Extended flexible sigmoidoscopy performed by colonoscopists for colorectal cancer screening: a pilot study.

BACKGROUND: Caecal intubation can be achieved by extended flexible sigmoidoscopy in 32% of patients. AIM: To assess the feasibility of extended flexible sigmoidoscopy performed by colonoscopists for colorectal cancer screening. METHODS: We enrolled 41 patients referred for screening flexible sigmoidoscopy. After purging, examination was performed with a colonoscope. All patients completed sigmoidoscopy (success in meeting referral goal); 93% and 71% had examination to the transverse or ascending colon, and caecum, respectively. Overall yield and right-sided polyps was 56% and 27%, respectively. Caecal intubation and complete examination with polypectomy took 6.0 +/- 2.5 and 18.3 +/- 5.1 min, respectively; with no complications. Twelve patients requested colonoscope withdrawal because of discomfort. Although 46% reported moderate to severe discomfort, 39% and 36%, respectively, were definitely or probably willing to repeat flexible sigmoidoscopy. RESULTS: Unsedated colonoscopy introduced as extended flexible sigmoidoscopy emphasizes the benefits of added yield rather than the negative image of withholding of discomfort relief. The patient can choose to accept the equivalent of an unsedated colonoscopy or reject the option based on perceived discomfort during extended flexible sigmoidoscopy performed by the colonoscopist. CONCLUSION: Extended flexible sigmoidoscopy is a feasible option in carefully selected patients, fully prepared and by an experienced colonoscopist.

Murine CD1d-restricted T cell recognition of cellular lipids.

NKT cells are associated with immunological control of autoimmune disease and cancer and can recognize cell surface mCD1d without addition of exogenous antigens. Cellular antigens presented by mCD1d have not been identified, although NKT cells can recognize a synthetic glycolipid, alpha-GalCer. Here we show that after addition of a lipid extract from a tumor cell line, plate-bound mCD1d molecules stimulated an NKT cell hybridoma. This hybridoma also responded strongly to three purified phospholipids, but failed to recognize alpha-GalCer. Seven of sixteen other mCD1d restricted hybridomas also showed a response to certain purified phospholipids. These findings suggest NKT cells can recognize cellular antigens distinct from alpha-GalCer and identify phospholipids as potential self-antigens presented by mCD1d.

1. Positron Emission Tomography of Thoracic Malignancies. Reduction of Myocardial Fluorodeoxyglucose Uptake Artifacts With a Carbohydrate Restricted Diet.

Purpose: To reduce the artifact caused by cardiac uptake of F-18 fluorodeoxyglucose (FDG); we investigated the change in myocardial FDG uptake after placing a group of patients on a carbohydrate-restricted diet.Methods: Case control study involving 130 whole body FDG PET scans. 73 scans were of patients on carbohydrate-restriction; the remaining 57 were without dietary restrictions. Dietary intake for the last meal prior to scanning was recorded for both groups. Coronal and axial images were assessed and scored based on myocardial FDG uptake the presence of associated image artifacts.Results: Of the 73 patients on the diet, 50 did not consume carbohydrates, while of the 57 patients without dietary restriction, 13 did not consume carbohydrates. Of the 67 patients from both groups who consumed carbohydrates prior to their PET scan, 17 (25.4%) had a clinically significant image artifact versus only 6 (9.5%) of the 63 patients who did not consume carbohydrates (P = 0.018) in their meals prior to scanning. The odds ratio was calculated to be 3.23 (confidence interval 1.09-10.00), indicating that the risk a clinically significant image artifact will occur is 3.23 times higher for patients who consume carbohydrates in their last meal prior to scanning.Conclusion: A substantial reduction in the prevalence of myocardial FDG uptake image artifacts among patients who did not consume carbohydrates was observed. A carbohydrate dietary restriction prior to scanning may play a significant role in increasing lesion detectability and in preventing false negative scans when imaging for thoracic neoplasm.

