Metastatic Testicular Cancer Research Articles

Contemporary surgical management of testicular seminoma.

Testicular cancer is the most commonly diagnosed cancer among young men in the United States. Seminoma comprises a little over half of all testicular germ cell neoplasms. After radial inguinal orchiectomy, management of seminoma is dictated by tumor stage and risk stratification. Dissemination patterns for metastatic testicular cancer are predictable and reproducible, initially metastasizing to the retroperitoneum before disseminating to the lungs or other viscera. Seminomas are exquisitely sensitive to radiation therapy and platinum-based chemotherapy. Approximately 80-85% of men presenting with early stage (clinical stage I) seminoma will not experience a relapse after radical orchiectomy alone. Therefore, surveillance has been supported by the National Comprehensive Cancer Network (NCCN) guidelines as the preferred management strategy. For those at higher risk of relapse, one or two cycles of single-agent carboplatin or radiation therapy are alternative options to reduce the risk of relapse. For patients with early disseminated seminoma (clinical stage IIA and IIB), radiation therapy or chemotherapy with three cycles of bleomycin, etoposide, cisplatin (BEP) or four cycles of etoposide and cisplatin (EP) are well-established options with excellent cure rates. However, these therapies may be associated with significant long-term toxicities. Primary retroperitoneal lymph node dissection (RPLND) in patients with low-volume metastatic seminoma has recently been evaluated for safety and efficacy in prospective clinical trials. Finally, though the role of surgery in patients with advanced seminoma (clinical stage IIC and III) is limited, a subset of patients with a residual mass following chemotherapy >3 cm suggestive of viable germ cell tumor on imaging may benefit from surgical resection. Herein we review the contemporary indications for surgery and outcomes for men with testicular seminoma.

Metastatic Testicular Cancer Patient with Synchronous Oral Squamous Cell Carcinoma Presented with Gastrointestinal Bleeding: A Case Report

Testicular cancer is a curable oncologic disease of males mostly aged 15-44 years. Most of the patients are successfully treated with radical orchiectomy. However, a delayed presentation may lead to a dismal prognosis. There are several risk factors including cryptorchidism, a first-degree relative with testicular cancer, hypospadias, childhood inguinal hernia, and military pollutant exposure, among others. The distant metastasis of testicular carcinoma to the lung, liver, and brain are widely described. We present a unique case of a 28-year-old male who presented with gastrointestinal (GI) bleeding. Later, it was discovered that he had a metastatic testicular carcinoma synchronous with an oral squamous cell carcinoma. Metastasis was detected by imaging including X-ray, computerized tomography (CT) of the chest, abdomen, and brain magnetic resonance imaging (MRI). The presence of two primary cancers concurrently is rare and indicates a poor prognosis. Because of the absence of risk factors in this patient, he was thought to be potentially exposed to depleted uranium from warfare due to his residence in Iraq. Markedly raised beta-human chorionic gonadotropin (b-HCG) titers indicate a possible non-seminomatous type; however, the exact type is unknown as the patient declined fine needle aspiration (FNA)/biopsy and orchiectomy. This case focuses on the atypical presentation and the importance of when to seek medical attention, as a delayed presentation can lead to a poor prognosis. Moreover, it heightens awareness that other malignancies may occur concurrently. As well as to emphasize on means that can be used to educate high-risk groups.

Robotic-assisted retroperitoneal lymph node dissection for stage II testicular cancer

ObjectiveTo evaluate the perioperative as well as early oncological outcomes of patients undergoing robotic retroperitoneal lymph node dissection for treatment of testicular cancer. MethodsWe conducted a prospective consecutive case series of patients undergoing robotic assisted retroperitoneal lymph node dissection for metastatic testicular cancer between May 2018 and July 2021 at our institution. Data were collected on patient and tumour characteristics, intraoperative and postoperative parameters, and functional and oncological outcomes. Descriptive statistics are presented. ResultsNineteen patients were identified; 18 (94.7%) completed the procedure robotically and one was converted to open surgery; 78.9% of patients had stage ≥IIB and 12 (63.2%) patients had undergone prior chemotherapy. The median operative time was 300 (interquartile range [IQR] 240–315) min. Median blood loss was 100 (IQR 50–175) mL. Median length of stay was 2 (range 1–11) days. All robotically completed patients commenced diet and passed flatus on Day 1 and were discharged by Day 3. The median lymph node yield was 40.5 (IQR 38–51) nodes. All patients undergoing nerve-sparing procedures recovered antegrade ejaculatory function. One patient had a Clavien-Dindo III complication (chylous ascites requiring drainage). At a median follow-up of 22.3 (IQR 16.3–24.9) months, one patient developed retroperitoneal recurrence, which was successfully treated with second-line chemotherapy; no other patients have had recurrences. ConclusionRobotic retroperitoneal lymph node dissection is a safe and feasible alternative to open surgery in appropriately selected patients, offering low morbidity. Early oncological outcomes are promising. Larger cohorts and longer follow-ups are required to validate our institution's findings.

