Gene expression levels of gamma-glutamyl hydrolase in tumor tissues may be a useful biomarker for the proper use of S-1 and tegafur-uracil/leucovorin in preoperative chemoradiotherapy for patients with rectal cancer.

PURPOSE: Preoperative chemoradiotherapy (CRT) using 5-fluorouracil (5-FU)-based chemotherapy is the standard of care for rectal cancer. The effect of additional chemotherapy during the period between the completion of radiotherapy and surgery remains unclear. Predictive factors for CRT may differ between combination chemotherapy with S-1 and with tegafur-uracil/leucovorin (UFT/LV). METHODS: The subjects were 54 patients with locally advanced rectal cancer who received preoperative CRT with S-1 or UFT/LV. The pathological tumor response was assessed according to the tumor regression grade (TRG). The expression levels of 18 CRT-related genes were determined using RT-PCR assay. RESULTS: A pathological response (TRG 1-2) was observed in 23 patients (42.6%). In a multivariate logistic regression analysis for pathological response, the overall expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, were significant, and the accuracy rate of the predictive model was 83.3%. The effects of the gene expression levels of GGH on the response differed significantly according to the treatment regimen. The total pathological response rate of both high-GGH patients in the S-1 group and low-GGH patients in the UFT/LV group was 58.3%. CONCLUSION: Additional treatment with 5-FU-based chemotherapy during the interval between radiotherapy and surgery is not beneficial in patients who have received 5-FU-based CRT. The expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, in tumor tissues can predict the response to preoperative CRT including either S-1 or UFT/LV. In particular, the gene expression level of GGH in tumor tissues may be a useful biomarker for the appropriate use of S-1 and UFT/LV in CRT.

Successful hyperbaric oxygen treatment of life-threatening hemorrhagic cystitis after allogeneic bone marrow transplantation.

Hemorrhagic cystitis (HC) is a major cause of morbidity after allogeneic bone marrow transplantation (BMT). Many therapies have been investigated to prevent or treat HC, but effective treatment for HC is still limited. While the efficacy of hyperbaric oxygen therapy has been established for HC due to chemotherapy and/or radiation therapy, its role in HC occurring after allogeneic BMT has yet to be defined. We report two cases of life-threatening late-onset HC after allogeneic BMT in children, which resolved after treatment with hyperbaric oxygen.

Neonatal hydronephrosis detected on routine health check-up.

BACKGROUND/PURPOSE: Prenatal dilatation of the urinary tract may be caused by obstructive defects, and it is known that 20% of normal fetuses have some degree of renal pelvic or calyceal dilatation, determined by sonographic examination. We analyzed the clinical course of patients found to have dilatation of the renal pelvis by ultrasound 1 month after birth, and compared prenatal and postnatal sonograms of each patient. METHODS: Between January 1996 and December 1998, renal ultrasounds were performed on 2,071 children at their 1 month routine health checks in our hospital. We found dilatation of the renal pelvis in 92 kidneys in 84 children and then compared these neonatal sonograms with the prenatal ultrasounds for each child. Ultrasound examinations were performed at 28 weeks of gestational age and 1 month after birth. Our criterion for diagnosis of hydronephrosis at 1 month of age was a renal pelvis measuring greater than 7 mm at the central echo complex. The medical records of patients found to have hydronephrosis were then reviewed. RESULTS: Eight patients had bilateral hydronephrosis, 2 had dilatation only in the right kidney and 74 had this finding only in the left kidney. Examination of 36 (39%) of these 92 kidneys revealed renal pelvic dilatation to be present both prenatally and neonatally. The dilatation ranged from 7 to 43 mm. No dilatation of the renal pelvis was seen on the other 56 fetal examinations. During the follow-up period, 2 patients (1 with bilateral and the other with right-sided hydronephrosis) were diagnosed with vesicoureteral reflux, the 1 patient with bilateral pelvic dilatation was found to have a vesico-ureteral junction obstruction. After full evaluation, the other children were found to have no anatomic abnormalities. CONCLUSIONS: We found 84 of 2,071 children showed dilatation of the renal pelvis on ultrasound examination performed at 1 month of age. Three (3.3%) of the 84 children required surgery to correct the neonatal hydronephrosis detected via this imaging modality. Interestingly, 88% of the children had only left-sided hydronephrosis, which did not predict an adverse outcome during the follow-up period. We conclude that neonatal hydronephrosis appears to be a relatively benign condition and the requirement of surgery is relatively slight.

Absence of brain parenchymal damage following intravascular injection of polytetrafluoroethylene paste.

