Immunotherapy of Genitourinary Malignancies

Most cancer patients are treated with some combination of surgery, radiation, and chemotherapy. Despite recent advances in local therapy with curative intent, chemotherapeutic treatments for metastatic disease often remain unsatisfying due to severe side effects and incomplete long-term remission. Therefore, the evaluation of novel therapeutic options is of great interest. Conventional, along with newer treatment strategies target the immune system that suppresses genitourinary (GU) malignancies. Metastatic renal cell carcinoma and non-muscle-invasive bladder caner represent the most immune-responsive types of all human cancer. This review examines the rationale and emerging evidence supporting the anticancer activity of immunotherapy, against GU malignancies

Rapid Increase of the Serum PSA Level in Response to High-Intensity Focused Ultrasound Therapy may be a Potential Indicator of Biochemical Recurrence of Low- and Intermediate-Risk Prostate Cancer

Objectives To determine the incidence and magnitude of the rapid increase in the serum PSA (riPSA) level after high-intensity focused ultrasound (HIFU) therapy for prostate cancer, and its correlation with clinical factors. Methods A total of 176 patients with localized prostate cancer underwent HIFU therapy. Serum riPSA was determined on the basis of the same criteria as those for “PSA bounce”, ie, an increase of ≥0.2 ng/ml with a spontaneous return to the prebounce level or lower. Patients were stratified according to neoadjuvant PSA level, T stage, risk group, age, Gleason score, pretreatment PSA level, post-treatment PSA nadir, and number of HIFU sessions. Results riPSA was seen in 53% of patients during a median follow-up period of 43 months. A PSA nadir was achieved within 3 months for 85.1% of the treatments. In all cases, onset of riPSA was seen two days after HIFU therapy, and the median magnitude was 23.69 ng/ml. A magnitude of >2 ng/ml was seen in 89.4% of cases. Univariate analysis revealed that patients with riPSA were associated with usage of hormonal therapy and the post-treatment PSA nadir level. Multivariate Cox regression analysis revealed that riPSA and the number of HIFU sessions were predictors of biochemical recurrence. A significant statistical association was found between the presence of riPSA and the risk of biochemical failure only in the low- and intermediate-risk group. Conclusion Patients treated with HIFU who experience post-treatment riPSA may have an increased risk of biochemical recurrence, especially in non-high-risk patients

Adult Wilms' tumor with calcification untreated for 5 years – a case report

BACKGROUND: Wilms' tumor is rarely found in adults and there are no established treatment guidelines for such tumors in adults. Whereas calcification is a common finding in neuroblastoma, it is considered uncommon in Wilms' tumor. CASE PRESENTATION: We report a case of adult Wilms' tumor with calcification in a 22-year-old man. He had been initially referred to our hospital with a chief complaint of right flank pain 5 years previously, when abdominal computed tomography had revealed focal calcification at the upper pole of the right kidney. Although we planned further assessment, he did not revisit our hospital again until 5 years later, again because of right flank pain. Ultrasound and computed tomography scan revealed a large mass lesion with calcification in the right kidney, invasive to the hepatic lobe. The patient underwent curative right nephrectomy and partial right hepatic lobectomy. Pathological analysis demonstrated a nephroblastoma (Wilms' tumor) with predominant epithelial histology infiltrating the hepatic lobe. The patient has been well without tumor recurrence for 15 months after surgery. CONCLUSIONS: Calcification may be a sign of slow tumor gowth and possibly a favorable prognosis in cases of adult Wilms' tumor

Surgical correction of buried penis after traffic accident – a case report

BACKGROUND: Buried penis, most commonly seen in children, is particularly debilitating in adults, resulting in inability to void while standing and it also affects vaginal penetration. We report a case of buried penis due to a traffic accident, which caused dislocation of the fractured pubic bone that shifted inside and pulled the penis by its suspensory ligament. CASE PRESENTATION: A 55-year-old man was admitted to our hospital with a chief complaint of hidden penis while in the sitting position. He had suffered a pelvic fracture in a traffic accident four years previously, and his penis was covered with suprapubic fat when he was in a sitting position. He was unable to have sexual intercourse. We performed a penile lengthening procedure, including inverse V-Y-plasty of the dorsal skin of the penile root, suspensory desmotomy and fat removal, under general anesthesia. There was a good cosmetic result with satisfactory penile erection, which allowed successful sexual intercourse after surgery. CONCULSION: We performed penile elongation surgery with inverse V-Y-plasty of the dorsal skin of the penile root, suspensory desmotomy, and fat removal. Surgical treatment of buried penis achieves marked aesthetic and functional improvement, and benefits the majority of patients, resulting in satisfactory erection and successful sexual intercourse

Her yol Roma'ya varmaz!

Taha Toros Arşivi, Dosya Adı: Taha Torosİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

Mast cells regulate CD4+ T-cell differentiation in the absence of antigen presentation

Producción CientíficaBackground: Given their unique capacity for antigen uptake, processing, and presentation, antigen-presenting cells (APCs) are critical for initiating and regulating innate and adaptive immune responses. We have previously shown the role of nicotinamide adenine dinucleotide (NAD+) in T-cell differentiation independently of the cytokine milieu, whereas the precise mechanisms remained unknown. Objective: The objective of this study is to further dissect the mechanism of actions of NAD+ and determine the effect of APCs on NAD+-mediated T-cell activation. Methods: Isolated dendritic cells and bone marrow–derived mast cells (MCs) were used to characterize the mechanisms of action of NAD+ on CD4+ T-cell fate in vitro. Furthermore, NAD+-mediated CD4+ T-cell differentiation was investigated in vivo by using wild-type C57BL/6, MC−/−, MHC class II−/−, Wiskott-Aldrich syndrome protein (WASP)−/−, 5C.C7 recombination-activating gene 2 (Rag2)−/−, and CD11b-DTR transgenic mice. Finally, we tested the physiologic effect of NAD+ on the systemic immune response in the context of Listeria monocytogenes infection. Results: Our in vivo and in vitro findings indicate that after NAD+ administration, MCs exclusively promote CD4+ T-cell differentiation, both in the absence of antigen and independently of major APCs. Moreover, we found that MCs mediated CD4+ T-cell differentiation independently of MHC II and T-cell receptor signaling machinery. More importantly, although treatment with NAD+ resulted in decreased MHC II expression on CD11c+ cells, MC-mediated CD4+ T-cell differentiation rendered mice resistant to administration of lethal doses of L monocytogenes. Conclusions: Collectively, our study unravels a novel cellular and molecular pathway that regulates innate and adaptive immunity through MCs exclusively and underscores the therapeutic potential of NAD+ in the context of primary immunodeficiencies and antimicrobial resistance.National Institutes of Health (grants R01NS073635 , R01MH110438 , R01HL096795 , U01HL126497 and R01AG039449)Instituto de Salud Carlos III (grant PI10/02 511)Fundación Ramón Areces (grant CIVP16A1843