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Predictive parameters of biologic behavior of early stage nonseminomatous testicular germ cell tumors.

BACKGROUND: Thirty percent of patients presenting with clinical stage A nonseminomatous testicular germ cell tumors in fact have pathologic stage B disease. This pilot study was performed to determine whether DNA content and cell cycle analysis by flow cytometry and single-cell cytophotometry can improve clinical staging in these patients. METHODS: The orchiectomy specimens of 102 patients with clinical stage A disease were analyzed retrospectively using histopathologic classification, flow cytometry, and single-cell cytophotometry. All patients had undergone retroperitoneal lymph node dissection. RESULTS: The multivariate analysis in this group of patients resulted in the following model: If the primary tumor consisted of 100% embryonal carcinoma, the patient was classified as high risk for retroperitoneal metastasis. If the patient was found to have less than 100% embryonal carcinoma in the primary tumor, the percent of aneuploid tumor cells in S-phase as identified by flow cytometry was most predictive for pathologic stage. Using this approach, 91% of all patients with pathologic stage B, and 77% of the patients with pathologic stage A were correctly classified; test efficiency was 82%. CONCLUSIONS: These results demonstrate an improvement in clinical staging in this group of patients. This paradigm, developed from retrospective analysis, will be tested prospectively in consecutive patients to determine if it is clinically useful.

Aneuploidy↗

Adult primary pure teratoma of the testis. The Indiana experience.

BACKGROUND: Pure testicular teratoma in adults is a relatively rare malignant tumor with the ability to invade and metastasize. Pure teratoma generally is believed to be less aggressive and less likely to progress, to present in lower stages, and to have better survival rates then other forms of germ cell tumor. Consequently, clinical stage A patients with pure testicular teratoma commonly have been considered to be managed best by surveillance. METHODS: A computerized database search identified 41 patients presenting to Indian University with pure teratoma in the orchiectomy specimen. These patients were further subdivided into four groups based on clinical stage, as follows: Group I, 18 patients with clinical Stage A disease; Group II, 4 patients with clinical Stages A-B1 disease based on questionable computed tomography findings; Group III, 3 patients with clinical Stage B1 disease; Group IV, 16 patients with advanced stage (B3-C) disease. The experience with these patients was reviewed. RESULTS: The overall risk of lymph node metastasis in retroperitoneal lymph node dissection (RPLND) and the risk of relapse after RPLND for patients with low stage pure testicular teratoma (groups I-III) were 40 and 16%, respectively. In patients with clinical Stage A teratoma, the risk of retroperitoneal metastasis in RPLND was 16.7% and the relapse rate was 11.1%. In addition, nearly 37% of referred patients with pure teratoma presented with advanced disease. CONCLUSIONS: These data provide additional confirmation of the metastatic potential of pure testicular teratoma. The proper management of the adult clinical stage A patient with primary pure teratoma of the testis should not necessarily differ from the management of any other histologic type of nonseminomatous testicular tumor. Accordingly, histologic diagnosis of pure teratoma should not mandate surveillance. Instead, patients must be given adequate information regarding management options, as are all other patients presenting with clinical Stage A nonseminoma.

Adolescent↗

Lymph node metastasis and retroperitoneal lymphadenectomy in ovarian cancer.

