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BAGKGROUND. 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. METHODS. 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. RESULTS. 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

BACKGROUND The sentinel lymph node biopsy (SLNB) is a diagnostic or staging option in the treatment of patients with cutaneous malignant melanoma (CMM) and is investigated intensively. A positive SLNB has appeared to identify patients who might have benefited from a lymph node dissection (LND). Intraoperative frozen section analysis (FSA) of the sentinel lymph node (SLN) during surgery would allow SLNB and LND to be performed in the same procedure. In the current study, we tested the reliability of FSA on the sentinel lymph node in patients with CMM. METHODS Before definitive treatment of their melanomas began, FSA was performed on the SLNBs of 58 patients, whose median age was 56 (22–81) years, and who were 55% male and 45% female. Serial sections (500 μm interval), stained with routine hematoxylin and eosin and immunohistochemistry (S-100 and HMB-45), obtained definitive histology of the sentinel lymph node. RESULTS Detection of the sentinel lymph node was possible in 56 patients (97%). Sixty-one SLNBs were performed in these patients. FSA detected metastases in 5 of 108 SLN (5%) in 5 patients. This was upgraded after definitive histology to 13 SLN (12%) in 11 patients (20%). Sensitivity of the FSA was 38%. After a median follow-up of 35 (range: 24–54) months, the false-negative rate of the SLN was 4% (2 patients). CONCLUSION The combination of the low sensitivity of FSA and a finding that only 12% of the SLNBs contained metastases does not justify routine use of FSA on the SLN of patients with CMM. Cancer 2000;89:1720–5. © 2000 American Cancer Society.

BACKGROUND The objectives of the study were to determine how often a sentinel lymph node is visualized by lymphoscintigraphy in breast carcinoma patients, how often the sentinel lymph node is identified during surgery, and the sensitivity of these procedures to identify the presence of axillary lymph node metastasis. METHODS A total of 136 patients were enrolled in 2 hospitals. Preoperative dynamic and static lymphoscintigraphy were performed; in addition, both a vital dye and a gamma detection probe were used intraoperatively. The tracers were injected into the primary lesion. Sentinel lymph node biopsy was followed by completion axillary lymph node dissection. The sentinel lymph nodes and other axillary lymph nodes were examined routinely and by immunohistochemical staining. RESULTS A sentinel lymph node was visualized by lymphoscintigraphy in 118 patients (87%). During the operation a sentinel lymph node was localized in 126 patients (93%). A total of 224 sentinel lymph nodes were harvested (average of 1.7 and range of 1–4 sentinel lymph nodes per patient). Of all the sentinel lymph nodes, 37 were blue (17%), 68 were radioactive (30%), and 119 were both blue and radioactive (53%). The sentinel lymph nodes contained metastatic disease in 56 patients (44%). Three sentinel lymph node biopsies were false-negative (sensitivity 95%). CONCLUSIONS Sentinel lymph node biopsy with preoperative lymphoscintigraphy after intralesional tracer administration and intraoperative use of both a gamma detection probe and a vital dye is a reliable technique for staging the axilla of breast carcinoma patients. Cancer 2000;88:2546–52. © 2000 American Cancer Society.

BACKGROUND. The potential of positron emission tomography (PET) with F-18-fluoro-2-deoxy-D-glucose (FDG) to detect primary tumors after unsuccessful conventional diagnostic workup was assessed in patients with metastatic disease from an unknown primary tumor. METHODS. Twenty-nine patients with various histologic types of metastases from an unknown primary site were studied after unsuccessful conventional diagnostic workup. The patients received 370 megabecquerels (MBq) (10 millicuries) FDG intravenously and whole body scans were made after 30 minutes after injection onward. RESULTS, All but one known metastatic tumor sites were visualized. Additional metastases were discovered in five patients. With FDG-PET the primary tumor was identified in 7 patients (24%): in 2 patients with carcinoma of the nasopharynx, in I patient with plasmacytoma of the base of the tongue, in 1 patient with carcinoma of the lung, in 1 patient with carcinoma of the colon, and in 2 patients with breast carcinoma. FDG-PET did not identify a primary tumor in the remaining 22 patients (76%). Despite a negative PET study, the primary lesion was identified in a later phase in 3 of these patients (14%). Survival was not altered by discovery of the primary tumor. CONCLUSIONS. A previously unknown primary turner was able to be identified with FDG-PET in 7 of 29 patients after an unsuccessful conventional diagnostic workup. However, the clinical relevance of PET information in this setting is limited. (C) 1998 American Cancer Society.

