Histone H3 messenger RNA in situ hybridization correlates with in vivo bromodeoxyuridine labeling of S-phase cells in rat colonic epithelium.

Measurements of cell cycle phase fractions, particularly S-phase, are useful for studies of cell biology and carcinogenesis. Up-regulation of histone gene expression is tightly coupled to the G1-S-phase transition of the cell cycle, and mRNA levels rise 30-100-fold during S-phase. Labeling of histone H3 mRNA using in situ hybridization (ISH) was assessed as a measure of S-phase cells and compared with that found using in vivo 5-bromodeoxyuridine (BrdUrd) labeling in formalin-fixed rat colonic crypts under baseline, modified 72-h starvation, and 24-h refeeding conditions. The labeling index scored in single-labeled sections by histone H3 ISH tightly correlated with that found by in vivo BrdUrd labeling (r = 0.99, p < 0.0001) and clearly discriminated between the control, starved, and refed states (P < 0.001). In 180 crypt sections double labeled using histone H3 ISH and BrdUrd, 92% of 1572 labeled cells exhibited both nuclear BrdUrd and cytoplasmic histone H3 label. It is concluded that histone H3 ISH is an accurate measure of the S-phase fraction and provides an alternative to in vivo BrdUrd labeling in rat colon. This finding warrants validation in human studies.

Fecal bile acids in two Japanese populations with different colon cancer risks.

Some workers have associated fecal bile acids with colon cancer frequency. They suggest that the risk for colon cancer increases with a rise in the level of total and degraded fecal bile acids. The Japanese in Hawaii, who are at high risk for this cancer, had higher concentrations of deoxycholic acid (a degraded bile acid) in their fecal specimens than did the people in Akita, Japan, who are at low risk. However, the findings for the other bile acids were unremarkable or inconsistent. These data were suggestive, but not strongly supportive, of a relationship between fecal bile acid patterns and colon cancer risk.

Screening practices and knowledge, attitudes, and beliefs about cancer among Hispanic and non-Hispanic white women 35 years old or older in Nueces County, Texas.

A telephone survey was conducted among women 35 years old or older in Nueces County, Tex., to assess ethnic differences between Hispanic and non-Hispanic white women in self-reported cancer-screening practices and knowledge, attitudes, and beliefs about cancer and to evaluate the effect of ethnicity as a predictor for screening practices. A total of 233 Hispanic and 332 non-Hispanic white women participated in the survey. Hispanics were younger and had lower educational and income levels. Overall, Hispanics had lower rates than did non-Hispanics of lifetime mammography (65% versus 79%), clinical breast examination (86% versus 96%), monthly performance of breast self-examination (37% versus 49%), and lifetime fecal occult blood testing (36% versus 69%). After control for confounding factors, Hispanics were still less likely to have ever had a clinical breast examination and fecal occult blood test. Our results suggest the need for more culturally sensitive health promotion efforts to improve knowledge about cancer and early detection practices among Hispanic women.

A dietary method for an epidemiologic study of gastrointestinal cancer.

The validity of a dietary recall questionnaire was tested among 50 men of Japanese ancestry, participating in a prospective epidemiologic study of gastrointestinal cancer in Honolulu. The questionnaire included 33 food items consumed in Hawaii and suggested as possibly carcinogenic or possibly protective. Estimated intakes of frequencies and amounts during the previous day and previous 7 days were obtained. The validity study consisted of a comparison of a 7 day diary of the frequencies and amounts of the 33 items with a subsequent recall of the same items. The sensitivity (proportion of men recording an item who subsequently recalled it) was better for 24 of the 33 items during the 7-day period than the 1-day period. The overall agreement between the two methods on whether the item was eaten or not was only marginally less for the 7 days than for the 1 day. Estimated intakes tended to be higher for the diary than the recall method. The Spearman rank correlation coefficients among persons recording the items generally were good (greater than 0.7) for items eaten habitually and for those associated with specific events. Further, rank order correlations for quantitative recell of particular food items has considerable validity and is a reasonable choice of method for studies of large groups concerning the role of particular food items in the etiology of cancer.

