Utilization of colorectal cancer screening tests: a 1997 survey of Massachusetts internists.

BACKGROUND: Physician noncompliance with screening recommendations has been a major barrier to effective colorectal cancer control. The overall objectives of this study were to assess the current attitudes and screening behavior of primary care physicians in light of new efficacy data, revised guidelines, improved technology, and more widespread insurance coverage. METHODS: Questionnaires inquiring about knowledge, beliefs, and practice patterns related to colorectal cancer screening were mailed in mid-1997 to 700 randomly selected Massachusetts internists. RESULTS: The overall response rate was 63%. Nearly 60% of respondents reported an increase in screening behavior during the past 5 years. Most (80%) were aware of at least one set of screening guidelines and 90% reported utilizing one or more recommended screening strategies. Fecal occult blood testing (FOBT), alone (47%) or in combination with flexible sigmoidoscopy (50%), was the preferred strategy for most respondents. Colonoscopy was rarely utilized (5%) despite high perceived effectiveness. Concern about patient compliance was a significant determinant of FOBT utilization, whereas perceived effectiveness, concerns about time or efficacy data, prior procedural training, date of licensure, and use of instructional materials were independent determinants of sigmoidoscopy utilization. CONCLUSION: Massachusetts' internists report high rates of utilization of select colorectal cancer screening strategies. Future studies must validate self-reported compliance and explore barriers to screening colonoscopy.

Attitudes toward colorectal cancer screening tests.

OBJECTIVE: To examine patient and physician preferences in regard to 5 colorectal cancer screening alternatives endorsed by a 1997 expert panel, determine the impact of patient and physician values regarding certain test features on screening preference, and assess physicians' perceptions of patients' values. DESIGN: Cross-sectional survey. SETTING: A general internal medicine practice at an academic medical center in 1998. PARTICIPANTS: Patients (N=217; 76% response rate) and physicians (N=39; 87% response rate) at the study setting. MEASUREMENTS AND MAIN RESULTS: Patients preferred fecal occult blood testing (43%) or colonoscopy (40%). In patients for whom accuracy was the most important test feature, colonoscopy (62%) was the preferred screening method. Patients for whom invasive test features were more important preferred fecal occult blood testing (76%; P <.001). Patients and physicians were similar in their values regarding the various test features. However, there was a significant difference between physicians' perceptions of which test features were important to patients compared with the patients' actual responses (P <.001). The largest discrepancy was for accuracy (patient actual 54% vs physician opinion 15%) and discomfort (patient actual 15% vs physician opinion 64%). CONCLUSIONS: Patients have distinct preferences for colorectal cancer screening tests that are associated with the importance placed on certain test features. Physicians incorrectly perceive those factors that are important to patients. Physicians should incorporate patient values in regard to certain test features when discussing colorectal cancer screening with their patients and when eliciting their screening preferences.

Lack of communication about familial colorectal cancer risk associated with colorectal adenomas (United States).

BACKGROUND: Sufficient evidence has accumulated to suggest that the first-degree relatives of patients diagnosed with colorectal adenomas before the age of 60 are at increased risk of colorectal cancer. The principal objective of this study was to assess the extent to which channels of communication exist between physicians, patients and their at-risk first-degree relatives regarding both familial risk and screening recommendations. METHODS: A telephone survey was conducted among 79 patients (age < or = 60 years) with newly diagnosed colorectal adenomas. Information regarding patient demographics, awareness of familial risk, physician recommendations, and extent of communication with family members about their risk status and need for screening was ascertained. RESULTS: Forty-four (56%) of the 79 eligible subjects completed the survey. Only 18 (41%) responders were aware that their first-degree relatives were at increased risk of colorectal cancer, and the majority claimed to have gained their awareness through sources other than their physicians. Only five (28%) of the 18 knowledgeable patients notified their at-risk relatives of their status, and only two (11%) communicated the need for screening. CONCLUSIONS: This survey demonstrates poor communication about familial colorectal cancer risk associated with colorectal adenomas, and highlights the need for novel strategies to both promote awareness and facilitate screening of at-risk relatives.

Cancer skills laboratories for medical students: a promising approach for cancer education.

