Evaluation of flexible ureteroscope with an omni-directional bending tip, using a JOYSTICK unit (URF-Y0016): an ex-vivo study.

PURPOSE: To compare the range of reach of our newly designed omni-directional ureteroscope (URF-Y0016), compared to the commonly used URF-P6, FlexX2s, and LithoVue™ scopes, in the upper, middle, and lower calyces in an ex-vivo pyelocaliceal model. METHODS: We fabricated a three-dimensional pyelocaliceal model of the upper, middle, and lower pole calyces using urethane and acrylic resin. The inner surface of the dome of each calyx was engraved with reference lines along eight directions, set at 10° of latitude from the top to the base of the dome, and at angles of 0-90°, to precisely determine the range of reach of each scope. The main feature of the URF-Y0016 scope is the omni-directional bending of the tip of the flexible ureteroscope, with the control of these four directions integrated into a handgun-type control unit with a joystick. The range of reach within each calyx was measured by four expert surgeons. RESULTS: The URF-Y0016 scope provided a greater range of reach along all directions in the lower pole calyx compared to URF-P6, FlexX2s, and LithoVue™ scopes (p < 0.001), particularly along the anterior-posterior direction in the lower lobe calyx. However, the URF-Y0016 scope did not influence the improvement of reach range in the upper and middle pole calyx compared to URF-P6, FlexX2s, and LithoVue™ scopes (p = 0.08, p = 0.296). CONCLUSION: The novel design of the URF-Y0016 could improve treatment outcomes for calyceal stones in the lower pole in practice.

CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence.

BACKGROUND: Multiple early gastric cancers (EGCs) may develop in 6-14% of patients even after achieving curative endoscopic submucosal dissection (ESD); however, a useful biomarker for predicting recurrence is not available. The present study investigated whether the expression of CD44 variant 9 (CD44v9), a functional cancer stem cell marker, in the primary gastric cancer tissue represents an indicator of recurrence. METHODS: Eighty-eight patients who underwent ESD for EGC from 2008 to 2010 were enrolled and monitored for recurrence for 3 years. The expression levels of CD44v9 in the tissue of initial EGCs were evaluated by immunohistochemistry, and the recurrence rate was compared between CD44v9-positive and CD44v9-negative groups. The mucin phenotype and expression of microRNA-21 (miR-21) and programmed cell death protein 4 (PDCD4) were also analysed. RESULTS: The recurrence rate of EGC was significantly higher in the CD44v9-positive group than in the CD44v9-negative group (hazard ratio (HR), 21.8; 95% confidence interval (CI), 5.71-83.1). However, mucin phenotypes and the expression of miR-21 and PDCD4 did not predict recurrence after ESD. Meanwhile, grade of gastric atrophy was also identified as a significant marker of multiple recurrence (HR, 4.95; 95% CI, 1.30-18.8). CONCLUSION: CD44 variant 9 expression represents a potential predictive marker for recurrence in EGC.

A prospective study on symptom generation according to spicy food intake and TRPV1 genotypes in functional dyspepsia patients.

BACKGROUND: Capsaicin is an ingredient of red peppers that binds to transient receptor potential vanilloid subtype 1 (TRPV1), and Koreans eat more capsaicin-rich food than do Japanese. This study aimed to compare symptom generation according to TRPV1 genotypes and the intake of spicy foods. METHODS: Consecutive functional dyspepsia (FD) patients who were evaluated at Konkuk University Medical Centre (Korea) and Keio University Hospital (Japan) were included. Questionnaires on spicy food intake, patient assessment of gastrointestinal symptoms (PAGI-SYM), patient assessment of quality of life, and hospital anxiety and depression scale were provided. Blood was sampled for the detection of TRPV1 polymorphisms, and upper gastrointestinal endoscopy was performed with biopsies. KEY RESULTS: Of 121 included subjects, 35 and 28 carried the TRPV1 CC and GG genotypes, respectively, with the prevalence rates not differing between Japan and Korea. The prevalence of FD subtypes did not differ with the spicy food intake, TRPV1 genotypes, or Helicobacter pylori infection. Neither TRPV1 polymorphisms nor H. pylori infections were related to scores on the PAGI-SYM questionnaires, but spicy food intake was positively correlated with the scores for stomach fullness (p = 0.001) and retching (p = 0.001). Using the linear regression analysis, stomach fullness was associated with spicy food intake (p = 0.007), whereas retching was related to younger age (p < 0.001) and female gender (p = 0.014). CONCLUSIONS & INFERENCES: Upper gastrointestinal symptoms are more common in subjects with a higher consumption of spicy foods, younger age and female gender, regardless of TRPV1 genotypes and the H. pylori infection status. Capsaicin-rich foods may induce stomach fullness.

