Hirofumi Izaki

Laparoscopic ureterolithotomy: our experience with 74 cases.

Objectives:  We retrospectively evaluated our experience with a relatively uncommon procedure, the laparoscopic ureterolithotomy, for the treatment of ureteral stones.

Role of phosphatidylinositol-3 kinase/Akt pathway in bladder cancer cell apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand

TRAIL/Apo2L is a pro‐apoptotic cytokine that is capable of inducing apoptosis in a wide variety of cancer cells but not in normal cells. Among various molecular strategies by which cancer cells evade apoptosis, PI3K/Akt signaling represents a dominant survival pathway. In this report, we investigated the role of PI3K/Akt pathway in TRAIL‐induced apoptotic death in human bladder cancer cells. We observed that RT4 cells had very low level of constitutively active Akt and were sensitive to TRAIL, whereas UM‐UC‐3 and T24 cells had higher levels of constitutively active Akt and were resistant to TRAIL. Downregulation of constitutively active Akt by PI3K inhibitors, wortmannin and LY294002, reversed cellular resistance to TRAIL. However, transfecting constitutively active Akt into RT4 cells increased Akt activity and inhibited TRAIL‐induced apoptosis. These results suggest that elevated Akt activity protects UM‐UC‐3 and T24 cells from TRAIL‐induced apoptosis, and the PI3K/Akt signaling might inhibit apoptotic signals. Thus, the modulation of Akt activity by combining pharmacological drugs or genetic alterations of the Akt expression could induce cellular responsiveness to TRAIL and PI3K/Akt signaling pathway could serve as a novel target for therapeutic intervention in bladder cancer. (Cancer Sci 2006; 97: 1093–1098)

The Radioprotective 105/MD-1 Complex Contributes to Diet-Induced Obesity and Adipose Tissue Inflammation

Recent accumulating evidence suggests that innate immunity is associated with obesity-induced chronic inflammation and metabolic disorders. Here, we show that a Toll-like receptor (TLR) protein, radioprotective 105 (RP105)/myeloid differentiation protein (MD)-1 complex, contributes to high-fat diet (HFD)-induced obesity, adipose tissue inflammation, and insulin resistance. An HFD dramatically increased RP105 mRNA and protein expression in stromal vascular fraction of epididymal white adipose tissue (eWAT) in wild-type (WT) mice. RP105 mRNA expression also was significantly increased in the visceral adipose tissue of obese human subjects relative to nonobese subjects. The RP105/MD-1 complex was expressed by most adipose tissue macrophages (ATMs). An HFD increased RP105/MD-1 expression on the M1 subset of ATMs that accumulate in eWAT. Macrophages also acquired this characteristic in coculture with 3T3-L1 adipocytes. RP105 knockout (KO) and MD-1 KO mice had less HFD-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance compared with wild-type (WT) and TLR4 KO mice. Finally, the saturated fatty acids, palmitic and stearic acids, are endogenous ligands for TLR4, but they did not activate RP105/MD-1. Thus, the RP105/MD-1 complex is a major mediator of adipose tissue inflammation independent of TLR4 signaling and may represent a novel therapeutic target for obesity-associated metabolic disorders.

Bilateral adrenal myelolipoma associated with adrenogenital syndrome

Abstract  Adrenal myelolipoma is a rare benign tumor, occasionally reported in association with endocrine disorders. We report herein a case of bilateral adrenal myelolipoma associated with adrenogenital syndrome caused by 21‐hydroxylase deficiency. A diagnosis of 21‐hydroxylase deficiency was confirmed by mutation analysis of the CYP21 gene. Our case represents only the second case of bilateral adrenal myelolipoma associated with adrenogenital syndrome caused by 21‐hydroxylase deficiency.

Transperitoneal versus retroperitoneal laparoscopic radical nephrectomy: a comparative study.

Objectives:  To compare perioperative outcome of transperitoneal and retroperitoneal approaches during laparoscopic radical nephrectomy (LRN) and to identify selection criteria for each approach.

Indications for laparoscopic adrenalectomy for non-functional adrenal tumor with hypertension: usefulness of adrenocortical scintigraphy.

Aim:  Laparoscopic adrenalectomy is currently indicated for biochemically and clinically functional adrenal tumors and potentially malignant tumors of the adrenal glands. Non‐functional adenomas greater than 5 cm in diameter of the adrenal gland are generally considered to represent potentially malignant tumors. The present study shows indications of laparoscopic adrenalectomy for non‐functional adrenal tumors with hypertension in a retrospective fashion.

Dual involvement of growth arrest-specific gene 6 in the early phase of human IgA nephropathy.

