Testis conserving chemotherapy in germ cell cancer: its potential to increase understanding of the biology and treatment of carcinoma-in-situ.

Prompted by recognition of the potential of chemotherapy to increase the success of testis conserving surgery in patients with germ cell cancer, background and outcome data are reviewed and their contribution to the ongoing debate about how germ cell cancer develops discussed. The review is based on three previous studies of: a) time trends in tumour size in 578 personal series of all stages of testis cancer treated since 1978; b) impact of chemotherapy on actuarial risk of tumours in contralateral testis examined on 1221 patients treated in trials through the Anglian Germ Cell Cancer Consortium; and c) testes conservation attempted using chemotherapy in 78 patients. Since 1978 tumour size has decreased from 4.8 to 3.0 cms while cure has gone from 77 to 97%. There was no overall long term reduction in second cancers beyond 10 years in stage 1 patients after orchidectomy alone compared to stage 1 or metastatic disease patients receiving chemotherapy though the incidence was non significantly lower up to 10 years particularly in those patients receiving etoposide based combination. Testis conservation was initially successful in 28 of 78 (36%). An additional 25 (32%) had no viable cancer in orchidectomy specimen. In the 28 primary tumours cured by chemotherapy there was a 26% late relapse rate between 5 and 10 years (all cured by orchidectomy) compared to less than 5% in those cured with established metastases. In conclusion, testis conservation with chemotherapy is safe and feasible, though relapse is too frequent for routine service use. Confirmation of the high frequency of late relapse by others has raised the question whether these recurrences are due to post pubertal events reinducing CIS in intrauterine oestrogen primed germ cells and highlights the potential of testes conservation studies to better understand germ cell cancer development.

Testicular microlithiasis: is it a benign condition with malignant potential?

OBJECTIVE: To review the findings of testicular ultrasonography (US) in patients referred for testicular symptoms including pain, swelling and infertility, and to determine the prevalence of testicular microlithiasis (TM) and ist relevance to the development of testicular cancer. METHODS: Records of 3,026 patients referred for testicular US between 1994 and 1999 were evaluated. The indications for testicular US diagnosis, management and relevant histological details were obtained from medical records. Patients with TM had an annual sonographic follow-up unless they had testicular cancer, in which case follow-up repeat US with clinical reviews was more frequent. RESULTS: TM was found in 54 patients (1.77%; median age 34 years, range 12-83 years). The median follow-up was 36 months (range 12-18 months). Sixteen of these patients had testicular malignancy (30%). The remaining 38 patients had hydrocele and epididymal cysts (14), varicocele (7), epididymitis (2) and small testes (8), with 14 patients having no other pathology. One patient with a small testis developed a seminoma while under surveillance. Another patient with metastatic embryonal-cell carcinoma at initial diagnosis was found to have a seminoma 4 years following chemotherapy. The relative risk of testicular tumours in the presence of TM was 13.2 (confidence interval 8.3-21.5). CONCLUSION: TM can no longer be regarded simply as a benign condition because of its association with testicular malignancy. In our series, 2 patients (5.2%) developed interval testicular cancers during follow-up US. There is no convincing evidence to suggest that TM might be premalignant. In rare instances of radiologically indeterminate cases, biopsy of the testis may be necessary.

Endoscopic bladder neck suspension revisited: long-term results of Stamey and Gittes procedures.

OBJECTIVE: To evaluate the long-term results of Stamey's and Gittes' procedures for genuine stress incontinence. METHODS: 72 needle procedures (34 Stamey; 38 Gittes) performed by a single surgeon between 1988 and 1994 were retrospectively reviewed. All patients had genuine stress incontinence on preoperative video-urodynamics. Review was at 3 months and thereafter clinically determined. Update information was gained by a patient satisfaction questionnaire. RESULTS: Data were available for 9 years for the Stamey group (mean 8.4 years) and 6 years for the Gittes' (mean 5.3 years). At 3 months, 93% were dry. There was a gradual attrition with 38% of the Stamey and 14% of the Gittes patients remaining dry or improved at 5 years. At 9 years, only 28% of the Stamey patients maintained their improvement. 26% of the original cohort underwent a second procedure. All patients who had repeat needle operations have failed. 48 questionnaires (67%) were returned. Only 25% of patients expressed satisfaction with their operation. CONCLUSION: Early success rates with endoscopic bladder neck suspension are replaced by long-term failures. The durability is poor with an ongoing recurrent incontinence rate. Repeat procedures are not worthwhile. Gittes' procedure appears to have an earlier failure rate compared to Stamey's operation.

