Combination of DNA methylation biomarkers with multiparametric magnetic resonance and ultrasound imaging fusion biopsy to detect the local spread of prostate cancer.

BACKGROUND: This study aimed to investigate the extent of field cancerization adjacent to index lesions in prostate cancer (PCa) by measuring DNA methylation of selected tumor suppressor genes in the perifocal tissue of PCa not visible on multiparametric magnetic resonanse imaging (mpMRI) for the safe zone of focal therapy identification. METHODS: A total of 272 patients were enrolled in this study, 44 patients' tissue biosamples were included in the field cancerization research, and 272 urine samples were included in the urine-based test development. Targeted biopsies were performed using the mpMRI/ultrasoundimage fusion system. RESULTS: Quantitative analysis revealed significantly higher DNA methylation levels of RARB, RASSF1, GSTP1 & APC genes in the index lesion compared with perifocal tissue samples 10 mm away from it (p < 0.0001). Notably, the RARB, GSTP1 & APC and RARB, RASSF1, GSTP1 & APC biomarker combinations exhibited the highest sensitivity and specificity comparing the extent of DNA methylation in index lesions and noncancerous prostate tissues 20 mm away (both area under the curve [AUC] = 0.98; p < 0.0001). The analysis of the potential urinary biomarkers showed that the combination of all four DNA methylation biomarkers with prostate-specific antigen (PSA) or PSA density (PSAD) in the blood significantly improves the detection of clinically significant PCa (csPCa). The combination of the four-biomarker test with PSAD allowed the identification of csPCa with ≥90% sensitivity and specificity. CONCLUSION: Thus, this study suggests that for focal therapy by region target hemi-ablation, the safe distance from the index lesion is no less than 10 mm. Noninvasive urine DNA methylation tests in combination with PSAD could be used for further follow-up of the patients, but larger prospective studies with external validation are needed.

Efficacy of focal high-dose-rate brachytherapy in the treatment of patients diagnosed with low or favourable: intermediate-risk prostate cancer-a protocol for a randomised controlled trial.

INTRODUCTION: Prostate cancer (PCa) is men's second most predominant cancer worldwide. Because the prostate-specific antigen test is used in diagnostics, PCa is more often diagnosed in the early stages, making radical treatment of the disease possible. However, it is estimated that over a million men worldwide suffer from radical treatment-related complications. Thus, focal treatment has been proposed as a solution, which aims to destroy the predominant lesson that determines the progression of the disease. The main objective of our study is to compare the quality of life and efficacy of patients diagnosed with PCa before and after the treatment with focal high-dose-rate brachytherapy and to compare results with focal low-dose-rate brachytherapy and active surveillance. METHODS AND ANALYSIS: 150 patients diagnosed with low-risk or favourable intermediate-risk PCa who meet the inclusion criteria will be enrolled in the study. Patients are going to be randomly assigned to the study groups: focal high-dose-rate brachytherapy (group 1), focal low-dose-rate brachytherapy (group 2) and active surveillance (group 3). The study's primary outcomes are quality of life after the procedure and time without biochemical disease recurrence. The secondary outcomes are early and late genitourinary and gastrointestinal reactions after the focal high-dose and low-dose-rate brachytherapies and evaluation of the importance and significance of in vivo dosimetry used for high-dose-rate brachytherapy. ETHICS AND DISSEMINATION: Bioethics committee approval was obtained before this study. The trial results will be published in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER: Vilnius regional bioethics committee; approval ID 2022/6-1438-911.

Urine Molecular Biomarkers for Detection and Follow-Up of Small Renal Masses.

