A review of the pathology and management of uterine papillary serous carcinoma and correlation with outcome.

Uterine papillary serous carcinoma (UPSC) accounts for 10% of endometrial carcinomas but a higher proportion of deaths due to its aggressive nature and poor response to chemotherapy and radiotherapy. In order to add to the knowledge of UPSC in the literature and to review our local practices, we examined the pathology, medical records, and management of all cases of UPSC (67 patients) treated in South East Scotland over a 10-year period and also evaluated the prognostic significance of the percentage of UPSC in endometrial pipelle and hysterectomy specimens. Although only 63% of initial diagnostic biopsies were reported to contain UPSC, rereview of the cases revealed UPSC in 98.5% of the preoperative biopsies. The percentage of UPSC in the tumors did not affect the outcome. Stage, positive omentum, and treatment with external-beam +/- intracavitary radiotherapy were significantly correlated with overall survival and progression-free survival by univariate analysis, but only stage (P < 0.01) was correlated with outcome on multivariate analysis. Chemotherapy did not affect outcome. UPSC may be difficult to diagnose in preoperative biopsies, particularly when present as part of a mixed tumor. Even a small percentage of UPSC in a diagnostic biopsy or hysterectomy specimen is correlated with a poor prognosis. This study emphasizes the need of a cooperative, prospective study on this distinct uterine carcinoma.

Symptom control and quality of life in people with lung cancer: a randomised trial of two palliative radiotherapy fractionation schedules.

AIMS: To determine whether palliation of chest symptoms from a 10 Gy single fraction (regimen 1) was equivalent to that from 30 Gy in 10 fractions (regimen 2). MATERIALS AND METHODS: Patients with cytologically proven, symptomatic lung cancer not amenable to curative therapy, with performance status 0-3, were randomised to receive either 30 Gy in 10 fractions or a 10 Gy single fraction. Local symptoms were scored on a physician-assessed, five-point categorical scale and summed to produce a total symptom score (TSS). This, performance status, Hospital Anxiety and Depression (HAD) score and Spitzer's quality-of-life index were noted before treatment, at 1 month after treatment and every 2 months thereafter. Palliation was defined as an improvement of one point or more in the categorical scale. Equivalence was defined as less than 20% difference in the number achieving an improvement in the TSS. RESULTS: We randomised 149 patients and analysed 74 in each arm. According to the design criteria, palliation was equivalent between the two arms. TSS improved in 49 patients (77%) on regimen 1, and in 57 (92%) patients on regimen 2, a difference of 15% (95% confidence interval [CI] 3-28) in the proportion improving between the two regimens. A complete resolution of all symptoms was achieved in three (5%) on regimen 1, and in 14 (23%) patients on regimen 2 (P < 0.001), a difference in the proportion between the two regimens of 21% (95% CI 10-33). A significantly higher proportion of patients experienced palliation and complete resolution of chest pain and dyspnoea with regimen 2. No differences were observed in toxicity. The median survival was 22.7 weeks for regimen 1 and 28.3 weeks for regimen 2 (P = 0.197). CONCLUSIONS: Although this trial met the pre-determined criteria for equivalence between the two palliative regimens, significantly more patients achieved complete resolution of symptoms and palliation of chest pain and dyspnoea with the fractionated regimen.

The Scottish and Manchester randomised trial of neo-adjuvant chemotherapy for advanced cervical cancer.

204 eligible patients were entered into a multicentre randomised trial of neo-adjuvant chemotherapy prior to radical radiotherapy. The aim of this study was to assess whether there was any survival advantage in patients undergoing chemotherapy and radiotherapy compared with those given radiotherapy alone. Patients were aged up to 70 years, performance status 0-1/2, with bulky stage IIb, stage III or stage IVa squamous or adenosquamous carcinoma. Three cycles of methotrexate 100 mg/m2 and cisplatin 50 mg/m2 were given at 2-weekly intervals before radical radiotherapy. 104 eligible patients received the combination treatment and 100 radiotherapy only. The two arms of the study were well balanced for tumour and patient characteristics. The response rate to chemotherapy was 49%, 33% of patients in the radiotherapy (XRT) alone arm and 45% of the combination arm were clinically free of tumour at the end of treatment. The median follow-up for surviving patients is 5.4 years (range: 11 months-8 years) and 84% have been followed-up for more than 4 years. 134 patients have died (68 XRT only, 66 combined arm). The median survival RT alone was 111 weeks (95% confidence interval (CI) 72-151 weeks), combination arm 125 weeks (95% CI 79-170 weeks). The estimated death ratio is 0.79 (P = 0.19, 95% CI 0.56-1.12). The estimated 3-year survival is 40% (95% CI 30-50%) RT only compared with 47% (95% CI 37-57%) in the combination arm. Acute and late toxicity of radiotherapy was not increased by the addition of chemotherapy.

Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules.

BACKGROUND: The optimum dose and fractionation schedule for the palliative irradiation of painful bone metastases is controversial. PURPOSE: To compare the efficacy, side-effects and effect on quality of life of two commonly used radiotherapy schedules in the management of painful bone metastases. MATERIALS AND METHODS: In a prospective trial, 280 patients were randomised to receive either a single 10 Gy treatment or a course of 22.5 Gy in five daily fractions for the relief of localised metastatic bone pain. RESULTS: Response rates have been calculated from 240 assessable treated sites of pain. The overall response rates were 83.7% (single treatment) and 89.2% (five fractions). The complete response rates were 38.8% (single treatment) and 42.3% (five fractions). The median duration of pain control was 13.5 weeks (single treatment) and 14.0 weeks (five fractions). None of these differences was statistically significant. There were no differences between the groups in the effect of treatment on a variety of quality of life parameters. CONCLUSIONS: It is concluded that a single 10 Gy treatment is as effective as a course of 22.5 Gy in five fractions in the management of painful bone metastases.

Autopsy findings in patients with mental handicap.

Autopsies were carried out on 60 mentally handicapped patients and the brain was examined in detail in all cases. The clinical records were studied and correlated with the pathological findings. A variety of pathological changes were found in the central nervous system, and there was a high incidence of microcephaly and gross abnormalities among the patients with epilepsy and neurological dysfunction. The incidence of Alzheimer's disease was very high among patients with Down's syndrome, but in those patients without Down's syndrome, the incidence appeared to be much the same as in the general population. The most common cause of death was respiratory disease, followed by cardiovascular disease. There was a high incidence of volvulus among the group with epilepsy. The findings are discussed, and reference made to the long-term care of the mentally handicapped. The study demonstrates the importance of the autopsy in terms of furthering knowledge in the field of mental handicap.

Early stage cervical cancer: psychosocial and sexual outcomes of treatment.

Eighty-three women, mean age 45 years, successfully treated by surgery (S) or radiotherapy (RT) for stage 1b cervical cancer were assessed a mean of 97 weeks post treatment. Forty to 50% reported persistent tiredness, lack of energy and weight gain. Sixty per cent had not resumed their full premorbid functional status. Mean scores for anxiety and depression were higher than general population means and this sample scored higher for psychological distress than published data quoted for disease free cancer patients. These women reported many concerns about cervical cancer, most commonly fear of recurrent disease (91%). More than one-third blamed themselves for the disease. There were no significant differences in functional outcome or psychological status between treatment groups or by age or time since treatment. Psychological distress scores were significantly correlated with physical complaints (P < 0.001) and functional outcomes (P < 0.02). For the 61 women who were sexually active, sexual function post-treatment was rated as significantly poorer than subjectively recalled premorbid sexual function (P < 0.005). RT treated patients were more likely to report pain on intercourse and loss of enjoyment. Psychological as well as physical problems were highly correlated with sexual outcome (P < 0.01) 44% were unable to talk adequately with their partners about their experience. The majority felt they needed more information about cervical cancer, its treatment and how to help themselves rehabilitate. Forty-nine per cent would have liked to have had counselling. Even with the same physical morbidity the functional, emotional and sexual status of these women could be improved by giving more attention to their psychological and sexual concerns.

Uterine sarcomas: a review of the Edinburgh experience from 1974 to 1992.

A retrospective review of patients treated for a uterine sarcoma in Edinburgh from 1974 to 1992 has been performed. Clinical details at presentation, tumour pathology, treatment and the outcome of treatment were all recorded. 82 patients' case notes were reviewed. 54 patients had died and 28 were alive (mean follow-up period 80.3 months). 39 patients had a malignant mixed mesodermal tumour, 12 patients had an endometrial stromal sarcoma, and 27 had a leiomyosarcoma. Using a modified FIGO staging retrospectively, 41 patients had Stage 1 disease, two patients had Stage 2, 16 patients had Stage 3, and 13 patients had Stage 4 disease. Definitive treatment of total abdominal hysterectomy and bilateral salpingo-oophorectomy was used in 69 patients, with 35 of these patients also receiving post-operative radiotherapy to the pelvis. 13 patients did not undergo surgery. Five of these patients received radical radiotherapy, three patients received palliative radiotherapy, and five patients were not treated. The overall median survival is 15 months and the 5-year actuarial survival is 31%. 25 of the 26 surviving patients had Stage 1 disease at presentation. Post-operative pelvic radiotherapy did not influence either survival or local tumour control. 51 of the 54 patients who relapsed had evidence of distant metastases. We conclude that total abdominal hysterectomy and bilateral salpingo-oophorectomy remains the treatment of choice for uterine sarcomas.