Coordinate up-regulation of low-density lipoprotein receptor and cyclo-oxygenase-2 gene expression in human colorectal cells and in colorectal adenocarcinoma biopsies.

Many colorectal cancers have high levels of cyclo-oxygenase 2 (COX-2), an enzyme that metabolizes the essential fatty acids into prostaglandins. Since the low-density lipoprotein receptor (LDLr) is involved in the uptake of essential fatty acids, we studied the effect of LDL on growth and gene regulation in colorectal cancer cells. DiFi cells grown in lipoprotein-deficient sera (LPDS) grew more slowly than cells with LDL. LDLr antibody caused significant inhibition of tumor cell growth but did not affect controls. In addition, LDL uptake did not change in the presence of excess LDL, suggesting that ldlr mRNA lacks normal feedback regulation in some colorectal cancers. Analysis of the ldlr mRNA showed that excess LDL in the medium did not cause down-regulation of the message even after 24 hr. The second portion of the study examined the mRNA expression of ldlr and its co-regulation with cox-2 in normal and tumor specimens from patients with colorectal adenocarcinomas. The ratio of tumor:paired normal mucosa of mRNA expression of ldlr and of cox-2 was measured in specimens taken during colonoscopy. ldlr and cox-2 transcripts were apparent in 11 of 11 carcinomas. There was significant coordinate up-regulation both of ldlr and of cox-2 in 6 of 11 (55%) tumors compared with normal colonic mucosa. There was no up-regulation of cox-2 without concomitant up-regulation of ldlr. These data suggest that the LDLr is abnormally regulated in some colorectal tumors and may play a role in the up-regulation of cox-2.

Razor blade surgery: use of the Castroviejo blade breaker and holder.

BACKGROUND: To remove skin lesions, many dermatologists use the razor blade which may be manipulated with or without the aid of an instrument. However, the techniques previously described employ the use of an entire razor blade. OBJECTIVE: To outline a technique that is easily performed with better control of the blade and with more precise cutting than by holding the blade by hand. This report reviews the merits of razor blade use in cutaneous surgery as well as the advantages of using the Castroviejo razor blade breaker. METHODS: The method for cutting double-edged razor blades and holding the sections with a Castroviejo blade breaker is described as well as a basic guide for selecting blade size for performing shave biopsies and shave excisions. CONCLUSIONS: Using the Castroviejo razor blade breaker and holder with cut razor blades is safe and allows better control and more precise cutting than using a complete double-edged blade alone.

Dominant enhancers of Egfr in Drosophila melanogaster: genetic links between the Notch and Egfr signaling pathways.

The Drosophila epidermal growth factor receptor (EGFR) is a key component of a complex signaling pathway that participates in multiple developmental processes. We have performed an F1 screen for mutations that cause dominant enhancement of wing vein phenotypes associated with mutations in Egfr. With this screen, we have recovered mutations in Hairless (H), vein, groucho (gro), and three apparently novel loci. All of the E(Egfr)s we have identified show dominant interactions in transheterozygous combinations with each other and with alleles of N or Su(H), suggesting that they are involved in cross-talk between the N and EGFR signaling pathways. Further examination of the phenotypic interactions between Egfr, H, and gro revealed that reductions in Egfr activity enhanced both the bristle loss associated with H mutations, and the bristle hyperplasia and ocellar hypertrophy associated with gro mutations. Double mutant combinations of Egfr and gro hypomorphic alleles led to the formation of ectopic compound eyes in a dosage sensitive manner. Our findings suggest that these E(Egfr)s represent links between the Egfr and Notch signaling pathways, and that Egfr activity can either promote or suppress Notch signaling, depending on its developmental context.

Endoscopic hemostasis of nonvariceal, non-peptic ulcer hemorrhage.