Thymidine phosphorylase activity in human bladder cancer: difference between superficial and invasive cancer.

The activity of thymidine phosphorylase (TdR-Pase), which is identical to platelet-derived endothelial cell growth factor (a potent angiogenic factor), was analyzed in primary human bladder cancer tissues. TdR-Pase activity in tissues was determined from the conversion rate of 5'-deoxy-5-fluorouridine to 5-fluorouracil. The mean activity in 37 bladder cancers and in 8 samples of normal bladder epithelial tissue was 108.5 and 19.2 microgram 5-fluorouracil/mg protein/h, respectively, showing a statistically significant difference. Among the cancer tissues, differences in activity were seen according to the stage and grade of tumors. Low-grade (grade 1) tumors had significantly lower activities than high-grade tumors, and high-grade invasive tumors showed significantly higher activities than low-grade superficial tumors. These results demonstrate that a high TdR-Pase activity in bladder cancer is associated with the tumor characteristics of invasion and malignant potential. Our conclusions support the hypothesis that angiogenesis that is mediated by this molecule may be involved in the development of invasive human bladder cancer, as suggested by T. O'Brien et al. (Cancer Res., 55: 510-513, 1995), and also suggest that TdR-Pase is a potential therapeutic target in human bladder cancer.

Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell trafficking across tumour vascular checkpoints.

T-cell trafficking at vascular sites has emerged as a key step in antitumour immunity. Chemokines are credited with guiding the multistep recruitment of CD8(+) T cells across tumour vessels. However, the multiplicity of chemokines within tumours has obscured the contributions of individual chemokine receptor/chemokine pairs to this process. Moreover, recent studies have challenged whether T cells require chemokine receptor signalling at effector sites. Here we investigate the hierarchy of chemokine receptor requirements during T-cell trafficking to murine and human melanoma. These studies reveal a non-redundant role for Gαi-coupled CXCR3 in stabilizing intravascular adhesion and extravasation of adoptively transferred CD8(+) effectors that is indispensable for therapeutic efficacy. In contrast, functional CCR2 and CCR5 on CD8(+) effectors fail to support trafficking despite the presence of intratumoral cognate chemokines. Taken together, these studies identify CXCR3-mediated trafficking at the tumour vascular interface as a critical checkpoint to effective T-cell-based cancer immunotherapy.

C-ERBB-2 gene amplification as a prognostic marker in human bladder cancer.

OBJECTIVES: To evaluate c-erbB-2 gene amplification and its prognostic significance in transitional cell carcinoma of the bladder. METHODS: Alterations in the gene copy number of c-erbB-2 were detected in 57 bladder tumor samples using a method based on the polymerase chain reaction. RESULTS: Eighteen tumors (32%) showed gene amplification of c-erbB-2, which correlated with tumor grade and stage. A strong association of c-erbB-2 amplification with patient survival was also found. The amplification resulted in a significantly poorer prognosis among the patients with high-grade and/or invasive tumors. Multivariate analysis revealed that c-erbB-2 amplification and tumor grade were independent prognostic factors. CONCLUSIONS: Our data indicate a possible role of the c-erbB-2 gene in the development of aggressive behavior in bladder tumors. Moreover, the use of c-erbB-2 gene amplification, together with tumor grade and stage, could provide an accurate basis for determining the prognosis of bladder cancer.

Increases in gastric histidine decarboxylase activity and plasma gastrin level in streptozotocin-induced type 1 diabetic rats.