Inflammatory Biomarkers for Outcome Prediction in Patients With Metastatic Testicular Cancer.

Germ cell tumors are the most common malignant tumors in male young adults. Platinum-based chemotherapy has dramatically improved the outcome of metastatic germ cell tumor patients and overall cure rates now exceed 80%. The choice of medical treatment can be guided by the prognosis estimation which is an important step during the decision-making process. IGCCCG classification plays a pivotal role in the management of advanced disease. However, histological and clinical parameters are the available factors that condition the prognosis, but they do not reflect the tumor’s molecular and pathological features and do not predict who will respond to chemotherapy. After first-line chemotherapy 20%-30% of patients relapse and for these patients, the issue of prognostic factors is far more complex. Validated biomarkers and a molecular selection of patients that reflect the pathogenesis are highly needed. The association between cancer-related systemic inflammation, tumorigenesis, and cancer progression has been demonstrated. In the last years, several studies have shown the prognostic utility of immune-inflammation indexes in different tumor types. This review analyzed the prognostic impact of inflammatory markers retrieved from routine blood draws in GCT patients.

A Case of Progressive Bleomycin Lung Toxicity Refractory to Steroid Therapy

Bleomycin is a common chemotherapy agent used to treat germinative tumors. Bleomycin-induced lung injury (BILI) is an uncommon but devastating adverse effect of its use. It occurs in 10-20% of patients receiving bleomycin, and the initial diagnosis is usually made by new-onset respiratory symptoms and reduced diffusing capacity for carbon monoxide (DLCO). Mainstay treatment includes discontinuing bleomycin, corticosteroids, and supplemental oxygen if needed. We present a case of a 38-year-old male who was found to have a severe presentation of bleomycin-induced lung injury after chemotherapy for metastatic mixed germ cell testicular cancer. During his course, he was treated with the standard of care regimen of corticosteroids and salvage therapy with infliximab but ultimately died from complications of his illness. This case report is noteworthy because our patient had progressive bleomycin-induced lung injury, despite discontinuing bleomycin many months prior, consistent high-dose corticosteroid treatment, and even salvage therapy. In all patients on bleomycin, pulmonary function monitoring is essential, and any complaints of dyspnea should prompt concern for bleomycin-induced lung injury. If initial treatment does not improve their condition, more aggressive measures may be necessary.

