Post-fertilization effect of bilateral primary testicular damage induced by unilateral cryptorchidism in the rat model.

Cryptorchidism, a common anomaly of the male genitalia, affects 2-4% of male infants. The post-fertilization effects of unilateral cryptorchidism model in the rat and the effects of antioxidant treatment were investigated. Six-week-old male Wistar rats were randomly separated into four groups. Unilateral cryptorchidism was induced in the right testis of three groups. One group was treated with saline intraperitoneally (i.p.) (Crypto), one group was treated with taurine (500 mg/kg, i.p.; Tau), and another group was treated with sivelestat (15 mg/kg i.p.; Siv). The control group was treated with saline i.p. The treatment was daily for 8 weeks. Five days before sacrifice, mating studies were performed. Body, testicular, and epididymal weights were recorded. Malondialdehyde (MDA) levels in the seminal vesicular fluid (SVF) were measured. Testicular levels of MDA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined bilaterally. TUNEL assay was used to examine DNA fragmentation bilaterally. Histological examination and the Johnsen score were used to evaluate morphological testicular alterations. The Crypto group demonstrated significantly lower right testicular and epididymal weights, significantly increased SVF-MDA levels, testicular MDA and 8-OHdG levels, and the apoptotic score bilaterally compared to the controls. Furthermore, histological evaluation revealed significantly reduced spermatogenesis and mild injury to the cryptorchid testes compared to the control. Treatment with both taurine and sivelestat significantly reduced SVF-MDA levels, testicular MDA, 8-OHdG, and apoptosis bilaterally compared to the Crypto group. Antioxidant treatment was unable to ameliorate spermatogenesis. Newborns delivered by females that mated with Crypto-males had significantly lower body weight compared with the respective animals from the control, Tau and Siv groups. The present study demonstrated that unilateral cryptorchidism-induced testicular damage can significantly affect the contralateral testis as well having further deleterious post-fertilization effect on the development of newborns. Treatment with antioxidants can partially improve the testicular damage bilaterally with beneficial effects for the newborns.

Initial evidence demonstrating the association between the vascular status in surgically resected renal parenchymal pathology and sexual function.

Our goal is to evaluate the association between histopathology of glomerulosclerosis (GS) and atherosclerosis (AS) in the nephrectomized normal parenchyma together with patients' background, and erectile dysfunction (ED) of patients treated with radical nephrectomy (RN) for renal cell carcinoma (RCC). ED was assessed with the International Index of Erectile Function in 65 patients who were less than age 70 years at the time of questionnaire. Glomeruli status was assessed by the extent of global GS. AS was graded based on lumen occlusion and frequency of involvement. Patients' backgrounds included any comorbidities, post-RN renal insufficiency, tumor pathology, demographics and social status. The presence of diabetes mellitus and lack of a spouse were independent predictors for severe ED, whereas G0/1 AS was an independent predictor for mild/no ED. The extent of global GS was significantly lower in patients with mild/no ED than in other patients. Our study represents the first report identifying healthy arterial status in the renal parenchyma as a significant indicator of favorable erectile function and that the evaluation of AS severity is not a superior indicator of severe ED in the presence of comorbidities or social status among patients treated with RN.

Blocking of the ATP sensitive potassium channel ameliorates the ischaemia-reperfusion injury in the rat testis.

There is increasing evidence that the effects of administered ATP sensitive potassium (KATP ) channel openers or blockers during ischaemia are still controversial in many organs/tissues. Testicular torsion detorsion which causes ischaemia-reperfusion (IR) injury, cannot be predicted, thus an effective drug should be administered during or after the ischaemia. The aim of this study was to examine whether the administration of KATP channel openers or blockers during ischaemia ameliorates IR injury in the testis. Eight-week-old male Sprague-Dawley rats were subjected to 2 h right testicular ischaemia followed by 24 h reperfusion. The selective mitochondrial (mito) KATP channel blocker, 5-hydroxydecanoate (5-HD) (40 mg/kg), the non-selective KATP channel blocker glibenclamide (5 mg/kg), the selective mito KATP channel opener diazoxide (10 mg/kg) and the non-selective KATP channel opener cromakalim (300 µg/kg) were administered intraperitoneally 15 min prior to the ischaemia or 75 min after the induction of ischaemia. Tissue damage was evaluated by malondialdehyde concentration, myeloperoxidase activity, histological evaluation and TdT-mediated dUTP nick end labelling assay in the testis. There was a significant increase in oxidative stress, neutrophil infiltration, histological damage and apoptosis in the testicular IR model. A significant reduction in the testicular IR injury was observed with the administration of glibenclamide, but not 5-HD, diazoxide or cromakalim during ischaemia. The administration of non-selective KATP channel blocker glibenclamide ameliorated the testicular IR injury. On the other hand, the selective mito KATP channel blocker, 5-HD and KATP channel openers did not reduce the testicular IR injury. These data suggest that blocking of the membrane KATP channel may have a protective effect during the testicular ischaemia. Glibenclamide could be an effective drug to manage the post-ischaemic injury caused by the testicular torsion-detorsion.