Imaging with prostate-specific membrane antigen (PSMA) in prostate cancer.

Radioimmunoscintigraphy using a radio-labelled antibody to prostate-specific membrane antigen (PSMA) has growing applications as a means of tissue-specific imaging based on functional characteristics and complements traditional staging investigations. Clinical applications in men with carcinoma of the prostate are being refined, and this study reports outcomes with this technique in our practice. Prostatic immunoscintigraphy scans were performed with In-111 CYT 356 in 49 men with carcinoma of the prostate, obtaining sequential images in two and three dimensions at 10 min, 24 and 48 h. Of the 49 men, 36 had clinically localized cancer, 10 had recurrent disease after radical radiotherapy or radical prostatectomy and three had rising PSA after primary endocrine treatment. Scan findings are discussed in the context of clinical management. Of the 36 men with clinically localized cancer, seven had increased uptake in regional and distant lymph nodes. Of these seven, three were treated with hormone manipulation, two by radical prostatectomy and two by radical radiotherapy. Among 10 patients who had recurrence after radical treatment of the primary tumour, scans showed local recurrence alone in four, and six had regional or distant metastases. Three patients treated with primary hormone manipulation had scans for rising PSA, and of these one had a positive regional node and two had distant soft tissue and bone metastases. In conclusion, prostatic radio-immunoscintigraphy scans highlight tissues involved by prostate cancer, including the prostate, lymph nodes, soft tissues and bone metastases as well as pelvic recurrence. Results may contribute to the clinical management of individual patients, although histological confirmation may be appropriate when considering alternative treatment. Prostate Cancer and Prostatic Diseases (2000) 3, 47-52

The management of residual masses after chemotherapy in metastatic seminoma.

OBJECTIVE: To review our experience in management of residual masses after chemotherapy for metastatic seminoma. PATIENTS AND METHODS: The study comprised a review of 107 patients with metastatic seminoma, treated with initial chemotherapy from 1978 to 1996. Forty-three patients had residual masses detected by computed tomography after chemotherapy, while 64 achieved a complete response. Residual masses were classified radiologically as <3 cm or >/=3 cm and as well- or poorly defined. Of the patients with residual masses, 19 underwent surgery, while 24 were observed. RESULTS: Viable cancer was present in six of 11 patients with well-defined residual masses of >/=3 cm (positive histology in three of six undergoing surgery and site relapses in three of five observed), one of 14 patients with poorly defined masses of >/=3 cm (negative histology in nine undergoing surgery and site relapse in one of five observed), and in none of 17 patients with residual masses of <3 cm (negative histology in four undergoing surgery and no site relapses in 13 observed; one additional patient in this group died from treatment complications). CONCLUSION: Patients with a complete response after chemotherapy, a residual mass of <3 cm and a poorly defined residual mass of >/=3 cm can be observed, reserving intervention for recurrent or progressive disease. Well-defined residual masses of >/=3 cm should be resected because there is a 55% likelihood of persistent tumour.

A lesson in the management of testicular cancer in a patient with a solitary testis.

Five per cent of patients with germ cell tumours of the testis will develop a further tumour in the contralateral testis. Standard treatment in such cases is a second orchidectomy, resulting in infertility, hormone replacement, and psychological morbidity. In this case report we explore the role of testis conservation in these patients and also show that there is a risk of removing a potentially normal testis if a histological diagnosis is not sought prior to orchidectomy.

Surgery as salvage therapy in chemotherapy-resistant nonseminomatous germ cell tumours.

