A comparative study of peri-operative outcomes for 100 consecutive post-chemotherapy and primary robot-assisted and open retroperitoneal lymph node dissections.

PURPOSE: To describe and compare differences in peri-operative outcomes of robot-assisted (RA-RPLND) and open (O-RPLND) retroperitoneal lymph node dissection performed by a single surgeon where chemotherapy is the standard initial treatment for Stage 2 or greater non-seminomatous germ cell tumour. METHODS: Review of a prospective database of all RA-RPLNDs (28 patients) and O-RPLNDs (72 patients) performed by a single surgeon from 2014 to 2020. Peri-operative outcomes were compared for patients having RA-RPLND to all O-RPLNDs and a matched cohort of patients having O-RPLND (20 patients). Further comparison was performed between all patients in the RA-RPLND group (21 patients) and matched O-RPLND group (18 patients) who had previous chemotherapy. RA-RPLND was performed for patients suitable for a unilateral template dissection. O-RPLND was performed prior to the introduction of RA-RPLND and for patients not suitable for RA-RPLND after its introduction. RESULTS: RA-RPLND showed improved peri-operative outcomes compared to the matched cohort of O-RPLND-median blood loss (50 versus 400 ml, p < 0.00001), operative duration (150 versus 195 min, p = 0.023) length-of-stay (1 versus 5 days, p < 0.00001) and anejaculation (0 versus 4, p = 0.0249). There was no statistical difference in complication rates. RA-RPLND had lower median lymph node yields although not significant (9 versus 13, p = 0.070). These improved peri-operative outcomes were also seen in the post-chemotherapy RA-RPLND versus O-RPLND analysis. There were no tumour recurrences seen in either group with median follow-up of 36 months and 60 months, respectively. CONCLUSIONS: Post-chemotherapy RA-RPLND may have decreased blood loss, operative duration, hospital length-of-stay and anejaculation rates in selected cases and should, therefore, be considered in selected patients. Differences in oncological outcomes require longer term follow-up.

Contemporary North-American population-based validation of the International Germ Cell Consensus Classification for metastatic germ cell tumors of the testis.

BACKGROUND: The International Germ Cell Consensus Classification (IGCCC) is the recommended stratification scheme for newly diagnosed metastatic seminoma (mSGCT) and non-seminoma germ cell tumor (mNSGCT) patients. However, a contemporary North-American population-based validation has never been completed and represented our focus. MATERIALS AND METHODS: We identified mSGCT and mNSGCT patients within the SEER database (2004-2015). The IGCCC criteria were used for stratification into prognostic groups. Kaplan-Meier (KM) derived actuarial 5-year overall survival (OS) rates were calculated. In addition, cumulative incidence plots tested cancer-specific (CSM) and other-cause mortality (OCM) rates. RESULTS: Of 321 mSGCT patients, 190 (59.2%) and 131 (40.8%), respectively, fulfilled good and intermediate prognosis criteria. Of 803 mNSGCT patients, 209 (26.1%), 100 (12.4%), and 494 (61.5%), respectively, fulfilled good, intermediate, and poor prognosis criteria. In mSGCT patients, actuarial KM derived 5-year OS was 87% and 78% for, respectively, good and intermediate prognosis groups (p = 0.02). In cumulative incidence analyses, statistically significant differences were recorded for CSM but not for OCM between good versus intermediate prognosis groups. In mNSGCT patients, actuarial KM derived 5-year OS was 89%, 75% and 60% for, respectively, good, intermediate, and poor prognosis groups (p < 0.001). In cumulative incidence analyses, statistically significant differences were recorded for both CSM and OCM between good, intermediate, and poor prognosis groups. CONCLUSIONS: Our findings represent the first population-based validation of the IGCCC in contemporary North-American mSGCT and mNSGCT patients. The recorded OM rates closely replicate those of the original publication, except for better survival of poor prognosis mNSGCT patients.

Imaging of Metastatic Germ Cell Tumors in Male Patients From Initial Diagnosis to Treatment-Related Toxicities: A Primer for Radiologists.

