Search

Anaplastic lymphoma kinase (ALK) translocation renal cell carcinomas (RCCs) have been reported by several independent groups in recent times. The clinical behavior and histopathologic characteristics of these carcinomas are not fully understood because of the paucity of cases reported. Here, we describe 2 cases of RCC harboring a novel striatin (STRN)-ALK fusion. The first case was a 33-year-old woman with no sickle cell trait who underwent nephrectomy for right renal mass and had late recurrence in para-aortic lymph nodes twice 10 and 12 years after initial surgery. After the second recurrence, she was carefully observed without any treatment. Twenty-six years after the initial nephrectomy, the second para-aortic lymphadenectomy was performed, and gastrectomy was performed for newly developed primary gastric cancer. The resected para-aortic lymph nodes were largely replaced by metastatic carcinoma. The second case was a 38-year-old man with no sickle cell trait who underwent cytoreductive nephrectomy followed by sunitinib therapy for metastatic RCC. In both cases, the tumor showed solid, papillary, tubular, and mucinous cribriform structures. Psammoma bodies were occasionally seen in the stroma. Tumor cells had a large nucleus and prominent nucleoli with predominantly eosinophilic cytoplasm. Rhabdoid cells and signet-ring cells were also observed. Intracytoplasmic mucin deposition and background mucinous stroma were confirmed. In the second case, tumor necrosis was seen in some areas. Tumor cells exhibited diffuse positive staining for ALK in both cases. ALK translocation was confirmed by fluorescent in situ hybridization, and further gene analysis revealed a STRN-ALK fusion. These cases provide great insights into ALK translocation RCCs.

Background Complications of peritoneal dialysis (PD) such as pain and catheter leakage are frequently reported. Delayed bowel perforation of a PD catheter is a rare adverse event but a serious complication associated with significant mortality. Bowel perforation of a PD catheter is difficult to differentiate from PD-related peritonitis and likely to result in a delay in diagnosis. Here, we report two cases of bowel perforation after PD catheter insertion by the stepwise initiation of PD using the Moncrief and Popovich technique (SMAP) and peritoneal wall anchor technique (PWAT). Case presentation The first case was a 53-year-old woman with end-stage renal disease (ESRD) due to diabetic nephropathy and a history of entero-adhesiolysis. She underwent PD catheter insertion by the SMAP with PWAT. Four months after PD catheter insertion, the catheter was found to perforate sigmoid colon. The second case was a 57-year-old woman with ESRD due to large polycystic kidney disease. She underwent the same procedure. After exteriorization of the catheter, she developed peritonitis due to perforation of the catheter tip into the bowel. Both patients were safely removed the catheter with uneventful recovery. Conclusion We reported two cases of a rare complication of PD catheter. The SMAP method, PWAT, enlarged kidneys and migration of the lower cuff may be risk factors of bowel perforation of a PD catheter.

Objective: To evaluate the clinical usefulness of effective renal plasma flow (ERPF) measured using preoperative mercaptoacetyltriglycine-3 (MAG3) renogram for the prediction of chronic renal insufficiency after nephrectomy. Methods: A total of 47 patients underwent preoperative MAG3 renal scintigraphy and subsequent unilateral nephrectomy. Correlations between the 5-year postoperative estimated glomerular filtration rate (eGFR) and the preoperative ERPF of the contralateral kidney (cERPF), ERPF of the diseased kidney (dERPF), total ERPF (tERPF), cERPF to dERPF ratio, serum creatinine (sCr) level, eGFR, as well as the influence of preoperative comorbidities (diabetes, hypertension) on the postoperative eGFR, were evaluated with both univariate and multivariate analyses. Results: Multiple linear regression analysis showed that preoperative cERPF significantly correlated with postoperative eGFR. However, a much stronger correlation was observed between the preoperative and postoperative eGFR. Multiple logistic regression analysis showed that only preoperative eGFR was a significant predicator of the development of advanced-stage chronic kidney disease (CKD). Conclusions: Preoperative MAG3 renogram is not superior to eGFR measurement as a prognostic indicator of long-term renal function after unilateral nephrectomy.

Background: Fulminant myocarditis involves various serious arrhythmias that sometimes have lethal consequences. The purpose of the present study was to investigate the electrocardiogram findings, arrhythmogenicity and abnormalities of the cardiac conduction system in children with fulminant myocarditis. Methods and Results: Between 1999 and 2008, 7 consecutive patients (mean age: 7 years) who suffered from fulminant myocarditis were included in the study. A 12-lead electrocardiogram, Holter monitoring and signal-averaged electrocardiograms were performed and compared between the acute, convalescent, and recovery phases in the 4 surviving patients. Also, electrophysiologic assessment was carried out during the convalescent phase. Five out of 7 patients developed complete atrioventricular block, 3 developed ventricular tachycardia, 2 had cardiac arrest, 2 developed sinus tachycardia, 1 developed ventricular fibrillation, 1 had advanced atrioventricular block, and 1 developed sick sinus syndrome. Among the surviving patients, all arrhythmias resolved during the convalescent and remote phases. No atrial or ventricular arrhythmias were induced in any patients during the programmed stimulation study. In the convalescent phase, no arrhythmias could be induced and there were no signs of any conduction abnormalities on electrophysiological assessment. Conclusions: Close follow-up should be performed to observe for the occurrence of any new arrhythmias and/or a decrease in cardiac function in children with fulminant myocarditis. (Circ J 2011; 75: 932-938)

Background This study was performed to investigate the incidence of arrhythmias in patients with Kawasaki disease (KD). Methods and Results Electrophysiologic studies (EPS) were performed in 40 patients (mean age: 10.3±5.1 years; 30 males, 10 females) with KD who had severe to moderate coronary artery disease. Clinical arrhythmias were documented in 4 patients (premature ventricular contractions, ventricular tachycardia, atrioventricular block, and ventricular fibrillation). Dual atrioventricular nodal pathways were demonstrated in 3 patients. Nonsustained atrial fibrillation was induced in 1 patient. The AH interval was prolonged in 2 patients. The Wenckebach rate was 164±37 beats/min, and 4 of the patients had a decreased Wenckebach rate. The maximum and corrected sinus node recovery times were 997±257 ms and 281±130 ms, respectively, and 7 patients were thought to be abnormal. The sino-atrial conduction time was 108±64 ms, and 2 patients had prolonged conduction times. Conclusions Although there was no relationship between coronary stenosis or obstruction and the EPS parameters, the incidence of abnormal sinus node and atrioventricular node function is apparently higher in KD patients than in the normal population. These functional abnormalities may possibly be caused by myocarditis or an abnormal microcirculation in the sinus node and atrioventricular node artery. In some patients, myocardial ischemia may provoke malignant ventricular arrhythmia. (Circ J 2008; 72: 274 - 280)

