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Consultant gynecologic oncologists from the regional Comprehensive Cancer Center assisted community gynecologists in the surgical treatment of patients with ovarian carcinoma when they were invited. For this report, the authors evaluated the effects of primary surgery by a gynecologic oncologist on treatment outcome.The hospital files from 680 patients with epithelial ovarian carcinoma who were diagnosed between 1994 and 1997 in the northern part of the Netherlands were abstracted. Treatment results were analyzed according to the operating physician's education by using survival curves and univariate and multivariate Cox regression analyses.Primary surgery was performed on 184 patients by gynecologic oncologists, and on 328 patients by general gynecologists. Gynecologic oncologists followed surgical guidelines more strictly compared with general gynecologists (patients with International Federation of Gynecology and Obstetrics [FIGO] Stage I–II disease, 55% vs. 33% [P = 0.01]; patients with FIGO Stage III disease, 60% vs. 40% [P = 0.003]) and more often removed all macroscopic tumor in patients with FIGO Stage III disease (24% vs. 12%; P = 0.02). When patients were stratified according to FIGO stage, the 5‐year overall survival rate was 86% versus 70% (P = 0.03) for patients with Stage I–II disease and 21% versus 13% (P = 0.02) for patients with Stage III–IV disease who underwent surgery by gynecologic oncologists and general gynecologists, respectively. The hazards ratio for patients who underwent surgery by gynecologic oncologists was 0.79 (95% confidence interval [95%CI], 0.61–1.03; adjusted for patient age, disease stage, type of hospital, and chemotherapy); when patients age 75 years and older were excluded, the hazards ratio fell to 0.71 (95% CI, 0.54–0.94) in multivariate analysis.The surgical treatment of patients with ovarian carcinoma by gynecologic oncologists occurred more often according to surgical guidelines, tumor removal more often was complete, and survival was improved. Cancer 2006. © 2005 American Cancer Society.

The current study reviews chronologic changes in the long term outcome of patients with metastatic nonseminomatous testicular germ cell tumors (NSTGCT) who were treated at a single institution during the past two decades. The 10-year survival of prognostic subgroups according to the classification of the International Germ Cell Consensus Classification Group (IGCCCG) and various other prognostic classifications is examined in time to evaluate whether cumulative experience has led to an improved outcome of patients with metastatic NSTGCT and to explore differences in outcome of prognostic subgroups. Two hundred ninety-nine patients with metastatic NSTGCT who were treated with cisplatin-based polychemotherapy during the period from 1977 to 1996 were staged retrospectively according to the Royal Marsden (RM) classification and the following prognostic classifications: IGCCCG, Indiana, Medical Research Council (MRC), and European Organization for Research and Treatment of Cancer (EORTC). The numbers of patients who were treated during the periods 1977–1986 and 1987–1996 were 146 and 153, respectively. Survival curves were constructed using the Kaplan–Meier method, and disease specific 10-year survival rates of prognostic subgroups treated during the two consecutive 10-year periods were compared using the log rank test. The median follow-up of surviving patients during the periods 1977–1986 and 1987–1996 was 14.7 years (range, 0.2–20.6 years) and 7.0 years (range, 0.4–11.4 years), respectively. The actuarial disease specific 10-year survival rate of patients with metastatic NSTGCT increased from 76% during the period 1977–1986 to 88% during the period 1987–1996 (relative risk [RR], 0.51; 95% confidence interval [95% CI], 0.29–0.89; P < 0.05). The 10-year survival rates of patients with good, intermediate, and poor prognoses according to the IGCCCG classification were 95%, 74%, and 37%, respectively, during the period 1977–1986 and 94%, 87%, and 66%, respectively, during the period 1987–1996. Patients with a poor prognosis according to the IGCCCG classification showed the greatest increase in 10-year survival (RR, 0.43; 95% CI, 0.18–1.04; P = 0.06). Analysis using the RM, Indiana, and EORTC classifications also showed an improved 10-year survival rate of patients with a poor prognosis who were treated during 1987–1996 compared with those who were treated during 1977–1986. The 10-year survival rate of patients with metastatic NSTGCT who were treated with cisplatin-based chemotherapy significantly increased from 76% during the period 1977–1986 to 88% during the period 1987–1996. This improvement during the cisplatin era resulted mainly from an increase in the survival of patients with metastatic disease who had a poor prognosis. These results indicate that the management of patients with NSTGCT is still improving. Cancer 2001;91:1304–15. © 2001 American Cancer Society.

