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Biomedical subjects

K M Grigor

Publications and source records attributed to K M Grigor.

At least 37 records · Page 2Linked to original sources
PubMed1993

Hormones and growth factors in germ cell neoplasia: general discussion.

Fetal germ cells migrate along the dorsal mesentery to the genital ridge, and migration in the bloodstream occurs in some animals. Malignant transformation may occur before migration, and it is possible that testicular germ cell tumours have a monoclonal origin, even when bilateral. Different tumour foci have homogeneous chromosomal abnormalities. Migrating germ cells may lodge in extragonadal sites and give rise to tumours. Mouse fetuses exposed to oestrogen and testosterone in utero have an increased incidence of testicular maldescent and teratoma. Oestrogens and mullerian inhibitory substance in the fetus may influence human testicular tumour development. Testicular tumour patients may have elevated serum oestrogen levels which may be related to prognosis. Increased serum FSH may stimulate germ cell tumour growth. Ultrastructural studies indicate that malignant transformation of germ cells occurs early, but final tumour differentiation does not occur till after the malignant cells have invaded extratubular tissue.

Animals↗
PubMed1993

A new classification of germ cell tumours of the testis.

The partially conflicting British and WHO classifications of testicular tumours are confusing and fail to give due prominence to their histogenesis from carcinoma in situ (CIS). Spermatocytic seminoma does not originate from CIS and should be renamed 'spermatocytoma'. All other germ cell tumours are gonocytomas arising from CIS cells which have many of the characteristics of the gonocytes of the early embryo and fetus. Gonocytomas are subdivided into seminoma, if they retain their gonocyte characteristics, or teratogenic gonocytoma if the tumour stem cell has differentiation potential. A new category of anaplastic germ cell tumour is intermediate between seminoma and teratogenic gonocytoma. The teratogenic gonocytoma is an epiblastoma if no differentiation is manifest, but may differentiate along embryonic lines into teratoma or may show extraembryonic differentiation towards yolk sac tumour or choriocarcinoma. The new classification uses unambiguous terminology and is midway between the British and WHO classifications. Those familiar with either of these classifications should have no difficulty in adapting to the new proposals, and the new classification should help others to acquire a better understanding of the biology and pathology of testicular germ cell tumours.

Humans↗
PubMed1993

Should the contralateral testis be biopsied? Round table discussion.

Testicular tumours are bilateral in 5.2% of cases although the incidence of bilaterality is affected by the mode of treatment of the primary tumour. A biopsy of the contralateral testis of testicular tumour patients will reveal carcinoma in situ in 5.5% of cases. In Denmark, most testicular tumour patients have a contralateral biopsy at the time of the primary orchidectomy, but in many countries general urologists and surgeons are not always aware of the advantages of simultaneous contralateral biopsy. Some specialist centres perform a contralateral biopsy as a secondary procedure once the patient has been referred. It has not been the policy in USA to take a contralateral biopsy at the initial orchidectomy, nor to offer a biopsy to patients after referral to a specialist centre. As a result of the discussions at this conference, urologists in USA will now be encouraged to take a contralateral biopsy at the time of initial surgery. If this is not performed, patients should be offered a biopsy after a full discussion of the advantages and possible side effects of the procedure so that informed consent can be given.

Biopsy↗
PubMed1993

Reproductive aspects of testicular germ cell cancer: general discussion.

Gonadal function is affected by both chemotherapy and radiotherapy in the treatment of testicular cancer. Leydig cells are more resistant than germ cells, but endocrine function is also affected. Sex life is affected by treatment for testicular cancer but major permanent sexual dysfunction is not common. Radiotherapy is more damaging to Leydig cells than chemotherapy and can also cause direct effects on Sertoli cells. Leydig cell dysfunction following chemotherapy is dose-dependent. Serum FSH levels may be elevated at the time of primary orchidectomy and this may be used to predict ultimate fertility in these patients. Fertility does not recover if FSH levels are greater than 24 IU/l which is twice the upper limit of normal. Retroperitoneal lymph node dissection does not cause erectile dysfunction, but may cause dry ejaculation unless a nerve sparing operation is performed by an experienced surgeon. LHRH analogues causes reduced testosterone secretion, impotence and loss of libido, and requires exogenous androgen therapy. CIS can be eradicated by 20 Gy fractionated radiotherapy. This dose has been shown to have some effect on Leydig cell function but this is not clinically significant in the first 5 years of follow-up. The effects of lower doses of irradiation, which may be less injurious to Leydig cells, are currently being investigated. The effects of chemotherapy on CIS is as yet unpredictable.

Follicle Stimulating Hormone↗
PubMed1993

How should we identify high risk testicular tumour patients? Round table discussion.

Various prognostic models are used to predict the outcome of testicular tumour patients, and these are usually based on serum tumour marker levels (AFP and hCG), number and size of metastases to para aortic nodes, lungs and supraclavicular nodes. Greater predictive accuracy can be achieved if 'dynamic markers' are used in addition to these pretreatment variables. Dynamic markers are assessed during treatment by examining the rate of tumour marker decline. Prognostic models can subdivide patients into good risk, intermediate risk, and very poor risk groups. Cisplatin may be replaced by the less toxic carboplatin in good risk patients. High dose chemotherapy with autologous bone marrow transplantation should only be considered for very poor risk patients. Prognosis may be worse if the patient is a smoker, or if he has a first degree relative with testicular cancer. New markers such as chromosomal abnormalities or gene mutations should be examined.

Clinical Trials as Topic↗
PubMed1993

Should high dose chemotherapy with, or without, autologous bone marrow transplant be included in the primary treatment of testicular cancer? Round table discussion.