BACKGROUND, The application of bleomycin is characterized by acute side effects, such as fever, chills, and sometimes hypotension and tachypnea. Furthermore, bleomycin is known to induce pneumonitis. There are several indications that the induction of cytokines by bleomycin is involved in the development of these side effects.METHODS, In this study, the authors determined the plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and transforming growth factor-beta (TGF-beta) before and after bleomycin infusion in 14 patients treated for disseminated nonseminomatous germ cell tumor.RESULTS, Compared with the pretreatment value, TNF-alpha was significantly increased 3, 4.5, and 24 hours after bleomycin infusion. For IL-1 beta and TGF-beta, no significant alterations were observed within 24 hours after administration of bleomycin.CONCLUSIONS. The increase in TNF-alpha after administration of bleomycin suggests a role for this cytokine in the development of the acute side effects and probably also in the occurrence of bleomycin-induced pulmonary toxicity. The involvement of IL-1 beta and TGF-beta deserve further study. (C) 1998 American Cancer Society.

BACKGROUND This retrospective study evaluates changes in sexual functioning after treatment for testicular cancer and investigates whether there is a relationship with different treatment modalities. METHODS A self-reported questionnaire was sent to 337 men who had been treated for testicular cancer at the University Hospital Groningen between 1977 and 1994. Medical information was obtained from the patient records. RESULTS A response was received from 287 men (85%); 264 patients were included in this study (78%). The mean patient age at follow-up was 37.7 years (range, 17-71 years). The mean follow-up period was 6.7 years (range, 0.25-18 years). Decrease in sexual functions was reported by 40% of patients (decrease in libido: 19%; arousal: 12% erection: 12.5%; orgasm: 19%; and ejaculation: 26%). Moreover, 23.5% of patients responding reported decreased sexual activity and 12.5% were dissatisfied with their sexual functioning. Patients with Stage II-IV nonseminoma who had been treated with polychemotherapy (PCT) with or without resection of residual retroperitoneal tumor mass (RRRTM) (PCT ± RRRTM) reported a significantly sharper decrease in sexual functioning than patients who had been followed with a wait-and-see policy (W & S) (Stage I nonseminoma patients). It was noteworthy that patients treated by PCT alone reported more sharply decreased sexual functioning than patients treated by PCT + RRRTM. Patients treated by radiotherapy (Stage I-IIA seminoma) did not report findings significantly different from the W & S group. CONCLUSIONS Testicular cancer patients are at risk for reduced sexual functioning, especially when treated by chemotherapy, with or without resection of residual tumor. Although chemotherapy may influence somatic aspects of sexual functioning, it appears that psychologic factors arising from the confrontation with testicular cancer play a strongly mediating (if not determining) role. Cancer 1997; 80:454-64. © 1997 American Cancer Society.

Background. Hyperthermic isolated limb perfusion (HILP) has been shown to be effective for locoregional metastases or local recurrent disease. Locoregional recurrences after previous HILP is an unsolved problem. Methods. HILP with cisplatin, 20-30 mg/l perfused limb volume, was performed in seven patients with recurrent melanoma (five with Stage IIIA and two with Stage IIIAB) after previous HILP with melphalan with or without dactinomycin. A cisplatin perfusion without local excision was performed in four patients; this treatment resulted in two complete responses and one partial response. In three patients, a cisplatin perfusion was performed with local excision of the in-transit metastases. Results. During a median follow-up of 20 months (range, 10-25 months), in five (83%) patients the tumor recurred locally after a median period of 5 months (range, 3-11 months). No systemic toxicity was observed. Local toxicity consisted of postperfusion edema and neurotoxicity in all patients. The edema resolved within 2 weeks, which was in contrast to persistent neurotoxicity. A severe motor-sensory neuropathy was observed in three (43%) patients and mild sensory neuropathy in four (57%) patients. Conclusions. The severe neurotoxicity and the high local recurrence rate do not justify the use of HILP with cisplatin for recurrent melanoma after previous HILP with melphalan with or without dactinomycin.

