Hyperthyroidism in non-seminomatous testicular germ cell tumors: two case reports and literature review.

Background: Human chorionic gonadotropin (hCG)-induced hyperthyroidism is a rare paraneoplastic syndrome observed in non-seminomatous testicular germ cell tumors, due to a cross-reaction between the ß-subunit of hCG with the thyroid-stimulating hormone receptor. The precise prevalence of this paraneoplastic phenomenon is unclear as, in the majority of cases, hyperthyroidism remains subclinical. Case presentation: Here, we present two cases of advanced metastatic non-seminomatous testicular germ cell tumors where patients exhibited signs and symptoms of thyrotoxicosis at primary diagnosis due to excessive serum ß-hCG elevation, with complete remission of symptomatology after the start of oncological treatments and no signs of relapse at the time of publication of this report. Additionally, we provide a comprehensive review of the existing literature concerning this uncommon occurrence. Conclusion: Despite being a rare event, the presence of hyperthyroidism or thyrotoxicosis without clear etiology in a young man should lead to consider less frequent causes such as testicular tumors. Even if patients typically have mild symptoms that resolve after chemotherapy, in rare cases, it can be a life-threatening condition that requires prompt recognition and specific intervention.

Spermatocytic Tumor: A Review.

Spermatocytic tumor (ST) is a very rare disease, accounting for approximately 1% of testicular cancers. Previously classified as spermatocytic seminoma, it is currently classified within the non-germ neoplasia in-situ-derived tumors and has different clinical-pathologic features when compared with other forms of germ cell tumors (GCTs). A web-based search of MEDLINE/PubMed library data was performed in order to identify pertinent articles. In the vast majority of cases, STs are diagnosed at stage I and carry a very good prognosis. The treatment of choice is orchiectomy alone. Nevertheless, there are two rare variants of STs having very aggressive behavior, namely anaplastic ST and ST with sarcomatous transformation, that are resistant to systemic treatments and their prognosis is very poor. We have summarized all the epidemiological, pathological and clinical features available in the literature regarding STs that have to be considered as a specific entity compared to other germ GCTs, including seminoma. With the aim of improving the knowledge of this rare disease, an international registry is required.

Immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR)-T cell therapy: Potential treatment options against Testicular Germ Cell Tumors.

Germ cell tumors (GCTs) represent a heterogeneous neoplasm family affecting gonads and rarely occurring in extragonadal areas. Most of patients have a good prognosis, often even in the presence of metastatic disease; however, in almost 15% of cases, tumor relapse and platinum resistance are the main challenges. Thus, novel treatment strategies with both improved antineoplastic activity and minor treatment-related adverse events compared with platinum are really expected. In this context, the development and the high activity demonstrated by immune checkpoint inhibitors in solid tumors and, subsequently, the interesting results obtained from the use of chimeric antigen receptor (CAR-) T cell therapy in hematological tumors, have stimulated research in this direction also in GCTs. In this article, we will analyze the molecular mechanisms underlying the immune action in the development of GCTs, and we will report the data from the studies that tested the new immunotherapeutic approaches in these neoplasms.

Nutritional support management in resectable gastric cancer.

Gastric cancer is the sixth most common malignancy in the world. However, its mortality has been decreasing in the last years thanks to improvement in diagnostics and therapeutics. Nevertheless, the high rate of malnutrition in patients with gastric cancer still has a major impact on the overall survival and quality of life of patients. The narrative review presents the most recent data on nutritional support in the resectable stages of gastric cancer, with a particular focus on perioperative strategies, and discusses malnutrition in gastric cancer, nutritional support before and after surgery, and the relationship between nutritional support and chemotherapy. Despite the predominantly methodological limitations related to the difficulty of performing randomized controlled trials on nutritional support in cancer patients, this review highlights important points. Nutritional counselling is essential starting from diagnosis. In limited or locally advanced forms (about 40% of cases), the therapeutic cornerstone is represented by gastric surgery. In most of these cases, perioperative chemotherapy is also indicated. Of note, nutritional support varies before and after surgery. In the preoperative period, the goal is to prepare the body for surgery, with available evidence recommending the prescription of immunonutrition (both oral and artificial, as appropriate). In the postoperative period, on the other hand, the objective is to facilitate recovery and adaptation to the new anatomy; an early and combined strategy (oral and enteral) seems to be the most suitable to pursue this. Unfortunately, rigorous data on the relationship between nutritional support and chemotherapy treatments used in resectable gastric cancer are not available. In the absence of strong scientific evidence, it may be useful to adopt a personalized multidisciplinary strategy for each patient wherein the chemotherapy programme is modulated based on nutritional status.

Supportive therapies in the prevention of chemotherapy-induced febrile neutropenia and appropriate use of granulocyte colony-stimulating factors: a Delphi consensus statement.

