Differences in the Central Energy Metabolism of Cancer Cells between Conventional 2D and Novel 3D Culture Systems.

The conventional two-dimensional (2D) culture is available as an in vitro experimental model. However, the culture system reportedly does not recapitulate the in vivo cancer microenvironment. We recently developed a tissueoid cell culture system using Cellbed, which resembles the loose connective tissue in living organisms. The present study performed 2D and three-dimensional (3D) culture using prostate and bladder cancer cell lines and a comprehensive metabolome analysis. Compared to 3D, the 2D culture had significantly lower levels of most metabolites. The 3D culture system did not impair mitochondrial function in the cancer cells and produce energy through the mitochondria simultaneously with aerobic glycolysis. Conversely, ATP production, biomass (nucleotides, amino acids, lipids and NADPH) synthesis and redox balance maintenance were conducted in 3D culture. In contrast, in 2D culture, biomass production was delayed due to the suppression of metabolic activity. The 3D metabolome analysis using the tissueoid cell culture system capable of in vivo cancer cell culture yielded results consistent with previously reported cancer metabolism theories. This system is expected to be an essential experimental tool in a wide range of cancer research fields, especially in preclinical stages while transitioning from in vitro to in vivo.

A risk stratification model based on four novel biomarkers predicts prognosis for patients with renal cell carcinoma.

BACKGROUND: Accurate prediction of the prognosis of RCC using a single biomarker is challenging due to the genetic heterogeneity of the disease. However, it is essential to develop an accurate system to allow better patient selection for optimal treatment strategies. ARL4C, ECT2, SOD2, and STEAP3 are novel molecular biomarkers identified in earlier studies as survival-related genes by comprehensive analyses of 43 primary RCC tissues and RCC cell lines. METHODS: To develop a prognostic model based on these multiple biomarkers, the expression of four biomarkers ARL4C, ECT2, SOD2, and STEAP3 in primary RCC tissue were semi-quantitatively investigated by immunohistochemical analysis in an independent cohort of 97 patients who underwent nephrectomy, and the clinical significance of these biomarkers were analyzed by survival analysis using Kaplan-Meier curves. The prognostic model was constructed by calculation of the contribution score to prognosis of each biomarker on Cox regression analysis, and its prognostic performance was validated. RESULTS: Patients whose tumors had high expression of the individual biomarkers had shorter cancer-specific survival (CSS) from the time of primary nephrectomy. The prognostic model based on four biomarkers segregated the patients into a high- and low-risk scored group according to defined cut-off value. This approach was more robust in predicting CSS compared to each single biomarker alone in the total of 97 patients with RCC. Especially in the 36 metastatic RCC patients, our prognostic model could more accurately predict early events within 2 years of diagnosis of metastasis. In addition, high risk-scored patients with particular strong SOD2 expression had a much worse prognosis in 25 patients with metastatic RCC who were treated with molecular targeting agents. CONCLUSIONS: Our findings indicate that a prognostic model based on four novel biomarkers provides valuable data for prediction of clinical prognosis and useful information for considering the follow-up conditions and therapeutic strategies for patients with primary and metastatic RCC.

The location of the bladder neck in postoperative cystography predicts continence convalescence after radical prostatectomy.

BACKGROUND: This study was conducted to determine whether the location of the bladder neck in postoperative cystography predicts recovery of continence after radical prostatectomy. METHODS: Between 2008 and 2015, 203 patients who underwent laparoscopic radical prostatectomy (LRP, n = 99) and robot assisted radical prostatectomy (RARP, n = 104) were analyzed. The location of the bladder neck was visualized by postoperative routine cystography, and quantitative evaluation of the bladder neck position was performed according to the bladder neck to pubic symphysis (BNPS) ratio proposed by Olgin et al. (J Endourol, 2014). Recovery of continence was defined as no pad use or one security pad per day. To determine the predictive factors for recovery of continence at 1, 3, 6 and 12 months, several parameters were analyzed using logistic regression analysis, including age (≤68 vs. > 68, BMI (≤23.4 vs. > 23.4 kg/m2), surgical procedure (LRP vs. RARP), prostate volume (≤38 vs. > 38 mL), nerve-sparing technique, vesico-urethral anastomosis leakage, and BNPS ratio (≤0.59 vs. > 0.59). RESULTS: The mean postoperative follow-up was 1131 days (79-2880). At 1, 3, 6 and 12 months after surgery, continence recovery rates were 25, 53, 68 and 81%, respectively. Although older age (> 68) and RARP were significant risk factors for incontinence within 3 months, neither was significant after 6 months. A high BNPS ratio (> 0.59) was the only significant risk factor for the persistence of incontinence at all observation points, up to 12 months. CONCLUSIONS: A lower bladder neck position after prostatectomy predicts prolonged incontinence.