OBJECTIVE: Polytetrafluoroethylene (PTFE) paste has been used for over 30 years to treat urinary incontinence and for 14 years to treat vesicoureteral reflux with little reported morbidity. Some investigators have been concerned by the use of PTFE as the implanted substance, because migration of PTFE particles from the site of injection in the periurethral and periureteral regions to the lungs and brain has been reported in animal studies. We injected PTFE paste intravascularly in dogs in order to investigate its effect on brain parenchyma. METHODS: A total of 12 mongrel dogs, weighing 11.5-17.5 kg, were divided into four groups. Group 1 (n = 3): injection of 0.5 ml of PTFE paste suspended in 50 ml of saline into a peripheral vein once a week for 4 weeks. Group 2 (n = 3): injection of 50 ml of saline into a peripheral vein once a week for 4 weeks as controls. Group 3 (n = 3): one injection of 0.1 ml of PTFE paste suspended in 20 ml of saline into the right carotid artery. Group 4 (n = 3): one injection of 20 ml of saline into the right carotid artery as controls. After an interval of 6 months, all animals were sacrificed and the lungs and brain removed. Brain from 1 animal in each group was dissolved in sodium hypochlorite solution, the resulting organ suspension was centrifuged, and the smear preparations of the precipitate examined by polarized light microscopy, scanning electron microscopy, and X-ray microanalysis. Brains from 2 animals in each group were fixed in formalin solutions, 6-micrometer sections were cut and stained with haematoxylin and eosin, Cajal stain for Purkinje fibre, and Luxol fast blue stain for myelin, and glial fibrillary acidic protein immunohistochemistry was carried for astrocytes using monoclonal mouse anti-GFAP (glial fibrillary acidic protein) at a dilution of 1:50 with an avidin-biotin-peroxidase complex method. RESULTS: PTFE particles were seen in the cerebral vessels in only those animals who had PTFE injected into the right carotid artery. The haematoxylin and eosin staining showed PTFE particles in vessels with focal foreign-body reaction, but no infarction. Luxol fast blue staining showed no demyelination around vessels containing the particles and the parenchyma. Cajal staining demonstrated no abnormality of nerve fibres, and there was no astrocytosis using GFAP immunohistochemical staining. CONCLUSIONS: Our findings indicate that following intravenous injection, there was no evidence of migration of PTFE to the brain. Small quantities of PTFE injected into the carotid arteries were associated with local foreign-body reaction, but no brain parenchymal tissue damage was found.

Abnormal innervation and altered nerve growth factor messenger ribonucleic acid expression in ureteropelvic junction obstruction.

The pathophysiology of ureteropelvic junction obstruction is unknown. Using specific antibodies, we studied specimens from 35 cases of ureteropelvic junction obstruction and 32 of normal ureteropelvic junction by immunohistochemistry using protein gene product 9.5 (a general neuronal marker), S100 (a supporting cell marker), synaptophysin (a neuromuscular junction marker) and nerve growth factor receptor. Nerve growth factor expression was examined at the messenger ribonucleic acid (mRNA) level using reverse transcription-polymerase chain reaction technique in 11 ureteropelvic junction obstruction specimens and 7 controls. The most striking finding was the marked reduction of protein gene product 9.5, synaptophysin and nerve growth factor receptor staining positive nerve fibers in the muscle layers of ureteropelvic junction obstruction compared to the normal ureteropelvic junction. Supporting nerve cell fibers (S100) were preserved in cases of ureteropelvic junction obstruction and normal ureteropelvic junction. A significantly less intense signal for nerve growth factor mRNA was found in the ureteropelvic junction obstruction specimens compared to normal ureteropelvic junction. These findings suggest that defective innervation may have an important role in the pathogenesis of ureteropelvic junction obstruction, and decreased nerve growth factor mRNA expression may be important in the etiology of ureteropelvic junction obstruction.

Serum intercellular adhesion molecule (ICAM-1), a marker of renal scarring in infants with vesico-ureteric reflux.

