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Elevated serum tumor markers in patients with testicular cancer after induction chemotherapy due to a reservoir of markers in cystic differentiated mature teratoma.

Elevated serum tumor markers in patients with testicular cancer after induction chemotherapy indicate in most instances the presence of residual malignant disease. We describe 2 patients with elevated tumor markers after chemotherapy and before retroperitoneal lymph node dissection who did not prove to have residual malignant disease but cystic differentiated mature teratoma with a high content of alpha-fetoprotein and beta-human chorionic gonadotropin, respectively, in the cysts. It is postulated that leakage of the contents of these cysts to the plasma compartment was responsible for maintaining elevated serum tumor marker levels. Recognition of such entities is of consequence since unnecessary salvage chemotherapy in these patients may be avoided.

Antineoplastic Combined Chemotherapy Protocols↗

Mortality in pediatric paratesticular rhabdomyosarcoma: a multivariate analysis.

We performed a retrospective analysis of 28 children presenting with confirmed paratesticular embryonal rhabdomyosarcoma to examine factors predictive of fatal outcome. Complete surgery, defined as radical inguinal orchiectomy with clear microscopic margins plus radical, retroperitoneal lymph node dissection with extirpation of all gross disease, was performed in 21 patients (75 per cent). All patients received chemotherapy and 20 received radiation therapy according to protocol. Of the patients 16 have survived for more than 5 years with no evidence of disease. Univariate analysis revealed that only the presence of parenchymal metastases at diagnosis (p less than or equal to 0.040) and unresectability (p less than or equal to 0.003) were significant predictors of fatal outcome. Multivariate analysis showed that unresectability was the most important predictor of mortality with an estimated relative risk of 5.8.

Adolescent↗

Changing concepts in the treatment of nonseminomatous germ cell tumors of the testis.

The development of effective chemotherapy for advanced nonseminomatous germ cell tumors of the testis has changed dramatically the outlook for this once uniformly fatal disease. We reviewed our experience with changing modalities of therapy during a 7-year period in the treatment of 152 patients with all stages of testis tumor. Survival rates have increased from 84 per cent for patients with stage A, B1 or B2 tumors treated with sandwich irradiation therapy and retroperitoneal lymph node dissection to 100 per cent for patients with node dissection with or without chemotherapy. Survival rates continuously free of disease for patients with advanced (stage B3 or C) disease have increased from 53 per cent in 1975 to 1977 to 82 per cent by the addition of platinum-based polychemotherapy and judicious lymphadenectomy. A unified plan of management for patients with low stage and advanced stage nonseminomatous testicular tumors has evolved.

Antineoplastic Agents↗

Correlation of vascular invasion and metastasis in germ cell tumors of testis--a preliminary report.

A preliminary study was conducted to correlate vascular invasion with metastasis in testicular tumors. A lectin-immunoperoxidase procedure was used to identify the vessels. Together with standard hematoxylin and eosin staining, the presence of tumor cells in vessels was detected. Primary tumor specimens from 37 cases and retroperitoneal lymph nodes from 10 cases of germ cell tumors were studied. The results showed good correlations between vascular invasion in primary tumors and metastasis to lymph nodes in nonseminomatous germ cell tumors, and between vascular invasion in retroperitoneal lymph nodes and the presence of other metastases. Eight of the 9 nonseminomatous germ cell tumor patients with vascular invasion had metastases, and all 4 patients that had vascular invasion in the lymph nodes had other metastases. However, there seemed to be no correlation between vascular invasion and clinical staging in cases with seminoma in which retroperitoneal lymph node dissection was not performed. These observations, although based on a limited number of cases, warrant more extensive investigations.

Blood Vessels↗

Recurrences in surgical stage I nonseminomatous germ cell tumors of the testis.

