Steroid receptors, pS2 and cathepsin D in early clinically node-negative breast cancer.

Four oestrogen-regulated proteins of reported prognostic value, oestrogen receptor (ER), progesterone receptor (PR), pS2 and cathepsin D (Cat D), have been quantified by immunoassays, and the latter studied by immunohistochemistry (IHC) in primary tumours from clinically node-negative early breast cancer patients, entered into a trial of breast conservation therapy in which all the patients received adjuvant tamoxifen. ER, PR and pS2 significantly co-correlated but none correlated with Cat D. ER, PR and pS2, but not Cat D, were significantly associated with tumour size and grade, although Cat D tended to show an inverse relationship with the latter. Cat D (radioimmunoassay) in pmol/mg significantly correlated with the IHC score for Cat D in carcinoma cells as well as the number of Cat D-expressing macrophages. At a median follow-up of only 16 months, recurrence was significantly more common in patients with tumours having negative status for ER, PR and pS2 but was not associated with Cat D status.

Identification of the presence and type of biliary microflora by immediate gram stains.

Immediate gram stains were performed on gallbladder bile aspirated at the start of an operation for biliary disease in 191 consecutive patients undergoing elective biliary surgery. The results of the gram stains were telephoned to the operating theater within 20 minutes of collection. The over-all accuracy rate of the telephone gram stain reports compared with the subsequent bile cultures was 77 percent. The incidence of false-positive results was 12 percent, and false-negative results were recorded in 7 percent. The organism was identified wrongly by the gram stain in 4 percent of patients. These results have improved with experience and the over-all accuracy rate of gram stains on bile over the last 6 months have been 87 percent.

Selecting patients requiring antibiotics in biliary surgery by immediate gram stains of bile at operation.

The value of selecting patients for antibiotic cover during biliary surgery by the use of immediate gram stains of bile was determined in a nonrandomized prospective study which compared two groups of patients. Group A consisted of 119 consecutive patients in whom antibiotics were administered during operation according to the results of immediate gram stains on bile. Group B included 101 patients, none of whom received antibiotics. In Group A gentamicin was given for gram-negative bacteria, ampicillin for gram-positive organisms, and no antibiotics were given if no bacteria were seen on the gram stain. In Group A the incidence of wound sepsis was 7 percent, compared with 22 percent in Group B (p less than 0.005). Septicemia occured in 2 percent of Group A, compared with 8 percent in Group B. It is concluded that immediate gram stains of bile will provide a means of selecting patients requiring antibiotic cover during biliary surgery; furthermore, this procedure is a practical way of reducing postoperative sepsis while avoiding unnecessary antibiotic administration.

Vasculitis of the gall bladder in rheumatoid arthritis and systemic lupus erythematosus.

Three cases of acute cholecystitis due to vasculitis of the gall bladder are described; one in a patient with rheumatoid arthritis, and two in association with systemic lupus erythematosus.

Mammographic identification and biopsy of occult breast cancer.

During a 9 year period we excised 70 suspicious non-palpable breast lesions detected by mammography. We found the most effective method of preoperative localisation to be insertion of a self retaining wire, and this procedure was facilitated by a Perspex grid incorporated in the mammography equipment. Thirty biopsies (43%) were found to be malignant, of which 14 contained invasive and 16 in situ carcinoma. The presence of malignancy could not be predicted from the mammographic appearance, although in situ cancer was always associated with microcalcification.

Complications of rectal anastomoses with end-to-end anastomosis (EEA) stapling instrument. Clinical and radiological leak rates and some practical hints.

The complications and results of rectal anastomoses carried out with the end-to-end anastomosis (EEA) stapling instrument on 50 patients by 5 consultant surgeons are recorded. There was a clinical leakage rate of 6% and a radiological leakage rate of 20% assessed by water-soluble contrast enema. The technique has advantages compared with hand-suture by allowing low anastomoses and preservation of sphincters and is accompanied by an acceptably low leakage rate. Despite the cost of disposable cartridges these advantages make the technique economical because of the avoidance of colostomies and reduction in hospital stay.

A randomised controlled trial to evaluate both the role and the optimal fractionation of radiotherapy in the conservative management of early breast cancer.

