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1.  Retroperitoneal Histology of Patients with Elevated Serum Alpha-Fetoprotein and Pure Seminoma at Orchiectomy 
Urology  2011;78(4):844-847.
Objectives
A histologic diagnosis of seminoma at orchiectomy with an elevation in serum alpha-fetoprotein (AFP) indicates the likelihood of unrecognized NSGCT elements. We report the retroperitoneal histology of a contemporary series of patients with pure seminoma at orchiectomy with an elevation in serum AFP that were managed as NSGCT.
Methods
We identified 22 patients between 1989 and 2009 with pure seminoma diagnosed at orchiectomy with an elevated serum AFP (> 15 ng/ml) either pre- or post-orchiectomy. Retroperitoneal histology and relapse data are reported.
Results
Median pre-orchiectomy and pre-chemotherapy serum AFP levels were 248 ng/ml (IQR 48, 4693) and 279 ng/ml (IQR 66, 5311), respectively. Percentage of patients with clinical stage I, II, and III was 5%, 50%, and 45%, respectively. Percentage of patients with IGCCCG good, intermediate, and poor risk status was 32%, 32%, and 36%, respectively. Twenty-one patients had induction chemotherapy followed by PC-RPLND. Overall, 67% of patients had NSGCT elements in the retroperitoneum. Histologic findings were pure teratoma in 38%, malignant transformation in 14%, and viable NSGCT in 14%. Fifty-nine percent had some component of teratoma in the RP. One patient (5%) had any seminoma in the RP, but this patient also had RP teratoma. Seven patients relapsed and received salvage chemotherapy. Actuarial relapse free survival at 5 and 10 years was 76% and 61% reflecting a high percentage of patients with stage II/III disease.
Conclusions
Pure seminoma at orchiectomy with an elevated serum AFP portends a high likelihood of harboring NSGCT elements in the RP.
doi:10.1016/j.urology.2011.02.002
PMCID: PMC4237276  PMID: 21782217
testicular cancer; seminoma; AFP; RPLND
2.  EVALUATION OF LYMPH NODE COUNTS IN PRIMARY RETROPERITONEAL LYMPH NODE DISSECTION 
Cancer  2010;116(22):5243-5250.
Background
Lymph node counts are a measure of quality assurance and are associated with prognosis for numerous malignancies. To date, investigations of lymph node counts in testis cancer are lacking.
Methods
Using the Memorial Sloan-Kettering Testis Cancer Database, we identified 255 patients treated with primary retroperitoneal lymph node dissection (RPLND) for nonseminomatous germ cell tumors (NSGCT) between 1999 and 2008. Features associated with node counts, positive nodes, number of positive nodes, and risk of positive contralateral nodes were evaluated with regression models.
Results
Median (IQR) total node count was 38 (27–53) and was 48 (34 – 61) during the most recent 5 years. Features associated with higher node count on multivariate analysis included high volume surgeon (p=0.034), clinical stage (p=0.036), and more recent year of surgery (p<0.001) while pathologist was not significantly associated with node count (p=0.3). Clinical stage (p<0.001) and total node count (p=0.045) were significantly associated with finding positive nodes on multivariate analysis. The probability of finding positive nodes were 23%, 23%, 31%, and 48% if the total node count was <21, 21 – 40, 41 – 60, and >60, respectively. With a median follow-up of 3.0 years all patients were still alive and 16 patients relapsed while no patient relapsed in the paracaval, interaortocaval, paraaortic, or iliac regions.
Conclusion
Our results suggest that >40 lymph nodes removed at RPLND improves the diagnostic efficacy of the operation. These results will be useful for future trials comparing RPLND, especially when assessing the adequacy of lymph node dissection.
doi:10.1002/cncr.25266
PMCID: PMC4174298  PMID: 20665486
Testicular neoplasms; Lymph nodes; Lymph node excision; Neoplasm staging
3.  BODY MASS INDEX IS ASSOCIATED WITH HIGHER LYMPH NODE COUNTS DURING RETROPERITONEAL LYMPH NODE DISSECTION 
Urology  2011;79(2):361-364.
