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A prospective controlled randomised trial to evaluate the effectiveness and safety of razoxane is reported. Some 603 patients with colo-rectal cancer having curative surgery entered the study, and all have been followed up for a minimum of five years. Statistical analysis showed that razoxane treatment had no effect either beneficial or adverse on the rates of recurrence or on five year survival of patients with colo-rectal cancer. It is possible that a more prolonged course of razoxane might have significantly influenced survival. The incidence of severe adverse reaction was low but it is of concern that one patient developed leukaemia. Should razoxane be considered for future use it is recommended that continuous low dose therapy be given for no longer than 12 months. No renal, hepatic, pulmonary or cardiac toxicity was noted.

Two hundred and nine children presenting consecutively with acute lymphoblastic leukaemia to a regional paediatric oncology unit were investigated to determine the prognostic significance of various factors at diagnosis. There was a strong positive correlation between the pretreatment haemoglobin level and the percentage of bone marrow blast cells in S phase of the cell cycle as assessed by flow cytometry. Patients with T- and B-cell leukaemia had significantly higher haemoglobin levels than non-B non-T patients. In patients with total white cell counts less than 20 X 10(9)/l, aged less than 13 years, and no mediastinal mass, there was no association of haemoglobin with length of first remission. However, among those with white blood counts greater than 20 +/- 10(9)/l there was a strong positive trend towards shorter remission with higher haemoglobin levels. Children with high white blood counts at diagnosis and low haemoglobin levels may have a better prognosis than predicted by the white blood count alone.

From July 1977 to July 1983, 120 children with non-Hodgkin's Lymphoma entered a randomised trial of combination chemotherapy and radiotherapy. The primary site was abdominal in 42 patients, mediastinal in 27 and in other sites in 51. Failure-free survival (FFS) at 4 years was 74% for the 41 patients with localised disease (Stages I and II) and 51% for the 79 with generalised disease (Stages III and IV). Patients with mediastinal primaries continued to relapse after the completion of 2 years' treatment, but FFS at 4 years for the 93 patients with non-mediastinal primaries was 65% for all stages combined. In the latter group, there was no benefit to patients randomised at the end of induction chemotherapy to receive adjuvant radiation 15 Grays in 10 fractions in 2 weeks to sites of previous bulky disease when compared to those not receiving such radiation (P = 0.6).

The knees of 20 patients with rheumatoid arthritis were each examined on two occasions on the same morning by three observers. Assessments were made of joint warmth, synovial thickening, effusion, instability, quadriceps power, bony enlargement, range of movement, and knee circumference, and were graded on a scale of 0-4. Analysis of the results shows close intraobserver agreement for all measurements but considerable interobserver variation for all subjective measurements.

Eighty-four children with acute lymphoblastic leukaemia (ALL) who had relapsed in bone marrow were studied to assess whether treatment would be more successful if relapse was detected before the disease became clinically evident. Patients whose relapse was detected by routine bone marrow examination before the disease became apparent were compared with those whose relapse was suspected from clinical examination or peripheral blood findings. In the former there was a lower percentage of blast cells in the marrow (p less than 0.02) and the patients suffered less from complications of the disease, but there was no difference in the incidence or duration of second remissions between the two groups.

Significant bacteriuria is associated with dementia, incontinence of faeces and of urine in long-stay hospital patients. Bacteriuria in these patients is a fluctuating condition: it occurred in 47% of an initially sterile control group during the course of a year. Management with urinary antiseptics and an initial course of antibiotics is more successful than antibiotics on demand. However, since the condition is so fluctuating, it is doubtful if any treatment is usually needed other than the prevention of faecal incontinence.