Mechanisms of Tumor Growth Inhibition by Depletion of γ-Glutamylcyclotransferase (GGCT): A Novel Molecular Target for Anticancer Therapy.

γ-Glutamylcyclotransferase (GGCT), which is one of the major enzymes involved in glutathione metabolism, is upregulated in a wide range of cancers-glioma, breast, lung, esophageal, gastric, colorectal, urinary bladder, prostate, cervical, ovarian cancers and osteosarcoma-and promotes cancer progression; its depletion leads to the suppression of proliferation, invasion, and migration of cancer cells. It has been demonstrated that the suppression or inhibition of GGCT has an antitumor effect in cancer-bearing xenograft mice. Based on these observations, GGCT is now recognized as a promising therapeutic target in various cancers. This review summarizes recent advances on the mechanisms of the antitumor activity of GGCT inhibition.

[Laparoscopic Partial Adrenalectomy for Primary Aldosteronism Combined with Cushing's Syndrome : Report of a Case].

A 65-year-old man was referred to our hospital with a chief complaint of hyperglycemia. Computed tomography showed left clear-bordered adrenal mass. The serum aldosterone/renin ratio was elevated, and the low-dose dexamethasone suppression test revealed no suppression of serum cortisol. Adrenal venous samplingdemonstrated excess secretion of cortisol from the left adrenal gland, and excess secretion of aldosterone from bilateral adrenal glands. Laparoscopic left partial adrenalectomy for primary aldosteronism combined with Cushing's syndrome was performed. The result was insulin withdrawal and the reduction of antihypertensive drugs.

[The urinary bacterial flora in patients with cutaneous ureterostomy].

Twenty-four patients with cutaneous ureterostomy at least 6 months after surgery were included in this study. Single-J ureteral catheters were indwelt in 7 patients. Pouch urine was cultured and analyzed from asymptomatic patients and from those with pyelonephritis. Forty-eight bacterial strains were isolated from asymptomatic patients. Thirty-five of these strains consisting of 18 species were isolated from the patients without ureteral catheters. Enterococcus (E.) faecalis (20.0%), Klebsiella pneumoniae (11.4%) and Proteus (P.) mirabilis (11. 4%) were isolated at high frequency. One methicilline-resistant coagulase-negative Staphylococcus (MRCNS) strain was isolated. Thirteen bacterial strains consisting of 8 species were isolated from the patients with ureteral catheters. E. faecalis (23.1%), Eschericia (E.) coli (23.1%) and Pseudomonas (P.) aeruginosa (15.4%) were isolated at high frequency. One E. coli strain harboring extended-spectrum beta lactamase (ESBL) and one MRCNS strain were isolated. Pyelonephritis occurred in 5 patients 14 times during follow-up for at least 6 months after surgery. The patients with ureteral catheters suffered from pyelonephritis (4/7, 57.1%) more frequently as compared to the patients without catheters (1/17, 5.9%) (p = 0.014). P. aeruginosa (26.9%), E. faecium (15.4%), and P. mirabilis (11.5%) were isolated inhigh frequency. One E. coli strain harboring ESBL and one P. mirabilis strain harboring ESBL were isolated. In conclusion, insertion of ureteral catheters in a cutaneous ureterostomy is a strong risk factor for pyelonephritis and development of antibiotic-resistant bacteria. Therefore, urine culture is important in these patients who are under surveillance.

[Several treatments with endovascular stent graft for ureteroarterial fistula after construction of cutaneous ureterostomy : report of a case].