MP46-10 ELUCIDATING THERAPEUTIC OPTIONS FOR TREATMENT-NAÏVE AND CISPLATIN-RESISTANT TESTICULAR CANCER

You have accessJournal of UrologyCME1 May 2022MP46-10 ELUCIDATING THERAPEUTIC OPTIONS FOR TREATMENT-NAÏVE AND CISPLATIN-RESISTANT TESTICULAR CANCER Julie-Ann Cavallo, Daniel Ranti, Elliot Merritt, Anna Tocheva, John P. Sfakianos, and Benjamin Hopkins Julie-Ann CavalloJulie-Ann Cavallo More articles by this author , Daniel RantiDaniel Ranti More articles by this author , Elliot MerrittElliot Merritt More articles by this author , Anna TochevaAnna Tocheva More articles by this author , John P. SfakianosJohn P. Sfakianos More articles by this author , and Benjamin HopkinsBenjamin Hopkins More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002612.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Platinum-based chemotherapy is the standard of care (SOC) for patients with advanced testicular cancer (TC). However, outcomes for platinum-refractory tumors remain poor. This project seeks to use functional diagnostic approach to both predict therapeutic response for patients with testicular cancer and evaluate the utility of alternate therapeutic strategies that may improve responses for patients with platinum-refractory disease. METHODS: Using an IRB-approved protocol, we obtained tissue from platinum-sensitive and -resistant TC patients. Tissue specimens were obtained from 13 tumors: 10 primary, 2 post-treatment, and 1 lymph node. To functionally model therapeutic responses for patients with TC, we used our RAPiDS (Rapid Assessment of Patient Drug Sensitivity) screens on primary patient-derived organoids (PDOs) to stratify patient response to SOC therapies and evaluate the relative sensitivity of the tumors to alternative therapeutic regimens. For these studies, we conducted screens with nine therapeutics in a clinically relevant range of concentrations to extract correlative drug response data within two weeks from dissociation. RESULTS: Using the RAPiDS protocol, we developed and evaluated drug sensitivities in five PDOs (Figure 1A). Normalized luminescence from Cell-TiterGlo cell viability assays were used to determine Area Under the Curve (AUC) as a function of drug concentration (Figure 1A and B). Heatmaps show the median centered z-score for these AUC values across the therapeutics screened in each patient to gauge relative sensitivity (Figure 1A). All of our screened TC cases showed sensitivity to one or more alternative therapies tested, regardless of PDO response to first- or second-line SOC (Figure 1B). CONCLUSIONS: This data suggests that RAPiDS could be used on TC PDOs to help guide the selection of treatment options within clinically relevant timelines, which has the potential to be useful, especially in metastatic and rare cancer settings where therapeutic options are limited. Additionally, we are currently investigating the utility of RAPiDS in refractory and metastatic TC. Source of Funding: Mount Sinai School of Medicine seed funds © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e776 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Julie-Ann Cavallo More articles by this author Daniel Ranti More articles by this author Elliot Merritt More articles by this author Anna Tocheva More articles by this author John P. Sfakianos More articles by this author Benjamin Hopkins More articles by this author Expand All Advertisement PDF DownloadLoading ...

Can whole-body MRI replace CT in management of metastatic testicular cancer? A prospective, non-inferiority study.

Concerns of imaging-related radiation exposure in young patients with high survival rates have increased the use of magnetic resonance imaging (MRI) in testicular cancer (TC) stage I. However, computed tomography (CT) is still preferred for metastatic TC. The purpose of this study was to compare whole-body MRI incl. diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) with contrast-enhanced, thoracoabdominal CT in metastatic TC. A prospective, non-inferiority study of 84 consecutive patients (median age 33years) with newly diagnosed metastatic TC (February 2018-January 2021). Patients had both MRI and CT before and after treatment. Anonymised images were reviewed by experienced radiologists. Lesion malignancy was evaluated on a Likert scale (1 benign-4 malignant). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated on patient and lesion level. The primary outcome was demonstrating non-inferiority regarding sensitivity of MRI compared to CT. The non-inferiority margin was set at 5%. ROC curves and interobserver agreement were calculated. On patient level, MRI had 98% sensitivity and 75% specificity compared to CT. On lesion level within each modality, MRI had 99% sensitivity and 78% specificity, whereas CT had 98% sensitivity and 88% specificity. MRI sensitivity was non-inferior to CT (difference 0.57% (95% CI -1.4-2.5%)). The interobserver agreement was substantial between CT and MRI. MRI with DWIBS was non-inferior to contrast-enhanced CT in detecting metastatic TC disease. www. gov NCT03436901, finished July 1st2021.

Delivering Chemotherapy to a Metastatic Poor Risk Testicular Cancer Patient on Hemodialysis

A standard curative intent approach of chemotherapy treatment for metastatic testicular cancer has been well established. However, there is little guidance for patients undergoing hemodialysis (HD) who require chemotherapy for this disease. Thus, we describe our treatment approach and rationale for a patient on HD with poor risk metastatic nonseminomatous germ cell tumor involving the testicle, lymph nodes, liver, and bone. After orchiectomy, five cycles of cisplatin and modified dose etoposide were delivered and strategically timed with HD. Treatment was complicated by significant neuropathy. Surgical resection of two liver lesions was performed after chemotherapy. Ten years post-chemotherapy, he remains free of clinical, biochemical, or radiological recurrence. While our patient remains free of disease after this treatment, the optimal chemotherapy and dialysis dose and schedule to maximize cure and minimize toxicity remains unknown.

A phase II trial evaluating the efficacy of cabozantinib in the treatment of patients with refractory germ-cell tumors (GCT).