This study was designed to evaluate the usefulness of real-time 3-dimensional echocardiography (RT-3DE) for evaluating coronary artery morphology in patients with Kawasaki disease.The diagnosis of coronary artery morphology in the acute phase of the disease is of prime importance for evaluating the likelihood of cardiovascular sequelae. Occasionally, visualization of the right coronary artery and bifurcated regions, including the circumflex artery, has proved challenging with traditional echocardiographic methods.A total of 111 patients with Kawasaki disease were studied. Coronary aneurysms were detected in 8 patients (4 had giant aneurysms), and coronary dilation was found in 11 patients. Coronary artery visualization was evaluated and scored as 1 of 4 grades, 0 to 3 points, for both 2-dimensional echocardiography (2DE) and RT-3DE. Evaluation criteria for each coronary artery were defined according to the American Heart Association classification of coronary angiographic features. Total scores for each patient and for individual coronary branches were compared between 2DE and RT-3DE.The total scores for coronary artery visualization were, respectively, showing a significantly higher score for RT-3DE than for 2DE (P.01). A mural thrombus could be clearly delineated in the giant coronary aneurysms by RT-3DE.RT-3DE is superior to 2DE for coronary artery visualization. This diagnostic system is expected to improve the screening of coronary artery abnormalities in Kawasaki disease.

Background Catheter ablation inside the Koch's triangle has a risk for complete atrioventricular block. Methods and Results The anatomic size of the coronary sinus (CS) and His bundle (HB) in children and the distance between them was studied using a 3-dimensional electroanatomical mapping system (CARTO). Fifty-three children (mean age, 11.8±3.7 years) without congenital heart disease (ie, 24 with atrioventricular re-entrant tachycardia, 18 with atrioventricular nodal re-entrant tachycardia, 7 with atrial tachycardia, 2 with ventricular tachycardia and 2 with atrial flutter) were studied. The size of the HB recording area was 148±97 mm2 and the size of the CS was 66±44 mm2. The size of the CS and the distance between the HB and CS (18±7 mm) were proportional to body weight, body length and body surface area. All patients underwent catheter ablation, including 25 ablations inside Koch's triangle. Catheter ablation was successful in 52 patients without any atrioventricular nodal injury. Conclusions The CS size and the distance between the HB and CS increased proportionally with children's growth. To know the distance from the HB to the ablation point is useful in avoiding atrioventricular node injury, and information about the length of Koch's triangle may provide supportive information when applying radiofrequency energy inside Koch's triangle without needing to use the CARTO system in children, but this merits further investigation. (Circ J 2007; 71: 1918 - 1921)

Background This study was performed to investigate the frequency and importance of supraventricular arrhythmia and sinus node (SN) dysfunction in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). Methods and Results Eight patients with CPVT (mean age: 16.8±8.1 years) underwent an electrophysiological study. SN recovery time (1,389±394 ms) was slightly prolonged, and 4 of 8 patients had abnormal values. Atrial flutter (AF) was induced by low-rate atrial pacing in 2 patients and by isoproterenol infusion in 1 patient. Atrial fibrillation (Af) was induced by isoproterenol infusion in 2 patients. One patient presented with Af during the follow-up period, and 2 of 4 patients with AF/Af presented with increased SN recovery time. Conclusions Patients with CPVT frequently have associated with SN dysfunction, and inducible atrial tachyarrhythmias, which indicate that the pathogenesis of CPVT is limited not only to the ventricular myocardium, but also to broad regions of the heart, including the SN and atrial muscle. (Circ J 2007; 71: 1606 - 1609)

Background The purpose of this study was to determine the appropriate recommendations for weaning off cardiopulmonary support (CPS) in children with fulminant myocarditis. Methods and Results Four consecutive patients diagnosed with fulminant myocarditis who were treated with CPS were enrolled (mean age: 9 years). The relationships between timing of weaning from CPS and various factors, including bleeding episodes, platelet count, serum concentration of the MB isoform of creatine kinase (CK-MB), echocardiographic findings, and the mixed venous blood oxygen saturation (SvO2), were retrospectively analyzed. All patients had CPS performed safely for a mean duration of 53.1 h without exchange of the circuit. Three of the 4 patients had a bleeding episode before discontinuation. The minimum platelet count occurred during weaning in all 4 patients. The peak serum CK-MB concentration when initiating CPS was higher than the peak value on the day of weaning. Echocardiographic findings before stopping CPS were similar to those after weaning. The SvO2 was 62.5% when initiating CPS and 71.3% before weaning. Conclusions In children with fulminant myocarditis CPS can be used without exchanging the circuit and can be discontinued before bleeding episodes become symptomatic, with improvement in the biomarkers and SvO2 on weaning off CPS. (Circ J 2007; 71: 1551 - 1554)

Congenital hydronephrosis is one of the most common anomalies found in humans and may cause renal failure in childhood. Half of the cases are due to obstruction at the ureteropelvic junction (UPJ). Here we report that mice lacking Id2, an inhibitor of basic helix-loop-helix (bHLH) transcription factors, exhibit hydronephrosis mimicking the characteristics of human cases such as unilaterality and male preponderance. Hydronephrosis was found even in Id2+/- mice. The penetrance was 67.2% in Id2-/- males, 48.8% in Id2+/- males, 28.0% in Id2-/- females and 20.0% in Id2+/- females. Distortion or high insertion of the ureter at the UPJ was frequently observed and these morphological changes were evident in late embryogenesis. Histologically, the muscle layer, where Id2 is normally expressed, was hypertrophic and/or irregular at the UPJ. Furthermore, gene expression analysis suggested that BMP4 (bone morphogenetic protein 4), which is known to be involved in the development of hydronephrosis, appears to function as an upstream factor of Id2. Our results thus raise the possibility that Id2 is a gene responsible for the pathogenesis of hydronephrosis in man.