When type 1 diabetes mellitus was induced in rats by injecting streptozotocin, histidine decarboxylase expression was abnormally up-regulated in a transcriptional level, and 7 d after the injection, the enzyme activity was increased about 3-fold over the control (p < 0.05). When the diabetic rats were administered with insulin for 3 d, the increased histidine decarboxylase activity returned to a normal level in addition to normalization of the plasma glucose level. The plasma gastrin level in the fasting state was also significantly elevated in the diabetic rats, and the insulin treatment normalized the level. In the diabetic rats, fasting gastric acid output increased significantly and gastric pH was lowered. These results suggest that the gastric histidine decarboxylase activity and plasma gastrin level are increased in connection with the depletion of insulin in streptozotocin-induced diabetic rats, and gastric acid secretion is stimulated at a basal level, presumably due to increases in the concentrations of histamine and gastrin in oxyntic mucosa.

[Results of treatment for germ cell tumor--dose intensity of chemotherapy and residual masses after chemotherapy].

We reviewed the treatment results in 44 patients with germ cell tumor and the significance of % dose intensity of Cisplatin and tumor marker half-life of induction chemotherapy and discussed the necessity of surgical resection of the postchemotherapy residual tumor. The 5-year survival rate calculated by the Kaplan-Meier method was 83.6% in total, and 95.2, 75.8 and 47.6% for good, intermediate and poor prognosis, respectively. Of the 29 metastatic cases treated by chemotherapy, 5 (17.2%) achieved complete response (CR) and 15 (51.7%) partial response, and % dose intensity of Cisplatin were 75.4% in total and 86.4 +/- 8.6, 71.6 +/- 11.1, 84.3 +/- 8.3 and 62.2 +/- 11.0% in CR, PR, NC and PD. Dose intensity was correlated with the clinical response and the prognosis. Of the 12 PR cases without teratoma elements, two had salvage surgery, five had additional chemotherapy and five were followed by surveillance. One case followed by surveillance died of the disease, another one with additional chemotherapy was alive with the disease and the others were alive with no evidence of disease. Surgical resection is an effective treatment to remove residual masses, but observation may also be considered in the cases without teratoma elements.

[Evaluation of usefulness of urinary nuclear matrix protein 22 (NMP22) in the detection of urothelial transitional cell carcinoma].

We evaluated the usefulness of urinary nuclear matrix protein 22 (NMP22) compared to urinary cytology in the detection of urothelial transitional cell carcinoma (TCC). Between July 1999 and March 2000, 227 patients complaining of microscopic or gross hematuria were analyzed. Twenty-four patients (10.6%) had urothelial TCC. The urinary NMP22 level was significantly higher in the patients with urinary TCC compared to the other patients. The sensitivity and specificity of the results obtained with urinary NMP22 were 58.3% and 84.2%, respectively, and those obtained by urinary cytology were 45.8% and 98.0%, respectively. False-positive results were obtained with urinary NMP22 in the patients with urinary diversion using intestine, bladder invasion from other cancers, urinary tract infection, and urolithiasis. The urinary NMP22 level was significantly associated with tumor stage, suggesting its usefulness for detection of urothelial TCC. However, although urinary NMP22 showed equal sensitivity for the detection of TCC, it was not superior to urinary cytology.

[Detection of human papillomavirus DNA in condyloma acuminatum of the urethra: a case report].

A case in a 35-year-old male with recurrence of the condyloma acuminatum of the urethra is presented and the involvement of human papilloma virus (HPV) with this disease is mentioned. The HPV-DNA in the excised specimen was detected by the dot blot hybridization method with radiolabelled RNA probes, and the type of the DNA was investigated by the Southern blot hybridization method with biotinylated DNA probes, which could detect the HPV-DNA of types 6, 11, 16, 18, 31, 33 and 35. These analyses demonstrated the HPV-DNA of type 11 and another unidentified type in our case. From the literature with regard to the etiology of this disease considering the risk of malignancy, we also emphasize the necessity for close observation of the patients with condyloma acuminatum, clinically benign, which contains the so-called malignant type HPV-DNA.

[Congenital mid-ureteral stricture: report of a case].

A rare case of congenital mid-ureteral stricture is reported. A 17-year-old woman was admitted with sudden onset of right flank pain. Intravenous urography demonstrated bilateral small renal calculi, left hydronephrosis and a stricture of the left ureter at the level of the pelvic brim. The diagnosis was determined as congenital mid-ureteral stricture because the ureter tapered smoothly from 25 mm to 5 mm in diameter at the stenotic site. She was successfully treated by partial ureterectomy with end-to-end anastomosis. Histopathologically, no dysplasia of muscular layer was recognized.

