Successful treatment of lymph node metastases recurring from gallbladder cancer

A 66-year-old woman who had undergone cholecystectomy for the treatment of gallbladder cancer 5 years and 10 months previously was referred to our center due to increased carbohydrate antigen (CA)19-9. Increased CA19-9 (136 U/ml) was the only abnormality detected on initial examination, and, despite various tests, clear signs of recurrence could not be detected. Subsequently, the patient was followed. Six months after the initial examination, dynamic computerized tomography confirmed lymphadenopathy. The results of fluoro-deoxy-glucose positron emission tomography suggested lymph node metastasis of the gallbladder cancer, and after consideration of the site of recurrence and the length of time between the primary surgery and detection of recurrence, the patient underwent extrahepatic bile duct resection and lymphadenectomy. Levels of CA19-9 normalized postoperatively, and, at the time of writing (26 months postoperatively), blood tests and diagnostic imaging revealed no signs of recurrence. Received: May 6, 2002 / Accepted: October 23, 2002 RID="*" ID="*" Offprint requests to: K. Tasaki     

CT imaging of the patulous eustachian tube--comparison between sitting and recumbent positions

OBJECTIVE: The objective was to evaluate the three-dimensional anatomy of the eustachian tube (ET) and its surrounding tissues of patulous ET patients in the sitting positions by the horizontal computed tomography (CT) system with the multiplanar reconstruction (MPR) technique, and to compare the findings with those obtained in the recumbent position. METHODS: Two patients with severe bilateral patulous ET were investigated. After performing temporal bone CT examination both in the sitting and recumbent position, MPR images of the ET were reconstructed and measurement was made on a workstation. RESULTS: The ET lumen was identified at most of the portion from the pharyngeal orifice to the tympanic orifice in both positions. At the cartilaginous portion, the air space in the ET lumen was larger in the sitting position than in the recumbent position. At the bony portion of the ET, there did not seem to be any significant difference in the results of measurement in both cases. CONCLUSION: For the first time, we were able to obtain reconstructed images of patulous ET patients in the sitting position and to compare the findings with those of the recumbent position. We suggest that this method is useful for better understanding of the ET and ET-related diseases such as patulous ET.     

Mixed Medullary-Papillary Carcinoma of the Thyroid with Lymph Node Metastases: Report of a Case

We report herein the case of a 77-year-old woman found to have mixed medullary-papillary carcinoma in the right thyroid with lymph node metastases 30 years after a left thyroidectomy. The preoperative values of serum calcitonin and carcinoembryonic antigen (CEA) were high, and fine-needle aspiration biopsy revealed class V, which led us to suspect papillary carcinoma. A right thyroidectomy with dissection of the right neck lymph nodes was performed. Histopathological examination of the tumor specimens revealed gradual borders between medullary carcinoma and papillary carcinoma with positive immunohistochemical staining to calcitonin, chromogranin A, CEA, and thyroglobulin. The serum levels of calcitonin and CEA decreased to normal after the operation. The point mutation of the RET proto-oncogene was found to be negative by a DNA analysis of the peripheral leukocytes. This cancer seemed not to be associated with multiple endocrine neoplasia type 2 syndrome. The presence of both medullary and papillary components in the thyroid with lymph node metastases is rare and may suggest that the tumor had arisen from a common stem cell.     

Inhibitory effects of clozapine and other antipsychotic drugs on noradrenaline transporter in cultured bovine adrenal medullary cells

The effects of clozapine and other antipsychotic drugs on noradrenaline (NA) transport were examined in cultured bovine adrenal medullary cells and in transfected Xenopus laevis oocytes expressing the bovine NA transporter. Incubation of adrenal medullary cells with clozapine (30–1000 ng/ml) inhibited desipramine (DMI)-sensitive uptake of [³H]NA in a concentration-dependent manner (IC₅₀=110 ng/ml or 336 nM). Other antipsychotic drugs such as haloperidol, chlorpromazine, and risperidone also decreased [³H]NA uptake (IC₅₀= 144, 220, and 210 ng/ml or 383, 690, and 512 nM, respectively). Eadie-Hofstee analysis showed that clozapine reduced V_max of uptake of [³H]NA and increased K_m. Furthermore, clozapine inhibited specific binding of [³H]DMI to plasma membranes isolated from bovine adrenal medulla (IC₅₀=48 ng/ml or 146 nM). Scatchard plot analysis of [³H]DMI binding revealed that clozapine decreased both B_max and K_d. Other antipsychotic drugs, including haloperidol, chlorpromazine, and risperidone, also reduced [³H]DMI binding to the membranes. In transfected Xenopus oocytes expressing the bovine NA transporter, clozapine inhibited [³H]NA uptake in a concentration-dependent manner similar to that observed in adrenal medullary cells. These results suggest that clozapine and haloperidol directly inhibit transport of NA by acting on the site of an NA transporter that influences both substrate transport and binding of tricyclic antidepressants. Received: 13 April 1999 / Final version: 2 November 1999     