While clinicians are devoting themselves to the study of the behaviour of ovarian cancer as well as to the search for more effective therapeutic modalities, little attention has been paid to an important route of metastasis in this group of diseases: retroperitoneal spread through the lymphatic pathway. The purpose of this report is to present a 5-year experience of a prospective study on lymph node metastasis in patients with ovarian cancer through retroperitoneal lymphadenectomy at the Peking Union Medical College Hospital. From June 1982 through May 1987, retroperitoneal lymph node dissection was performed in 105 cases of ovarian cancer. Seventy-seven (73.3%) were histologically diagnosed as cancer of epithelial origin, and 28 (26.7%) as germ-cell tumours. The overall incidence of retroperitoneal positive nodes was 54.3% (57/105). The incidence of positive pelvic nodes was 46.7% (49/105), and that of positive para-aortic nodes was 37.5% (30/80). In 69 patients who underwent systemic lymphadenectomy, 39 were found to have glandular involvement; in these 39 patients both aortic and pelvic nodes were positive in 19 cases (48.7%), aortic nodes were positive and pelvic nodes negative in 7 cases (18.0%), and pelvic nodes were positive and aortic nodes negative in 13 cases (33.3%). Preoperative lymphography was performed in 30 cases. The positive and negative correspondence rates with the pathological findings were both 83.3%. In 38 cases in which the primary cancer originated in the left ovary, 17 (44.7%) were found to have positive pelvic nodes, whereas in 25 cases with primary cancer arising in the right ovary only 2 (8%) had metastasis of the ipsilateral pelvic nodes. The lymph nodes obtained from 22 patients with positive nodes and sufficient preoperative chemotherapy were carefully examined under the microscope for the effects of the drugs. Some cellular degeneration of the lymph node metastasis was observed in only one of the 15 cases of epithelial cancer, and no response at all was noted in three cases of immature teratoma. Cellular degeneration accompanied by extensive necrosis was demonstrated in the metastatic tumours of the lymph nodes in all four cases of endodermal sinus tumour. Seventy-two patients were followed-up for at least 2 1/2 years. The rate of complete remission was 46.7% (14/30) in patients with negative nodes, but only 33.3% (14/42) in those with positive nodes. However, the difference was not statistically significant.

Antineoplastic Combined Chemotherapy Protocols↗

Management of lymphatic fistulas by total parenteral nutrition.

Lymphatic fistula is a rare surgical complication, which mainly occurs after cervical or retroperitoneal lymph node dissection and which frequently requires a surgical repair. A small series of nine postoperative lymphatic fistulas treated conservatively with total parenteral nutrition (TPN) is reported. All the patients were malnourished at the beginning of the TPN, and all exhibited an objective improvement of their nutritional status after completion of the treatment. Due to the interruption of the enteral alimentation or to the nutritional repletion, spontaneous closure of the fistula was achieved in eight of nine patients treated with TPN longer than 1 week. The authors conclude that whenever the immediate surgical repair is not recommended, or it is not successful, a 2- to 3-week course of TPN may be used with the chance of spontaneous healing. In any case, patients conservatively treated by TPN can undergo a delayed operation with minimal risk because of the improved nutritional status.

Chylothorax↗

Redo retroperitoneal lymphadenectomy for germ cell tumor.

Redo retroperitoneal lymph node dissection (RPLND) for the treatment of germ cell tumors (GCTs) is an uncommonly performed procedure. We report on 9 patients who underwent redo RPLND at the University of Wisconsin (UW) between January 1988 and December 1990. Indications for redo RPLND include: residual retroperitoneal mass after initial RPLND and chemotherapy, normal alpha-fetoprotein (AFP) and beta subunit of human chorionic gonadotropin (B-HCG), otherwise negative metastatic workup, and evidence that the mass is resectable. Overall, 6 of 9 patients are alive with no evidence of disease at a mean follow-up of thirty-two months. Preoperative evaluation, histopathology, morbidity, and technical aspects of this procedure, which is a critical part of the management of GCT, are reviewed.

Adult↗

Treatment of the residual retroperitoneal mass after chemotherapy for advanced seminoma.

Although resection of the residual retroperitoneal mass after chemotherapy for nonseminomatous testicular cancer is standard practice, controversy exists as to the appropriate management of the residual mass after chemotherapy for advanced seminoma. A literature review suggests that 15 to 25 per cent of such masses will contain residual cancer, suggesting that retroperitoneal lymph node dissection is appropriate in these patients.

Adult↗

Surgical treatment of stage-I non-seminomatous germ cell testis tumor. Final results of a prospective multicenter trial 1982-1987. Testicular Tumor Study Group.