Background Gas6 is a growth factor that causes proliferation of mesangial cells in the development of glomerulonephritis. Gas6 can bind to three kinds of receptors; Axl, Dtk, and Mer. However, their expression and functions are not entirely clear in the different glomerular cell types. Meanwhile, representative cell cycle regulatory protein p27 has been reported to be expressed in podocytes in normal glomeruli with decreased expression in proliferating glomeruli, which inversely correlated with mesangial proliferation in human IgA nephropathy (IgAN). Methods The aim of this study is to clarify Gas6 involvement in the progression of IgAN. Expression of Gas6/Axl/Dtk was examined in 31 biopsy proven IgAN cases. We compared the expression levels with histological severity or clinical data. Moreover, we investigated the expression of Gas6 and its receptors in cultured podocytes. Results In 28 of 31 cases, Gas6 was upregulated mainly in podocytes. In the other 3 cases, Gas6 expression was induced in endothelial and mesangial cells, which was similar to animal nephritis models. Among 28 podocyte type cases, the expression level of Gas6 correlated with the mesangial hypercellularity score of IgAN Oxford classification and urine protein excretion. It also inversely correlated with p27 expression in glomeruli. As for the receptors, Axl was mainly expressed in endothelial and mesangial cells, while Dtk was expressed in podocytes. In vitro, Dtk was expressed in cultured murine podocytes, and the expression of p27 was decreased by Gas6 stimulation. Conclusions Gas6 was uniquely upregulated in either endothelial/mesangial cells or podocytes in IgAN. The expression pattern can be used as a marker to classify IgAN. Gas6 has a possibility to be involved in not only mesangial proliferation via Axl, but also podocyte injury via Dtk in IgAN.

Laparoscopic Findings of Transverse Testicular Ectopia

Transverse testicular ectopia (TTE) is an extremely rare congenital anomaly in which both testes descend through the same inguinal canal. We report an 8-month-old male with TTE and hypospadias. To help manage the patient, we conducted laparoscopy to elucidate the anatomy of the spermatic cord of the ectopic testis. On laparoscopy, we clearly identified the spermatic cord of the right ectopic testis. In addition, the laparoscopic guide was helpful when doing the trans-septal orchidopexy, in that the ectopic testis could be precisely discriminated without confusion as to the laterality of the testes. Long-term follow-up at 32 months confirmed that both testes were properly positioned in the scrotum and had a good consistency.

Clinical research of renal vein control using Hem‐o‐lok clips in laparoscopic nephrectomy

Abstract  Control of the renal vein represents a crucial step in laparoscopic nephrectomy. Although endovascular gastrointestinal anastomosis (GIA) staplers have generally been used for renal vein control because of the large diameter of the vessel, Hem‐o‐lok clips have recently been used for renal artery control. GIA staplers are expensive and can malfunction on rare occasions, resulting in severe complications. We evaluated renal vein control using Hem‐o‐lok clips (adaptive vascular width 7–16 mm) in laparoscopic nephrectomy. Since April 2004, we have ligated renal arteries using Hem‐o‐lok clips. From June 2004, this method was applied for renal vein control in 40 laparoscopic nephrectomies. After renal pedicle dissection, renal pedicle ligation was accomplished using extra large (XL) Hem‐o‐lok clips on both the renal arteries and veins by placing two clips on the patient side and one clip on the specimen side. Ligation times for obtaining renal vein control were compared between XL Hem‐o‐lok clips and GIA staplers in 40 cases before June 2004. Vascular control using XL Hem‐o‐lok clips was successful in all 40 cases, without any slipping of clips or uncontrolled bleeding. After renal pedicle dissection, ligation time for achieving renal vein control was 167.0 ± 48 s (range: 122–295 s) using XL Hem‐o‐lok clips (mean, three clips) and 68 ± 24.0 s (range: 54–150 s) using a GIA stapler. XL Hem‐o‐lok clips allow safe and reliable control of renal veins in laparoscopic nephrectomy. Ligation time is only 100 s longer than using a GIA stapler. In addition, costs are reduced by more than 90% compared to GIA stapling.

Strategy for Repeat Prostate Biopsy: Predictors of Positive Biopsy and Additional Biopsy Location

Purpose: We analyzed patterns of tumor distribution in radical prostatectomy specimens from patients with repeat biopsies to determine additional appropriate biopsy locations for repeat biopsy. Methods: Between January 2000 and June 2005, a total of 382 patients underwent transrectal ultrasound-guided prostate biopsy. Of these, 47 patients underwent repeat biopsy. Radical prostatectomy was performed for 7 of 22 cancer-positive cases. The 7 specimens were superimposed to create an idealized prostate gland at 3 levels: apex, mid-prostate, and base. We compared these tumor maps with those from 35 initial biopsy positive patients. Results: Prostate cancer was detected in 22 of 47 patients who underwent repeat biopsy. Tumor mapping showed that tumors detected on repeat biopsy in comparison with tumor maps of initial biopsy were dense at the periurethral area of the apex in prostate. Conclusions: Additional biopsy cores taken from periurethral area of the apex on repeat biopsy might further enhance the detection of cancers.