Prediction of relapse after lymph node dissection for germ cell tumours: can salvage chemotherapy be avoided?

Salvage chemotherapy has been used by some oncology centres for patients with residual malignant or immature elements in retroperitoneal lymph node dissections removed for metastatic non-seminomatous germ cell tumours. However, surveillance of these patients shows that many are cured by surgery alone. 118 retroperitoneal lymph node dissections for metastatic non-seminomatous germ cell tumours were reviewed and the morphology seen within them was quantified. 28 of these had immature or malignant elements and had been treated by surveillance before administration of further chemotherapy. The proliferation rate in these cases was assessed by immunochemistry. The proliferation index and the amount of embryonal carcinoma (EC) were both predictors of recurrence and therefore the need for further chemotherapy. Patients with greater than 25% of EC had an 84% chance of relapse and those with a Ki-67 index of greater than 50% had a 71% chance of relapse. The two tests had a positive predictive value of 83% and 71%, respectively. Patients with such a high risk of recurrence could be considered for post-operative adjuvant therapy at this point whilst others would be suitable for a watchful waiting approach.

Computed tomography 21 days after chemotherapy, three-dimensional estimates of metastatic volume and the need for surgery in patients with germ cell cancer.

OBJECTIVE: To assess whether the response visible on computed tomography (CT) 21 days after the first course of chemotherapy in patients with nonseminomatous germ cell tumour predicts the need for surgery and whether three-dimensional (3D) reconstruction adds to the diagnostic accuracy. PATIENTS AND METHODS: CT scans from 52 patients treated with cisplatin-based chemotherapy were assessed for tumour shrinkage by measuring the changes of a one-dimensional (1D) measurement of the maximum transverse diameter, and comparing CT scans before, 21 days after the first course and at the end of chemotherapy (1D method). In a subset of patients, using a special formula, the 1D-derived 2D and 3D shrinkage (2Dder and 3Dder) were compared with four other computed or calculated methods (1D, 2D, 3Dcalc, 3Dcomp). RESULTS: At day 21, in 32 of 52 patients (62%) there was < 50% tumour shrinkage using the 1D assessment; 21 of them (66%) needed surgery, compared with none of the 20 patients with > 50% tumour shrinkage by day 21 (chi2 = 22.83, P < 0.001). The 1D method showed significantly less shrinkage than all the other methods but when this was used to derive a 3D shrinkage, assuming the mass to be spherical (3Dder), it was not statistically different from that of 3Dcomp. CONCLUSIONS: The assessment of the response from 1D CT scan estimates 21 days after initiating chemotherapy identifies a subgroup of patients who have a high probability of needing surgery. Although expected to be more accurate, the 3Dcomp estimate of tumour shrinkage was no better than the 3Dder estimate.

Abdominal relapse in stage 1 nonseminomatous germ cell tumours of the testis managed by surveillance or with adjuvant chemotherapy.

OBJECTIVE: To assess the impact on patterns of recurrence of adjuvant chemotherapy in patients with stage 1 nonseminomatous germ cell tumours (NSGCT) of the testis, who have a high likelihood of relapse on surveillance if certain risk factors are identified in the orchidectomy specimen, and thus the theoretical need for retroperitoneal lymph node dissection (RPLND). PATIENTS AND METHODS: The incidence of abdominal relapse was recorded in 417 men presenting with stage 1 NSGCT over the past 18 years. Up to 1986, 161 men were managed by surveillance alone, and abdominal relapse occurred in 26. From 1986 onwards, men with positive risk factors in the orchidectomy specimen were offered two courses of chemotherapy; 60 accepted and one relapsed in the abdomen, and 196 underwent surveillance and 19 relapsed in the abdomen. RESULTS: Abdominal relapse was significantly reduced from 16% before 1986 to 8% afterward (P = 0.014). Mortality from testicular tumour or treatment toxicity remained low, at 0.6% before 1986 and 2.0% since then. CONCLUSION: The need for RPLND in stage 1 NSGCT remains highly doubtful.

Carcinoma in situ in the testis.

Carcinoma in situ (CIS) of the testis is a common precursor of germ-cell tumours in adults and adolescents, with the exception of spermatocytic seminoma. This article reviews existing knowledge on the pathobiology, genetic aspects and epidemiology of CIS, discusses current hypotheses concerning pathogenesis and invasive progression of germ-cell neoplasms and provides guidelines for diagnosis and clinical management of CIS.

Repeat epididymovasostomies: are they worthwhile?

OBJECTIVE: To establish whether it is worthwhile repeating epididymovasostomy in men with persistent obstructive azoospermia. PATIENTS AND METHODS: The study included 24 men with obstructive azoospermia, persisting after previous surgery for blockage in the body or tail of the epididymes, who underwent repeat epididymovasostomy proximal to the previous anastomoses. Semen was re-analysed after 6 and 12 months, and information about pregnancy self-reported or determined by postal survey. RESULTS: The postoperative sperm concentration was >107 /mL in 15 patients (62%) and 10 female partners became pregnant (41%). Antisperm antibodies were present in nine patients and three of their partners became pregnant after the man received steroid therapy. Unilateral revision did not produce a favourable outcome. CONCLUSION: Having defined a favourable group of men with obstructive azoospermia by scrotal exploration, i.e. those with caudal epididymal blocks and patent vasa deferentia, initial technical failure should not preclude surgical revision of the anastomoses in selected cases.

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.

