Biomedical subjects
Publications and source records attributed to H Schraffordt Koops.
We have been able to study the karyotypes and measure the DNA content in both the primary nonseminomatous germ cell tumor of the testes and the residual mature teratoma after chemotherapy of the same patient. Based on these and other studies, the mechanism of therapy-related differentiation in germ cell tumors of the testes is discussed.
We present the result of the cytogenetic study of a case of osteosarcoma that revealed a very complex karyotype with a modal chromosome number of 93 and several structural chromosomal abnormalities.
The use of isolated regional perfusion in an adjuvant setting for stage I melanoma of the extremity continues to be controversial. The present retrospective study evaluates the past 20 years' experience by comparing 227 perfused patients from Groningen with 238 matched controls from five hospitals in The Netherlands and Westphalia (a region of West Germany bordering the Netherlands). All patients underwent wide local excision for a primary extremity melanoma of 1.5 mm or greater in thickness. A proportional hazards regression analysis for recurrence of disease and survival identified the significant prognostic factors, of which tumor thickness was the most important. Corrected for these factors, it was not possible to demonstrate a statistically significant effect for perfusion in terms of time to limb recurrence (P = .61), time to regional lymph node metastasis (P = .11), time to distant metastasis (P = .73), disease-free interval (P = .42), and survival (P = .90). No statistically significant differences were seen for adjuvant perfusion in any of the subgroups.
High-grade soft tissue sarcomas of the extremities continue to pose problems of local disease control and deaths from distant metastases. Between 1969 and 1976, eight patients with primary and six with recurrent high-grade soft tissue sarcomas of the extremities were treated by isolated regional perfusion with cytostatics and local excision. None received systemic adjuvant chemotherapy or external-beam radiotherapy. During the follow-up (median, 13 years) five patients (36%) developed distant metastases. One was cured after resection of a pulmonary metastasis. In one other patient (7%) recurrent local disease was diagnosed after 48 months; he was cured after resection of the local lesion followed by postoperative external beam radiotherapy. The actuarial 5-year and 10-year survival was 69%. Treatment caused no cardiovascular complications and there was no postoperative mortality.
In the treatment of osteosarcoma, it is possible to differentiate between systemic therapy and local regional treatment. Systemic treatment of human patients with osteosarcomas consists in adjuvant chemotherapy. This has considerably improved the prognosis in these cases. The primary object in local regional treatment is to prevent local recurrences and to preserve function. As regards extremities, the aim is to preserve the limbs. In the present investigations, the value of regional chemotherapy by isolated regional perfusion with cis-platinum to dogs is studied. This approach was based on the hypothesis that considerable necrosis of tumours may be produced after perfusion with cis-platinum, thus making extremity-saving surgery possible. Isolated regional perfusion with cis-platinum (30 mg/litre of extremity volume) was performed in nine dogs with osteosarcomas of an extremity. A marked effect on the tumour was detectable on the basis of clinical, radiological and histological parameters. In the opinion of the present authors, regional perfusion with cis-platinum may contribute to extremity-saving treatment of osteosarcomas in dogs and human subjects. However, further studies will be required in order to achieve more adequate quantitation an improvement of local effects. In view of the synergy with cis-platinum, the latter may possibly be attained by the addition of hyperthermia (temperatures above 41.5 degrees C).
Fifty-four patients with Stage I nonseminomatous testicular germ cell tumors (NSTGCT) were treated from 1982 to 1984. In 1982 and 1983, the orchidectomy was followed by an exploratory laparotomy to conclude the dissemination study. In 1984, laparotomy was performed only if indicated. The mean follow-up was 29 months. A relapse occurred in 11 patients (20%). The relapse rate in patients who underwent exploratory laparotomy was as high as that in patients who did not. All patients treated for relapse by chemotherapy and surgery entered a complete remission for at least 1 year. It proved impossible to establish criteria for prediction of a subsequent relapse. Both serum tumor marker assays and roentgenography are important aids in diagnosing a relapse. With careful follow-up of Stage I NSTGCT patients, a wait-and-see attitude can be adopted until a relapse occurs.
