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Stage II nonseminomatous germ cell tumors of the testis: an analysis of treatment options in patients with low volume retroperitoneal disease.

The management of patients with nonseminomatous germ cell tumors of the testis and low volume retroperitoneal disease remains controversial. We analyzed the treatment modalities of 56 patients divided into 3 groups: group I--18 clinical stage I cancer patients who had pathological stage II disease after retroperitoneal lymph node dissection, group II--31 patients with abdominopelvic computerized tomography abnormalities of 5 cm. or less with or without positive biological markers and group III--7 patients with persistently positive biological markers after orchiectomy with normal abdominopelvic computerized tomography scans. In group I 4 of 18 patients received chemotherapy after retroperitoneal lymph node dissection. Two patients met criteria for post-dissection chemotherapy, but they did not receive it and subsequently had relapse. Of the remaining 12 patients who were observed after dissection only 1 (8 per cent) had relapse. In group II 19 of 31 patients were treated with initial chemotherapy: 13 (68 per cent) achieved a complete response, while 6 required retroperitoneal lymph node dissection after chemotherapy. Of 31 patients 12 were treated with initial retroperitoneal lymph node dissection and 9 (75 per cent) received post-dissection chemotherapy. In group III 5 of 7 patients were treated with initial retroperitoneal lymph node dissection and 3 of the 5 subsequently required chemotherapy. Of the 7 patients 2 received initial chemotherapy and achieved a complete response. All 56 patients are without disease at 4+ to 106+ months (median 28 months). We conclude that patients with the characteristics of groups II and III should be managed initially with chemotherapy, with retroperitoneal lymph node dissection reserved for patients who fail to achieve a complete response. In group I retroperitoneal lymph node dissection is sufficient initial treatment if pathological evaluation of the retroperitoneal lymph nodes does not meet our criteria for post-dissection adjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

Unusual neoplasms detected in testis cancer patients undergoing post-chemotherapy retroperitoneal lymphadenectomy.

Approximately 30% of patients with disseminated testis cancer who receive platinum-based chemotherapy will experience normalization of tumor markers but have persistent, radiographically evident disease in the retroperitoneum. These patients usually undergo retroperitoneal lymph node dissection. Of 557 patients undergoing post-chemotherapy retroperitoneal lymph node dissection at our university medical center 45 (8.1%) had neoplastic elements distinct from the classical germ cell tumor types within the resected specimens. Examples include various sarcomas in 19 patients (3.7%), other nonsarcomatous nongerm cell cancers in 18 (3.2%) and cystic atypical choriocarcinoma in 8 (1.4%). No distinct patient characteristics or histological patterns in the primary tumor are predictive of these unusual findings in the retroperitoneal lymph node dissection specimen, although sampling error in the orchiectomy specimen could be the reason for this lack of correlation. Surgical resection of these chemoresistant tumors is potentially curative, with disease-free survival in 13 of 19 patients (68.4%) with sarcoma, 10 of 18 (55.6%) with nonsarcomatous cancer and 7 of 8 (87.5%) with cystic atypical choriocarcinoma at a mean followup of 30.6, 42.5 and 24.7 months, respectively.

Combined Modality Therapy

Complications of primary retroperitoneal lymph-node dissection for low-stage testicular cancer.

The surgical complications encountered in 478 patients who underwent primary retroperitoneal lymph-node dissection for clinical stage A and B nonseminomatous testicular cancer during the period ranging from 1982 to 1992 were reviewed. There were 54 complications in 51 patients (10.6%), and there was no surgery-related mortality. There were 16 minor complications and 38 major complications. The most frequent complication encountered was superficial wound infection, and many of the major complications were related to small-bowel obstruction and atelectasis. The incidence of complications was significantly lower in patients operated on during the last 6 years of the study (1987-1992). The complication rate was lower in patients who underwent modified unilateral procedures than in those who had bilateral dissections. The ejaculation rate of patients undergoing nerve-sparing procedures was 98%. This study reinforces the conclusion that primary retroperitoneal lymph-node dissection is an operation yielding minimal morbidity and no long-standing effect.

Ejaculation

Is adjuvant chemotherapy necessary for patients with stage B1 testicular cancer?

