Phase II clinical trial of preoperative combined chemoradiation for T3 and T4 resectable rectal cancer: preliminary results.

PURPOSE: Although preoperative chemoradiation for high-risk rectal cancer may improve survival and local recurrence rate, its adverse effects are not well defined. This prospective study evaluated the use of preoperative chemoradiation for T3 and T4 resectable rectal cancer, with special emphasis on treatment morbidity, pathologic remission rate, quality of life, and anorectal function. METHODS: Forty-two patients (30 men, 12 women) were enrolled in the study. Median distance of the distal tumor margin from the anal verge was 6.5 cm. Preoperative staging was based on digital rectal examination, endorectal ultrasound, and computed tomography. None of the patients had distant metastases. All patients had 45 Gy (1.8 Gy/day in 25 fractions) over five weeks, plus 5-fluorouracil (350 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33. Quality of life was assessed with the European Organization for Research and Treatment of Cancer 30-item quality-of-life questionnaire (QLQ-C30) and its colorectal cancer-specific module (QLQ-CR38) questionnaires. Objective anorectal function was assessed by anorectal manometry and pudendal nerve terminal motor latency. Surgery was performed 46 (range, 24-63) days after completion of adjuvant therapy. RESULTS: Nineteen patients (45 percent) had Grade 3 or 4 chemoradiation-induced toxic reactions. Four patients developed intercurrent distant metastases or intraperitoneal carcinomatosis at completion of chemoradiation. Thirty-eight patients underwent surgical resection: abdominoperineal resection, anterior resection, and Hartmann's procedure were performed in 55 percent, 39 percent (11 of 15 patients had a diverting stoma), and 5 percent, respectively. Major surgical complications occurred in 7 patients (18 percent) and included anastomotic leak (n = 1), pelvic abscess (n = 1), small-bowel obstruction (n = 3), and wound breakdown (n = 2). Final pathology was Stage 0 (no residual disease), I, II, and III in 6 (16 percent), 7 (18 percent), 9 (24 percent), and 16 (42 percent) patients, respectively. There was a deterioration, after chemoradiation and surgery, in the quality of life on all subscales assessed, with physical, role, and social function being most severely affected. The symptoms most adversely affected were micturition, defecation, and gastrointestinal problems. Body image and sexual enjoyment deteriorated in both men and women. Chemoradiation alone led to prolonged pudendal nerve terminal motor latency in 57 percent of 7 patients assessed. CONCLUSION: Preliminary results have identified defined costs with preoperative chemoradiation, which included treatment-induced toxicity, a high stoma rate, and adverse effects on quality of life and anorectal function.

Acceptance of screening for colorectal cancer by flexible sigmoidoscopy.

OBJECTIVE: To determine the acceptance rate of screening by flexible sigmoidoscopy in a sample of general practice patients aged 50 to 60, and the acceptability of the procedure among those undergoing the test. SETTING: Recruitment took place in selected general practices in Melbourne, Australia. Flexible sigmoidoscopies were performed at the local public hospital. PATIENTS AND METHODS: 187 patients aged between 50 and 60, and without bowel symptoms, were seen by one of 12 non-randomly selected general practitioners during the study period. At the conclusion of routine consultation general practitioners discussed colorectal screening with eligible patients and recommended that they attend a free screening clinic at the local hospital. The patients who attended the clinic underwent flexible sigmoidoscopy performed by experienced endoscopists. Clinic attenders completed a questionnaire which measured perceptions of the screening visit. RESULTS: The attendance rate was 49%. All clinic attenders were satisfied with the care received at clinic. Sixty five per cent of people experienced either no discomfort or mild discomfort, while 15% of people experienced moderate or severe pain. A bloated feeling was common (80%), with around 36% of people experiencing moderate or extreme bloating. Most people said that they were not at all embarrassed (64%), though 9% reported moderate or extreme embarrassment. Seventeen people (19%) were found to have polyps. CONCLUSIONS: Although the procedure was acceptable to those who underwent the screening test, further research on effective recruitment strategies is required if a full scale flexible sigmoidoscopy screening programme is to be considered feasible.

Topoisomerase II levels during granulocytic maturation in vitro and in vivo.