The most serious problem regarding a laparoscopic partial nephrectomy is how to perform bloodless excision without causing renal ischemia in a limited working space. We report the case of a 65-year-old man with left small renal cell carcinoma in the posterior mid zone who underwent a laparoscopic partial nephrectomy through a retroperitoneal approach by carrying out the ligation of the tumor-feeding artery, but without clamping the renal pedicle. Both preoperative abdominal computed tomography (CT) and intraoperative ultrasonography revealed the tumor to be fully encapsulated. The tumor-feeding artery could be exposed by dissection from the renal hilum and, after an arterial ligation, tumor resection with a safety margin was smoothly performed with minimal bleeding. Postoperatively, CT revealed a limited defect of the renal parenchyma and excretory pyelography showed no urine leakage or urinary tract obstruction. The preoperative and postoperative creatinine levels were 0.66 and 0.69 mg/dL, respectively. As a result, a tumor-feeding artery ligation with a laparoscopic partial nephrectomy for left renal cell carcinoma in the posterior mid zone is considered to be an effective surgical modality which avoids renal ischemia and pelvic heat injury.

Background: To assess the prognostic usefulness of the nuclear area index (NAI), a new nuclear morphometric parameter expressed as the mean nuclear area (MNA) ratio of cancer to normal transitional cells in patients with bladder cancer, who have undergone radical cystectomy. Methods: Measurements of the nuclear areas of cancer and normal transitional cells were carried out on the histological slides of 73 patients with bladder cancer. The clinical usefulness of MNA, NAI, grade, and TNM categories for the prediction of the cause-specific survival of the patients was examined. Results: The median values of MNA and NAI in the 73 patients were 39 µm2 and 1.2, respectively. Cause-specific survival rates of the patients were calculated according to stage (T1–2 vs T3–4), grade (grade 2 vs grade 3), MNA (

We studied 24 patients with severe coronary artery lesions to assess myocardial perfusion and left ventricular contractile reserve simultaneously using low-dose dobutamine quantitative electrocardiographically gated single-photon emission computed tomography in patients with Kawasaki disease. Low-dose dobutamine infusion was started after an injection of technetium-99m tetrofosmin at rest. Myocardial contractile reserve was evaluated using the post-stress and low-dose dobutamine images, and myocardial perfusion was evaluated using the stress and rest images. Quantitative electrocardiographically gated single-photon emission computed tomography during low-dose dobutamine infusion is a useful and safe method for the combined evaluation of myocardial contractile reserve and myocardial perfusion.

Purpose: The purpose of this study was to investigate the prognostic value of measuring glucose metabolism of primary prostate cancer lesions, using 2-Deoxy-2-[F-18]Fluoro-D-Glucose positron emission tomography (FDG-PET). Procedures: Forty-two patients with prostate cancer were investigated with FDG-PET, and standardized uptake value (SUV) of the prostate was calculated. After PET study, radical prostatectomy was performed in 17 patients (RPT group), and endocrine therapy in 25 patients (ET group). Relapse-free survival curves were created by the Kaplan-Meier method. Results: In the RPT group, the patients with high SUV had a poorer prognosis compared to those with low SUV (P = 0.033). In the ET group, the patients with high SUV were likely to have a poorer prognosis with low significance at a level of P = 0.087. Conclusions: FDG-PET appeared to have a defined prognostic value for patients with prostate cancer undergoing radical prostatectomy, and more patients need to be studied for patients undergoing endocrine therapy. (Mol Imag Biol 2002;4:99–104)

1. The disposition of SM-11355, an anticancer platinum complex for hepatocellular carcinoma, was investigated in dog by measuring platinum (Pt) and radioactivity levels following intrahepatic arterial administration of (14)C-SM-11355 suspended in Lipiodol, an oily lymphographic agent. Plasma and excretion profiles were monitored in six animals, with tissue distribution studied after 1 day, 4 and 13 weeks (n = 2/time point). 2. SM-11355 was released very slowly into the systemic circulation from Lipiodol, resulting in very low levels of Pt compounds in plasma, urine, faeces and organs. Plasma levels of Pt and radioactivity declined with apparent half-lives of 5-7 weeks. Excretion continued even at 3 months after the administration with proportions excreted for Pt and radioactivity up to 30-60% in urine and 8-10% in faeces. 3. The Pt and radioactivity in the liver accounted for 80-100% of the dose at 1 day and for 20-50% at 13 weeks after the administration, predominately as intact SM-11355. The concentrations were highest in the left lobe of the liver, the administration site, but levels in the remainder of the liver were also markedly higher than those in plasma and other tissues. 4. The results strongly support the concept that SM-11355 targets the liver with highly selectivity and sustained release of Pt compounds.

Retroperitoneal cystic lymphangioma is a rare benign tumor. Most patients eventually experience some symptoms that necessitate therapeutic intervention. Excision is the treatment of choice, and some cases of laparoscopic resection have been reported. We report another case of a huge retroperitoneal cystic lymphangioma that was successfully excised laparoscopically with the SAND balloon catheter. Large cystic lymphangioma was downsized by puncturing and aspirated with the SAND balloon catheter. Laparoscopic surgical technique should be considered for treatment of selected cystic lesions of retroperitoneal origin.