OBJECTIVE: To determine if serum intercellular adhesion molecule (ICAM-1) levels correlate with renal scarring in children with vesico-ureteric reflux (VUR). PATIENTS AND METHODS: Serum ICAM-1 levels were measured in 81 children (29 boys and 52 girls, age range 2 months-13 years) with VUR using an enzyme-linked immunosorbent assay (ELISA) and compared with levels in a control group of 24 children (16 boys and eight girls, age range 2 days-13 years) with no urological abnormalities. RESULTS: The mean serum ICAM-1 level in the control group was 202 +/- 79 ng/mL (mean +/- 1 SD) compared with 347 +/- 96 ng/mL in children with VUR (P < 0.001). Fifteen of 26 children under 2 years of age demonstrated renal scarring while 18 of 44 children older than 2 years exhibited renal scarring. The mean serum ICAM-1 level in patients who were < 2 years of age and had renal scarring was 408 +/- ng/mL, significantly higher than in those who had no renal scarring (296 +/- 68 ng/mL, P < 0.01). In contrast, there was no difference in serum ICAM-1 levels in patients > 2 years of age with or with no renal scarring (353 +/- 87 and 325 +/- 91 ng/mL, respectively). CONCLUSION: Serum ICAM-1 levels are significantly higher in children with VUR and may represent a valuable marker of tubular damage in younger children with VUR.

Particles found in lung and brain following subureteral injection of polytetrafluoroethylene paste are not teflon particles.

We injected 0.3 ml. of polytetrafluoroethylene paste (Polytef) behind the left submucosal ureter in 4 mini-pigs and 4 dogs, and 2 dogs and 2 mini-pigs underwent sham operation and acted as controls. Two mini-pigs were injected with 0.5 ml. polytetrafluoroethylene (Teflon) suspended in 50 ml. of normal saline into a peripheral vein and 2 dogs were injected with 0.5 ml. polytetrafluoroethylene into a bladder vein. In addition, 4 dogs were injected with 0.1 ml. polytetrafluoroethylene paste suspended in 20 ml. saline into the right carotid artery. The lungs and brain from half of the animals who had subureteral and intravascular injection of polytetrafluoroethylene paste as well as sham operated animals were dissolved in sodium hypochlorite solution. The resulting organ suspensions were then centrifuged and the smear preparations of the precipitate were examined by polarized light microscopy, scanning electron microscopy and x-ray microanalysis. Polytetrafluoroethylene paste suspended in saline acted as positive control for polytetrafluoroethylene particles. Lungs and brain from the remaining animals were fixed in formalin solution. The brain and lungs of animals who underwent subureteral injection with a minimal amount of polytetrafluoroethylene paste carefully placed in the submucosal plane showed no evidence of polytetrafluoroethylene on histological examination, polarized light microscopy, scanning electron microscopy and x-ray microanalysis.

Urinary levels of N-acetyl-beta-D-glucosaminidase: a simple marker for predicting tubular damage in higher grades of vesicoureteric reflux.

We examined urinary N-acetyl-beta-D-glucosaminidase (NAG) levels in 84 children with grade III to grade V primary vesicoureteric reflux and in 31 controls. Age and sex of patients were similar in controls and patients and none had evidence of urinary infection at the time of testing. The mean urinary NAG activity levels in non-refluxing controls was 4.98 IU/g Cr, standard error (SE) 0.756. The mean urinary NAG activity levels in grade III patients (n = 43) was 6.024 IU/g Cr (SE 0.898), in grade IV (n = 28) 9.059 IU/g Cr (SE 1.317), and in grade V (n = 13) 17.298 IU/g Cr (SE 5.124). In this study, only patients with grade IV and V vesicoureteric reflux demonstrated significantly elevated NAG levels and within these grades of reflux, high NAG activity was confined to those patients who had associated renal scarring. NAG estimation in these patients with reflux nephropathy may be a useful simple additional test to assess tubular damage.

Endoscopic correction of vesico-ureteric reflux in duplex systems.

Between May 1984 and April 1990, 37 children with vesico-ureteric reflux (VUR) in 43 duplex systems were treated by endoscopic subureteric Teflon injection (STING). There were 32 girls and 5 boys; the duplex systems were complete in 27 refluxing units and incomplete in 16 refluxing units. All patients had high-grade reflux. In incomplete duplicated systems, VUR was corrected in 14 (87.5%) after a single injection of polytef paste and 2 patients required 2 injections to correct VUR. Of the 27 refluxing units with complete ureteral duplication, reflux was corrected in 16 (59%) units after a single injection of polytef paste, and 3 (11%) units showed improvement of VUR to grade I or II after 1 injection; no further treatment was given. 7 units with complete ureteral duplication required 2-4 injections for correction of VUR. STING failed to correct VUR in 1 duplex system which required a re-implantation. In 93% of refluxing units where VUR was corrected by a single injection, the quantity of polytef paste used was less than 0.3 ml. 36 (97%) of patients were discharged home on the day of the procedure. All patients were followed up for 2-8 years. Of the corrected ureters, there were no recurrences in the incomplete duplicated ureters. 3 of the completely duplicated ureters showed recurrence of reflux at follow-up micturating cystography.(ABSTRACT TRUNCATED AT 250 WORDS)

2,8-Dihydroxyadenine urolithiasis due to partial deficit in adenine phosphoribosyltransferase: a case report.