A 78-year-old man underwent a radical cystectomy and the construction of a cutaneous ureterostomy for bladder cancer. He had an 8 Fr single-J ureteral catheterindwelt for stomal stenosis caused by parastomal hernia. Thirty-one months after the operation, the patient was admitted with gross hematuria. Contrast-enhanced computed tomography showed a highly suspicious left uretero-iliac artery fistula (UIAF), which was finally diagnosed by angiography. A covered endovascular stent graft was placed in the left iliac artery, and the gross hematuria was resolved. Six months after the endovascular stenting, he had recurrent gross hematuria and underwent additional treatment with placement of a secondary stent graft. Two months later, a pseudoaneurysm developed in the left iliac artery, and emergency angiography was performed to treat an impending rupture of the aneurysm. During the angiography, a thrombus formed in the left iliac artery, and he died due to multiple organ failure caused by an infective thrombus and sepsis. Endovascular stent graft placement is a safe and effective treatment to manage the acute phase of ureteroarterial fistula. However, the long-term effectiveness of this treatment remains to be established.

Spinal Transection Switches the Effect of Metabotropic Glutamate Receptor Subtype 7 from the Facilitation to Inhibition of Ejaculation.

Metabotropic glutamate receptor subtype 7 (mGluR7) is a member of the group III mGluRs, which localize to presynaptic active zones of the central nervous system. We previously reported that mGluR7 knockout (KO) mice exhibit ejaculatory disorders, although they have normal sexual motivation. We hypothesized that mGluR7 regulates ejaculation by potentiating the excitability of the neural circuit in the lumbosacral spinal cord, because administration of the mGluR7-selective antagonist into that region inhibits drug-induced ejaculation. In the present study, to elucidate the mechanism of impaired ejaculation in mGluR7 KO mice, we eliminated the influence of the brain by spinal transection (spinalization). Unexpectedly, sexual responses of male mGluR7 KO mice were stronger than those of wild-type mice after spinalization. Histological examination indicated that mGluR7 controls sympathetic neurons as well as parasympathetic neurons. In view of the complexity of its synaptic regulation, mGluR7 might control ejaculation by multi-level and multi-modal mechanisms. Our study provides insight into the mechanism of ejaculation as well as a strategy for future therapies to treat ejaculatory disorders in humans.

Prognostic nutritional index of early post-pembrolizumab therapy predicts long-term survival in patients with advanced urothelial carcinoma.

Pembrolizumab has been widely used to treat advanced urothelial carcinoma that has progressed after first-line platinum-based chemotherapy. Because its clinical benefits are limited, biomarkers that can predict a good response to pembrolizumab are required. The prognostic nutritional index (PNI), calculated using the serum albumin level and peripheral lymphocyte count, has been evaluated as a predictive biomarker in cancer immunotherapy. The present study investigated the application of PNI as a predictive biomarker for pembrolizumab response in patients with advanced urothelial cancer. A retrospective study was conducted on 34 patients treated with pembrolizumab at Shiga University of Medical Science Hospital between January 2018 and July 2022. The posttreatment PNI (post-PNI) was calculated within 2 months of starting pembrolizumab. The present study investigated the association between post-PNI and objective response, overall survival (OS) and progression-free survival (PFS). The patient cohort was stratified into two categories, high and low post-PNI groups, with a cutoff value of post-PNI at 40. The higher post-PNI group demonstrated a better disease control rate than the lower post-PNI group (complete response + partial response + stable disease, 75 vs. 21%, P=0.004). Regarding median OS, the higher post-PNI group exhibited a significantly longer survival time than the lower post-PNI group (23.1 vs. 2.9 months, P<0.001). Similarly, the higher post-PNI group exhibited a significantly longer PFS than the lower post-PNI group (10.2 vs.1.9 months, P<0.001). Multivariate analysis showed that a higher post-PNI value was an independent predictor for OS (hazard ratio, 0.04; 95% confidence interval, 0.01-0.14; P<0.001) and PFS (hazard ratio, 0.12; 95% confidence interval, 0.04-0.35; P<0.001). The present study indicated that the post-PNI was a predictor of favorable clinical outcomes in patients treated with pembrolizumab for advanced urothelial carcinoma.