OBJECTIVE: To review our experience of surgical staging for residual masses after chemotherapy in patients with nonseminomatous germ cell tumour (NSGCT) and positive tumour markers. PATIENTS AND METHODS: Of 107 patients with metastatic NSGCTs treated surgically after chemotherapy from 1978 to 1995, 30 (median age 30.5 years, range 20-52) had positive tumour markers. These patients were reviewed and the outcome compared with 77 patients who had normal tumour marker values. RESULTS: Of the 77 patients with negative markers undergoing surgical/pathological staging, 71 (92%) became continuously disease-free, including 37 of 50 (74%) with viable NSGCT in excised specimens. Seventeen of 30 (57%) with raised marker levels undergoing similar surgery for chemotherapy-resistant tumour became disease-free, including 11 of 22 with viable NSGCT in the excised specimens. CONCLUSION: Although the outcome after surgery is better in patients with negative tumour markers, it is clear that surgery is curative for patients with localized chemotherapy-resistant masses. There is a need for continued debate on the timing of salvage surgery and subsequent chemotherapy.

A single-centre observational study of surgery and late malignant events after chemotherapy for germ cell cancer.

OBJECTIVE: To review the impact of surgical staging after treatment on the late malignant events in an unselected group of patients treated with chemotherapy for germ cell cancer of the testis over the last 16 years. PATIENTS AND METHODS: The study comprised 256 patients treated between 1978 and 1994 who were reviewed for late relapse and development of second germ cell and non-germ cell cancer. RESULTS: At diagnosis, 142 patients had clinical stage 2, 30 stage 3 and 84 stage 4 disease; 57 patients relapsed within 20 months of treatment, while late germ-cell cancer relapses (> or = 24 months after treatment) occurred in six patients. Of patients relapsing early or late, 42% and 33%, respectively, received surgery after treatment. Only two of those relapsing late remain progression-free with further treatment. Four patients developed germ cell cancer in the contralateral testis, while six developed second non-germ cell cancers. CONCLUSION: Late events occurred in 6.2% of 256 patients in this series, from 29 to 141 months after treatment. Given that the late relapse rate of six of 256 (2.3%) is less than the incidence of mature teratoma at routine retroperitoneal lymph node dissection, more patients may eventually relapse. These results suggest that there might be a case to evaluate the use of ultrasonographic surveillance of the retroperitoneum and testis at 5, 10 and 20 years, in addition to extending routine surveillance.

Verrucous carcinoma of the renal pelvis: case presentation and review of the literature.

Squamous cell carcinoma (SCC) of the renal pelvis is an uncommon tumour that has occasionally been associated with horseshoe kidney. The verrucous form of well-differentiated SCC has not been described previously at this site. We describe such a tumour in a 41-year-old man, who presented with gross haematuria and recurrent pyelonephritis caused by staghorn calculi within a horseshoe kidney. Histology showed extensive keratinising squamous metaplasia of the pelvic urothelium with an area of verrucous acanthosis and underlying invasion of the pelvic smooth muscle by broad tongues of squamous epithelium without atypia. Local lymph nodes were not involved by tumour. Immunohistochemistry and polymerase chain reaction revealed no evidence of human papillomavirus infection. The literature regarding verrucous carcinoma of the urothelial tract is reviewed.

beta hCG as a prognostic marker in adenocarcinoma of the prostate.

AIMS: To assess the importance of immunohistological detection of beta-human chorionic gonadotrophin (beta hCG) in localised prostatic adenocarcinoma with regard to prognosis and clinical applications. METHODS: Eighty consecutive cases of clinically localised adenocarcinoma of the prostate were studied retrospectively. Immunohistological analysis on formalin fixed, paraffin wax embedded prostate tissue from transurethral resections was related to clinical outcome and survival. Prognosis was also related to tumour grade. RESULTS: beta hCG was detected in 12 cases. Nine of these patients were found to have metastases (75%) at follow up and 11 (92%) were dead within 18 months. There was no correlation with grade and prognosis in this group. Of the 68 beta hCG negative cases, 21 had developed metastases (31%) and 25 (37%) had died within 18 months. In the beta hCG negative group there was an association between histological grade and survival. CONCLUSION: The demonstration of beta hCG in prostatic adenocarcinoma identifies a group of patients with poor prognosis, irrespective of histological grade. This additional information will be extremely valuable in the subsequent clinical management of such patients.

A study of spermatozoal motility in type 1 diabetes mellitus.