Inherited metabolic diseases resulting in urolithiasis secondary to urinary excretion of insoluble substances are rare but often present as urinary obstruction of renal insufficiency. We herein report a case of partial adenine phosphoribosyltransferase deficiency associated with 2,8-dihydroxyadenine urolithiasis. In family members the propositus and his younger brother are homozygotes for defective APRT genes, and who exhibits the type II phenotype designated APRT*J (Japanese type).

[Statistical studies on bacteria isolated from urinary tract infections(report 5)].

We examined bacteria isolated from urine of patients in our urological department from 1985 through 1987. A total of 2,566 strains were isolated from outpatients. They were 834 strains of gram-positive coccus (32.5%). E. coli (20.8%) was isolated most frequently, followed by Proteus sp. (12.6%), Enterococcus (9.6%), P. aeruginosa (6.7%), S. epidermidis (5.5%), and K. pneumoniae (3.7%) and others. A total of 784 strains were isolated from inpatients. They were 313 strains of gram-positive coccus (39.9%). Enterococcus (22.6%) was isolated most frequently, followed by P. aeruginosa (10.1%), S. marcescens (9.7%), E. coli (8.2%), S. epidermidis (7.9%), and K. pneumoniae (4.3%) and others. Gram-positive bacterium occupied a larger proportion of the total-isolates from both outpatients and inpatients, than in our previous examination. Fewer P. aeruginosa and Enterococcus were isolated from outpatients, and fewer P. aeruginosa from inpatients than previously. More S. marcescens were isolated from inpatients than previously. S. marcescens, E. cloacae, C. freundii, S. epidermidis, and S. aureus all isolated from outpatients showed a higher sensitivity to all drugs we tested than those isolated from inpatients.

[Epidermoid cyst of the scrotum: report of a case].

A 61-year-old male visited our hospital with the chief complaint of a mass in the right scrotum on October 4, 1985. Under the diagnosis of intrascrotal tumor, the mass was resected surgically. It was a subcutaneous tumor, and had no relation to any intrascrotal organ, such as testis, epididymis or spermatic cord. The mass was 7 x 6 x 5 cm. Pathological diagnosis was epidermoid cyst of the scrotum. Epidermoid cyst of the scrotum is a rare disease and only 7 cases have been reported in Japan.

[Statistical studies on bacteria isolated from urinary tract infections (report 4)].

The statistics and drug sensitivity tests of bacterial florae isolated from the urinary tract in 1983 and 1984 were reviewed. Of the 2,222 strains isolated from outpatients, 593 (26.7%) were gram positive cocci, 21.4% were E. coli, 11.3% were Enterococcus, 10.4% were Proteus sp., 10.0% were P. aeruginosa, 5.6% were Alcaligenes sp., 4.2% were S. epidermidis and the rest were others. Of the 507 strains isolated from hospitalized patients, 107 (33.5%) were gram positive cocci, 20.3% were Enterococcus, 16.2% were P. aeruginosa, 9.1% were E. coli, 7.7% were Enterobacter sp. 7.5% were S. epidermidis, 4.9% were Proteus sp., S. marcescence and the rest were others. The percentage of E. coli, K. pneumoniae and S. epidermidis detected in the isolates from the outpatients and that of K. pneumoniae, Proteus sp. and S. epidermidis detected from the inpatients were lower than in previous reports. The percentage of P. aeruginosa and Enterococcus detected in the isolates from both groups of patients were higher than in previous reports. The major isolates (9 species) from the outpatients were more susceptible to the antimicrobial agents tested than those from the inpatients. The susceptibility of gentamicin, tetracycline and nalidixic acid to the major isolates was lower than in previous reports. During the past 2 years, we have been routinely using on inpatients the so-called new generation cefem antibiotics to treat urinary tract infections. This might be why the number of isolates of Enterococcus has increased especially in the isolates from inpatients.

[5 cases of renal pelvis and ureteral tumor].

The clinical results of three renal pelvic tumors and two ureteral tumors, experienced at Shimizu City Hospital between 1983 and 1985 are reviewed. The average age of the 5 patients was 56.8 years. The ratio of men to women was 4 to 1. The right side was involved in 4 cases and the left side in 1 case. The initial symptom was gross hematuria in all cases. Results of urinary cytology were positive in 3 cases. The prognosis of the patients with a high grade and high stage tumor was poor.

