Evaluation of new occult blood tests for detection of colorectal neoplasia.

BACKGROUND: Hemoccult II, the guaiac-based fecal occult blood test used in most colorectal cancer screening programs, has an unsatisfactory sensitivity for asymptomatic colorectal neoplasms. We evaluated the relative performance of four fecal occult blood tests, directed against various components of the hemoglobin molecule. METHODS: All tests, Hemoccult II, HemoccultSENSA (a more sensitive guaiac test), HemeSelect (an immunochemical test specific for human hemoglobin), and HemoQuant (the heme-porphyrin assay), were performed by 107 patients with symptomatic colorectal cancer and 81 patients with predominantly asymptomatic adenoma. Hemoccult-SENSA and HemeSelect were performed by 1,355 screenees. RESULTS: HemeSelect and Hemoccult-SENSA had significantly higher sensitivity for colorectal cancer (97% and 94%, respectively) than the other tests. HemeSelect had the highest sensitivity for adenomas; in 45 patients with large (> or = 10 mm) adenomas, sensitivity was 76% for HemeSelect, 60% for HemoccultSENSA, and 42% for both Hemoccult and HemoQuant. In the screenees, estimated specificity was 97.8% for HemeSelect and 96.1% for Hemoccult-SENSA. CONCLUSIONS: HemeSelect and Hemoccult-SENSA have the highest levels of sensitivity for detection of colorectal neoplasia, but the immunochemical test HemeSelect provides the best combination of specificity and sensitivity.

A comparison between single and double dose intravenous Timentin for the prophylaxis of wound infection in elective colorectal surgery.

A prospective, randomized, single-blind, controlled clinical trial was undertaken to determine whether two doses of systemic Timentin provided superior prophylaxis against postoperative sepsis in elective colorectal surgery compared with a single dose of the same antibiotic. Timentin, a combination of ticarcillin and clavulanic acid was administered intravenously (3.1 g) at the commencement of operation to all patients, and this was repeated after 2 hours in those patients randomized to receive a second dose. The wound infection rate was 11 percent in the 143 patients completing follow-up and receiving a single dose, and 13 percent in the 128 patients receiving two doses of Timentin (P greater than 0.05). The rates of postoperative septicemia 3 vs. 4 percent and intra-abdominal abscess 5 vs. 8 percent were similar. Multivariate analysis of the factors likely to affect postoperative would infection rate demonstrated an association with the type of hospital, public or private, wound infection rate 16 and 6 percent, respectively (P less than 0.01), and the surgeon group defined by the number of patients contributed greater than 25 or less than 25, wound infection rate 6 and 18 percent, respectively (P less than 0.05). We concluded that a single dose of intravenous Timentin was as effective as two doses for prophylaxis against surgical infection and that the surgeon group and the hospital in which the operation took place were statistically significant predictors of postoperative wound infection.

Sessile adenomas of the rectum: a personal series 1974-1984.

Sessile (villous) tumours of the rectum are uncommon and individual surgeons are unlikely to have wide experience in their management. A study was made of a unique personal series (AMC) of 104 cases encountered from 1974 to 1984; minimum duration of follow-up was 5 years. Clinically obvious rectal cancers were excluded from the study. Ages ranged from 42 to 89 years (mean 64.9 years) with a male:female ratio of 1.5:1. The commonest clinical presentations of sessile tumours of the rectum were rectal bleeding (45%) and altered bowel habit (38%). Hypokalaemia was a very uncommon presenting symptom (1%). These tumours ranged in longitudinal diameter from 1 to 9 cm, with 66% of cases greater than 3 cm and 33% of cases greater than 5 cm. The incidence of malignancy in sessile adenomas greater than 3 cm (27%) was more than triple that of adenomas less than 3 cm (8%) and the presence of induration on rectal examination was the most reliable clinical indicator of the presence of malignancy. Local transanal diathermy excision was a satisfactory form of treatment for most sessile tumours of the rectum (benign and malignant); especially if they were less than 3 cm (0% recurrence rate). It had the added advantage of preserving the anal sphincter and was possible in a higher proportion of sessile tumours in the lower half of the rectum (89%) than those in the upper half of the rectum (42%). The overall recurrence rate after local transanal excision was 8% for benign sessile adenomas and 33% for those containing invasive carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiosarcoma of the colon. Report of a case with long-term survival.

