Correlation between extraocular muscle enlargement and thyroid autoantibodies in thyroid eye disease.

PURPOSE: This study aimed to investigate the factors affecting extraocular muscle enlargement in thyroid eye disease (TED). STUDY DESIGN: Retrospective study. METHODS: The thyroid-stimulating hormone (TSH) receptor antibody (TRAb), thyroid-stimulating antibody (TSAb), antithyroid peroxidase antibody (ATPO), and antithyroglobulin antibody (ATG) levels in patients diagnosed with TED who underwent orbital magnetic resonance imaging were assessed. The control group comprised the contralateral eye of patients who underwent orbital magnetic resonance imaging (MRI) for unilateral eyelid tumors or orbital disease. The thickness of the bilateral rectus muscles and superior oblique muscles was measured on orbital MRI. Muscle enlargement was classified as unilateral/bilateral and symmetric/asymmetric. The effects of age, sex, smoking history, TSH, thyroid hormone, and thyroid autoantibodies on the muscle thickness and number of enlarged muscles were assessed by use of simple and multiple regression analyses. RESULTS: The TED and control groups comprised 41 and 44 cases, respectively. The positivity rate of TSAb in patients with TED was 92.7% higher than that of the other autoantibodies. Muscle enlargement was observed in 29 of the 41 cases (70.7%). Older age and higher TSAb levels were identified as significant factors affecting the total muscle thickness and number of enlarged muscles. Bilateral muscle enlargement and asymmetrical muscle enlargement were observed in 17 (58.6%) and 23 (79.3%) of the 29 cases, respectively. The TSAb levels and age had no significant effect on the type of muscle enlargement. CONCLUSIONS: TSAb showed significant associations with extraocular muscle enlargement. Measurement of TSAb, rather than of TRAb, may be more useful for diagnosing extraocular muscle enlargement in patients with TED.

Effects of Pparγ1 deletion on late-stage murine embryogenesis and cells that undergo endocycle.

Peroxisome proliferator-activated receptor (PPAR) γ1, a nuclear receptor, is abundant in the murine placenta during the late stage of pregnancy (E15-E16), although its functional roles remain unclear. PPARγ1 is encoded by two splicing isoforms, namely Pparγ1canonical and Pparγ1sv, and its embryonic loss leads to early (E10) embryonic lethality. Thus, we generated knockout (KO) mice that carried only one of the isoforms to obtain a milder phenotype. Pparγ1sv-KO mice were viable and fertile, whereas Pparγ1canonical-KO mice failed to recover around the weaning age. Pparγ1canonical-KO embryos developed normally up to 15.5 dpc, followed by growth delays after that. The junctional zone of Pparγ1canonical-KO placentas severely infiltrated the labyrinth, and maternal blood sinuses were dilated. In the wild-type, PPARγ1 was highly expressed in sinusoidal trophoblast giant cells (S-TGCs), peaking at 15.5 dpc. Pparγ1canonical-KO abolished PPARγ1 expression in S-TGCs. Notably, the S-TGCs had unusually enlarged nuclei and often occupied maternal vascular spaces, disturbing the organization of the fine labyrinth structure. Gene expression analyses of Pparγ1canonical-KO placentas indicated enhanced S-phase cell cycle signatures. EdU-positive S-TGCs in Pparγ1canonical-KO placentas were greater in number than those in wild-type placentas, suggesting that the cells continued to endoreplicate in the mutant placentas. These results indicate that PPARγ1, a known cell cycle arrest mediator, is involved in the transition of TGCs undergoing endocycling to the terminal differentiation stage in the placentas. Therefore, PPARγ1 deficiency, induced through genetic manipulation, leads to placental insufficiency.

Insulin stimulates transport of organic anion compounds mediated by organic anion transporting polypeptide 2B1 in the human intestinal cell line Caco-2.

