Biomedical subjects
G D Steele
Publications and source records attributed to G D Steele.
The National Cancer Data Base. Report on colon cancer.
BACKGROUND: Commission on Cancer data from the National Cancer Data Base (NCDB) report time trends in stage of disease, treatment patterns, and survival for patients with selected cancers. The most current data (1993) for patients with colon cancer are described. METHODS: Five calls for data yielded 3,700,000 cases of cancer for the years 1985 through 1993 from hospital cancer registeries across the U.S., including 36,937 cases of colon cancer from 1988 and 44,812 from 1993. RESULTS: Interesting trends are as follows: (1) the elderly ( > 80 years) present with earlier stage disease than younger patients; (2) the National Cancer Institute recognized cancer centers have more patients with advanced disease than other types of hospitals; (3) all ethnic groups have generally similar stages of disease at presentation, except for African-Americans who have a slightly higher incidence of Stage IV disease; (4) the proximal migration of the primary cancer continues with 54.7% of primary colon cancer arising in the right colon in 1993 compared with 50.9% in 1988; (5) an interaction between grade and stage of cancer seems present; and (6) patients with Stage III colon cancer who received adjuvant chemotherapy had a 5% improvement in 5-year relative survival. CONCLUSIONS: The NCDB data are useful for reporting what cancer treatments are being administered and what outcomes are occurring in the U.S. The data suggest an important biologic role for grade of cancer. They also suggest that African-Americans and other ethnic groups have the same outcome as non-Hispanic whites but that access to medical care may still be less. Finally, the utility of adjuvant therapy for Stage III colon cancer may just be beginning to be appreciated.
Wound recurrence following laparoscopic colon cancer resection. Results of the American Society of Colon and Rectal Surgeons Laparoscopic Registry.
INTRODUCTION: Multiple case reports have suggested that laparoscopic resection of colon cancer may alter the pattern or incidence of cancer recurrence. All reports lack a significant denominator to evaluate the incidence of surgical wound recurrence. We hypothesized that wound recurrence incidence is not increased by laparoscopic resection of colon cancer. METHODS: A prospective registry was initiated under the auspices of The American Society of colon and Rectal Surgeons, American College of Surgeons, and Society of American Gastrointestinal Endoscopic Surgeons in 1992. Patients having laparoscopic colon resection were voluntarily entered and followed until June 1995. Recurrences were evaluated by the primary surgeon and reported to the registry. RESULTS: A total of 504 patients treated for cancer were identified in the registry. A minimum follow-up of one year was obtained for 480 of 493 evaluable patients (97.4 percent). Wound recurrence was identified in five patients (1.1 percent). Recurrence status was unknown in 18 patients (3.8 percent). CONCLUSION: Wound recurrence rates appear to be low. Although length of follow-up is limited, patterns of recurrence from previous studies suggest that 80 percent of recurrences should have occurred within one year. Given the limitations of a Phase II study, the hypothesis that recurrence rate is low is supported. However, prospective randomized trials are needed to establish if any difference in wound recurrence rates after laparoscopic or open resection of colorectal cancer exists.
Ubiquitin fusion proteins are overexpressed in colon cancer but not in gastric cancer.
A cDNA clone (AF3) encoding the ubiquitin A gene 52 amino acid extension fusion protein (UbA52) was isolated from a subtracted cDNA library of human colorectal carcinoma minus adjacent normal mucosa. In Northern hybridization the mRNA signal for UbA52 was greater in surgical samples of colonic carcinoma (T) than in paired adjacent normal (N) tissues in 24 of 29 cases (T/N = 3.4 +/- 0.5, P < 0.01). An oligonucleotide probe specific for only the 52 amino acid extension confirmed the overexpression of UbA52. In contrast, there was no overexpression of UbA52 mRNA in gastric cancer samples (n = 7, T/N = 1.0 +/- 0.3). The mRNA of several ribosomal proteins, and of another ubiquitin A gene fusion protein, UbA80, with an 80 amino acid extension of ribosomal protein S27a, have been reported to be over-expressed in colon cancer, but not as yet at the protein level. Using rabbit antisera to the ribosomal protein component S27a we demonstrate over-expression of S27a at the protein level in colonic (n = 5), but not gastric (n = 6) carcinomas. Therefore it is likely that both UbA80 and UbA52 are overexpressed in colon cancer, but not in gastric cancer.
The National Cancer Data Base report on gastric cancer.