OBJECTIVE. This review describes the influence of histology and metastatic sites on prognosis in male patients with metastatic germ cell tumors (GCTs) and explains the role imaging in assessing therapeutic response, residual disease, recurrence, sand treatment-related toxicities. CONCLUSION. Seminomatous and nonseminomatous GCTs differ in imaging appearance, pattern of spread, and prognosis, and an organ-based approach is helpful in prognostication. Multimodality imaging aids in accurate staging, prognostication, characterization of treatment response, and identification of therapy-related toxicity.

Mechanism of metastasis to the spermatic cord and testis from advanced gastric cancer: a case report.

BACKGROUND: The spermatic cord and testis are very rare sites for metastasis from gastric cancer. Although several mechanisms have been suggested to explain this unusual metastasis, the actual mechanism remains unclear. We report a case of right spermatic cord and testicular metastasis, review its imaging findings, and suggest a mechanism of tumor spread. CASE PRESENTATION: A 61-year-old man complained of a palpable mass in the right inguinal area. He had been treated with distal gastrectomy with chemotherapy for advanced gastric cancer 5 years ago. Computed tomography, ultrasound, and magnetic resonance imaging showed a mass surrounding the right spermatic cord, involving the right testis. Another mass was observed in the aortocaval space, presumed to be a metastatic lymph node. The imaging features of the right testicular lesion were different than those of the primary testicular cancer. The lesions at both sites showed similar radiologic features of abundant internal necrosis, which is consistent with metastatic lesions. Pathology confirmed metastatic adenocarcinoma. He underwent a series of chemotherapy sessions, and all metastatic masses had partially decreased in size at the 5-month outpatient follow-up. CONCLUSIONS: The imaging features of testicular mass and spermatic cord involvement are important clues for accurate differential diagnosis of metastasis from other primary tumors in patients with a history of stomach cancer. This unusual metastasis can be explained via retrograde tumor spread along the lymphatic channels in terms of concurrent aortocaval lymph node metastasis. A suspicion of metastasis should not be overlooked, even if a patient has undergone curative treatment, including surgery and adjuvant chemotherapy, many years ago.

Surgical management of growing teratoma syndrome: robotic-assisted thoracoscopic resection of mediastinal teratoma.

BACKGROUND: Growing teratoma syndrome is a rare condition defined by the presence of enlarging metastatic lesions on serial imaging that arise after or during systemic chemotherapy for nonseminomatous germ cell tumors. Lesions commonly occur in the retroperitoneum, mediastinum, or lung and are notoriously unresponsive to conventional chemoradiotherapy. METHODS: In this study, we present a dynamic case of a 26-year-old male, who had undergone surgical resection and systemic bleomycin treatment for a metastatic nonseminomatous germ cell tumor, and later developed recurrent masses in his posterior mediastinum seen on surveillance imaging. Tumor markers remained normal. These lesions were resected via a right robot-assisted thoracoscopic approach with the da Vinci Xi®. RESULTS: The operation was completed successfully with an unremarkable postoperative hospital course. The robotic-assisted right thoracoscopic approach allowed for a minimally invasive dissection with good visualization and minimal morbidity when compared to previous cases of surgically resected mediastinal teratomas. Final pathology demonstrated mature teratomatous elements within a setting of inflammation and necrosis. CONCLUSIONS: Robot-assisted thoracoscopic management of metastatic mediastinal lesions in the setting of this rare condition is safe and feasible.

Genomic Features for Therapeutic Insights of Chemotherapy-Resistant, Primary Mediastinal Nonseminomatous Germ Cell Tumors and Comparison with Gonadal Counterpart.