Active surveillance (AS) is the best strategy for small renal masses (SRMs) management; however, reliable methods for early detection and disease aggressiveness prediction are urgently needed. The aim of the present study was to validate DNA methylation biomarkers for non-invasive SRM detection and prognosis. The levels of methylated genes TFAP2B, TAC1, PCDH8, ZNF677, FLRT2, and FBN2 were evaluated in 165 serial urine samples prospectively collected from 39 patients diagnosed with SRM, specifically renal cell carcinoma (RCC), before and during the AS via quantitative methylation-specific polymerase chain reaction. Voided urine samples from 92 asymptomatic volunteers were used as the control. Significantly higher methylated TFAP2B, TAC1, PCDH8, ZNF677, and FLRT2 levels and/or frequencies were detected in SRM patients' urine samples as compared to the control. The highest diagnostic power (AUC = 0.74) was observed for the four biomarkers panel with 92% sensitivity and 52% specificity. Methylated PCDH8 level positively correlated with SRM size at diagnosis, while TFAP2B had the opposite effect and was related to SRM progression. To sum up, SRMs contribute significantly to the amount of methylated DNA detectable in urine, which might be used for very early RCC detection. Moreover, PCDH8 and TFAP2B methylation have the potential to be prognostic biomarkers for SRMs.

Cutaneous Melanoma with Tonsillar Metastasis: Treatment with Cryoablation.

Metastasis of cutaneous melanoma to the oral cavity is a rare condition. Male patient with cutaneous melanoma metastasis to right tonsil 2 years after radical skin lesion resection was treated with surgery: tonsillectomy and later resection of soft palate were performed. Two years later the patient was diagnosed with progressive disease to right tonsil and soft palate. Rapid inoperable relapse was detected six months later. The patient underwent two procedures of palliative cryoablation of the metastasis. Postoperative course was uneventful. Patient died 7 months later due to progression of the disease. Cryoablation alone or together with surgery may be a relatively safe option for treatment of inoperable disease of head and neck tumours.

Von Hippel-Lindau syndrome and renal tumours: radiological diagnostic and treatment options. A case report and literature review.

BACKGROUND: Von Hippel-Lindau disease (VHL) is a rare autosomal dominant syndrome diagnosed for 1 out of 36000-45000 newborns and 90% of the patients have a clinical manifestation before 65 years of age. Affected individuals have an increased risk of developing tumours in several organs or their systems. The most common tumours are retinal or central nervous system hemangioblastomas (60-80%) and VHL-associated renal lesions. Contrast-enhanced computer tomography (CECT) is the gold standard for the diagnosis and characterization of renal tumours. The best treatment option for VHL syndrome-caused renal tumours are nephron-sparing treatment techniques (cryotherapy, radiofrequency, or microwave ablation), which require imaging control. All these innovative treatment techniques are extremely important for VHL patients, because they increase the quality of life by staving off renal dialysis and preventing distant metastases. CASE REPORT: Our case report presents a 16-year-old female with multiple renal cysts observed on ultrasound examination and clinically and molecularly diagnosed with Von Hippel-Lindau syndrome (deletion of the entire VHL gene). After that, for past 11 years multiple renal tumours were removed by cryoablation and patient monitoring on contrast-enhanced magnetic resonance (MRI) and CECT control scans was conducted. CONCLUSIONS: Active multidisciplinary patient follow-up, routine radiological examinations, and correct treatment tactics allow controlling the  progression of renal cell carcinoma and other tumours associated with VHL syndrome, maintaining a normal organ function for a long time, and preventing distant metastases and fatal disease outcomes.

Small Intestinal Inflammatory Myofibroblastic Metastasis in the Left Ventricle.

Inflammatory myofibroblastic tumors (IMTs) are rare and usually appear in childhood and adolescence. These tumors often take a benign course, but tend to reoccur in a quarter of cases and metastasize locally. Distant IMT metastases are extremely uncommon. To our knowledge, metastatic spread to the heart has not been reported. We present a case of a 43-year-old woman with small intestinal IMT metastatic spread to the cavity of the left ventricle, stomach, liver, vertebra, and pelvic bones. The cardiac tumor was resected, and the patient survived for 9 months. She dies because the progression of IMT at other sites.

Extralobar pulmonary sequestration.

Prevalence of pulmonary sequestration accounts for up to 6.4% of all congenital pulmonary malformations. We report on a 40-year-old woman who underwent excision of an aberrant solid retroperitoneal mass in the left subdiaphragmatic area. The mass was identified to be an extralobar pulmonary sequestration. The diagnosis could be made without surgery by percutaneous tissue biopsy and imaging. We encourage keeping in mind pulmonary sequestration anomaly presenting as an aberrant retroperitoneal mass. The aim of this case report is to increase awareness about the condition and review the criteria for its definitive diagnosis and treatment.