The aim of the study was to examine an aspect of male fertility in patients with Type 1 diabetes mellitus (n = 17) compared to healthy control subjects (n = 16) using parameters of sperm motility, measured using a computerized image analysis system (the Hamilton Thorn Research HTM-2030 Motility Analyzer), as indicators of potential fertility. Within the diabetic group no correlations were found between sperm motility and age, age of onset of diabetes, duration of diabetes or glycated haemoglobin. When the diabetic and control groups were compared, track speed, path velocity, progressive velocity, and lateral head displacement were not significantly different, whereas linearity and linear index, measures of straightness of swimming, were significantly greater in the diabetic subjects (59.2% vs 69.8%, p = 0.0005 and 76.4% vs 83.6%, p = 0.0016, respectively). We conclude that diabetic men, in the absence of complications, do not appear to be at a disadvantage in terms of sperm motility compared to healthy individuals.

Pelvic floor physiology in women with faecal incontinence and urinary symptoms.

Anorectal manometry, balloon proctometrography, measurement of anorectal angles and videourodynamics were used to investigate 45 asymptomatic women and 13 with faecal incontinence and urinary symptoms, nine of whom also had stress urinary incontinence. The anorectal angle was measured and videourodynamics performed on 17 constipated women with urinary symptoms. Mean (s.e.m.) values obtained with anorectal manometry were lower in women with faecal incontinence and urinary symptoms than in controls (maximum resting pressure 42.5(8.1) versus 82.5(9.3) cmH2O, P = 0.001; maximum attained pressure 80.5(13.7) versus 216.2(11.2) cmH2O, P = 0.001; maximum squeeze increment 35.3(7.5) versus 141.6(10.0) cmH2O, P = 0.001), indicating a weakened puborectalis and external anal sphincter. Mean(s.e.m.) anorectal angles at rest, squeeze and strain were all significantly greater in the doubly incontinent women than in those with constipation (114(3.8) versus 93(5.9) degrees, P = 0.01; 103(2.5) versus 78(3.5) degrees, P < 0.001; 120(2.9) versus 104(4.2) degrees, P = 0.01). Urinary incontinence was worse in the doubly incontinent than in the constipated women (eight of nine versus one of eight with grade 2a or higher, P = 0.002). These results suggest that doubly incontinent women have a significantly weakened pelvic floor and that this should be taken into account before any planned surgery for urinary incontinence.

Comparison of laparoscopic and open ligation of the testicular vein.

Scrotal varicoceles undoubtedly contribute to subfertility in an as yet undefined group of patients. The best method of treatment of varicoceles, however, remains controversial. Laparoscopic testicular vein ligation has recently been offered as a new option. We examined the feasibility of laparoscopic testicular vein ligation (n = 11) compared with standard high ligation (n = 11). The mean post-operative stay in the open group was 25.6 h compared with 7.1 h in the laparoscopic group. Analgesic requirements were a mean of 4.73 Co-proxamol tablets for the open group and 0.18 tablets for the laparoscopic group. All operations were successful. Laparoscopic ligation of the testicular vein is an effective treatment of varicocele with decreased post-operative morbidity.

Simultaneous dynamic electromyographic proctography and cystometrography.

The rectum and bladder share a common origin and work in harmony; disturbance in one may lead to a similar problem in the other. The two have, however, not previously been investigated dynamically and simultaneously. A new system has been devised allowing dynamic integrated electromyographic proctography to be performed simultaneously with cystometrography in 41 patients (28 women and 13 men). Of 16 women with chronic constipation who underwent the combined study, ten were shown to have obstructed micturition. Eight of these ten women exhibited an inappropriate contraction of the puborectalis muscle during micturition, compared with one of the six with normal micturition (P = 0.02). Of the patients with obstructed micturition, seven of eight women with a rectocele also had anismus, compared with none of four women with a rectocele among those who were able to micturate normally (P = 0.02). Eight of the ten women with obstructed micturition thus had a proctological abnormality that explained the urological symptoms. Of 12 women with idiopathic faecal incontinence who underwent the combined study, eight were shown to have genuine stress incontinence of urine. In seven of these the severity was shown to be of type 2a or greater, indicating that pelvic floor dysfunction may be the causal factor of both rectal and urinary symptoms. The combined study shows abnormalities in one system that could explain similar symptoms in the other.