Z. Fireman

Family history of colorectal cancer as a marker of potential malignancy within a screening program

Epidemiologic studies have shown that asymptomatic adult relatives of colorectal cancer patients are at increased risk for developing this tumor. A prospective, published pilot study confirmed this added risk and demonstrated the importance of the family history of cancer as a marker of potential malignancy. The study group was enlarged to include 471 asymptomatic adult, first degree relatives of patients having large bowel neoplasia (cancer or adenomatous polyps) but without polyposis syndromes. These first degree relatives were screened by fecal occult blood examinations and flexible sigmoidoscopy, followed by colonoscopy when indicated. Adenomatous polyps or cancer were found in 8.1% of the study group as compared with 3.7% in a comparison group of screenees, not having the same family history of neoplasia and undergoing similar screening tests. Of the study group the age‐adjusted rate for colorectal adenomas or cancer increased threefold (P < 0.001) for subjects older than 40 years and an even higher fivefold relative risk was found for large bowel cancer only (P = 0.01). This was true even if there was only one relative with colorectal neoplasia (P < 0.01) but was even more pronounced among those having more than one affected relative. The results confirm the usefulness of the family history, of even one member with large bowel neoplasia, in isolating a group at high risk for these lesions. This group would most likely benefit from regular cancer and adenomatous polyp screening particularly when older than 40 years.

Intestinal Cancer in Patients with Crohn's Disease: A Population Study in Central Israel

A population study of Crohns disease (CD) during the years 1970-1980 was performed in a defined area in central Israel with 1,400,000 inhabitants. Three hundred and sixty-five patients with definite CD were identified, and a complete follow-up was obtained with particular attention to intestinal cancer. The mean follow-up time was 9.95 years (range, 1-49 years). Forty-four per cent of the patients were operated on, but only a few had total colectomy or bypass operations. Only one patient developed colorectal cancer after 7 years of disease. The observed to expected ratio for this cancer was 1.14 at 10 years of disease and 0.73 at 20 years of disease. The incidence of colorectal cancer was not significantly different from the expected in the population. None of the patients developed small-bowel cancer. At least five patients had extraintestinal malignancies. A review of the literature showed conflicting results with regard to cancer risk in CD. The risk was not significantly increased in the two existing population studies, including the present one.

The causes of hypoxemia in elderly patients during endoscopy.

Changes in arterial gas tensions were determined in 114 patients undergoing elective gastrointestinal endoscopic examinations with standard or pediatric gastroscopes or colonoscopes. All patients were premedicated intravenously with 0.5 mg of atropine and 10 mg of diazepam. In addition, two thirds received a narcotic, either 50 mg of meperidine or 0.05 mg of the short acting drug fentanyl. The choice of instrument or premedication was usually sequential. There was significant depression of the arterial oxygen tension (Pao2), of 17.4%, immediately following premedication that included a narcotic but not with diazepam alone. Significant reduction of the Pao2 persisted during upper endoscopy if a standard gastroscope was used and meperidine or fentanyl was included in the premedication. If a narrow diameter gastroscope was employed, only meperidine was associated with persistent depression of the Pao2. To minimize hypoxia in elderly patients during upper endoscopy, no narcotic or only a short acting one should be included in their premedication, and a narrow diameter instrument should be used for the examination.

Familial colon cancer in the Tel‐Aviv area and the influence of ethnic origin

The family history of colon cancer was investigated in 38,823 individuals (2,129 families) who comprised a control and an oncology patient series from Tel‐Aviv and nearby areas. A significant increased risk for colon cancer was observed among first‐degree relatives of colon cancer patients when compared to controls. When the patient sample was divided into two groups based on country and continent of birth—European (Ashkenazim) and other (non Ashkenazim)—the relatives of the nonAshkenazi subjects showed a greater relative risk for colon cancer (P < 0.05). Colon cancer was found to be less frequent in nonAshkenazim than in Ashkenazim controls. These findings suggest that although the colon cancer frequency in the nonAshkenazi group is lower, the genetic component may be more important than for the Ashkenazi sample. The nonAshkenazi Jews may represent distinct subgroups that differ with respect to either primary genetic susceptibility to colorectal cancer and/or they may have been subjected to peculiar, environmental carcinogenic exposures when compared to their Ash‐kenazim brethren.

Arterial Oxygen Tension Changes in Elderly Patients Undergoing Upper Gastrointestinal Endoscopy: II. Influence of the Narcotic Premedication and Endoscope Diameter

Changes in arterial oxygen and carbon dioxide tensions were determined in 56 patients, mean age 67 years, during elective upper gastrointestinal endoscopy with standard or pediatric instruments. All the patients received intravenous atropine, diazepam, and either meperidine or fentanyl premedication. There was an immediate and significant fall in PaO2 levels (20.3%-16.5%) after both narcotic injections. The oxygen tension remained significantly depressed during the endoscopic examinations except in the group receiving fentanyl premedication and examined with the narrow pediatric instrument. To minimize hypoxemia in elderly patients during endoscopy, a short-acting narcotic or, preferably, no narcotic at all should be used in the premedication, and a narrow, pediatric instrument be used.

