Biomedical subjects
Publications and source records attributed to B J Jenkins.
This report describes a patient who underwent a partial orchidectomy for testicular cancer, having already had a radical orchidectomy of the contra lateral side. He subsequently fathered two children. This policy may have a role in the management of men with an early germ cell tumour in a solitary testis who have not completed their family.
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An increased long-term morbidity rate after transurethral compared with open prostatectomy has recently been claimed on the basis of retrospective studies of operations done up to 20 years ago. These studies have led to a demand for a prospective trial. Most reports show that peri-operative mortality following prostatectomy is virtually confined to unfit men over 80 years old. Before agreeing to participate in a trial we examined our operative mortality in this group of patients. Between 1981 and 1987, 123 octogenarians underwent transurethral prostatectomy: 64 operations were elective and 59 were performed for retention. There were 2 operative deaths (1.6%), both from gram-negative septicaemia despite prophylactic antibiotics. There were no additional deaths in the first 12 months following surgery. Few of these patients would have been considered fit to undergo an open prostatectomy. Any proposed randomised trial would have to exclude such high risk patients until it can be shown that open prostatectomy is equally safe.
Of 134 males with traumatic rupture of the urethra seen between 1967 and 1989, 10 have been lost to follow-up and 124 have been followed up for 1 to 22 years (mean 8); 100 patients had a pelvic fracture (3 with associated rectal injury) and 24 had perineal injuries. Prior to referral 31 patients (25%) had undergone treatment in addition to suprapubic cystostomy. Wherever possible, strictures were managed by optical urethrotomy (33) or intermittent dilatation (4). In 2 patients only a suprapubic cystostomy was possible. Skin inlay urethroplasty in 1 or 2 stages was performed in 75 cases, an end-to-end anastomosis with or without resection of the symphysis pubis in 7 and a scrotal tube pull-through in 3. The immediate and long-term results depended on the severity of the original injury. With minimal displacement the management was simple and the long-term prognosis good, a single urethrotomy being sufficient in 22 patients. Where there was considerable displacement the initial management was more difficult and there was a high incidence of long-term complications: of 73 patients treated by urethroplasty or end-to-end anastomosis, significant post-operative infection occurred in 11 (15%) and restenosis in 15 (20%), of whom 7 required a revision urethroplasty. Data in respect of potency were recorded in 80 patients: 28 of these were impotent, 20 of the 28 having sustained an injury with considerable displacement.
The cysteine-rich keratin proteins of the hair cuticle are derived from a multigene family that has been highly conserved during mammalian evolution. We have recently characterized one cuticle keratin gene isolated from a sheep lambda library, and Southern blot analysis of that clone suggested the presence of a second related gene. In the present paper sequencing of the second gene has now indicated that it is a pseudogene, a finding supported by a lack of expression in vivo. The pseudogene appears to have arisen by gene duplication, possibly from the adjacent functional gene. Key mutations seem to have occurred in the promoter and processing signals of this gene to render it non-functional and two in-frame termination codons are present in the coding region. A possible recombination point between sequences encoding glycine-rich repeats was identified that could have lead to the creation of the in-frame termination codons.
The quality of life in 72 patients who had shown a complete response to radiotherapy, using a modified bladder symptom score and the Nottingham health profile, was compared with the quality of life in a similar control group matched for age and sex. There was no significant difference in either group. The records of 69 patients who had undergone post-radiation salvage cystectomy were reviewed, looking specifically at surgical complications. There were 3 post-operative deaths (5%), 3 pulmonary emboli and 3 fistulae--with some overlap of complications. Five patients who underwent cystectomy for intractable symptoms in the apparent absence of recurrent tumour were found to have residual cancer in the excised specimens.
A genetic locus associated with familial Alzheimer disease (FAD) and a candidate gene, APP, encoding the amyloid protein precursor have both been assigned previously to chromosome 21, and, in a few FAD families, mutations of APP have been detected. However, obligate crossovers between APP and FAD have also been reported in several FAD pedigrees, including FAD4, a large kindred showing highly suggestive evidence for linkage of the disorder to chromosome 21. In case the apparent APP crossover in FAD4 actually represented an intragenic recombination event or segregation of different mutations in different family branches, we have performed a more detailed assessment of APP as a candidate gene in this family. The entire coding region of the APP gene was sequenced for FAD4 and for FAD1, a second large kindred. No mutations were found, indicating that, in at least one chromosome 21-linked FAD pedigree, the gene defect is not accounted for by a mutation in the known coding region of the APP gene. A total of 25 well-characterized early- and late-onset FAD pedigrees were typed for genetic linkage to APP, to assess the percentage of FAD families predicted to carry mutations in the APP gene. None of the FAD families yielded positive lod scores at a recombination fraction of 0.0. To estimate the overall prevalence of FAD-associated mutations in the beta A4 domain of APP, we sequenced exons 16 and 17 in 30 (20 early- and 10 late-onset) FAD kindreds and in 11 sporadic AD cases, and we screened 56 FAD kindreds and 81 cases of sporadic AD for the presence of the originally reported FAD-associated mutation, APP717 Val----Ile (by BclI digestion). No APP gene mutations were found in any of the FAD families or sporadic-AD samples examined in this study, suggesting that the mutations in exons 16 and 17 are a rare cause of FAD. Overall, these data suggest that APP gene mutations account for a very small portion of FAD.
Contrary to the traditional doctrine of delayed intervention in post-hysterectomy injuries of the ureter or bladder, the policy at our department has been to operate as soon as possible after the diagnosis is made. Of 68 patients (25 with vesicovaginal fistulas and 43 with ureteral injuries) early intervention was possible in 40 (59%). Primary healing was obtained in all patients. These results suggest that there is no disadvantage in early repair.