Organic anion transporting polypeptide 2B1 (OATP2B1) is the major uptake transporter in the intestine, and transports various clinically used therapeutic agents. Insulin acts through the insulin receptor in targeted cells, and Rab8A is one of the insulin signaling pathways. The small intestine in humans also expresses insulin receptor and Rab8A. It has been reported that insulin stimulates peptide transporter 1 (PEPT1) expression at the apical membrane and increases uptake of PEPT1 substrates in small intestine epithelial model cells (Caco-2 cells). However, the effect of insulin on OATP2B1 in the small intestine has not been fully investigated. We found that Rab8A was associated with OATP2B1-mediated estrone-3-sulfate (E3S) uptake. Insulin stimulated the uptake of E3S by Caco-2 cells and the enhancement was sustained for 120 min. The Vmax value of E3S uptake significantly increased upon insulin exposure. Caco-2 cells treated with insulin showed increased OATP2B1 expression at the cell surface. The apical-to-basal transport of E3S was also increased by insulin. The increase of E3S transport was inhibited by the cold condition (4 °C) or the OATP2B1 inhibitor, taurocholate. These results indicate that insulin acts on the small intestine to increase OATP2B1-mediated absorption.

Reactive oxygen species derived from xanthine oxidase interrupt dimerization of breast cancer resistance protein, resulting in suppression of uric acid excretion to the intestinal lumen.

The prevalence of hyperuricemia/gout increases with aging. However, the effect of aging on function for excretion of uric acid to out of the body has not been clarified. We found that ileal uric acid clearance in middle-aged rats (11-12 months) was decreased compared with that in young rats (2 months). In middle-aged rats, xanthine oxidase (XO) activity in the ileum was significantly higher than that in young rats. Inosine-induced reactive oxygen species (ROS), which are derived from XO, also decreased ileal uric acid clearance. ROS derived from XO decreased the active homodimer level of breast cancer resistance protein (BCRP), which is a uric acid efflux transporter, in the ileum. Pre-administration of allopurinol recovered the BCRP homodimer level, resulting in the recovering ileal uric acid clearance. Moreover, we investigated the effects of ROS derived from XO on BCRP homodimer level directly in Caco-2 cells using hypoxanthine. Treatment with hypoxanthine decreased BCRP homodimer level. Treatment with hypoxanthine induced mitochondrial dysfunction, suggesting that the decreasing BCRP homodimer level might be caused by mitochondrial dysfunction. In conclusion, ROS derived from XO decrease BCRP homodimer level, resulting in suppression of function for uric acid excretion to the ileal lumen. ROS derived from XO may cause the suppression of function of the ileum for the excretion of uric acid with aging. The results of our study provide a new insight into the causes of increasing hyperuricemia/gout prevalence with aging.

Quercetin-3-rhamnoglucoside (rutin) stimulates transport of organic anion compounds mediated by organic anion transporting polypeptide 2B1.

Quercetin-3-rhamnoglucoside (rutin) has a wide spectrum of biochemical and pharmacological activities. Rutin is absorbed mainly in its unmetabolized form. Organic anion transporting polypeptide (OATP) 2B1 is a major uptake transporter in the intestine. Thus, it is important for the prevention of adverse events to understand drug interactions mediated by OATP2B1 in the absorption process. This study assessed the effect of rutin on transport by OATP2B1. Rutin stimulated the uptake of estrone-3-sulfate (E-3-S), taurocholic acid (TCA), cholic acid (CA) and rosuvastatin by OATP2B1, but not p-coumaric acid or ferulic acid. The EC50 of rutin for transport by OATP2B1 was 2.32 µm. The Km value of E-3-S for OATP2B1 in the presence of rutin (9.21 µm) was almost the same as that in the absence of rutin (8.53 µm). On the other hand, the Vmax of E-3-S transport by OATP2B1 in the presence of rutin (270 pmol/mg protein/min) was 1.2-fold higher than that in the absence of rutin (218 pmol/mg protein/min). Moreover, the expression level of OATP2B1 on the cell membrane was increased by treatment with rutin for 5 min without alteration of the total OATP2B1 expression level. Moreover, the increase in the localization of OATP2B1 at the cell surface was detected by the immunocytochemistry. The stimulatory effect of rutin is a little weak but may affect the absorption of OATP2B1 substrates, because rutin is taken daily in foods and its intestinal concentration would reach the stimulatory range of OATP2B1.