Primary mediastinal nonseminomatous germ cell tumors (PMNSGCT) frequently become refractory to chemotherapy, and no effective salvage therapy exists. We performed genomic profiling on a series of 44 PMNSGCT and compared the results with those from chemorefractory, metastatic pure seminomatous (Sem, n = 22) and nonseminomatous (NS, n = 86) testicular germ cell tumors. Archival tissues were sequenced by a hybrid capture-based technology (FoundationONE; Foundation Medicine, Inc., Cambridge, MA). Microsatellite instability (MSI) and tumor mutational burden (TMB, mutations [mut]/Mb) were determined.Statistically significant differences in genomic alterations (GA) of PMNSGCT versus NS included higher TP53 pathway GA (p < .0001), PIK3CA pathway GA (p < .0001), and lower cell-cycle pathway GA (p = .0004). There were no MSI-high PMNSGCT cases. Mean TMB was similar between the groups, but there were more ≥10 mut/Mb in the PMNSGCT group versus NS (11.4% vs. 4.6%).The GA identified in PMNSGCT were similar to the findings from NS, with differential opportunities for targeted therapies and immunotherapies. Further study of precision treatments appears warranted.

High-dose radiation therapy is needed for intracranial control and long-term survival in patients with non-seminomatous germ cell tumor brain metastases.

PURPOSE: The presence of brain metastases (BM) in patients with non-seminomatous germ cell tumor (NSGCT) is associated with poor prognosis. While radiation therapy (RT) is an important treatment for patients with NSGCT BM, there is a paucity of data on the optimal regimen. We sought to investigate the impact of RT on clinical outcomes in patients with NSGCT BM. METHODS: Patients with NSGCT BM who received RT at our institution from 2002 to 2017 were included. Sixty-three consecutive patients were identified. Clinical factors associated with intracranial control (ICC) and overall survival (OS) were evaluated using cox regression analysis and Kaplan Meier method. RESULTS: Median age was 31 years and number of BM was three. Fifteen patients presented with BM at diagnosis, while 48 developed BM at a median time of 8.4 months from diagnosis. At a median follow-up of 3.6 years, ICC and OS were 39.7% and 30.1%. On multivariate analysis, ICC (hazard ratio [HR] = 0.93, p = 0.03) and OS (HR = 0.93, p = 0.005) were both significantly associated with biologically effective dose (BED) of RT. The 4-year OS of patients who received BED < 39Gy, 39 Gy, 40-50 Gy, and ≥ 50 Gy were 0%, 14.7%, 34.1%, and 70.0%, respectively. Patients who achieved ICC after RT were able to achieve long-term survival (4-year OS 68.1% vs. 0%, p < 0.0001). CONCLUSIONS: Our data supports that a higher BED is required for durable ICC, and that ICC is needed for patients with NSGCT to achieve long-term survival. Prospective studies evaluating radiation dose-escalation for the treatment of NSGCT BM should be considered.

Reclassification of good-risk seminoma: prognostic factors, novel biomarkers and implications for clinical management.

Germ cell tumors represent 11% of the cancers diagnosed in adolescent males and are the most common solid tumors in adult men between the ages of 20 and 35. Pure seminoma accounts for around 50% of all testicular germ cell tumors. The prognostic classification of the International Germ Cell Cancer Collaborative Group for good-prognosis seminoma includes both nodal disease and pulmonary visceral metastases. In this article, we analyzed recent data on prognosis and outcome of good-prognosis seminoma to revise the traditional classification of the disease and improve tailored treatment.

A case of cervical spinal mass with cord compression and rib bone metastasis from presumably burned-out seminomatous testicular germ cell tumor.

Most germ cell tumors are located in the gonads however there are instances where these tumors are located elsewhere in which are termed extragonadal germ cell tumors. When primary lesion of the testicular tumor has regressed, the term "burned-out testicular tumor" has been proposed. We herein report the first case of burned-out seminoma of the testis presenting as a cervical spinal mass causing cord compression with bone metastasis.

OCT4 immunohistochemistry after staging laparoscopic retroperitoneal lymphadenectomy for testicular tumor.