BACKGROUND: Previous Commission on Cancer studies from the National Cancer Data Base (NCDB) have examined time trends in stage of disease, treatment patterns, and survival for selected cancers. The most current (1991) data for gastric cancer are described here. METHODS: Three Calls for Data have yielded a total of 16,992 case reports of gastric cancer for 1985, 1986, and 1991, from hospital cancer registries across the U.S. RESULTS: Gastric cancer was the 15th most frequent cancer reported to the NCDB. The proportion of all reported cancers that were gastric in the two time intervals studied were essentially the same. In 1991, 20.8% of the cases were reported in minorities. Only 46% of gastric cancer cases were staged by the American Joint Committee on Cancer (AJCC) system in 1985 to 86, compared with 77% in 1991. More advanced stages were reported for younger patients, but less advanced stages were noted in the Asian population. Of all patients reported, 41.4% had no reported cancer-directed surgery, 41.1% had partial or hemigastrectomy, and 6.7% had total gastrectomy. More extensive surgery was associated with patients with Stage III disease than with Stages I and II, as might be expected. Survival after treatment remained poor (5-year relative survival; 43% for Stage I, 37% for Stage II, 18% for Stage III, and 20% for Stage IV). CONCLUSION: Improvements in treatment will emerge allowing survival to serve as a better guide for the quality of care in the future. In the interim, the frequency of American Joint Committee on Cancer staging in patient charts and the fraction of patients with Stages I and II as opposed to Stages III and IV disease (as a measure of prompt diagnosis) may serve as measure of how quickly these cancers are being diagnosed.
Effect of membrane free fatty acid alterations on the adhesion of human colorectal carcinoma cells to liver macrophages and extracellular matrix proteins.
Epidemiologic studies have linked diets high in animal fat with colon carcinogenesis. A number of animal tumor models have shown that diets rich in omega-3 fatty acids inhibit colon carcinogenesis while diets rich in omega-6 fatty acids promote tumor growth. This study examines whether modification of the membrane fatty acid composition of both moderately (CX-1) and poorly differentiated (MIP-101 and Clone A) human colorectal carcinoma cells alters their interaction with Kupffer cells and extracellular matrix proteins (collagen type IV, fibronectin and laminin). The cells were treated with 15-16 micrograms/ml of docosahexanoic acid (22:6, omega 3) or linoleic acid (18:2,omega 6). Gas chromatography showed significant alterations in the membrane fatty acid composition of the human colorectal cancer cell lines. Binding assays were performed by measuring adherence of 51Cr-labelled tumor cells to Kupffer cell monolayers or to immobilized proteins. Omega-3 treatment significantly decreased the Kupffer cell binding of only the CX-1 line while omega-6 treatment decreased binding of all three cell lines. In contrast both omega-3 and omega-6 treatment of MIP-101 cells decreased binding to the extracellular matrix proteins with the omega-6 effect being more pronounced. These results indicate that the binding characteristics of the colon cancer cells to both Kupffer cells and extracellular matrix proteins may be determined in part by the membrane fatty acid composition. Decreased adherence to extracellular matrix proteins may lead to increased cell motility and invasiveness. Since Kupffer cell binding precedes tumor cell phagocytosis and killing, decreased binding may improve tumor cell survival.
Laparoscopic Bowel Surgery Registry. Preliminary results.
UNLABELLED: Laparoscopic surgery has evolved rapidly since 1989. The American Society of Colon and Rectal Surgeons, the Society of American Gastrointestinal Endoscopic Surgeons, and the American College of Surgeons Commission on Cancer jointly sponsored a registry to identify as early as possible the patterns of practice and acute complications of laparoscopic colectomy. METHODS: Cases were voluntarily registered by community and academic surgeons. Information was entered in the EPI-5 database. RESULTS: One thousand fifty-six cases were contributed by 118 surgeons; 763 patients were completed laparoscopically. The most common indication for surgery was cancer in 453 patients. The right colon (n = 364) and sigmoid (n = 294) were most frequently resected. Respondents felt adequate cancer resections were performed. Although several unique complications were noted, intraoperative complications were similar in type and frequency to open cases. CONCLUSION: Laparoscopic colorectal surgery can be performed with acceptable complications. It remains unclear if this approach is adequate for long-term management of colon and rectal cancer.
Management and survival of patients with adenocarcinoma of the colon and rectum: a national survey of the Commission on Cancer.