Pretreatment marrow blast cells were studied in 38 boys and 27 girls (aged 1-14) with acute lymphoblastic leukaemia by flow cytometry after staining with propidium iodide.The percentage of blast cells in the S phase of the cell cycle ranged from 1% to 40% (median 6%). A correlation was found between the percentage of cells in S and the morphological classification of the French American British Cooperative Group (FAB), presence of T or B cell markers, haemoglobin concentration, blast size, bone pain, platelet count, and an inverse correlation with coarse granule and block staining with Periodic-acid-Schiff (PAS).63 of the 65 children attained complete remission. During the first 24 months of follow up there were fewer relapses (P = 0·054), and deaths (P = 0·004) in those children with 6% or fewer blasts in S phase. The difference was most marked in the first 12 months with 4 relapses out of 33 in the group with 6% or fewer cells in S compared with 13/30 in the group with > 6% cells in S.In order to investigate the prognostic significance of the pretreatment proliferative studies in greater detail, remission duration was correlated with 17 presenting features. Each feature was correlated individually and then the simultaneous effect of all the features was assessed by stepwise multiple regression.Only 3 features of the disease at diagnosis were individually correlated with duration of remission. These were% cells in S (P < 0·001), log white cell blood count (WBC) (P < 0·01) and the presence of T- or B-cell surface markers (P < 0·05). However, the multiple regression analysis showed that cell markers were not an independent prognostic feature, whereas the percentage cells in S and log WBC were independently and significantly correlated with duration of first remission (P < 0·001 in each case).

An 'arteriosclerosis score' has been devised in an attempt to differentiate between vascular and ideopathic chronic brain failure. The score was found to correlate closely with the ADL score, but not with MSQ score, nor with a battery of seven psychological tests. There are, however, close intercorrelations between certain psychological tests and the MSQ. This paper describes a series of tests, their correlations with each other in a group of elderly people, difficulties in their administration and the practical problems inherent in assessing drugs intended to be used in the prevention or treatment of brain failure.

A histologic analysis of 75 consecutive cases of Wilms' tumor in the Manchester (England) hospital region has been carried out. A classification based on the tubular status is described. A comparison of the histologic findings with the clinical staging and survival was undertaken, and it was found that the histologic classification was significantly correlated with both stage and survival.

Quantitative studies of non-nodular thyroid glands without focal thyroiditis obtained from consecutive autopsies on women aged over 20 yr showed a decrease in colloid content and an increase in stromal tissues with advancing age. When focal lymphocytic thyroiditis was present these changes were increased. This observation supports the theory that low-grade auto-immune processes can mimic or accelerate the ageing process but does not indicate that they initiate it.

A large controlled clinical trial with the admission of 1005 patients was carried out using tamoxifen as adjuvant treatment for women with operable carcinoma of the breast. Results were analysed for the first 906 evaluable patients randomised up to December 1981. After mastectomy premenopausal women were randomised to receive either an irradiation menopause or tamoxifen 20 mg daily for one year. Postmenopausal women were randomised to receive either tamoxifen 20 mg daily for one year or no systemic treatment (controls). Analysis at five years suggested that for premenopausal women there was no significant difference between an irradiation menopause and tamoxifen in terms of survival, local recurrence, or distant metastases. Tamoxifen had no appreciable side effects. For postmenopausal women there was a trend in favour of tamoxifen with regard to survival and incidence of distant metastases, and the difference became statistically significant for those patients with four or more positive axillary nodes. If long term results of these studies show only an improved quality of remaining life with tamoxifen, then this drug could be an important contribution to adjuvant treatment.

A right adrenal phaeochromocytoma is described in a 64-year-old man. Metastases to bone and subsequent death following cord compression occurred within 2 years of diagnosis. Twenty-seven cases in the English literature have been reviewed since 1968. In three of these, the pathological proof was unsatisfactory for the diagnosis of malignancy, and one further case was inadequately documented. The variation in incidence of malignancy found in large retrospective series may relate to inconsistency in pathological criteria, as well as to selective reporting of cases.

Thirty-one children and adolescents with malignant melanoma were treated at the Christie Hospital and Holt Radium Institute between 1945 and 1977. Locations of primary lesions included head-neck 14, trunk nine, and extremity eight. Twenty-five patients had clinically localized tumor at diagnosis, four had regional disease, and two had generalized tumor. Surgery was the primary modality of therapy. Fifteen patients survive without active disease from two years to more than 18 years, and 16 patients died of disease.