[Metastatic renal tumor originating from esophageal cancer: report of 2 cases].

We report 2 cases of esophageal cancer metastatic to the kidney. The first case was in a 57-year-old man who complained of severe right flank pain. He had underwent an operation for esophageal cancer 2 months previously. A computerized tomography (CT) scan revealed a wedge-shaped, low-density mass in the right kidney. Right nephrectomy revealed squamous cell carcinoma. He has remained free of recurrence 3 months postoperatively. The second case was in a 57-year-old man with esophageal cancer treated by radiation therapy. Severe right flank pain and gross hematuria appeared after 1 year. A CT scan showed a wedge-shaped, low-density tumor in the right kidney accompanied with a tumor thrombus in the inferior vena cava. Right nephrectomy as well as resection of the thrombus were performed. Pathological diagnosis was squamous cell carcinoma. He died of cancer 2 months postoperatively.

[Clinical study on torsion of appendix in intrascrotal organ].

We reviewed 12 cases of torsion of appendix in the intrascrotal organ treated surgically and discussed its clinical features. An accurate diagnosis could be made in 5 of the 12 patients before operation because they had a palpable localized tender nodule at the affected area, but not in the other 7 patients because their whole scrotal contents had become swollen with time. The histological study on 6 patients with testicular swelling revealed their spermatogenesis intact. Therefore, we believe that torsion of the appendix in the intrascrotal organ has little influence on future fertility, and thus, correct preoperative diagnosis may diminish the necessity for surgical treatment.

[A case of CEA and CA19-9 producing recurrent transitional cell carcinoma in an Indiana pouch after total cystectomy].

A 73-year-old female with transitional cell carcinoma (TCC) of the bladder underwent total cystectomy and Indiana pouch replacement in April, 1992. Histological examination revealed grade 3 TCC. In February 1995, she complained of gross hematuria. Intravenous pyelography (IVP) revealed a right non-functional kidney and filling defect in the Indiana pouch. We suspected colon cancer in the Indiana pouch because the levels of serum carcino-embryonic antigen (CEA) and CA19-9 were elevated. Endoscopic biopsy of intrapouch tumor was done. Pathological examination revealed grade 2 TCC. In July 1995, right nephroureterectomy with resection of Indiana pouch was performed and the surgical specimen revealed renal pelvic and ureteral cancer, grade 2 TCC. The levels of serum CEA and CA19-9 returned to the normal range 21 days after the operation. CEA and CA19-9 histochemical stain of renal pelvic and ureteral cancer were positive. Also CEA-, CA19-9-positive cells were detected in the specimens of the bladder tumor from the total cystectomy performed in 1992. This rare case is discussed and the literature is reviewed.

[A survey of radical surgery without neoadjuvant therapy for patients with stage B and C prostatic carcinoma].

There has been much controversy regarding radical surgery for both localized and locally extensive carcinoma of the prostate. We analyzed the outcome of radical prostatectomy and the preoperative evaluation in order to assess the indication of radical prostatectomy. Fifty-six patients with clinical stage B or C prostate cancer were treated by radical prostatectomy without neoadjuvant therapy. Endocrine therapy was added to the non-curative cases postoperatively. Preoperative evaluation was compared with pathological results and survival, and furthermore the usefulness of the preoperative PSA and PSA half-life were investigated. The mean follow-up period was 44.5 months. The accuracy of the grade and the clinical stage were 58.9% and 23.2%, respectively. Organ-confined disease was seen in patients with an initial PSA level less than 30 ng/ml. Postoperative PSA half-life is significantly prolonged in cases with poorly differentiated adenocarcinoma or lymph node involvement and may be a predictor of PSA failure. The cause-specific 5-year survival rates were 92.7% on the whole, 92.9% for well differentiated, 96.7% for moderately differentiated, 85.7% for poorly differentiated, 100% for stage B1, 95.0% for stage B2 and 86.8% for stage C. These results indicated that patients with an initial PSA level of less than 30 ng/ml will benefit from radical prostatectomy.

[Clinicopathological study of influential factors on prognosis in patients with renal cell carcinoma].