Background. Hyperpentaploidy in testicular nonseminomatous germ cell tumors (TNSGCT) has been associated with progression of disease of patients who initially had TNSGCT in Stage 1. Methods. The authors used flow cytometry to investigate the relationship between ploidy and the clinical behavior in TNSGCT, focusing on hypertetraploid values (DNA index, > 2.00). Results. Patients with TNSGCT containing an aneuploid stemline with a hypertetraploid value more often had higher clinical stage of disease and a higher chance of relapse in advanced stages. The presence of multiple aneuploid stemlines in the tumors was found more frequently in patients who had higher clinical stage disease. Conclusions. The results suggest that the presence of highly aneuploid or multiple aneuploid stemlines in TNSGCT are associated with a clinically more malignant behavior.

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; P0.05). 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.

The sentinel lymph node biopsy (SLNB) is a diagnostic or staging option in the treatment of patients with cutaneous malignant melanoma (CMM) and is investigated intensively. A positive SLNB has appeared to identify patients who might have benefited from a lymph node dissection (LND). Intraoperative frozen section analysis (FSA) of the sentinel lymph node (SLN) during surgery would allow SLNB and LND to be performed in the same procedure. In the current study, we tested the reliability of FSA on the sentinel lymph node in patients with CMM.Before definitive treatment of their melanomas began, FSA was performed on the SLNBs of 58 patients, whose median age was 56 (22-81) years, and who were 55% male and 45% female. Serial sections (500 micrometer interval), stained with routine hematoxylin and eosin and immunohistochemistry (S-100 and HMB-45), obtained definitive histology of the sentinel lymph node.Detection of the sentinel lymph node was possible in 56 patients (97%). Sixty-one SLNBs were performed in these patients. FSA detected metastases in 5 of 108 SLN (5%) in 5 patients. This was upgraded after definitive histology to 13 SLN (12%) in 11 patients (20%). Sensitivity of the FSA was 38%. After a median follow-up of 35 (range: 24-54) months, the false-negative rate of the SLN was 4% (2 patients).The combination of the low sensitivity of FSA and a finding that only 12% of the SLNBs contained metastases does not justify routine use of FSA on the SLN of patients with CMM.

The objectives of the study were to determine how often a sentinel lymph node is visualized by lymphoscintigraphy in breast carcinoma patients, how often the sentinel lymph node is identified during surgery, and the sensitivity of these procedures to identify the presence of axillary lymph node metastasis.A total of 136 patients were enrolled in 2 hospitals. Preoperative dynamic and static lymphoscintigraphy were performed; in addition, both a vital dye and a gamma detection probe were used intraoperatively. The tracers were injected into the primary lesion. Sentinel lymph node biopsy was followed by completion axillary lymph node dissection. The sentinel lymph nodes and other axillary lymph nodes were examined routinely and by immunohistochemical staining.A sentinel lymph node was visualized by lymphoscintigraphy in 118 patients (87%). During the operation a sentinel lymph node was localized in 126 patients (93%). A total of 224 sentinel lymph nodes were harvested (average of 1.7 and range of 1-4 sentinel lymph nodes per patient). Of all the sentinel lymph nodes, 37 were blue (17%), 68 were radioactive (30%), and 119 were both blue and radioactive (53%). The sentinel lymph nodes contained metastatic disease in 56 patients (44%). Three sentinel lymph node biopsies were false-negative (sensitivity 95%).Sentinel lymph node biopsy with preoperative lymphoscintigraphy after intralesional tracer administration and intraoperative use of both a gamma detection probe and a vital dye is a reliable technique for staging the axilla of breast carcinoma patients.

This article reports on three patients with intestinal bleeding due to metastases from a nonseminomatous testicular tumor (NSTT) to the gastrointestinal tract. Involvement of the gastrointestinal tract is rare. The mode of spread is either by hematogenous dissemination or by direct extension from involved paraaortic lymph nodes. The symptoms of these patients are briefly described. Early recognition and efficient supportive care are essential in the management of such patients.

The close observation of patients treated for testicular cancer led to the suspicion of intrathoracic and/or mediastinal metastases on radiologic examination in a number of patients without other evidence of relapse. This report presents two patients with combined seminomatous and nonseminomatous germ cell tumors with isolated sarcoid reactions of hilar and interlobular lymph nodes, detected concomitant with diagnosis and 12 months after diagnosis, respectively. Histologic examination appears to be imperative in these cases to avoid unnecessary chemotherapy.