Semen quality and serum testosterone, LH, and FSH levels were studied in 54 patients with a unilateral nonseminomatous tumor of the testis-14 before and 40 after orchiectomy.Semen analyses before and after orchiectomy gave essentially no different results: a poor semen quality was found in most men. The additional effect of a recent orchiectomy on semen quality was not demonstrable in the patients described here.Before orchiectomy, increased testosterone levels were found in patients with a β-hCG-producing tumor. After orchiectomy serum testosterone levels were decreased, and LH and FSH levels increased. With β-hCG-producing tumors FSH was suppressed after orchiectomy, and testosterone levels did not exceed those in patients with a tumor not producing β-hCG.The results of semen analysis and of hormonal studies after orchiectomy suggest a dysfunction of the remaining "normal" testis. Diminished spermatogenesis and insufficient testosterone production by the Leydig cells clearly indicate anomalies already present before orchiectomy.

In search of an abnormality in Leydig cell function in patients with testicular cancer, serum levels of testosterone, oestradiol, LH and FSH were compared in 3 groups of men.Group I comprised 26 patients studied after recent orchidectomy for a testicular carcinoma, group II 8 patients operated for benign testicular lesions and group III 8 normal controls. In group II normal testosterone values were found as a result of increased LH release. In group I patients, however, testosterone levels often were low, despite elevated LH levels and increased LH capacity. Evidently, in these patients a partial Leydig cell insufficiency may be present, which does not recover within one year of orchidectomy.After removal of one testis for benign disease, normal testosterone levels are maintained by increased LH levels. After orchidectomy for testicular carcinoma a partial Leydig cell insufficiency may be revealed, which seems to have a permanent character. A pre-existent Leydig cell insufficiency of the remaining testis in patients with testicular cancer indicates a bilateral testicular defect.

Summary The continuous 24-h infusion of ifosfamide (IFX) with mesna was studied in 44 patients with therapyresistant or relapsing ovarian cancer. All patients had stage III disease and had been pretreated with at least one combination comprising an alkylating agent and a cisplatin analogue (22, with one combination; 16, with two; and 6, with three or more). The median number of IFX cycles received was two. Of 40 evaluable patients, 2 achieved a complete response, 5 showed a partial response and 6 had stable disease. A total of 27 patients had tumor progression after one or two treatment cycles. All seven responders had responded to previous treatment for a median duration of 5 months (range, 5–41 months). No patient who progressed during alkylating-agent treatment responded to IFX given subsequently. The median progression-free period was 6 months (range, 4–12 months), and the median overall survival was only 6 months, indicating the advanced stage of disease in these patients. The median overall survival in progressive patients was 5 months (range 2–13+months) and that in the remaining group was 13 months (ranges 3+-24 months) (P<0.05). This treatment was moderately well tolerated. Grade 3 nausea and vomiting occurred in 27% of cycles and grade 3-4 leukopenia was observed in 47%, but thrombocytopenia was hardly ever found. In eight patients there was a deterioration of renal function. Among a total of 131 cycles, the dose was reduced for only 9 due to myelotoxicity and for 3 due to nephrotoxicity. IFX seems to be active only in patients who have relapsed after responding to previous cytotoxic treatment.

To investigate the mechanism of adrenal suppression by high-dose MPA, we performed direct and indirect stimulation tests in postmenopausal women with disseminated breast cancer who were receiving MPA and in a postmenopausal breast cancer control group.

Antipyrine plasma clearance and rates of metabolite formation were measured on four occasions in eight patients with disseminated nonseminomatous testicular cancer. Antipyrine tests were performed before, during (2X), and after treatment with a combination of cisplatin (P), vinblastin (V), and bleomycin (B). Pretreatment values were compared with a male control group (n=14) matched for age and body weight. Antipyrine plasma clearance was 20% higher in patients with testicular cancer (first experiment) than in the control group. This difference was mainly due to a 35% higher clearance for production of 3-hydroxymethylantipyrine (HMA), while clearance for production of norantipyrine (NORA) and 4-hydroxyantipyrine (OHA) was not significantly different from the control group. A reduction in CLHMA was observed after complete remission (fourth experiment), indicating that the presence of the tumor may be related to a selective increase of HMA formation. Treatment with the PVB combination resulted in a 30% increase in antipyrine plasma clearance (second and third experiments), whereas the rates of formation of the main metabolites of antipyrine were all increased to the same extent. These accelerating effects of PVB treatment persisted for at least 6 weeks after the start of the last treatment cycle.

The effects of oral MPA, 300 mg t.i.d., on adrenal function in postmenopausal patients with disseminated breast cancer were evaluated. The levels of serum cortisol, ACTH, androstenedione, DHEA-S, LH, FSH, GH, and prolactin in 22 patients receiving MPA were compared with those in another group of 28 postmenopausal patients in whom levels were measured before treatment.

