Ondrus D

Metastatic spermatocytic seminoma. A case report with light microscopic, ultrastructural, and immunohistochemical findings.

A case of a metastatic spermatocytic seminoma with metastases to homolateral retroperitoneal paraaortic lymph nodes in a 50‐year‐old man is described. The metastases were detected 18 months after orchiectomy. A retroperitoneal biopsy with cytoreductive lymphadenectomy was performed followed by radiotherapy and consecutively by combination chemotherapy. The patient died 25 months after orchiectomy of complications arising after a second course of chemotherapy. No signs of further tumor spread were observed. Autopsy was not performed. The tissue of the metastases fulfilled the light microscopic criteria for spermatocytic seminoma and ultrastructurally showed intercellular communications with typical intercellular bridges. The absence of placental alkaline phosphatase in tumor cells is also consistent with this diagnosis. The metastases differed from the primary tumor in the presence of focal lymphocytic infiltration and granulomatous reaction. This patient represents the first fully documented case of a metastasizing spermatocytic seminoma.

Orchiectomy alone for clinical stage I nonseminomatous germ cell tumors of the testis (NSGCTT): a minimum follow-up period of 5 years.

Aims and background Surveillance after orchiectomy alone has gained great popularity in the management of stage I NSGCTT. Preliminary results were enthusiastic, but critical voices have been raised against general use of this option as routine management. In an effort to identify patients at high risk of relapse, there has been a search for adverse prognostic factors of stage I nonseminomatous germ cell testicular tumors (NSGCTT). The aim of the study was to identify those patients in whom a surveillance policy is less likely to be successful. Methods Eighty patients with stage I NSGCTT were followed for at least 5 years. They were assigned to their respective clinical stage on the basis of physical examination, chest X-ray, CT of the retroperitoneum and post-orchiectomy tumor markers. The criteria for inclusion in clinical stage I were normal results of these examinations. The policy of surveillance consisted of regular follow-up with tumor markers, chest X-ray and CT of the retroperitoneum. Patients who relapsed were treated with cisplatin-containing chemotherapy. In all patients, diagnostic delay, pre-orchiectomy tumor markers, T staging category, size, histopathology and vascular invasion in the primary tumor, and semen analysis were recorded. Results Follow-up revealed that 51 of the 80 patients (63.7%) were free of disease 61-110 months (mean, 83.1) after orchiectomy. Relapse was detected in 29 patients (36.3%) 3-58 months (mean, 13) after orchiectomy. The overall survival rate was 95%. The main risk factors of relapse were: vascular invasion, a major embryonal carcinoma and a minor teratoma component in the primary tumor, and low sperm count before orchiectomy. Conclusions The authors recommend the following risk-adapted treatment procedures: retroperitoneal lymph node dissection in patients with vascular invasion and a major teratoma component, adjuvant chemotherapy in patients with vascular invasion and a major embryonal carcinoma component, and surveillance policy in patients without vascular invasion.

Delayed orchiectomy after chemotherapy in patients with advanced testicular cancer.

Introduction: The therapeutic procedures in the management of testicular cancer are determined by histological findings in the removed testis and by the extent of the disease at the time of diagnosis. However, all advanced tumors could be treated by primary chemotherapy regardless of the histological findings. The current imaging techniques (ultrasound of the testis, abdominal and chest CT examination) and laboratory tests (determination of serum tumor markers AFP and hCG) provide sufficient evidence for the presence of cancer. When the diagnosis of advanced tumor is evident, it is possible to start the treatment without orchiectomy. The aim of this study was to evaluate the advantages of neo-adjuvant chemotherapy with delayed orchiectomy in the management of advanced testicular cancer. Material and methods: A total of 36 patients with advanced germ cell testicular cancer underwent primary PVB or BEP chemotherapy without previous orchiectomy. Mean age of patients was 32 years. Detailed medical, surgical and urological examination showed pulmonary metastases and/or extensive abdominal tumorous masses imitating acute abdominal crisis and impaired drainage of the kidney due to ureteral obstruction. Searching for the origin, testicular tumor was detected. Eleven patients had a bulky disease in the retroperitoneum (Stage IIC), two had enlarged retroperitoneal lymph nodes (Stage IIB), two had enlarged mediastinal lymph nodes (Stage III) and other 16 patients had also pulmonary metastases, and 5 pts had pulmonary metastases only. The patients were treated with cisplatin-containing combination chemotherapy. Following completion of chemotherapy, orchiectomy was performed alone or simultaneously with retroperitoneal lymph node dissection (RPLND) and/or lung metastasectomy in cases with persistent residual mass. Following orchiectomy the patients were regularly checked and in cases with viable malignant tumor found in the testis sequential chemotherapy was administered. Similarly when the relapse of the disease was detected, the patients were treated with sequential chemotherapy. Results: Complete disappearance of metastases was observed in 12 patients following chemotherapy alone. The residual mass persisted in 24 patients (in 22 out of them in the retroperitoneum and in two patients also in the lungs) and was removed surgically. The viable tumor in the removed tissue was found in one patient. Delayed orchiectomy was performed simultaneously with surgical removal of residual mass in the retroperitoneum in 24 patients and as a separate procedure in 12 patients who have been considered to be complete responders following chemotherapy alone. Residual viable tumor in testicular specimen was found in three patients, necrotic or fibrotic tissue in 18, and mature teratoma in 15 patients. Overall survival of the patients was 26/36 (72.7%) at mean of 56.9 months (range 7–145 months, median 50 months) since the start of the treatment. Conclusions: In patients with advanced germ cell testicular cancer preference must be given to the early beginning of intensive chemotherapy without the need of tissue diagnosis of primary tumor that should be obtained by orchiectomy. Benefit of this therapeutic approach is the timely management of acute abdominal and/or pulmonary symptoms of life-threatening distant metastases.