Mature teratoma is often found in resected retroperitoneal residual tumor masses (RRTM) after chemotherapy for disseminated nonseminomatous testicular germ cell tumors (NSTGCT). The aim of this report is to describe the clinical course of patients after resection of residual teratoma, with particular emphasis on relapse with either growing mature teratoma or secondary non-germ cell malignancy.During the period 1979-1995, 113 patients underwent a laparotomy for resection of RRTM after chemotherapy for NSTGCT. Only patients with mature teratoma in the RRTM were included in the current study, and data on the patients who experienced relapse were studied in detail.Mature teratoma was found in 51 patients (45.1%) with RRTM resected after chemotherapy. Nine of these 51 patients (17.6%) relapsed; the relapses resulted from growing mature teratoma in 5 patients (9.8%), secondary non-germ cell malignancy in 3 patients (5.9%), and recurrent germ cell malignancy in 1 patient (2.0%). The primary treatment for all relapsing patients was surgical excision. All five patients with growing mature teratoma are alive without evidence of disease, as is the patient with recurrent germ cell malignancy. One of the three patients with non-germ cell malignancy died of disease, and the remaining two are alive with disease.Long term follow-up after resection of postchemotherapy residual teratoma is indicated because a proportion of patients develop growing mature teratoma or a secondary non-germ cell malignancy. The treatment for these recurrences should be complete surgical excision.

The potential of positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) to detect primary tumors after unsuccessful conventional diagnostic workup was assessed in patients with metastatic disease from an unknown primary tumor.Twenty-nine patients with various histologic types of metastases from an unknown primary site were studied after unsuccessful conventional diagnostic workup. The patients received 370 megabecquerels (MBq) (10 millicuries) FDG intravenously and whole body scans were made after 30 minutes after injection onward.All but one known metastatic tumor sites were visualized. Additional metastases were discovered in five patients. With FDG-PET the primary tumor was identified in 7 patients (24%): in 2 patients with carcinoma of the nasopharynx, in 1 patient with plasmacytoma of the base of the tongue, in 1 patient with carcinoma of the lung, in 1 patient with carcinoma of the colon, and in 2 patients with breast carcinoma. FDG-PET did not identify a primary tumor in the remaining 22 patients (76%). Despite a negative PET study, the primary lesion was identified in a later phase in 3 of these patients (14%). Survival was not altered by discovery of the primary tumor.A previously unknown primary tumor was able to be identified with FDG-PET in 7 of 29 patients after an unsuccessful conventional diagnostic workup. However, the clinical relevance of PET information in this setting is limited.

The application of bleomycin is characterized by acute side effects, such as fever, chills, and sometimes hypotension and tachypnea. Furthermore, bleomycin is known to induce pneumonitis. There are several indications that the induction of cytokines by bleomycin is involved in the development of these side effects.In this study, the authors determined the plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and transforming growth factor-beta (TGF-beta) before and after bleomycin infusion in 14 patients treated for disseminated nonseminomatous germ cell tumor.Compared with the pretreatment value, TNF-alpha was significantly increased 3, 4.5, and 24 hours after bleomycin infusion. For IL-1beta and TGF-beta, no significant alterations were observed within 24 hours after administration of bleomycin.The increase in TNF-alpha after administration of bleomycin suggests a role for this cytokine in the development of the acute side effects and probably also in the occurrence of bleomycin-induced pulmonary toxicity. The involvement of IL-1beta and TGF-beta deserve further study.

This retrospective study evaluates changes in sexual functioning after treatment for testicular cancer and investigates whether there is a relationship with different treatment modalities.A self-reported questionnaire was sent to 337 men who had been treated for testicular cancer at the University Hospital Groningen between 1977 and 1994. Medical information was obtained from the patient records.A response was received from 287 men (85%); 264 patients were included in this study (78%). The mean patient age at follow-up was 37.7 years (range, 17-71 years). The mean follow-up period was 6.7 years (range, 0.25-18 years). Decrease in sexual functions was reported by 40% of patients (decrease in libido: 19%; arousal: 12% erection: 12.5%; orgasm: 19%; and ejaculation: 26%). Moreover, 23.5% of patients responding reported decreased sexual activity and 12.5% were dissatisfied with their sexual functioning. Patients with Stage II-IV nonseminoma who had been treated with polychemotherapy (PCT) with or without resection of residual retroperitoneal tumor mass (RRRTM) (PCT +/- RRRTM) reported a significantly sharper decrease in sexual functioning than patients who had been followed with a wait-and-see policy (WS) (Stage I nonseminoma patients). It was noteworthy that patients treated by PCT alone reported more sharply decreased sexual functioning than patients treated by PCT + RRRTM. Patients treated by radiotherapy (Stage I-IIA seminoma) did not report findings significantly different from the WS group.Testicular cancer patients are at risk for reduced sexual functioning, especially when treated by chemotherapy, with or without resection of residual tumor. Although chemotherapy may influence somatic aspects of sexual functioning, it appears that psychologic factors arising from the confrontation with testicular cancer play a strongly mediating (if not determining) role.