Classification of the distribution of cavernous nerve fibers around the prostate by intraoperative electrical stimulation during laparoscopic radical prostatectomy.

We investigated the distribution of cavernous nerve (CN) fibers around the prostate by electrical nerve stimulation during laparoscopic radical prostatectomy to classify the distribution of the CN fibers. Electrical stimulation was performed on 30 consecutive patients with localized prostate cancer; middle of the neurovascular bundle (NVB, point A), base of the NVB (point B), the rectal wall 1 cm posterolateral to the NVB (point C) and the lateral aspect of the prostate (point D). We measured the intraurethral pressure at the midportion to detect the changes in intracavernosal pressure. The mean maximum changes were 10.5 ± 7.9, 11.6 ± 8.8, 9.6 ± 7.4 and 6.7 ± 7.0 cm H(2)O at points A, B, C and D, respectively. The patterns of CN fiber distribution were divided into four groups: type 1 (23%), the bundle corresponding to the NVB; type 2 (7%), the bundle from the rectal wall to the prostate; type 3 (27%), the plate including NVB and posterolateral to NVB; and type 4 (43%), the plate between the rectal wall posterolateral to the NVB and the lateral aspect of the prostate. Distribution of the CNs in a bundle-like formation was considered to account for 30%, whereas a plate-like formation accounted for 70%. Understanding these four patterns of CN fiber distribution should facilitate accurate CN-sparing radical prostatectomy.

[Oral allergy syndrome in patients with Japanese cedar pollinosis].

Patients with pollinosis sometimes complain of oral symptoms (itching and tingling with or without edema of the lips, mouth and tongue) after eating fresh fruits and vegetables. This condition has been termed Oral Allergy Syndrome (OAS). Twenty-three patients with Japanese cedar pollinosis and OAS for fresh fruits and vegetables were included in this study. Their mean age was 31.3 years (range = 5 to 62). The fruits that caused OAS in these patients included melon, apple, peach, and kiwi fruit. Most patients with OAS exhibited hypersensitivity to more than two foods. Specific IgE antibodies to inhaled allergens of mite, Japanese cedar pollen, birch pollen, melon, apple, peach, and kiwi were evaluated using the Pharmacia CAP system. Eleven of the 16 subjects with specific IgE antibodies for birch pollen, did not suffer symptoms during the birch and alder pollen season. In subjects with specific IgE antibodies for fruits, 13 out of 20 patients showed specific IgE antibodies for apple, and 8 out of 9 patients with OAS for apples were also positive for specific IgE antibodies for apples. On the other hand, 17 patients had no specific IgE antibodies for melon, and only two patients and one patient showed specific IgE antibodies for kiwi fruit and peach, respectively. These results suggest that the evaluation of specific IgE antibodies to birch pollen and apple may be useful for diagnosing OAS in patients with Japanese cedar pollinosis.

[The evaluation of Fas/Fas ligand system in renal cell carcinoma--the effect of preoperative interferon-alpha therapy].