BACKGROUND: The Commission on Cancer (COC) of The American College of Surgeons periodically reviews criteria for evaluation of the care of patients with cancer related to diagnosis, treatment, rehabilitation, and follow-up. The COC annually performs a national survey of practices for several cancer sites. STUDY DESIGN: Data collection forms for carcinoma of the colon and rectum were field-tested and then forwarded to participating hospitals. The study included a long-term survey to permit evaluation of five-year survival rates and a short-term survey to review current practices and time trends. Specific questions were asked concerning disease presentation, preoperative evaluation, surgical treatment, postoperative care, use of adjuvant therapy, and disease status at the last follow-up examination. RESULTS: A total of 39,502 reports from 943 hospitals were analyzed, including 12,682 patients with carcinoma of the colon diagnosed in 1983, 16,527 patients with carcinoma of the colon diagnosed in 1988, 4,597 patients with carcinoma of the rectum diagnosed in 1983; and 5,696 patients with carcinoma of the rectum diagnosed in 1988. Patterns of care, including changes in presentation, diagnostic and therapeutic management, and survival rates, are presented. Specific data showing results for various ethnic groups are also included. CONCLUSIONS: The distribution of cases by anatomic site was consistent with a hypothesis of rightward migration of colon carcinoma. Colon and rectal carcinomas in African-Americans were reported in more advanced stages and with corresponding decreases in survival rates. Some patterns of nonoptimal diagnostic use were noted. The increasing use of sphincter-sparing surgical alternatives for carcinoma of the rectum was evident. Adjuvant therapy was not widely used during this period. This study suggests evolving patterns of evaluation, increased preservation of continence, and improved but varying survival among ethnic groups. It further suggests that survival as measured across these 943 hospitals may be lower than that attained at some individual centers.
Biopsy of lesions of the colon, rectum, and anus.
Most lesions of the colon, rectum, and anus can be biopsied only by using an endoscopic device. Adequate patient and bowel preparation, close communication with the pathologist, and meticulous handling and documentation of the specimen are required to ensure an accurate histologic diagnosis. Although somewhat controversial, most investigators agree that all but the smallest neoplasms of the colon and rectum should be excisionally biopsied when possible, incisionally biopsied when excision is not feasible, and destroyed if they are multiple, small, and not suspected of malignancy. Future studies will focus on the cellular biologic characteristics of the biopsy specimen to define more accurately the appropriate treatment plan and prognosis for patients.
The National Cancer Data Base report on colorectal cancer.
BACKGROUND: Previous Commission on Cancer studies have examined time trends in stage of disease, treatment patterns, and survival for colorectal cancer. Reported herein are the most current 1993 National Cancer Data Base (NCDB) data on colorectal cancer. METHODS: Two "calls for data," one in 1990 and one in 1991, have yielded a total of 71,560 colon cancer reports and 33,409 rectal cancer reports from hospital registries across the country. RESULTS: For colon cancer, continuation of the time trend toward proximal migration was reported. For both colon and rectal cancer, American Joint Committee on Cancer staging was used increasingly as the standard of appropriate cancer diagnosis. Increased use of multimodal treatment was reported for both colon and rectal cancers. African-American and non-Hispanic white, low-income patients were reported to have later stages of both colon and rectal cancers. CONCLUSIONS: The NCDB provides a useful longitudinal perspective on the diagnosis and treatment of colon and rectal cancers.
Human ribosomal protein L37 has motifs predicting serine/threonine phosphorylation and a zinc-finger domain.
Ribosomal protein L37 mRNA is overexpressed in colon cancer. The nucleotide sequences of human L37 from several tumor and normal, colon and liver cDNA sources were determined to be identical. L37 mRNA was approximately 375 nucleotides long encoding 97 amino acids with M(r) = 11,070, pI = 12.6, multiple potential serine/threonine phosphorylation sites and a zinc-finger domain. The human sequence is compared to other species.
The National Cancer Data Base. A mechanism for assessment of patient care.
BACKGROUND: A mechanism for cancer patient care assessment was created. Data evaluations will enable clinicians and hospital staffs to appraise trends and compare their results with state, regional, and national figures. METHODS: Data are collected annually on all forms of cancer from all parts of the country, including patient characteristics, tumor characteristics, first-course treatment, and follow-up. RESULTS: Data for one or more years were received from a total of 1071 hospitals. This large, convenience sample of United States cancers included approximately 220,000 cases from 1985, 272,000 cases from 1988, and 409,000 cases from 1990. The seven most commonly reported cancers were breast, lung, prostate, colon, cervix, bladder, and rectum. In a 1993 National Cancer Data Base (NCDB) Annual Review, several disease categories and special subjects were analyzed, including colorectal, breast, and prostate cancer, melanoma, cancer in children and adolescents, cancer in hispanics, time trends in TNM staging, as well as NCDB data quality and hospital participation. CONCLUSIONS: A multipurpose partnership between the NCDB and the Cancer Liaison Physician Network of the Commission on Cancer will be formed at the state and local level to promote NCDB participation as well as to disseminate the NCDB clinical findings. Additional sites will be covered in Annual Reviews, and highlights of those reports will be provided to Liaison Physicians of the Commission who are actively involved in the care of cancer patients to inform them of the latest findings.
