Nonseminomatous Germ Cell Tumors Of Testis Research Articles

Laparoscopic Retroperitoneal Lymph Node Dissection for Stage I Nonseminomatous Germ Cell Testis Tumors: The First Case Series in Iran

To report laparoscopic retroperitoneal lymph node dissection (RPLND) as an approach for management of low-stage nonseminomatous germ cell testis tumors (NSGCT). Between August 2002 and December 2008, 19 patients with stage I NSGCT underwent RPLND in our center. Mean operation time was 340 minutes (range, 250 to 360 minutes). Procedure in 2 (10.5%) patients was converted to open. Four (21%) patients had tumors with pure histopathology while other 15 (79%) had mixed histopathology. The mean number of removed lymph nodes was 11 (range, 6 to 14). Pathology revealed lymph node involvement in 8 (42%) patients, including 6 (75%) viable tumors and 2 (25%) teratoma. After on average 47-month follow-up (range, 3 to 70 months), recurrence occurred in 2 (10.5%) patients, who underwent open retroperitoneal lymph node dissection after chemotherapy, and surgical pathology revealed teratoma in one and fibrotic tissue in another. No patient developed systematic metastasis during followup period. Our results show that compared with open surgery, RPLND has same oncologic outcome, but lower, and can be recommended for management of patients with low stage NSGCT.

On the necessity for postchemotherapy surgery for residual abdominal masses in metastatic nonseminomatous germ cell tumors (NSGCT) of testis

5088 Background: Residual abdominal masses after chemotherapy for metastatic NSGCT of testis may contain viable tumor-derived tissue which can be a nidus for relapse of disease, particularly when the tissue is frankly malignant. This justifies routine retroperitoneal lymph node dissection (RPLND) for large masses where malignant tissue is found at an appreciable rate. Yet RPLND is often carried out for smaller, or even absent, residual masses and differentiated teratoma (TD) is commonly found. There is little data on the consequence of leaving these smaller masses in situ, which is the practice in some units in the UK. Methods: 51 patients were identified from the MRC patients entered into the TE20 trial of 3 vs 4 cycles of BEP for good prognosis metastatic NSGCT who fell into the following category: metastatic NSGCT, residual abdominal mass only, unresected post-chemotherapy, response evaluation: CR or PR marker -ve. Collaborators were asked to report on mass size, relapse status, whether an operation was ever performed and the latest CT appearance. Results: 51/51 responses were received. Follow-up from the end of chemotherapy was >3years in all but two cases and the median was 5 years. When later surgery was carried out, for persistence or enlargement of the masses, the specimens contained TD with or without necrosis. One patient suffered a relapse one year after the surgery which took place 4.5 years after chemotherapy. Of the 41 patients who did not undergo surgery, 37 were considered on subsequent CTs to have normal appearances without further treatment. Conclusions: For patients with small residual masses in good prognosis metastatic disease no short or medium term benefit from routine surgery would have been seen. Its role in this situation is therefore questionable. For larger (>14mm) masses the need for routine surgery merits further study. [Table: see text] No significant financial relationships to disclose.

MP-21.16 (Podium): Primary laparoscopic retroperitoneal lymph-node dissection for clinical stage I nonseminomatous germ-cell testis tumor: long term results

MP-21.16 (Podium): Primary laparoscopic retroperitoneal lymph-node dissection for clinical stage I nonseminomatous germ-cell testis tumor: long term results

836: Patterns and Detection of Relapse in Clinical Stage I Nonseminomatous Germ Cell Testis Tumors on Surveillance: Recommendations for Follow-Up