A retrospective analysis of patients with surgical stage I nonseminomatous germ cell tumors of the testis was done in an attempt to define the pathogenesis of treatment failure. Of 138 patients 126 (91 per cent) remain free of disease, with a median followup of 5 or more years, and 12 (9 per cent) suffered relapse an average of 9 months after orchiectomy and retroperitoneal lymph node dissection. The majority of recurrences were in the lungs. Of 12 patients who had recurrence 6 were salvaged and are alive without evidence of disease 3 or more years after the second complete remission. A history of scrotal surgery or scrotal violation, the extent of the primary tumor and the presence of sarcomatous elements in the primary were not statistically significant risk factors in this study. A higher recurrence rate with embryonal carcinoma than with teratocarcinoma was not statistically significant.

Adolescent↗

Selected experience with surgery and combination chemotherapy in the treatment of nonseminomatous testis tumors.

We treated 208 patients with newly diagnosed nonseminomatous germ cell tumors of the testis between January 1975 and March 1978. Patients with stages I and II disease underwent retroperitoneal lymph node dissection, and the majority of patients with stage II neoplasm received adjuvant chemotherapy afterwards. Patients with stage III and palpable stage II neoplasm had initial chemotherapy with or without subsequent surgery. The over-all cure rates were 96 per cent (76 of 79) for patients with stage A, 94 per cent (31 of 33) with stage IIA, 83 per cent (35 of 42) with stage IIB and 35 per cent (15 of 43) with stage III disease. The stage of disease at the time of diagnosis, local extent of the primary tumor, nodal category in stages I and II cancer, and chemotherapy were factors influencing relapse rate and over-all survival.

Adolescent↗

Adjuvant vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy regimen with and without maintenance in patients with resected stage IIB testis cancer.

A total of 42 patients with stage IIB nonseminomatous germ cell tumors of the testis after orchiectomy and retroperitoneal lymph node dissection received adjuvant chemotherapy with the modified vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum regimen. Of the patients 29 had N2B and 13 had N3 nodal categories. Adjuvant vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy was given with maintenance in the first 24 patients and without maintenance (2 months of chemotherapy) in the subsequent 18. Chemotherapy with maintenance was given for 1 year and began with 2 inductions 3 to 4 weeks apart: 600 mg./m.2 intravenous cyclophosphamide, 30 mg. intravenous bleomycin, 1 mg./m.2 intravenous actinomycin D and 4 mg./m.2 intravenous vinblastine on day 1, 20 mg./m.2 bleomycin daily by continuous 24-hour induction on days 1 to 3 and 120 mg./m.2 intravenous cis-platinum with mannitol-induced diuresis on day 4. Maintenance with 6 mg./m.2 intravenous vinblastine and 1 mg./m.2 intravenous actinomycin D every 3 weeks was initiated 3 weeks after the second induction for the remainder of the year. Adjuvant vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy without maintenance was given for 2 months and used 3 inductions identical to those described previously. Complete remission has been maintained in 41 of 42 patients: all 24 who received maintenance chemotherapy and 17 of 18 who did not. One patient had a relapse with sarcoma and 6 required broad-spectrum antibiotics for fever during myelosuppression. A temporary increase in the serum creatinine of more than 2 mg. per cent occurred in 1 patient. Chronic renal failure or pulmonary fibrosis was not seen. Our results show that vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy is effective in the prevention of recurrences in patients with resected stage IIB disease, and suggest that adjuvant chemotherapy is equally effective with or without maintenance.

Adolescent↗

Treatment of testicular tumors arising in patients with previous inguinal and/or scrotal surgery.

Of 20 patients with testicular tumors that occurred after previous inguinal and/or scrotal surgery 6 with seminomas were treated with traditional radiation therapy that included the ipsilateral groin, while 14 with nonseminomatous tumors were treated with retroperitoneal lymph node dissection with or without chemotherapy. No patient suffered inguinal lymph node metastases. Based on the satisfactory results in these patients to date and the lack of subsequent detectable recurrence of tumor we do not advocate additional treatment to the superficial inguinal lymph nodes and scrotum.