Cryptosporidiosis. Report of a fatal case complicated by disseminated toxoplasmosis.

A middle-aged woman suffered from chronic diarrhea and malnutrition as a result of a small intestinal infection with a coccidial protozoan--Cryptosporidium. This parasite has been found among a wide range of reptilian, avian and mammalian hosts, but rarely in human beings. This woman ultimately died as a result of disseminated toxoplasmosis of the type usually encountered in an adult whose immune responses were compromised. There was clinical evidence of both humoral and cellular immunologic incompetence, such as depressed levels of complement and immunoglobulins, and decreased T cell reactivity, respectively. The former could be accounted for on the basis of malnutrition causing deficient protein synthesis, and the latter may have been a manifestation of altered function of transformed T cells.

Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience.

PURPOSE: To evaluate the rates of tumor downstaging after preoperative chemoradiation for locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative chemoradiotherapy (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. RESULTS: The pathological tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4NI in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor downstaging occurred in 72 (62%) cases. Only 3% of cases had pathologic evidence of progressive disease. Pretreatment tumor size (< 5 cm vs. > or = 5 cm) was the only factor predictive of tumor downstaging (p < 0.04). A decrease of > 1 T-stage level was accomplished in 45% of those downstaged. Overall, a sphincter-saving (SP) procedure was possible in 59% of patients and an abdominoperineal resection (APR) was required in 41 % of cases. Factors predictive of SP included downstaging (p < 0.03), age > 40 years (p < 0.007), pretreatment tumor distance, 3 to 6 cm from the anal verge (p < 0.00001), tumor size <6 cm (p < 0.02), mobility (p < 0.004), tumor stage 6 cm from the anal verge, SP was performed in 14 of the 15 (93%) patients with a CR and 32 of 33 (97%) of patients with residual disease (p < 0.00004). CONCLUSIONS: Significant tumor downstaging results from preoperative chemoradiation allowing sphincter sparing surgery in over 40% of patients whose tumors were located < 6 cm from the anal verge and who otherwise would have required colostomy.

Simple computer quantitation of spleen-to-liver ratios in the diagnosis of hepatocellular disease.

Increased splenic uptake of radiocolloids is a helpful sign in the scintigraphic diagnosis of various hepatocellular diseases, but little attempt has been made to quantify this physiologic phenomenon. We have devised a simple computer method that compares average splenic activity to average right-lobe liver activity. The method is reproducible (r = 0.97) and exhibits little interobserver variation (r = 0.99). One hundred clinically normal subjects were found to have a nearly symmetrical distribution of S/L ratios around a mean of 0.77, with a s.d. of 0.20. Fifteen subjects normal by biopsy were found to have a similar mean spleen-to-liver (S/L) ratio of 0.74. Based upon a normal range of 0.37 to 1.17 (0.77 +/- 2 s.d.), elevated S/L ratios were found in fatty metamorphosis (85%), cirrhosis (67%), and chronic hepatitis (43%). Abnormal S/L ratios in the range from 1.17 to approximately 1.4 were not visually obvious. Overall sensitivity of the S/L ratio in these three diseases is 69%. When combined with the other scintigraphic indications of hepatocellular disease (nonhomogenous colloid uptake, hepatomegaly, splenomegaly, and bone-marrow colloidal uptake), the liver scan was found to have a sensitivity of 93%.

Late mortality after partial gastrectomy.

A 10-year prospective study of Hawaii Japanese males with partial gastrectomy shows that the age-adjusted mortality rates in men with partial gastrectomy were slightly higher than in those with an intact stomach, but the difference failed to achieve statistical significance. This excess of mortality is due, in part, to excess smoking by men who had ulcers of the stomach. Although death due to stroke and lung cancer showed the most substantial deviations from the base population, this can be attributed only in part to the tendency of men with these diseases to be smokers. Other factors, possibly related to nutrition, also contribute to the increased risk of mortality from these diseases. Death from coronary heart disease, an illness with a substantial association with smoking in men with an intact stomach was less frequent in men with gastrectomy but the difference was not statistically significant. It would appear that men with partial gastrectomy had other characteristics that weakened the impact of smoking upon coronary disease risk--low blood pressure, low serum cholesterol, low body weight and increased alcohol consumption.