You have accessJournal of UrologyPodium 28, Monday, May 21, 2007, 10:00 am - 12:00 pm1 Apr 2007836: Patterns and Detection of Relapse in Clinical Stage I Nonseminomatous Germ Cell Testis Tumors on Surveillance: Recommendations for Follow-Up David Kakiashvili, Lynn Anson-Cartwright, Jeremy F.G. Sturgeon, Padraig R. Warde, Peter Chung, Malcolm Moore, Lisa Wang, Julian Azuero, and Michael A.S. Jewett David KakiashviliDavid Kakiashvili More articles by this author , Lynn Anson-CartwrightLynn Anson-Cartwright More articles by this author , Jeremy F.G. SturgeonJeremy F.G. Sturgeon More articles by this author , Padraig R. WardePadraig R. Warde More articles by this author , Peter ChungPeter Chung More articles by this author , Malcolm MooreMalcolm Moore More articles by this author , Lisa WangLisa Wang More articles by this author , Julian AzueroJulian Azuero More articles by this author , and Michael A.S. JewettMichael A.S. Jewett More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)31076-0AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "836: Patterns and Detection of Relapse in Clinical Stage I Nonseminomatous Germ Cell Testis Tumors on Surveillance: Recommendations for Follow-Up." The Journal of Urology, 177(4S), p. 279 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 177Issue 4SApril 2007Page: 279 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information David Kakiashvili More articles by this author Lynn Anson-Cartwright More articles by this author Jeremy F.G. Sturgeon More articles by this author Padraig R. Warde More articles by this author Peter Chung More articles by this author Malcolm Moore More articles by this author Lisa Wang More articles by this author Julian Azuero More articles by this author Michael A.S. Jewett More articles by this author Expand All Advertisement PDF downloadLoading ...

Laparoscopic and Open Retroperitoneal Lymph-Node Dissection for Clinical Stage I Nonseminomatous Germ-Cell Testis Tumors

Laparoscopic retroperitoneal lymph node dissection (L-RPLND) has been reported as efficacious for staging of the retroperitoneum in patients with stage I nonseminomatous germ-cell testis tumors (NSGCT). However, reports are limited to a few centers, and this procedure has yet to be widely accepted as an alternative to open retroperitoneal lymph node dissection (O-RPLND). Thus, we compared our contemporary open and laparoscopic experience with RPLND. A retrospective chart review identified 28 patients who underwent either open (N = 6) or laparoscopic (N = 22) RPLND for clinical stage I NSGCT since 2000. Each patient received the appropriate modified template dissection. Perioperative demographic data, histologic nodal status, and recurrence data were evaluated. The mean follow-up was similar in the two groups. The mean operative time was not significantly different (313 minutes for L-RPLND v 284 minutes for O-RPLND). However, L-RPLND did have a significantly shorter hospitalization (1.2 v 8.5 days). Significantly more lymph nodes were removed with O-LPLND than with L-RPLND (mean 33 v 17). There was a single recurrence outside the modified template after both L-RPLND and O-RPLND and one within-the-template recurrence in the O-RPLND group. The L-RPLND is associated with less blood loss and a shorter hospital stay than O-RPLND, whereas the lymph-node yield of O-RPLND is greater. However, during the critical early follow-up period, the oncologic effectiveness and morbidity of L-RPLND for clinical stage I NSGCT appears similar to that of O-RPLND.

Gene expression profiling of early- and late-relapse nonseminomatous germ cell tumor and primitive neuroectodermal tumor of the testis.

To better understand the molecular mechanisms that underlay the development and progression of nonseminomatous germ cell tumor of testis (NSGCTT) as well as malignant transformation of teratoma and primitive neuroectodermal tumor (PNET). We studied the gene expression profiles of 17 retroperitoneal NSGCTTs (10 yolk sac tumors, 3 embryonal carcinomas, 4 teratomas) and 2 PNETs obtained from patients with two clinical outcomes. Tissue samples were obtained from the Indiana University. One group of NSGCTT and PNET patients developed metastases within 2 years (early-relapse) of initial successful treatment, and the other group developed metastases after 2 years (late-relapse). Gene expression in these groups of patients was quantified using cDNA microarrays and real-time relative quantitative PCR. We demonstrate that the gene expression profiles of these tumors correlate with histological type. In addition, we identify type-specific genes that may serve as novel diagnostic markers. We also identify a gene set that can distinguish between early-relapse and late-relapse yolk sac tumors. The expression differences of these genes may underlie the differences in clinical outcome and drug response of these tumors. This is the first study that used gene expression profiling to examine the molecular characteristics of the NSGCTTs and drug response in early- and late-relapse tumors. These results suggest that two molecularly distinct forms of NSGCTTs exist and that the integration of expression profile data with clinical parameters could enhance the diagnosis and prognosis of NSGCTTs. More importantly, the identified genes provide insight into the molecular mechanisms of aggressive NSGCTTs and suggest intervention strategies.

