC. Conclusion: This study tests a simple SS formula to provide an estimated prognosis for both gastric adenocarcinoma and esophageal cancer in an effort to provide a general prognosis using clinical factors likely to be readily available before pathologic staging or other more expensive and invasive testing is obtained. Although this study was limited by the relatively small number of cases of GAC and EC, the SS may be a useful tool to clinicians and patients as an estimate of cancer stage.

Traveler's diarrhea affects a substantial number of travelers to high-risk areas of the world. The key to controlling this troublesome disease is prevention. The most important preventive measures depend on educating patients to consume only safe foods and pure water. Physicians cannot overemphasize the importance of avoiding high-risk foods and of boiling water if a safe water supply is not available. Prophylactic medications are a secondary consideration and should be prescribed with discretion. In most cases, diarrhea is mild and self-limited, requiring only fluid and electrolyte replacement and perhaps an antidiarrheal agent. In moderate to severe cases, the addition of an antimicrobial agent may be of benefit. Until an efficacious polyvalent vaccine is developed, caution and common sense, together with discretionary dietary and hygienic practices, are the best defenses against traveler's diarrhea. The ultimate solution is greatly improved sanitation and personal hygiene, especially in high-risk countries. However, only dreamers will consider waiting for this transformation to occur.

A patient with vigorous achalasia is presented who had marked smooth muscle hypertrophy and eosinophilic infiltration of the esophagus identical to that seen in patients with eosinophilic gastroenteritis. Eosinophilic infiltration of the esophagus probably represents a variant of the eosinophilic gastroenteritis syndrome and may predispose to an esophageal motor disorder.

The effect of the unconjugated bile acids, cholic, deoxycholic, chenodeoxycholic, and ursodeoxycholic acids, and of the conjugated bile acid taurocholic acid on the mucosal-to-serosal transport and tissue uptake of the naturally occurring folate derivative, 5-methyltetrahydrofolate (5-CH3H4PteGlu) was examined in everted sacs of rat jejunum. Each of the unconjugated bile acids examined inhibited the transport and tissue uptake of 5-CH3H4PteGlu in a concentration dependent manner. At low concentrations (0.01-0.1 mM) of cholic and deoxycholic acids, no structural or functional damage to the intestinal mucosa occurred and the transport of 5-CH3H4PteGlu was inhibited competitively with Ki values of 0.114 mM and 0.055 mM for cholic and deoxycholic acids, respectively. The greater inhibition of 5-CH3H4PteGlu transport by unconjugated bile acids at 1 mM can be attributed to observed structural and functional damage to the intestinal mucosa. The addition of 2 mM lecithin to the mucosal medium failed to prevent the inhibitory effect of 0.1 mM deoxycholic acid on the transport of 0.5 microM 5-CH3H4PteGlu. Compared with the effect of unconjugated bile acids, the conjugated bile acid taurocholic acid (0.01-5 mM) showed no effect on the transport and tissue uptake of 5-CH3H4PteGlu. The results of this study show that intestinal transport and tissue uptake of 5-CH3H4PteGlu are inhibited by unconjugated bile acids in a dose-dependent fashion. The clinical and physiological implications of these observations are discussed.

Employing a continuous bile collection, we measured the bile secretion of porphyrins, haem (iron protoporphyrin IX regardless of oxidation state) and bilirubin in five healthy subjects. The baseline values for the flow of porphyrins in the bile were: 4.7 +/- 1.9 nmol/h uroporphyrin, 27.3 +/- 3.8 nmol/h coproporphyrin and 39.2 +/- 11.7 nmol/h protoporphyrin. Bile haem flow was 59.7 +/- 12.6 nmol/h, and that of bilirubin 23.8 +/- 8.2 mumol/h. Following haem injection (6.4 mumol/kg) the flow of protoporphyrin but not of the other porphyrins was reduced, and the bile haem flow increased (232 +/- 109.5 nmol/h), while the flow of bilirubin did not increase significantly. A few patients with representative porphyrias showed the expected increase in copro- and protoporphyrin in the bile. The patient with coproporphyria exhibited a bile flow of coproporphyrin of 1470 +/- 133 nmol/h and of protoporphyrin of 334 +/- 29 nmol/h; haem infusion significantly reduced the bile flow of both porphyrins (to 649 +/- 101 for copro- and 215 +/- 36 nmol/for protoporphyrin). The patient with protoporphyria had an increased protoporphyrin flow, yet haem infusion caused no reduction in protoporphyrin flow (106 +/- 7 after v. 81.4 +/- 13 nmol/h before haem). In conclusion, we found that haem and porphyrins are normal constituents of bile, and that injected haem appears in bile. Bile bilirubin did not rise within 12 h after haem infusion a finding which warrants further investigation.

At endoscopic examination of 7 exophytic, 20 infiltrative, and 11 ulcerating gastric carcinomas, correct visual diagnosis was made in 82%. Guided biopsy and brushing cytology together yielded a positive pathologic diagnosis in 84%. When endoscopic appearance, biopsy, and cytology were collated, a correct diagnosis was achieved in 97% of cases. Infiltrative and ulcerated lesions required the most assiduous study.

The intestinal transport of 5-methyltetrahydrofolate and pteroylmonoglutamate was examined in everted sacs of rat jejunum exposed to compounds which increase intracellular cyclic adenosine-3', 5'-monophosphate. Adenyl cyclase stimulators (hydrocortisone and prostaglandin), phosphodiesterase inhibitors (3-isobutyl-l-methylxanthine, aminophylline and papaverine), and dibutyryl adenosine-3',5'-cyclicmonophosphate added to the mucosal medium inhibit the mucosal-to-serosal transport of physiological concentrations of 5-methyltetrahydrofalate and pteroylmonoglutamate. Transport inhibition is correlated with the ability of these agents to increase cellular cyclic adenosine-3', 5'-monophosphate. The active, carrier-mediated transport system of folate compounds is highly sensitive to the increase in cyclic adenosine-3', 5'-monophosphate level, while the diffusion system is insensitive. These data indicate that the active transport system of folates is modulated by cellular cyclic adenosine-3', 5'-monophosphate.

The effect of ethanol and other aliphatic alcohols on the intestinal transport of 5-methyltetrahydrofolate and folic acid was examined using everted sacs from rat jejunum. Ethanol added to the mucosal medium inhibited the transport of both folate compounds in a parallel manner, and the inhibition increased with increasing ethanol concentration (0.5-10% v/v). Ethanol at 3% v/v in the mucosal medium caused: depression in the pH dependency of the active transport of 5-methyltetrahydrofolate; higher inhibition in the transport of low concentration (0.1 microM) than high concentration (10 microM) of 5-methyltetrahydrofolate, and inhibition in the active accumulation against a concentration gradient of 5-methyltetrahydrofolate and L-leucine. Methanol, propanol and butanol also inhibited the transport of the folate compounds; and in general, the inhibitory effect increased with the increase in the number of carbon atoms in the hydrophobic chain. This study indicates that ethanol and other alcohols inhibit the intestinal transport of folates, that the degree of inhibition is related to the concentration and chain length of the alcohol, that the inhibition is not specific for folates and finally that the mechanism of inhibition is multifactorial.