Between January 1986 and August 1996, 120 patients were diagnosed with renal cell carcinoma (RCC) at Kanagawa Cancer Center. In this study, we analyzed these patients in view of the clinicopathological factors, which affect the prognosis of these patients with univariate and multivariate analysis using Cox's proportional hazard model. Of these 120 patients, 40 patients (33%) died of RCC during this period. The cause specific survival rate was 65% after 5 years and 57% after 10 years. Univariate analysis showed some factors, performance status, symptoms, tumor size, histological grade, local invasion (pT), venous involvement (pV), lung metastasis, lymph-node metastasis, and bone metastasis, affected the prognosis. Furthermore, multivariate analysis using Cox's proportional hazard model showed that performance status, pT, pV, lung metastasis, lymphnode metastasis, and bone metastasis independently affected the prognosis. In summary, TMN factors and performance status importantly affect the prognosis of RCC patients.

[A case of intrascrotal hemangioma].

Intrascrotal hemangioma is rare. A case is presented and the literature is reviewed. A 35 year-old male with the complaint of a painless right scrotal mass underwent right high orchiectomy because the mass was hard and difficult to separate from the right testicle in scrotal exploration. Histologic study revealed that the tumor consisted of a venous hemangioma and the greater part of it was displaced by organized connective tissue. It is extremely rare for a case of intrascrotal hemangioma to require orchiectomy.

[A case of poorly differentiated adenocarcinoma of prostate with neuroendocrine differentiation].

A 59-year-old man was diagnosed with clinical stage D1 poorly differentiated prostatic adenocarcinoma (PAC). The patient was treated with total androgen blockade therapy. The tumor recurred 18 months later. Digital rectal examination revealed a large, stony-hard prostate. The serum PSA level was within normal limits. Pathological examination of the prostate revealed conventional adenocarcinoma with large numbers of neuroendocrine (NE) cells. The patient died 3 months after the diagnosis of PAC with NE differentiation, 22 months after the initial diagnosis of prostate cancer.

[Extracorporeal shock wave lithotripsy for urinary calculi in an ileal reservoir following reconstruction of the urinary bladder].

A new method for reconstruction of the urinary bladder was introduced by Taguchi in 1977. It consisted of two components; making of pseudo-urethra and the reconstruction of urinary reservoir in the pelvis. The latter was made of the ileum and the peritoneum with temporary use of Japanese paper. This operative method was applied to a 28-year-old female patient when she had cystectomy and bilateral ureterostomy. Thereafter she had has no trouble for 13 years. However, her recent rentogenogram showed urinary tract calculi in the reservoir. Endoscopic treatment was not indicated because of the deformed reservoir and the inflexible pseudourethra. Thus, extracorporeal shock wave lithotripsy (ESWL) was applied to the case with successful results. We herrin reported the case and discussed the usefulness of ESWL for urinali calculi in the ileal reservoir.

Greater loss of productivity among Japanese workers with gastro-esophageal reflux disease (GERD) symptoms that persist vs resolve on medical therapy.

BACKGROUND: Gastro-esophageal reflux disease (GERD) impairs quality of life; however, the association between GERD and work productivity has not been well investigated in Japan. This study was designed to compare the impact of GERD on productivity between Japanese workers with GERD symptoms that persisted vs resolved on medical therapy. METHODS: A cross-sectional Web-based survey was conducted in workers. The impact of GERD on work and daily productivity was evaluated using a Web-reported Work Productivity and Activity Impairment Questionnaire for patients with GERD and a GERD symptom severity Questionnaire. Demographic information, clinical history, and satisfaction with GERD medication were also ascertained. KEY RESULTS: A total of 20 000 subjects were invited to the survey. After the exclusion of patients with a history of gastrointestinal (GI) malignancy, peptic ulcer, upper GI surgery, and unemployment, 650 participants were included in the analysis. Participants with persistent GERD symptoms reported a significantly greater losses of work productivity (11.4 ± 13.4 h/week), absenteeism (0.7 ± 3.1 h/week), presenteeism (10.7 ± 12.6 h/week), costs (20 100 ± 26 800 JPY/week), and lower daily productivity (71.3% [95% confidence interval, 69.0-73.7]) than those whose symptoms were alleviated with medications. The level of dissatisfaction with GERD medications among participants with persistent GERD symptoms was significantly correlated with loss of work and daily productivity (p < 0.001). CONCLUSIONS & INFERENCES: GERD places a significant burden on work and daily productivity despite medical therapy. Ineffective GERD therapy is associated with greater productivity loss.