RISK ADAPTED MANAGEMENT WITH ADJUVANT CHEMOTHERAPY IN PATIENTS WITH HIGH RISK CLINICAL STAGE I NONSEMINOMATOUS GERM CELL TUMOR

We propose that patients with high risk, clinical stage I nonseminomatous germ cell tumors receive 2 cycles of chemotherapy initially, instead of undergoing surgery or observation. A total of 59 patients with high risk, clinical stage I nonseminomatous germ cell tumor received risk adapted adjuvant chemotherapy. Until June 1987, 20 patients were treated with 2 courses of adjuvant cisplatin, vinblastine and bleomycin at 3-week intervals. After June 1987 another 39 patients were treated with 2 cycles of bleomycin, etoposide and cisplatin. Long-term results with this treatment strategy have been excellent with limited morbidity. Adjuvant chemotherapy may be of particular value in patients with compromised followup.

Long-term results after inferior vena caval resection during retroperitoneal lymphadenectomy for metastatic germ cell cancer

Purpose: The long-term sequelae of inferior vena caval (IVC) resection during retroperitoneal lymph node dissection for metastatic nonseminomatous germ cell testis tumor (NSGCT) were assessed. Methods: Between December 1973 and September 1996, 2126 of our patients underwent RPLND for retroperitoneal nodal metastases from NSGCT; 955 had bulky disease (stages B2, B3, or C) after cytoreduction chemotherapy. Of this latter group, 65 patients (6.8%) required infrarenal IVC resection during tumor excision for cure. Our protocol does not include IVC reconstruction in such cases. Indications for IVC resection included tumor encasement or encroachment, postchemotherapy desmoplastic compression, or thrombus with tumor or clot in which cavotomy and thrombectomy cannot be performed. Results: Twenty-four of the 65 patients (postoperative follow-up period range, 11 months to 16 years; median, 89 months) were alive and able to be examined or interviewed by written and/or phone survey to assess the long-term morbidity of their IVC resection. Based on the 1994 American Venous Forum International Consensus Committee reporting standards, the clinical classifications of these 24 patients were C 0A (4), C 3S (4), C 4A (2), C 4S (13), and C 6A (1). Long-term disability was mild or absent in 75% of these patients. Conclusion: Only 1 (4.2%) of the patients surveyed had chronic venous sequelae that would fulfill the accepted criteria for subsequent elective IVC reconstruction. Despite recent reports of IVC reconstruction demonstrating relatively good patency rates and low morbidity, the addition of such a complex, time-consuming procedure to extensive retroperitoneal lymph node dissection for metastatic NSGCT involving IVC resection is generally not necessary. (J Vasc Surg 1998;28:808-14.)

LAPAROSCOPIC RETROPERITONEAL LYMPHADENECTOMY FOR CANCER OF THE TESTIS

Laparoscopic retroperitoneal lymph node dissection (RPLND) is a technically advanced procedure that has been undertaken for the management of low-stage nonseminomatous germ cell testis tumor. Although it has been shown to be an effective staging technique, its role as a therapeutic operation is currently unknown. Laparoscopic RPLND requires longer operative times but offers the patient all the advantages of minimally invasive surgery, such as less postoperative pain and shorter hospitalization and convalescence. The role of laparoscopic RPLND for the evaluation of residual abdominal masses following chemotherapy is currently being examined.