AIMS: Postoperative radiotherapy is routinely used in early breast cancer employing either 50 Gy in 25 daily fractions (long course) or 40 Gy in 15 daily fractions (short course). The role of radiotherapy and shorter fractionation regimens require validation. MATERIALS AND METHODS: Patients with clinical stage I and II disease were randomised to receive immediate radiotherapy or delayed salvage treatment (no radiotherapy). Patients receiving radiotherapy were further randomised between long (50 Gy in 25 daily fractions) or short (40 Gy in 15 daily fractions) regimens. The primary outcome measure was time to first locoregional relapse. Reported results are at a median follow-up of 16.9 years (interquartile range 15.4-18.8). RESULTS: In total, 707 women were recruited between 1985 and 1992: median age 59 years (range 28-80), 68% postmenopausal, median tumour size 2.0 cm (range 0.12-8.0); 271 patients have relapsed: 110 radiotherapy, 161 no radiotherapy. The site of first relapse was locoregional158 (64%) and distant 87 (36%). There was an estimated 24% reduction in the risk of any competing event (local relapse, distant relapse or death) with radiotherapy (hazard ratio = 0.76; 95% confidence interval 0.65, 0.88). The benefit of radiotherapy treatment for all competing event types was statistically significant (X(Wald)(2) = 36.04, P < 0.001). Immediate radiotherapy reduced the risk of locoregional relapse by 62% (hazard ratio = 0.38; 95% confidence interval 0.27, 0.53), consistent across prognostic subgroups. No differences were seen between either radiotherapy fractionation schedules. CONCLUSIONS: This study confirmed better locoregional control for patients with early breast cancer receiving radiotherapy. A radiotherapy schedule of 40 Gy in 15 daily fractions is an efficient and effective regimen that is at least as good as the international conventional regimen of 50 Gy in 25 daily fractions.

The natural history of malignant thyroid lymphomas.

Twelve patients with malignant thyroid lymphomas seen over a 12-year period were reviewed. Two of these patients developed intra-abdominal lymphoma and a third, adult coeliac disease. Treatment by radiotherapy and thyroxine was effective, with thyroid excision mainly reserved for obstructing lesions. Prognosis was not affected by local metastases. A plea is made for open thyroid biopsy and accurate clinical staging of patients with this disease.

The value of preliminary bone scanning in staging and assessing the prognosis of breast cancer.

Preliminary bone scans have been performed on all patients with early breast cancer. The incidence of positive scans has been recorded and several factors determining scan status have been enumerated. Particular attention has been focused on the natrual history of scan positive and scan negative patients. Eighteen per cent of stage I and 41 per cent of stage II cancers had positive bone scans. Scan results were correlated with age, menopausal status, tumour position, tumour size and histological node status. Postmenopausal patients were found to have a significantly increased risk of being scan positive (P less than 0-01). Follow-up studies have confirmed that the lesions demonstrated by scanning actually represent metastatic foci. At 18 months 85-7 per cent of scan positive patients had evidence of disseminated disease compared with only 11-4 per cent of scan negative patients (P less than 0-01). Clinically overt advanced disease evolves from positive scan lesions. It is clear that a significant percentage of patients felt to have early breast cancer already have widely disseminated disease at the initial presentation. The biological significance of bone scan lesions makes a sensitive screening test for dissemination an essential part of the preliminary assessment of patients with breast cancer. Bone scans provide an excellent prognostic index at a patient's initial assessment.

Fine needle aspiration cytology in the management of euthyroid goitre.

The role of fine needle aspiration cytology was examined in a series of 115 euthyroid patients referred with thyroid enlargement presenting consecutively to a joint medical and surgical thyroid clinic from April 1985 to December 1986. Needle aspiration was performed at first clinic attendance and repeated two to six months later in 39 subjects. Patients were classified according to cytological features of the thyroid aspirate. A diagnosis of benign colloid goitre was made in 59 patients, lymphocytic thyroiditis in 11, thyroid cyst in 32 and in addition there were 13 reports of suspicious or malignant cytological features. Malignancy was confirmed histologically in six patients in this group and five more had follicular adenomata. There were two false positive reports of 'suspicious' cytological features. During a median period of observation of 11.4 months one false negative cytological diagnosis has emerged in a further patient with follicular adenoma. Accuracy in the diagnosis of thyroid neoplasia of 97 per cent has thus been achieved. Fine needle aspiration cytology has replaced isotope and ultrasound scanning in our practice. The number of 99mTc scans performed in the investigation of goitre fell from 77 in 1984 to three in 1986. Neoplastic tissue was removed at operation in 40 per cent of cases proceeding to surgery (20 subjects), compared with a predicted rate of 9.6 per cent if all solitary nodules had been removed. Aspiration cytology performed at first clinic attendance has led to improved selection of patients for surgery and hence economy in their management.