[Small intestinal metastasis from renal cell carcinoma: a case report].

A 52-year-old man who had been treated with sorafenib for lung metastasis of renal cell carcinoma (RCC) presented to our hospital with iron-deficiency anemia. He had undergone right nephrectomy for RCC (clear cell carcinoma, pT1bN0M0) 11 years ago and lung metastasis developed 6 years after the surgery. Although upper gastrointestinal endoscopy and colonoscopy were performed on suspicion of gastrointestinal bleeding, no abnormality was detected. Capsule endoscopy and single balloon small bowel endoscopy disclosed a hemorrhagic submucosal tumor in the jejunum. Laparoscopic partial jejunectomy was performed, and pathological examination indicated metastatic RCC to the small intestine. After the operation, anemia improved but he died 8 months later because of intrabronchial bleeding from the metastatic lesion of the lung. Metastatic RCC of the small intestine is relatively rare, its diagnosis is difficult. Recently, new diagnostic tools such as capsule endoscopy and balloon-assisted endoscopy have been developed, and they are useful in diagnosing gastrointestinal bleeding (OGIB) which can not be detected by traditional enteroscopy. If patients with advanced RCC show gastrointestinal bleeding of uncertain etiology, we should perform aggressive examination of the digestive tract with these diagnostic tools.

Transcriptome analysis of a dog model of congestive heart failure shows that collagen-related 2-oxoglutarate-dependent dioxygenases contribute to heart failure.

Fibrosis is an important pathological mechanism in heart failure (HF) and is associated with poor prognosis. We analyzed fibrosis in HF patients using transcriptomic data. Genes differentially expressed between normal control and congestive HF (CHF) dogs included P3H1, P3H2, P3H4, P4HA2, PLOD1 and PLOD3, which belong to the 2-oxoglutarate-dependent dioxygenases (2OGD) superfamily that stabilizes collagen during fibrosis. Quantitative polymerase chain reaction analysis demonstrated 2OGD gene expression was increased in CHF samples compared with normal left ventricle (LV) samples. 2OGD gene expression was repressed in angiotensin converting enzyme inhibitor-treated samples. These genes, activated the hydroxylation of proline or lysin residues of procollagen mediated by 2-oxoglutaric acid and O2, produce succinic acid and CO2. Metabolic analysis demonstrated the concentration of succinic acid was significantly increased in CHF samples compared with normal LV samples. Fibrosis was induced in human cardiac fibroblasts by TGF-ß1 treatment. After treatment, the gene and protein expressions of 2OGD, the concentration of succinic acid, and the oxygen consumption rate were increased compared with no treatment. This is the first study to show that collagen-related 2OGD genes contribute to HF during the induction of fibrosis and might be potential therapeutic targets for fibrosis and HF.

γ-Glutamylcyclotransferase, a novel regulator of HIF-1α expression, triggers aerobic glycolysis.

Metabolic reprogramming leading to aerobic glycolysis, termed the "Warburg effect," is a critical property of cancer cells. However, the precise mechanisms underlying this phenomenon are not fully understood. A growing body of evidence indicates that γ-glutamylcyclotransferase (GGCT), an enzyme involved in glutathione homeostasis that is highly expressed in many types of cancer, represents a promising therapeutic target. In this study, we identified GGCT as a novel regulator of hypoxia-inducible factor-1α (HIF-1α), a transcription factor that plays a role in hypoxia adaptation promoting aerobic glycolysis. In multiple human cancer cell lines, depletion of GGCT downregulated HIF-1α at the mRNA and protein levels. Conversely, in NIH3T3 mouse fibroblasts, overexpression of GGCT upregulated HIF-1α under normoxia. Moreover, depletion of GGCT downregulated HIF-1α downstream target genes involved in glycolysis, whereas overexpression of GGCT upregulated those genes. Metabolomic analysis revealed that modulation of GGCT expression induced a metabolic switch from the citric acid cycle to glycolysis under normoxia. In addition, we found that GGCT regulates expression of HIF-1α protein via the AMPK-mTORC1-4E-BP1 pathway in PC3 cells. Thus GGCT regulates the expression of HIF-1α in cancer cells, causing a switch to glycolysis.