Controversy exists concerning the role of adjunctive chemotherapy in patients with regional nodal involvement. A randomized study reported a 48% relapse rate for patients with positive nodes (stage B1 or stage B2), all of whom were salvaged by full-dose platinum-based chemotherapy. In a series of patients with positive nodes who received two cycles of adjunctive chemotherapy postoperatively, the relapse rate was only 2%. In order to evaluate the effect of retroperitoneal lymph node dissection on relapse rates in patients with stage B1 testicular cancer, a retrospective review of a series of 39 patients was performed. Criteria for inclusion included pathologic stage B1 (less than six positive nodes, located in the primary landing site, with no node greater than 2 cm in diameter and no extracapsular lymph node extension). Patients who fulfilled the criteria along with normalization of tumor markers were followed-up expectantly after retroperitoneal lymph node dissection. Thirty-nine patients were followed from 1 to 10 years with the median duration of follow-up of 3.5 years. Ten of the 39 patients had modified retroperitoneal lymph node dissections with preservation of antegrade ejaculation. The other 29 had full retroperitoneal lymph node dissections. Three relapses were seen, one patient with retrocrural and pulmonary metastases and two patients with pulmonary metastases only for a relapse rate of 8% (three of 39). Patients with stage B2 disease received adjunctive chemotherapy with two or three cycles of platinum-based chemotherapy. We conclude that retroperitoneal lymph node dissection alone is adequate treatment for the majority of patients with pathologic stage B1 testicular cancer. In that subset of patients, adjunctive chemotherapy should be reserved for relapse.

Cisplatin

Non-seminomatous testis tumors: a plan of management based in 96 patients to improve survival in all stages by combine therapeutic modalities.

To develop a plan of management based on the clinical and pathologic stage of the tumor the results of treatment of 96 consecutive patients with non-seminomatous testis tumors have been analyzed. There were no exclusions and all patients were treated, including 17 with advanced stage C disease. All patients underwent retroperitoneal lymph node dissection as primary treatment but the judicious use of adjuvant therapeutic modalities improved survival in all stages of disease. Chemotherapy was the most important adjuvant and postoperative radiation therapy was reserved for patients with extensive retroperitoneal metastatic disease. Results indicate that a modified unilateral thoracoabdominal retroperitoneal lymph node dissection can effectively remove the retroperitoneal nodes. Of 57 patients 50 with stage A or B tumor survived after lymph node dissection without radiation therapy. Compared to an operation alone prophylactic adjuvant chemotherapy improved survival from 82 to 93 per cent for patients with minimal disease (stage A or B1). Postoperative irradiation therapy combined with cyclic chemotherapy improved survival for patients with advanced retroperitoneal disease compared to an operation and radiation alone or an operation and chemotherapy alone. An aggressive approach that combined operation with chemotherapy, radiation therapy or both, has salvaged 8 of 17 patients with disseminated metastatic disease (stage C). The over-all survival rate for these 96 patients is 78 per cent. A plan of management has evolved, which is based on retroperitoneal lymph node dissection followed by the judicious use of adjuvant chemotherapy and radiation therapy as determined by pathologic findings.

Choriocarcinoma

Management of yolk sac carcinoma of the testis clinical stage I: lymphadenectomy vs. no lymphadenectomy.

Thirty seven patients with Stage I yolk sac tumor of the testis were registered at the Instituto Nacional de Enfermedades Neoplasicas (I.N.E.N.), Lima-Peru from 1962 through 1980. Eighteen patients underwent retroperitoneal Lymph node dissection. The age incidence was 5 to 29 months except for two patients 50 and 84 months of age each. Bilateral retroperitoneal lymph node dissection was performed in seventeen patients; unilateral dissection was performed in one patient. In two patients both had one positive node at lymphadenectomy (2/18: 11%). Eleven patients (61.11%) are alive and with no evidence of disease in between 7 to 26 years post lymphadenectomy. Seven patients (38.89%) died: 4/18 (22.22%) because of progression of the disease and three patients because of no neoplastic cause. Nineteen patients did not have retroperitoneal lymph node dissection: seven patients (36.84%) are alive with no evidence of disease and 12 patients (63.16%) died: 8/19 (42.10%) because of progression of the disease and 4/19 (21%) with no neoplastic disease. In conclusion, patients with localized disease (Clinical Stage I) benefit from retroperitoneal lymph node dissection when compared to a similar group of patients not submitted to lymphadenectomy.

Child, Preschool

Sodium nitroprusside-induced hypotension in radical thoraco-abdominal dissection of retroperitoneal lymph nodes.

Blood loss and replacement in 57 consecutive otherwise healthy young patients undergoing radical thoraco-abdominal dissection of retroperitoneal lymph nodes is reviewed. Twenty-five patients received nitroprusside (hypotensive group); 32 patients (normotensive group) did not. Blood loss varied significantly between the hypotensive and normotensive groups: the mean loss (+/- SEM) was 920 +/- 72 ml for the hypotensive group compared with 1341 +/- 98 ml for the normotensive group (P < 0.001). The total blood requirement for the normotensive patients was three times that of the hypotensive group. The difference between the two groups was more apparent in patients with advanced disease.