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Body weight and lean body mass are different reflections of the nutritional status of patients receiving cancer chemotherapy. In the present study, the relation between lean body mass and body weight during cytostatic treatment was investigated in 3 groups of newly-diagnosed children and young adults with acute lymphocytic leukemia, osteosarcoma, or a small round cell sarcoma. Body weight and lean body mass were determined before and after an initial period of cytostatic treatment. Lean body mass was derived from total body water volume, which was assessed by deuterium oxide dilution. A significant dissociation between body weight and lean body mass was observed in leukemia patients (n = 8, P = 0.008, paired t-test), and in osteosarcoma patients (n = 13, P = 0.001). No dissociation was found in patients with a small round cell sarcoma (n = 8, P = 0.839). We conclude that during cancer chemotherapy periodic assessment of body weight may give a false picture of the preservation of lean body mass. Considering the course of body weight alone may prevent the establishment of a timely diagnosis of malnutrition, which is mandatory for optimal supportive care.
The gonadal functions were studied in 54 patients with disseminated nonseminomatous testicular tumors who had been subjected to combination chemotherapy (cisplatin, vinblastine, and bleomycin [PVB]) and surgery (hemiorchiectomy, retroperitoneal lymph node dissection or removal of retroperitoneal residual tumor after chemotherapy) and in 17 patients with a stage I tumor subjected to hemiorchiectomy exclusively. In the patients treated with chemotherapy, the plasma testosterone levels remained at the lower limit of normal and the luteinizing hormone (LH) levels remained elevated for 2 years after completion of treatment. The follicle-stimulating hormone (FSH) levels also remained significantly elevated, but showed a tendency to decrease after 2 years. Semen analysis was performed in 25 patients; of the other patients, 18 had no antegrade ejaculation, eight had undergone a vasectomy and three patients did not cooperate. Before treatment, 72% of the patients showed azoo- or oligozoospermia; 2 years after discontinuation of the chemotherapy, 48% had azoo- or oligozoospermia while 28% had more than 60 X 10(6) spermatozoa/mL. However, interestingly the proportion of patients with azoospermia had increased from 4% to 28%. In the course of this study, eight pregnancies occurred; one ended in an early spontaneous abortion; the other seven pregnancies ran an uncomplicated course. Seven healthy children were born. In 17 patients with a stage I tumor treated by hemiorchiectomy only, the testosterone, LH and FSH levels were also observed for 2 years; until 2 years after treatment, the testosterone levels remained lower and the FSH levels remained higher than normal. Insufficiency of the Leydig's cells in the unaffected gonad appeared to be responsible for the altered hormone concentrations in the blood.
This study concerns the sexual functions of 101 patients who had undergone bilateral retroperitoneal lymph node dissection for stage I or II nonseminomatous testicular cancer between 1969 and 1982. All patients were without evidence of disease after at least 4 years of follow-up. Antegrade ejaculation was present in 12 patients, while 89 patients experienced "dry ejaculation." Urine collected after intercourse or masturbation from 75 patients with dry ejaculation showed retrograde ejaculation in 55 and lack of ejaculatory emission into the urethra in 20 patients. Regarding other sexual functions, 17 patients had a diminished sexual desire (especially those patients who had received radiotherapy), 12 experienced difficulty reaching organism, and 6 complained of erectile dysfunction. The incidence of a contralateral hydrocele developing after retroperitoneal lymph node dissection seems to correlate with ligation of the contralateral spermatic vessels and their lymphatics. A review of the literature is presented comparing the types of dissection with the incidence of sexual disorders after retroperitoneal lymph node dissection. Since preserving normal ejaculation and fertility is important, a modified or unilateral retroperitoneal lymph node dissection, when required, is advocated. In patients, with stage I disease the therapy may be limited to an orchiectomy without lymph node dissection. In patients with retroperitoneal lymph node metastases combination chemotherapy with cisplatin and tumor excision gives good results. Patients with true retrograde ejaculation can be treated with alpha-sympathomimetic drugs such as imipramine HCl, and thus be offered the chance of fatherhood by coitus.