PURPOSE: Data indicate that the use of prophylactic granulocyte colony-stimulating factors (G-CSFs) for chemotherapy-induced febrile neutropenia (FN) in routine practice is not consistent with guideline recommendations. The initiative "supportive care for febrile neutropenia prevention and appropriateness of G-CFS use" was undertaken to address the issue of inappropriate prescription of G-CSFs and to improve guideline adherence in the treatment of FN. METHODS: In a two-round Delphi procedure, 36 medical oncologists reviewed clinically relevant recommendations on risk assessment, the appropriate use of G-CSFs, and the prevention of FN based on available literature and individual clinical expertise. RESULTS: The consensus was reached on 16 out of 38 recommendations, which are backed by evidence from randomised clinical trials and routine clinical practice. The medical oncologists agreed that the severity of neutropenia depends on patients' characteristics and chemotherapy intensity, and therefore, the risk of severe neutropenia or FN should be assessed at each chemotherapy cycle so as to initiate prophylaxis with G-CSFs if required. The use of biosimilar G-CSFs, with similar efficacy and safety profiles to the originator biologic, has improved the availability and sustainability of cancer care. The timing of supportive therapy is crucial; for example, long-acting G-CSF should be administered 24-72 h after chemotherapy administration. Each biological agent has a recommended administration dose and duration, and it is important to follow these recommendations to avoid complications associated with under-prophylaxis. CONCLUSION: It is hoped that these statements will help to increase adherence to guideline recommendations for appropriate G-CSF use and improve patient care.

Testicular tumors in the "elderly" population.

Germ cell tumors arise in childhood but peak at around 30 years of age. They are the most common cancers in males under the age of 35. Over 95% arise in the testes while a minority originate in extragonadal sites such as the anterior mediastinum, or mainly in childhood the pineal gland or the sacrococcygeal area. These tumors show an extraordinary sensitivity to chemotherapy (and for seminoma, also to radiation) and cure rates are relatively high even in second or subsequent relapses. Very few data are present in the literature regarding patients diagnosed after 50 years and no specific trials have been conducted in this setting. Nearly all patients reported in the literature had testicular cancers, with occasional reports of extragonadal tumors. Despite the fact that > 50 years may be considered an "elderly" population, these patients are treated with the same cisplatin containing combinations as their younger counterparts with consequent higher toxicity. In this review we will present epidemiological and clinical data from this rare population of patients with testicular cancer.

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.

Vitamin D Deficiency in Testicular Cancer Survivors: A Systematic Review.

Testicular cancer (TC) is the most frequent tumor in young males. In the vast majority of cases, it is a curable disease; therefore, very often patients experience a long survival, also due to their young age at diagnosis. In the last decades, the role of the vitamin D deficiency related to orchiectomy has become an increasingly debated topic. Indeed, vitamin D is essential in bone metabolism and many other metabolic pathways, so its deficiency could lead to various metabolic disorders especially in long-term TC survivors. In our article, we report data from studies that evaluated the incidence of hypovitaminosis D in TC survivors compared with cohorts of healthy peers and we discuss molecular mechanisms and clinical implications.

Case Report: Exceptional Response to Second Line Temozolomide Therapy in a Patient With Metastatic Adrenocortical Carcinoma.

Background: In a recently published retrospective case series, Temozolomide was found active as second line approach in advanced ACC patients. The disease control rate obtained, however, was short-lived. We report here an ACC patient with extensive metastatic disease who obtained a remarkable long lasting response with this alkylating agent. Case Presentation: a 22-year-old female patient with ACC presented at our Medical Oncology Department in poor general condition due the presence of extensive metastatic pulmonary involvement. The disease had progressed to etoposide, doxorubicin and cisplatin plus mitotane therapy. Second line temozolomide therapy was prescribed leading to a progressive improvement of patient general conditions. The disease restaging after 12 cycles revealed a complete response of lung lesions and the patient was free from progression for 14+ months. Conclusion: Temozolomide therapy could be exceptionally efficacious in the management of ACC patients. The molecular mechanisms of sensitivity and resistance to this drug should be carefully studied, in order to select the patients destined to obtain a significant clinical benefit to the drug.

Serum tumour markers in germ cell tumours: From diagnosis to cure.

Germ cell tumors (GCTs) represent the best and the only example of solid tumors curable in the large majority of patients. GCTs are one of the few malignancies for which specific biochemical markers have been identified: human chorionic gonadotropin (HCG) and alfa-fetoprotein (AFP). Due to their specificity and sensitivity they constitute formidable tools in the diagnosis and monitoring of treatment for GCTs. As a tumor mass marker, lactate dehydrogenase (LDH) is also considered. Tumor markers are expressed in 15-20% of seminoma and 60-80% of non-seminoma. With the aim to increase sensitivity and specificity, recent studies have proposed miRNAs as serum biomarkers. This review will focus on role of serum tumor markers in diagnosis, staging, prognosis, monitoring of response, and finally follow-up of GCTs.

The Role of Nutritional Support in Cured/Chronic Patients.