Upper airway obstruction due to goitre: detection, prevalence and results of surgical management.

A group of 132 women and 12 men with goitre were studied to determine the prevalence of upper airway obstruction caused by the goitre. Inspection of flow-volume loops was used to detect upper airway obstruction and this suggested that 44 subjects (31 per cent) had the condition. Of these 44 subjects 19 per cent were men, which was a greater proportion than could be accounted for by chance. Flow-volume loops after surgery were recorded on 43 patients of whom 29 were from the group thought to have had upper airway obstruction. Comparison of measurements before and after surgery showed no important change in the 14 without, and improvement in 27 of those with, upper airway obstruction. Analysis indicated two failures of treatment and four probable false-positives among the group with upper airway obstruction. Inspection of the flow-volume loop had a 78 per cent specificity and 100 per cent sensitivity in detecting upper airway obstruction whereas an FEV:PEF ratio above 8 had a specificity of 94 per cent and a sensitivity of 64 per cent in this respect. Ultrasonography and plain radiography of the upper airway accurately predicted retrosternal extension of the goitre but did not predict upper airway obstruction. It is recommended that all patients with symptomatic goitre should have a flow volume loop recorded.

Whole gut irrigation: a survey of patient opinion.

Patients' assessment of whole gut irrigation via a nasogastric tube has been obtained by a questionnaire answered by 79 of 99 patients who received this method of bowel preparation before operation on the large bowel or colonoscopy. Abdominal pain during the irrigation was experienced by 13 patients (17 per cent) and nausea and vomiting occurred in 24 (30 per cent). Intubation with a nasogastric tube and the discomfort of prolonged sitting on a commode were considered the most disagreeable aspects of the procedure. Fifty-six patients (71 per cent) would have agreed to the irrigation being repeated if necessary and many patients preferred whole gut irrigation to previous 'orthodox' bowel preparations that they had experienced.

Cyclin/proliferation cell nuclear antigen immunohistochemistry does not improve the prognostic power of Dukes' or Jass' classifications for colorectal cancer.

Immunohistochemistry of cyclin/proliferation cell nuclear antigen (PCNA) is an attractive alternative to tumour cell proliferation activity determined by flow cytometry which has been shown to be independently predictive of survival in patients with colorectal carcinoma and to enhance Dukes' classification. Dukes' and Jass' histopathological classifications were determined in 91 patients who had undergone curative resection for cancer of the colon (n = 51) or rectum (n = 40) and followed up for a minimum of 10 years. PCNA immunohistochemistry was possible in 79 tumours. Univariate analysis revealed that Jass' (P < 0.0001) and Dukes' classifications (P < 0.0002) were powerful predictors of survival but that the PCNA index had little prognostic power (P = 0.4). Multivariate analysis of both classifications showed similar predictive power and the PCNA index improved the prediction of survival when used with either classification for patients with colon cancer (chi 2 = 5.3, 1 d.f., P = 0.02 for each combination). The PCNA index, however, was not predictive for rectal cancer. Patients with the lowest PCNA index had the worst prognosis.

Limitations of biopsy in preoperative assessment of villous papilloma.

Between January 1975 and December 1979, 58 patients were diagnosed as having villous papilloma of the large bowel. A retrospective review was performed and all histologic specimens were re-examined by one gastrointestinal histopathologist (H.T.). On review, 19 (23 per cent) lesions were reclassified as not being villous papilloma. Results of preoperative biopsy examinations were misleading in 13 of the 29 patients who had biopsy procedures reported by any member of the histopathology department. When the assessment of malignancy in the initial biopsy specimens was compared with that of the final histologic diagnosis, there were ten (34 per cent) false-negative and three (10 per cent) false-positive reports. Even when the excised specimens were reviewed for malignancy by a specialist gastrointestinal histopathologist, there were seven (24 per cent) false-negative results.