TPS428 Background: While the majority of patients with metastatic testicular cancer are cured with first-line cisplatin-based chemotherapy, 20-30% of patients will relapse following initial treatment. Many will still be cured with second and even third-line chemotherapy options, but there remains a need for new therapeutic approaches for patients with relapsed/refractory disease. Cabozantinib is an oral tyrosine-kinase inhibitor (TKI) with multiple targets including c-MET, VEGF, RET, and AXL. Testicular GCT have low rates of somatic mutations, though have been shown to be associated with a gain of chromosome 7, a portion of which encodes c-MET. When hepatocyte growth factor (HGF) binds to its c-MET receptor, cell proliferation, migration, invasion, and apoptosis escape occurs. In addition, compared to normal testicular tissue, testicular GCT have been shown to have higher rates of VEGF expression. Based on these findings, we proposed a phase 2 trial with cabozantinib in patients with relapsed/refractory GCT. Methods: This phase II, single arm, open label trial with a Simon two-stage design is evaluating cabozantinib 60mg daily in patients with relapsed/refractory GCT. Eligible patients are adult men and women with GCT (seminoma, non-seminoma, or ovarian GCT) that have progressed after first-line cisplatin-based combination chemotherapy in addition to at least 1 salvage regimen and are considered incurable with standard therapies. Patients with primary mediastinal non-seminoma, late relapse, and treated stable brain metastases are eligible. 12 patients will be enrolled initially in the first stage of the Simon two-stage design. If at least one complete response (CR), partial response (PR), or stable disease (SD) for ≥3 months is achieved, the trial will be deemed worthy of further investigation and 9 additional patients will be enrolled. Patients will be treated daily with cabozantinib until time of progression or unacceptable toxicity. Primary outcome is clinical benefit rate (proportion of CR, PR, and SD for ≥3 months using RECIST 1.1, modified to include tumor markers, AFP and hCG). Secondary outcomes include objective response rate, progression-free survival, overall survival, and tolerability and toxicity of cabozantinib. Exploratory evaluation of MET overexpression by IHC and amplification by next generation sequencing in correlation with response will be performed. This study is currently enrolling patients. As of September 20, 2021, the prespecified goal for the Simon stage 1 has been met, and 7 of planned 21 patients have enrolled. Clinical trial information: NCT04876456.

Thromboembolic Events During Treatment with Cisplatin-based Chemotherapy in Metastatic Testicular Germ-cell Cancer 2000–2014: A Population-based Cohort Study

BackgroundCisplatin-based chemotherapy (CBCT) in testicular cancer (TC) is associated with elevated venous thromboembolism (VTE) risk, but trials evaluating the safety and efficacy of thromboprophylaxis are lacking. ObjectiveTo evaluate the arterial thromboembolism (ATE) and VTE incidence and risk factors during first-line CBCT for metastatic TC, and the effect of thromboprophylaxis on VTE and bleeding. Design, setting, and participantsIn a population-based study, 506 men administered first-line CBCT during 2000–2014 at three university hospitals in Norway were included. Clinical variables were retrieved from medical records. Outcome measurements and statistical analysisPatients with ATE and VTE diagnosed at initiation of or during CBCT until 3 mo after completion were registered. Age-adjusted logistic regression was performed to identify possible VTE risk factors. Results and limitationsOverall, 69 men (13.6%) were diagnosed with 70 thromboembolic events. Twelve men (2.4%) experienced ATE. Overall, 58 men (11.5%) experienced VTE, of whom 13 (2.6%) were prevalent at CBCT initiation, while 45 (8.9%) were diagnosed with incident VTE. Age-adjusted logistic regression identified retroperitoneal lymph node metastasis >5 cm (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.01–3.91), central venous access (OR 2.84, 95% CI 1.46–5.50), and elevated C-reactive protein (>5 mg/l; OR 2.38, 95% CI 1.12–5.07) as incident VTE risk factors. Thromboprophylaxis (n = 84) did not influence the risk of VTE (VTE incidence with or without prophylaxis 13% vs 8%, p = 0.16). The incidence of bleeding events was significantly higher among those who received thromboprophylaxis than among those without thromboprophylaxis (14.5% vs 1.1%, p < 0.001). ConclusionsWe found a high rate of thromboembolism incidence of 13.6%. Thromboprophylaxis did not decrease the risk of VTE but was associated with an increased risk of bleeding. Patient summaryWe found a high rate of thromboembolism (13.6%) during cisplatin-based chemotherapy for metastatic testicular cancer. Prophylactic treatment against thromboses did not reduce the thrombosis frequency, but it resulted in a high incidence of bleeding events.