Objectives. To assess the diagnostic accuracy of the World Health Organization (WHO) grading system for renal cell carcinoma (RCC) in terms of nuclear size evaluation. Furthermore, the prognostic usefulness of the nuclear area index (NAI), a new nuclear morphometric parameter expressed as the mean nuclear area (MNA) ratio of cancer to normal tubular cells, is investigated. Methods. Measurement of the nuclear areas of cancer and normal tubular cells was performed on the histologic slides from the 76 patients with RCC, and the distribution of MNA and NAI was compared among the WHO grades. The clinical usefulness of MNA, NAI, grade, and TNM categories for the prediction of the progression-free and cause-specific survival of the patients was examined. Results. MNA for cancer cells and NAI significantly increased according to the grade. NAI was 1.0 or less in 9 of the 10 patients with G1 tumors and more than 1.0 in 12 of the 13 patients with G3 tumors, whereas the NAI ranged widely from 0.53 to 2.0 in 53 patients with G2 tumors. By multivariate analysis, including grade and TNM categories, NAI and MNA were independent variables for survival in all the patients as well as for cancer progression in localized disease. Conclusions. WHO G2 RCCs are actually composed of tumors with varying nuclear size, and the prognosis of the patients with G2 tumors varied as well. NAI could provide improved prognostic information for the patients with RCC, especially in G2 cases.

Anomalous origin of the right coronary artery is a relatively rare coronary artery anomaly which is known to cause myocardial ischemia and sudden death. Association of anomalous origin of the right coronary artery with congenital bicuspid aortic valve is even rarer with only a few cases being reported previously. We describe, for the first time, MDCT findings of anomalous origin of the right coronary artery associated with congenital bicuspid aortic valve.

Objectives. To compare the prognostic value of stereologically estimated volume-weighted mean nuclear volume (MNV) with other nuclear morphometric parameters using pretreatment needle-biopsy specimens of prostate cancer. Methods. The MNV, mean nuclear area, form factor, and coefficients of variation for nuclear area (VNA) and form factor were measured on pretreatment needle biopsy specimens from 66 patients with prostate cancer (clinical Stage B, n = 9; Stage C, n = 14; and Stage D, n = 43), all of whom underwent androgen deprivation therapy. The prognostic value of those morphometric parameters, as well as Gleason score and clinical stage, was examined in terms of cause-specific patient survival using univariate and multivariate analysis (Cox proportional hazard model). Results. Univariate analysis of the nuclear morphometric parameters revealed that MNV, mean nuclear area, VNA, coefficient of variation for form factor, and clinical stage were significant prognostic factors for cause-specific patient survival. However, when the patients with Stage D disease were selectively analyzed for survival, only the VNA was a significant prognostic parameter. Furthermore, the multivariate analysis, including the morphometric parameters, clinical stage, and Gleason score revealed that only VNA and clinical stage were independent variables. Conclusions. The present comparative study could not demonstrate any prognostic superiority of MNV over other nuclear morphometric parameters in patients with prostate cancer.

Postmenopausal osteoporosis is caused mainly by a deficiency of oestrogen with rapid bone loss. To target oestrogen to the bone effectively, we have synthesized and evaluated the effects of a novel hybrid compound of oestrogen and bisphosphonate, SM-16896. The tissue distribution pattern and pharmacological potential are reported. Although the affinity for calf uterine oestrogen receptor was very low (IC50: 73.3 μM; 1/25000 of that of 17β-oestradiol (2.84 nM)), SM-16896 showed oestrogenic activity. SM-16896 (1 μM) induced a 4.5-fold transcriptional activity in rat osteosarcoma UMR-106 cells compared with vehicle-treated control, when we used the expression vector for human oestrogen receptor and a CAT reporter plasmid containing an oestrogen-responsive element. The distribution of SM-16896 after a subcutaneous administration to 7-week-old female rats was examined by radioluminography using 3H-labelled SM-16896. At 30 min after the administration, significant radioactivity was detected in the bone. At 24 h after administration, a high level of radioactivity was detected in the bone, but in the uterus it was only at a background level. Daily subcutaneous administration of 0.5 mg kg−1 SM-16896 for 12 weeks (five times per week) to 13-week-old ovariectomized rats suppressed the ovariectomized-induced reduction in bone mineral density. A bone mineral density ratio of 120% was maintained compared with sham-operated rats, whereas a relatively low suppression of uterine weight was observed (about 50% loss compared with sham-operated rats). In the same experiment, the implantation of a 17β-oestradiol time-release pellet (0.25 mg/pellet/90 days) almost completely suppressed the reduction of both the bone mineral density and uterine tissue weight. It is likely that the effect of SM-16896 on bone was due to its oestrogenic activity, since 1.0 mg kg−1 SM-18108, the bisphosphonate moiety of this compound, had no effect on bone in 7-week-old ovariectomized rats. The results suggest that SM-16896, a bisphosphonate-conjugated oestrogen, showed a preference profile in the uterus and bone due to its characteristic distribution pattern compared with the natural oestrogen analogue 17β-oestradiol. Thus, bisphosphonate-conjugated oestrogens have the potential to improve patient compliance in oestrogen therapy by minimizing adverse effects and reducing the frequency of medication.

Bland-White-Garland syndrome (BWG) is a rare disorder that includes abnormalities of the coronary arteries that cause severe myocardial ischemia or infarction in infancy. In this case report, we describe an infant with BWG evaluated by dual single photon emission computed tomography using thallium-201 and I-123 beta-methyl-p-iodophenyl-pentadecanoic acid before and after surgery.

BACKGROUND To evaluate the clinical usefulness of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) compared with histopathological grading, clinical stage and serum prostatic specific antigen (PSA) level in the detection and characterization of prostate cancer. METHODS Forty-four patients with histologically proven prostate cancer and five control subjects with benign prostatic hyperplasia (BPH) were prospectively investigated with FDG-PET prior to treatment. RESULTS By visual inspection, FDG accumulation was positive in 28 patients with prostate cancer (sensitivity 64%), whereas all were negative in the control group. FDG-PET in three patients with lymph node metastases did not show any high intrapelvic accumulations corresponding to metastatic sites. Among 12 patients with multiple bone metastases which were detected with 99m-HMDP bone scintigraphy, nine (75%) showed moderate to high FDG accumulation at the sites of bone metastases. Quantitatively, FDG accumulation in prostate cancer was significantly higher than in BPH and there was a tendency for FDG uptake of tumors to be higher with higher histological Gleason grades. Furthermore, FDG uptake in tumors with lymph node and/or bone metastasis was significantly higher than that of localized stages. However, the correlation between PSA and FDG uptake in the prostate cancer was very weak for clinical relevance. CONCLUSIONS Although FDG-PET was not sensitive enough to detect prostate cancer in clinical use, it is suggested that glucose metabolism in prostate cancer tended to be higher in patients with tumors of advanced stages.

