Management of clinical stage I testicular seminoma: active surveillance versus adjuvant chemotherapy.

PURPOSE: Surveillance after orchiectomy alone has become popular in the management of clinical stage I nonseminomatous germ cell testicular tumors (CSI NSGCTT), and adjuvant chemotherapy has been accepted in high-risk CSI NSGCTT. Because of the late toxicity of standard radiotherapy in CSI testicular seminoma (SGCTT), this therapeutic approach has been accepted also in the management of CSI SGCTT. In the current study, we analyzed single-center experience with risk-adapted therapeutic approaches (active surveillance and adjuvant chemotherapy) in patients with CSI SGCTT. PATIENTS AND METHODS: The study analyzed a total of 90 patients collected at a single center from April 2008 to March 2015 with CSI SGCTT who were stratified into two groups according to risk-adapted therapeutic approaches. RESULTS: In the group A (low-risk CSI SGCTT-no rete testis invasion, tumor size <4 cm, pT1 stage), which consisted of 74 patients who underwent surveillance, relapse occurred in seven (9.5 %) patients after a mean follow-up of 14.5 months. In the group B (high-risk CSI SGCTT-rete testis invasion, tumor size >4 cm or pT ≥ 2 stage), which consisted of 16 patients who were treated with adjuvant chemotherapy, relapse occurred in two (12.5 %) patients after a mean follow-up of 13.8 months. Overall survival of patients in both groups was 100 %. The statistically significant difference in progression-free survival between these two groups was not found. CONCLUSIONS: Radiotherapy is currently not recommended as an adjuvant treatment in CSI SGCTT patients. The benefit of using risk-adapted therapeutic approaches in CSI SGCTTs patients is evident.

[Surgical treatment of metastases and its impact on prognosis in patients with metastatic colorectal carcinoma]. / Chirurgická liecba metastáz a jej vplyv na prognózu u pacientov s metastatickým kolorektálnym karcinómom.

BACKGROUND: Approximately one quarter of patients with colorectal carcinoma (CRC) have distant metastases at initial dia-gnosis and almost 50% will develop them during the disease course. Only radical surgical resection of metastases improves clinical outcome and offers a chance of longterm survival. Initially unresectable metastases can become resectable after downsizing with systemic therapy. MATERIALS AND METHODS: Retrospective analysis included 21 patients with metastatic colorectal carcinoma (mCRC) who were treated from 2006 to 2012 and underwent resection/ ablation of metastases. Fourteen patients had resection at initial dia-gnosis of metastatic disease and seven patients achieved operability of metastases after systemic treatment. The aim of the analysis was to evaluate surgical treatment of metastases and its impact on prognosis in patients with mCRC in correlation with clinical pathological  genetic factors. RESULTS: The median age of patients was 59 years. Fourteen patients had metastases in the liver, one patient had metastases in the lungs, two patients had combination of hepatic and extrahepatic metastases and four patients had metastases in other regions. During median followup of 47 months, 17 patients experienced disease progression and 13 patients died. Median progression free survival (PFS) after surgical resection/ ablation of metastases was 17 months (95% CI 13.8820.12), and median overall survival (OS) was 48 months (95% CI 38.7757.23). KRAS mutation was detected in 47.6% of patients and BRAF mutation in 9.5% of patients. Patients with BRAF mutation had worse PFS (median = 10 months vs 17 months; p = 0.523) and OS (median = 22 months vs 51 months; p = 0.05) compared to patients with BRAF wildtype. No difference was observed in PFS and OS between the patients with one or more metastatic lesions and between the patients who underwent resection/ ablation of metastases initially or after systemic treatment. CONCLUSION: These data suggest that resection/ ablation of metastases significantly improves prognosis of patients with mCRC and support the notion that mutated BRAF has a strong negative prognostic significance also in the group of patients, who undergo surgical resection/ ablation of metastatic lesions.

Pineal germ cell tumors: review.

BACKGROUND: Primary intracranial germ cell tumors represent a rare category of neoplasms, which occur in children and young adults. The WHO classification divides intracranial tumors into germinomas and non-germinomas. The most frequent locality of these tumors is pineal and suprasellar region. Clinical signs and symptoms depend on the localization of the tumour - they most commonly include signs of increased intracranial pressure, Parinauds syndrome, bitemporal hemianopsy and signs of endocrine deficiency. Gadolinium enhanced MRI scan of the brain is the imagining examination of choice in the diagnostic strategy of intracranial germ cell tumors. However, the imagining studies do not provide sufficient information about histological type; therefore, biopsy is necessary. The exception represents cases with characteristically increased levels of tumor markers (AFP and ß-HCG) measured in the serum and cere-brospinal fluid. CASE: A pineal germ cell tumor was observed in a 26-year-old male with presentation of an eye-sight disorder with focusing difficulty and photophobia, accompanied by intensive fatigue and sleepiness, nausea with occasional vomiting, intermittent headaches and Parinauds syndrome. MRI examination of the brain showed tumor expansion in the pineal region and in the right part of the mesencephalon. Radical extirpation of the tumor in the pineal region was performed. The follow-up MRI scan of the brain revealed relapse of the disease. The patient underwent craniospinal radiation therapy with subsequent postoperative chemotherapy (regimen cisplatin and etoposide), three cycles in total. Currently, the patient is 30 months after finishing of oncological treatment in clinical remission of the disease. CONCLUSION: The treatment and prognosis of this neoplasm differ between particular categories. Germinomas have better survival rates than non-germinomas. A 5-year survival rate of germinoma patients after application of radiotherapy alone was > 90% of cases. The addition of chemotherapy lead to a decrease of the dose and minimalization of the irradiated area, with achievement of fewer side effects without a decrease of the curability. Non-germinomas are less radiosensitive than germinomas, but after the application of the adjuvant chemotherapy, survival benefit was achieved. However, the optimal management of these tumors remains controversial.