Effect of oxidative stress on expression and function of human and rat organic anion transporting polypeptides in the liver.

Reactive oxygen species (ROS) have physiological function and involve alteration of physical state. However, it is not clear effect of oxidative stress on pharmacokinetics. Organic anion transporting polypeptides (human: OATPs, rodent: Oatps) are important for uptake of endogenous and exogenous compounds into hepatocytes. Thus, alteration of OATPs/Oatps expression level may affect pharmacokinetics of various drugs. In this study, we investigated the alteration of OATPs/Oatps expression levels and function by oxidative stress, and the effect of alteration of those on pharmacokinetics of a typical OATPs/Oatps substrate pravastatin. OATPs/Oatps expression levels and function were altered by H2O2-induced oxidative stress in in vitro experiments. The alteration of Oatps expression by oxidative stress also occurred in in vivo experiments. Oatp1a1, Oatp1a4 and Oatp1b2 expression in the liver were decreased in rats fed powdery diet containing 2% inosine, which induces oxidative stress through activation of xanthine oxidase, for 1 day. The decrease in Oatps expression levels by oxidative stress caused the suppression of pravastatin uptake to the liver, and resulted in high plasma concentration of pravastatin and low biliary excretion. In conclusion, oxidative stress induces alteration of OATPs/Oatps expression and function in hepatocytes, resulting in alteration of pharmacokinetics of their substrates.

Intestinal ischemia-reperfusion suppresses biliary excretion of hepatic organic anion transporting polypeptides substrate.

PURPOSE: Intestinal ischemia-reperfusion (I/R) causes gut dysfunction and promotes multi-organ failure. The liver and kidney can be affected by multi-organ failure after intestinal I/R. Organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) are recognized in a broad spectrum from endogenous compounds to xenobiotics, including clinically important drugs. Therefore, it is important for understanding the pharmacokinetics to obtain evidence of alterations in OATPs and OATs expression and transport activities. In the present study, we investigated the expression of rat Oatps and Oats after intestinal I/R. METHODS: We used intestinal ischemia-reperfusion (I/R) model rats. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Plasma concentration and biliary excretion of sulfobromophthalein (BSP), which is used as a model compound of organic anion drugs, were measured after intravenous administration in intestinal I/R rats. RESULTS: Although Oat1 and Oat3 mRNA levels were not altered in the kidney, Oatp1a1, Oatp1b2 and Oatp2b1 mRNA levels in the liver were significantly decreased at 1-6 h after intestinal I/R. Moreover, Oatp1a1 and Oatp2b1 protein expression levels were decreased at 1 h after intestinal I/R. Plasma concentration of BSP, which is a typical substrate of Oatps, in intestinal I/R rats reperfused 1 h was increased than that in sham-operated rats. Moreover, the area under the concentration-time curve (AUC0₋90) in intestinal I/R rats reperfused 1 h was significantly increased than that in sham-operated rats. The total clearance (CL(tot)) and the biliary clearance (CL(bile)) in intestinal I/R rats reperfused 1 h were significantly decreased than those in sham-operated rats. CONCLUSIONS: Oatp1a1 and Oatp2b1 expression levels are decreased by intestinal I/R. The decreases in these transporters cause alteration of pharmacokinetics of organic anion compound. The newly found influence of intestinal I/R on the expression and function of Oatps may be a key to perform appropriate drug therapy.

Intestinal ischemia-reperfusion increases efflux for uric acid via paracellular route in the intestine, but decreases that via transcellular route mediated by BCRP.