A case of angiosarcoma of the large bowel is presented. The tumor occurred in a 16-year-old girl who presented with lower abdominal pain and rectal bleeding. A sigmoid colectomy was performed. Although macroscopic omental and pelvic peritoneal metastases were noted at operation, she did not receive adjuvant therapy and was alive and well more than three years after surgery. The literature on colonic angiosarcoma is also reviewed.

Impact of a hospital-based register on the management of familial adenomatous polyposis.

Colorectal cancer in familial adenomatous polyposis is a preventable disease in at-risk relatives of patients with primary cases. Until the recent establishment of a register in Western Australia, there has been no registration of pedigrees or central organization of surveillance in Australia. In the present study, the experience of 20 such families who were associated with The Royal Melbourne Hospital was documented, with an analysis of the reasons for any failure of management. The impact of a hospital-based register on the management of the disease was studied. In each family, results were categorized according to whether "at-risk" relatives had been diagnosed at surveillance examinations, and whether the Hospital register were involved. Before involvement with the register, 24 family members presented with symptomatic polyposis after the first affected case had been diagnosed. Eighteen of these had colorectal cancer at diagnosis, and 16 subjects now are dead. Identifiable reasons for the failure of surveillance were family communication failure (two cases), family denial (two cases), failure of the hospital clinic (two cases) and a failure to cover extended branches of families who were living locally (nine cases), interstate (four cases) or overseas (three cases). In contrast, only two (6%) of 33 affected cases that were identified at a planned surveillance endoscopy had colorectal cancer at diagnosis. Without the active surveillance of at-risk family members, lethal delays in diagnosis are likely to occur. Most reasons for failure potentially are correctable by a dedicated registry that is responsible for notifying clinicians and patients about the timing of surveillance procedures.

Phase I clinical trial of drug-monoclonal antibody conjugates in patients with advanced colorectal carcinoma: a preliminary report.

Melphalan (MEL), an alkylating agent, has been modified to a derivative, N-acetylmelphalan (N-AcMEL), which can be conjugated to anticolon cancer monoclonal antibodies (MoAbs 30.6, I-1, and JGT) and used for immunochemotherapy. The final immunoconjugates possess potent cytotoxicity and specificity in preclinical studies. In a phase I clinical study, N-AcMEL-MoAb conjugates were administered via the hepatic artery to 10 patients, nine of whom had disseminated colorectal cancer (including the liver) and one of whom had Dukes' C colon cancer that had been resected. The selection of MoAb was based on the immunoperoxidase staining of the primary colon cancer tissue. Thus far doses of 1000 mg/m2 MoAb conjugated to 20 mg/m2 of N-AcMEL have been administered with no significant side effects, whereas MEL unconjugated to monoclonal antibodies would have caused myelosuppression in a proportion of patients at the same dosage. Serum antimouse antibody responses were noted in all of the patients; febrile reactions were noted with higher doses but were easily controlled with antipyretics, antihistamines and, if necessary, steroids. Serum sickness developed in one patient who was given a second course of treatment in the presence of human antimouse antibody, but the episode was self-limiting. Eight of the 10 patients had evaluable disease. Subjective improvement was noted in almost all of the patients examined, and 33%, or 3 of 9, of the treatments (nine courses of treatment in eight patients with evaluable disease; one of the patients had two courses of treatment) led to antitumor responses (minor response) by objective assessment with computed tomography of the liver. It is important to note that treatment with N-AcMEL-MoAb conjugates was safe at a dose of 20 mg/m2 of N-AcMEL, whereas the efficacy of such a form of treatment remains to be determined.