After chemotherapy for a metastatic nonseminomatous germ cell tumor, pulmonary masses may be seen on a computed tomography scan. These residual masses may contain one of three histologic elements: necrosis, mature teratoma, or cancer. Because surgical resection of masses containing only necrosis is unnecessary, the authors aimed to predict the histology of these residual masses.Six study groups contributed patient data on a total of 215 patients undergoing thoracotomy after cisplatin-based induction chemotherapy for metastatic testicular nonseminomatous germ cell tumors. Logistic regression analysis was used to estimate the probability of necrosis, mature teratoma, and cancer in relation to predictors known before thoracotomy.The pulmonary mass histology was necrosis in 116 patients (54%), mature teratoma in 70 (33%), and cancer in 29 (13%). Necrosis was found at thoracotomy in 89% of those patients with necrosis at retroperitoneal lymph node dissection (RPLND). Other predictors included the primary tumor histology, prechemotherapy tumor marker levels, change in mass size during chemotherapy, and the presence of a single, unilateral mass. Multivariate combination of predictors yielded reliable models (goodness-of-fit tests, P0.20), which discriminated necrosis well from other histologies, especially if RPLND histology was available (area under the receiver operating characteristic curve, 0.86).This analysis indicated subgroups of patients with a high probability of necrosis and a low risk of cancer for whom close follow-up of the residual pulmonary mass might be considered. In most patients, a RPLND should be performed before a thoracotomy is considered, because the probability of necrosis is generally higher at thoracotomy than at RPLND and the histology at RPLND is a strong predictor of the histology at thoracotomy.

Hyperthermic isolated limb perfusion (HILP) has been shown to be effective for locoregional metastases or local recurrent disease. Locoregional recurrences after previous HILP is an unsolved problem.HILP with cisplatin, 20-30 mg/l perfused limb volume, was performed in seven patients with recurrent melanoma (five with Stage IIIA and two with Stage IIIAB) after previous HILP with melphalan with or without dactinomycin. A cisplatin perfusion without local excision was performed in four patients; this treatment resulted in two complete responses and one partial response. In three patients, a cisplatin perfusion was performed with local excision of the in-transit metastases.During a median follow-up of 20 months (range, 10-25 months), in five (83%) patients the tumor recurred locally after a median period of 5 months (range, 3-11 months). No systemic toxicity was observed. Local toxicity consisted of postperfusion edema and neurotoxicity in all patients. The edema resolved within 2 weeks, which was in contrast to persistent neurotoxicity. A severe motor-sensory neuropathy was observed in three (43%) patients and mild sensory neuropathy in four (57%) patients.The severe neurotoxicity and the high local recurrence rate do not justify the use of HILP with cisplatin for recurrent melanoma after previous HILP with melphalan with or without dactinomycin.

Hyperpentaploidy in testicular nonseminomatous germ cell tumors (TNSGCT) has been associated with progression of disease of patients who initially had TNSGCT in Stage I.The authors used flow cytometry to investigate the relationship between ploidy and the clinical behavior in TNSGCT, focusing on hypertetraploid values (DNA index,2.00).Patients with TNSGCT containing an aneuploid stemline with a hypertetraploid value more often had higher clinical stage of disease and a higher chance of relapse in advanced stages. The presence of multiple aneuploid stemlines in the tumors was found more frequently in patients who had higher clinical stage disease.The results suggest that the presence of highly aneuploid or multiple aneuploid stemlines in TNSGCT are associated with a clinically more malignant behavior.

Tumor nuclear DNA content was determined by flow cytometry in routinely prepared paraffin blocks from 25 primary malignant melanomas of the extremities. Twelve of the tumors were aneuploid, and 13 were euploid. In this series the presence of aneuploidy appeared to have no prognostic value.