Adult

[Radical lymphadenectomy in non-seminomatous testis tumors using radionuclide detector (author's transl)].

This paper presents first experiences with a new method of bilateral retroperitoneal lymph node dissection in cases of nonseminomatous testis tumors: lymph node-bearing tissue - labeled by conventional lymphoscintigraphy - is intraoperatively directly detected by means of a semiconductor and then removed. In our experience this nuclide detector-directed lymph node dissection seems to be a remarkable improvement of retroperitoneal lymph node dissection because of higher effectiveness, more careful surgical technique and shortened time of operation.

Adolescent

Localization of solitary and multiple metastases in stage II nonseminomatous testis tumor as basis for a modified staging lymph node dissection in stage I.

Because of a continuing need for pathological staging of clinical stage I testicular tumors an investigation was performed to determine the primary sites of metastatic involvement of the retroperitoneal lymph nodes and to define narrowly limited ipsilateral areas of lymph node dissection strictly for the purpose of staging. Surgical/pathological localization of solitary metastases provides the most direct evidence of primary lymphatic spread. There were 214 consecutive patients with stage II disease (excluding bulky disease) evaluated with respect to localization relative to the side of the involved testis and the number of metastases up to 5 cm. Solitary metastases of 5 cm. or less were found in 74 patients, 53 patients had 5 or less lymph nodes of 2 cm. or less and 87 patients had more than 5 lymph nodes of between 2 and 5 cm. Solitary nodes of the right testis tumor were located with decreasing frequency in the upper and lower interaortocaval, lower paracaval and precaval, upper precaval and right common iliac, upper paracaval and upper preaortic zones. Primary deposits of the left testis tumor were seen predominantly in the upper para-aortic zone. Upper preaortic and lower para-aortic zones were involved infrequently, and other areas were affected only in rare cases. These data contradict the assumption of a testicular lymph center located at the openings of the testicular veins into the vena cava and left renal vein, respectively. Multiple metastases were spread over the entire retroperitoneum, except for the external iliac regions. Hilar/suprahilar metastases were seen infrequently. Ipsilateral areas are defined according to primary involvement. A modified retroperitoneal lymph node dissection within ipsilateral areas is proposed as a staging operation for clinical stage I disease and a radical retroperitoneal lymph node dissection is indicated for pathological stage II disease.

Humans

Vascular considerations in postchemotherapy. Retroperitoneal lymph-node dissection: Part I--Vena cava.

A total of 42 patients underwent inferior vena cava resection (n = 40) or intraluminal tumor thrombectomy (n = 2) during retroperitoneal lymph-node dissection (RPLND) for bulky abdominal metastatic nonseminomatous germ-cell cancer (7% of all postchemotherapy RPLND cases). The three indications for caval resection included tumor clearance (38%), caval scar occlusion (14%), and caval tumor thrombus (48%). En bloc caval resection to achieve tumor clearance was justified by subsequent nodal pathology (cancer in 63% of specimens, teratoma in 31% specimens). Caval resection in the presence of scar occlusion was required de facto by virtue of its incorporation in the specimen. Caval resection or thrombectomy is indicated for intraluminal tumor thrombus because thrombus pathology (cancer, 35%; teratoma, 45%; fibrosis, 20%) reflected nodal pathology in 71% of cancer cases, 78% of teratoma cases, and 100% of fibrosis cases. The complications of caval resection were generally transitory. The 71% survival rate justifies this intensive surgical approach because these patients had exhausted all chemotherapeutic options.

Adolescent

Stage II nonseminomatous testicular cancer: a 10-year experience.

Between 1970 and 1980, 82 patients with pathologic stage II nonseminomatous germ cell testicular carcinoma were treated at the University of Minnesota. Of the 30 patients treated with a retroperitoneal lymph node dissection, 22 (77%) relapsed. Of the 18 patients treated with retroperitoneal lymph node dissection and adjuvant radiotherapy, 12 (63%) relapsed. Sixteen patients received adjuvant chemotherapy before 1976, and 14 (87.5%) relapsed. After 1976, 18 patients received adjuvant chemotherapy (11 with cisplatin) and 2 (11%) have relapsed. No patient treated with cisplatin-based adjuvant chemotherapy has relapsed. The toxicity has been modest. Cisplatin-based chemotherapy is an effective and a safe adjuvant therapy for stage II nonseminomatous germ cell testicular carcinoma.

Antineoplastic Combined Chemotherapy Protocols

Laparoscopic retroperitoneal lymphadenectomy: multi-institutional analysis.

