Should extragonadal germ cell tumors be included in studies of families with testicular germ cell tumors?

Background

Family history is among the few established risk factors for testicular germ cell tumor (TGCT). Approximately 1.4% of newly diagnosed TGCT patients report a positive family history of TGCT. Sons and siblings of TGCT patients have four- to six fold and eight- to tenfold increase in TGCT risk, respectively. In twins of men with TGCT the relative risk of testicular cancer is 37.5 (12.3-115.6). Nevertheless, information about the occurrence of TGCT in relatives of patients with extragonadal germ cell tumor is limited.

Case report

A 24 year-old male patient was diagnosed with a mediastinum tumor and was submitted to image-guided biopsy, which revealed a seminoma. Two months later, his non-identical asymptomatic twin brother was submitted to an elective ultrasound of the testes, which showed a left testicular mass of 4.2 cm. This patient underwent orchiectomy revealing a seminoma of the left testis. There are no other cases of seminoma or other types of cancers reported in first-degree relatives in this family.

Conclusions

Although familial aggregations of TGCT have been well described, to the best of our knowledge, no data concerning the association of gonadal and extragonadal germ cell tumor in relatives has been previously reported. Further investigation on this association is warranted and may help in improving our knowledge of familial pattern inheritance.     

Incidental gallbladder cancer: what management?

Gallbladder cancer (GBC) represents 3.8% of all gastrointestinal cancers and usually known to be of a poor prognosis. In 0.2–2.9% of cases, this cancer is found in cholecystectomy specimens. A better understanding of spread mode of this tumor helps a better surgical management. The aim of the present review is to underline the management of GBC based on the comprehension of risk factors and anatomic features. A Medline, PubMed database search was performed to identify articles published from 2000 to 2011 using the keywords ‘carcinoma of gallbladder’, ‘incidental gallbladder cancer’, ‘gallbladder neoplasm’ and ‘cholecystectomy’. Some pathological situations such as chronic lithiasis and biliopancreatic junction abnormalities have been clearly identified as predisposing to GBC. Laparoscopy increases peritoneal and parietal tumor dissemination, thus, it should not be performed when GBC is suspected. Most determinant prognostic factors are nodal, perineural and venous involvement, invasion of the cystic duct and the tumor differentiation. The simple cholecystectomy is sufficient for tumors classified as T1a; for other cancers exceeding the muscularis, radical re-resection is required due to the high risk of recurrence. This aggressive surgery improved the overall survival of patients. There is still no standard adjuvant treatment; patients should be included in prospective trials.     

Evaluation of pregnancy-specific β1-glycoprotein in patients with non-seminomatous testicular germ cell tumors

Serum SP-1 levels were measured serially in 94 patients with non-seminomatous germ cell tumors to evaluate its clinical significance as a tumor marker. In 12 out of 80 patients (15%) with active tumors serum SP-1 was found to be elevated, whereas serum HCG and AFP in the same sample were raised in 53 and 45% respectively. Elevation of serum SP-1 levels was always associated with raised HCG levels, and with AFP in 7 patients. During chemotherapy, serum SP-1 and HCG disappeared when a complete remission was obtained. In contrast to HCG, serum SP-1 failed to detect tumor progression in two patients. Serum HCG and AFP are superior as tumor markers to serum SP-1.     

Radiobiologic response of medulloblastoma cell lines: involvement of β-catenin?

Medulloblastoma (MB) is the most common brain malignancy in children. Whole neural axis irradiation is the treatment of choice, but it often results in long-term neurocognitive and developmental impairment. Only insights into MB biology will lead to improved therapeutic outcome. Wingless (WNT) signalling deregulation occurs in up to 25% of sporadic tumors, but the specific role of nuclear β-catenin and its involvement in the radioresponse remains unsettled. Therefore we studied the γ-radiation response of two MB cell lines from cellular and molecular points of view. Our data show that the p53 wild-type cell line is more sensitive to ionizing radiations (IR) than the p53 mutated line, but apoptosis is also induced in p53-mutated cells, suggesting an alternative p53-independent mechanism. In addition, this study is the first to demonstrate that γ-rays trigger the WNT system in our in vitro models. Further studies are required to test if this could explain the radiosensitivity of MB and the favorable prognostic value of nuclear β-catenin in this tumor.     

How does a normal human cell become a cancer cell?

The mechanism by which cells become cancerous has been studied in several different species and cell types. Here, we will focus on the mechanism by which a normal human cell becomes a cancer cell and specifically discuss genes that researchers have used to transform cells. Studying how those genes affect cellular immortalization and transformation will help researchers understand more about cancer biology, find new treatments for cancer and/or improve cell survival during gene therapy.     

Management of CNS disease in ALK-positive non-small cell lung cancer: Is whole brain radiotherapy still needed?

Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (3 to 5% of all non-small cell lung cancers) carries a particularly high risk of central nervous system dissemination (60% to 90%). As the use of ALK inhibitors improves treatment outcomes over chemotherapy, the determent of central nervous system metastases has become an increasingly relevant therapeutic dilemma considering young age and possible extended overall survival. The goal of brain metastases management is to optimize both overall survival and quality of life, with the high priority of neurocognitive function preservation. Unfortunately in the first year on crizotinib, the pioneering ALK inhibitors, approximately one third of these patients fail in the central nervous system, which is explained by an inadequate central nervous system drug penetration through the blood-brain barrier. Central nervous system-directed radiotherapy represents the most important strategy to control intracranial disease burden and extend the survival benefit with crizotinib. The role of whole brain irradiation in the treatment of brain metastases diminishes, as this technique is associated with the risk of neurocognitive decline. Stereotactic radiotherapy represents an alternative technique that delivers ablative doses of ionizing radiation to the limited volume of oligometastatic brain disease, offering sparing of the adjacent brain parenchyma and reduced neurotoxicity. The next generation ALK inhibitors were designed to cross the blood-brain barrier more efficiently than crizotinib and achieve higher concentration in the cerebrospinal fluid, offering prominent ability to control central nervous system spread. In the phase III ALEX trial the intracranial control was significantly better with alectinib as compared to crizotinib and it translated into survival benefit. Other next generation ALK inhibitors (i.e. ceritinib, brigatinib, lorlatinib) also demonstrated promising activity in the central nervous system.     

C-reactive protein; a potential marker of second cancer and cardiovascular disease in testicular cancer survivors?

IntroductionC-reactive protein (CRP) is a marker of cardiovascular disease (CVD). There is conflicting evidence regarding CRP as a marker of future cancer. We studied whether CRP predicts CVD and consecutive cancer in testicular cancer survivors (TCSs).Patients and methodsDuring 1998–2001, 586 TCSs with a high sensitivity CRP ?10 mg/L were identified median 11 (4–21) years after treatment (FU-1). A second follow-up survey (FU-2) was conducted median 8 (6–9) years after FU-1. At FU-2 we obtained information about post-FU-1 CVD (cardiovascular death, nonfatal myocardial infarction, stroke, revascularisation or heart failure). Information about post-FU-1 non-germ cell cancer and cardiovascular death in all patients were retrieved from the Cancer Registry of Norway.ResultsAfter FU-1 31 (5.3%) of 586 patients developed non-germ cell cancer (excluding localised prostate cancer), while 28 (4.9%) developed CVD. Cox regression analyses showed that patients with CRP ?1.5 mg/L had 2.21 (95% CI 1.04–4.70) times higher risk of developing non-germ cell cancer and 2.79 (95% CI 1.22–6.34) times higher risk for CVD compared to patients with CRP <1.5 mg/L at FU-1.ConclusionIn long-term TCSs, CRP may serve as a potential marker of cardiovascular events and a second cancer.     

Testicular teratomas: a growing problem?

Testicular teratomas represent a specific entity within the group of germ-cell tumours. They may comprise elements of all three germ layers. In contrast to prepubertal benign teratomas observed in infants and adolescents, postpubertal teratomas originate from the malignant germ-cell precursor. Given the good prognosis and curability of most patients with germ-cell tumour, medical oncologists and urological surgeons must be well acquainted with the principles of teratomas management. Surgery plays the decisive part in teratomas treatment, as these tumours are resistant to radio- and, to some extent, chemotherapy. In this article we concentrate on the management of post-chemotherapy resection of teratomatous masses, with special attention to the phenomenon of ‘growing teratoma syndrome’ and somatic-type transformation of teratomas. To understand the nature of teratomas better, we begin with a glimpse of their biological, molecular and immunohistochemical features. Managing germ-cell tumours, teratomas in particular, in high-volume reference centres is of utmost importance to maintain and increase the survivorship rate in these patients.     

T-regulatory cell modulation: the future of cancer immunotherapy?

T-regulatory cells suppress anti-tumour immunity in cancer patients and in murine tumour models. Furthermore, their activity is likely to have an effect on the effectiveness of immunotherapeutic treatments for cancer. Here we describe the current status of developing clinical strategies for modulating Treg activity in cancer patients.     

Epithelial cancer cell migration: a role for chemokine receptors?

We investigated the possibility that chemokine gradients influence migration of human ovarian epithelial tumor cells. Of 14 chemokine receptors investigated, only CXCR4 was expressed on ovarian cancer cells. CXCR4 mRNA localized to a subpopulation of tumor cells in ovarian cancer biopsies. Ovarian cancer cell lines and cells freshly isolated from ascites expressed CXCR4 protein. The CXCR4 ligand, CXCL12, was found in ascites from 63 patients. CXCL12 elicited intracellular calcium flux and directed migration and changes in integrin expression in ovarian cancer cells. CXCR4 may influence cell migration in the peritoneum, a major route for ovarian cancer spread, and could be a therapeutic target.     

Eukaryotic cell encystation and cancer cell dormancy: is a greater devil veiled in the details of a lesser evil?

Cancer cell dormancy is the main cause of cancer recurrence and failure of therapy as dormant cells evade not only the anticancer drugs but also the host immune system. These dormant cells veil themselves from detection by imaging and/or using biomarkers, which imposes an additional problem in targeting such cells. A similar form of hibernation process known as encystation is studied in detail for pathogenic unicellular eukaryotic microorganisms. By examination using microarray gene expression profiles, immunocytochemistry tools, and siRNAs during the process of encystation, understanding the covert features of cancer cell dormancy as proposed could be possible. This knowledge can be extended to dormant cancer cells to uncover the mechanisms that underlie this ghost, yet dangerous state of human cancers. We propose a strategy to induce dormancy and exit this state by application of knowledge gained from the encystation induction and retrieval processes in pathogenic eukaryotic microorganisms. Given that early detection and characterization of dormant malignant tumor cells is important as a general strategy to monitor and prevent the development of overt metastatic disease, this homology may enable the design of therapies that could either awake the dormant cell from dormancy to make it available for therapies or prolong such a phase to make cancer appear as a chronic disease.KEYWORDS : Cancer cell dormancy, cancer recurrence, encystation, metastasis