An abdominal repair for complete rectal prolapse.

A modified sling rectopexy to the sacrum was performed in a series of 104 patients with complete rectal prolapse during 1975-86. A sling of mersilene mesh was sutured to the front of the sacrum and to the sides of the rectum without enclosing its anterior surface. A postoperative mortality of 2% and morbidity of 23% were found. Control of the prolapse was achieved in over 90% of cases and the continence rate rose from a preoperative level of 37% to 86% postoperatively. This form of abdominal repair is an effective method of correcting complete rectal prolapse in the majority of cases.

Curative local excision of rectal adenocarcinoma.

The records of all 28 patients with rectal adenocarcinoma treated by potentially curative local excision by one surgeon (A.M.C.) between 1970 and 1984 were reviewed. Patient age, sex, tumour size, site, degree of differentiation and level of invasion are reported. The procedure was associated with no mortality and minimal morbidity. Twenty-two patients, followed for an average of 51 months, have either died of other causes or remain free of recurrent or disseminated malignancy. Six patients have required further surgery for local recurrence. Of these, one patient has had a repeat local excision while the remaining five patients have had an abdominoperineal excision of the rectum. All six patients, followed since the second operation for an average of 50 months, are free of further recurrent or disseminated disease. The results reported in this review suggest that in a selected group of patients with rectal adenocarcinoma curative local excision may offer a safe alternative to more radical forms of surgery.

Metastatic 'early' colorectal cancer.

If colorectal carcinomas where the primary tumours are confined to the wall are considered 'early', the likelihood of lymph node metastasis in these tumours is 21% and for those that do not extend beyond the submucosa it is 13%. Because of the renewed interest in local treatment of small accessible rectal tumours and the use of colonoscopy for the removal of 'polyps' with invasive carcinoma, we analysed our long-term cancer survival figures for 'early' cancers in this combined surgical series spanning more than 30 years. The presence of regional lymph node metastasis in 'early' rectal cancer was associated with a significantly (P = 0.001) reduced proportion of long-term survivors (56%) compared to those without nodal involvement (79%). Long term survival in 'early' colonic cancer was less influenced (P less than 0.05) by whether lymph node metastasis was present (73%) or not (77%). The authors conclude that until more information is available with regard to the risk of lymph node spread from 'early' tumours, resection is advised for all invasive tumours of the colon in good risk patients, but the indications for local excision of 'early' rectal cancers can be extended in view of the ease of careful follow-up and the use of salvage procedures in those with recurrence.

Antibody-dependent cellular cytotoxicity (ADCC) in colorectal carcinoma. I. Favorable prognosis in female patients.

In an immunological study of 288 colorectal carcinoma patients, we investigated the relationship between survival and preoperative in vitro antibody-dependent cellular cytotoxicity (ADCC) against the colonic carcinoma cell line HT-29. A highly significantly favorable (p = 0.001) association was found in the 20 female patients with ADCC. Nearly all (97%) of the 66 patients with ADCC were blood group O, but blood group per se did not relate to survival, nor could staging explain the survival association with ADCC. The mechanism whereby ADCC or its in vivo expression confers a survival advantage is unknown but we suggest that it derives from immunoreactivity against blood group A antigens produced inappropriately in the carcinomatous epithelium of the group O and B patients.

Immunoglobulins intrinsic to colorectal carcinoma: an unfavorable prognostic association with IgM.

Immunoglobulin (Ig) eluates prepared from cell membrane fractions of 50 colorectal carcinomas were found to contain significantly (P less than .001) less IgA and IgM and marginally less IgG than normal colon mucosa. IgA and IgG were present in all tumors, but IgM was present in only 20 of 50 tumors (40%). Small (less than or equal to the median vol) tumors contained significantly (P less than .05) more IgA and IgG per gram tissue than did large tumors. Tumors with a large (greater than the median) proportion of stroma contained more IgG than did those with less stroma. No associations were found between Ig and amount of viable-appearing tumor tissue, necrosis, mucin production, and staging. Patients whose tumors contained measurable amounts of IgM had a significantly (P = .012) shorter survival than did patients without intrinsic IgM (12 and 27 mo at the 75th percentile, respectively). The difference could not be explained by conventional staging.