Modified unilateral laparoscopic retroperitoneal lymph node dissection was attempted in 20 patients with nonseminomatous testicular cancer. The procedure was completed in 18 men at a median operative length of 6 hours. Median estimated blood loss was 250 cc and median number of lymph nodes removed was 14.5. Nodal disease spread was noted in 3 of 18 patients (17%). Most patients were hospitalized for 3 days or less and had returned to normal activity levels within 2 to 3 weeks. Antegrade ejaculation was preserved in all 20 patients. Significant complications occurred in 6 of 20 patients (30%), with bleeding being the most common adverse event encountered. In 2 patients an abdominal incision and completion of the procedure by open retroperitoneal lymph node dissection were required due to significant bleeding following injury to the gonadal vessels. With a median followup of 10 months (range 2 to 25), 2 men had pulmonary disease recurrence and none had abdominal recurrence. Laparoscopic retroperitoneal lymph node dissection can be completed successfully in patients with stage I testicular cancer and may be most appropriate in those with limited risk of metastatic disease spread. The morbidity may be largely attributed to a steep learning curve. The efficacy of laparoscopic retroperitoneal lymph node dissection compared with standard techniques and determination of its role in patients with testicular cancer will require longer followup in larger groups of patients.

Adolescent

The treatment of infantile embryonal carcinoma (Yolk-Sac Tumour) of the testis in children.

The case histories of five patients with an infantile embryonal carcinoma are presented. Personal observations and data from the literature indicate that treatment of this tumour is dependent on the patient's age. Non-operative staging is possible under age 1 (alpha 1-foetoprotein and CT-scan). Staging should include a laparotomy in patients aged between 1 and 2 years. Under age 2, retroperitoneal lymph node dissection is indicated only if metastases are demonstrable. From age 2 on, retroperitoneal lymph node dissection should be performed if possible: unilaterally in the absence, and bilaterally in the presence of retroperitoneal metastases. Chemotherapy is required only in cases with metastases. Radiotherapy is not indicated in the treatment of infantile embryonal carcinoma.

Bleomycin

Recurrent testis cancer: seeding from retroperitoneal nodes after complete remissions by chemotherapy.

Routine retroperitoneal lymph node dissection is generally not required after a complete remission is achieved by chemotherapy in initially disseminated nonseminomatous testis cancer. However, in patients with multiple relapses retroperitoneal lymph node dissection should be considered even if the retroperitoneum is unremarkable by radiographic staging. We report on a patient with initial stage III disease in whom a complete clinical response to chemotherapy was achieved multiple times but there was repeatedly re-seeding of the lungs from an undetected focus of nodal cancer later proved by retroperitoneal lymph node dissection. Controversies in management as well as potential mechanisms of drug resistance are discussed.

Adult

Malignant gonadal stromal tumor.

A case of malignant gonadal stromal tumor is reported, and the 24 cases reported in the English and Japanese literature are reviewed. A thirty-four-year-old male visited our hospital with a painless tumor in the left scrotum. Left high orchiectomy was performed under a diagnosis of testicular tumor, and histologic examination of the resected specimen demonstrated that it was a malignant gonadal stromal tumor. There has been no evidence of disease for forty-one months following surgery. Of the 15 cases reported in the English literature, retroperitoneal lymph node dissection was performed in 3 cases, and metastasis was present in the resected lymph nodes in 2 of the cases. These 3 patients survived with no evidence of disease for follow-up periods ranging between six months and five years. However, lymph node metastasis was observed in 5 of 6 patients who underwent orchiectomy alone or in combination with radiation to the retroperitoneal lymph nodes. The 3 patients described in the Japanese literature who had received high orchiectomy and retroperitoneal lymph node dissection survived with no evidence of disease for follow-up periods ranging from eighteen months to forty-one months following surgery. These findings indicate that retroperitoneal lymph node dissection is useful as a treatment for malignant gonadal stromal tumor. However, the prognosis for patients with advanced disease is very poor, because neither chemotherapy nor radiotherapy is effective. Corroborative study of many patients is necessary to understand the pathophysiology of malignant gonadal stromal tumor and to develop useful treatments.

Adult

[Clinical studies of testicular tumor. II. Analysis of 30 patients with nonseminomatous testicular tumor].