Phase II study of everolimus in refractory testicular germ cell tumors

BACKGROUND Testicular germ cell tumors (TGCTs) represent a highly curable disease; however, a small proportion of patients develop disease recurrence. Loss of the tumor-suppressor gene phosphatase and tensin homolog marks the transition from intratubular germ cell neoplasia to invasive GCT and is correlated with disease progression. Inactivation of phosphatase and tensin homolog is associated with deregulation of the PI3K/Akt pathway and increased mammalian target of rapamycin signaling. This study aimed to determine the efficacy and toxicity of a mammalian target of rapamycin inhibitor, everolimus, in patients with refractory TGCTs. METHODS From December 2011 to February 2015, 15 patients with refractory GCTs were enrolled in the phase II study. All patients were pretreated with at least 2 cisplatin-based therapies; 4 tumors (26.7%) were absolutely refractory to cisplatin and 9 patients (60.0%) had visceral nonpulmonary metastases. Everolimus was administered at a dose of 10mg daily until progression or unacceptable toxicity. The primary end point was the objective response rate, according to Response Evaluation Criteria in Solid Tumors. RESULTS No objective response was observed, but 6 patients (40.0%) achieved 12-week progression-free survival. During a median follow-up period of 3.6 months (range: 1-35.1mo), all patients experienced disease progression and 11 patients (80.0%) died. Median progression-free survival was 1.7 months (95% CI: 1.1-4.0mo) and median overall survival was 3.6 months (95% CI: 2.0-11.0mo). CONCLUSIONS This study failed to achieve its primary end point and our data suggest limited efficacy of everolimus against unselected heavily pretreated refractory TGCTs. CONDENSED ABSTRACT Everolimus showed limited efficacy in unselected heavily pretreated refractory TGCTs. Prolonged disease stabilization could be achieved in selected patients.

Bilateral testicular germ-cell tumors--a single centre long-term experience.

Objectives: The incidence of bilateral testiculartumors (BTT) had increased over the preceding decade. The aim of thepresent study is to analyse a group of patients with BTT and tohigh-light the need for long-term follow-up of patients treated in asingle centre. Material and methods: 27 (2.8%) out of960 patients with germ-cell testicular tumors (GCTT), treated between4/1977 and 8/2001, developed bilateral disease. All of themunderwent radical orchiectomy (in one patient was done delayedorchiectomy after primary chemotherapy due to advanced disease).Additional treatment was planned according to the histologic type andclinical stage of the disease, and previous treatment as well. Thesurvival data were reviewed. Results: 24 out of 27 patients(88.9%) developed the 2nd tumor metachronously (median interval66 months, range, 4–197 months) and three (11.1%) had synchronousBTT. Only 7 patients (25.9%) had identical histological types onboth sides (6 of them with pure seminomas, one with embryonalcarcinoma). Two of three synchronously developed BTT had differenthistologic types on both sides. GCTT of one histologic type wereobserved in respect of the first tumor: 11 seminomas, three embryonalcarcinomas, in respect of the 2nd tumor: 10 seminomas, three embryonalcarcinomas, in respect of the 2nd tumor: 10 seminomas, three embryonalcarcinomas and one mature teratoma. GCTT of more than one histologictype were observed in respect of the first and the 2nd tumors: 6 mixedGCTT with seminoma component and 7 without seminoma component. Majorityof BTT was presented in clinical stage I (in respect of the first tumorin 70.4%, in respect of the 2nd tumor in 62.9%). Themedian duration of the follow-up after the diagnosis of the first GCTTwas 149 months (range, 13–288 months) and after the diagnosis ofthe contralateral GCTT was 68 months (range, 1–167 months).Twenty-five patients (92.6%) were alive with NED at their lastfollow-up visit. Two patients died by mean of 22.5 months (range,21–24 months) after the 2nd orchiectomy. Conclusions: Allpatients with unilateral GCTT have an increased risk of developing acontralateral testicular tumor, even decades after diagnosis. Managementshould be individualised for each patient.