An immunohistochemical study was conducted to examine the expression of p53 and bcl-2 proteins in RCC (renal cell carcinoma) with sarcomatoid change in order to determine whether abnormalities in those proteins are associated with an enhanced malignant potential of RCC. Paraffin-embedded tissues from 11 patients with RCC, in which sarcomatoid change was prominent, were stained using anti-p53, bcl-2 and Ki-67 antibodies. Immunoreactivities for these antibodies were compared between the sarcomatoid components and corresponding basic histologic (clear or papillary) components in individual cases. Measurement of the mean nuclear areas of each component was also performed using an image analyzer system. There was no substantial increase in immunoreactivity for p53 or bcl-2 proteins in sarcomatoid components as compared with basic components. In contrast, the percentage of Ki-67-positive cells and the mean nuclear area were significantly larger in sarcomatous components than in basic components. The expression of p53 and bcl-2 proteins was not likely to play a major role in the sarcomatoid change of RCC.

Background: Pelvic lymph node dissection (PLND) is an important staging method for men with clinically localized prostate cancer. We report our experience with staging PLND and the impact of lymph node metastasis on long-term prognosis. Methods: One hundred forty-eight consecutive patients who underwent staging PLND for clinically localized prostate cancer were retrospectively studied. Patients were evaluated for the presence and number of lymph node metastases, treatment (prostatectomy vs. radiotherapy), and endocrine therapy, and analyzed with respect to disease progression and survival. The mean follow-up period was 52.9 months (range, 2.3 to 165.8 months). Results: Thirty-two patients (21.6%) had pelvic lymph node metastases, the incidence of which markedly decreased from 32.3% in 1982 to 1987 to 6.7% in 1994 to 1997. The intervals to disease progression and cancer death were significantly shorter in patients with positive lymph nodes (P < 0.001). In stage D1 disease, patients who underwent a radical prostatectomy tended to be free of progression longer than those receiving radiotherapy or conservative therapy (P= 0.0546). Other factors, such as early endocrine therapy, the extent of lymph node involvement and the Gleason score of the primary tumor did not predict disease progression or survival. Conclusion: These data suggest a decreasing trend in the incidence of lymph node metastasis in the PSA era. Although longer disease-free intervals were observed in radical prostatectomy-treated patients, the impact of an aggressive approach to stage D1 disease awaits further studies.

In order to investigate if and when the bcl-2 oncoprotein is activated in bladder tumorigenesis and its relationship with p53 overexpression and patient survival, we studied bcl-2 and p53 expression immunohistochemically in matched normal urothelium, dysplasia and cancer specimens selected by step-sectioning from 54 radically resected bladders for non-metastatic transitional cell carcinoma (TCC). In normal urothelium and mild dysplasia, bcl-2 was restricted to the basal cell compartment, while in moderate and severe dysplasia its expression was detectable also in the upper regions. Excess bcl-2 immunoreactivity was found in 27 (50%) of carcinomas, and a larger proportion of high-grade TCCs showed bcl-2 expression compared with that of low-grade TCCs (P < 0.05). Overexpression of p53 protein showed a increasing trend toward the progression of bladder tumorigenesis (P < 0.01) and a significant reciprocal correlation was found between bcl-2 and p53 expression in either various dysplasias (P < 0.01) or carcinoma (P < 0.05). With the evolution from mild dysplasia to carcinoma in individual cases, loss of bcl-2 expression was more frequently observed in superficial (P < 0.02) or low-grade carcinoma (P < 0.05) than in muscle-invasive or high-grade carcinoma. Furthermore, patients with negative immunostaining for both bcl-2 and p53 in cancer lesions had a significantly more favorable prognosis compared with those with positive immunostaining for the oncoproteins (P < 0.05), although bcl-2 by itself did not predict patient survival. We suggest that aberrant activated bcl-2, which is seen earlier than p53, appears to facilitate bladder tumorigenesis and to enhance tumor aggression in some extent.

Background This study investigated the relationships between the numeric aberrations of chromosome 17 and p53 expression, the proliferating cell nuclear antigen labeling index (PCNA-LI) and histopathology, to determine their prognostic significance in bladder cancer. MethodsUsing in situ hybridization (1SH) with a biotin-labeled chromosome-specific DNA probe, the copy number of pericentromeric sequences in chromosome 17 were detected within interphase nuclei in formalin-fixed paraffin-embedded sections from 59 nonmetastasized transitional cell carcinomas (TCCs) of the urinary bladder. Expression of p53 and PCNA-LI were determined in serial sections by an immunohistochemical method. Results The percentage of hyperdiploid cells for chromosome 17 correlated with p53 overexpression (P< 0.002), PCNA-LI (P< 0.002), increasing tumor grade (P< 0.002) and advanced pathologic stage (P< 0.002). The average percentage of hyperdiploid cells was lower in tumors with negative p53 expression than in tumors with p53 overexpression (P< 0.002). Also, more polysomic TCCs were found in muscle-invasive than in superficial cases (P< 0.01), and there was a difference in both p53 overexpression or PCNA-LI between disomic and polysomic TCCs (P

Morphological similarities between renal oncocytomas and 'oncocytic' renal cell carcinomas (RCCs) make a differential diagnosis in many cases difficult. A series of 41 renal oncocytomas has been analysed by microsatellite markers from chromosomes 1, 2, 3p, 6q, 8p, 9, 10, 13q, 14q, 17, and 21, alterations of which are known to be involved specifically in non-papillary and chromophobe RCCs. Only eight of the 41 renal oncocytomas showed loss of heterozygosity (LOH). LOH at chromosomes 1 and 14 occurred in four tumours each and at chromosomes 2, 8, and 9 in one tumour each. Combined LOH at chromosomes 1, 9, and 14 and also at chromosomes 1 and 14 occurred in one case each. No LOH was seen at any other genomic sites. The lack of combination of LOH at specific chromosomal sites differentiates renal oncocytomas from other renal cell tumours with overlapping phenotypes. Applying the microsatellite assay described here, the diagnosis can be established within 2 days, from fresh as well as from paraffin-embedded material.

