Phase II study of (2" R)-4'-O-tetrahydropyranyladriamycin (THP) in patients with advanced or recurrent gastric cancer. Clinical study group of THP for gastric cancer in Japan

A multi-institutional collaborative phase II study of (2"R)-4-O-tetrahydropyranyladriamycin (THP) was performed by intravenous administration to patients with advanced or recurrent gastric cancer. The administration schedules were (1) 40-60 mg/body every 3 or 4 weeks and (2) 20-40 mg/body once a week. Of 58 registered patients, 49 cases were eligible and 37 cases were evaluable for response. The therapeutic results were 1 CR, 4 PR, 14 NC and 18 PD. The response rate of the evaluable cases was 13.5%. The side effects were mainly bone marrow suppression and digestive symptoms. In particular, the frequency of leukopenia was a high 75.5%, while there was a decrease in hemoglobin in 38.8% and anorexia in 30.6%. The frequency and severity of alopecia, which is a known problem with anthracyclines, were slight, and no abnormal electrocardiograms were observed.     

The McCoy laryngoscope, external laryngeal pressure, and their combined use

The efficacy of the McCoy laryngoscope, external laryngeal pressure, and their combination to improve the laryngoscopic view was evaluated in 219 patients and compared with the Macintosh laryngoscope. An experienced laryngoscopist performed laryngoscopy twice using the Macintosh laryngoscope and the McCoy laryngoscope in a random sequence, and external laryngeal pressure was applied in each laryngoscopy with the laryngoscopist's right hand. The laryngoscopic view obtained was graded on our modified Cormack's method. Without external laryngeal pressure, the McCoy laryngoscope provided a better laryngoscopic view than that obtained by the Macintosh laryngoscope (P < 0.001, signed rank test), but the view was worse than that with the Macintosh laryngoscope under external laryngeal pressure (P < 0.001). The McCoy laryngoscope combined with external laryngeal pressure provided a better view than the Macintosh laryngoscope with external laryngeal pressure (P < 0.001).     

Membranous glomerulonephritis with nephrotic syndrome associated with chronic lymphocytic leukemia

A 66-year-old woman was admitted to our hospital for evaluation of edema of the extremities. Laboratory findings suggested that she had nephrotic syndrome and chronic lymphocytic leukemia (CLL). Renal biopsy (with PAM staining) showed a spike formation in the capillary wall. Immunofluorescent staining revealed deposition of immunoglobulin G (IgG) and the third component of complement in the glomerular basement membrane. Electron microscopy showed fibrillary deposits in the subepithelium. These findings indicated membranous glomerulonephritis (MGN). In addition, focal segmental sclerosis and interstitial lymphocytic infiltration were observed in the renal biopsy specimen. In CLL patients nephrotic syndrome occurs rarely. Even if the complication occurs, MGN is not frequent. Both diseases are suspected to occur in association with each other, and immunologic abnormality contributes to their coexistence. Although administration of prednisolone and endoxan improved leukocytosis, proteinuria was not sufficiently improved with combination therapy.     

Glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) polymorphisms and urothelial cancer risk with tobacco smoking.

The objective of this study was to examine the association between the genetic polymorphism of glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) genes and urothelial cancer risk in relation to smoking status. In this study, 325 Japanese patients with urothelial transitional cell carcinoma and 325 healthy controls were compared for frequencies of GSTM1, T1 and NAT2 genotypes. The frequencies of GSTM1 null genotype and NAT2 slow genotype were significantly higher in the cases than in the controls (adjusted odds ratio (OR) 1.37, 95% confidence interval (CI) 1.01-1.87, adjusted OR 3.09, 95% CI 1.69-5.63, individually). Furthermore, the risk of GSTM1 null genotype and NAT2 slow genotype was higher among smokers (adjusted OR 1.48, 95% CI 1.01-2.15, adjusted OR 4.28, 95% CI 1.96-9.36, individually). The regression analysis of cancer risk as a function of the amount of smoking showed that the susceptibility of people who had GSTM1 null genotype increased from 45 pack-years, while the susceptibility of people with NAT2 intermediate or slow genotype increased rapidly from 25 pack-years, compared with non-smokers. A multiplicative interaction between NAT2 intermediate or slow genotype and pack-years of smoking was found (P<0.001), but GSTM1 null genotype was not (P=0.06). Our results indicate that the GSTM1 null genotype and NAT2 intermediate or slow genotype are associated with an increased risk of urothelial cancer in relation to smoking amounts. Furthermore, the interaction between NAT2 intermediate or slow genotype and pack-years of smoking has a strong impact on urothelial cancer.     