Intraoperative ultrasound imaging of the liver at the time of colorectal cancer resection.
OBJECTIVES: To evaluate the accuracy of intraoperative ultrasound (IOUS) liver imaging at the time of primary colorectal cancer resection, which might eliminate incurable patients from adjuvant chemotherapy trials or permit earlier resection of curable metastases. DESIGN: A prospective trial of routine IOUS liver imaging during resections of primary colorectal cancer. The rate of detection of occult metastases by IOUS imaging alone and the false-negative rate over 22.7 months of follow-up were determined. SETTING: A tertiary care referral center in Boston, Mass. PATIENTS: Fifty-five patients undergoing 56 operations for colorectal carcinoma between May 1990 and June 1992. MAIN OUTCOME MEASURES: The rate of detection, by IOUS imaging alone, of otherwise occult hepatic metastases, the total number of patients with metastases detected at any time during follow-up, and the rate of false-negative findings on IOUS imaging and direct examination. RESULTS: Occult hepatic metastases were detected by IOUS imaging alone in 5% of patients. Restriction of IOUS imaging to patients with T3 or T4 lesions or recurrent cancers would have identified all metastases and increased the detection rate to 10%. Occult metastases were detected by IOUS imaging alone in 12.5% of patients with T3, N0 lesions. The rate of false-negative findings on IOUS imaging was 13% overall, 0% for patients with T1 or T2 lesions, 3% for patients with node-negative findings, and 7% for patients with T3, N0 lesions. CONCLUSIONS: The small increment in the detection of occult metastases by IOUS liver imaging does not warrant its use in all patients with colorectal cancer. Selective use in patients with T3 or T4 lesions or recurrent cancers increased the incremental gain in detection. The observed frequency of occult metastases in patients with T3, N0 lesions is sufficient to impact on results of adjuvant chemotherapy trials. Longer follow-up in more patients is needed to determine whether a negative IOUS study is an additional favorable prognosticator in patients with T1 and T2 lesions and node-negative findings.
Role of staging laparoscopy in the treatment of hepatic malignancy.
Despite current radiologic imaging capabilities, 40% to 70% of patients with primary or metastatic hepatic malignancies are found to have unresectable disease at the time of laparotomy. The present study evaluates the use of laparoscopy in the staging of hepatic malignancy. Twenty-nine patients underwent staging laparoscopy prior to a planned laparotomy for resection of a hepatic malignancy that was deemed resectable by computed axial tomographic scan and ultrasonography. Twelve patients had primary hepatic malignancies, and 17 had metastatic malignancies. Laparoscopy demonstrated evidence of unresectability in 48% (14 of 29) of patients studied. Four patients had unsuspected cirrhosis, and 10 had unresectable or extrahepatic metastatic disease. Patients who underwent laparoscopy alone had shorter mean hospital lengths of stay than historical controls who underwent laparotomy alone. We conclude that diagnostic laparoscopy should precede laparotomy for planned resection of hepatic malignancies.
The impact of intraoperative ultrasonography on surgery for liver neoplasms.
To analyze the effect of IOUS on surgical decision making, we performed a retrospective study of 45 patients who had exploratory laparotomy and IOUS for liver neoplasms. Preoperative lesion detection was compared with intraoperative findings. The effect of IOUS on the choice of surgical procedure was analyzed. Preoperative imaging detected 67% of lesions, 78% when combined with surgical inspection and palpation, and 97% were recognized by IOUS. Surgery was modified in 23 of 45 cases (51%); 19 of those 23 cases (83%) were based on IOUS findings alone. IOUS demonstrated superior lesion detection over noninvasive preoperative liver imaging, and IOUS significantly affected surgical decision making.
Localization of tumor-associated glycoprotein DF3 in normal, inflammatory, and neoplastic lesions of the colon.