BACKGROUND: Most medical students graduate without the skills necessary to assist patients in cancer control. To address this problem, the authors developed a cancer skills laboratory for second-year medical students. METHODS: The skills laboratory consists of two hours of training, with 15 minutes allotted per station (six to eight students assigned per station). Faculty and fellows lead the stations on prostate cancer, breast cancer, colorectal cancer, skin cancer, counseling for smoking cessation, and a discussion of anti-tobacco advertisements. Students completed pre- and post-laboratory surveys consisting of ten brief questions. RESULTS: Overall, 94% of eligible students in 1997 and 1998 completed the surveys. Using a five-point scale, self-rated skill level increased from 2.12 to 3.83 when all modalities were averaged (p < .001). CONCLUSIONS: Cancer skills laboratories are a promising new means for cancer education.

A comparison of virtual and conventional colonoscopy for the detection of colorectal polyps.

BACKGROUND: Virtual colonoscopy is a new method of imaging the colon in which thin-section, helical computed tomography (CT) is used to generate high-resolution, two-dimensional axial images. Three-dimensional images of the colon simulating those obtained with conventional colonoscopy are then reconstructed off-line. We compared the performance of virtual and conventional colonoscopy for the detection of colorectal polyps. METHODS: We prospectively studied 100 patients at high risk for colorectal neoplasia (60 men and 40 women; mean age, 62 years). We performed virtual colonoscopy immediately before conventional colonoscopy. We inserted a rectal tube and insufflated the colon with air to the maximal level that the patient could tolerate. We administered 1 mg of glucagon intravenously immediately before CT scanning to minimize the degree of smooth-muscle spasm and peristalsis and to reduce the patient's discomfort. RESULTS: The entire colon was clearly seen by virtual colonoscopy in 87 patients and by conventional colonoscopy in 89. Fifty-one patients had normal findings on conventional colonoscopy. In the other 49, we identified a total of 115 polyps and 3 carcinomas. Virtual colonoscopy identified all 3 cancers, 20 of 22 polyps that were 10 mm or more in diameter (91 percent), 33 of 40 that were 6 to 9 mm (82 percent), and 29 of 53 that were 5 mm or smaller (55 percent). There were 19 false positive findings of polyps and no false positive findings of cancer. Of the 69 adenomatous polyps, 46 of the 51 that were 6 mm or more in diameter (90 percent) and 12 of the 18 that were 5 mm or smaller (67 percent) were correctly identified by virtual colonoscopy. Although discomfort was not specifically recorded, none of the patients requested that virtual colonoscopy be stopped because of discomfort or pain. CONCLUSIONS: In a group of patients at high risk for colorectal neoplasia, virtual and conventional colonoscopy had similar efficacy for the detection of polyps that were 6 mm or more in diameter.

Implementation of on-site screening sigmoidoscopy positively influences utilization by primary care providers.

BACKGROUND & AIMS: Sigmoidoscopy is an effective screening strategy for colorectal cancer that is not widely used by primary care providers. The aim of this study was to assess the impact of "academic detailing" in the form of an outreach educational seminar combined with implementation of on-site sigmoidoscopy services performed by university-based gastroenterologists on provider compliance. METHODS: A controlled trial was initiated at 9 urban neighborhood health centers, including 4 intervention and 5 comparison sites. Baseline data on provider attitudes and practice patterns were collected using a validated questionnaire. Outcome measures included a year 1 follow-up survey of provider attitudes and quarterly review of screening sigmoidoscopy referrals using appointment logs to assess utilization. RESULTS: Overall self-reported compliance rates for screening sigmoidoscopy increased by 36% (baseline, 24%; year 1, 60%) for the intervention group vs. only 7% (baseline, 19%; year 1, 26%) for the comparison group (P = 0. 001). When stratified by site, compliance rates increased at each intervention site (range, 7%-92%) but at only 2 control sites. Use of screening sigmoidoscopy was also significantly greater at the intervention sites (47% vs. 4%; P

Reversible ischemic colitis in a high endurance athlete.

Ischemic colitis is a rare but serious consequence of long distance running. Herein we report a well documented case of severe ischemic colitis in an elite class marathon athlete in whom an extensive diagnostic evaluation, including magnetic resonance angiography and hypercoagulation profile, was performed. Our results suggest that physiologic shunting due to splanchnic vasoconstriction, intravascular volume depletion due to chronic dehydration, and possibly some element of hypercoaguability due to secondary polycythemia may have been causative factors. The patient's full recovery, both clinically and endoscopically, with conservative treatment and ability to resume a vigorous training schedule further support a reversible nonocclusive etiology.

Feasibility of high-volume screening sigmoidoscopy using a flexible fiberoptic endoscope and a disposable sheath system.