[Testicular scanning in intrascrotal lesions].

Testicular scanning with technetium-99m sodium pertechnetate was performed on 152 patients with a variety of intrascrotal lesions. Scrotal images were obtained serially in the perfusion, tissue phase, illustrating the features of each phase in various clinical conditions. The relationship of scrotal imaging to the overall clinical presentation and evaluation of these patients is emphasized in testicular torsion of the testicular appendix, epididymitis, abscess, trauma, tumor, spermatocele, and varicocele. Technical problems of the scanning are also discussed.

PIP: Testicular scanning with technetium-99m sodium pertechnetate was performed on 152 patients with various intrascrotal lesions. Prior to scanning, the patients were given an oral dose of 200 mg KD104 to control thyroid gland's exposure to radiation. Scrotal images were obtained 16 times with 2 seconds' interval in the perfusion phase and twice with 5 minutes' interval in the tissue phase. The rate of correct diagnosis by scrotal images were 100% for testicular torsion and acute epididymitis, significantly high for scrotal abscess and varicocele, 40-50% for testicular tumor, and low in the cases of hydrocele, testicular trauma and spermatocele. In testicular torsion, a rounded cold area and a halo of dartos perfusion were observed. Scrotal imaging proved to be useful for post-operative diagnosis of testicular vascularity also. In "missed" testicular torsion, scrotal scan showed a "halo sign" in the tissue phase due to intensified vascularity in the dartos, and a "nubbin sign" in the perfusion phase due to the increased perfusion of spermatic cord vessels. In acute epididymitis scrotal scan showed increased activity spanning spermatic cord vessels and scrotum in the perfusion phase, and increased curvilinear activity in the tissue phase. In scrotal abscess increased perfusion from spermatic cord vessels and pudendal artery were observed in the perfusion phase. In the tissue phase increased dartos perfusion and a cold area due to the formation of abscess was observed. In varicocele, increased perfusion in the location which corresponded to the pampiniform plexus of the vein was observed in venous phase.

[Two cases of metastatic renal tumor].

In this report, two cases of metastatic renal tumor are described. The first case is a 58-year-old female who had branchiogenic carcinoma. She had found a left neck tumor, before asymptomatic macrohematuria developed. The second case is a 25-year-old female who had choriocarcinoma. She had no urological symptoms. In both cases, unilateral nephrectomy was performed. Seventy nine cases of metastatic renal tumor in survivals have already been reported.

[Statistic studies on bacteria isolated from urinary tract infections (report 3)].

The following results were obtained from the statistical studies and drug sensitivity tests of bacterial florae isolated from the urinary tract in 1981 and 1982. Of the 2,029 strains isolated from out-patients, 627 (30.9%) were gram positive cocci, 24.1% were E. coli, 9.4% were Proteus spp., 9.2% were Enterococci, 8.9% were S. epidermidis, 7.0 % were K. pneumoniae, 5.7% were P. aeruginosa and the rest were others. Of the 754 strains isolated from hospitalized patients, 276 (36.6%) were gram positive cocci, 16.8% were Enterococci, 11.4% were S. epidermidis, 11.1% were P. aeruginosa, 8.8% were Proteus spp, 7.2% were E.coli, 6.5% were K.pneumoniae and the rest were others. The number of Proteus spp., P. aeruginosa and Enterococci detected in the isolates from the out-patients and that of E.coli, K. pneumoniae and Proteus spp., detected in the isolates from the in-patients were smaller than in previous reports. More non-fermentative gram-negative bacilli and S. epidermidis were detected in the isolates from both patients were than in previous years. The major isolates i.e., 9 species, from out-patients were more susceptible to the antimicrobial agents tested. The susceptibility of TC and SBPC to major isolates was lower than in previous years. During the past two years, we have been routinely using on inpatients the so-called third generation cefem antibiotics to treat urinary tract infections. This might be why the number of isolates of gram positive cocci has increased especially isolates from inpatients.

[Influence of operative procedures on prostatic tissue concentration of antibiotics].

The changes of prostatic tissue concentration of antibiotics by operative procedures have not been studied extensively. We measured the concentration of antibiotics in the rat prostatic tissues minced and agitated in the irrigation fluid, as a model of TUR-simulation. Our results suggest that TUR reduced the concentration of antibiotics in the prostatic tissues when compared to open prostatectomy.