PURPOSE: Uric acid is thought to be one of the most important antioxidants in human biological fluids. Intestinal ischemia-reperfusion (I/R) is an important factor associated with high rates of morbidity and mortality. Reactive oxygen species (ROS) are responsible for intestinal I/R injury. The aim of this study was to clarify the efflux for uric acid from the intestine after intestinal I/R. METHODS: We used intestinal ischemia-reperfusion (I/R) model rats. Serosal to mucosal flux for [¹4C]-uric acid was assessed by using Ussing-type diffusion chambers. BCRP/Bcrp expression was assessed by Western blot analysis. Caco-2 cells were used for a model of the intestinal epithelium, and rotenone was used as a mitochondrial dysfunction inducer. RESULTS: Serosal to mucosal flux for uric acid was increased after intestinal I/R, and that for mannitol was also increased. Ko143, which is a BCRP inhibitor, did not affect the uric acid transport. The decreasing uric acid transport mediated by Bcrp was caused by decrease in the level of Bcrp homodimer, bridged by an S-S bond. The suppression of Bcrp S-S bond formation was associated with mitochondrial dysfunction. Moreover, BCRP S-S bond formation activity was decreased by rotenone in Caco-2 cells. CONCLUSIONS: Serosal to mucosal flux for uric acid is significantly increased via the paracelluler route, but that via the transcellular route mediated by Bcrp is decreased after intestinal I/R. The decreasing uric acid flux mediated by Bcrp is caused by suppression of Bcrp S-S bond formation. This suppression of Bcrp S-S bond formation may be related to mitochondrial dysfunction.

The decrease in farnesoid X receptor, pregnane X receptor and constitutive androstane receptor in the liver after intestinal ischemia-reperfusion.

PURPOSE: Intestinal ischemia-reperfusion (I/R) damages remote organs, including the liver, and promotes multi-organ failure (MOF). However, the molecular mechanisms underlying acute liver injury after intestinal I/R have not been completely elucidated. Farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR) regulate metabolizing enzymes and transporters, and coordinately prevent hepatotoxicity reflecting an inability of appropriate excretion of endogenous toxic compounds. In this study, we assessed FXR, PXR and CAR expression levels and their localization levels in nuclei in the liver after intestinal I/R. We also investigated the effect of IL-6 on FXR, PXR and CAR expression levels and their localization levels in nuclei in in vitro experiments. METHODS: We used intestinal I/R model rats. Moreover, HepG2 cells were used in in vitro study. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Nuclear receptor localization in nuclei was analyzed by Western blotting using nuclear extracts. RESULTS: FXR and PXR expression levels began to be decreased at 3 h, and FXR, PXR and CAR expression levels were decreased at 6 h after intestinal I/R. The localization levels of FXR, PXR and CAR in nuclei began to be decreased at 3 h, and all of them were decreased at 6 h after intestinal I/R. In HepG2 cells, FXR, PXR and CAR expression levels were decreased by 0.5-1 ng/mL, 0.5-100 ng/mL and 100 ng/mL IL-6 treatment for 24 h, respectively. FXR, PXR and CAR localization levels in nuclei were suppressed by 0.5-10 ng/mL, 10-100 ng/mL and 10-100 ng/mL IL-6 treatment for 24 h, respectively. CONCLUSIONS: FXR, PXR and CAR expression levels are decreased in the liver after intestinal I/R. IL-6 is one of main causes the decreases in expressions of these receptors.

Long-term recurrence-free survivor after laparoscopic removal of solitary adrenal metastasis from endometrial adenocarcinoma.

Solitary adrenal metastasis from endometrial adenocarcinoma is extremely rare. We report herein the case of a laparoscopically resected solitary adrenal metastasis originating from endometrial adenocarcinoma. The patient was a 55-year-old woman who had undergone total abdominal hysterectomy for stage IIIc endometrial carcinoma, followed by 7 courses of adjuvant chemotherapy comprising carboplatin and paclitaxel. However, the patient developed an isolated right adrenal metastasis 15 months postoperatively. The solitary adrenal metastasis (diameter, 5.7 cm) was removed laparoscopically. The patient has now been in good health without recurrence for 5 years and 7 months after laparoscopic surgery. To the best of our knowledge, this is the first case of solitary adrenal metastasis originating from endometrial adenocarcinoma that is controlled for the long term by successful laparoscopic resection.