OBJECTIVES: Sigmoidoscopy is an effective screening test for colorectal cancer but has yet to have a major impact on mortality because, in part, of inadequate utilization by physicians. To address concerns of inefficient use of time and resources, we examined the feasibility of high volume, single-day flexible sigmoidoscopy (FS) screening sessions using an innovative fiberoptic sigmoidoscope with a disposable sheath system. METHODS: All City of Boston employees over the age of 50 yr (n = 6137) were invited by mail to undergo a screening FS at Boston City Hospital (BCH). Respondents (n = 564) were contacted by phone by the program coordinator on receipt of a prepaid postcard and were scheduled (n = 227) consecutively into 15-min slots on 1 of 6 1/2-day (3-h) weekend sessions. Preregistration was completed at BCH during the week before each session and included enrollment, completion of a brief risk questionnaire, documentation of informed consent, and bowel prep instructions. Procedures were performed by three physician endoscopists rotating among four endoscopy rooms per session. Each room was staffed with a nurse to aid in patient care and a technician to set up equipment. RESULTS: A total of 198 of the 227 (87%) scheduled patients underwent screening FS during the three sessions. Physicians performed a mean of 3.5 procedures per room per hour, or 4.7 procedures per hour overall, with a mean depth of scope insertion of 51 +/- 10 cm and a mean procedure time of 4.7 +/- 3.3 min. Equipment set-up time and patient turnaround time averaged 4.6 +/- 1.7 min and 11.0 +/- 6.0 min, respectively. Polyps were detected in 29 (14.6%) patients, and a Dukes' A cancer was detected in one (0.5%). The only complication was a cardiac arrhythmia. A crude estimate of direct costs approximated $ 75 per examination. CONCLUSION: High volume, single-day FS using the fiberoptic sigmoidoscope with a disposable sheath system offers an effective strategy for enhancing physicians compliance, and possibly patient compliance, with screening sigmoidoscopy through more efficient use of time and resources.

Proliferation and differentiation of a human colon cancer cell line (CaCo2) is associated with significant changes in the expression and secretion of insulin-like growth factor (IGF) IGF-II and IGF binding protein-4: role of IGF-II.

The extent to which the insulin-like growth factor (IGF) system contributes to the initiation and progression of colon cancer remains poorly defined. We recently reported that a majority of human colon cancers express and secrete the potent mitogen IGF-II and at least two inhibitory binding proteins, IGFBP-2 and IGFBP-4. In the present study we measured the expression and secretion of IGF-II, IGFBP-2, and IGFBP-4 in relation to growth and differentiation of CaCo2 human colon cancer cells, which undergo spontaneous enterocytic differentiation in culture. Under the conditions of the present study, CaCo2 cells demonstrated an initial rapid phase of growth between Day 2 through days 7-9 of culture, followed by a significant retardation in the growth between days 9-13. Alkaline phosphatase (ALP) activity, a marker of enterocytic differentiation, progressively increased between Days 7-13 in culture, temporally correlating with post-confluent phase of negligible growth. These changes in growth and differentiation were accompanied by > 80% decline in the relative concentration of IGF-II messenger RNA (mRNA) between Days 2-13. In contrast, the relative mRNA concentrations of inhibitory binding proteins (IGFBP-2 and IGFBP-4) increased rapidly to 200% of Day 2 values by Days 5-7 before returning to baseline levels by Day 13. The relative protein concentrations of the three factors measured in the conditioned media of the cells followed a pattern very similar to that measured for the mRNA levels. While the changes in the relative protein concentrations and mRNA levels of IGF-II and IGFBP-4 were statistically significant, the changes measured in the RNA and protein levels of IGFBP-2 were not, as a result of large inter experimental variations. Thus these results suggested that CaCo2 cell differentiation may require an attenuation of IGF-II effects. To confirm the latter possibility, additional studies were conducted with a specific neutralizing antibody against IGF-II. Incubation of CaCo2 cells with anti-IGF-II antibodies from Day 0 through Day 7 significantly retarded the growth of the cells and was accompanied by a significant increase in the concentration of Alkaline phosphatase activity per 10(6) cells. Recently, we reported a potent inhibitory role of IGFBP-4 in the growth of colon cancer cells. In the present studies, a possible important role of IGF-II is illustrated not only in the growth but also in the differentiation of colonic cells. Our studies thus suggest that differential expression of IGF-II and IGFBPs may be playing a critical role in both proliferation and differentiation of colonocytes.