Objectives
Lymph node counts are a proposed measure of quality assurance for numerous malignancies. Investigation of patient factors associated with lymph node counts are lacking. We sought to determine if body mass index (BMI) is associated with lymph node counts in patients treated with a primary retroperitoneal lymph node dissection (RPLND).
Methods
Using the Memorial Sloan-Kettering Testis Cancer Database, we identified 255 patients treated with a primary RPLND for nonseminomatous germ cell tumors (NSGCT) from 1999–2008. The associations between BMI and node counts were evaluated using linear regression models in univariate and multivariable models adjusting for features reported to predict higher node counts (year of surgery, stage, and surgeon volume).
Results
Median BMI (IQR) was 26.1 (23.4 – 28.7) and median (IQR) total node count was 38 (27–53). Median total node count for patients with a BMI <25, 25–<30, and >30 was 35, 42, and 44 nodes, respectively. In a univariate analysis, higher BMI was significantly associated with higher total node counts (coefficient 0.7 nodes for each 1 unit increase in BMI; p=0.026). Features associated with higher node count on multivariate analysis included high volume surgeon (p=0.047), pathologic stage (p=0.017), more recent year of surgery (p<0.001), and higher BMI (p=0.009).
Conclusion
Our results suggest for the first time that BMI is independently associated with higher lymph node counts during a lymph node dissection. If confirmed by others, these results may be important when using lymph node counts as a surrogate for adequacy of a lymph node dissection.
doi:10.1016/j.urology.2011.04.050
PMCID: PMC4170790  PMID: 22173172
Testicular neoplasms; Lymph nodes; Lymph node excision; Neoplasm staging; Body mass index
4.  CONTEMPORARY LYMPH NODE COUNTS DURING PRIMARY RETROPERITONEAL LYMPH NODE DISSECTION 
Urology  2010;77(2):368-372.
Objective
Recent observations suggest that surgeon volume is associated with lymph node counts during retroperitoneal lymph node dissection (RPLND). We report our contemporary single-surgeon experience with lymph node counts during primary RPLND for nonseminomatous germ cell tumors (NSGCT).
Methods
Using the Memorial Sloan-Kettering Testis Cancer Database, we identified 124 consecutive patients treated with primary RPLND by a single experienced surgeon for NSGCT between 2004 and 2008. Predictors of positive nodes and number of positive nodes were evaluated with logistic and linear regression models adjusting for year of surgery and clinical stage.
Results
Positive lymph nodes were observed in 37 (30%) while 87 (70%) patients were pN0. Mean total node count was 51 (SD= 23) during the 5 year study period. Mean node counts for the paracaval, interaortocaval, and paraaortic regions were 8 (SD= 6), 17 (SD= 9), and 26 (SD= 15), respectively. In a multivariate analysis, higher total node count was significantly associated with finding positive nodes (odds ratio 1.02 for each additional node counted; p=0.037) and finding multiple positive nodes (coefficient 0.04 for each additional node counted; p=0.004). Year of surgery (p<0.001) was associated with higher total node counts, while clinical stage and pathologist were not (p>0.5 for each).
Conclusion
The average total node count for a primary RPLND by an experienced surgeon is approximately 50 nodes with nearly half of the nodes originating in the paraaortic region. These results will be useful when assessing the adequacy of lymph node dissections for testis, renal, and upper tract urothelial malignancies.
doi:10.1016/j.urology.2010.05.020
PMCID: PMC4012337  PMID: 21109294
Testicular neoplasms; Lymph node excision; Neoplasm staging; Retroperitoneal space; Lymph nodes
5.  Preservation of Ejaculation in Patients Undergoing Nerve-Sparing Post-Chemotherapy Retroperitoneal Lymph Node Dissection for Metastatic Testicular Cancer 
Urology  2008;73(2):328-332.
Purpose
We evaluated clinical parameters associated with recovery of ejaculation following nerve-sparing post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) for non-seminomatous germ cell tumor.
Methods
We queried our institutional database for all patients who underwent nerve-sparing PC-RPLND between 1995 and 2005 using a bilateral template. Nerve-sparing was carried out whenever technically feasible and oncologically prudent. Antegrade ejaculation was defined as any seminal fluid expulsion and was determined by patient report. We evaluated recovery of antegrade ejaculation based on clinical and pathologic parameters and fit a logistic regression model to determine which pre-operative variables are associated with antegrade ejaculation.