The majority of patients who present with acute upper gastrointestinal hemorrhage are found to be bleeding from acid peptic disease including ulcer, esophagitis and gastritis, and variceal disease. Mallory-Weiss tear, Dieulafoy's lesion, cancer, and other rare lesions account for the bleeding source in the remaining patients. Endoscopic hemostasis may be effective in many of the conditions, but only Mallory-Weiss tear and Dieulafoy's lesion are encountered frequently enough to be clinically significant.

Benign colorectal polyps. Endoscopic surveillance guidelines and effects on colorectal cancer risk.

In the past several years, there have been major advances in the understanding of colorectal cancer from both the clinical and basic science level. Although there are various techniques for colorectal cancer screening and surveillance, the most cost-effective approach has yet to be determined. As molecular biology techniques are improved and incorporated into clinical practice, identification of high-risk populations seems possible. With future advances in endoscopy and imaging, patient compliance can be improved. With the proper combination of both clinical and basic science techniques, it seems reasonable that a further reduction in the mortality from colorectal cancer can be accomplished.

Completeness of hospital cancer case reporting from the SEER Program of the National Cancer Institute.

BACKGROUND: To ascertain the quality of data entering a population-based reporting system, an essential requirement is to study levels of completeness of case-ascertainment and reporting. This study represents an effort to quantify completeness of case reporting in the SEER (Surveillance, Epidemiology, and End Results) Program of the National Cancer Institute. METHODS: Hospitals in each of the participating SEER areas were stratified according to their annual hospital cancer caseload for the year 1987. Within each caseload stratum, a random sample of hospitals was selected for inclusion in this study. Files in the medical record, pathology, and radiation oncology departments in each hospital were reviewed for SEER reportable cases. These cases were then matched against SEER case listings to identify unreported cases. RESULTS: The crude estimated completeness of reporting for 1987 in the six participating SEER areas was 97.7% and the registry-caseload standardized rate was 96.8%. Variation was noted by SEER registry, hospital cancer caseload, and casefinding source (hospital department). Three-quarters of unreported cases were of invasive disease and one-fourth were in situ, primarily of the cervix uteri. CONCLUSIONS: There is variation in completeness of casefinding among SEER registries, hospital size, and hospital department source. Additional factors that appear to be related to case ascertainment are cancer site or type and who performs the casefinding function (hospital registry or central registry staff).

Study of completeness of the surveillance, epidemiology and end results (SEER) program case ascertainment by hospital size and casefinding source.

Factors that may enter into the completeness/incompleteness of reporting include: 1. The competence and diligence of staff. 2. Familiarity with the record systems used within each hospital department. This limited review suggested that hospitals employing their own staff for case ascertainment achieved somewhat higher completeness of reporting rates compared with institutions that relied on central registry circuit riders to pick up cases. 3. Where cases are identified through computer listings by diagnosis, errors in the coding of some cases may result in the exclusion of these cases. 4. The use of ambiguous diagnostic terms may contribute to missing cases.

Cloning and sequencing of a gene encoding a glutamate and aspartate carrier of Escherichia coli K-12.

A gene encoding a carrier protein for glutamate and aspartate was cloned into Escherichia coli K-12 strain BK9MDG by using the high-copy-number plasmid pBR322. The gene (designated gltP) is probably identical to a gene recently cloned from E. coli B (Y. Deguchi, I. Yamato, and Y. Anraku, J. Bacteriol. 171:1314-1319). A 1.6-kilobase DNA fragment containing gltP was subcloned into the expression plasmids pT7-5 and pT7-6, and its product was identified by a phage T7 RNA polymerase-T7 promoter coupled system (S. Tabor and C. C. Richardson, Proc. Natl. Acad. Sci. USA 82:1074-1078) as a polypeptide with an apparent mass of 38 kilodaltons. A portion of the gltP polypeptide was associated with the cytoplasmic membrane. The nucleotide sequence of the 1.6-kilobase fragment was determined. It contained an open reading frame capable of encoding a highly hydrophobic polypeptide of 395 amino acids, containing four possible transmembrane segments. Uptake of glutamate and aspartate was increased 5.5- and 4.5-fold, respectively, in strains containing gltP plasmids. Glutamate uptake was insensitive to the concentration of Na+ and was inhibited by L-cysteate and beta-hydroxyaspartate. These results suggest that gltP is a structural gene for a carrier protein of the Na(+)-independent, binding-protein-independent glutamate-aspartate transport system.