Detection of p21ras mutations in colorectal adenomas and carcinomas by enzyme-linked immunosorbent assay.

BACKGROUND: Point mutations of the ras protooncogene, primarily within codons 12 and 13, are commonly identified in colorectal carcinomas and large adenomas. Despite data suggesting that ras genotyping may have clinical significance with respect to colorectal cancer screening and prognosis, more widespread use has been limited because of the lack of a suitable assay system. The principal objective of this study was to assess the feasibility and validity of a qualitative enzyme-linked immunosorbent assay (ELISA) for detecting the four most common ras mutations in human colorectal tumors at the protein (p21ras) level. METHODS: Tissue homogenates (11-121 micrograms) from endoscopically or surgically resected colorectal adenomas, carcinomas, and normal mucosae were evaluated by a commercially available ELISA (Oncogene Science, Inc. Cambridge, MA) for mutant p21ras containing arginine position 12 (arg12), valine position 12 (val12), aspartate position 12 (asp12), and aspartate position 13 (asp13) amino acid substitutions. Portions of the same tissue from an initial series of 27 specimens also were subjected to mutant-enriched polymerase chain reaction (PCR) and/or PCR amplification with subsequent DNA sequence analysis to validate the ELISA data. RESULTS: Forty-seven adenomas, 9 carcinomas, and 14 normal mucosae were assayed. Mutations were identified in 16 (34%) of the adenomas (7-asp12, 7-val12, 2-asp13), 3 (33%) of the carcinomas (1-asp12, 1-arg12, 1-asp13), and none of the normal mucosae by ELISA: Polymerase Chain Reaction and DNA sequencing analyses demonstrated identical results for 21 of the 23 (91%) and 14 of 16 (88%) homogenates tested, respectively. The ELISA demonstrated an overall sensitivity of 80-86%, specificity of 90-92%, positive predictive value of 86-100%, and negative predictive value of 86-91%. CONCLUSIONS: The ELISA is a feasible and valid approach for identifying p21ras mutations in human colorectal adenomas and carcinomas.

Growth and intestinal differentiation are independently regulated in HT29 colon cancer cells.

The polar-planar compound hexamethylene bisacetamide (HMBA) can inhibit HT29 colon carcinoma cell growth and induce a more benign phenotype, as defined by decreased anchorage-independent clonogenicity, loss of a cell surface malignancy marker, and decreased in vivo tumorigenicity. The principle aim of this study was to determine whether HMBA's effects on HT29 cell growth and biologic behavior correlate with effects on intestinal differentiation. Parallel studies were performed with sodium butyrate (NaBT), a potent inducer of intestinal differentiation. HT29 cell growth, proliferation, and markers of intestinal differentiation were assayed after short- and long-term treatment with HMBA, NaBT, or the combination. Both 5 mM HMBA and 5 mM NaBT were potent inhibitors of monolayer growth; in combination their effects were nearly additive. Inhibition of DNA synthesis was detectable within 6 h of treatment and was preceded by down-regulation of c-myc expression. Soft agar clonogenicity was also decreased by 90%, > 99%, and > 99% by HMBA, NaBT, and the combination, respectively. Despite these parallel effects on growth and in vitro markers of a benign phenotype, effects on intestinal differentiation were discordant. NaBT induced significant increases in membrane-associated alkaline phosphatase activity, cytosolic mucin content, PAS+/diastase-resistant cells, and ultrastructural evidence of intestinal cell differentiation. HMBA not only failed to induce markers of intestinal differentiation, but attenuated NaBT's effects when used in combination. These data suggest that growth and intestinal differentiation may be independently regulated in HT29 cells. They also suggest that expression of intestinal markers of differentiation is not a prerequisite for the acquisition of a more benign phenotype.

Human colon cancer cells express ICAM-1 in vivo and support LFA-1-dependent lymphocyte adhesion in vitro.