Thirty-eight patients with metastatic melanoma were investigated for lymphocyte function immediately prior to chemo-immunotherapy. The pre-treatment immune tests were compared with normal control values and with response to therapy. The "non-responder" group (but not "responder") had significantly reduced values for lymphocyte, null-cell and E-rosette-cell counts compared with controls. Lymphocytoxicity ( using a Chang target cell) showed the same pattern, with depression of direct and K-cell cytotoxic capacity in non-responders compared with controls. Eight patients were studied sequentially whilst on treatment, and demonstrated considerable change (not statistically significant) in lymphocytotoxicity, an untreated "control" patient showed little variation. "Recall"-antigen skin testing showed no statistically significant difference between the patient groups. The data indicate that "non-T-cell activity" may be associated with response to chemo-immunotherapy.

Levonantradol is a cannabis derivative. Cannabinoid anti-emetics are being assessed in cancer chemotherapy but have been little used in radiotherapy to date. A pilot study and randomised trial compared the anti-emetic effect of a standard drug (Chlorpromazine 26 mg) with Levonantradol at two doses (0.5 and 0.75 mg) in patients receiving palliative single fraction radiotherapy to sites likely to cause nausea and vomiting. Most patients were out-patients. Both drugs were well tolerated. The frequency of vomiting was similar in all three groups in both the pilot study and randomised trial.

A histological analysis of the tumors from the first Medical Research Council (M.R.C.) Nephroblastoma Trial was carried out. Material from 104 out of the 111 concluded cases was suitable for assessment. The degree of tubular differentiation and the presence or absence of glomeruli, cysts and papillary structures were correlated with clinical stage and survival. A significant association was found with regard to tubular differentiation. Papillary structures appeared to be important, but the number of cases was small. The presence of either glomeruli or cysts was not a statistically significant feature as regards prognosis.

Thirty-two variables at diagnosis of acute lymphoblastic leukaemia (ALL) were studied in an unselected population-bases series of 209 children. Twelve variables had individually a statistically significant effect on the duration of first remission. A multivariate analysis using data on the 199 children who went into complete remission showed that all significant variation in remission times could be explained by only 3 variables acting simultaneously. These were the total white blood count (WBC) at diagnosis, the Franco-American-British (FAB) classification of blast morphology and the percentage of lymphoblasts with PAS+ coarse granules or blocks. A simple scoring system (for WBC add 1 if less than 20 X 10(9)/1, add 2 if 20 - 50 X 10(9)/1, add 3 if greater than or equal to 50 X 10(9)/1; for L2 or L3 leukaemia add 1; for PAS+ less than 5% add 1) separated patients into risk groups with widely different median lengths of first remission. Application of the risk score improves the prediction of the outcome of treatment, and the clinical trials, allows more accurate stratification, less extensive data collection and simpler analysis.

A single-film intravenous pyelogram was performed on 87 children with acute lymphoblastic leukemia at presentation. The kidney size was measured and a standard deviation score based on patient height was calculated. There was a tendency of renal enlargement, with 21 patients (24%) having scores of over 1 SD and 6 (7%) over 2 SD. A trend of shorter duration of first remission with increasing renal size was shown to be statistically significant (P = 0.036). This trend was not quite statistically significant (P = 0.087) whenthe analysis was confined to 54 "better-risk" patients (WBC less than 20 X 10(9)/liter and no mediastinal mass), and was much weaker and not significant in 33 "poor-risk" patients (P = 0.62).

Full skeletal survey was performed on 193 consecutive children presenting over a 6-year period with acute lymphoblastic leukaemia (ALL). A record was made of the degree of bone pain in these patients and 60 others presenting immediately prior to the availability of skeletal surveys. Bone pain was present in 76 out of 253 patients (30%) and radiological bone changes characteristic of leukaemia in 125 out of 193 (65%). A significant correlation was found between the severity of bone pain and the number of bones involved on X ray (r = 0.25, P = less than 0.001), but not between initial white cell counts and bone score (r = -0.14, P = 0.08). There was no significant correlation between the degree of bone pain and survival or length of first remission (P = 0.29 and 0.86). Similarly, the extent of radiological bone disease was of no prognostic significance with relation to survival (P = 0.41) or length of first remission (P = 0.21).