Final results of a prospective multicenter trial are presented comparing modified (ipsilateral) and radical retroperitoneal lymph node dissection (RLND) with regard to staging accuracy, curativity, and preserved ejaculation in stage-I non-seminomatous testis tumor. In 168 patients after modified and 67 patients after radical RLND, no differences were found in relapse rates (17 and 15%, respectively; median follow-up 30 months); in frequency of retroperitoneal relapse (2.4 and 1.5%, respectively), and intra-/postoperative complications (12 and 10%, respectively). Postoperative ejaculation was antegrade in 74 and 34%, (p less than 0.001), retrograde in 11 and 12% respectively. Normozoospermia was found in 50% of patients postoperatively vs. 20% preoperatively. Results are discussed in view of other alternatives. Modified RLND is considered an optimal approach to stage-I non-seminomatous germ cell testis tumor, outside specific trials.

Adult↗

Cytoreductive surgery in disseminated non-seminomatous germ cell tumours of testis.

Between 1977 and 1988, 67 patients underwent surgical removal of residual metastatic deposits following an aggressive chemotherapy regimen (cisplatin, vincristine, methotrexate and bleomycin alternating with etoposide, actinomycin D and cyclophosphamide) for disseminated germ cell tumours of the testis (stage IIB or above). Ninety-one surgical procedures were performed. There were 63 (69 per cent) retroperitoneal lymph node dissections, 16 (18 per cent) thoracotomies, three (3 per cent) hepatic resections, three (3 per cent) craniotomies, five (5 per cent) delayed orchidectomies and one anterolateral decompression of the vertebral column. Nine (13 per cent) patients required a repeat retroperitoneal node dissection and one patient needed a repeat thoracotomy to remove recurrent metastatic deposits during the period of follow-up. Multivisceral resections and vascular reconstruction procedures were required in 20 (30 per cent) patients undergoing retroperitoneal node dissection. Fifty-five (82 per cent) patients remain in complete remission with a mean follow-up period of 49.6 months (range 2-121 months). Nine (13 per cent) patients died with metastatic disease between 2 months to 4 years after operation. There were three deaths in the perioperative period (4 per cent). The histology of the resected metastases revealed undifferentiated active tumour in 20 (30 per cent) patients, differentiated mature teratoma in 29 (43 per cent) patients and fibrosis/necrosis in 18 (27 per cent) patients. Twelve (60 per cent) patients with undifferentiated elements and 15 patients (60 per cent) with raised preoperative tumour markers (poor prognostic categories) are in complete remission. Cytoreductive surgery in patients with metastatic germ cell tumours offers the best chance of remission following chemotherapy even in poor prognostic group categories.

Adolescent↗

[Value of limited dissection of residual retroperitoneal masses after chemotherapy for malignant non-seminoma tumors of the testis. Apropos of 74 cases].

Since asplatin salts have been used in chemotherapy, the efficiency of this treatment has changed the destiny of advanced forms of testicular cancer. The universally recommended treatment of post-chemotherapy residual retroperitoneal tumor masses is radical retroperitoneal lymph node dissection. Results of our 74 limited expresses of these tumor masses confirm that the chosen treatment was appropriate. It guarantees the future and limits genital sequellae in young patients. It is perfectly consistent with the therapeutic history of this model in cancerology: precisely defined indications for the therapeutic means of a pluridisciplinary pool of resources always increases efficiency, reduces the need for invasive treatment, and limits sequellae.

Combined Modality Therapy↗

[A case of teratoma of the testis with retroperitoneal lymph nodes involved with malignant teratoma after chemotherapy].