The role of actinin-4 in bladder cancer invasion.

OBJECTIVES: To examine actinin-4 expression levels in bladder cancer, in particular its levels during cellular growth and invasion. Actinin-4 is an actin-binding protein that is associated with cell motility and cancer metastasis. METHODS: Relative messenger ribonucleic acid (mRNA) and protein expression of actinin-4 in normal bladder and bladder cancer cell lines was determined by quantitative real-time polymerase chain reaction and Western blot analysis. Actinin-4 expression was also localized in bladder cancer cells and tissues using immunohistochemistry. The growth and invasion activity of bladder cancer cells was evaluated using cell growth and in vitro cell invasion assays, and compared with that of bladder cancer cells treated with actinin-4 small interfering ribonucleic acids. RESULTS: Actinin-4 mRNA and protein levels were elevated in bladder cancer cells that are known to exhibit increased growth and invasion activity. Protein expression was predominantly observed in the cytoplasm of the invasive bladder cancer cells and tissues. Treatment of bladder cancer cell lines with actinin-4 small interfering ribonucleic acids suppressed the invasive potential of the cells, but did not alter their growth. CONCLUSIONS: The current study demonstrates that actinin-4 mRNA and protein levels are elevated in bladder cancer cells lines that exhibit increased growth and invasion activity. In addition, actinin-4 knockdown inhibited invasion of bladder cancer cells, but did not alter their growth. In conclusion, we hypothesize that the accumulation of actinin-4 in the cell cytoplasm is related to an increased susceptibility of tumor invasion and metastasis.

[A case of retroperitoneal serous cyst resected by laparoscopic surgery].

A 40-year-old woman was referred to our hospital because of pain extending from the left lateral abdomen to the left inferior limb. The abdominal computed tomography (CT) revealed an 8x7x12 cm retroperitoneal serous cystic mass. The serum carcinoembryogenic antigen (CEA) level was slightly elevated to 2.7 ng/ml. Therefore, we suspected it to be malignant, and we performed laparoscopic resection carefully. The retroperitoneal cyst was not adherent to the surrounding tissues and was easily dissected and removed under laparoscopy. Carbohydrale antigen (CA)19-9, CA125 and CEA levels in the fluid were elevated, but a cytology of the fluid was negative and no malignant sign was seen in the cyst wall. To our knowledge, this is the second reported case of retroperitoneal serous cyst resected by laparoscopic surgery in the Japanese literature.

Effect of vascular endothelial growth factor and its receptor inhibitor on proliferation and invasion in bladder cancer.

BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors are major regulators of cancer cell growth and metastases. We investigated the association between serum VEGF levels and clinicopathological parameters in bladder cancer patients. We also evaluated the effects of VEGF and its receptor inhibitor on proliferation and invasion in bladder cancer cell lines. METHODS: Serum VEGF levels were measured in 52 patients with bladder cancer and 45 healthy controls. In highly invasive bladder cancer cell lines (T-24, UMUC-3 and J82), we assessed the effect of VEGF on proliferation and invasion of bladder cancer cell lines. The effect of VEGF receptor (VEGFR) tyrosine kinase inhibitor against bladder cancer cell lines was also measured. RESULTS: Serum levels of VEGF were significantly higher in patients with muscular invasive bladder cancer than in patients with superficial bladder cancer (p < 0.005). VEGF increased tumor proliferation in a dose-dependent manner in all cell lines. VEGFR-2 tyrosine kinase inhibitor inhibited proliferation in all three cell lines, and inhibited invasion in T24. CONCLUSIONS: In bladder cancer, the serum VEGF level correlates significantly with muscular invasiveness. This study suggests that VEGF promotes tumor proliferation and invasion through VEGFR-2. VEGF-targeted therapy may be effective in treating invasive bladder cancers.