OBJECTIVES: In order to investigate the effect of preoperative interferon (IFN)-alpha on Fas/Fas ligand (FasL) system, we examined Fas and FasL expression and the occurrence of apoptotic cell death in a preoperative therapy group, and in a control group using surgically resected renal cell carcinoma (RCC) tissues. METHODS: Ten cases were served as the preoperative therapy group, and sixteen cases as the control group. IFN-alpha was administered at five megaunits daily intramuscularly for two weeks in the preoperative therapy group. Immunohistochemistry for Fas and FasL, and terminal-deoxynucleotidyl-transferase (TdT)-mediated digoxigenin-dUTP nick end-labeling (TUNEL) were employed. We defined the labeling index (LI) as percentage of Fas- or FasL-positive cells in carcinomatous cells, and apoptotic index (AI) as percentage of TUNEL-positive cells in carcinomatous cells. RESULTS: Significant correlations were found between the LIs of Fas and AIs in all 26 cases. LIs of Fas and AIs of the preoperative therapy group were significantly higher than those of the control group. FasL expression was detected in nine out of ten cases in the preoperative therapy group, and in fourteen out of sixteen cases in the control group. There were no significant differences in LIs of FasL between two groups. CONCLUSION: These data suggest that apoptosis via the Fas/FasL system is functional, and that preoperative IFN-alpha treatment may up-regulate the Fas/FasL system in RCC. On the other hand, we need to investigate about an immune-escape mechanism through the FasL expression considering the relatively frequent expression of FasL in our results in RCC from now.

Sarcomatoid carcinoma of the urinary bladder: 3 case reports.

Three cases of sarcomatoid carcinoma of the urinary bladder are considered. The patients were 2 males, aged 68 and 81 years, and a 79-year-old female. Transurethral resection of the bladder tumor (TUR-BT) and consecutive radical cystectomy were performed in all patients. Local progression of bladder tumors just after TUR-BT was recognized in the 2 younger patients, each of whom died due to recurrence after radical cystectomy. Because of the extremely aggressive malignant potential of sarcomatoid carcinomas, the indications for TUR-BT should be carefully assessed and suitable therapeutic strategies should be examined further.

Expression of bcl-2, p53 oncoprotein, and proliferating cell nuclear antigen in renal cell carcinoma.

OBJECTIVES: This study was designed to examine the immunohistochemical expression of bcl-2, p53, and proliferating cell nuclear antigen (PCNA) and the relation of this expression to clinicopathological characteristics and prognosis in renal cell carcinoma (RCC). METHODS: The expression of bcl-2, p53 protein, and PCNA was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 53 patients whose clinicopathological data had already become clear. RESULTS: The expression of the bcl-2 protein was recognized in 34 cases (64%); the expression of the p53 protein, however, was seen in only 1 case. Bcl-2 positivity was not associated with any pathological parameters or prognosis. If the percentage of PCNA-positive cancer cells as compared to the total amount of cancer cells was defined as a labeling index (LI), a high PCNA LI number correlated significantly with a high T category, high grade, venous invasion, and shortened survival. Among the conventional pathological parameters, the T category, nuclear grade, and venous invasion had the most significant effect on prognosis. A multivariate analysis in the parameters of PCNA, T category, nuclear grade, and venous invasion demonstrated that only nuclear grade had a significant effect on prognosis. CONCLUSIONS: The inhibitory effect of the bcl-2 gene on apoptosis related to tumor development is not clear, and the expression of the p53 protein is uncommon in RCC. PCNA seems to be a good objective and quantitative marker of the biological malignant potential in RCC, although the assessment of malignant potential in combination with conventional pathological parameters is indispensable.

Anomalous junction of the pancreaticobiliary duct accompanied by gallbladder cancer and obstructive jaundice in a patient with high serum and bile cytokine levels.

We report a case of anomalous junction of the pancreaticobiliary duct (AJPBD) associated with gallbladder cancer and obstructive jaundice in a patient with high serum and bile cytokine levels. The patient was a 63-year-old woman who complained of right hypochondralgia. Ultrasound, computed tomography, percutaneous transhepatic cholangiography, and endoscopic retrograde cholangio-pancreatatography revealed dilation of the bile ducts, an elevated lesion of the gallbladder, and AJPBD. She underwent percutaneous transhepatic cholangio-drainage (PTCD) for obstructive jaundice. However, the total bilirubin concentration remained high 7 days after PTCD. Her serum interleukin 6 level was 57,359 pg/ml before PTCD, and gradually decreased to 10 pg/ml after PTCD. Bile interleukin 6 level was 10 pg/ml before PTCD, 8997 pg/ ml 3 h after PTCD and gradually decreased there after. Serum and bile levels of tumor necrosis factor alpha and hepatocyte growth factor were high before and after PTCD. The patient underwent an extended cholecystectomy and resection of the extrahepatic bile duct. The resected specimen showed two elevated lesions of the gallbladder which, microscopically, revealed moderately differentiated tubular adenocarcinoma. These findings suggest that pre-existing inconspicuous inflammation of the biliary tract due to reflux of pancreatic juice is involved in elevation of serum and bile cytokines, and that cytokines may participate in gallbladder carcinogenesis associated with AJPBD.