Adolescent↗

Adjuvant chemotherapy in non-seminomatous testis cancer: "mini-VAB" regimen: long-term followup.

Since 40 to 50 per cent (range 20 to 80 per cent) of patients with stage II non-seminomatous germ cell tumors of the testis suffer relapse after orchiectomy and retroperitoneal lymph node dissection, relatively non-toxic adjuvant chemotherapy (consisting of vinblastine, actinomycin D, bleomycin and chlorambucil) was given to 62 patients after lymphadenectomy. Of these patients 82 per cent remained free of disease with a 4-year median followup and 18 per cent had relapse. Retrospective analysis reveals that no patient (0 of 33) with stage IIA and 38 per cent (11 of 29) with stage IIB disease had relapse. Patients with histologic evidence of extranodal extension of disease (N3 category) had the highest relapse rate (62 per cent). Based on our experience we recommend that patients with resected stage IIB disease, particularly those with extranodal extension of tumor, receive aggressive adjuvant chemotherapy.

Antineoplastic Agents↗

Lymphangiography in patients with malignancy in a non-descended testicle.

Lymphangiography was performed on 23 patients with malignancy in non-descended testicles, 14 of whom had seminomatous and 9 non-seminomatous tumors. Lymph node metastases were shown by lymphangiography in 8 patients: 3 in lumbar nodes, 1 in iliac nodes alone and 4 in lumbar and iliac lymph nodes. Microscopic metastases were shown in lumbar nodes at retroperitoneal lymph node dissection in 2 patients when the lymphangiograms were negative. Iliac lymph node metastases are rare in testicular tumors but may be seen in tumors of non-descended testicles, alone or in combination with lumbar metastatic disease. This information is extremely important for the radiologist as well as the clinician in the management of patients.

Adult↗

Primary leiomyosarcoma of the epididymas.

The fourth case of leiomyosarcoma of the epididymis is reported. It is suggested that radical orchiectomy, followed by frequent postoperative examinations, is an adequate method of treatment. Retroperitoneal lymph node dissection does not seem to be indicated.

Castration↗

Lipoplastic lymphadenopathy simulating malignant lymphoma and pelvic lipomatosis: Report of a case and review of the literature.

The second known cases of pelvic lipoplastic lymphadenopathy is presented. Roentgenographic studies including lymphangiography were instrumental in the diagnostic evaluation but a histopathologic diagnosis was essential to exclude a neoplastic process. The etiology and natural history of this disease are indeterminant but seemed to pursue a benign 17-year course in our patient. A retroperitoneal lymph node dissection is not indicated unless encroachment on adjacent pelvic viscera causes mechanical obstruction.

Diagnosis, Differential↗

Laparoscopy in urology.

Mention of all of the procedures in urology that have been attempted, or are being done, laparoscopically is beyond the scope of this article. The laparoscopic procedures outlined in this article are gaining increasing support as surgeons attempt to redefine gold standard minimally invasive therapies in the new millennium. Additional procedures, such as laparoscopic retroperitoneal lymph node dissections for low-stage, nonseminomatous germ cell testicular cancers and laparoscopic renal cryoablation of small renal cancers, are soon to be added to this list. As laparoscopic instrumentation and equipment continue to improve, it will become possible to explore even more procedures laparoscopically. Advances in imaging techniques, lasers, miniaturized robotics, and other areas may further define what is meant by the term minimal access surgery in the decades to follow.

Cryptorchidism↗

Positron emission tomography in the clinical staging of patients with Stage I and II testicular germ cell tumors.