Androgen receptor axis-targeted agents are not superior to conventional hormonal therapy for treatment of metastatic prostate cancer.

The present study aimed to use real-world Japanese data to compare the treatment outcome of conventional hormonal therapy to that of using androgen receptor axis-targeted (ARAT) agents for patients with metastatic castration-resistant prostate cancer. The overall survival between the conventional hormonal therapy group and the ARAT agent therapy group was compared using a group of 75 Japanese patients who were treated for metastatic castration-resistant prostate cancer. A subgroup analysis was carried out and the risk factors that affected overall survival (OS) were determined. The median OS from the time of prostate-specific antigen recurrence was 73.1 months in the ARAT group and 45.2 months in the conventional treatment group (P=0.414). Although OS tended to be slightly longer in the ARAT group, the difference between the groups was not significant. Subgroup analysis suggested that the therapeutic outcome of using ARAT agents tended to be less beneficial in patients who were older, and in those with a higher tumor volume or low Gleason grade. In conclusion, use of ARAT agents did not impart a significant survival benefit to patients with metastatic castration-resistant prostate cancer when compared with survival rates in response to conventional therapy. However, there was some clinical benefit when ARAT agents were used after patients developed castration-resistant prostate cancer. These findings suggest that up-front therapy using ARAT agents at the time of the initial hormone therapy can impart clinical benefit in Japanese patients with metastatic prostate cancer.

Long-Term Prostate-Specific Antigen Response on a Low-Dose Cabazitaxel Regimen for Metastatic Castration-Resistant Prostate Cancer: A Case Report.

BACKGROUND Cabazitaxel is a second-generation taxane approved for patients with metastatic castration-resistant prostate cancer (CRPC). Although cabazitaxel improves overall survival when used following docetaxel chemotherapy, duration of the clinical response is relatively short, and few patients achieve a long-term response. CASE REPORT A 71-year-old man with prostate adenocarcinoma with an initial prostate-specific antigen (PSA) level of 4956 ng/ml, Gleason score 4+5 and cTxN0M1b was referred to our department for treatment. Several therapeutic approaches, including androgen deprivation therapy, with a combination of bicalutamide and a luteinizing hormone-releasing hormone analogue, and 4 sequential hormonal therapies including flutamide, estramustine, enzalutamide, and abiraterone, all failed to prevent disease progression. Subsequently, after 5 cycles of docetaxel chemotherapy were also ineffective, cabazitaxel chemotherapy at a dose of 20 mg/m² together with prednisone and pegfilgrastim was initiated. The patient developed grade 4 thrombocytopenia during the first 4 cycles, and the dosage of cabazitaxel had to be tapered to 12.5 mg/m² by the fifth cycle. In subsequent cycles, the treatment was continued without grade 4 thrombocytopenia or any other toxicities ³grade 3. The patient achieved a long-term clinical response over 4 years and his PSA level continued to decrease, from 29.8 ng/ml at treatment initiation to a nadir of 2.0 ng/ml after the 60th cycle. CONCLUSIONS The present case is a rare example of a sustained response to low-dose cabazitaxel, and suggests its potential as a treatment option for metastatic CRPC patients. In our patient, this approach achieved a good clinical response with manageable toxicity over the long term.

Single Short Retention Instillation of Pirarubicin Prevents Intravesical Recurrence of Low-risk Non Muscle Invasive Bladder Cancer.

BACKGROUND: This study evaluated the efficacy of a single instillation of pirarubicin with a short retention time for preventing intravesical recurrence of low-risk non-muscle-invasive bladder cancer. PATIENTS AND METHODS: We analyzed 165 patients with low-risk non-muscle-invasive bladder cancer who underwent transurethral surgery. Single instillation of pirarubicin with 15-min retention time immediate after surgery was performed in 47 (28%) patients. The other patients (118, 72%) were treated without instillation therapy. The primary endpoint was recurrence-free survival. RESULTS: Median overall follow-up was 50 (range=6-134) months. Recurrence-free survival at 1 and 5 years was 91% and 72%, and 79% and 54% in the group treated with pirarubicin, and that treated with surgery alone, respectively (p=0.031). Cox's hazard analysis revealed lack of instillation and larger tumor size (>10 mm) as significant factors for risk of recurrence. No adverse events regarding intravesical chemotherapy were observed. CONCLUSION: Pirarubicin instillation with 15-min retention time can prevent intravesical recurrence of low-risk bladder tumors.