Late effects of radiation therapy for cancer of the uterine cervix.

This report presents follow-up information on 497 women diagnosed with cancer of the uterine cervix in Connecticut and California between 1932 and 1951 who received only radiation as their initial course of therapy. Patients entered into the study were all treated before age 55 and all were five-year-survivors following treatment in order to eliminate early deaths due to the cervical cancer. Three radiologic dosage groups (high, medium, and low) were formed with 93, 244, and 160 patients, respectively. For all dosage groups combined 108 subsequent cancers were observed more than 5 yr after cancer treatment compared with 64 expected (P less than 0.01). Sites for which subsequent cancers were significantly (P less than 0.05) in excess of expectation were rectum, ovary, lung, vulva and vagina, small intestine, oropharynx, and central nervous system excluding brain. The ratio of observed to expected cases of subsequent cancers rose only slightly with increasing radiologic dose. No significant differences in overall survival patterns for the three dosage groups were found. For all dosage groups survival was poorer than in the corresponding segment of the general population.

Cutaneous mucinosis of infancy.

Cutaneous mucinosis is a term that has been used to describe a group of diseases or conditions in which accumulation of mucin in the skin is a prominent feature. The cutaneous mucinoses includes myxedema (both diffuse and localized), lichen myxedematosus (papular mucinosis), lipoid proteinosis, follicular mucinosis, cutaneous focal mucinosis, cutaneous myxoid cyst, and others. All of these diseases share distinct histologic features. I examined a 16-month-old infant with a case of cutaneous mucinosis that had unique clinical and histologic features, unlike any of the known mucinoses.

Staging of cancer of the colon and cancer of the rectum.

A retrospective analysis of 1,826 cases (924 colon, 902 rectal) from ten institutions provided the basis of this study on the staging of cancer of the colon and rectum. The general rules of the American Joint Committee on the relationship between times and the staging of cancer have been followed. These represent modifications of the originally formulated TNM system of the Union Internationale Contre Le Cancer (UICC) which has been designed as a clinical-diagnostic classification, not applicable to cancer of inaccessible sites or structures requiring postsurgical treatment pathologic assessment of therapeutically removed specimens. Inadequacies of the clinical data requested for our study required adoption of the pTNM evaluation method of classification. Multiple regression analysis of the data demonstrated a relationship between survival and the following: depth of penetration (T), status of regional lymph nodes (N), and presence or absence of distant metastasis (M). This was similar for both sites. Basically, for the rectum it was in consonance with the original Dukes' classification (A, B, and C), and was remarkably applicable to the colon. The survival data for the two sites were so similar as to suggest the use of one set of pTNM categories not only for the postsurgical-treatment pathologic evaluation, but also for the stage grouping definitions. Strongly recommended for cancer of all sites is the development of General Oncology Data Forms to be included in the clinical charts and records of all patients with cancer.

Time trends in survival in acute lymphocytic leukemia.

Comparison of patients under 20 years of age with acute lymphocytic leukemia diagnosed in 1955-64 with those whose disease was diagnosed in 1965-69 revealed a marked improvement in median survival time, from 9.5 to 16.8 months. This improvement occurred among patients with less favorable hematologic and symptomatic characteristics as well as among patients with more favorable ones. However, a shift in patient characteristics was consistent with the concept of diagnosis earlier in the natural history of the disease. In the more recent period, fewer patients were classified as severely disabled, and a somewhat higher proportion were in more favorable categories with respect to platelet count, percent of polymorphonuclear leukocytes, organomegaly, and bleeding or infection. Initial treatment was markedly different during the two time periods; this reflected a shift toward the use of combinations of chemotherapeutic agents and steroids.