In this study, 105 non-papillary renal cell carcinomas (RCCs) have been examined for allelic loss at the chromosome 8p12-21.1, 9p21, and 14q24.2-qter regions, each by two highly polymorphic microsatellites. Loss of heterozygosity (LOH) was detected at both chromosome 8p and 9p in 33 per cent of the cases and at chromosome 14q in 45 per cent of the tumours. A correlation of variables such as size, grade, and stage of tumours with these specific genetic alterations showed that loss of chromosomes 8p and 9p, and especially loss of chromosome 14q regions, is significantly associated with a higher grade of tumour and the combined LOH at these chromosomal sites with advanced tumour stage. These genetic alterations did not show any correlation with the size of non-papillary RCCs. This study suggests that genetic markers at the above-mentioned chromosomal sites can predict the clinical outcome of non-papillary RCCs.

Background: This study was conducted to determine if there are any specific histologic features that are associated with lymph node metastasis in renal cell carcinoma (RCC). Methods: TNM classification, histologic grade, mean nuclear volume, cell type, and histologic architecture of the tumors were evaluated in 66 patients who had undergone nephrectomy and lym-phadenectomy for RCC. In the 18 patients with positive lymph node metastasis, both primary lesions and metastatic lymph nodes were evaluated. Results: Lymph node status was correlated with primary tumor stage, venous involvement, and distant metastasis. The tumor grade was higher, and the mean nuclear volume was larger, in both primary and metastatic lesions of RCCs with lymph node metastasis than in tumors with no metastasis. In primary lesions of RCCs with lymph node metastasis, clear cell, alveolar, or cystic patterns were observed less frequently, and granular or spindle/pleomorphic cells and papillary or solid patterns, were observed more frequently, as compared to those lesions without metastasis. Comparison between primary and metastatic lesions in individual patients revealed no significant difference in grade or mean nuclear volume. The development of new cell types or histologic architectures, which was not noted in the primary lesions, was also a rare event in the metastatic lesions. Conclusion: Several characteristic histologic features, which may reflect the increased metastatic potential of the tumor, were observed in both primary and metastatic lesions in cases of RCC with lymph node metastasis. No substantial difference in histologic features was observed between the primary or metastatic lesions of individual patients.

BACKGROUND Although renal cell carcinoma (RCC) is often heterogeneous, the histological classification of RCC in Japanese Urological Association (JUA) is designed to select only the dominant histological components. We evaluated whether this system could provide an adequate information concerning the prognosis of the patients. METHODS Histological slides of 130 cases with RCC were microscopically evaluated. We classified these cases according to the JUA classification, and also checked the presence or absence of each histological components (3 cell types and 5 histological architectures) regardless of whether or not they were dominant. Univariate and multivariate analysis were then performed to determine the histological components which have prognostic impact on patient survival. RESULTS Multivariate analysis demonstrated that only spinde/pleomorphic cells and solid architecture were the significant prognostic parameters. The presence of these histological components was not correctly shown in the JUA classification. CONCLUSION The histological classification of RCC in JUA did not provide enough information about the presence of the important prognostic parameters. This system should be modified to describe all the histological components regardless of whether they are dominant or not.

Background: This study was performed to evaluate the frequency of local tumor extension and its effect on disease progression after radical prostatectomy. Methods: The study consisted of 66 consecutive men who underwent radical prostatectomy for clinically localized prostate cancer without any prior hormonal therapy. Cases were stratified according to pathologic findings. Sites of capsular penetration were also evaluated. Results: The overall incidences of lymph node metastases, seminal vesicle invasion, capsular penetration, and positive surgical margin were, respectively, 23%, 32%, 55% and 35%. The disease progression rate in patients with positive lymph nodes differed significantly from that in those without nodal metastases (P < 0.0001). Although seminal vesicle invasion, capsular penetration, or positive surgical margin had an adverse effect on prognosis, the difference in progression missed statistical significance, when patients with positive lymph node metastases were excluded. The most common site of capsular penetration was posterolateral, in the area of the neurovascular bundle. Conclusions: Extraglandular tumor extension and positive surgical margins are common features of radical prostatectomy specimens. A nerve-sparing operation should be performed selectively and with great caution. The markedly adverse effect of lymph node involvement on progression must be accounted for when evaluating other variables relating to progression.

Background: It is well recognized that the histology of renal cell carcinoma (RCC) is often heterogenous. It is also believed that the prognosis of patients with large tumors is generally poorer than those with small tumors. However, there has been no detailed study on changes in histological features of RCCs associated with tumor growth. This study was conducted to investigate whether there are any specific histological changes related to tumor size and to study the prognostic value of histological parameters in RCCs. Methods: The presence or absence of each histological component (3 cell types and 5 histological architectures) was investigated in 110 RCCs. The tumor size-associated changes in the histological composition of the RCCs were evaluated, and the prognostic significance of the histological parameters was analyzed using univariate and multivariate analysis. Results: The percentage of RCCs with multiple cell types increased with tumor size, whereas increases in multiplicity were not as prominent in the histological architectures. Several characteristic changes, however, were observed in both cell types and architectures. RCCs with a pure clear cell, pure alveolar pattern or cystic architectural pattern decreased, while those with granular or spindle/pleomorphic cell types, or papillary or solid architectural patterns increased with tumor size. A univariate analysis revealed that a clear cell type and an alveolar or cystic architectural pattern were associated with a better prognosis, while spindle/pleomorphic cells and a solid architecture pattern correlated with a poorer prognosis. Multivariate analysis of cell types and architectures showed, however, that only the presence of spindle/pleomorphic cell types and a solid architecture were independent prognostic variables. Conclusion: The histological composition of RCCs varied according to the size of the tumor. Sarcoma-tous components increased with tumor size and were independently associated with a poor prognosis. Further study is warranted to correlate specific genetic alterations with tumor growth-related histo-logical changes in RCCs.