Pro-GA, a Novel Inhibitor of γ-Glutamylcyclotransferase, Suppresses Human Bladder Cancer Cell Growth.

BACKGROUND/AIM: γ-Glutamylcyclotransferase (GGCT), a key enzyme involved in glutathione metabolism, catalyzes a specific reaction that generates 5-oxoproline and free amino acids from the γ-glutamyl peptide. Inhibition of GGCT is a promising therapeutic strategy for the treatment of various cancers. MATERIALS AND METHODS: Immuno-histochemistry was used to evaluate GGCT expression in bladder tumors. The growth inhibitory effect of pro-GA, a novel GGCT inhibitor, in the presence or absence of mitomycin C (MMC) was assessed in three distinct bladder cancer cell lines. RESULTS: Over half of the clinical bladder tumor samples overexpressed GGCT. Pro-GA reduced the growth of all bladder cancer cell lines in a dose-dependent manner, and increased the anti-tumor effect of MMC. CONCLUSION: Inhibition of GGCT using pro-GA provides a novel therapeutic strategy for the treatment of bladder cancers.

Changes in renal function following nedaplatin-containing chemotherapy in patients with urothelial carcinoma unfit for cisplatin.

The present study evaluated the impact of nedaplatin-containing chemotherapy on renal function in 35 patients with urothelial carcinoma (UC) between 2001 and 2014 who were unfit for cisplatin treatment. As comparative controls, the present study also examined 35 patients with the same disease who underwent cisplatin-containing chemotherapy during the same period. The changes in the estimated glomerular filtration rate (eGFR) prior to and following the administration of nedaplatin during each cycle of chemotherapy was investigated. The present study also reported the overall response rates and adverse events in each group. A total of 31 cycles of the gemcitabine/nedaplatin regimen and 66 cycles of the methotrexate/epirubicin/nedaplatin regimen were administered. In the nedaplatin group, the mean eGFRs prior to and following chemotherapy were 45.4 and 47.8 ml/min/1.73 m2, respectively. The eGFR of the post-chemotherapy group was significantly increased (P<0.001). On the other hand, in the cisplatin group, the eGFR following chemotherapy was significantly lower than the rate prior to chemotherapy (P<0.001). The overall response rates were 30.4 and 66.7% in the nedaplatin and cisplatin groups, respectively. In the two groups, myelosuppression was the most common side effect, but the occurrence rates in both groups were similar, and these adverse events were manageable. With regard to nephrotoxicity, nedaplatin-containing chemotherapy for cisplatin-unfit patients with UC is a safe treatment modality.

Prediction of intravesical recurrence of non-muscle-invasive bladder cancer by evaluation of intratumoral Foxp3+ T cells in the primary transurethral resection of bladder tumor specimens.

Patients with a history of non-muscle-invasive bladder cancer sometimes have recurrence of tumors after transurethral resection of bladder tumor treatment. To find factors related to the recurrence of non-muscle-invasive bladder cancer, we examined tissue specimens taken at transurethral resection of bladder tumor as an initial treatment. We revealed the association between prognosis of non-muscle-invasive bladder cancer and infiltration of Foxp3+ T cells that suppress anti-tumor immunity in 115 primary non-muscle-invasive bladder cancer patients retrospectively identified and followed for at least 3 months after primary transurethral resection. In immunohistological staining, we counted the number of cells positive for CD3 and positive for CD3 and Foxp3 together and calculated the percentage of Foxp3+ T cells among the CD3+ T cells. The recurrence-free survival rate was calculated by the Kaplan-Meier method, and a Cox regression analysis of recurrence factors was performed. The median (interquartile range) percentage of Foxp3+ T cells in all cases was 17.1% (11.9, 11.4-23.3%). Compared by risk stratification, it was 11.4% (10.4, 7.8-18.2%) in the low-risk group (n = 32), 16.8% (12.6, 11.6-24.2%) in the intermediate-risk group (n = 45), and 22.0% (9.7, 16.4-26.1%) in the high-risk group (n = 38). The Kaplan-Meier survival analysis indicated that the Foxp3+ T cell high group (≥ 17.1%) had a worse RFS rate than did the low group (< 17.1%) (P = 0.006). In multivariate analysis, the percentage of Foxp3+ T cells was an independent risk factor for intravesical recurrence (hazard ratio 2.25). Thus, peritumoral Foxp3+ T cell infiltration was correlated to risk stratification and recurrence-free survival. Therefore, the percentage of Foxp3+ T cells in tumor specimens may predict a risk for intravesical recurrence.