Results
A total of 341 patients had PC-RPLND during the study period, 136 (40%) with nerve sparing techniques. Post-operative antegrade ejaculation was reported by 107/136 (79%) of patients with information available. On the multivariable analysis, a right-sided primary testicular tumor (OR 0.4, 95% CI: 0.1, 1.0, p=0.044) and residual masses ≥5 cm (OR 0.1, 95% CI: 0.0, 0.7, p=0.020) were associated with retrograde ejaculation. However, 40/54 (74%) with right-sided primary tumors and 4/9 (44%) with mass ≥5 cm reported antegrade ejaculation. The 5-year relapse free survival was 98% with a median follow up of 39 months (IQR 19, 66).
Conclusions
Nerve-sparing PC-RPLND is associated with excellent functional return of antegrade ejaculation, is feasible in select patients with bulky disease, and has excellent oncologic outcomes.
doi:10.1016/j.urology.2008.08.501
PMCID: PMC3665266  PMID: 19022490
Testicular Cancer; Chemotherapy; Surgery; Ejaculation; Retroperitoneal Lymph Node Dissection
6.  The Total Number of Retroperitoneal Lymph Nodes Resected Impacts Clinical Outcome Following Chemotherapy for Metastatic Testicular Cancer 
Urology  2010;75(6):1431-1435.
Background
Following the multidisciplinary management of metastatic germ cell tumor, approximately 10 to 15% of patients with the histologic finding of fibrosis or teratoma will suffer disease recurrence. We evaluated the prognostic significance of the total number of lymph nodes obtained at post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND).
Materials and Methods
From 1989 to 2006, a total of 628 patients underwent PC-RPLND and were found to have either fibrosis or teratoma. Following Institutional Review Board approval, complete clinical and pathologic data were obtained from our prospective testis cancer surgical database. A Cox proportional hazards regression model was constructed to evaluate the association of the total number of lymph nodes obtained at PC-RPLND on disease recurrence.
Results
On pathologic evaluation, 248 (57%) patients had fibrosis and 184 (43%) patients had teratoma. The median number of lymph nodes resected was 25 (IQ range 15, 37). On multivariable analysis, increasing post-chemotherapy nodal size and decreasing lymph node counts were significant predictors of disease recurrence (p=0.01, 0.04, respectively). For patients with 10 nodes removed, the predicted 2 year relapse free probability was 90%, compared to 97% when 50 nodes were removed.
Conclusion
Our data suggests that the total number of lymph nodes removed and analyzed is an independent predictor of disease recurrence following PC-RPLND. This has implications both for the urologist to assure completeness of resection and for the pathologist to meticulously assess the pathologic specimens.
doi:10.1016/j.urology.2009.11.076
PMCID: PMC3654386  PMID: 20299079
testis cancer; surgery; chemotherapy; lymph node count
7.  TI-CE High-Dose Chemotherapy for Patients With Previously Treated Germ Cell Tumors: Results and Prognostic Factor Analysis 
Journal of Clinical Oncology  2010;28(10):1706-1713.
Purpose
We previously reported a dose-finding and phase II trial of the TI-CE regimen (paclitaxel [T] plus ifosfamide [I] followed by high-dose carboplatin [C] plus etoposide [E] with stem-cell support) in germ cell tumor (GCT) patients predicted to have a poor prognosis with conventional-dose salvage therapy. We now report the efficacy of TI-CE with prognostic factors for disease-free survival (DFS) and overall survival (OS) in our full data set of 107 patients.
Patients and Methods
Eligible patients had advanced GCTs with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, incomplete response [IR] to first-line therapy, or relapse/IR to ifosfamide-cisplatin–based conventional-dose salvage). Univariate and multivariate analyses (MVAs) of prognostic factors were performed. The predictive ability of the Einhorn and Beyer prognostic models was assessed.