OBJECTIVES: To evaluate the accuracy of fluorodeoxyglucose positron emission tomography (PET) compared with computed tomography (CT) staging in patients with Stage I and II testicular germ cell tumors (GCTs). METHODS: From January 1995 to July 1997, in 37 patients with clinical Stage (CS) I (n = 25) and CS II (n = 12) GCT (24 nonseminomas, 13 seminomas), PET and CT were compared in the initial staging. After PET, the patients with nonseminomatous GCT were staged surgically by retroperitoneal lymph node dissection and the patients with seminomatous GCT were followed up clinically. RESULTS: Correct staging by PET was achieved in 34 of 37 patients compared with correct CT staging in 29 of 37 patients. Of 10 metastatic lesions, 7 and 4 were detected by PET and CT, respectively. PET did not show false-positive signals. PET was unable to detect vital cancer with a maximal diameter less than 0.5 cm or teratoma at any size. CONCLUSIONS: PET was useful for detecting viable tumor in lesions that are visible on CT scan and, thus, it may omit false-positive CS II lesions. However, PET was not able to identify mature teratoma. In this study, PET did not improve the staging in patients with CS I tumor.

Germinoma↗

Stage II nonseminomatous testis cancer: the roles of primary and adjuvant chemotherapy.

Historically, a retroperitoneal lymph node dissection (RPLND) has been the primary treatment of stage II nonseminomatous germ cell tumor (NSGCT) patients, whereas chemotherapy has been used in the adjuvant setting. Increasing evidence of the efficacy of chemotherapy has led to additional treatment possibilities for stage II patients. Both chemotherapy and RPLND have a role in the primary therapy of stage II NSGCT, and both modalities can be used as secondary adjunctive therapy. Management of these patients now requires a renewed emphasis on risk stratification and on the integration of patient preferences into the management algorithm.

Antineoplastic Agents↗

Testicular cancer.

The following article provides a comprehensive review of male germ cell tumors; the pathology and the clinical manifestations of the tumors are discussed, as are the modern concepts of clinical staging. Patients with bulky stage II and stage III non-seminomatous germ cell tumors are treated with chemotherapy. The new international classification system has provided a very useful way to categorize these patients by prognosis. Patients with good- or intermediate-risk tumors may be treated with 3 courses of cisplatin, etoposide, and bleomycin (BEP) or 4 courses of etoposide and cisplatin (EP), and more than 90% of these patients will survive. Randomized trials have shown that, if only 3 courses of chemotherapy are to be given, the substitution of carboplatin for cisplatin and the omission of bleomycin are deleterious to outcome. Patients who still have a significant residual mass and normal markers after treatment should undergo a surgical resection of the residual tumor. Patients who are classified by the international classification system as having poor-risk tumors have about a 50% likelihood of survival, and many of these patients will require surgical resection of a residual tumor after chemotherapy. No randomized trial has proved a regimen to be superior to that of 4 courses of BEP. Currently, an ongoing trial is evaluating the effect of the early use of high-dose therapy in combination with hematopoietic rescue in patients with these types of tumors. Patients with small-volume stage II tumors are generally treated with retroperitoneal lymph node dissection (RPLND). About 25% of the patients selected for this procedure will actually have pathologically negative nodes. Those with positive nodes may elect to receive adjuvant chemotherapy (2 courses of BEP), which will almost always prevent relapse. An alternate approach for patients willing to comply with monthly follow-up is surveillance, with chemotherapy deferred until relapse is noted. About 50% of these patients will be cured with surgery (as many as 75% have microscopic disease only). With careful follow-up, those destined to relapse can be treated promptly and at a time when they have small-volume tumors and an excellent prognosis if they go on to receive chemotherapy. Patients with clinical stage I nonseminomatous germ cell tumors may also undergo RPLND, although an acceptable alternative for these patients is surveillance. The advantages and the disadvantages of each approach are discussed. The overall risk of recurrence is about 30%, but there have been patient groups defined that may vary in risk from 10% to 15% up to 50% or more. Patients with advanced seminoma are treated with chemotherapy. When this procedure is used, outcomes are favorable and all patients are either in good- or intermediate-risk groups, according to the international classification system. Patients with small-volume stage II tumors are treated with radiotherapy. Radiation is also generally used for the treatment of clinical stage I patients, although surveillance is growing in prominence as a means to treat these patients. Late effects of treatment are also discussed in this article. Ejaculatory function can be preserved in most patients who have early stage tumors and who undergo RPLND and in some patients who undergo surgery after chemotherapy. The most troubling effect of chemotherapy is the development of etoposide-induced leukemia, a unique--and fortunately rare--clinical entity.