SURVEILLANCE FOR STAGE I TESTICULAR SEMINOMA: Is It A Good Option?

Postorchidectomy treatment options in patients with stage I seminoma include surveillance (reserving treatment for patients who relapse), adjuvant radiation therapy (RT), and adjuvant chemotherapy. Adjuvant retroperitoneal RT remains the treatment of choice in most centers; however, the success of surveillance in stage I nonseminomatous germ cell testis tumors, the establishment of curative chemotherapy for advanced disease, and the improvements in CT have led to re-examination of the standard treatment approach. The available data from the surveillance and adjuvant RT series suggest that almost 100% of patients with stage I testicular seminoma are cured, whichever approach is chosen. This article presents an overview of the available information on all treatment options, the pros and cons of each approach, and indications for where surveillance fits into the armamentarium of clinicians dealing with this disease.

Cost and risk benefit in the management of clinical stage II nonseminomatous testicular tumors

Two similarly effective treatment options exist for managing clinical low volume Stage II nonseminomatous germ cell testis tumors (NSGCT). Primary retroperitoneal lymph node dissection (RPLND) (with immediate adjuvant chemotherapy or chemotherapy at relapse) and primary chemotherapy have resulted in similar survival rates in large series. Because the chance for cure is similar with either approach, the cost and morbidity of therapy should be considered important discriminating factors in deciding which option to pursue for an individual patient. The purpose of this study was to undertake a cost/benefit and risk/benefit analysis of these two options using data and costs from the Indiana University experience. The overall direct costs for 100 patients undergoing primary RPLND were compared with the total direct costs of 100 patients receiving primary chemotherapy for low volume Stage II disease, including the costs of adjuvant chemotherapy, salvage chemotherapy in relapsing patients, and routine follow-up for a 5-year period. In addition, the two treatment options were analyzed relative to survival, late relapse, acute and chronic toxicity, (including fertility), and perioperative morbidity. In this analysis, the overall 5-year costs of RPLND were significantly less than the costs of primary chemotherapy. The two options did not differ significantly in terms of survival or quality of life. Patients receiving RPLND were found to have an advantage also in terms of fertility, toxicity, and late relapse. Treatment decisions for patients with clinical low volume Stage II NSGCT may be based on cost/benefit and risk/benefit considerations, including relative toxicity, long term cure rate, and individual patient preference. Patient compliance with follow-up, the specific expertise of the physicians, and the availability of specialized therapeutic care ultimately may influence such decisions.

Usefulness of inferior mesenteric artery preservation in retroperitoneal lymph node dissection

— In stage II and III non-seminomatous germ-cell testis tumor, retroperitoneal lymph node dissection is generally advised, often associated with systemic chemotherapy. Most Authors report ligature and section of the inferior mesenteric artery without any complication. We reviewed some papers by Valdoni and co-workers about preservation and peeling of the afore-mentioned artery in colo-rectal radical surgery; such procedure is technically feasible and oncologically reliable and ensures good perfusion of the descending colon, especially in the case of vascular anomalies (accessory left colic flexure artery, mono- or bilateral absence of middle rectal artery). In fact those patients subjected to retroperitoneal lymph node dissection may request colonic resection in the future; therefore preservation of the inferior mesenteric artery may represent an example of surgical foresight.

