Sphincter-sparing treatment for distal rectal adenocarcinoma.

BACKGROUND: Studies suggest that the anal sphincter can be preserved in some patients with distal rectal adenocarcinoma (DRA), but this has not been validated in any prospective multi-institutional trial. METHODS: To test the hypothesis that the anal sphincter can be preserved in some patients with DRA, the Cancer and Leukemia Group B and collaborators reviewed 177 patients who had T1/T2 adenocarcinomas < or = 4 cm in diameter, which encompassed < or = 40% of bowel wall circumference, and were < or = 10 cm from the dentate line. Of the 177 patients, 59 patients who were eligible for the study had T1 adenocarcinomas and received no further treatment; 51 eligible T2 patients received external beam irradiation (5400 cGY/30 fractions 5 days/week) and 5-fluorouracil (500 mg/m2 IV d1-3, d29-31) after local excision. RESULTS: At 48 months median follow-up, 6-year survival and failure-free survival rates of the eligible patients are 85% and 78% respectively. Three patients died of unrelated disease. Two patients were treated for second primary colorectal tumors; both remain disease free (NED). Another eight patients died of disease, four with distant recurrence only. One T1 patient is alive with distant disease. Two T1 and seven T2 patients experienced isolated local recurrences; all underwent salvage abdominoperineal resection (APR). After APR, one T1 and four of seven T2 patients were NED at the time of last visit (2-7 years). One T1 patient died of local and distant disease. Three of seven T2 patients died with distant disease. CONCLUSIONS: We conclude that sphincter preservation can be achieved with excellent cancer control without initial sacrifice of anal function in most patients. After local recurrence, salvage resection appears effective, but longer follow-up time of local and distant disease-free survival is advised before extrapolation to patients with T3 primaries.

Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome.

OBJECTIVE: To update the analysis of technical and biologic factors related to hepatic resection for colorectal metastasis in a large single-institution series to identify important prognostic indicators and patterns of failure. SUMMARY BACKGROUND DATA: Surgical therapy for colorectal carcinoma metastatic to the liver is the only potentially curable treatment. Careful patient selection of those with resectable liver-only metastatic disease is crucial to the success of surgical therapy. METHODS: Two hundred forty-four consecutive patients undergoing curative hepatic resection for metastatic colorectal carcinoma were analyzed retrospectively. Variables examined included sex, stage of primary lesion, size of liver lesion(s), number of lesions, disease-free interval, ploidy, differentiation, preoperative carcinoembryonic antigen level, and operative factors such as resection margin, use of cryotherapy, intraoperative ultrasound, and blood loss. RESULTS: Surgical margin, number of lesions, and carcinoembryonic antigen (CEA) levels significantly control prognosis. Patients with only one or two liver lesions, a 1-cm surgical margin, and low CEA levels have a 5-year disease-free survival rate of more than 30%. Disease-free interval, original stage, bilobar involvement, size of metastasis, differentiation, and ploidy were not significant predictors of recurrence. The pattern of failure correlates with surgical margin. Routine use of intraoperative ultrasound resulted in an increased incidence of negative surgical margin during the period examined. CONCLUSIONS: Surgical resection or cryotherapy of hepatic metastasis from colorectal cancer is safe and curable in appropriately selected patients. Biologic factors, such as number of lesions and carcinoembryonic antigen levels, determine potential curability, and surgical margin governs the patterns of failure and outcome in potentially curable patients. Optimization of selection criteria and surgical resection margins will improve outcome.

Evaluation of common breast problems: guidance for primary care providers.

The evaluation of common breast problems requires an assessment of the patient's risks and symptoms and a thorough physical examination. When indicated, appropriate imaging studies should be done, the patient should be referred to a surgeon or a breast specialist, and operative interventions should be used.

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.

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.

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.

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.

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.

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.

Clinical highlights from the National Cancer Data Base: 1995.

The National Cancer Data Base, a joint project of the American Cancer Society and the American College of Surgeons Commission on Cancer, provides a mechanism for periodic assessment of hospital-based cancer patient care. From the National Cancer Data Base's annual summary, health care professionals can evaluate trends in patient care to make more efficient treatment decisions. This article provides a first look at highlights of the 1995 annual summary.

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.

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.

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.

Clinical highlights from the National Cancer Data Base: 1994.

The National Cancer Data Base, a joint project of the American Cancer Society and the American College of Surgeons Commission on Cancer, provides a mechanism for periodic assessment of hospital-based cancer patient care. From the National Cancer Data Base's annual summary, health care professionals can evaluate trends in patient care to make more efficient treatment decisions. This article provides a first look at highlights from the 1994 annual summary.

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.