A prospective study of bone marrow fibrosis was made in a group of 40 children with acute lymphoblastic leukaemia to see whether it affected the prognosis or course of the disease. Secondary myelofibrosis (SMF) was present at diagnosis in 57% of the cases. It was not statistically significantly related to the prognosis or course of the disease. Thus, although trephine biopsy occasionally provided useful information in different diagnosis and when aspiration was difficult, it provided little information of use for management.

Data relating to 1022 patients with early breast cancer who were entered into a clinical trial have been analysed to assess the importance of various factors in predicting prognosis. Clinical stage was the major determinant of prognosis, and in each stage patients with a breast tumour 2 cm or less in maximum diameter had a significantly better survival than patients with larger tumours. Patients aged between 40 and 49 years and premenopausal patients had relatively favourable prognosis. Site of the tumour within the breast, whether it was situated on the left or the right side, the patient's martial status and the number of pregnancies did not appear to have any influence.

Patients with early breast cancer (n = 1022) were treated between March 1970 and October 1975 in a prospective clinical trial. The results are presented after follow-up of 5-10 years. Clinical stage I cancer cases (n = 714) were randomly allocated to treatment by simple mastectomy and postoperative radiotherapy, or simple mastectomy alone. There was no statistically significant difference in overall survival between the two groups. There was a significant reduction in the frequency of local recurrence in those who received early postoperative radiotherapy compared with those who did not. Clinical stage II cancer cases (n = 308) were randomly allocated to treatment by simple mastectomy and postoperative radiotherapy or radical mastectomy alone. There was no statistically significant difference in survival or in the frequency of local recurrence between the two groups.

A consecutive series of 209 children with acute lymphoblastic leukaemia (ALL) presenting to a regional referral unit between 1970 and 1977 was studied. The following morphological features in the initial bone marrow were recorded: blast size, percentage periodic acid-Schiff (PAS) and oil-red-O (ORO) positivity, percentage of blasts with vacuoles, and acid phosphatase positivity. The blasts were also coded according to the FAB (L13) classification. When analysed separately, increasing blast size was significantly related to the length of first remission (P = 0.01). However, this was almost entirely due to its association with the FAB L2 type of disease which also had a highly significant influence on length of first remission (P less than 0.0001) independent of all other factors. Patients with L3 disease had blasts with heavy vacuolation, ORO positivity and displayed monoclonal surface immunoglobulin and their prognosis was very poor. The percentage of vacuolated blasts and ORO positivity otherwise showed no influence on prognosis. Fine granularity of PAS staining in lymphoblasts showed no prognostic value but the trend of longer remission duration with increase in percentage of PAS coarse granularity and blocks, was statistically significant (P = 0.006). This relationship was partly due to a correlation with the presence of mediastinal mass and L2 disease, but was still independent of all other prognostic factors. In a smaller number (39) of the series of patients on whom cell surface markers were available, we were unable to demonstrate a correlation between T-derived blasts and the L1 and L2 classification; but there was a strong correlation with polar acid phosphatase positivity in T-derived blasts.

Four hundred nineteen cases of carcinoma of the larynx (1962-1965, Christie Hospital) treated primarily by radiation with surgery in reserve for cases where radiation failed, are reviewed. Two hundred ninety-one of these cases were glottic carcinomas and cure rates, and contribution from subsequent surgery is indicated in detail. Finally the overall results are compared with a larger series of 605 cases (1955-1961). Five-year cure rate in early cases is consistent at 89 percent; likewise in the latest cases at 30 percent, the intermediate group appear to have improved by some 8 percent over the period outlined. The overall cure rate is 70 percent.