Primary chemotherapy in the management of low stage (IIA and IIB) non-seminomatous germ cell testicular tumours

In a prospective study a total of 65 patients in clinical stages IIA and IIB non-seminomatous testicular tumours were treated by primary chemotherapy followed by retroperitoneal lymphadenectomy in cases with residual disease. The patients were given a combination of cisplatin, vinblastine and bleomycin, or also etoposide. Sixty-two patients (95.4%) achieved complete response: 39 (60%) by chemotherapy alone and 23 (35.4%) following surgical removal of residual disease. Three patients died; there were two drug-related deaths during PVB chemotherapy, one patient had progression of disease following chemotherapy and died as a result of disease dissemination.Three patients relapsed from complete response following chemotherapy, two of them died within 19 and 29 months after the onset of therapy. The third patient received second-line chemotherapy and gained complete response again. Of the 65 patients, 60 (92.3%) survive with no evidence of disease. The follow-up period ranged from 6 to 79 months (mean 39.4 months, median 39 months).

Testosterone Deficiency and Bone Metabolism Damage in Testicular Cancer Survivors

The aim of the study was to investigate the influence of therapeutic modalities and sexual hormone levels on changes in bone mineral density (BMD) in testicular cancer (TC) survivors. In a cross-sectional descriptive, long-term follow-up study, a total of 1,249 long-term TC survivors were evaluated according to treatment modality: orchiectomy (OE) only, OE + chemotherapy (CT), or OE + radiotherapy (RT). Luteinizing hormone (LH), total testosterone (TST), marker of bone resorption (β-carboxyl-terminal cross-linking telopeptide of type I collagen—CTx), and BMD were evaluated. Standard statistical techniques were used to test the differences between groups of patients. TST decrease was observed in 46/313 TC survivors after OE alone, in 103/665 after OE + CT, and in 66/271 after OE + RT. LH increase was observed in 23/313 TC survivors after OE alone, in 154/665 after OE + CT, and in 43/271 after OE + RT. CTx increase was observed in 116/313 TC survivors after OE alone, in 324/665 after OE + CT, and in 82/271 after OE + RT. Osteopenia/osteoporosis occurred in 136/313 TC survivors after OE alone, in 298/665 after OE + CT, and in 139/271 after OE + RT. TC survivors after RT have statistically significant decreased TST levels, increased LH and nonsignificant worse BMD (osteopenia/osteoporosis) in comparison with TC survivors after OE alone or CT. TST decrease and LH increase were statistically significant, more frequently observed in patients with osteopenia/osteoporosis. Examination of TST is an important part of follow-up in TC survivors with bilateral as well as unilateral disease. The important part of standard examination algorithm should be also the osteological examination of TC survivors mainly in patients with androgen deficiency.

Recent patterns in cutaneous melanoma descriptive epidemiology in the Slovak Republic.

An increase in melanoma incidence in the Slovak Republic (SR) is evident during approximately the same time and maybe caused by changes in socio-economic status. The paper analyses national trends in incidence, mortality, survival and clinical stages of invasive cutaneous melanoma in the SR from 1968-2007. The trends in incidence and mortality have been extracted between 1968-2007 period by the joinpoint regression analysis, clinical stages were analysed in 1978-2003. Survival data were extracted from the national database resources. Socio-economic changes, which reflected in increase in the number of holiday makers to seaside and mountainous destinations happened in the country in the y.1989. Subsequently, according to joinpoint in 1997, acceleration of increment of the incidence values of melanoma was recorded in both sexes. Mortality was increasing in males continuously, in females the stabilization was registered after the year 1999. Lower rates of relative survival might be influenced by delayed accessibility to adjuvant treatment. The number of cases diagnosed in clinical stage I increased significantly. The changes in the intensity and excessive sunbathing during vacations might be one of many factors that participate in subsequent acceleration of the increment of incidence not only in the SR.