Surgical treatment of primary hyperparathyroidism in the elderly.

Twelve patients aged over 70 with primary hyperparathyroidism (persistent hypercalcaemia and raised serum parathyroid hormone concentrations) underwent parathyroidectomy, which was well tolerated by all. After operation serum calcium concentrations returned to normal and the commonest symptoms before operation (muscle weakness, malaise, and mild to severe dementia), although not related in severity to the degree of hypercalcaemia, improved. Mental function was greatly improved. The findings suggest that primary hyperparathyroidism should be sought in any elderly patient with hypercalcaemia and that more such patients with the diagnosis should be considered for parathyroidectomy irrespective of age.

Carcinoembryonic antigen in management of colorectal carcinoma.

Carcinoembryonic antigen (C.E.A.) estimation has been used in the preoperative assessment of colorectal carcinoma patients and has been shown to give a useful guide to the presence of metastatic disease and ultimately to a poor prognosis if the serum concentration is 100 ng/ml or more. C.E.A. has been shown to be a more reliable index of tumour spread than either clinical examination or serum alkaline phosphatase estimation. Raised C.E.A. levels of less than 100 ng/ml do not, however, necessarily imply a poor prognosis. Routine C.E.A. estimation may have a valuable role in the assessment of the colorectal cancer patient by identifying those likely to benefit from postoperative chemotherapy.The test has also been assessed in a group of patients attending cancer follow-up clinics after radical resection of a colorectal tumour. Raised C.E.A. occurred in most of those developing recurrent disease, and in several patients a rising C.E.A. level preceded clinical or biochemical evidence of recurrence. C.E.A. estimation is a superior guide and of clinical importance when applied to the follow-up of the colorectal cancer patient.

Long-term thyroxine treatment and bone mineral density.

Studies of the effect of thyroxine replacement therapy on bone mineral density have given conflicting results; the reductions in bone mass reported by some have prompted recommendations that prescribed doses of thyroxine should be reduced. We have examined the effect of long-term thyroxine treatment in a large homogeneous group of patients; all had undergone thyroidectomy for differentiated thyroid cancer but had no history of other thyroid disorders. The 49 patients were matched with controls for age, sex, menopausal status, body mass index, smoking history, and calcium intake score; in all subjects bone mineral density at several femoral and vertebral sites was measured by dual-energy X-ray absorptiometry. Despite long-term thyroxine therapy (mean duration 7.9 [range 1-19] years) at doses (mean 191 [SD 50] micrograms/day) that resulted in higher serum thyroxine and lower serum thyrotropin concentrations than in the controls, the patients showed no evidence of lower bone mineral density than the controls at any site. Nor was bone mineral density correlated with dose, duration of therapy, or cumulative intake, or with tests of thyroid function. There was a decrease in bone density with age in both groups. We suggest that thyroxine alone does not have a significant effect on bone mineral density and hence on risk of osteoporotic fractures.

Serum thyroglobulin in thyroid cancer.

Serum thyroglobulin (Tg) was measured in 274 patients with differentiated thyroid cancer; 266 had previous thyroidectomy, which had been followed by ablative iodine-131 in 183 cases. Neither the presence nor the titre of anti-Tg antibodies appeared to affect Tg assays. Serum Tg reflected the presence or absence of cancer in 83% of 164 patients not receiving thyroxine (T4). This concordance improved to 97.5% in 158 patients tested while receiving T4. 34 patients in remission were tested both on and off T4 therapy; in all these patients the Tg level when receiving T4 was less than 5 micrograms/l. In 19 of 21 patients with cancer T4 treatment did not suppress Tg. Serum Tg thus provides an excellent marker for the presence or absence of thyroid cancer in patients taking T4, even if anti-Tg antibodies are present. It is proposed that monitoring of patients by assay of serum Tg should supplant routine assessment by radioactive-iodine scans of the neck or whole body.