Cystic lymph node metastasis in papillary thyroid carcinoma.

BACKGROUND: Thyroid cancer, especially papillary carcinoma, metastasizes most often into cervical lymph nodes. Cervical ultrasound and ultrasound-guided fine-needle aspiration biopsy are the most sensitive modalities in detecting locoregional neck recurrence. OBJECTIVE: The aim of this study was to illustrate the ultrasound spectrum of lymph node metastases from papillary thyroid carcinoma. PATIENTS AND METHODS: During 1998-2002 years due to suspicion of recurrence of thyroid cancer, 75 ultrasound-guided fine-needle aspiration biopsies of regional lymph nodes were performed. Ultrasound examination of 75 patients with thyroid cancer (56 women and 19 men; mean age of patients was 54.67+/-12.89 years) was performed. All biopsies were performed on nonpalpable lesions (lymph node short axis < or =1.5 cm). RESULTS: A total of 75 ultrasound-guided fine-needle aspiration biopsies of regional lymph nodes under suspicion of malignancy were performed. Only 5 (6.7%) of the 75 lymph nodes were cystic with internal septation. Other 70 (93.3%) lymph nodes were solid. Cytopathological results of 75 ultrasound-guided fine-needle aspiration biopsies from regional cervical lymph nodes were noninformative in 4 (5.3%) cases, benign - 40 (53.4%), suspicion - 4 (5.3%), and malignant - 27 (36.0%) cases. Eighteen patients underwent surgery for regional lymph nodes. All cystic metastases were confirmed to be papillary thyroid carcinoma on pathologic examination. CONCLUSION: Ultrasound cannot exactly distinguish benign from malign lesions, but sonographic appearance can suggest malignancy and help in selection of the correct lymph nodes to aspirate with ultrasound-guided fine-needle aspiration biopsy. Cystic lymph node metastases may occur in papillary thyroid carcinoma. Cystic neck lesion patients with thyroid papillary carcinoma should always be verified with fine-needle aspiration biopsy.

[The frequency of malignant disease in cytological group of suspected cancer (ultrasound-guided fine-needle aspiration biopsy of nonpalpable thyroid nodules)]. / Piktybines ligos daznumas itariamo vezio (suspitio) citologineje grupeje (nepalpuojamu skydliaukes mazgu ultragarsu kontroliuojama aspiracine biopsija plona adata).

BACKGROUND: Fine-needle aspiration biopsy is the most important procedure for differentiating benign thyroid nodules from malignant ones. Traditionally, findings of fine-needle aspiration biopsy are divided into four categories: nondiagnostic, benign lesions, suspected cancer, and malignant lesions. Group suspicious for cancer largely involves follicular neoplasms as well as lesions with cytological features of malignancy. OBJECTIVE: The purpose of this study was to establish the value of ultrasound-guided fine-needle aspiration biopsy in the diagnosis of nonpalpable thyroid cancer and to assess the frequency of malignant disease in the group of suspected cancer. PATIENTS AND METHODS: A total of 184 patients with nonpalpable thyroid nodules (less than 1.5 cm in diameter) were examined by means of ultrasound-guided fine-needle aspiration biopsy. Patients were included in the study based on sonographic findings implicating possible malignant nature of nodules. RESULTS. During 1997-2002, 204 ultrasound-guided fine-needle aspiration biopsies of thyroid nodules were performed; findings were nondiagnostic in 5.9% of cases. In 59.8% of cases, cytological examination revealed benign lesions; in 11.8%, suspected cancer; and in 22.5%, malignant lesions. Eighty-five patients underwent subsequent surgery with histological examination of specimens obtained. In 45 cases, cytological diagnosis of malignant or suspected thyroid cancer was confirmed by histological examination after surgery. CONCLUSION: We conclude that ultrasound-guided fine-needle aspiration biopsy has a high accuracy in the diagnostic evaluation of nonpalpable thyroid nodule with cytological features of malignancy. However, fine-needle aspiration biopsy is not effective diagnostic method for differentiating benign thyroid nodules from malignant ones in follicular neoplasm group.