Twenty to thirty percent of patients with clinical stage I testicular tumor have metastases in the retroperitoneum. The aim of this study was to evaluate the role of OCT4 immunohistochemistry in histopathologic diagnosis of lymph node metastases in patients with nonseminomatous germ cell testicular tumors. All clinical stage I patients with staging laparoscopic retroperitoneal lymphadenectomy from 2001 until 2009 were included. Archived materials of dissected lymph nodes were reassessed and additional immunohistochemical staining with OCT4 antibody was performed in patients diagnosed as free from metastases. Each slide was visually estimated for the percentage of tumor cells showing nuclear immunoreactivity for OCT4. The study included 93 patients, of which 30 (32.3%) had initially positive retroperitoneal lymph nodes. Of the remaining 63 patients, materials were missing for 5 patients, so additional immunohistochemical staining was performed in 58 patients. Of these, two (3.4%) patients were OCT4 positive, suggesting a conclusion that they were initially misdiagnosed as stage I and metastasis free. OCT4 proved its value in detecting retroperitoneal metastases. Staging laparoscopic retroperitoneal lymphadenectomy for nonseminomatous germ cell testicular tumors in clinical stage I is a reasonable option for selected patients.

Laparoscopic Retroperitoneal Lymph Node Dissection for Clinical Stage I Nonseminomatous Germ Cell Tumors of the Testis: Safety and Efficacy Analyses at a High Volume Center.

PURPOSE: The prognosis of stage I nonseminomatous germ cell tumor of the testis is favorable. Early and late side effects of treatment may affect quality of life and survival. We determined the tolerability, safety and efficacy of laparoscopic retroperitoneal lymph node dissection in patients with stage I nonseminomatous germ cell tumor of the testis at a high volume center. MATERIALS AND METHODS: Unilateral laparoscopic retroperitoneal lymph node dissection was prospectively recorded in 225 patients from 2000 to 2014. Since 2007, patients have been treated at a multidisciplinary clinic and were proposed surgery as an alternative to surveillance or adjuvant chemotherapy. The indication for adjuvant chemotherapy changed during the study period. Descriptive statistics and regression analyses were used to evaluate the domains of safety and oncologic outcomes. RESULTS: A total of 221 patients were evaluable. Median operative time was 200 minutes. Conversion to open surgery was done in 20 cases (9%). A median of 14 nodes (IQR 11-20) was retrieved. Grade greater than 2 complications in 8 cases (3.6%) increased as the number of retrieved nodes increased. Antegrade ejaculation was maintained in 98.6% of patients. Nodal metastases were found in 29 patients (13%), of whom 7 underwent adjuvant chemotherapy. There were 14 recurrences (6.3%), including 8 of 192 (4.2%) associated with no nodal metastases and 6 of 22 (27.3%) associated with nodal metastases in patients not undergoing adjuvant chemotherapy. At regression analyses lymph node ratio was the only significant factor predictive of recurrence and of the administration of any chemotherapy (each p <0.001). Operative time, the number of retrieved nodes and conversions improved with time. CONCLUSIONS: In the context of a high volume center laparoscopic retroperitoneal lymph node dissection was safe and its oncologic efficacy was comparable to that of open surgery. Select patients with stage I nonseminomatous germ cell tumor could be offered laparoscopic retroperitoneal lymph node dissection as an alternative to other options.

Nodule Size After Chemotherapy and Primary-Tumor Teratoma Components Predict Malignancy of Residual Pulmonary Nodules in Metastatic Nonseminomatous Germ Cell Tumor.

BACKGROUND: The treatment goal for visceral metastatic nonseminomatous germ cell tumor (NSGCT) is to remove any residual teratoma or viable NSGCT after chemotherapy. However, this provides no therapeutic benefit to patients whose metastases necrotize on their own. This study therefore analyzed NSGCTs with pulmonary metastases to determine preoperative factors that predict necrosis and could help identify patients who might be treated with monitoring rather than surgery. METHODS: The study retrospectively analyzed 41 patients (135 metastatic pulmonary nodules) treated from 1997 to 2016 for NSGCT who showed tumor marker normalization after chemotherapy. Relationships between clinicopathologic characteristics and necrosis in resected pulmonary specimens were analyzed. RESULTS: Receiver operating characteristic analysis of the pulmonary nodules showed 9 mm to be the optimal cutoff length for predicting necrosis. The logistic regression model showed that absence of teratoma components in the primary tumor and all pulmonary nodules shorter than 10 mm after chemotherapy both were independent predictors of pathologic necrosis in pulmonary specimens. No patients experienced late recurrence (i.e., > 2 years afterward). CONCLUSIONS: The presence of teratoma components in primary tumors and nodular size after chemotherapy predict the pathology of residual pulmonary nodules. Patients whose residual nodules all are shorter than 10 mm and who have no primary-tumor teratoma components might be candidates for careful monitoring before pulmonary resection.