The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in the uterine cervix and cervical squamous neoplasia.

This is a retrospective study, in which PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA) was used in the assessment of 20 cases of FIGO stage IB cervical carcinoma, 30 cases of CIN, 10 cases of koilocytosis and 20 cases in which the transformation zone was histologically normal. The results showed that in the normal transformation zone the proliferative compartment was confined to the first 1-2 suprabasal cell layers. In CIN the pattern of staining corresponded to the grade of the lesion. In viral wart lesions occasional koilocytes demonstrated strong nuclear staining. In all cases of stage IB cervical carcinoma the PC10 index was high, irrespective of tumor grade response to treatment.

Endometrial carcinoma: does the addition of intracavitary vault caesium to external beam therapy postoperatively result in improved control or increased morbidity?

A retrospective analysis of treatment for endometrial carcinoma is reported here. From 1987 to 1989, 138 patients were referred to the oncology department following total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer. Forty-seven patients were not prescribed postoperative radiotherapy; 31 had Stage I well differentiated adenocarcinoma with minimal myometrial invasion, while the remaining 16 patients were considered unfit for postoperative radiotherapy. There were no instances of local relapse amongst the 31 patients with minimal myometrial invasion. The remaining 91 patients all received external beam irradiation to the pelvis and, according to the preference of the individual therapist, 51 were prescribed additional intracavitary vault caesium-137. Patients receiving postoperative radiotherapy were analysed according to whether or not they received additional intracavitary vault caesium. The two groups were also analysed for incidence of vaginal vault recurrence and treatment related morbidity. In the group receiving additional intracavitary treatment more patients had Stage II or III disease (P < 0.05), and had greater depth of myometrial invasion (P < 0.05). Vaginal vault recurrence was not observed in patients receiving intracavitary therapy in addition to external beam therapy. Four patients (10%) receiving external beam therapy alone developed vaginal vault recurrence. The incidence of Kottmeier-Perez grade 2 or 3 bowel toxicity following treatment was significantly higher in those patients receiving combined treatment (18% vs. 2.5%; P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Stage IB cervical carcinoma: a clinical audit.

All patients with FIGO Stage IB cervical cancer registered with the Department of Clinical Oncology at the Western General Hospital, Edinburgh, during the 6 years from 1979 to 1984 have been reviewed, as part of a continuing programme of clinical audit. Of the 140 patients with Stage IB disease, 68 (49%) were treated by primary surgery of whom 44 (31%) also received adjuvant radiotherapy. Radical radiotherapy was the definitive treatment for 69 patients (49%). Three patients (2%) were not treated with curative intent. The crude 5-year survival rate for all cases was 72% and the cause-specific 5-year survival rate was 78%. Local tumour control at 5 years was 72%. There was no significant difference in outcome between the surgically treated and irradiated groups of patients. Age, histology and nodal status did not influence outcome. Irradiated patients with bulky tumours fared significantly worse than the other patients who received radical radiotherapy. Multivariate analysis of all patients revealed no significant independent prognostic variables. Primary surgery appears to confer no benefit over radical radiotherapy in terms of either survival or local control. Treatment-related late bladder and bowel morbidity was, however, significantly worse in irradiated patients.

Cisplatinum and prednimustine, an active regimen for advanced epithelial ovarian cancer.

80 patients with advanced epithelial ovarian carcinoma were treated for 6 months with cisplatinum and prednimustine following initial surgery. Response to treatment was assessed by second-look surgery. The objective response rate was 69% with 38% achieving a complete response for up to 55 months. The toxicity of this regimen was acceptable. Statistically, de-bulking or partial de-bulking had a significant beneficial effect on the likelihood of a complete response. The best survival figures were associated with maximum de-bulking. The combination of cisplatinum and prednimustine is a new and active regimen for operable advanced epithelial ovarian carcinoma.

Akathisia in neuroleptic medicated mentally handicapped subjects.

Sixty-six neuroleptic medicated mentally handicapped subjects in a hospital were studied to determine the prevalence of drug-induced akathisia. Tardive dyskinesia was also rated on the AIMS scale. Only motor manifestations of akathisia could be assessed as the subjective component of akathisia was difficult to elicit in this population with difficulties in verbal communication. As all the subjects had been on neuroleptics for at least 3 years, only chronic akathisia could be studied. Five subjects had akathisia. Correlational analysis did not reveal any specific associations with any of the demographic, clinical and pharmacological variables studied. A step-wise multiple regression analysis indicated that younger age could be a predictor. Tardive dyskinesia was associated in two of the subjects. The overall conclusion was that 7% of the subjects had chronic akathisia and no specific risk factors could be identified.