Nerve-sparing Robot-assisted Retroperitoneal Lymph Node Dissection: The Monoblock Technique

BackgroundRetroperitoneal lymph node dissection (RPLND) is a treatment option for men with stage 1 or 2 testis cancer and the standard of care for men with postchemotherapy retroperitoneal residual disease. Given the morbidity of RPLND, four important surgical modifications have been proposed: minimally invasive access, nerve-sparing resection, template resection, and en-bloc resection. ObjectiveTo describe the surgical steps and perioperative outcomes of robotic nerve-sparing unilateral template RPLND with en-bloc resection (roboRPLND-NS+). Design, setting, and participantsFrom 2017 to 2019, five patients with suspicion of retroperitoneal metastatic testicular cancer on abdominopelvic computed tomography underwent roboRPLND-NS+ at a single referral center. All surgeries were carried out by a single surgeon who has performed more than 500 extended and more than 50 super-extended robot-assisted lymph node dissections. Surgical procedureA lateral transperitoneal robotic approach with a da Vinci Xi Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) in six-arm configuration was used. The sympathetic chains, postganglionic sympathetic fibers, and hypogastric plexus were preserved as much as possible to ensure a nerve-sparing procedure. The template borders consisted of the renal vein cranially, the ureter laterally, the interaortocaval space medially, the common iliac artery caudally, and the psoas muscle dorsally for the right and left modified RPLND templates. Lymph nodes and the surrounding fatty tissue were progressively resected from the common iliac vessels and the abdominal aorta using the split-and-roll technique, and all of the template tissue was resected as a single specimen. Intraoperative and postoperative complications were recorded. MeasurementsLymph node yield and perioperative and postoperative oncological and functional outcomes were measured. Results and limitationsThe median patient age was 38 yr (interquartile range [IQR] 32–41) and the median operative time was 274 min (IQR 238–280). Node metastases were pathologically confirmed in three patients. The median number of lymph nodes removed was 19 (IQR 18–21), and the median number of positive lymph nodes was 2 (IQR 1–3). No patient experienced intraoperative or postoperative complications. The postoperative hospital stay was either 3 or 4 d. Maintenance of antegrade ejaculation was achieved in all patients. After median follow-up of 15 mo (IQR 14–30), all patients were alive and no recurrence was observed. Limitations include the low number of patients and the single surgeon experience. ConclusionsRoboRPLND-NS+ is a safe and feasible technique that allows removal of a high number of lymph nodes with good functional outcomes. Short-term survival outcomes were excellent, with no recurrences or deaths recorded. Patient summaryWe describe a feasible and safe robot-assisted surgical procedure for removal of lymph nodes in patients with testicular cancer. Our technique has potential to decrease the medical problems arising as side effects of the surgery while achieving good cancer control.

A presumed extragonadal germ cell tumor that turned out to be a gastric cancer—a case report

A solely retroperitoneal mass in males in combination with elevated serum Alpha-Fetoprotein (AFP) and beta-human choriogonadotropin (β-HCG) levels is highly indicative of a metastatic testicular cancer. Although testicular cancers are rare, they represent the most common diagnosed cancer in males between 14 and 40 years. However, in cases without evidence of a primary testicular tumor, the rare diagnosis of a retroperitoneal extragonadal germ cell tumor (EGCT) must be assumed. Here, we describe the first published case of a 66-year-old man presenting with this typical clinical picture and the diagnosis of an AFP and β-HCG producing advanced gastric cancer with retroperitoneal lymph node metastases mimicking a primary retroperitoneal EGCT. The final diagnosis was only made by gastroscopy performed after a CT-guided retroperitoneal lymph node biopsy revealed an adenocarcinoma, suggesting an upper gastrointestinal tract primary origin. However, a specific initial anamnesis and also in the primary staging, including a full-body CT-scan there was no hint for another primary tumor. Only the slightly unusual extension of the retroperitoneal mass up to the ligamentum hepatoduodenale and the pylorus, as well as the atypical age made us question our initial diagnosis. This extraordinary case is of special clinical interest to all practising physicians and once again highlights the importance of keeping rare differential diagnosis such as AFP-producing gastrointestinal tumors in mind.