Most patients with metastatic testicular cancer can be cured by standard chemotherapeutic regimes but the group of high risk patients fail to respond adequately. The results of salvage chemotherapy trials including high dose chemotherapy (HDCT) plus autologous bone marrow transplantation (ABMT) or peripheral stem cell reinfusion (PSCR) suggest a dose response relationship indicating that the inclusion of HDCT + ABMT/PSCR could also have the potential of increasing survival of high risk patients in first line treatment. Therefore, in a coordinated international clinical trial HDCT + ABMT should be compared with the standard chemotherapy. The standard drug treatment worldwide for testicular cancer is PEB (cisplatin, etoposide, bleomycin) x3 for good risk and x4 for high risk patients, but there is cumulating evidence that VIP (cisplatin, ifosfamide, etoposide) is more effective for poor risk patients. Therefore in the randomized trial standard dose VIP would be compared with high dose carboplatin, etoposide and ifosfamide or cyclophosphamide (CEI or CEC). Because of the toxicity and expense of HDCT + ABMT it must be discussed whether this treatment could be given upfront to all patients with high risk criteria, or only to patients with poor response under standard dose induction chemotherapy (intensification or consolidation). If HDCT is considered for first line chemotherapie the group of patients with very poor prognostic criteria have to be selected very carefully to avoid overtreatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Impact of the environment on reproductive health: executive summary.

The papers presented at the workshop on the "Impact of the Environment on Reproductive Health" are published in this issue of the EHP Supplements. After the formal presentation of the papers, the authors and scientists met to discuss the important aspects of environmental issues affecting human reproductive health. This Executive Summary was compiled by the organizers and editors of the workshop and the proceedings.

Animals↗
PubMed1993

Regional and geographical variations in infertility: effects of environmental, cultural, and socioeconomic factors.

Fertility is affected by many different cultural, environmental, and socioeconomic factors, especially in developing countries where poverty and infections are commonplace. Environmental factors play a major role in infertility in Africa. One of the most important health problems in sub-Saharan Africa is the high rate of infertility and childlessness. The African society has a strong traditional heritage, and the study of the patterns of infertility in this part of the world would be incomplete without consideration of the sociocultural and environmental factors. The most cost-effective approach to solving the infertility problems in Africa is prevention and education. In Mexico, problems of reproductive health are associated with pregnancy in adolescents, sexually transmitted diseases and genitourinary neoplasms. Infertility affects 10% of couples, usually as a result of asymptomatic infection. Education, poverty, nutrition, and pollution are problems that must be tackled. The government has taken positive action in the State of São Paulo in Brazil, where gender discrimination is a major factor affecting women's health and reproductive outcomes. The implementation of new policies with adequate funding has resulted in marked improvements.

Africa↗
PubMed1989

Management of localised prostatic carcinoma.

Localised carcinoma of the prostate may be amenable to radical curative therapy. Staging pelvic lymphadenectomy is controversial but is the only means of demonstrating lymph node spread accurately. Five patients in a group of 16 who presented apparently with localised prostatic carcinoma, and who had negative bone scan and CT scan, were shown at operation to have metastatic carcinoma involving their lymph nodes; 3 of 8 patients with high grade tumours were free of lymph node metastases. Without staging lymphadenectomy, these patients may have been inappropriately treated.

Humans↗
PubMed1988

Effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: interim report from the Medical Research Council Subgroup on Superficial Bladder Cancer (Urological Cancer Working Party).

A randomised control trial of intravesical instillation of mitomycin C was conducted in 457 patients with cancer of the bladder that was confined to the submucosa on histological examination. The events studied were the recurrence free rate, the recurrence rate/year, and the number of new tumours developing/year. At the initial cystoscopy the tumours were completely resected and the patients randomised to have no instillation of mitomycin C, a single instillation of 40 mg in 40 ml of water at that cystoscopy, or a single instillation and then four further instillations. All patients had follow up cystoscopies every three months for the first year, twice in the second year, and yearly thereafter. After a median of 12 months, follow up information was available for 397 patients. Patients receiving both the single instillation of mitomycin C and the instillations at five cystoscopic examinations had significantly lower yearly recurrence rates and tumour rates than those in the control group, and the group receiving multiple instillations fared significantly better than those receiving a single instillation. The figures on progression to invasive cancer were too small to allow conclusions to be drawn.

Administration, Intravesical↗
PubMed1985

Urethral dysplasia and bladder cancer in cystectomy specimens.

Sixty-five patients had a cystectomy for a solitary bladder tumour (28) or multifocal lesions (37). The histological extent of the disease within the bladder was correlated with mucosal abnormalities within the urethra. The presence of multifocal or solitary bladder disease was not an accurate predictor of the presence or absence of urethral dysplasia. Details of mortality and morbidity associated with one-stage cysto-urethrectomy are presented and it is concluded that irrespective of whether the bladder contains a solitary or multifocal tumour, complete cysto-urethrectomy should be considered as the treatment of choice whenever cystectomy for attempted cure is indicated.

Adult↗
PubMed1984

Histopathological review of transitional cell carcinoma of the upper urinary tract.

A histopathological review of 30 patients with transitional cell carcinoma (TCC) of the upper urinary tract showed that 21 patients had dysplastic epithelium adjacent to the tumour, irrespective of the degree of invasion; 20 patients had multifocal disease with some degree of dysplasia or carcinoma elsewhere. It is concluded that radical surgery should be performed whenever possible, even in the superficial low grade tumour.

Adult↗