Improvements in Clinical Oncology, due to earlier diagnoses and more efficient therapeutic strategies, have led to increased numbers of long-term survivors, albeit many with chronic diseases. Dealing with the complex care needs of these survivors is now an important part of Medical Oncology. Suitable diet and physical activity regimes will be important in maintaining their health. This paper will review what we know and what we can do in the near future for these patients.

Immunosenescence in Testicular Cancer Survivors: Potential Implications of Cancer Therapies and Psychological Distress.

Testicular cancer (TC) is the most frequent solid tumor diagnosed in young adult males. Although it is a curable tumor, it is frequently associated with considerable short-term and long-term morbidity. Both biological and psychological stress experienced during cancer therapy may be responsible for stimulating molecular processes that induce premature aging and deterioration of immune system (immunosenescence) in TC survivors, leading to an increased susceptibility to infections, cancer, and autoimmune diseases. Immunosenescence is a remodeling of immune cell populations with inversion of the CD4:CD8 ratio, accumulation of highly differentiated memory cells, shrinkage of telomeres, shift of T-cell response to Th2 type, and release of pro-inflammatory signals. TC survivors exposed to chemotherapy show features of immunological aging, including an increase in memory T-cells (CD4+ and CD8+) and high expression of the senescence biomarker p16INK4a in CD3+ lymphocytes. However, the plethora of factors involved in the premature aging of TC survivors make the situation more complex if we also take into account the psychological stress and hormonal changes experienced by patients, as well as the high-dose chemotherapy and hematopoietic stem cell transplantation that some individuals may be required to undergo. The relatively young age and the long life expectancy of TC patients bear witness to the importance of improving quality of life and of alleviating long-term side-effects of cancer treatments. Within this context, the present review takes an in-depth look at the molecular mechanisms of immunosenescence, describing experimental evidence of cancer survivor aging and highlighting the interconnected relationship between the many factors modulating the aging of the immune system of TC survivors.

Primary mediastinal germ cell tumors.

BACKGROUD: Germ cell tumors (GCTs) are a group of neoplasms usually arising in the gonads, and very rarely in sites outside the gonads, mainly in the retroperitoneum, the anterior mediastinum, and pineal gland or the coccyx (mainly in childhood). The prognosis of nonseminoma primary mediastinal GCTs (PMGCTs), is considered to be poorer compared to its retroperitoneal or gonadal counterparts and, according to the International Germ Cell Cancer Collaborative Group, it is considered by definition as a "poor risk" disease. MATERIAL AND METHODS: Our review highlights the clinical features, prognostic factors, and therapeutic strategies in PMGCTs, as described in medical literature. So far available data were obtained through a Medline search of English-language papers. RESULTS: Due to the rarity of the disease, there are no prospective studies comparing different treatment strategies. For this reason, oncology societies recommend treating PMGCTs like other GCTs, according to general risk categories. CONCLUSION: Because of the rarity of the disease, poor categorization, and the lack of novel therapeutic strategies, an International database is required to obtain more information on these tumors. Additional efforts should be done, with the aims to find effective novel therapeutic agents.

Recommendations for surveillance and follow-up of men with testicular germ cell tumors: a multidisciplinary consensus conference by the Italian Germ cell cancer Group and the Associazione Italiana di Oncologia Medica.

BACKGROUND: No compelling evidence is available about surveillance and follow-up of patients with testicular germ cell tumour (TGCT). METHODS: In the light of the best clinical evidence, the Italian Germ cell cancer Group (IGG) and the Associazione Italiana di Oncologia Medica (AIOM) set up a multidisciplinary national consensus conference, involving 42 leading experts and 3 TGCT survivors. A minimum of 50% of votes was required in order to achieve a consensus recommendation on 29 questions. RESULTS: Recommendations have been summarized in three tables, divided by stage I seminoma, stage I nonseminoma and the advanced disease, which may be useful for clinicians to appropriately choose the clinical investigation and its timing during the surveillance and follow-up of TGCT patients based on an accurate estimation of their risk of disease relapse. CONCLUSIONS: The IGG-AIOM consensus recommendations may help clinicians to choose appropriate clinical investigations for the surveillance and follow-up of TGCT patients.

Psychosocial Issues in Long-Term Survivors of Testicular Cancer.

Testicular cancer is the most frequent tumor in young males aged 15-39 years. As cure rates are currently around 90%, the prevalence of survivors is increasing. However, a disease-free condition does not necessarily correspond to a life free of physical and psychosocial health problems. The aim of this review was to explore psychosocial morbidity among testicular cancer survivors. A literature search was conducted in three electronic databases (PubMed, Medline, and Embase). The results of the search on cancer survivors were then combined with those of the search on psychosocial concerns and work performance. Eighty-four publications met the inclusion criteria. Physical, psychological, work-related problems and changing perspectives about work and life in general influenced life and career decisions among testicular cancer survivors. Individual health, sexual relationships and work problems, affect several important aspects of survival and significantly influence the QoL of long-term survivors.

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.