Testicular sperm extraction (TESE) may provide spermatozoa for attempts at fertility with assisted reproduction; however, the physiological effects of TESE on testicular function are not well understood. In order to evaluate the effects of TESE on the testis, 64 patients were evaluated after TESE for non-obstructive azoospermia with physical examinations, serial scrotal sonography, histological analyses and evaluation of the success of repeated sperm retrieval attempts. At 3 months after TESE, 82% of evaluated patients had ultrasonographic abnormalities in the testis suggesting resolving inflammation or haematoma at the biopsy site. By 6 months, these acute inflammatory changes typically resolved leaving linear scars or calcifications. Two patients had documented impaired testicular blood flow, with complete devascularization of the testis for one patient after TESE with multiple biopsies. Repeat TESE procedures were far more likely to retrieve spermatozoa if the second TESE attempt was performed >6 months after the initial TESE procedure (80%), relative to those performed within 6 months (25%). Transient adverse physiological effects are common in the testis for up to 6 months after TESE. In addition, permanent devascularization of the testis can occur following TESE procedures with multiple biopsies. The risk of this complication may be minimized by using an open biopsy technique with optical magnification to directly identify testicular vessels.

Renal cell carcinoma (RCC), the most common human kidney cancer, is frequently infiltrated with tumorassociated macrophages (TAM) that can promote malignant progression. Here, we show that TAMs isolated from human RCC produce substantial amounts of the proinflammatory chemokine CCL2 and immunosuppressive cytokine IL-10, in addition to enhanced eicosanoid production via an activated 15-lipoxygenase-2 (15-LOX2) pathway. TAMs isolated from RCC tumors had a high 15-LOX2 expression and secreted substantial amounts of 15(S)-hydroxyeicosatetraenoic acid, its major bioactive lipid product. Inhibition of lipoxygenase activity significantly reduced production of CCL2 and IL-10 by RCC TAMs. In addition, TAMs isolated from RCC were capable of inducing in T lymphocytes, the pivotal T regulatory cell transcription factor forkhead box P3 (FOXP3), and the inhibitory cytotoxic T-lymphocyte antigen 4 (CTLA-4) coreceptor. However, this TAMmediated induction of FOXP3 and CTLA-4 in T cells was independent of lipoxygenase and could not be reversed by inhibiting lipoxygenase activity. Collectively, our results show that TAMs, often present in RCCs, display enhanced 15-LOX2 activity that contributes to RCC-related inflammation, immunosuppression, and malignant progression. Furthermore, we show that TAMs mediate the development of immune tolerance through both 15-LOX2-dependent and 15-LOX2-independent pathways. We propose that manipulating LOX-dependent arachidonic acid metabolism in the tumor microenvironment could offer new strategies to block cancer-related inflammation and immune escape in patients with RCC. Cancer Res; 71(20); 6400-9. Ó2011 AACR.

Critical examination of the most advanced pattern of spermatogenesis from open diagnostic testis biopsy allows prediction of sperm retrieval success with testicular sperm extraction. In this study population spermatozoa were retrieved in 58% of attempts. When this testicular sperm was used with intracytoplasmic sperm injection, clinical pregnancy rate was 55% for men with nonobstructive azoospermia.

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Varicocelectomy can increase serum testosterone for infertile men with varicoceles. Although improvement in serum testosterone does not necessarily cause a direct improvement in semen quality, varicocelectomy may improve hormonal and spermatogenic function.

Purpose Chemokines are involved in cancer-related inflammation and malignant progression. In this study we evaluated expression of CCR8 and its natural cognate ligand CCL1 in patients with urothelial carcinomas of bladder and renal cell carcinomas. Experimental Design We examined CCR8 expression in peripheral blood and tumor tissues from patients with bladder and renal carcinomas. CCR8-positive myeloid cells were isolated from cancer tissues with magnetic beads and tested in vitro for cytokine production and ability to modulate T cell function. Results We demonstrate that monocytic and granulocytic myeloid cell subsets in peripheral blood of cancer patients with urothelial and renal carcinomas display increased expression of chemokine receptor CCR8. Up-regulated expression of CCR8 is also detected within human cancer tissues and primarily limited to tumor-associated macrophages (TAMs). When isolated, CD11b+CCR8+ cell subset produces the highest levels of pro-inflammatory and pro-angiogenic factors among intratumoral CD11b myeloid cells. Tumor-infiltrating CD11b+CCR8+ cells selectively display activated Stat3 and are capable of inducing FoxP3 expression in autologous T lymphocytes. Primary human tumors produce substantial amounts of the natural CCR8 ligand CCL1. Conclusions This study provides the first evidence that CCR8+ myeloid cell subset is expanded in cancer patients. Elevated secretion of CCL1 by tumors, increased presence of CCR8+ myeloid cells in peripheral blood and cancer tissues indicate that CCL1/CCR8 axis is a component of cancer-related inflammation and may contribute to immune evasion. Obtained results also implicate that blockade of CCR8 signals may provide an attractive strategy for therapeutic intervention in human urothelial and renal cancers.

Varicocelectomy can increase serum testosterone for infertile men with varicoceles. Although improvement in serum testosterone does not necessarily cause a direct improvement in semen quality, varicocelectomy may improve hormonal and spermatogenic function.

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