This paper describes a case of laparoscopically resected leiomyoblastoma, with a review of the literature. A 39-year-old man was found having a submucosal tumor (SMT) in the posterior wall of the stomach. It was diagnosed as leiomyoma preoperatively. Laparoscopic local excision of the stomach including the tumor was carried out. Pathological diagnosis of the resected apecimen was leiomyoblastoma, but mitotic figures were lacked. We evaluated the tumor asbenign and did no additional operation. Recent examination one year and four months after the laparoscopic operation showed no gastric deformity nor sign of recurrence. The patient's quality of life is the same as before the operation. Leiomyoblastoma is a rare tumor among various gastric SMTs. If it is small in size, the differential diagnosis from leiomyoma of leiomyosarucoma is difficult to make. Therapy of leiomyoblastoma usually comprises prophylactic lymphadenectomy and gastrectomy, considering the malignancy. Local resection is rarely performed. Howerver, for small gastric SMTs of with preoperative diagnosis whether benign or malignant is difficult, the treatment of choise may be a minimal invasive laparoscopic resection first, and if pathological diagnosis is malignant, additional radical operation is followed. Such strategy will spare unnecessary gastorectomies.

The effect of unilateral nephrectomy on the growth of bladder tumors was investigated in male F344 rats treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) for 6 weeks by means of macroscopical and microscopical examinations. Unilateral nephrectomy 4 weeks after the initiation of BBN administration significantly increased both the number and the volume of visible tumors per rat as compared with the sham-operated group. Histological examination also revealed that the numbers of papillonodular hyperplasia and cancer per basement membrane were significantly increased by unilateral nephrectomy. The results imply a growth-enhancing effect of unilateral nephrectomy on carcinogenesis of the rat bladder.

Background: Disease progression after Bacillus Calmette-Guerin (BCG) instillation therapy for bladder cancer is not rare. The purpose of this study was to evaluate the outcome of patients treated with BCG for superficial bladder cancer, focusing on the patients who developed invasive disease during follow-up. The possible mechanism and risk factors for early progression after BCG therapy are discussed. Methods: A total of 25 patients with superficial bladder cancer (pTa, pT1, and/or pTis) were treated with intravesical BCG instillation (80 mg in 80 mL saline) once a week for eight weeks. Four of the 25 patients received maintenance therapy with BCG (once a month for 3 to 10 months). Patients were followed every three months and underwent cystoscopy, biopsy, and urinary cytology at these intervals. Disease progression was defined as invasion to muscle or prostate, or development of metastatic disease. Clinicopathological features of the patients, especially those with progression, were analyzed. Results: Progression was observed in six of the 25 patients (including four of 19 patients with carcinoma in situ and two of five patients treated prophylactically with BCG). The average time to progression was 8.7 months. Four patients died of cancer despite intensive treatment. Two patients are alive: one without evidence of disease after cystectomy and the other with metastatic disease. Conclusions: Proper patient selection, careful follow-up, and immediate aggressive therapy in case of progression were considered to be important factors to obtain satisfactory results with BCG therapy for bladder cancer.

The high spatial resolution of multislice computed tomography (MSCT) permits direct visualization of the coronary artery system. In this report, we describe coronary artery abnormalities in a young adult with Kawasaki disease. MSCT detected a giant coronary artery aneurysm, coronary artery stenosis in the first diagonal artery, and a multi-layered structure in the right coronary artery and the left circumflex artery. These findings corresponded well to those obtained by coronary angiography. MSCT has the potential to be the standard diagnostic tool for the follow-up evaluation of coronary artery disease in adolescents and young adults with Kawasaki disease.

A 21-year-old female patient underwent emergency cesarean section and a postoperative hematoma occurred at the site of the uterine incision. The patient underwent laparotomy for hemostasis. An 3 cm perforation at the posterior wall of the bladder was identified. The bladder was repaired in two layers with an absorbable suture. Three days later she developed a fever of over 38 degrees C. Despite therapy with several antimicrobial agents, her fever persisted and the wound was opened. Computed tomography scan revealed an abscess at the site where the hematoma had formed. We present a case of severe wound infection that was caused by Mycoplasma hominis infection after cesarean section. Bladder perforation associated with cesarean section is uncommon. Mycoplasma hominis should be considered as a causative organism if an antimicrobial resistant infection occurs at the surgical site after a cesarean section.

Objective To test the hypothesis that textural changes in the carotid intima–media complex (IMC) detected by B-mode ultrasound are associated with the difference of remodeling process in earlier atherosclerotic involvement in patients with Kawasaki disease (KD) and coronary artery lesions (CALs). Methods Eighteen patients with KD and CALs (mean age 17.2 years), 17 patients with heterozygous familial hypercholesterolemia (FH) (mean age 16.9 years) and 15 age-matched healthy controls (Cont) were assessed and compared for carotid intima–media thickness (CIMT), elastic property ( E p ), and first- and second-order statistics. Results KD showed significantly higher gray scale median (GSM) than FH and Cont. KD and FH showed significantly higher CIMT, entropy and lower angular second moment than Cont, but no significant difference was found between KD and FH. Conclusion Higher GSM in KD may indicate alteration of tissue components and heterogeneity of IMC, suggesting the development of arteriosclerotic vascular remodeling after vasculitis. This is distinct from that of atherosclerosis with lower GSM often observed in FH.

Background To test the hypothesis that textural changes in the carotid intima-media complex (IMC) on visual inspection by B-mode ultrasound are associated with early atherosclerotic involvement in patients with heterozygous familial hypercholesterolemia (FH). Methods 55 patients (mean age 13.4 years) were categorized into three groups according to the degree of thickness in IMC (intima-media thickness [IMT]) (groups I–III) and 15 healthy controls within the same age range as the patients were assessed for first- and second-order statistics and visual scoring of textural changes in IMC (1, normal; 2, proximal interface disruption; 3, granulation). Results There was no significant difference in first-order statistics among the four groups. As for second-order statistics, groups II (moderately increased IMT) and III (markedly increased IMT) had significantly higher entropy and lower angular second moment than group I (normal IMT) and control. Likewise, groups II and III received significantly higher visual scoring than group I. Visual scoring correlated with entropy ( r = 0.57) and angular second moment ( r = −0.50). Multiple regression analysis identified entropy (beta = 0.52) and visual scoring (beta = 0.42) as significant determinants of IMT. Conclusions These findings demonstrate that higher visual scoring may indicate dishomogeneity of IMC, suggesting early medial infiltration. This seems to be a simple visual marker to more effectively identify high-risk young patients with FH.