Lymphocyte fluorescence polarization changes after phytohemagglutinin stimulation in the diagnosis of colorectal carcinoma.

A lymphocyte fluorescence polarization test that measures reactivity to phytohemagglutinin (PHA) has permitted discrimination of a majority of patients with colorectal carcinoma from noncancer individuals. The test involves separation of two lymphocyte fractions from 20 ml venous blood on a modified leukocyte separation gradient, incubation with PHA for 45 minutes, addition of fluorescein diacetate, and analysis of change in fluorescence polarization. Of 19 colorectal patients tested preoperatively, 13 had a positive stimulation index, 3 a zero index, and 3 a negative index. Of 7 patients with other malignant neoplasms, a positive value was obtained in 6 and a negative value in 1. Of 14 patients with other diseases, a negative value was obtained in 9, zero in 3, and positive in 2. Of 31 normal donors a negative value was obtained in 27, zero in 2, and weak positive in 2. This rapid test promises to develop into a useful cancer-diagnostic method, and elucidation of its biological basis should identify a new cancer marker.

Lymphoid hyperplasia: a major prognostic feature in 519 cases of colorectal carcinoma.

The size of the regional lymph nodes, germinal center, and paracortical areas, and the degree of perivascular lymphocyte cuffing (PLC) at the edges of 519 carcinomas of the large bowel have been analyzed microscopically and assessed quantitatively. Hyperplasia of these lymphoid areas, defined as relative or absolute size exceeding the median for the tumor stage, has been related to cancer-specific survival data for each of Dukes' Stages A, B, and C, and for disseminated disease commonly referred to as Stage D. Germinal center hyperplasia was associated with a major survival advantage in Stage B (P = 0.003) and in Stage C (P = 0.04) if present in tumor-involved lymph nodes. Paracortical hyperplasia related favorably to survival in Stages B and C; in Stage C such hyperplasia was most favorable if present in tumor-involved lymph nodes (P = 0.009). PLC related to favorable survival data only in Stage B. Lymphoid hyperplasia showed no correlation with survival in Stages A and D.

Mucinous colorectal carcinoma: immunopathology and prognosis.

A total of 519 colorectal carcinomas were examined for the presence or absence of mucinous differentiation by means of microscopical morphometry. Of these, 28% had objectively measurable amounts of mucinous tumour epithelium. Tumours with > 50% mucinous areas (14%) had significantly poorer prognosis than non-mucinous in stages A and C, while mucinous differentiation did not correlate with prognosis in stages B and D. Lymph nodes regional to mucinous tumours had significantly less paracortical response, and those with < 50% mucinous differentiation, significantly less perivascular lymphocyte cuffing at the tumour margins. These lymph node and stromal compartments are putative T-lymphocyte areas, and hence our findings suggest that mucinous tumours are either less stimulatory or perhaps inhibitory of cell-mediated immunity.

Concealed rectal prolapse.

In a series of 97 patients with rectal prolapse 36 were unaware that the prolapse was occurring. Failure to recognize the prolapse may cause delay in diagnosis and inappropriate treatment. In most instances the prolapse was considered to be primary and responded well to surgical repair; however, in a few patients the prolapse seemed to follow prolonged straining, and in these surgical repair is not so successful.

The treatment of fistulas following irradiation damage.

Fistulas following irradiation treatment of uterine cancer present special problems. They are seldom isolated injuries. Because of the depressed response of connective tissue, direct repair can seldom be carried out. For rectovaginal fistulas a defunctioning colostomy is the usual first stage, and this may in time result in spontaneous closure. Repair can only be achieved by carefully planned operations where non-irradiated tissue is used to close the defect.