Intercellular adhesion molecule-1 (ICAM-1) is a cell surface adhesion glycoprotein that mediates leukocyte adhesion through interaction with the leukocyte CD11/CD18 adhesion complex. The aim of this study was to determine whether ICAM-1 is expressed by normal or neoplastic colonic epithelial cells. Immunohistochemical studies on human colonic tissue demonstrated focal ICAM-1 expression by colonic carcinomas but not by normal colonic epithelium. ICAM-1 expression by colonic carcinomas showed a positive correlation with the presence of a peritumoral inflammatory infiltrate. Surface expression of ICAM-1 was also observed in HT-29 cultured human colon cancer cells by both immunohistochemistry and enzyme immunoassay. Interferon-gamma and interleukin-1 beta significantly increased ICAM-1 surface expression by HT-29 cells in a dose-dependent manner. Upregulation of ICAM-1 surface expression became evident some hours after cytokine stimulation and was inhibited by both actinomycin D and cycloheximide, indicating a requirement for de novo RNA and protein synthesis. HT-29 monolayers supported adhesion of human lymphocytes as determined by a quantitative 111In-labeled leukocyte adhesion assay. Adhesion was mediated in part via interaction of ICAM-1 on HT-29 cells with lymphocyte function-associated antigen-1 (CD11a/CD18) on lymphocytes, as defined by using blocking monoclonal antibodies. Expression of ICAM-1 and/or other leukocyte adhesion receptors by neoplastic epithelial cells may play a role in directing leukocyte trafficking and leukocyte-epithelial cell interactions in colonic carcinoma.

Pneumocystis carinii pneumonia complicating somatostatin therapy of Cushing's syndrome in a patient with metastatic pancreatic islet cell carcinoma and Zollinger-Ellison syndrome.

Described is the case of a 73-yr-old woman with metastatic pancreatic islet carcinoma that manifested initially as Zollinger-Ellison syndrome followed by onset of endogenous Cushing's syndrome, who developed Pneumocystis carinii pneumonia while on therapy with a long-acting somatostatin analog. Although P. carinii pneumonia has been observed in patients with Cushing's syndrome associated with other conditions, this is the first reported case in a patient with Zollinger-Ellison syndrome. Heightened awareness of the possibility of opportunistic infections in patients receiving somatostatin therapy for Cushing's syndrome of any cause, particularly Zollinger-Ellison syndrome, may be warranted.

A three-dimensional system for long-term culture of human colorectal adenomas.

Studies of the adenoma-carcinoma sequence in the colon and rectum have been limited by the paucity of experimental models of adenoma growth and progression. Progress recently was reported in the development of monolayer culture systems. The principal objective of this study was to develop a primary culture system for colorectal adenomas that would simulate three-dimensional in vivo growth. We used a calcium alginate encapsulation technique that was previously described for established tumor cell lines. Briefly, fresh resected specimens were washed, minced into small multicellular particles called microadenomas, and encapsulated in 1% calcium alginate pellets. The pellets were maintained in minimum essential medium containing 10% fetal bovine serum at 37 degrees C in humidified atmosphere of 95% air, 5% CO2. Ten of eleven adenomas, including six tubular, three tubulovillous, and one villous have been successfully cultured for 34 to 162 days. Cell viability was confirmed histologically by light and electron microscopy. The cells were characterized as epithelial by morphologic features and ultrastructural studies, which showed a high degree of cellular differentiation, including villous brush borders and many desmosomes. Both tubular and villuslike structures have been observed in vitro, correlating in some cases with the histology of the parent adenoma. Measurements of proliferative activity by [3H]thymidine autoradiography or immunohistochemical staining with the monoclonal antibody Ki-67 demonstrated growth fractions of 9% to 25%. A simple, highly efficient primary culture system was developed for the long-term maintenance of adenomas that promotes three-dimensional growth patterns and growth rates analogous to those seen in vivo. This model provides an opportunity to develop an experimental system for longitudinal studies of pathologic and molecular parameters in adenoma progression to carcinoma.

Effects of FUdR on primary-cultured colon carcinomas metastatic to the liver.

Hepatic arterial infusion of fluorodeoxyuridine (FUdR) has demonstrated efficacy in the treatment of metastatic colorectal carcinoma of the liver. In this study, the direct cytotoxic effect of FUdR was measured on ten metastatic and two primary-site colorectal carcinomas in a primary culture assay system. Overall, clinically achievable concentrations of FUdR (0.4 to 4 microM) induced partial cell kill in 75% of tumors, including a greater than 50% reduction in viable tumor cell number in only two tumors and less than 50% in the remaining seven. Total cell kill was not observed in any tumor. Three tumors were resistant to these FUdR concentrations. Tumor sensitivity correlated with the size of the tumor growth fraction. Increasing the exposure time to FUdR from 3 to 7 days approximately doubled the magnitude of the response. 5-Flurouracil and cisplatin, at clinically achievable concentrations, were more toxic to metastatic tumor cells than FUdR. Because of the limited chemosensitivity of metastatic colorectal tumor cells to FUdR in vitro, we postulate that other mechanisms besides direct cytotoxicity contribute to the clinical efficacy of FUdR in vivo.