Isolated Testicular Recurrence of AML in Patients With Chronic GVHD >1 Year Following Allogeneic Stem Cell Transplant.

BACKGROUND: Patients with chronic graft-versus-host disease (cGVHD) following allogeneic transplant for myeloid leukemias seem to experience a reduced risk of relapse than comparable patients without cGVHD. It is unclear to what extent extramedullary sites are impacted by a graft-versus-leukemia effect. DESIGN/METHOD: Case Series and review of the literature. RESULTS: We present 2 cases of pediatric patients with Acute Myelogenous Leukemia who developed isolated testicular relapse more than a year following hematopoietic stem cell transplantation despite having had extensive cGVHD. Both patients were off immunosuppression and cGVHD medications when testicular relapse occurred. At time of relapse, these patients were negative for minimal residual disease in the marrow and the marrow contained all donor cells by engraftment studies. No evidence was found for lymphocyte infiltration into the affected testicle in either patient. CONCLUSIONS: Although a reduction of marrow relapse can be appreciated in patients with myeloid leukemias and chronic GVHD, this graft-versus-leukemia process may be less robust in extramedullary sites and careful surveillance should be maintained to allow early intervention before overt marrow involvement.

Real Time Metastatic Route Tracking of Orthotopic PC-3-GFP Human Prostate Cancer Using Intravital Imaging.

The cellular basis of metastasis is poorly understood. An important step to understanding this process is to be able to visualize the routes by which cancer cells migrate from the primary tumor to various distant sites to eventually form metastasis. Our laboratory previously developed single-cell in vivo imaging using fluorescent proteins to label cancer cells. In the present study, using PC-3 human prostate cancer cells labeled with green fluorescent protein (GFP) and orthotopic tumor transplantation, we have imaged in live mice various highly diverse routes by which PC-3 cells metastasize superiorly and inferiorly to distant sites, including in the portal area, stomach area, and urogenital system. Imaging began at day 9, at which time distant metastasis had already occurred, and increased at each imaging point at days 10, 13, 14, and 16. Metastatic cells were observed migrating superiorly and inferiorly from the primary tumor as well as in lymphatic channels and trafficking in various organ systems demonstrating that PC-3 has multiple metastatic routes similar to hormone-independent advanced-stage prostate cancer in the clinic.

Retroperitoneal Lymph Node Dissection: Anatomical and Technical Considerations from a Cadaveric Study.

PURPOSE: Metastatic testis cancer in the retroperitoneum presents a technical challenge to urologists in the primary and post-chemotherapy settings. Where possible, bilateral nerve sparing retroperitoneal lymph node dissection should be performed in an effort to preserve ejaculatory function. However, this is often difficult to achieve, given the complex neurovascular anatomy. We performed what is to our knowledge the first comprehensive examination of the anatomical relationships between the sympathetic nerves of the aortic plexus and the lumbar vessels to facilitate navigation and nerve sparing during bilateral retroperitoneal lymph node dissection. MATERIALS AND METHODS: The relative anatomy of the infrarenal vasculature (lumbar vessels, right gonadal vein and inferior mesenteric artery) was investigated in 21 embalmed human cadavers. The complex relationships between these vessels and the sympathetic nerves of the aortic plexus were examined by dissection of an additional 8 fresh human cadavers. RESULTS: Analysis of the infrarenal vasculature from 21 cadavers demonstrated that the position of the right gonadal vein and the inferior mesenteric artery may be useful to locate the right superior lumbar vein and the first pair of infrarenal lumbar arteries as well as the common lumbar trunk (vein) and the second pair of infrarenal lumbar arteries, respectively. Furthermore, the lumbar splanchnic nerves supplying the aortic plexus were most often positioned anteromedial to the respective lumbar vein. CONCLUSIONS: The current study describes the complex neurovascular relationships that are crucial to performing successful nerve sparing retroperitoneal lymph node dissection. Surgical techniques are also discussed. Collectively, these results may help surgeons decrease the rate of postoperative retrograde ejaculation and/or anejaculation.