Discussing disease progression and end-of-life decisions.

Because most patients now want to know the truth about their diagnosis and prognosis, the ability to discuss the cancer diagnosis, disease recurrence, or treatment failure, and to solicit patients' views about resuscitation or hospice care, are important verbal skills for oncologists and other oncology health care providers. Moreover, the ability to clearly articulate a treatment plan or elicit patient preferences for treatment are a prerequisite to informed consent. Despite these imperatives, clinicians do not routinely receive training in key communication skills that could enable them to accomplish these tasks. A body of literature is available, however, that identifies communication strategies that can (1) facilitate the establishment of a close rapport with the patient, (2) identify the patient's information preferences, (3) ensure comprehension of key knowledge and information, (4) address the patient's emotions in a supportive fashion, (5) elicit the patient's key concerns, and (6) involve the patient in the treatment plan. In this article, we use dialogues between a physician and a hypothetical patient with advanced ovarian cancer to illustrate how communication techniques can be applied to accomplish these goals. We identify important benefits of the use of these techniques for both the physician and patient, and pose several questions regarding the training of physicians in this area.

A review of some tumors of interest for demographic study in Hawaii.1974.

Because of its multiracial character, Hawaii presents a unique opportunity to carry out demographic investigations of the etiology of certain common cancers. Tumors with substantially different incidence rates among the major ethnic groups in the Islands, or between a given immigrant group and its country of origin, are of particular interest for such studies. Among the cancer sites meeting these criteria, nasopharynx, stomach, prostate, large bowel, liver, female breast, uterine corpus, ovary, bladder, and thyroid are particularly prominent.

Fecal occult blood testing for colorectal cancer in an ethnically diverse population.

Fecal occult blood test kits were distributed throughout the ethnically diverse Hawaiian Islands during a 3-week period in 1989. Occult blood was detected in 1,631 persons (11.8%). At least 83% of the participants with positive tests sought medical advice. Subsequently, 76 (4.7%) were diagnosed as having colorectal adenomas and an additional 1.4% had malignant neoplasms (3 gastric and 20 colorectal adenocarcinomas). Three quarters of the colorectal cancers were localized and node-negative. Participation in this program and the type of diagnostic studies done on participants with positive tests varied according to sex and ethnicity. Therefore, these demographic variables must be considered in designing fecal occult blood screening programs.

HLA antigens in stomach cancer.

HLA antigens were identified for 99 Japanese patients with stomach cancer and for 222 controls in Hawaii. There were 68 patients with the intestinal/other histological type of stomach cancer and 31 patients with the diffuse type who may be genetically predisposed towards developing the disease. No significant differences in antigen frequency were noted between cases of the diffuse or intestinal/other histological type and the controls, or between the diffuse and intestinal/other type stomach cancer cases.

Analysis of fecal bile acids and diet among the Japanese in Hawaii.

Fecal samples of 165 Japanese men in Hawaii, age 43 to 74, were analyzed for bile acid content by their conversion to the methyl ester and the trimethylsilyl ether derivative followed by separation on a gas chromatograph. The arithmetic mean of total bile acids for the 165 specimens was 10.96 mg/g dry weight feces. Each of the following bile acids was detectable in over 77% of the fecal specimens: cholic, deoxycholic, lithocholic, and cholanic acid. The intake of Western foods was not positively correlated with the fecal content of secondary or modified bile acids, even though other workers have observed that these bile acids predominated in persons from Westernized countries. Two of the Japanese foods were negatively correlated with the levels of modified bile acids, which suggested that these foods contributed to a decrease in modified bile acids in fecal specimens. Fecal bile acid measurements appeared to be associated with age, but not with weight, height, or serum cholesterol levels.