This report describes a case of teratoma with retroperitoneal lymph nodes involved with malignant teratoma (enteric adenocarcinoma) after extensive chemotherapy for the original testicular cancer. A 18-year-old man with a mixed cell tumor (embryonal carcinoma+teratoma+yolk sac tumor) received three courses of VAB-6 chemotherapy for bulky mass following inguinal orchiectomy. He was referred to Tochigi Cancer Center for treatment of a residual mass. He was treated with resection of the mass combined with left nephrectomy due to severe adhesion and pathological diagnosis of the resected lymph node was mature teratoma with a massive necrotic tissue. Two courses of BEP chemotherapy were given to the patient following the surgery. Six months after completion of chemotherapy, a retroperitoneal mass of 1.5 cm in diameter, was detected by CT scan. Standard retroperitoneal lymph node dissection was performed and the pathological diagnosis of the lymph node was teratoma with malignant transformation containing enteric adenocarcinoma. Teratomatous portion of the primary lesion was precisely re-examined and adenocarcinoma, similar histology to the retroperitoneal mass, was identified. He received two courses of EAP chemotherapy (Cis-platin+etoposide+doxorubicin) as an adjuvant chemotherapy following the surgery and he is alive with no evidence of recurrence for 21 months. Presence of non germ cell malignancy after chemotherapy in testicular cancer has been regarded as a rare phenomenon. Flow cytometric DNA analyses of both embryonal carcinoma and teratoma in the primary lesion, mature teratoma and teratoma with malignant transformation of the retroperitoneal lymph node disclosed that these tumors were all aneuploid tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[A case report of infantile testicular cancer: dissection of paraaortic lymph node involvement indicated by gradual rise in serum alpha-fetoprotein after orchiectomy].

We present a case of a 32-month-old boy with teratoma accompanied by yolk sac carcinoma and embryonal carcinoma of the right testicle. To treat the gradual rise in serum AFP value 3 months postoperatively, he received combined chemotherapy including VCR, CPM and ADM followed by bilateral retroperitoneal lymph node dissection. The preaortic lymph node disclosed, pathologically, yolk sac carcinoma and embryonal carcinoma, which demonstrated neither degeneration nor necrosis despite remarkable decrease in serum AFP value after the chemotherapy. The patient had normal AFP value and no evidence of recurrent disease 36 months after the lymph node dissection. We emphasize the discrepancy between the response of the tumor marker after the chemotherapy and the histologic alteration. Furthermore, the management of infantile testicular cancer is discussed.

Child, Preschool↗

Clinical stage I nonseminomatous germ cell tumors of the testis in childhood and adolescence: an analysis of 31 cases.

A 20-year single-institution experience of clinical stage I nonseminomatous germ cell tumors of the testis (NSGCTT) in childhood and adolescents was reviewed in relation to clinical characteristics, treatment modalities, and survival. Thirty-one patients with clinical stage I NSGCTT were seen between 1980 and 2000: 14 children and 17 adolescents. Yolk sac tumors and/or teratomas occurred in the children, whereas mixed histologies, including embryonal carcinoma, were predominant in the adolescents. After orchiectomy, the children were assigned to surveillance and the adolescents to active treatment: 16 underwent retroperitoneal lymph node dissection (RPLND) and 1 had adjuvant cisplatin-based chemotherapy because of a high-risk histology. Three of the 14 children (21.4%) relapsed 3, 7, and 8 months after orchiectomy: all 3 had yolk sac tumors and presented with increased alpha-fetoprotein levels. No patients had retroperitoneal relapse; two recurred locally and one in the lung. All three children were treated with cisplatin-based chemotherapy with or without surgery. Among the 16 adolescents undergoing RPLND, 4 (25%) had nodal metastases. Three of the 12 patients (25%) who had negative nodes at RPLND relapsed in the lung 3, 7, and 8 months after RPLND. All were treated with cisplatin-based chemotherapy with or without surgery. Five-year relapse-free and overall survival rates for the whole series were 80.6% and 100%, respectively. This series enabled the authors to pinpoint several important aspects of stage I NSGCTT in children and adolescents. In particular, almost all the childhood cases had the same yolk sac tumor histology, the children tended to have localized disease, and an increased alpha-fetoprotein level had a very high predictive value, suggesting that follow-up should include AFP measurements. A conservative approach is the best option in children, while adolescent NSGCTT behaves like the adult disease and management must include similar treatment strategies.