This article reports on three patients with intestinal bleeding due to metastases from a nonseminomatous testicular tumor (NSTT) to the gastrointestinal tract. Involvement of the gastrointestinal tract is rare. The mode of spread is either by hematogenous dissemination or by direct extension from involved paraaortic lymph nodes. The symptoms of these patients are briefly described. Early recognition and efficient supportive care are essential in the management of such patients.

A case of fatal acute renal failure during treatment with 1,1-diaminomethyl cyclohexane sulphato platinum II (TNO-6) is reported. Pathologic investigation showed focal tubular necrosis with interstitial infiltration and edema. Despite the development of proteinuria no changes of the glomeruli were found, either by light or electron microscopic investigation. The pathologic changes caused by TNO-6 are similar to those found in renal failure caused by cisplatin (CDDP).

Ninety-one patients with disseminated testicular non-seminomas were treated with 3 to 4 cycles of cisplatin, vinblastine, and bleomycin (PVB) induction chemotherapy followed by cisplatin and vinblastine maintenance therapy for 1 year. The follow-up of these patients ranges from 24 to 66 months. Forty-nine (54%) patients achieved complete remission by chemotherapy alone and 14 (15%) were rendered free of tumor by surgery after chemotherapy, for a total complete remission rate of 69%. Three complete responders relapsed within 13 months, and two died. One additional complete responder died of a noncancer-related cause. One of the surgical complete responders relapsed and died. Overall, 58 (64%) patients remain free of disease. The 5-year survival is 95% for complete responders, 32% for partial responders, and 72% overall. This combination regimen has significantly improved the survival of disseminated testicular cancer patients, equaling that of Stage II patients in older literature.

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.

The localization and size of a high-grade soft tissue sarcoma of an extremity are generally the limiting factor in limb-saving surgery. Since 1982 nine patients with a high-grade soft tissue sarcoma of an extremity, which usually requires amputation, have been treated by intraarterial chemotherapy, preoperative and postoperative radiotherapy, and surgery. The limb was saved in eight patients (89%). During a median follow-up of 24 months (mean follow-up 32 months, range 12 to 64 months) one local recurrence and four distant metastases were diagnosed. Three patients developed complications due to the intraarterial chemotherapy, a motor and sensory neuropathy of the sciatic nerve was diagnosed in one patient, and two patients developed a flexion contracture of the knee. The results obtained in this small series show that the combination of intraarterial doxorubicin, preoperative and postoperative radiotherapy, and surgery is feasible in limb-saving treatment of primarily "unresectable" high-grade soft tissue sarcomas of the extremities without increasing the risk of a local recurrence.

In this report, the pathologic findings and the results of cellular DNA measurements of a tumor that on first presentation seemed to be a classical parosteal osteosarcoma are described. After resection 8 months later, part of the tumor appeared to display highly malignant features. DNA flow cytometry of this part of the tumor showed an aneuploid cell population. The aggressive nature of the tumor was confirmed by the development of lung metastases approximately 1 year after resection of the primary tumor.

Investigating the mechanisms underlying maturation of metastases of nonseminomatous germ cell tumors on administration of chemotherapy, the histologic characteristics of primary testis tumors was compared to the histologic characteristics of their retroperitoneal metastases in three historical patient groups. The metastases in Group I (20 patients) were not treated; those in Groups II (nine patients) and III (24 patients) were treated, respectively, with three cycles of dactinomycin and with four cycles of cis-diammine-dichloroplatinum, vinblastine, and bleomycin, before retroperitoneal lymph node dissection. In Group III there was a significant increase of metastases consisting of differentiated teratoma only, as compared to the metastases of Group I. However, both with and without chemotherapy, the metastases contained fewer areas of differentiated teratoma than the primary lesions. Metastases containing differentiated teratoma with and without other components, with one exception in Group III, were derived from primary tumors containing mature areas as well. Components other than mature teratoma were almost completely eradicated in Group III. These findings strongly suggest that selective destruction of components other than differentiated teratoma causes the mature histologic characteristics in the metastases upon administration of chemotherapy. The results do not support the hypothesis of induction of differentiation by the chemotherapeutic agents.