Serum and bile interleukin 6 after percutaneous transhepatic cholangio-drainage.

BACKGROUND/AIMS: This study was designed to assess the correlation of interleukin 6 (IL-6) with jaundice reduction by percutaneous transhepatic cholangio-drainage (PTCD) for obstructive jaundice. METHODOLOGY: We measured serum and bile IL-6 concentrations by enzyme linked immuno-sorbent assay before and after PTCD in 26 patients with obstructive jaundice. The patients were divided into two groups according to their bilirubin decrease rate. RESULTS: Serum IL-6 levels measured before and after PTCD in the slowly decreasing bilirubin group ("poor" group) were significantly higher than those of the rapidly decreasing bilirubin group ("good" group). Measures of bile IL-6 in the "poor" group remained high from 3 to 14 days after PTCD in comparison with the "good" group. CONCLUSIONS: These results suggest that circulating IL-6, as well as IL-6 in the bile, may be involved in the pathogenesis of obstructive jaundice, and play an important role in preventing the resolution of obstructive jaundice after PTCD.

[Changes in serum and bile tumor necrosis factor alpha before and after percutaneous transhepatic cholangio-drainage for obstructive jaundice].

The aim of this study was to evaluate the correlation between tumor necrosis factor alpha (TNF alpha) and jaundice reduction by percutaneous transhepatic cholangio-drainage (PTCD) in patients with obstructive jaundice. Thirty patients who had undergone PTCD were divided into two groups: those with rapidly decreasing bilirubin (the fast group; n = 21) and those with slowly decreasing bilirubin (the slow group; n = 9). We compared clinical features before PTCD between groups. We also compared serum and bile TNF alpha before and after PTCD in the fast group with those in the slow group. The rate of patients with recurrence of malignancy in other organs involved in the etiology of obstructive jaundice was significantly higher in the slow group than in the fast group. Before and after PTCD, serum and bile TNF alpha were significantly higher in the slow group than in the fast group. These results suggest that TNF alpha may play an important role in the protracted recovery from obstructive jaundice after PTCD.

[Radiation therapy for advanced gastric cancer].

Thirteen patients with advanced gastric cancer treated by palliative radiotherapy were retrospectively analyzed. The radiation sites were abdominal cavities in 8 cases, superficial masses in 5 and lung metastasis in one. The purposes were to diminish mass size in 5 cases, to relieve pain in 3 and to reduce stenosis in 6. The total doses were more than 40 Gy in 10 patients. In 2 cases, the intracavitary irradiation was performed using 192Ir. In one case, radiation had to be stopped at the dose of 22.5 Gy because of poor general condition. Partial response was obtained in 6 of 12 cases (RP, 50%). The sites of responders were superficial lesions in 4 and hepatic hilar mass in 2, which were given intracavitary as well as external radiation. Pain relief was achieved in all patients suffering from it. One of 3 cases with esophageal stenosis showed marked improvement in swallowing. Two patients showed a decrease in the levels of tumor markers. Five patients had side effects of more than grade 2. Two of them were grade 3, one thrombocytopenia and one diarrhea. The median survival time of all cases was 9 months, and 5 patients could shift to home care. These results suggest that palliative radiotherapy could be one of the most useful locoregional therapies for advanced gastric cancer, in the aspect of improvement of patient's QOL.

[Methotrexate/5-fluorouracil therapy in gastric cancer with peritoneal metastasis].

Eighteen patients with gastric cancer with peritoneal metastasis were treated with methotrexate/5-fluorouracil sequential therapy. In four patients, a partial response was obtained and in another four, symptomatic relief was obtained by the therapy. As side effects, BM suppression was seen in 9 and GI symptoms in 6 patients. Intraaortic, low-dose and 3-hour-interval procedure are recommended in the therapy.