Adolescent↗

Midaortic pseudoaneurysm complicating extensive endovascular stenting of aortic disease.

We report a case of successful surgical management of a potentially life-threatening complication of aortoiliac stent placement. A 59-year-old man who had Leriche syndrome underwent bilateral iliac artery and infrarenal aortic stent placement at another institution. His history was significant for retroperitoneal lymph node dissection at 19 years of age for testicular cancer. One week after stent placement, the patient was readmitted with abdominal pain, poor oral intake, and diffuse intermittent tenderness. Evaluation with computed tomographic scanning and endoscopy was unremarkable, and the patient was discharged. He was admitted to our institution 1 week later with persistent abdominal pain. A computed tomographic scan of the abdomen revealed a large pseudoaneurysm of the abdominal aorta. The patient underwent urgent exploration, and exclusion of his infrarenal aorta was achieved with aortobifemoral bypass grafting. After the operation, the patient's course was complicated by a large paraduodenal hematoma, which resulted in a gastric outlet obstruction, which was managed without operation. This case illustrates a potential life-threatening complication of extensive stent placement for aortoiliac occlusive disease. Injury to the abdominal aorta must be considered in a symptomatic patient after the placement of stents in the aortoiliac region, beyond the immediate periprocedural period.

Abdominal Pain↗

Treatment in germ cell tumours: state of the art.

Although the majority of patients with disseminated germ cell tumours can be cured with cisplatin-based chemotherapy, mortality is still up to 20%. Several prognostic factors have been identified to differentiate between patients with a good, intermediate or poor prognosis. In this review we discuss the recent chemotherapy trials, which were designed to reduce toxicity in good-prognosis patients and to improve efficacy in intermediate- and poor-prognosis patients. In good-prognosis patients it is obvious that the omission of bleomycin and the replacement of cisplatin by carboplatin has no place in first-line standard treatment. The reduction of four standard courses of bleomycin, etoposide and cisplatin (BEP) to three is shown possible in one study, but a confirmatory study is currently ongoing in the EORTC. In intermediate- and poor-prognosis patients, the use of new agents or alternating regimens (with or without shortened intervals) did, by now, not improve final outcome. The role of high-dose chemotherapy remains to be determined. Against this background, four courses of standard-dose BEP should still be considered treatment of first choice in the majority of patients with disseminated germ cell tumours. Furthermore, the policy in clinical stage I disease has been reviewed. In clinical stage I seminoma patients the policy is to apply adjuvant radiotherapy, while the strategy in patients with non-seminomatous tumours (surveillance, retroperitoneal lymph node dissection or adjuvant chemotherapy in high-risk patients) depends highly on the local situation, such as the operating skills of the urologist, and on the possibilities for tight follow-up. Of patients with true resistance for up-front BEP chemotherapy 90% will normally die. In patients who achieve a complete response on first-line chemotherapy, but relapse thereafter 30% will have no evidence of disease with second-line chemotherapy (VIP). In this group of patients results with high-dose chemotherapy seem promising, but its value should preferentially be determined in either a randomized fashion or by long-term follow-up from a large group of patients according to a similar protocol. The use of post-chemotherapy surgery is an essential part of management for metastatic non-seminomatous germ cell tumours, while the majority of residual masses in pure seminoma will disappear spontaneously, and frequent follow-up is recommended instead of surgical intervention.

Antimetabolites, Antineoplastic↗