Comparison of human papillomavirus genotyping and cytology triage,COMPACT Study: Design,methods and baseline results in 14 642 women

Although cytology‐based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing for cervical screening increases detection of high‐grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV‐positive women to avoid over‐referral to colposcopy may be setting specific. As Japan requires data that have been generated domestically to modify screening guidelines, we conducted a 3‐year prospective study, COMparison of HPV genotyping And Cytology Triage (COMPACT), to evaluate the potential role of HPV16/18 partial genotyping and cytology for primary HPV screening. In total, 14 642 women aged 20 to 69 years undergoing routine screening at 3 centers in Hokkaido were enrolled. Conventional cytology and HPV testing were carried out. Women with abnormal cytology or HPV16/18 positivity underwent colposcopy. Those with 12 other high‐risk (hr) HPV types underwent repeat cytology after 6 months. Primary study endpoints were detection of high‐grade cervical disease defined as CIN2/CIN3 or greater as determined by consensus pathology. Prevalence of cytological abnormalities was 2.4%. hrHPV, HPV 16, and HPV 18 were detected in 4.6%, 0.9%, and 0.3% of women, respectively. HPV16/18 were detected in all (8/8) invasive cervical cancers and in all (2/2) adenocarcinomas in situ. Both cytological abnormalities and hrHPV positivity declined with increasing age. This is the first Japanese study to investigate the role of partial genotyping and cytology in an HPV‐based screening program. Results should help policy‐makers develop guidelines for future cervical screening programs and management of cervical abnormalities based on HPV genotype.     

Phototoxicity studies of pazufloxacin mesilate,a novel parenteral quinolone antimicrobial agent--in vitro and in vivo studies

Phototoxicity of pazufloxacin mesilate (PZFX mesilate), a novel parenteral quinolone antimicrobial agent, were evaluated in vitro and in vivo studies. In vitro, phototoxicity for cultured cells of PZFX, which is active principle of PZFX mesilate, was studied, and stability for long-wavelength ultraviolet (UVA) was examined. In vivo, phototoxicity tests in guinea pigs and rats, and photoallergenicity tests in guinea pigs were conducted. In the phototoxicity test on cultured cells, CHL/IU cells were irradiated UVA of 300-3000 mJ/cm2 in the presence of PZFX, ofloxacin (OFLX), lomefloxacin (LFLX) or sparfloxacin (SPFX) at 10 micrograms/mL. Phototoxic potencies for cultured cells of the quinolones tested were SPFX > LFLX > OFLX > PZFX. In addition, changes in ultraviolet absorption spectrum and residual rate of PZFX, OFLX, LFLX and SPFX were examined after UVA irradiation of 300-3000 mJ/cm2 to each solution. PZFX was stable for UVA compared with OFLX and LFLX. In the phototoxicity test of guinea pigs, each quinolone was administered intraperitoneally daily for 7 days, and UVA of about 11 J/cm2 was irradiated at 30 minutes after the last administration. Dose levels of each quinolone were 65 and 130 mg/kg of PZFX mesilate (dose levels converted to PZFX: 50 and 100 mg/kg), 50 and 100 mg/kg of nalidixic acid (NA), 100 mg/kg of OFLX, enoxacin (ENX), ciprofloxacin (CPFX), LFLX and SPFX. Grade of skin reaction (erythema) at 24 hours after UVA irradiation decreased in the order: SPFX > CPFX > NA > ENX = OFLX > LFLX > PZFX mesilate. Thus, PZFX mesilate was found to have the weakest phototoxicity. In the maximum plasma concentration of quinolones from 0.5 to 2.5 hours after administration, corresponding to the time of UVA irradiation, the concentration of the group administered PZFX mesilate was about 4.1 times higher than that of CPFX group, and about 1.3 times higher than that of SPFX group. The area under the blood concentration-time curve (AUC0.5-2.5) of the group administered PZFX mesilate was the same as that of SPFX group, and about 3.2 times larger than that of CPFX group. These data showed that phototoxicity of PZFX mesilate was also weaker than that of CPFX or SPFX in consideration of AUC0.5-2.5. In the phototoxicity test of rats injected intravenously, no phototoxicity was observed at 130 mg/kg of PZFX mesilate. In the photoallergenicity test of guinea pigs, no photoallergenicity was observed by PZFX mesilate. As mentioned above, from in vitro studies PZFX was found to be stable for UVA irradiation compared with OFLX and LFLX, and phototoxicity for cultured cells of PZFX was weaker than that of SPFX, LFLX or OFLX. In addition, from in vivo studies phototoxicity of PZFX mesilate was found to be weaker than that of NA, OFLX, ENX, CPFX, LFLX or SPFX, and no photoallergenicity was observed. Therefore, photosensitive potency of PZFX mesilate might be less than that of other quinolones.