[Case of renal arterial pseudoaneurysm after laparoscopic partial nephrectomy].

A 41 year-old man with a history of diabetes mellitus underwent computed tomography for screening on August 2007. The CT revealed an enhancing 3.0 cm mass in the middle pole of the left kidney. We diagnosed as renal cancer, clinical stage T1aN0M0. Then he underwent laparoscopic left partial nephrectomy. The pathological result was renal cell carcinoma, G2 > G1, pT1a. On post operative day 12, he appeared a gross hematuria and dysuria, then he was rehospitalized due to drop of hemoglobin and bladder tamponade. Enhanced CT showed left renal artery pseudoaneurysm. He underwent selective coil embolization of left renal artery pseudoaneurysm. After that he repeated gross hematuria, and appeared bladder tamponade again. On POD 65 he underwent selective coil embolization again. Since then the patient recovered uneventfully.

[Clinical study of prostate specific antigen failure after radical prostatectomy for prostate cancer: a single center experience].

Between January 1996 and December 2007, 111 patients with prostate cancer underwent radical prostatectomy, including 34 who received preoperative hormonal therapy. In this study, we reviewed 77 patients who did not undergo neoadjuvant hormonal therapy. The mean age was 65.5 years old and followup time was 40.7 months. The clinical stage was T1c in 60 patients, T2 in 16, and T3 in 1. Prostate specific antigen (PSA) at diagnosis ranged from 3.44 to 46.08 ng/ml (mean 10.18). At our institution, PSA failure after surgery was defined as PSA elevation above 0.2 ng/ml. The pathological stage was pT2 in 59 patients, pT3a in 11, pT3b in 7 and pN + (obturator lymph node) in none. The surgical margin was positive in 29.3% of the pT2 patients and 68.8% of the pT3 patients. Sixteen patients (20.8%) had PSA failure. PSA values at diagnosis and pathological T stage were significantly relevant to PSA failure. Patients with PSA failure underwent radiation therapy or hormonal therapy as a salvage adjuvant therapy. The PSA level was controlled well in majority of the patients. Only one patient died of cancer. In conclusion, 33 out of 111 patients who underwent radical prostatectomy had PSA failure. Sixteen of the 77 patients who were not given neoadjuvant therapy had PSA failure. The significant factors related to PSA failure were PSA values at diagnosis and pathological T stage.

Low transscrotal orchidopexy is a safe and effective approach for undescended testes distal to the external inguinal ring.

OBJECTIVES: To review the results of a low transscrotal orchidopexy in patients with palpable undescended testes located distal to the external inguinal ring. METHODS: Between July 1998 and June 2005, transscrotal orchidopexy with a single low scrotal incision was performed in 32 patients for 49 undescended testes. The indication was an undescended testis that lay distal to the external ring and could be pulled down manually into the scrotum under general anesthesia. RESULTS: All testes that were treated with the low transscrotal approach were successfully fixed in the middle or lower portion of the scrotum. The mean operative time was significantly shorter for the low transscrotal orchidopexy (45.2 min) than for the inguinal orchidopexy (66.6 min) for 107 undescended testes at similar locations. The median follow-up duration was 39.1 months; all testes except 1 (97.7%) were located in a good position within the scrotum and had a good consistency; 1 testis ascended postoperatively and required inguinal orchidopexy. No inguinal hernias or hydroceles occurred after the surgery. CONCLUSIONS: Low transscrotal orchidopexy appears to be an excellent alternative to the standard inguinal orchidopexy for undescended testes located distal to the external inguinal ring.