In carcinoid patients a tumour of enterochromaffin cell origin is present, which dependent on the site of origin can result in increased serotonin production. Metastasized carcinoids are often diagnosed by measuring 5-hydroxyindoleacetic acid excretion in the urine. This excretion, however, can be influenced by food intake. On the other hand, serotonin measured in blood platelets is unaffected by food intake and, in addition, is found to be more sensitive. Therapy of metastasized carcinoids is directed at tumour reduction or only reduction of symptoms. Tumour reduction can be achieved surgically or by embolization. Combination chemotherapy has a maximum response percentage of about 33%. Over the last few years, both octreotide and interferon alpha have been used in these patients. They rarely result in a reduction of the tumour size (10-20%). Symptom reduction is achievable in most patients with these agents, however. Recently, increasing knowledge obtained concerning the various serotonin receptors and their antagonists is now being used in the treatment of patients with a metastasized carcinoid. In the future it is expected that the different modalities will be combined increasingly.

Recombinant human IL-6 (rhIL-6) is a pleiotropic cytokine with stimulatory actions on the hematopoietic system, the immune system and hepatocytes. Clinical interest in the use of this cytokine was raised because of its thrombopoietic properties and also because of its anti-tumor activity, which was shown in vitro and in the preclinical setting. Various studies show that doses up to 10 μg/kg/d rhIL-6 before and after chemotherapy are tolerable and the most frequent side-effects encountered consist of flu-like symptoms. Furthermore, a consistent decrease in hemoglobin was reported during rhIL-6 treatment. This was probably due to hemodilution, although a change in ferrokinetics, may also at least partly, explain the anemia.An evident increase of platelets has been observed in various studies. After chemotherapy, rhIL-6 seemed to hasten platelet recovery, without affecting platelet nadir. Preliminary data from studies investigating the value of rhIL-6 as an anti-tumor agent in renal cell carcinoma and melanoma reported low response rates, between 8 and 14%. The results of rhIL-6 in ameliorating chemotherapy induced bone-marrow depression and especially thrombocytopenia, are promising and merit further phase III studies.

A 23-year-old woman with metastatic Sertoli-Leydig cell tumor was treated with cisplatin, vinblastine, and bleomycin. Hemolytic uremic syndrome appeared, while no evidence of residual tumor was found. Infusion of fresh frozen plasma together with aspirin and dipyridamole resulted in recovery of microangiopathic hemolytic anemia and thrombocytopenia. Renal insufficiency, however, persisted.

In four patients with disseminated papillary or follicular thyroid carcinoma metastatic sites could be demonstrated by scintigraphy with 201Tl. Uptake was present during TSH suppression with thyroid hormone administration. In three of the four cases 201Tl scanning revealed metastases while 131I uptake after triiodothyronine with-drawal was absent. In one patient 201Tl demonstrated some metastatic sites while both 131I uptake and thyroglobulin levels wer negative. Uptake of 201Tl in these metastases is at least partially, unrelated to the TSH and thyroglobulin levels or to the 131I-accumulating capacity. Scintigraphy using 201Tl might be helpful for the detection of metastatic thyroid carcinoma in those cases where 131I uptake is absent.

Thirty-one patients with disseminated malignant melanoma were treated with a combination chemotherapy of bleomycin, dacarbazine and vindesine. Five complete responses, and five partial remissions occurred. One patient survived for over 2 years without evidence of disease. This combination of drugs may give better results, as far as complete recovery and long-term survival are concerned, than single-agent therapy with dacarbazine.

This report describes a 53-year-old white woman with metastatic gestational trophoblastic neoplasia that recurred after evacuation of an accidental pregnancy and did not respond sufficiently to treatment with a combination of methotrexate, actinomycin D, and chlorambucil. After second-line treatment with a combination of cisplatin, etoposide, and bleomycin, there was a complete remission. Afterward, the patient suffered from a moderate bleomycin pneumonitis, which resolved spontaneously. She is now free of disease and feeling well 60 months after her last treatment.

A 62-year-old woman developed subacute renal failure after the repeated administration of ifosfamide (IFX), despite its combination with continuous sodium 2-mercaptoethane sulfonate (mesna) infusion. Biopsy findings, the possible underlying mechanism, and the existing literature are discussed.

Summary Twenty-one patients with disseminated malignant melanoma were treated with a combination of carboplatin and cytosine arabinoside. Two complete and three partial remissions occurred. No complete cross-resistance was found with a regimen containing 5-(dimethyltriazeno)imidazole-4-carboxamide (DTIC) in two patients. It is suggested that this regimen might be studied further as a second-line treatment for patients who fail on DTIC-containing treatment.