Nine patients (Group A) with histologically proven, nonseminomatous testicular cancer were treated with cisplatin (CDDP) according to the Einhorn regimen. Renal function studies including the measurement of the effective renal plasma flow (ERPF) and the glomerular filtration rate (GFR) were performed prior to the chemotherapy and then after treatment on days 10 and 21 of the first course. In order to prevent CDDP-induced nephrotoxicity, verapamil (a calcium entry blocker) and cimetidine were given along with CDDP. The results were compared with others from another group of nine patients (Group B) treated with CDDP, but without verapamil and cimetidine. In Group A there was much less of a decrease in ERPF as compared to Group B on day 21. In addition, the decrease in GFR on days 10 and 21 was totally prevented in the verapamil- and cimetidine-treated group.

During the period from February to October 1983, 21 patients with malignant melanoma of the extremities were treated by hyperthermic regional isolated perfusion with L-phenylalanine mustard (melphalan). The melphalan dose for each patient was determined by the tissue volume of the perfused region, using a dose of 10 mg/l perfused tissue. Despite an average increase of melphalan dosage of 18% above the maximum for iliac perfusions recommended in the literature, no increase in toxic tissue reactions was observed after hyperthermic iliac perfusions. The same dose of 10 mg/l perfused tissue was used in hyperthermic axillary perfusions, resulting in an average decrease of melphalan dosage of 14% below the minimum recommended in the literature. By applying a constant dose per unit tissue volume, a standardization of treatment is achieved. This excludes variations like body weight, age, type of complexion, and hair color, which so far have determined dosimetry.

From 1973 through 1979, inguinal node biopsy was performed to stage the disease process in 179 clinical Stage I patients with malignant melanoma of the lower extremity, who were all treated by hyperthermic regional perfusion as well. Of the 179 tumors, 12% were intermediate risk (0.75-1.44 mm) and 88% were high risk (greater than or equal to 1.5 mm); all had a Clark level of IV or V. The Rosenmuller node at the caudal margin of the saphenous hiatus was elected for inguinal node biopsy. This biopsy supplies a fair amount of information about the entire inguinal node region: a malignant node was found in 16 patients (9%); no other metastatic nodes were found in 11 (73%) of 15 subsequent therapeutic node dissections; the 16th had metastatic parailiac nodes as well. Two patients of the remaining 163 had only metastatic parailiac nodes, without metastatic inguinal nodes. Of the remaining 161 histologic Stage I patients, 23 (14%) developed inguinal node metastases in the course of the follow-up. In 17 (74%) these metastases occurred within 2 years of perfusion. Ten of the 23 showed simultaneous general metastases. The vast majority of the inguinal node metastases developed in patients with a tumor greater than or equal to 5 mm. The 5-year survival was 81%, i.e. 84% in females versus 69% in males, the difference being significant (P less than 0.01). A tumor thickness greater than or equal to 5 mm implied a significantly less favorable prognosis as to development of inguinal node metastases associated with general metastases than a tumor thickness less than 5 mm. The benefit of the inguinal node biopsy was related to the difference in 5-year survival between the group with inguinal node metastases at perfusion (69%) and the group who developed inguinal node metastases during the follow-up (24%). The difference was great (45%) but statistically not significant. The data seem to warrant the conclusion that, after perfusion therapy, inguinal node biopsy is sufficient to stage the disease process at a tumor thickness less than or equal to 5 mm. Given a tumor thickness less than or equal to 5 mm, elective groin dissection might improve the chance of survival.

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.

Three cases of malignant hemangiopericytoma in one family are reported. To our knowledge familial occurrence of malignant hemangiopericytoma has not been described before. Two of these lesions occurred in the head and neck region and one case presented as an intraabdominal tumor. Consanguinity of the parents seems to be likely, suggesting an autosomal recessive mode of inheritance in our family, whereas the similarity in age of onset in these three patients was apparent.

Renal function in 24 patients with disseminated nonseminomatous testicular carcinoma treated with combination chemotherapy including cis-platinum was examined prospectively. Renal function was monitored by several determinations of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and serum creatinine, and beta-2-microglobulin. A reduction in GFR and ERPF was found at the end of the induction chemotherapy and at six weeks thereafter. Median GFR and ERPF decreased both 23% (P less than 0.01). Serum creatinine and beta-2-microglobulin concentrations however did not rise. It is suggested that under the influence of chemotherapy with platinum the production of creatinine and beta-2-microglobulin is decreased rendering their serum levels unsuitable as parameters of renal function.