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A total of 143 patients with superficial G2 (pTa, pT1) bladder cancer (48 G2pTa; 95 G2pT1) presenting between 1970 through 1987 were reviewed. Of 48 patients with G2pTa followed for up to eighteen years, G3 recurrence developed only in 1 (2.0%), and invasive cancer (greater than pT2) developed only in 2 (4.2%). They both received radiotherapy and have responded completely. There have been no cancer-related deaths. In contrast, in the 95 patients in whom the basement membrane had been breached (pT1), higher grade tumor (G3) developed in 11 (11.5%), and 15 (16%) had recurrences with invasion of muscle (greater than pT2). Among these there were 7 (7.3%) cancer-related deaths.
The original pre-treatment histological sections from 125 patients with invasive (T2/T3) transitional cell bladder cancer treated by radical radiotherapy were studied; 63 tumours responded completely to radiation and 62 did not; 55 of 72 tumours containing areas of squamous metaplasia and 27 of 36 staining for beta-human chorionic gonadotrophin failed to respond to radiotherapy; 26 of 28 tumours showing both squamous metaplasia and beta-human chorionic gonadotrophin did not respond to radiation, whereas 40 of 45 tumours without either of these features responded. The DNA ploidy of 86 tumours in the series was measured by flow cytometry; 11 of 27 aneuploid and 30 of 59 diploid tumours responded to irradiation. Squamous metaplasia and beta-human chorionic gonadotrophin in bladder cancer indicate resistance to radiotherapy but DNA ploidy does not.
Twenty-nine patients with primary hyperparathyroidism underwent double-tracer subtraction scanning after injection of 201Tl as thallous chloride for thyroid and parathyroid images followed by 99mtechnetium as sodium pertechnetate for thyroid images prior to surgical exploration of the neck. The operative findings were correlated with the scans. All 23 adenomas (100%) and 13 of 18 (72%) hyperplastic glands were correctly localized. The ability of the scan to identify abnormal parathyroids was determined by the gland mass rather than whether the tissue was adenomatous or hyperplastic as all 32 (100%) abnormal glands weighing more than 180 mg were successfully localized in contrast to four of nine (44%) glands weighing less than 180 mg. An additional technique, in which emission tomography was carried out after subtraction scintigraphy, was used on 11 patients in the series. In all 11, the site of a single abnormal gland was predicted by the conventional subtraction scan: in nine of these patients, emission tomography provided additional localization of the gland in the anteroposterior plane.
A retrospective analysis of the prognostic value of pretreatment histology and expression of human chorionic gonadotrophin (B-hCG) was carried out in 100 invasive (T2/T3) transitional cell carcinomas of the bladder treated in a uniform manner. After transurethral resection of the tumour, all patients received a course of radical radiotherapy, with salvage cystectomy for those who failed to respond. Forty-nine of 100 patients responded to radiation; thus 51 did not. Forty-seven of 60 (78%) patients whose tumours contained areas of squamous differentiation and 22 of 29 (76%) of tumours staining positively for HCG failed to respond to radiotherapy. Twenty-two of 23 (96%) patients with tumours that had both these features did not respond to radiotherapy. The other histological features studied (grade of tumour, necrosis, inflammation, vascular invasion, and growth pattern) appeared unrelated to each other or to clinical outcome.
A group of 29 patients underwent salvage node dissection for residual retroperitoneal masses following orchiectomy and combination chemotherapy for advanced testicular cancer between 1980 and 1988. The results confirm that surgery for residual retroperitoneal masses following combination chemotherapy is worthwhile and whenever possible the sympathetic chain should be preserved.
Poorly differentiated (G3) cancers are known to have a worse prognosis than other superficial bladder tumours. In the period 1976 to 1987, 53 patients with G3pT1 disease were treated by radical radiotherapy with a 5-year survival rate of 64%. Thirteen patients (25%) developed an invasive tumour during the follow-up period. The presence of secondary carcinoma in situ was associated with a poor prognosis. These results are better than those reported for transurethral resection alone and suggest that radiotherapy is the treatment of choice in G3 superficial tumours.
Beta human chorionic gonadotrophin (beta HCG) was measured in 127 urine and 85 serum samples from 175 untreated patients with urothelial cancer. Serum levels of beta HCG were substantially elevated in 16 of 21 patients (76%) with widespread metastases but in only 2 of 64 patients (3%) with disease confined to the pelvis. Urine beta HCG levels were moderately raised in 11 of 25 patients (44%) with locally advanced disease, but greatly elevated in 5 of 7 patients (71%) with metastases. Measurement of serum and/or urine beta HCG appears to be an efficient diagnostic marker for the presence of distant metastases in bladder carcinoma.
One hundred and forty six patients with advanced germ cell testicular tumours (38 seminomas and 108 malignant teratomas) treated by combination chemotherapy were studied over 10 years. Most of the improvement seen was in patients with malignant teratoma undifferentiated. In the most recently treated patients (1984-1987) 75% of drug resistant cases were malignant teratoma intermediate compared with 26% in the series treated between 1978-1983. The microscopic features of 52 primary testicular tumours were compared with features seen in excised retroperitoneal lymph nodes after completion of chemotherapy. Primary malignant teratoma intermediate had a higher incidence of viable malignancy in the excised tissue than malignant teratoma undifferentiated. Mature teratoma or fibronecrotic tissue within resected tissue was associated with a good prognosis. If resection was complete patients with drug resistant malignant teratoma intermediate had a more favourable prognosis than drug resistant malignant teratoma undifferentiated. It is advised that retroperitoneal node dissection should be considered in the management of patients with advanced germ cell testicular tumours, and that as complete a resection as possible be attempted to avoid the danger of missing residual disease.