The Role of Alkaline Phosphatase Isoenzymes as Tumor Markers for Testicular Germ Cell Tumors

The role of serum alkaline phosphatase as a tumor marker for testicular germ cell disease was investigated in 26 patients with testicular seminoma and 13 with nonseminomatous germ cell testis tumors. Placental alkaline phosphatase-like enzyme was elevated in 50% of the stage I seminoma patients and in all patients with stages II to III disease. In addition, liver (tissue unspecific) alkaline phosphatase was elevated in 10 and 83% of the patients, respectively. Lactic dehydrogenase and β-human chorionic gonadotropin (β-HCG) were detected in 50 to 60% of the patients with stage I seminoma. By combining placental alkaline phosphatase-like enzyme, lactic dehydrogenase and β-HCG, 75% of the stage I and 100% of the stages II and III seminoma patients could be identified correctly. Placental alkaline phosphatase-like enzyme in serum also occurred with nonseminomatous germ cell tumor but less frequently, while liver alkaline phosphatase was not detected at all. Thus, placental alkaline phosphatase-like enzyme and liver alkaline phosphatase were predominantly determined in the serum of patients with seminoma.In studies of tumor tissues from 31 of these patients, those with normal serum placental alkaline phosphatase-like enzyme levels had significantly lower tissue placental alkaline phosphatase-like enzyme levels than patients with elevated serum levels (p <0.01). Seminoma tissues showed significantly higher levels of placental alkaline phosphatase-like enzyme and liver alkaline phosphatase than nonseminomatous germ cell tumors (p <0.01), explaining the infrequent elevation of serum placental alkaline phosphatase-like enzyme and liver alkaline phosphatase found in patients with nonseminomatous germ cell tumors.

Surgical Treatment of Stage-I Non-Seminomatous Germ Cell Testis Tumor

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.

Orchiectomy only for clinical stage I nonseminomatous germ cell testis tumors: Comparison with pathologic stage I disease

Twenty-three men with nonseminomatous germ cell tumors confined within the tunica albuginea of the testis and negative metastatic evaluation were placed on surveillance after radical orchiectomy. Metastatic disease developed in 3 for a relapse rate of 13 percent. During the same period, 17 men with pathologic Stage I disease were followed up in the same manner, and metastatic disease developed in 3 for a relapse rate of 18 percent. All six men were treated with either combination chemotherapy or retroperitoneal lymphadenectomy, and all are alive without disease for at least two years from end of therapy. If strict criteria are followed, surveillance has a place in the management of carefully selected young men with clinical Stage I disease.

Small Bowel Intussusception: an Unusual Complication of Retroperitoneal Lymph Node Dissection

Modified bilateral retroperitoneal lymph node dissection is used widely in the staging and treatment of patients with nonseminomatous germ cell testis tumors. Complications are uncommon and include vascular injury, infertility and small bowel obstruction from fibrous adhesions. Small bowel intussusception following retroperitoneal lymph node dissection has not been reported previously. We report 2 cases of small bowel intussusception after retroperitoneal lymph node dissection, and discuss the etiology and possible preventive measures. (J. Urol., 142: 826–827, 1989)

Initial assessment of tumor-associated antigen CA-125 in patients with ovarian, cervical, and testicular tumors.

Serum CA-125, a glycoprotein antigen, has been measured in serum of patients with ovarian cancer, cervical cancer, or nonseminomatous germ-cell tumor of testis. Increased concentrations were found in 21 of 27 patients with epithelial ovarian cancer and two of three patients with ovarian teratoma. Changes in CA-125 concentrations in serum during chemotherapy mirrored the progress of the disease as assessed by clinical and radiological evidence. Although CA-125 provides no real asset for diagnosis, it should have value as a marker for monitoring response to chemotherapy.