Plasma Cytokines Correlated With Disease Characteristics, Progression-Free Survival, and Overall Survival in Testicular Germ-Cell Tumor Patients

Micro‐Abstract We performed a translational study and found a correlation among overall survival, progression‐free survival, and circulating cytokines in metastatic testicular germ‐cell tumor patients. Association between baseline clinicopathologic features and plasma cytokines was also assessed. Plasma cytokines could be a potential biomarker for identification of high‐risk patients. Background: Cytokines are the communicators of immune system and are involved in all immune responses. The aim of this study was to assess the correlation among plasma cytokines, patient and tumor characteristics, and clinical outcome in chemonaive testicular germ‐cell tumor (TGCT) patients. Patients and Methods: This study included 92 metastatic chemotherapy‐naive TGCT patients treated with platinum‐based chemotherapy from July 2010 to March 2014. Plasma was isolated before first administration of chemotherapy, and the concentration of 51 plasma cytokines were analyzed using multiplex bead arrays. Results: At a median follow‐up of 33.2 months (range, 0.1‐54.8 months), 10.9% of patients experienced disease progression, and 7.6% died. Several cytokines were associated with different baseline clinicopathologic features. Elevated plasma levels of interferon (IFN)‐&agr;2, interleukin (IL)‐2R&agr;, IL‐16, hepatocyte growth factor (HGF), and monocyte chemotactic protein (MCP)‐3 were significantly associated with worse progression‐free survival and overall survival (OS). Moreover, elevated levels of stem‐cell growth factor (SCGF)‐&bgr; were also associated with worse OS. Patients with elevated levels of all 6 cytokines experienced significantly worse outcomes compared to patients who had fewer than 6 cytokines elevated (hazard ratio = 12.06; 95% confidence interval, 7.39‐19.49; P = .002 for progression‐free survival, and hazard ratio = 39.65; 95% confidence interval, 25.03‐62.18; P < .00001 for OS, respectively). Results were independent of International Germ Cell Cancer Collaborative Group criteria. Conclusion: We found a correlation among progression free‐survival, OS, and circulating cytokines in TGCT. This suggests the existence an association between plasma cytokines and baseline clinicopathologic features in TGCT. Plasma cytokines could be used for identification of high‐risk patients who are candidates for new therapeutic approaches.

Trends in prostate cancer incidence and mortality before and after the introduction of PSA testing in the Slovak and Czech Republics

AIMS AND BACKGROUND As two neighboring countries in central Europe with national cancer registries, the Slovak (SR) and Czech Republics (CR) are countries with a medium global rate in the occurrence of prostate cancer. This paper analyzes the incidence of prostate cancer and mortality before and after the introduction of PSA testing in the two Republics and the possible reasons for any differences discovered and compares the results with selected regions and countries of the world. STUDY DESIGN AND RESULTS In the Slovak Republic, prostate cancer incidence (age-adjusted to the world standard population) has risen from 14.6/100,000 in 1968 (95% CI, ±1.5772) to 36.2/100,000 in 2005 (95% CI, ±2.0678). The estimated annual increase in the incidence during the period 1968-1991 (before nationwide PSA testing) was 0.421; from 1991 (when nationwide PSA testing began) to up to 2003 it was 0.941. Mortality rates grew from 7.3/100,000 in 1968 to 14.9/100,000 in 2005. In spite of the geographic proximity of the two countries, the increase in incidence occurred faster in the Czech than in the Slovak Republic, from 15.8/100,000 in 1977 (95% CI, ±0.9748) to 59.5/100,000 in 2005 (95% CI, ±1.7187). The estimated annual increase in incidence in the Czech Republic for the period of 1977-1991 was 0.581. From 1991 (when national PSA testing began) until 2003, it was 1.981. In the period before 1991, mortality rose more sharply in the Czech than in the Slovak Republic, whereas after the introduction of PSA testing mortality stabilized more quickly in the Czech than in the Slovak Republic. In the Slovak Republic, a significant reduction in mortality was observed after 2002 and has continued to the present and probably is not affected only by the results connected with the increase in PSA testing. CONCLUSIONS The difference in the incidence and mortality of prostate cancer in the Slovak and the Czech Republics results from a difference in the intensity of PSA testing as well as from the introduction of complex, more effective treatment in advanced clinical stages.