Paraneoplastic hyperthyroidism in hCG-secreting metastatic testicular cancer

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Thromboembolic events in metastatic testicular cancer treated with cisplatin-based chemotherapy.

BACKGROUNDTesticular germ cell tumor (TGCT) is the most curable solid tumor and most common cancer among men 18-39 years. While cisplatin-based chemotherapy has significantly lengthened the survival of patients with TGCT, it is associated with a high rate of thromboembolic events (TEE).AIMTo summarize our single-center experience highlighting patients who were diagnosed with TGCT and received platinum-based chemotherapy, with special attention to those patients who suffered a TEE.METHODSA retrospective analysis of the medical records and imaging studies of 68 consecutive individuals who were diagnosed with TGCT and received platinum-based chemotherapy at our Institution in a metropolitan community between January 1, 2014 and December 31, 2019.RESULTSA total of 19 (28%) patients experienced a TEE following orchiectomy which occurred during chemotherapy in 13 (68%) of these patients. Patients with a higher pathologic stage (stage III) were significantly (P = 0.023) more likely to experience a TEE compared to patients who had a lower stage. Additionally, patients who were treated with 3 cycles of bleomycine, etoposide, and cisplatin and 1 cycle of etoposide and cisplatin or 4 cycles of etoposide and cisplatin were significantly 5 (P = 0.02) times more likely to experience a TEE compared to patients who were treated with only 3 cycles of bleomycine, etoposide, and cisplatin.CONCLUSIONDue to numerous factors that predispose to a TEE such as large retroperitoneal disease, higher clinical stage, greater number of chemotherapy cycle, central venous catheter, cigarette smoking, and possible cannabis use, high-risk ambulatory patients with TGCT treated with cisplatin-based chemotherapy may benefit from prophylactic anticoagulation. Randomized studies to evaluate the safety and efficacy of prophylactic anticoagulants are warranted in this young patient population generally devoid of medical co-morbidities.

Myeloablative chemotherapy in testicular cancer patient

Chemotherapy is the standard treatment for metastatic testicular cancers. The autologous hematopoietic stem cell transplantation is a salvage option for relapsed patients. The paper presents a case of a 20-year-old patient with stage IIIC non-seminoma treated with BEP chemotherapy and autologous transplantation of stem cells, which allowed to achieve durable remission.

Physiological properties and characteristic reactions of hydroxyurea

As it was mentioned in the previous paper, we observed the mechanism of action the interesting drug, first synthesized back in 1869 for the first time, called Hydroxyurea. A century later, phase I and II trials began to test its safety in humans with solid tumors. It was first approved by the FDA in 1967 for the treatment of neoplastic diseases and is presently approved for the treatment of melanoma, resistant chronic myelocytic leukemia (CML), and recurrent, metastatic testicular and ovarian cancer. Sickle cell disease is a genetic disorder that decreases life expectancy by 25 to 30 years. Individuals are diagnosed with sickle cell disease if they have one of several genotypes that result in at least half of their hemoglobin being hemoglobin S (HbS). Sickle cell anemia refers specifically to the condition associated with homozygosity for the Hb S mutation (Hb SS). Several other hemoglobin mutations, when occurring with an Hb S mutation, cause a similar but often milder disease than sickle cell anemia. In addition to reduced life expectancy, patients with sickle cell disease experience chronic pain and reduced quality of life. Painful crises, also known as vaso-occlusive crises, are the most common reason for emergency department use and hospitalization, and acute chest syndrome is the most common cause of death. Prior to the approval of hydroxyurea for use in sickle cell disease, patients with this condition were treated only with supportive therapies. These measures included penicillin in children to prevent pneumococcal disease, routine immunizations, and hydration and narcotic therapy to treat painful events. Red blood cell transfusions increase the blood’s oxygen carrying capacity and decrease the concentration of cells with abnormal hemoglobin, but chronic transfusion therapy predictably leads to iron overload and alloimmunization. Therapies such as hydroxyurea that raise fetal hemoglobin (Hb F, α2γ2) levels are promising because they effectively lower the concentration of Hb S within a cell, resulting in less polymerization of the abnormal hemoglobin.Hydroxyurea’s efficacy in sickle cell disease is generally attributed to its ability to raise the levels of Hb F in the blood; however, the mechanisms by which it does so are unclear. Early studies suggested that hydroxyurea is cytotoxic to the more rapidly dividing late erythroid precursors, resulting in the recruitment of early erythroid precursors with an increased capacity to produce HbF.

The Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Metastatic Testicular Cancer.

We investigated the prognostic utility of pre-chemotherapy neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic germ cell tumors (GCTs) undergoing first-line chemotherapy. We utilized two institutional databases to analyze the pretreatment-derived NLR (dNLR). Predictive accuracy was evaluated using the Cox proportional hazard model adjusted for the international germ cell cancer collaborative group (IGCCCG) risk classification. Discriminatory accuracy was evaluated by determining the area under the receiver operating characteristic curve (AUROC). In total, 569 of 690 patients had available dNLR (IGCCCG: good, 64%; intermediate, 21%; poor, 16%). The 5-year and 10-year overall survivals (OSs) for good, intermediate, and poor risk groups were 96.2%, 92.8%, and 62.7% and 93.9%, 90.3%, and 62.7%, respectively. A dNLR of 2 provided the best discriminatory accuracy with an AUROC of 0.58 (95% CI: 0.52–0.65, p = 0.01) for progression-free survival (PFS), whereas for OS, a dNLR of 3 provided the best discriminatory accuracy with an AUROC of 0.62 (95% CI: 0.53–0.70, p < 0.01). A dNLR > 2 was associated with a hazard ratio (HR) of 1.99 (95% CI: 1.27–3.12, p < 0.01) for PFS, which lost its effect after adjustment for IGCCCG (HR: 1.44, 95% CI: 0.90–2.30, p = 0.13). For OS, a dNLR >3 was associated with an HR of 3.00 (95% CI: 1.79–5.01, p < 0.01), but lost its effect after adjustment for IGCCCG. Systemic inflammation plays a role in metastatic GCT, but its prognostic utility beyond established algorithms is limited. The general prognostic value of NLR can be seen across a number of tumors, although the consistency and magnitude of the effect differ according to cancer type, disease stage, and treatment received. We identified that an elevated NLR was associated with an adverse PFS and OS, but not independent of the IGCCCG risk classification. dNLRs >2 and >3 were associated with an adverse PFS and OS, respectively, in patients with metastatic GCT receiving first-line chemotherapy, but not independent of the IGCCCG risk classification.

Surgical Management of Retrocrural Disease in Germ Cell Tumors: Outcomes and Evolution of Practice.

Residual retrocrural disease in testis cancer following chemotherapy is a surgical challenge. We sought to assess the outcomes and evolution with surgical management of residual retrocrural disease. We identified 2,788 testicular cancer patients from 1990 to 2010 who underwent retroperitoneal surgery for metastatic testicular cancer at our institution. Patients who also underwent postchemotherapy staged or concurrent retrocrural dissections were stratified for analysis. Surgical approach, clinical characteristics, additional procedures, complications and outcomes were evaluated. Retrocrural dissection was performed in 211 patients. Histology of retrocrural disease demonstrated teratoma in 72%, necrosis in 15.2%, active germ cell cancer in 8.1% and malignant transformation in 2.4%. Our preferred surgical approach to the retrocrural space has evolved over time. Earlier approaches from 1990 to 1995 favored a single thoracoabdominal incision (17, 25%), midline transabdominal incision (22, 32.4%), or with a concurrent or staged thoracotomy (29, 42.6%). A transabdominal/transdiaphragmatic approach at the time of midline retroperitoneal lymph node dissection has been used more frequently in 55% of contemporary cases, decreasing the need for thoracotomies. Patients undergoing a transabdominal/transdiaphragmatic approach had fewer complications (p=0.006) and required fewer associated procedures (p=0.001) and a shorter length of stay (5 vs 6 days, p=0.184). Metastatic testis cancer to the retrocrural space is surgically challenging however complete resection is needed to maintain an expected excellent oncologic outcome. Coordination between urological and thoracic surgeons for an individualized approach is important. We have found that a transabdominal/transdiaphragmatic approach where appropriate has resulted in fewer complications.

The cardiac impact of cisplatin-based chemotherapy in survivors of testicular cancer: a 30-year follow-up.