Metastasis of Prostate Adenocarcinoma to the Testis.

INTRODUCTION: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. CASE REPORT: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. CONCLUSION: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period.

Lymph Node Yield in Primary Retroperitoneal Lymph Node Dissection for Nonseminoma Germ Cell Tumors.

PURPOSE: The number of lymph nodes removed at surgery for various malignancies has diagnostic and prognostic value. However, there are limited data on the significance of the number of nodes removed at retroperitoneal lymph node dissection performed for testicular nonseminoma germ cell tumors. MATERIALS AND METHODS: From 1979 to 2012 primary open retroperitoneal lymph node dissection was performed by a single experienced surgeon for clinical stage I/II testicular nonseminoma germ cell tumor in 157 patients. Node count was available in 111 cases (71%). Factors associated with total node count and nodes with viable cancer were assessed by linear regression. The association between node count and time to relapse was assessed by multivariate Cox proportional hazards models controlled for adjuvant chemotherapy. RESULTS: The median total lymph node count was 28 (IQR 19-38). Patient age, cancer laterality, body mass index, clinical stage, time from orchiectomy to retroperitoneal lymph node dissection, pathologist and lymph node dissection year were not associated with total lymph node count. A viable germ cell tumor was found in 70 patients (63%). Total node yield was not associated with nodal cancer metastasis. After lymph node dissection 17 patients (16%) received adjuvant chemotherapy. At a median 57-month followup 18 cases (17%) relapsed after primary retroperitoneal lymph node dissection. Increasing total node count was associated with a decreased risk of relapse on univariate and multivariate analysis (HR 0.96, 95% CI 0.92-0.99, p = 0.03 and HR 0.94, 95% CI 0.89-0.99, p = 0.017, respectively). CONCLUSIONS: No analyzed clinical or pathological variable was associated with the node yield of primary retroperitoneal lymph node dissection. However, there may be a relationship between the total node yield at retroperitoneal lymph node dissection and the risk of relapse.

Minimally invasive post-chemotherapy retroperitoneal lymph node dissection for nonseminoma.

INTRODUCTION: We present our experience with minimally-invasive retroperitoneal lymph node dissection (MI-RPLND) in the post-chemotherapy (PC) setting for residual masses in patients with nonseminoma. MATERIALS AND METHODS: Nineteen men who underwent PC MI-RPLND (14--laparoscopic, 5--robotic) for low-volume residual disease (no more than 5 clinically enlarged retroperitoneal masses, size < 5 cm, no adjacent organ or vascular invasion) between 2006 and 2011 were identified. Clinicodemographic information and pathological outcomes were reported. RESULTS: Median age of our study population was 32 (interquartile range [IQR]: 28-39). Most patients presented with clinical stage II disease (63%) and were categorized as good risk (90%) by the International Germ Cell Consensus Classification. Median size of residual masses on PC imaging was 2.1 cm (IQR: 1.7-3). Full-template bilateral RPLND was completed in 53% of cases, and modified left-sided RPLND in 47%. Median operative time was 370 minutes (IQR: 320-420), and median estimated blood loss was 300 cc (IQR: 150-450). Median length of stay was 3 days (IQR: 2-3). Five patients (26%) experienced a postoperative 30 day complication, but none were higher than Clavien grade II. On final pathology, median number of lymph nodes removed was 12 (IQR: 8-23), and 8 patients (42%) had residual teratoma. No patient experienced a recurrence at median follow up of 24 months (IQR: 5-76). CONCLUSIONS: PC MI-RPLND is a feasible option in a select group of patients with acceptable patient morbidity and short-term outcomes. Longer follow up is required to determine the oncologic efficacy of this approach.