Results
Most patients were platinum refractory and had an IR to first-line chemotherapy. There were 54 (5%) complete and eight (8%) partial responses with negative markers; 5-year DFS was 47% and OS was 52% (median follow-up, 61 months). No relapses occurred after 2 years. Five (24%) of 21 primary mediastinal nonseminomatous GCTs are continuously disease free. On MVA, primary mediastinal site (P < .001), two or more lines of prior therapy (P < .001), baseline human chorionic gonadotropin ≥ 1,000 U/L (P = .01), and lung metastases (P = .02) significantly predicted adverse DFS. Poor-risk patients did worse than good- or intermediate-risk patients according to both Beyer (P < .002) and Einhorn (P < .05) models.
Conclusion
TI-CE is effective salvage therapy for GCT patients with poor prognostic features. Mediastinal primary site and two or more lines of prior therapy were most predictive of adverse DFS. Beyer and Einhorn models can assist in predicting outcome.
doi:10.1200/JCO.2009.25.1561
PMCID: PMC3651604  PMID: 20194867
8.  Surgery for retroperitoneal relapse in the setting of a prior retroperitoneal lymph node dissection for germ cell tumor 
Recognition of the therapeutic role of retroperitoneal lymph node dissection (RPLND) in the setting of testicular germ cell tumors (GCTs) is of utmost importance. Although the histologic findings of RPLND provide diagnostic and prognostic information, the adequacy of initial RPLND is an independent predictor of clinical outcome. Despite the advent of effective cisplatin-based chemotherapy for testicular GCTs, patients who have undergone suboptimal surgery at the time of initial RPLND are compromised. Despite the initial enthusiasm surrounding anatomic mapping studies, the use of modified RPLND templates has the potential to leave a significant number of patients with unresected retroperitoneal disease. Teratomatous elements are particularly common. Patients with retroperitoneal relapse following initial RPLND should be treated with reoperative RPLND and chemotherapy and can expect long term survival rates nearing 70% when treated in tertiary centers by experienced surgeons.
doi:10.4103/0970-1591.60452
PMCID: PMC2878419  PMID: 20535295
Recurrence; relapse; reoperative; retroperitoneal lymph node dissection; testicular cancer
9.  Clinical Outcome and Predictors of Survival in Late Relapse of Germ Cell Tumor 
Journal of Clinical Oncology  2008;26(34):5524-5529.
Purpose
Late relapse (LR) of germ cell tumor (GCT) is a well recognized entity associated with poor survival. We report on our experience with LR and determine predictors of survival.
Patients and Methods
From 1990 to 2004, 75 patients were managed for LR of GCT at our institution. Clinical and pathologic parameters were reviewed. Estimates of cancer-specific survival were generated using the Kaplan-Meier method, and a Cox proportional hazards model was used to assess potential predictors of outcome.
Results
The median time to LR was 6.9 years (range, 2.1 to 37.7 years). Overall, 56 patients (75%) had LR in the retroperitoneum, including 25 (93%) of 27 patients initially managed without retroperitoneal lymph node dissection. The 5-year cancer-specific survival (CSS) was 60% (95% CI, 46% to 71%). Patients who underwent complete surgical resection at time of LR (n = 45) had a 5-year CSS of 79% versus 36% for patients without complete resection (n = 30; P < .0001). The 5-year CSS for chemotherapy-naive patients was significantly greater than patients with a prior history of chemotherapy as part of their initial management (5-year CSS, 93% v 49%, respectively). In multivariable analysis of pretreatment parameters available at the time of LR, the presence of symptoms (hazard ratio [HR] = 4.9) and multifocal disease (HR = 3.0) were associated with an inferior CSS.
Conclusion
The data suggest that meticulous control of the retroperitoneum is critical to prevent LR in the retroperitoneum. In multivariable analysis, patients with a symptomatic presentation and those with multifocal disease have a significantly decreased survival. Survival is greatly improved if complete surgical excision of disease is attained.
doi:10.1200/JCO.2007.15.7453
PMCID: PMC2651099  PMID: 18936477
10.  CRITICAL ELEMENTS IN FELLOWSHIP TRAINING 
Urologic oncology  2009;27(2):199-204.
doi:10.1016/j.urolonc.2008.09.018
PMCID: PMC2724648  PMID: 19285234

Results 1-10 (10)