A case-control study of dietary intake and other lifestyle risk factors for hyperplastic polyps.

BACKGROUND & AIMS: Despite the high prevalence of the hyperplastic polyp, little is known about its etiology. The aim of this study was to assess the relationship between diet and other lifestyle factors and the presence of colorectal hyperplastic polyps. METHODS: Information on diet and other known or suspected risk factors for colorectal cancer or adenoma was collected among 81 subjects with hyperplastic polyps and 480 controls. RESULTS: The multivariate-adjusted odds ratio (OR) for hyperplastic polyps for individuals in the upper vs. the lower quartile was 0.30 (95% confidence interval [CI], 0.10-0.88) for dietary fiber, 0.32 (95% CI, 0.11-0.96) for dietary calcium, 0.90 (95% CI, 0.27-2.95) for total fat, and 2.02 (95% CI, 1.05-3.91) for alcohol consumption. Compared with individuals in the lower category, those in the upper category of body mass index had a higher risk for hyperplastic polyps (OR, 4.50; 95% CI, 1.84-10.97). Cigarette smoking was associated with a higher risk (OR, 1.97; 95% CI, 1.02-3.81 for > 20 pack-years vs. never), whereas an inverse association was seen for use of aspirin and other nonsteroidal anti-inflammatory drugs (OR, 0.29; 95% CI, 0.12-0.67 for once per day or more vs. never). CONCLUSIONS: Hyperplastic polyps share common lifestyle risk factors with colorectal adenomas and carcinomas.

The effect of partial gastrectomy on lipoproteins and other characteristics.

Among 6860 50-77 year old men of Japanese ancestry examined in Honolulu 291 were known to have had a gastrectomy for benign gastric (189) or duodenal (102) ulcer, and 132 had documented peptic ulcer disease treated medically. Total serum cholesterol averaged 12 mg% lower in the surgical group than in the general population (p less than 0.01) while the medically treated men had intermediate values. Fasting lipoprotein determinations done in a sub-sample showed that the lower total cholesterol in the surgical group was due to depressed LDL, while HDL was higher in the operated men than in either the general population or the medically treated patients (p less than 0.01). The surgical patients were heavier users of cigarettes, beer and coffee and averaged about 10 lb. lighter than either the medically treated patients or the rest of the population. However, in multivariate analysis these differences did not not account for the differences in lipoproteins. A small decrement in blood pressure in the surgical patients as compared to the rest of the population became non-significant when weight and others factors were taken into account.

Interobserver variability in endoscopic ultrasonography: a prospective evaluation.

BACKGROUND: Endoscopic ultrasonography (EUS) is an imaging modality that is now widely used to stage gastrointestinal malignancies. Few studies have addressed the issue of interobserver variability in the interpretation of EUS, particularly as it pertains to the staging of rectal carcinoma. METHODS: Twenty-six patients with a diagnosis of rectal carcinoma were evaluated prospectively by three endoscopists. One performed sigmoidoscopy, the second (primary endosonographer) performed an EUS staging examination with full knowledge of the patient history and sigmoidoscopic appearance of the lesion, and the third endoscopist (secondary endosonographer) performed EUS blinded to this information. The results of the respective examinations were then compared. RESULTS: When the EUS findings of the endosonographers were compared, T stage agreed in 88% of patients, with the following kappa coefficients: T1 (kappa = 0.00); T2 (kappa = -0.04); T3 (kappa = -0.05); T4 (kappa = 0.00). Interrator N stage agreed in 73% of patients (kappa = 0.42). CONCLUSION: Our study prospectively evaluated interobserver variation in staging rectal carcinoma by EUS. The protocol that was followed provides a useful template that eliminated potential observer bias. Fair agreement was demonstrated regarding lymph node assessment. Although the raters agreed in 88% of the patients, kappa statistic analysis did not reach significant agreement, due to this institution's preponderence of UT3 lesions. Thus, validation of our findings in a setting where a broader spectrum of disease is encountered is required.