Clinical findings and results of various treatments were discussed for 30 patients with nonseminomatous testicular tumor (NSTT) who had been treated from August, 1968 to March, 1985. Radioimmunoassays were positive for AFP in 19 of the 22 evaluated patients (86.4%) and were positive in 14 of the 19 evaluated patients (73.7%). These positive rates are consistent with those reported by others. Abnormal pre-treatment level of hCG-beta did not always indicate poor clinical courses, since in patients under stage III A pre-treatment level of hCG-beta did not correlate to either treatment results or clinical courses, even in patients with bulky metastasis such as stage IIIB1, B2 or C their treatment results and clinical courses seemed to be primarily determined by the size and extent of metastasis. However, pre-treatment measurement of hCG-beta was useful to predict in primary and/or metastatic tumor the presence of choriocarcinoma element which could not be found with conventional histopathological studies. Most of our 14 patients at stage I were subjected to radical orchiectomy and retroperitoneal lymph node dissection followed by post-surgical management with radiotherapy or chemotherapy. With these treatments only one of the stage I patients had a recurrence. However, adjuvant therapy may not be necessary for them because of a low recurrence rate following retroperitoneal lymph node dissection and the high cure rate with intensive chemotherapy including CDDP for the early stage of recurrence, when a close follow-up would be possible. We treated only 2 patients at stage II A. One of these 2 patients became free of the disease by intensive chemotherapy including CDDP (24 months after the start of treatment). In stage II A, a high recurrence rate has been reported, following retroperitoneal lymph node dissection without post-surgical adjuvant chemotherapy, which indicates that these patients should be treated with adjuvant chemotherapy, including CDDP. All 4 patients in stage II B or III treated mainly by chemotherapy without CDDP died of the disease at around one year after treatment. However, the five-year survival rate was improved to 40% in 10 advanced patients with these stages who had been treated mainly with recent chemotherapy regimen including CDDP. The recent development of chemotherapy regimen including CDDP has been able to lead many patients with advanced stage to a curable status. However, the appropriate treatment for some patients with bulky and extensive metastasis remains to be established. More aggressive treatment such as cytoreductive surgery may be necessary for such patients.

Choriocarcinoma

Predictive parameters in biologic assessment of low-stage retroperitoneal lymph-node dissection.

In all, 30% of patients felt to have clinical stage A nonseminomatous testis cancer in fact have pathologic stage B disease. Although patients with clinical stage A nonseminoma currently enjoy a very high change for cure, a better assignment of therapy at diagnosis could lead to an overall decrease in the morbidity of treatment. This study analyzed orchiectomy specimens from 102 patients with clinical stage A nonseminomatous testis cancer, all of whom underwent pathologic staging via retroperitoneal lymph-node dissection (RPLND). Various parameters of the orchiectomy specimen were analyzed to determine whether or not clinical staging could be improved on the basis of these factors. Statistical analysis resulted in the following model. If the orchiectomy specimen consisted of 100% embryonal carcinoma the patient was classified as being at high risk for retroperitoneal metastasis. In the absence of this finding the aneuploid cell line as determined by flow cytometry was considered. If the percentage of aneuploid cells in the S phase was less than 29% the patient was felt to be at low risk for retroperitoneal metastasis. If this percentage was greater than 29% the patient was classified as being at high risk. Using this paradigm, 77% of pathologic stage A patients and 91% of pathologic stage B patients were correctly classified. The test efficiency was 82%. This pilot study resulted in an interesting model that should be tested prospectively in consecutive patients to determine whether it is clinically useful.

Aneuploidy

Chyloperitoneum following treatment for advanced gynecologic malignancies.

BACKGROUND: Chyloperitoneum is an uncommon complication following retroperitoneal surgery. Blunt abdominal trauma, abdominal surgery, abdominal or pelvic radiation, cirrhosis, lymphoma, tuberculosis, and congenital defects of lacteal formation may also lead to chylous ascites. CASES: Two patients developed chylous ascites after treatment for gynecologic malignancies. One, who also received pelvic and abdominal radiation, developed chylous ascites 11 months after retroperitoneal lymph node dissection for advanced endometrial cancer. She was treated with a diet low in fat and high in medium-chain triglycerides, as well as with intravenous hyperalimentation. She had recurrences of chylous ascites, which responded to paracentesis and intravenous hyperalimentation. The second patient developed chylous ascites 2 months after retroperitoneal lymph node dissection for advanced fallopian tube cancer. She was treated with a medium-chain triglyceride diet, which resulted in resolution of her symptoms. CONCLUSION: Chyloperitoneum is an uncommon complication following treatment for gynecologic malignancies. Our second case is the first reported in which retroperitoneal lymph node dissection for gynecologic malignancy resulted in chyloperitoneum. However, because gynecologic malignancies frequently metastasize to the periaortic lymph nodes, chylous ascites may be an important cause of morbidity following treatment.

Adenocarcinoma