Testicular Cancer: Prognostic Implications of Vascular Invasion

In a retrospective study the primary tumors of 33 patients with seminomas and 53 with nonseminomatous germ cell tumors were re-evaluated for vascular invasion. The significance of vascular invasion was analyzed in respect to the appearance of visceral metastases and the effect of adjuvant chemotherapy. Vascular invasion was demonstrated in 27 per cent of the patients with seminomas and 53 per cent with nonseminomatous germ cell testis tumors, while visceral metastases appeared in 9 and 32 per cent, respectively. Without adjuvant chemotherapy all 13 patients with nonseminomatous germ cell testis tumors and vascular invasion had metastases, compared to only 3 of 13 without vascular invasion (p less than 0.0005). Of 9 patients with seminoma and vascular invasion 3 had tumor progression, compared to 1 of 24 without vascular invasion (p greater than 0.05). With adjuvant chemotherapy only 1 of 15 patients (7 per cent) with nonseminomatous germ cell testis tumors and vascular invasion had metastases, compared to 100 per cent of 13 without this treatment. No significant correlation was noted between pT stage versus vascular invasion and pT stage versus tumor progression. The results demonstrate the importance of vascular invasion in the staging of and choice of treatment for early nonseminomatous germ cell testis tumors.

Nonseminomatous Germ Cell Tumor of the Testicle: Does Extensive Staging of the Primary Tumor Predict the Likelihood of Metastatic Disease?

To assess the hypothesis that local extent of the primary lesion in patients with nonseminomatous germ cell tumors of the testicle can predict disseminated disease, clinicopathological correlations of the primary tumor and metastases were determined in a retrospective review of 120 patients treated at our institution from 1970 to 1982. Pathological staging was available for all 93 patients with subdiaphragmatic disease and the primary tumor was examined by routine histological techniques in all cases. Increased primary tumor stage, as evidenced by invasion into the tunica vasculosa or extension into the rete testis, epididymis and/or lower or upper spermatic cord, was associated with metastatic disease in 91, 96, 97 and 97 per cent of the patients, respectively. Only 9 per cent of the patients with pathological stage A disease had vascular invasion compared to 45 and 67 per cent of those with stages B and C disease, respectively (p less than 0.01). Furthermore, metastases and/or eventual dissemination occurred in 84 per cent of the patients with clinical stage A disease and vascular invasion, and in only 23 per cent of those without vascular invasion (p less than 0.01). Size of the primary tumor was not of predictive value. Local extension of the primary lesion was common with embryonal carcinoma but it was not demonstrated when the predominant histological type was teratoma or teratocarcinoma, although metastases were present in 37 and 46 per cent of the latter cases, respectively. The implications of these findings, especially with regard to expectant management for clinical stage A nonseminomatous germ cell testis tumors, are discussed.

Role of chemotherapy and surgery in the treatment of thoracic metastases from nonseminomatous germ cell testis tumor.

The role of chemotherapy and of surgery in the management of pulmonary metastases from nonseminomatous germ cell tumors (NSGCT) has been analyzed. Thoracic metastases were classified as minimal, if the diameter of the largest was 2 cm or less and five or fewer nodules were present in each lung, and advanced if any metastasis was over 2 cm in diameter and/or six or more nodules were present in either lung field, and/or mediastinal disease, hilar metastasis or pleural effusion was present. Complete thoracic remission (CR) with chemotherapy alone occurred in 49/67 (73%) patients, 86% with minimal and 68% with advanced disease. Absence of concomitant retroperitoneal metastases at the beginning of chemotherapy was associated with better prognosis than when retroperitoneal metastases were present (CR 85% vs 68%, respectively). The histologic type of testis tumors did not influence CR rates of pulmonary metastases. Approximately one half of patients with clinical evidence of retroperitoneal metastases at the beginning of chemotherapy achieving pulmonary CR with chemotherapy alone had clinical evidence of retroperitoneal disease after chemotherapy. Six patients had thoracotomy to document CR to chemotherapy by resection of necrotic tissue. Six patients had thoracotomy to achieve CR by resection of residual neoplasm. The keys to success were a favorable response to chemotherapy and complete resection of any residual tumor. Considering all stages of NSGCT and provided no adjuvant chemotherapy was given, thoracic surgery will be responsible for elimination of thoracic metastases in an estimated 2–5% of patients after adequate chemotherapy. Such intervention is curative in patients with pulmonary metastases only but in those with concomitant retroperitoneal metastases, the final outcome will frequently be decided by the response to chemotherapy and/or the resectability of retroperitoneal metastatic deposits.