Adolescent↗

Lymph node metastasis of ovarian cancer: a preliminary survey of 74 cases of lymphadenectomy.

Retroperitoneal lymph node dissection was performed in 74 cases of various types of ovarian malignancies. Fifty-three (71.6%) were histologically confirmed as cancer of epithelial origin and 19 (25.7%) as germ cell tumors. The results indicate that lymphatic metastasis is an exceedingly important route of spreading of this group of malignant diseases. The overall incidence of retroperitoneal positive nodes was 56.8% (42/74). In 49 cases undergoing systemic lymphadenectomy 32 were found to have glandular involvement, of which both aortic and pelvic nodes were positive in 17 cases (53.1%), aortic nodes positive but pelvic negative in six (18.8%), and pelvic nodes positive but aortic negative in nine (28.1%). In 32 cases with primary cancer that originated from the left ovary, 17 (53.1%) were found to have positive pelvic nodes, whereas in 19 cases with cancer arising from the right ovary, only one (5.3%) had metastasis of ipsilateral pelvic nodes. The routes of lymphatic spreading and the significance of lymphadenectomy in ovarian cancer are discussed.

Female↗

The role of thoracotomy in managing postchemotherapy residual thoracic masses in patients with nonseminomatous germ cell tumours.

OBJECTIVE: To evaluate the clinical outcome and identify prognostic variables in patients with nonseminomatous germ cell tumours undergoing postchemotherapy thoracotomy for residual masses, as the role of this procedure is controversial. PATIENTS AND METHODS: Of 385 patients who underwent postchemotherapy retroperitoneal lymph node dissections between 1988 and 1998, 105 also had 130 thoracotomies. The clinical presentation, chemotherapy regimens, marker status, primary tumour histology, pathology of all resected masses, and clinical outcome of these 105 patients were analysed. RESULTS: The overall discordance rate for synchronous thoracic and retroperitoneal masses was 28%; that for asynchronous thoracic and retroperitoneal masses was 57%. Independent prognostic factors for residual thoracic teratoma or cancer were teratoma (mature or immature) in the primary tumour or retroperitoneal teratoma or cancer. Although three of 12 patients with residual thoracic cancer remained with no evidence of disease, residual thoracic cancer is an independent prognostic factor (P < 0.001) against disease-free survival. CONCLUSION: Postchemotherapy thoracotomy yields important prognostic information, and is therapeutic for most patients with teratoma and a subset with residual viable cancer. The prognostic criteria predictive of fibrosis are not sufficiently accurate to omit resection of residual thoracic masses.

Antineoplastic Combined Chemotherapy Protocols↗

Spermatic cord liposarcoma in a young boy.

We report on a spermatic cord liposarcoma arising in a 16-year-old boy. Treatment consisted of radical orchiectomy without retroperitoneal lymph node dissection, and adjuvant radiation and chemotherapy. The patient has survived 14 months without evidence of recurrence. Paratesticular localization of liposarcoma in patients less than 20 years old is rare. The tumor has no particular characteristic. Treatment consists of radical orchiectomy and the role of retroperitoneal lymphadenectomy is controversial.

Adolescent↗

Early clinical stages of nonseminomatous testis cancer. Evaluation of the primary treatment and follow-up procedures of the SWENOTECA project.