Indocyanine Green Angiography-assisted Laparoendoscopic Single-site Varicocelectomy.

OBJECTIVE: To study the efficacy of a new laparoscopic varicocelectomy technique using indocyanine green (ICG) angiography. METHODS: Laparoendoscopic single-site (LESS) varicocelectomy using ICG angiography was performed in a single institution on 11 patients with a grade 2 or 3 varicocele. Adult men (N = 9, 82%) who were apparently infertile and had a varicocele, as well as prepubertal boys (N = 2, 18%) with testicular growth retardation, underwent a LESS varicocelectomy using ICG angiography. After the separation of testicular veins, arteries, and lymphatics, ICG was injected intravenously, and arterial and venous blood flows were observed by ICG fluorescence. Spermatic veins were cauterized by bipolar forceps and cut. The spermatic artery and lymphatics were preserved. RESULTS: The mean time to the arterial phase (AP) from the ICG injection was 34.9 seconds and the mean time to the venous phase was 58.3 seconds. The mean interval from the arterial phase to the venous phase was 23.3 seconds, and in all cases, this time interval facilitated the identification of arteries and veins. The rates of residual varicocele 3 and 6 months after surgery were 9.1% and 0%, respectively. Serious postoperative complications were not observed nor were adverse events induced by ICG. CONCLUSION: ICG angiography appears to be safe and appears to facilitate the detection of artery and veins during LESS varicocelectomy. Continuing investigations of efficacy are required of this new and promising procedure in a larger number of patients.

Diagnostic criteria for stomal obstruction of tubeless cutaneous ureterostomy by use of (99m)tc-mercaptoacetyltriglycine diuretic renography.

PURPOSE: To evaluate (99m)Tc-mercaptoacetyltriglycine diuretic renograms for diagnosing stomal obstruction in tubeless cutaneous ureterostomy. MATERIALS AND METHODS: Cutaneous ureterostomy was performed in 29 patients (56 renal units) with a minimum follow-up period of 12 months. Stomal obstruction was evaluated with (99m)Tc-mercaptoacetyltriglycine diuretic renography 3 months after surgery. Regions of interest were drawn that completely encircled and snugly fit the kidney, renal pelvis, and ureter. The data analyses were performed with half-times to tracer clearance following furosemide (0.5 mg/kg) administration. RESULTS: The mean half-times to tracer clearance were 6.90±6.30, 5.25±4.29, and 8.75±7.63 minutes in the total, ipsilateral, and contralateral kidneys, respectively, in side relationships between the ureter and the stoma. There were significant differences between the ipsilateral and contralateral kidneys in the mean half-time to tracer clearance (p=0.038). Forty-eight renal units (85.7%) had a half-time to tracer clearance of less than 15 minutes, and all 48 renal units had no hydronephrosis. On the other hand, 5 renal units (8.9%) had a half-time to tracer clearance of more than 20 minutes, and these 5 renal units required the insertion of stent catheters or became atrophic. CONCLUSIONS: (99m)Tc-mercaptoacetyltriglycine diuretic renography was very useful for diagnosing stomal obstruction of tubeless cutaneous ureterostomy. The upper limit of the half-time to tracer clearance for unobstructed systems was 15 minutes, which allowed for the confident exclusion of stomal obstruction in tubeless cutaneous ureterostomy.