Heterogeneous responses of human colon carcinomas to hexamethylene bisacetamide.

Primary cultures of resected human colon carcinoma were used to study differentiation agents directly on the biologically relevant cancer cells rather than on highly selected established cell lines. To achieve primary cultures which remained viable and replicating for several days, carcinomas were partly digested to epithelial organoids, which were selectively plated with high efficiency on collagen I-bovine serum albumin films in specially formulated serum-free medium. A monoclonal antibody, 29-15, was identified which binds to a cell surface epitope expressed on 16 of 21 invasive colon carcinomas of the Dukes' B2, C, or D histopathology classes, but not expressed on any of 11 noninvasive benign tumors (adenomas) at identical antibody titer. Noncytotoxic concentrations of the differentiation agent, hexamethylene bisacetamide (HMBA), induced the loss of the 29-15 epitope from HT29 colon carcinoma cells. HMBA also induced HT29 cells to lose the capacity for anchorage-independent growth with a similar dose-response curve and time course to the loss of 29-15 epitope. Twelve primary cultured human colon carcinomas exhibited differential responses when exposed to 1 to 7 mM HMBA for 7 days. Four moderately to well-differentiated carcinomas lost expression of the 29-15 epitope at each HMBA concentration. The tumor growth fraction was decreased in each tumor, with a mean decrease of 76% at 5 mM HMBA. A dose-dependent induction of nonproliferating tumor colonies, lacking [3H]thymidine labeling, occurred in three of the four carcinomas. In six other tumors, including those at less differentiated stages, HMBA induced the opposite effect: a two- to threefold increase in the tumor growth fraction at the optimal value of 5 mM HMBA, an increase in mean colony size, and no loss of the 29-15 malignancy epitope. No effects were observed in the two other carcinomas tested. Thus HMBA was able to induce growth arrest and loss of the malignancy epitope 29-15 in those carcinomas already at an advanced stage of differentiation, and to exert a growth stimulating effect on those carcinomas apparently at more immature stages.

Video endoscopy by nurse practitioners: a model for colorectal cancer screening.

The use of paramedical personnel to perform sigmoidoscopy as a screening test for colorectal cancer has been advocated as a means of increasing the availability of this test to the population at risk. A model system has been developed utilizing flexible videosigmoidoscopy performed by nurse practitioners with videotape review by physician endoscopists. Of the 100 patients studied, 36 were found to have polyps. Near excellent concordance (k = 0.72) was observed between the nurse practitioner's findings and those of the physician. Using the physician's review as the standard, overall sensitivity and specificity of the nurse practitioner's examinations were 75% and 94%, respectively. In conclusion, videosigmoidoscopy performed by nurse practitioners and reviewed by physician endoscopists is a feasible approach to colorectal cancer screening since it is safe, provides videotape documentation to ensure quality control, and expands available resources for the performance of this examination.

New chemotherapeutic drug sensitivity assay for colon carcinomas in monolayer culture.

Ten previously untreated colon carcinomas were tested for chemotherapeutic drug sensitivity in primary monolayer culture. Colon carcinomas were partly digested to groups of epithelial cells which plated with a mean efficiency of 42 +/- 9% (SE) on a collagen I-bovine serum albumin substrate in serum-free medium, producing patches of tightly adherent epithelial cells. The cultured cells were judged epithelial by the presence of cytokeratins, an epithelial cell surface epitope, junctional complexes, and brush borders. Each carcinoma was plated in 40 to 60 Petri dishes (35 mm), yielding a mean of 28 +/- 8 (SE) colonies per dish (6832 +/- 1952 cells). Drugs tested in duplicate plates were mitomycin C, cisplatin, streptozotocin, and 5-fluorouracil at 0.1, 1, 10, and 100 micrograms/ml, and at 0.1, 1, and 2x the peak tolerated drug concentration in serum. Twenty-four h after plating, any nonadherent cells were removed, and the adherent tumor cells were continuously exposed to the drugs for 3 days. Each drug induced colony lysis in a dose-dependent manner in responsive tumors. Drug-resistant, cycling cells were identified by [3H]thymidine incorporation in colonies which were not lysed by drug treatment. Each of the ten carcinomas exhibited inherent resistance to one or more chemotherapy drugs within the concentration ranges clinically achievable.