A cancer-prone case with a background of methylation of p16 tumor suppressor gene.

PURPOSE AND EXPERIMENTAL DESIGN: To date, the presence of p16 gene promoter methylation associated with loss of protein expression has been demonstrated frequently in digestive tract cancers. In this study, we tested for the methylation status of p16 promoter in normal tissue specimens using the methylation-specific PCR technique to examine whether p16 methylation already existed in the background of tumors. RESULTS: Aberrant promoter methylation of p16 gene was detected in 1 of 40 esophageal and 1 of 69 gastric and no colorectal epithelium specimens, and these 2 specimens were derived from the same patient. We also found the same methylation change in both tumor and blood cell DNA. CONCLUSION: These results suggested that the p16 gene was inactivated by methylation in normal background cells of this patient and that other additional factors may promote tumor development in his esophageal and gastric tissues.     

Hypogammaglobulinaemia in a patient with ring chromosome 21

An 8 year old boy with ring chromosome 21 who was susceptible to sinorespiratory infections due to hypogammaglobulinaemia is reported. He presented with the characteristic features of monosomy 21 syndrome, such as psychomotor retardation, hypertonia, large saccular ears, prominent nasal bridge, micrognathia, thrombocytopenia, and patent ductus arteriosus. His serum IgG concentration was less than 1.5 g/l at 3 years and 6 months of age after repeated hospitalisations with pneumonia, otitis media, and convulsions. Regular replacement of intravenous gammaglobulin effectively reduced such infectious episodes. A predisposition to infection in patients with ring chromosome 21 may be explained by hypogammaglobulinaemia and merit treatment with gammaglobulin.

     

Ultrasound in urodynamics

Recent developments of ultrasound imaging have contributed much to the understanding of urodynamics in patients with lower urinary tract symptoms (LUTS). These include ultrasound estimated bladder weight (UEBW), transrectal power Doppler imaging of the prostate and transrectal ultrasonography during voiding (voiding TRUS). UEBW, which is obtained by measuring the thickness of the anterior bladder wall using a 7.5 MHz probe, represents well the degree of bladder hypertrophy caused by obstruction. This parameter is, accordingly, of clinical use in the evaluation of obstruction. The UEBW predicted the presence of obstruction as determined by pressure-flow study with a diagnostic accuracy of 73%. Transrectal power Doppler imaging of the prostate has made it easy to detect prostatic vessels and furthermore to obtain their resistive index (RI). Accumulating data suggest strongly that RI reflects the intraprostatic pressure. More interestingly, RI decreases significantly during voiding in normal subjects but not in patients with benign prostatic hyperplasia. Thus, this method is of particular use in monitoring noninvasively the dynamic change in intraprostatic pressure during voiding. Voiding TRUS makes it possible to monitor the movement of not only the posterior urethra but also the prostate during voiding. Based on our recent study, the anterior fibromuscular stroma (AFMS) seems to contract to open the urethra. Although the physiological function of the AFMS in the prostate remains unknown, AFMS may play a significant role in normal micturition. Due to its noninvasiveness and ease of application, ultrasound imaging would play a vital role in the diagnostic process for patients with LUTS in future.