Plasma amino acids in patients with senile dementia and in subjects with Down's syndrome at an age vulnerable to Alzheimer changes.

Plasma concentration of tryptophan, tyrosine, leucine and thiamine were reduced in senile dementia of Alzheimer type. In Down's syndrome, where Alzheimer-type histology appears consistently at an early age, there was a definite type of abnormality, raised concentrations of isoleucine, leucine, phenylalanine and cystine. Because of the competition between amino acids for transfer into the brain, either or both of these types of change could lie in the aetiological chain underlying the development of Alzheimer pathology. Alternatively, these patterns could reflect the requirements of aberrant central/peripheral protein turnover.

Neuroleptic-induced parkinsonian side effects in the mentally handicapped.

Sixty-seven neuroleptic-mediated mentally handicapped subjects in a hospital were studied to determine the prevalence of Parkinsonian side effects. A Parkinsonism scale was devised and administered. Sixty-one per cent of the sample had mild to moderately severe side effects. Sex, age, cumulative and current chlorpromazine doses, cumulative and current anticholinergic doses and anti-epileptic medication status did not predict the Parkinsonism scores. Overt brain damage was not a predictor. The difference between the neuroleptic medicated group and neuroleptic free matched controls was highly significant indicating that the Parkinsonian type of movement disorder was related to neuroleptic medication.

Hepatitis B in a hospital for the mentally subnormal in South Wales.

The resident population in a long-stay hospital for the mentally handicapped was surveyed in order to assess evidence for past and present infection with the Hepatitis B virus. The authors found a 0.5% prevalence of carriage of Hepatitis Be Antigen and do not recommend mass vaccination of staff and residents in this hospital.

Tardive dyskinesia in neuroleptic medicated mentally handicapped subjects.

Sixty-seven neuroleptic medicated mentally handicapped subjects in a hospital were rated on two occasions for abnormal involuntary movements on three scales: Abnormal Involuntary Movements (AIMS), Rockland and Parkinsonism scales, with 6 months between each assessment. Inter-rater and test-retest reliabilities were high. The data from the second assessment was analyzed. Prevalence of tardive dyskinesia (TD) was 21% on AIMS, 42% on the Rockland scale; 60% had parkinsonism. Multiple stepwise regression analysis revealed that age, sex, current neuroleptic and anticholinergic dose, antiepileptic medication, psychosis, cumulative anticholinergic dose were not significant predictors of TD as determined by AIMS. Parkinsonism and cumulative neuroleptic dose were significant predictors of and correlated positively with AIMS score. TD subjects formed 35% of the parkinsonian group. Overt brain damage was not a significant predictor of AIMS score and the difference between the neuroleptic medicated and neuroleptic free group on AIMS scores was highly significant.

Microcephaly: a review of genetic implications in its causation.

Microcephaly is a clinical sign rather than a nosological entity. It may even represent the extreme of normal variation. In pathological cases, it is always caused by an interruption of the neurobiologic processes of induction and cellular migration, or by a catastrophic insult to the central nervous system. The prime cause of this may be environmental or genetic. There is strong evidence for genetic heterogeneity, even among cases of 'true' or 'primary' microcephaly. Various taxonomies for the classification of microcephaly are discussed, taking into account environmental causation and various genetic mechanisms.

Folate metabolism and problem behaviour in mentally handicapped epileptics.

Two groups of mentally handicapped residents were studied consisting of 32 epileptics on anti-epileptic medication and 32 non-epileptic controls. The epileptic group showed a significantly low serum folate level compared with the non-epileptic control group. Serum vitamin B12 and behaviour rating did not show any significant difference between two groups. Comparison of patients receiving phenytoin and those who were not showed significantly lower serum folate in the sub-group receiving phenytoin, but there was no significant difference between the sub-groups with respect to vitamin B12 or behaviour problem rating.

Long survival after cardiac arrest: case report and neuropathological findings.

A 14-year-old male survived for nearly 3 years following a cardiac arrest. During this period he remained unconscious and electroencephalogram recordings indicated a virtual absence of neocortical activity. Clinically there was some retention of brainstem function evidenced by spontaneous respiration, eye movements, cough and swallow reflex. He was in a persistent vegetative state until his death. We believe this to be one of the longest surviving cases to be recorded. Neuropathological findings correlated with the clinical picture, and demonstrated the selective vulnerability of various areas within the brain. The brain was reduced in weight to 880 g. There was extensive necrosis affecting the cortex and basal ganglia and the cerebellum showed severe loss of Purkinje and granule cells. In certain nuclei of the thalamus there was neuronal loss and gliosis. There was relative sparing of the brain stem. The superimposed effects of retrograde degeneration is demonstrated in various sites.