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The current report describes a secondary malignancy developing in a retroperitoneal mature residual lesion 6 years after chemotherapeutic treatment of a disseminated nonseminomatous testicular tumor. The histologically malignant component was not present in the primary tumor and consisted of polygonal and fusiform cells with focal tubular formations, resembling primitive neuroectodermal tissue. Immunoperoxidase staining for alpha-fetoprotein and the beta-subunit of human chorionic gonadotropin remained negative, whereas focal positivity for S100 protein was observed. Neuron specific enolase positivity was equivocal. The DNA contents of both the mature components in the primary and the metastatic retroperitoneal tumor and in the various malignant components of the primary tumor, were in the hypotriploid range. In the malignant component of the retroperitoneal metastasis, a hypertriploid peak was observed. These findings suggest further clonal evolution in a phenotypically mature, genotypically abnormal residual metastatic tumor after chemotherapy. It is stressed that the mature appearance of the residual lesions may be deceiving and that these lesions are highly susceptible to resume malignant behavior.
A comparative retrospective study of patients with primary malignant melanomas of the extremities, Clark level IV/V and tumor thickness greater than or equal to 1.5 mm, was performed in Sydney (Australia) and Groningen (The Netherlands). The efficacy of wide local excision combined with adjuvant regional perfusion (Groningen) was compared with that of wide surgical excision only (Sydney). Patients were classified by sex and tumor location. There were only sufficient numbers of female patients with a tumor of the lower extremity available for this comparative study. All patients were stage I and none received prophylactic lymph node dissection. Age, tumor location, tumor thickness, depth of infiltration and ulceration were taken into account and the factors studied within this group were 10-year disease-free rate, 10-year survival rate, and local and regional recurrences. Women with a melanoma of the leg (excluding the foot) who had been treated by excision and adjuvant regional perfusion, had a significantly better 10-year disease-free rate (P less than 0.0005), a significantly higher 10-year survival rate (0.010 less than P less than 0.025) and significantly fewer local/regional recurrences (P less than 0.0005) than women treated by wide local excision only. For tumors of the foot, however, no significant differences in 10-year disease-free rate, 10-year survival rate or local/regional recurrences were observed after perfusion.
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The introduction of chemotherapy has greatly changed the treatment of osteosarcoma. During the preoperative phase the tumor response to chemotherapy can be assessed in various ways. This paper discusses the clinical, histological and radiological response to preoperative chemotherapy in three patients. Changes in conventional roentgenograms following chemotherapy can reflect the effect of chemotherapy on the primary tumor. This can be important in planning further chemotherapy or surgery.
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Thirty-three patients with a non-seminomatous germ cell tumor of the testis in clinical stage I were treated only by orchidectomy. The very careful follow-up--with tumor marker assays every 3 weeks, chest X-rays every 6 weeks and CT-scans of the lungs and retroperitoneum every 3 months--revealed metastases in 7 of the patients (21%). All these relapses were diagnosed within 6 months of the orchidectomy. Para-aortic node metastases were found in 5 of the 7 patients, with additional inguinal node metastases in 1 and additional lung metastases in 1; 2 patients had only lung metastases. Six of the 7 patients with a relapse were given chemotherapy (PVB); 1 patient refused chemotherapy. In view of residual disease a surgical excision was performed; it revealed necrosis as well as mature teratoma. All 33 patients are still alive, the post-orchidectomy follow-up period being 12-38 months.
Protein analyses were performed in 15 cyst fluids (CF) from mature teratoma (TD) and in 15 corresponding sera from 9 nonseminomatous germ cell tumor patients. Qualitatively, many similarities between the protein compositions of CF and corresponding sera were seen. Quantitative comparisons suggested free diffusion of plasma proteins into the cyst lumen in nine cases, whereas in five CF a decreased size selectivity of the blood-TD barrier was observed. From the quantitative data it was concluded that the significantly increased CCF/Cserum concentration ratios for the tumor markers alpha-fetoprotein (8/14), human chorionic gonadotropin (3/14), and carcinoembryonic antigen (13/13) as well as for lysozyme (12/13), ferritin (12/13), and fibronectin (3/6) were either due to local synthesis or to concentrating properties of the TD cells. The results of the current study encourage further research for new tumor-associated proteins in cyst fluids.