Western blotting, indirect immunolocalization, flow cytometry, and a functional assay for drug-induced strand breakage were utilized to examine topoisomerase (topo) II levels during granulocytic maturation in HL-60 human progranulocytic leukemia cells and in samples of normal human marrow. Indirect immunofluorescence revealed that the intensity of the signal for topo II in unsynchronized log phase HL-60 cells varied widely. Indirect immunolabeling combined with propidium iodide staining and two-parameter flow cytometry revealed that topo II levels increased an average of 2-fold as cells progressed from G1 to G2/M. When HL-60 cells were induced to mature toward granulocytes, topo II levels progressively decreased and became undetectable by functional assays, by indirect immunoperoxidase staining, and by Western blotting with an antibody which identified Mr 170,000 and Mr 180,000 forms of topo II. Similar changes were detected during normal granulocytic maturation in human marrow in vivo. Western blotting revealed that levels of the Mr 170,000 (proliferation-associated) isoform of topo II were highest in marrow fractions enriched in progranulocytes and myelocytes, intermediate in unfractionated marrow from normal volunteers, and undetectable in mature granulocytes. The Mr 180,000 topo II polypeptide was also diminished or absent from mature granulocytes. In further experiments, marrow samples from normal volunteers were subjected to flow cytometry after labeling of topo II and various cell surface markers. Levels of the Mr 170,000 topo II polypeptide in CD34-positive cells (multipotent and committed progenitors from several hematopoietic lineages) were indistinguishable from levels observed in the HL-60 leukemia cell line. These results suggest that topo II levels in highly proliferative normal human myeloid cells in vivo approach levels found in corresponding neoplastic cell lines in vitro. Conversely, as the same cells mature into granulocytes in vivo or in vitro, levels of both molecular weight forms of topo II diminish. These results provide a framework for the further investigation of topo II levels and drug sensitivity in human leukemia.

Carney's triad.

A 26 year old female presented with partial expression of Carney's triad. This is the first Australian report of the condition. The role of surgery and the need for vigilance to detect the occurrence of the complete triad are stressed.

Microcomputer system for the analysis of muscle function.

Though skeletal muscle function has recently been increasingly studied, a system for routine clinical examination in patients is not widely available. A microcomputer based system has been developed for the measurement and analysis of force-frequency characteristics, relaxation rate, fatiguability and endurance in the adductor pollicis muscle. The mobile system consists of a modified displacement transducer fitted with a linear-output Hall-effect sensor, a specially designed signal processing unit and a microcomputer for control of both the electrical stimulus and a suite of menu-driven, user-interactive programs. One hundred normal volunteers have been studied to produce a normal database for comparison with malnourished surgical patients. The system compares favourably with other systems in use for objective measurement of skeletal muscle function and introduces a refined technique for evaluating endurance.

Muscle power after glucose-potassium loading in undernourished patients.

The force-frequency characteristics and maximal relaxation rate of the adductor pollicis muscle were measured before and after 48 hours of intravenous loading with glucose (104.5 kJ (25 kcal)/kg/24 h) and potassium (20 mmol(mEq)/500 ml glucose) in eight undernourished patients about to undergo surgery. Both variables of skeletal muscle performance, which were depressed when compared with data from 100 healthy volunteers, improved significantly after glucose-potassium loading. The improvement was accompanied by restoration of muscle glycogen values and return of respiratory exchange ratios towards unity. These results imply that if muscle power is a yardstick for preoperative nutritional rehabilitation then a simple regimen of energy-electrolyte repletion may be cost effective in preparing undernourished patients for major surgery.

Aspiration cytology and ultrasonography of cold thyroid nodules.

Over an 18 month period, 50 'high risk' patients with solitary or dominant cold thyroid nodules on 99m Tc-pertechnetate scanning, have undergone fine needle aspiration biopsy cytology (ABC) under general anaesthetic prior to thyroidectomy. Histological malignancy was confirmed in only four patients (8%). Cytological malignancy was suspected or confirmed in six patients, each having a false positive rate of 4%. There were no false negative reports. Ultrasonography, performed pre-operatively in 37 of the patients, did not significantly add to the overall patient management. ABC appears to be safe, simple and sufficiently accurate to incorporate its use routinely in the pre-operative assessment of thyroid nodules.

Calcific enterolith perforation: an unusual complication of small bowel anastomosis.

A 61 year old man presented with peritonitis which at laparotomy was found to be due to an enterolith perforation of a blind end of a previous side-to-side ileal anastomosis.