During a 5-year period, 588 consecutive patients with nonseminomatous testicular germ cell cancer were included by 16 hospitals into the Swedish-Norwegian Testicular Cancer Project (SWENOTECA). A total of 370 (63%) had early clinical stages (CS1, CS1Mk+ and CS2A), and 345 (93%) of these patients underwent pathological staging (PS) by retroperitoneal lymph node dissection (RPLND). The overall clinical staging accuracy was 75%, with no significant difference between hospitals with low, medium or high patient accrual rate. Addition of bipedal lymphography did not improve the clinical staging accuracy compared to evaluation of the retroperitoneum by CT alone. Tumor serum markers before and close monitoring of the levels after orchiectomy gave valuable information regarding risk of retroperitoneal metastases. After a median follow-up period of 5 years 30 (13.8%) of 217 patients with PS1 disease relapsed, only 3 of them later than 18 months from the RPLND. Short orchiectomy to RPLND time interval, vascular invasion and absence of teratoma elements in the primary tumour were significant predictors of relapse in PS1 cases according to multivariate analysis. Unilateral RPLND was not associated with higher relapse rate than a bilateral procedure, but significantly reduced the risk of dry ejaculation after RPLND. None out of 122 PS2 patients who received adjuvant cisplatin-based chemotherapy after RPLND relapsed, despite the fact that 37 of them had only undergone a unilateral RPLND. Repeated CT examinations and most routine blood tests except serum alpha foeto protein (AFP), beta subunit of human chorionic gonadotropin (HCG) and lactate dehydrogenase (LD) may safely be omitted in the follow-up period for patients who have been pathologically staged with RPLND, provided that effective adjuvant chemotherapy has been given to the PS2 patients.

Antineoplastic Combined Chemotherapy Protocols↗

[Retroperitoneal lymph node metastasis in patients with ovarian cancer].

From 1979 to 1987 retroperitoneal lymph node dissection was performed at the Tokyo University Hospital in 41 cases (pelvic lymph node biopsy was done in 4 cases, pelvic lymphadenectomy in 23 cases, pelvic and paraaortic lymphadenectomy up to the renal vessels in 14 cases) of Stage Ia to IV ovarian cancer following cytoreductive surgery. The incidence of retroperitoneal positive nodes was 11.1% (2/18) in Stage I, 50.0% (5/10) in Stage II, 50.0% (5/10) in Stage III and 0% (0/3) in Stage IV (FIGO criteria without considering the pathologic findings of retroperitoneal lymph nodes). The positive rate of lymph node involvement in Stage II and Stage III was significantly higher than that in Stage I. The tumors involving both ovaries were more likely to metastasize to retroperitoneal lymph nodes. Enlargement of tumors and increased ascites were not the risk factors of retroperitoneal lymph node metastasis. These data suggest that the occurrence of retroperitoneal lymphatic spread in ovarian cancer is comparable to that in uterine cancer and increased by involvement of both ovaries and extension to other pelvic tissues.

Adult↗

Is postchemotherapy retroperitoneal surgery necessary in patients with nonseminomatous testicular cancer and minimal residual tumor masses?

PURPOSE: At least one third of the patients with metastatic testicular cancer are rendered tumor-free by cisplatin-based chemotherapy. One may question, therefore, the routine use of postchemotherapy retroperitoneal lymph node dissection (RLND), especially if the residual masses are less than 20 mm in diameter. To define the role of such surgery, we analyzed the postchemotherapy histology in testicular cancer patients with minimal residual disease. PATIENTS AND METHODS: Seventy-eight patients with advanced nonseminomatous testicular cancer underwent RLND after three to four cycles of cisplatin- or carboplatin-based chemotherapy. In all patients, the largest diameter of the residual retroperitoneal mass was less than 20 mm. RESULTS: Complete fibrosis/necrosis was found in 51 patients, mature teratoma in 22, and vital malignant germ cell tumor in five. In two of the latter five patients, alphafetoprotein (AFP) had increased immediately before RLND. In the 76 patients with normal pre-RLND tumor markers, the presence of undifferentiated malignant teratoma (MTU) in the primary tumor and normal prechemotherapy tumor markers were independent parameters predicting complete fibrosis/necrosis, which was demonstrated in all 15 patients with these two pretreatment parameters. CONCLUSIONS: Postchemotherapy RLND can be omitted in patients with MTU in the primary tumor who have normal AFP/human chorionic gonadotropin (AFP/HCG) before chemotherapy and whose residual retroperitoneal mass is less than 20 mm in diameter. If the pre-RLND tumor markers are normal, RLND should be performed in all other patients with small residual masses, even in the presence of a normal computed tomography (CT) and particularly if regular follow-up of the patients is not guaranteed.

Adolescent↗