Disorders of ejaculation.

Following John Hunter's example set over 200 years ago, it is clear that there is much to study and understand in disorders of ejaculation. Congenital malformations and their relationship to genetic disorders are now more clearly understood: these are matters of the utmost importance in the present era of assisted reproduction, if perpetuation of serious anomalies, such as fibrocystic disease, is to be avoided. Surgically induced injuries that impact upon male reproductive function are now recognized and largely preventable by careful attention to preservation of normal structures during extirpative surgery. Much work remains to be done on functional disorders, especially on the side effects of drug therapy, where some insight may be gained into the function and disorders of the basal ganglia--the 'dark basements of the mind'.

Seminal megavesicles with adult polycystic kidney disease.

Adult polycystic kidney disease has been found in association with pathological dilatation of the seminal vesicles in six patients. These men appeared normal on clinical examination, but had azoospermia or severe oligozoospermia. They were investigated by scrotal exploration with vasography, renal and transrectal ultrasound scans (TRUS), and percutaneous puncture of the seminal vesicles in one case, before and after resection of the ejaculatory ducts. This revealed that the gross dilatation of the seminal vesicles was not caused by obstruction, but appeared to be due to atonicity (megavesicles). These ultrasonic appearances, when described previously, were incorrectly thought to be due to seminal vesicle cysts.

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.

Retrograde embolization and causes of failure in the primary treatment of varicocele.

OBJECTIVE: To assess retrograde embolization for the treatment of varicocele and to examine the causes of surgical and radiological treatment failure. PATIENTS AND METHODS: Of 154 patients with clinical varicocele associated with subfertility or symptoms who were treated, 100 underwent surgical high ligation, retrograde embolization under fluoroscopic control was attempted in 84 and 30 had both forms of treatment. Venographic findings were defined in those patients for whom embolization proved impossible and in those in whom prior high ligation had failed. Among subfertile patients, 64 had semen analyses before and at least 3 months after the procedure available for comparison. Those patients undergoing both radiological and surgical procedures were sent questionnaires to evaluate their experience. RESULTS: Retrograde embolization was technically successful in 68 (81%) of the 84 patients. Two early failures were associated with venous spasm provoked by technical inexperience, while difficulties in the remainder were caused by anomalous venous anatomy. In patients who had recurrent varicocele after previous ligation, venography showed incomplete ligation of collateral channels; 14 of 18 patients were successfully re-treated by embolization. The sperm concentration improved significantly in 83% of patients undergoing embolization and in 63% of those surgically ligated. Patients who underwent both procedures expressed a strong preference for embolization. CONCLUSION: In centres where there is a skilled interventional radiologist, embolization is an effective alternative to surgical ligation of varicocele. Carried out under local anaesthesia as an out-patient procedure, it is cost-effective, associated with minimal morbidity and most patients are able to return to normal daily activities immediately.

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.

Management of urological tumours in pregnancy.

Urological tumours are rare in pregnancy and may be mistaken for other, more common conditions such as urinary infection, pyelitis, threatened abortion or pre-eclampsia. With modern imaging techniques, especially ultrasonography and NMR, the diagnosis can be accurately established. In collaboration with obstetric and medical colleagues, the urologist can deal with these tumours safely and effectively, provided that the timing and extent of treatment are carefully tailored to the stage of the pregnancy.

Evaluation by magnetic resonance imaging of the inferior vena cava in patients with non-seminomatous germ cell tumours of the testis metastatic to the retroperitoneum.

OBJECTIVE: To assess the role of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) in evaluating suspected occlusion of the inferior vena cava (i.v.c.) in patients with abdominal nodal metastases from non-seminomatous germ cell tumours, thus giving information that may be helpful in planning surgery and for determining the need for anticoagulant therapy. PATIENTS AND METHODS: Five patients with abdominal nodal metastases in whom occlusion of the i.v.c. was suspected on computed tomography (CT) were imaged using a 1.5 T MRI scanner. The MRI findings were compared with those from CT. RESULTS: The MR images successfully and clearly detected partial and total occlusions of the i.v.c. by both intraluminal thrombus and extrinsic compression. The technique also clearly detected extensive collateral venous circulation in several cases and in one a cavernous transformation of the i.v.c. In all patients, the MRI studies provided better information than that from CT. CONCLUSION: MRI, and particularly MRA, is a comparatively new technique that is non-invasive and offers the potential of evaluating vascular structures with no need for ionizing radiation or contrast media. This technique, if available, should be chosen for imaging the i.v.c. in patients suspected of having compression or occlusion of the i.v.c.

Bladder replacement by ileocystoplasty: the final treatment for interstitial cystitis.

OBJECTIVE: To develop and improve the technique of bladder replacement with ileum in patients with interstitial cystitis. PATIENTS AND METHODS: A consecutive series of 27 patients (23 women and four men, median age 61 years, range 40-79) with chronic severe interstitial cystitis refractory to conservative therapies underwent cystectomy and bladder replacement using an ileal pouch. The relief of pain was assessed over a median follow-up of 30 months (range 2-48). RESULTS: Pain relief was complete in all patients and the median neo-bladder capacity was 520 mL (range 350-700). Only four patients required intermittent self-catheterization to drain post-micturition residual urine. Bladder calculi formed in two patients and were removed successfully at cystoscopy. CONCLUSION: Bladder replacement with ileum in the form of the Kock pouch is an effective surgical treatment for intractable interstitial cystitis.