BACKGROUND: The expression of DF3 was assessed by a monoclonal antibody in normal, inflammatory, and neoplastic conditions in the large bowel. METHODS: Using immunohistochemistry, expression was examined in formalin-fixed paraffin-embedded biopsy and resection samples of 19 normal colonic mucosal specimens, 49 inflammatory lesions, 34 adenomas, and 38 primary colonic adenocarcinomas. In addition, Western blots of normal colonic mucosa and adenocarcinoma were examined. RESULTS: DF3 expression was detected in 84% of the adenocarcinomas with coarse membrane staining, intense positivity of luminal secretions, and focal cytoplasmic and intracytoplasmic vacuole staining. Nine of 32 areas of transitional mucosa revealed reactivity along apical membranes in crypt cells. Five adenomas containing carcinoma revealed DF3 positivity in the malignant areas only, whereas the remaining 29 were negative. Staining was membrane, luminal, and intracytoplasmic. Two examples of active ulcerative colitis revealed focal reactivity along the apical membrane of crypt cells. No other areas of staining were noted, including 12 cases containing dysplasia. Four of 10 other inflammatory lesions also revealed similar membrane reactivity in crypt cells. Normal colonic mucosa was nonreactive. Examples of normal colonic mucosa were negative for DF3 by Western blot analysis, whereas two carcinoma samples that reacted immunohistochemically were positive. CONCLUSIONS: DF3 is not detectable in normal colonic tissues. It is expressed focally and predominantly along the apical membrane of crypt cells in some inflammatory lesions and in the transitional mucosa of primary adenocarcinomas. Most adenocarcinomas of the colon and adenomas with foci of invasive carcinoma demonstrate reactivity in the cytoplasm and luminal secretions.
Preoperative and postoperative combination chemotherapy for potentially resectable gastric carcinoma.
BACKGROUND: Median survival of patients with local-regional gastric carcinoma is 10 months. Resection of the primary tumor and regional lymph nodes, with tumor-free margins (curative resection), has been the most effective treatment for local-regional gastric carcinoma. However, median survival of patients with curative resection of gastric carcinoma is 24 months, and the 5-year survival rate is about 20%. A single institution pilot study has established the feasibility of administering two courses of chemotherapy preoperatively and three courses postoperatively. In another study, a 15% pathologically documented complete response (pathologic complete response) has been reported in unresectable gastric carcinoma treated with etoposide, doxorubicin, and cisplatin. PURPOSE: Our purpose was to increase the curative resection rate in potentially resectable gastric carcinoma and to delay or eliminate micrometastases and thus improve survival. We also evaluated clinical and pathologic response to chemotherapy. METHODS: Forty-eight previously untreated patients with potentially resectable gastric carcinoma received a chemotherapy regimen (EAP) consisting of etoposide (120 mg/m2 intravenously over a 2-hour period on days 4, 5, and 6), doxorubicin (20 mg/m2 as a 10-minute intravenous infusion on days 1 and 7), and cisplatin (40 mg/m2 as a 1-hour intravenous infusion on days 2 and 8). Patients received three courses of chemotherapy before resection, and responding patients received two courses postoperatively. Clinical and pathologic response rates, toxicity, patterns of treatment failure, and survival times were assessed. RESULTS: A median of three courses (range, 1-5) of preoperative therapy was administered; six (12%) of the 48 patients had clinical complete response, and nine (19%) had partial response. Forty-one (85%) underwent surgery; 37 (90%) of these 41 (77% of the 48 patients) had a curative resection. There were no pathologic complete responses. Median survival for all patients is 15.5 months (range, 2-29+ months). Therapy was discontinued because of the toxic effects in one patient before surgery and in six patients after surgery. Doses were reduced in 37 patients (77%), mainly because of hematologic toxicity. Nineteen (40%) were hospitalized because of toxic effects, including 15 patients who developed fever with neutropenia. Grade 3 or 4 nausea and vomiting occurred in 15 patients and grade 3 or 4 diarrhea in seven patients. One death was directly related to chemotherapy. CONCLUSIONS: These data support that administration of preoperative and postoperative chemotherapy for local-regional gastric carcinoma is feasible in a multi-institutional setting. Our findings demonstrate that this EAP regimen is modestly active but is associated with substantial toxicity. IMPLICATIONS: Use of preoperative chemotherapy in resectable gastric carcinoma merits further evaluation, but more effective drug regimens will be required before a controlled trial is initiated.
Nucleotide and deduced amino acid sequence of human ribosomal protein L18.
Ribosomal protein L18 mRNA is overexpressed in human colorectal cancer compared to normal colon tissue. We report the nucleotide sequence of human L18 cDNA derived from a normal colon source. There were no mutational changes in segments of L18 cDNA derived from two tumor sources. The L18 cDNA was 690 base pairs long and predicts a single open reading frame of 564 nucleotides, encoding 188 amino acids with a M(r) = 21,621, it is homologous to rat L18 and Xenopus laevis L14.