Three hundred and two previously untreated patients with Stage IA-IVB Hodgkin's disease were reviewed to determine the prognostic significance of mediastinal involvement. Mediastinal bulk disease was defined as either a maximal mediastinal width of 7.5 cm or more, or a ratio of the maximum width of mediastinal disease to the maximum chest diameter of greater than or equal to 0.33, or a ratio of the maximum width of mediastinal disease to the chest diameter at T5-T6 greater than or equal to 0.33, or as an area of mediastinal disease greater than or equal to 100 cm2. Bulk disease outside the chest was defined as a mass of lymph nodes measuring 5 cm or more in any axis. The presence of mediastinal bulk disease was of adverse prognostic significance for remission duration and survival in patients with Stage IA-IIB Hodgkin's disease, but for patients with more advanced disease the effect of mediastinal bulk on remission duration and survival was not statistically significant. The mediastinal bulk variable which most significantly related to prognosis was the ratio of the maximum mediastinal disease to the chest diameter at T5-T6.

From November 1977 to July 1983, 82 children with T leukaemia/lymphoma entered a randomised trial of combination chemotherapy and radiotherapy. Twenty-five were designated T lymphoma and 57 T leukaemia, 28 having greater than 100 x 10(9)1(-1) blasts in peripheral blood at diagnosis. Twenty-seven patients with mediastinal primaries who were treated on the companion non-Hodgkin lymphoma (NHL) trial were comparable in all respects to the T lymphoma patients and the results of treatment were therefore combined and analysed together. Overall 4-year survival (48-53%) and failure-free survival (FFS) (37-40%) were similar in all groups except the 28 with T leukaemia and WCC greater than 100 X 10(9)1(-1) (20% and 13%). There was a significant advantage in FFS for patients randomised to receive low dose mediastinal radiation, and this was most marked in patients with T lymphoma (66% vs 18%, P = 0.006).

A double-blind, placebo-controlled trial was carried out on 109 aged patients with minimal or with moderate chronic brain failure to assess the effectiveness of piracetam (2.4 g per day) in preventing the progression of dementia. Patients received piracetam or placebo each for 6 weeks, the order of treatment being at random. The results of 19 psychological tests, repeated at 6-weekly intervals, showed that piracetam produced statistically significant improvement in only one of them and then only during the first 6 weeks of treatment. These findings, therefore, do not support the usefulness of piracetam in the treatment of such patients.

A randomized double blind trial of the drug Solcoseryl given by intra-arterial infusion was carried out on 57 patients with pre-gangrene of the lower limb. A sequential analysis was carried out and the trial stopped when the results showed a statistically significant result in favour of the active drug.

A study of testicular histology has been made in 44 boys treated with combination chemotherapy for acute lymphoblastic leukaemia. At the time of testicular biopsy 21 boys were still receiving cytotoxic drugs and 23 had completed their chemotherapy some time earlier. Evidence of leukaemic infiltration was seen in 5 (11%), interstitial fibrosis in 24 (55%), and basement-membrane thickening in 6 (14%). The mean tubular fertility index in the 44 biopsies was 50% of that in age-matched controls, and 18 of the biopsies had a severely depressed tubular fertility index (40% or less). Three variables had a highly significant effect on the tubular fertility index: previous therapy with cyclophosphamide or cytosine arabinoside (greater than 1 g/m2) depressed the tubular fertility index, whereas with increasing time after completion of chemotherapy the tubular fertility index improved. The prognosis for fertility in these subjects is not known. Long-term surveilance is necessary.

During 1968-1978, 68 children presented in six centres in the United Kingdom with lymphoblastic mediastinal masses. The disease was classified as acute lymphoblastic leukaemia (ALL) in 49 children whose bone marrow aspirates contained > 20% lymphoblasts, and as lymphoma (Sternberg lymphosarcoma - LS) in 19 with < 20% marrow infiltration. Male predominated in both groups, and children with ALL had more visceromegaly and lymphadenopathy, lower haemoglobin levels and platelet counts, and higher white cell counts. The most common chest x-ray finding in both groups was a nonspecific anterior mediastinal mass, but the appearances varied considerably and could be classified into three categories, which are illustrated. Pleural effusions were present in 44%. Cell surface-marker studies showed T cell characteristics in 14 of the 17 patients tested. Response to treatment and complications, such as central nervous system (CNS) and testicular relapse, were similar in ALL and LS, and were related to the size of the initial tumour load. Median remission lengths were 37 weeks for ALL and 89 weeks for LS patients. Leukaemic transformation occurred in 47% of LS children. Compared with the outcome in ALL children without mediastinal mass, the results of treatment were poor, regardless of the protocol used, and prophylactic therapy to the CNS reduced the frequency of, but did not eliminate, CNS disease.