Mesenchymal stem cells - a promising perspective in the orofacial cleft surgery.

Autologous bone grafts provide the golden standard for closure of oronasal fistulas in the cleft palate. Augmentation may be performed also by homografts and various xenogenic or alloplastic materials to prevent morbidity at the donor site but they may cause many problems (transmission of infections, immune response etc.). All the mentioned approaches also often reveal recurrences of the fistulas and prolong suffering of the cleft patients. Combination of mesenchymal stem cells (MSCs) and so called "platelet gel" seems to be a perspective method in this way. The platelet gel contains hydroxyapatite particles mixed with platelet rich plasma coagulated under effect of the calcium ions. The MSCs from the pelvic bone marrow aspirate are cultivated on a scaffold (collagen membrane) for 3-4 weeks before placement into the cleft defect. The method provides promising results in the alveolar clefts. Authors document a successful case of the secondary surgery in 25-year-old man with the unilateral complete cleft (Fig. 5, Ref. 10).

Bevacizumab in combination with chemotherapy in the first-line treatment of metastatic colorectal carcinoma.

Colorectal carcinoma (CRC) is a malignancy of worldwide increased incidence. The vast majority of all CRC cases occur in patients older than age 50. The initial stage at the time of diagnosis has a strong influence on the overall survival (OS). According to AJCC sixth edition system, 5-year stage-specific survivals are over 90% in stage I, but only approximately 8% in stage IV [1]. Chemotherapy in combination with biological treatment has improved response rates (RR), with prolongation of progression free survival (PFS) and OS. Important role in treatment of metastatic colorectal carcinoma (mCRC) plays surgical resection of metastases. Multidisciplinary cooperation between medical oncologist, surgeon, radiologist and radiotherapist is necessary to achieve the best therapeutic results. The aim of our analysis was to describe the efficacy of bevacizumab used in combination with chemotherapy in the first-line setting and to evaluate frequency of thromboembolic complications during the treatment. The analysis included 58 patients with mCRC, who have been treated with first-line chemotherapy in combination with bevacizumab at the St. Elizabeth Cancer Institute in Bratislava since 2006 and first assessed for the first therapeutic results in October 2010. The clinical benefit after the treatment represented by overall response rate (ORR) and stable disease (SD) was achieved in 87.93% of patients, and surgical resection of metastases after therapy underwent 12.07% of patients. Median time to progression (TTP) was 8 months and median OS evaluated in October 2011 was 27 months. Mutation status of KRAS gene had no influence on the effectiveness of treatment and BRAF mutations exhibited a strong negative prognostic significance. Thromboembolic complications were present in 17.24%.

An unusual presentation of testicular cancer.

We report two rare cases of patients presenting with unusual symptoms, which led to the diagnosis of a germ cell tumor. Metastatic germ cell tumor of testis involving the gastrointestinal tract and causing the occult gastrointestinal bleeding is described in the first case. The second patient is reported to have limbic encephalitis with positive serum for Ma2 antibodies (antibodies against neuronal proteins) and parallel malignant germ cell tumor diagnosis (Fig. 4, Scheme 2, Ref. 12). Full Text (Free, PDF) www.bmj.sk.

STK11/LKB1 germline mutations in the first Peutz-Jeghers syndrome patients identified in Slovakia.

Peutz-Jeghers syndrome (PJS) is characterized by number of hamartomatous polyps in the gastrointestinal tract and by mucocutaneous hypermelanocytic lesions at different sites. Older patients have an increased risk of the cancers of small intestine, stomach, pancreas, colon, esophagus, ovary, testis, uterus, breast and lung. In majority of PJS cases, the germline mutations in serine/threonine kinase STK11/LKB1 gene were found to be associated with disease. Here we report the results of a first mutational screen of STK11/LKB1 in PJS patients characterized in Slovak population. The first patient with unusual carcinoma of duodenum was a sporadic case and carried c.842delC change residing in a mutational C6 repeat hotspot. Neither the polyp nor the tumor of the patient displayed the loss of heterozygosity at the site of mutation suggesting different mechanism involved in the formation of polyp and tumor in this case. The second patient belonged to a three-generation family with typical PJS features but not cancers. Interestingly, the patient displayed concomitant occurrence of adenomatous and hamartomatous polyps. Molecular analysis revealed an IVS2+1A>G mutation that alters the second intron 5' splice site and was shown to lead to aberrant splicing mediated by the U12-dependent spliceosome. The same mutation was present in the 9 affected members of the family but in none of their normal relatives. We also observed novel c. IVS2+61G>A unclassified variant, and recurrent IVS2+24G>T and 3UTR+129C>T polymorphisms. Based on the achieved results, we could offer predictive genetic testing and counseling to other members of the patient's families.