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. METHODS: Over a 7-year period, 100 consecutive patients (median age 62 years, range 20-80) underwent LRN for a renal tumor with clinical stage T1a-T3a. The first choice approach was retroperitoneal. The transperitoneal approach was chosen in selected cases based on tumor characteristics. Thirty-three patients underwent the transperitoneal approach, and 67 had the retroperitoneal approach. Perioperative parameters including operative time, blood loss and complications and pathology data were retrospectively analyzed. RESULTS: Overall, 33 transperitoneal laparoscopic radical nephrectomies (TLRN) and 67 retroperitoneal laparoscopic radical nephrectomies (RLRN) were carried out. There was a statistically significant difference between the two groups in terms of size (5.3 vs 3.0 cm, P < 0.0001) and clinical T stage (higher in the TLRN group, P < 0.0001) of the tumors. Intraoperative complications included bradycardia, pneumothorax, renal vein injury, and renal artery injury in the TLRN group, and pneumothorax in the RLRN group. There were no differences in terms of operative time, blood loss and tumor grade between the two groups. CONCLUSIONS: Retroperitoneal and transperitoneal approaches yielded excellent surgical outcomes. The transperitoneal approach should be chosen based on tumor size and location to minimize vascular injury.

[Laparoscopic ureterolithotomy for ureteral calculi: three case reports].

With the development of extracorporeal shock wave lithotripsy (ESWL), improved endourologic instrumentation, and medical dissolution therapy, the need for open ureterolithotomy has become less common. Open operation is occasionally necessary when less invasive techniques fail. As in many of the surgical specialties, laparoscopy has become more common in urologic surgery. We recently experienced three cases of ureteral stones, which were treated by laparoscopic ureterolithotomy. The stones were all large and impacted stones. The patients were a 73-year-old man and two 34-year-old men. All procedures were performed by a retroperitoneal approach. We used Roticulator endo mini-shears resourcefully, when we incised the ureteral wall. After surgery, all three patients were stone-free, and hydronephrosis was improved.

[Case of tuberculous epididymitis caused by intravesical BCG therapy].

Intravesical Bacillus Calmette-Guerin (BCG) therapy is commonly used against superficial urothelial carcinoma, especially carcinoma in situ (CIS). We report a case of tuberculous epididymitis that occurred during a course of intravesical BCG therapy. A 76-year-old man had received intravesical BCG therapy for multiple superficial bladder cancer and CIS in prostatic urethra after transurethral resection of bladder tumor (TUR-Bt). He recognized hard nodules in the left scrotum after 4 times intravesical BCG therapy. Skin fistula in scrotum occurred 5 months later. We performed left orchiectomy with scrotum skin resection. Histological diagnosis was tuberculous epididymitis. Postoperatively, he was administered chemotherapy consisting of isoniazid, refampin and ethambutol.

Prognostic significance of serum hepatocyte growth factor in clear cell renal cell carcinoma: comparison with serum vascular endothelial growth factor.

No adequate serum predictive biomarker currently exists, which can identify the activity of renal cell carcinoma (RCC). We investigate the association of serum hepatocyte growth factor (HGF) and serum vascular endothelial growth factor (VEGF) levels with clinicopathologic parameters in untreated clear cell RCC patients. We measured serum levels of HGF and VEGF in 45 patients with untreated clear cell RCC and 45 healthy controls using an enzyme-linked immunosorbent assay (ELISA). Patients with clear cell RCC had significantly higher serum HGF and VEGF concentrations than healthy subjects: median, 1070.7 versus 728.3 pg/ml (p<0.0001) for HGF; and median, 397.5 versus 245.6 pg/ml (p=0.0003) for VEGF. We found a significant correlation between serum level of HGF and clinical stage and tumor grade. Survival of patients with high serum HGF (>1150 pg/ml) was significantly reduced compared to patients with low serum HGF concentrations (p=0.0044). In patients with nuclear grade 2 or high stage RCC, the higher serum HGF group exhibited significantly lower cause-specific survival (p=0.0087 and p< 0.05, respectively). No significant difference was observed between serum VEGF levels and cause-specific survival rate. Serum HGF might be a diagnostic and prognostic indicator in clear cell RCC, especially for patients with grade 2 or high stage RCC.