The relative value of fecal occult blood tests and flexible sigmoidoscopy in screening for large bowel neoplasia

The secondary prevention of colorectal cancer is based on the early detection of noninvasive cancer and removal of adenomatous polyps. The two commonly used screening tests are flexible sigmoidoscopy and guaiac fecal occult blood testing. Both were performed simultaneously and independently on 1176 asymptomatic volunteers followed by colonoscopic examination if either occult blood or a neoplasm was detected. Neoplasia (adenomatous polyps or cancer) were found in 48 screenees. Only ten had positive stool occult blood while 45 were detected by sigmoidoscopy. Analysis of sensitivity for neoplasia was 93.8% for sigmoidoscopy but only 20.8% for the occult blood tests, while the positive predictive values for neoplasia were 100% and 23.8% respectively. The fecal occult blood test detected only 18% of screenees with adenomas and 60% with invasive cancer. Flexible sigmoidoscopy detected 95% and 80% respectively. Analysis (kappa statistic) demonstrated little agreement between the two tests (P > 0.05), indicating that they are diagnosing different neoplasia. Evaluation of expected gain in diagnosing neoplasia, by combining both tests, gave 18% for the fecal blood test and 94% for the endoscopic test. These results confirm the complementary value of performing both tests, but especially the high sensitivity and predictive value positive of flexible sigmoidoscopy for adenomas, including those with severe dysplasia, and the converse for the fecal occult blood test. This latter test must be recommended and used within a screening program with caution and full understanding of its limitations.

Reproducibility studies and effects of bowel preparations on measurements of rectal epithelial proliferation.

Measurements of rectal epithelial proliferation (REP), using tritiated labelled thymidine, correlate with colonic epithelial proliferation, risk for cancer and response to therapies. There have been criticisms regarding its reproducibility and the possible deleterious effects of bowel preparations on this biomarker. We studied paired observations on 7 patients repeated without bowel preparation, 11 repeated after tap-water enema, and 8 repeated after PEG-electrolyte solution or extract of senna purgative and found no significant differences between paired observations. In addition, in a high-risk group for colorectal cancer, 31 persons received PEG or senna preparation and their REP was not significantly different from that of 23 examined without these preparations. Thus, REP is a reproducible biomarker and not affected by several commonly used bowel preparations.

Selective screening for colorectal tumors in the Tel-Aviv area: Relevance of epidemiology and family history

A selective screening program for the early detection of colorectal tumors was carried out in the Tel‐Aviv area. The criteria for inclusion were based, in part, on relevant epidemiologic data which showed that European‐ and American‐born immigrants were at the highest risk for developing this cancer, followed by Israeli‐born Jews. The Tel‐Aviv area, because of its large elderly population of European origin, has a high incidence of colorectal cancer. Families of patients with colon cancer are known to have an increased risk for developing colon tumors. These relatives were actively searched for, and were, along with the control group, examined by Hemoccult testing and flexible sigmoidoscopy. The colon tumor (cancer or adenomatous polyps) rate was 6.3% in the group with a family history of colon cancer, as contrasted to 3.8% in a similar control group without this history. This increased yield, greater than usually found in an unselected population, emphasizes the economic value of selective screening utilizing relevant epidemiologic data and the family history.

Influence of demographic parameters on rectal epithelial proliferation

Measurement of rectal epithelial proliferation is now being used as a biomarker for assessing risk for colorectal cancer and response within dietary intervention studies. We examined the possible confounding effects of demographic parameters on the proliferation of 52 healthy middle-aged volunteers without known risk factors for colorectal cancer. No significant effects on proliferation of age, sex or ethnic grouping were found other than marked urban-rural differences amongst men. We hypothesise that these could be explained by differences in dietary habits and their deleterious effects in the older male population. Careful matching of controls are probably needed in order to demonstrate the minor changes in mucosal proliferation that could reflect risk for neoplasia. Further human studies are needed to examine the effects of diet and extremes of age on proliferation.

Rectal epithelial proliferation characteristics of first degree relatives of sporadic colon cancer patients

Hyperproliferation of rectal epithelium is characteristic of families at high genetic risk for large bowel neoplasia, but has not been well-documented in families of sporadic colorectal cancer patients. This was studied in 119 such first degree relatives and 44 comparison subjects without this family history. All screened negative for large bowel neoplasia. Within the family group proliferation was significantly higher in the men and those aged less than 45 years, also higher (insignificantly) in non-Europeans and those having greater than 1 first degree colorectal cancer relative. In comparison to the nonfamily group the labelling index (LI) of the relatives showed a significant negative correlation with age (R = -0.20, P = 0.03). Within this family group the probability of having an elevated LI (greater than 6.0%) was greatest in the young (less than 50 years old) men (odds ratio = 2.0). Measurements of rectal epithelial proliferation (REP) in these first degree relatives, at a young age, might help delineate a high risk subgroup for prospective primary and secondary intervention.