The effects of oral administration of nordihydroguaiaretic acid (NDGA), an antioxidant and inhibitor of arachidonic acid metabolism, on rat bladder carcinogenesis were examined. Six‐week‐old male Fischer 344 rats were given drinking watar containing 0.05% N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine for 4 weeks. Following this 4‐week period, diet containing 5% sodium saccharin (SS) with or without 0.1% NDGA supplement was given to the rats for 36 weeks. The incidences of papillary or nodular (PN) hyperplasia and of papilloma in the group treated with SS plus NDGA were significantly lower than those in the group treated with SS alone. The number of PN hyperplasic foci per 10 cm of basement membrane in rats treated with SS plus NDGA was also lower than that in the group treated with SS alone. These results suggest that NDGA has an anti‐tumor‐promoting effect on rat bladder carcinogenesis.

A 76-year-old-man was admitted to our hospital for a recurrent bladder tumor. He had received intravesical bacillus Calmette-Guérin (BCG) treatment for a transitional cell carcinoma of the bladder. A follow-up cystoscopy revealed a solitary papillary tumor in the left bladder wall. A transurethral cold cup biopsy revealed a nephrogenic adenoma without any evidence of malignant cells. We discuss the pathogenesis of nephrogenic adenoma and suggest that prolonged cystitis caused by intravesical BCG may play an etiological role.

In patients with Kawasaki disease (KD), serial evaluation of coronary artery aneurysms (CAAs) and luminal narrowing is essential for risk stratification and therapeutic management. Therefore, non-invasive assessment of the status of the coronary artery is of utmost importance in patient management. Multislice spiral computed tomography (MSCT) permits non-invasive visualization of the entire coronary artery system and was used in the evaluation of 4 patients with KD. CAAs and high-grade coronary artery stenoses were detected by MSCT and corroborated the findings of coronary angiograms performed within the previous 2 years. MSCT has the potential to be the standard diagnostic tool in adolescents with KD.

In the clinical study of prostate cancer, the effect of androgen ablation on glucose metabolism in cancer tissue has not been elucidated. The purpose of this study was to investigate the change in glucose utilization due to endocrine therapy for prostate adenocarcinoma. Ten patients with histologically proven prostate cancer were prospectively investigated with (18)F-fluorodeoxyglucose and positron emission tomography (FDG PET) prior to and after the initiation of endocrine therapy. FDG uptake was calculated to measure glucose utilization in cancer tissue. The change in FDG accumulation was compared with changes in serum prostate specific antigen (PSA) level and prostate size. FDG accumulation in the prostate decreased in all patients 1-5 months after the initiation of hormone therapy. The serum PSA level and prostate size measured on computerized tomography (CT) also decreased in these periods. A decrease in FDG accumulation was also demonstrated in metastatic sites. In this study, there appeared to be a decrease in FDG uptake in prostate cancer after endocrine therapy not only in primary prostate cancer lesions but also at metastatic sites, suggesting that the glucose utilization by tumours was suppressed by androgen ablation.

Objectives. To perform pelvic venoablation with ethanol injection into the deep dorsal vein for the treatment of 10 patients with venogenic erectile dysfunction. This procedure was easily performed without any selective embolization technique. The efficacy and safety of this technique are discussed. Methods. A total of 10 patients with veno-occlusive dysfunction, severe enough to make vaginal insertion impossible, underwent pelvic venoablation with ethanol. The mean patient age was 67.1 years. Under spinal anesthesia, after the venous leaks were identified by cavernosography, a 20-gauge flexible needle was inserted into the deep dorsal vein. The pelvic venogram obtained with deep dorsal venography was included in what was revealed by the venogram obtained with cavernosography. A mixture of absolute ethanol and contrast medium (4:1) was used as a sclerosing agent. Under fluoroscopic control, the sclerosing agents were injected into the deep dorsal vein through a flexible needle. Success was defined as the ability to achieve vaginal insertion without the aid of any drugs, vasoactive injections, penile prosthesis, or vacuum device. Results. The follow-up ranged from 25 to 37 months (mean 32.3). At the short-term follow-up visit (less than 6 months), 7 patients (70%) reported erections sufficient for vaginal insertion; at the long-term follow-up visit, 5 men (50%) reported sustained, sufficient potency and 5 (50%) reported persistent erectile dysfunction. No serious complications occurred. Conclusions. Our pelvic venoablation technique using ethanol was effective, minimally invasive, and cost-effective.

Since amphiphilic drugs are known to interact with biomembranes, we investigated local vessel damage and thrombosis which might be brought about by intravenous dosing using chlorpromazine (CPZ) as a representative compound. CPZ-induced hemolysis was suppressed by an increase in sucrose concentration in the medium, characterizing this hemolysis to be colloid-osmotic lysis, which includes the enhancement of membrane phospholipid fluidity and consequent small pore formation in the membranes. This was supported by the observation that hemolysis by filipin, not featuring the stage of small pore formation, was not affected by sucrose. [14C]Glucose-entrapping liposomes were degraded by CPZ, and this degradation was enhanced by an increase in the intravesicle glucose concentration. These results indicated that the compound could induce colloid-osmotic lysis in erythrocytes and artificial membrane vesicles. CPZ also injured cultured porcine aortic endothelial cells (PAEC), as evidenced by lactate dehydrogenase (LDH) leakage. This injury was also suppressed by increase in sucrose concentration in the medium, suggesting that colloid-osmotic lysis again occurred. When rats were intravenously injected with CPZ, local endothelial cell (EC) injury and associated thrombus formation were observed, suggesting that CPZ's action was also evident in vivo. To our knowledge, this is the first finding which suggests that an intravenously dosed amphiphilic drug can injure local ECs based on a colloid-osmotic lysis mechanism leading to thrombosis.