Thirty-eight patients with metastatic melanoma were evaluated immunologically prior to chemoimmunotherapy. The assays used included recall antigen skin hypersensitivity; lymphocyte count; nonspecific T, non-T, and K cell lymphocytotoxicity; and T and B cell rosette enumeration. Survival curves were computed for each of four ranges of values of a given immunologic test. The higher ranges of positive skin tests, lymphocyte count, cytotoxicity, and T and B subpopulation numbers were consistently associated with the longer survivals. The differences reached statistical significance for non-T cell cytotoxicity and B and T cell peripheral blood counts. Pretreatment immune reactivity, particularly that involvingg non-T cell function, appears related to length of survival.

Analysis of 86 patients who underwent salvage cystectomy following a radical course of radiotherapy for bladder cancer and 37 patients who underwent primary cystectomy has shown a greater survival for women than men. The following factors were associated with a significant deterioration in survival: 1. Age at time of cystectomy: post-operative mortality and tumour recurrence are greater over the age of 70. 2. Non-function of one kidney on IVU. 3. Grade 3 tumour on cystectomy specimen. 4. pT3 or pT4 tumour on cystectomy specimen.

An analysis of survival time of 57 West European patients with hepatocellular carcinoma was carried out to define which of several possible factors (age, sex, cirrhosis and raised serum alpha-foetoprotein (AFP)) influenced survival. Although survival was significantly longer in younger patients (P less than 0.02) and in patients with normal serum AFP (P less than 0.01), multivariate analysis showed that significant variation in survival time is better explained by the single factor, the presence of cirrhosis, than by AFP level. This does not seem to apply for patients with this tumour in Africa and the Far East, and there may be a fundamental difference in the natural history of the tumour between high- and low-incidence areas.

Pretreatment serum beta 2m levels were estimated in 65 patients with multiple myeloma. After correction for changes in renal function, the level of beta 2m attributable to multiple myeloma (beta 2m-m) no longer correlated with the serum creatinine, but showed a strong correlation with the total body myeloma cell mass (P = 0.002). There was an inverse correlation between beta 2m-m and the Karnofsky performance status of patients at presentation (P = 0.001). Patients with a pretreatment beta 2m-m level of less than the median value of 2.94 mg/l survived significantly longer than those with a raised level (P = 0.0008).

Low white cell counts are performed in many laboratories by a visual method as the method of choice. In this study, the visual count has been compared to that obtained by the Coulter Model "S". The results obtained by the two methods show very close correlation, thus allowing the Coulter Model "S" to be used with confidence for all low white cell counts provided certain precautions are taken.

An extended follow up to a maximum of 34 years was carried out on a series of 1461 patients who had been entered into a randomised clinical trial comparing immediate postoperative radiotherapy (treated group) with an optional delayed radiotherapy policy (watched group) after Halsted radical mastectomy for operable breast cancer. Long term survival was compared separately in patients with negative and positive axillary nodes and in two periods when different techniques of radiotherapy were used. No significant differences were noted in survival overall or in any subgroup. In patients with negative axillary nodes treated in the earlier period when the "quadrate" radiotherapy technique was used, however, the difference in survival was of borderline significance (p = 0.052), to the benefit of the watched group. Because of the large numbers of patients entered and the long follow up any possible harmful or beneficial effect of immediate postoperative radiotherapy would have been apparent in the results of this trial. The absence of any such effect implies that postoperative radiotherapy given to prevent or delay local recurrence of breast cancer is unlikely to be associated with a detectable effect on survival.