AimsCisplatin-based chemotherapy (CBCT) is essential in the treatment of metastatic testicular cancer (TC) but has been associated with long-term risk of cardiovascular morbidity and mortality. Furthermore, cisplatin can be detected in the body decades after treatment. We aimed to evaluate the long-term impact of CBCT on cardiac function and morphology in TC survivors 30 years after treatment.Methods and resultsTC survivors treated with CBCT (1980–94) were recruited from the longitudinal Norwegian Cancer Study in Testicular Cancer Survivors and compared with a control group matched for sex, age, smoking status, and heredity for coronary artery disease. All participants underwent laboratory tests, blood pressure measurement, and 2D and 3D echocardiography including 2D speckle-tracking strain analyses. Ninety-four TC survivors, on average 60 ± 9 years old, received a median cumulative cisplatin dose of 780 mg (IQR 600–800). Compared with controls, TC survivors more frequently used anti-hypertensive (55% vs. 24%, P < 0.001) and lipid-lowering medication (44% vs. 18%, P < 0.001). TC survivors had worse diastolic function parameters with higher E/e′-ratio (9.8 ± 3.2 vs. 7.7 ± 2.5, P < 0.001), longer mitral deceleration time (221 ± 69 vs. 196 ± 57ms, P < 0.01), and higher maximal tricuspid regurgitation velocity (25 ± 7 vs. 21 ± 4 m/s, P = 0.001). The groups did not differ in left or right ventricular systolic function, prevalence of arrhythmias, or valvular heart disease. Cumulative cisplatin dose did not correlate with cardiac parameters.ConclusionNo signs of overt or subclinical reduction in systolic function were identified. Long-term cardiovascular adverse effects three decades after CBCT may be limited to metabolic dysfunction and worse diastolic function in TC survivors.

S1398 Biliary Stricture in a Patient With Metastatic Mixed Germ Cell Tumor (MGCT) of the Testis: A Case Report

INTRODUCTION: Testicular cancer is the most common malignancy in American males between the ages of 15–35. Up to 95% of testicular cancers are GCTs and the most common site for metastatic spread is the retroperitoneal lymph nodes. However, the spread of the retroperitoneum rarely involves the biliary tree. We present an unusual case of MGCT of the testis with metastases to the retroperitoneal lymph nodes causing biliary stricture and common bile duct dilation. To the best of our knowledge, this is the first reported case of biliary stricture caused by metastatic testicular cancer. CASE DESCRIPTION/METHODS: An 18-year-old man with no significant past medical history presented to our emergency department with a two-week history of progressive abdominal pain and weight loss. A complete physical examination was normal except for a tender abdomen without rebound tenderness. Laboratory findings on admission revealed signs of obstructive jaundice with elevated transaminases and elevated total bilirubin. CT of the abdomen showed large retroperitoneal masses measuring 14.2 cm extending into porta hepatis region with dilatation of the biliary ducts. Further evaluation including testicular palpation and ultrasound revealed a small testicular nodule. There was an abnormal elevation of testicular markers (serum beta-human chorionic gonadotropin level was 77,193 IU/ml) which subsequently led to suspicion of testicular cancer. He underwent a biopsy of the retroperitoneal mass, which confirmed a metastatic MGCT with embryogenic and choriocarcinoma components originating from the testis. He underwent a cycle of chemotherapy with etoposide, ifosfamide, and cisplatin during his hospital stay. ERCP performed showed a severe irregular biliary stricture over the lower third of the main bile duct with malignant appearance, and the upper third of the main bile duct was severely dilated secondary to stricture. A biliary sphincterotomy was performed and biliary tree balloon sweep was conducted with no significant findings. A plastic stent was placed into the common bile duct to maintain patency and demonstrated good flow. Follow-up labs demonstrated improvement in LFTs and bilirubin levels. DISCUSSION: This is a rare case of obstructive jaundice and biliary stricture in a patient with a MGCT (non-seminomatous) of the testis that metastasized to the retroperitoneal space. After ERCP with endoscopic bile duct stenting, it was noted that the jaundice and bile duct dilation resolved and symptoms improved.Figure 1.: Coronal contrast – enhanced CT image of upper abdomen demonstrates intra- and extra hepatic biliary dilation with abrupt cut-off at the upper common bile duct (black arrow), caused by confluent retroperitoneal lymphadenopathy extending into the hepatic hilum (white arrow).