REP-1 gene mutations in Japanese patients with choroideremia

· Background: Choroideremia (CHM) is an X-linked progressive dystrophy of the choroid, retinal pigment epithelium, and retina. Recently, the REP-1 gene was isolated and the causative mutations in the gene were detected in patients with CHM. In a previous study, we described a Japanese family with CHM who had a mutation in the REP-1 gene. In the present study, we performed extensive analysis of the REP-1 gene in patients with CHM from several institutions in Japan. · Methods: Twenty-six patients with CHM and 5 unaffected females from 22 independently ascertained families were examined. Exons 1–15 of the REP-1 gene were screened by single-strand conformation polymorphism. The DNA fragments suspected of any variations were directly sequenced. · Results: Fifteen different mutations, including one previously reported mutation, were detected in 18 families. In addition, carrier status was proven in four unaffected females found to be heterozygous for the mutant allele. · Conclusions: Fifteen different mutations of the REP-1 gene were detected in 18 Japanese families. There were no hot spots for the mutations and no missense mutations. The results show that REP-1 gene defects cause CHM in Japanese patients, and the mutations in these Japanese patients differed from the mutations reported for CHM patients in Europe, Canada, and America except for R267X and 1313delTC. These findings suggest that the mutations occurred independently in the Japanese patients. Received: 13 August 1998 Revised version received: 16 November 1998 Accepted: 9 December 1998     

Use of ultrasound-guided percutaneous needle biopsy in the diagnosis of mediastinal tumors

We herein report the usefulness of ultrasoundguided percutaneous needle biopsy for histological diagnosis in 18 patients with mediastinal tumors. Computed tomography revealed these tumors to be in contact with the chest wall. The preoperative diagnosis was thymoma in 7 patients, germinoma in 5, neurogenic tumor in 3, and other in 3. The most commonly encountered indication for an ultrasound-guided percutaneous needle biopsy was an anterior mediastinal lesion (78%; 14 of 18 patients). In 16 (89%) of the 18 patients, the biopsy diagnosis corresponded to the post-operative diagnosis. No complications were encountered in any of the patients. This new technique of ultrasound-guided percutaneous needle biopsy is both relatively simple and highly accurate and may thus be useful for outpatients. Preoperative ultrasound-guided percutaneous needle biopsy is thus considered to be a safe and reliable method for the histological diagnosis of mediastinal tumors, and a good alternative to traditional biopsy techniques such as mediastinoscopy or thoracotomy.Presented at the 11th Biennial Asian Congress on Thoracic and Cardiovascular Surgery, Kuala Lumpur, Malaysia, November, 21–25, 1993.     

Acute toxicity,percutaneous absorption and effects on hepatic mixed function oxidase activities of 2,4,4′-trichloro-2′-hydroxydiphenyl ether (Irgasan® DP300) and its chlorinated derivatives

Acute toxicity of 2,4,4-trichloro-2-hydroxydiphenyl ether (Irgasan^® DP300) (I) and its three chlorinated derivatives, 2,3,4,4-tetrachloro-2-hydroxydiphenyl ether (II), 2,4,4,5-tetrachloro-2-hydroxydiphenyl ether (III) and 2,3,4,4,5-pentachloro-2-hydroxydiphenyl ether (IV), in mice were examined by intraperitoneal injection. The LD₅₀ values of Irgasan DP300, II, III and IV were 1,090, 710, 650 and 430 mg/kg, respectively.The percutaneous absorptions of these tritiated compounds were also examined by the application on the backs of mice. The radioactivities in most tissues reached to the maximal levels at 12 h or 18 h after dosing, which corresponded to 11–76% of the maximal levels given by the oral administration (Kanetoshi et al. 1988a). These results show the high percutaneous absorbability of Irgasan DP300 and its chlorinated derivatives.The intraperitoneal administrations of III and IV to rats induced hepatic microsomal aminopyrine N-demethylase and aniline 4-hydroxylase activities similarly to phenobarbital. These chlorinated derivatives also increased cytochrome P-450 content, and the activities of aminopyrine N-demethylase and N-methylaniline N-demethylase in hepatic microsomes from mice. The extents of the increases were similar to those by phenobarbital and 3-methylcholanthrene.     

Hyperthermo-chemotherapy combined with cytoreductive surgery for the treatment of gastric cancer with peritoneal dissemination

Continuous hyperthermic peritoneal perfusion (CHPP) with anticancer agents (mitomycin C and cisplatin) in warm saline was performed in patients with peritoneal dissemination of gastric cancer following resection of the primary lesion. The effect of CHPP was examined by a second-look operation. This study includes 41 cases of gastric cancer with peritoneal dissemination but without liver metastasis treated during the past 6 years. The overall median survival was 14.6 months to 64.2 months from CHPP to death and the 3-year survival rate was 28.5%. Second look surgery revealed a remarkable diminution in the degree of peritoneal dissemination in 7 (50%) of 14 patients with disappearance of ascites after only one course of CHPP in 7 (77.8%) of 9 patients. Long-term 3 year-survival was noted in 4 (9.8%) patients on CHPP. Side effects were renal insufficiency in 2 (5%) patients, leukopenia in 2 (5%) patients, and perforation of the small intestine in 1 (2%) patient. These results suggest the effectiveness of CHPP in the treatment of gastric cancer with peritoneal dissemination.

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Resumen La perfusión hipertérmica continua (PHTC) con agentes anticancerosos (mitocina G y cisplatino) y solutión salina fue realizada en pacientes con cáncer gástrico con diseminación peritoneal después de resección de la lesión primaria, y el efecto de PHTC fue determinado mediante reexploración (operación de second look, OSL). La población de pacientes está constituída por 41 casos de cáncer gástrico con diseminación peritoneal pero sin metástasis hepáticas, tratdos en el curso de los últimos 6 años. La sobrevida media global fue de 437 dias (rango 28 a 1925 días) desde la PHTC hasta la muerte y la tasa de sobrevida a 3 años fue 28.5%. La OSL reveló una notoria disminución de la diseminación peritoneal en 7 (50%) de 14 casos y desaparición de la ascites después de sólo un ciclo de PHTC en 7 de 9 casos con ascitis. Sobrevida de 3 años ocurrió en 4 casos. Los efectos colaterales fueron insuficiencia renal en 2 casos (5%), leucopenia en 2 casos (5%) y perforación del intestino delgado en 1 caso (2%). Los anteriores resultados sugieren que la PHTC es eficaz en el tratamiento del cáncer gástrico con diseminación peritoneal.

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Résumé La perfusion péritonéale continue hyperthermique (PPCH) avec des agents anticancéreux comme le mitomycine C et la cis-platine avec sérum physiologique chauffé a été instaurée lorsqu'une carcinose d'origine gastrique a été trouvée. Les effets de la PCH ont été évalués chez 16 patients lors d'un second-look (SL). Cette étude concerne 41 patients avec carcinose péritonéale sans métastase hépatique observés au cours des 6 dernières années. La survie globale médiane était de 437 jours (extrêmes 28 à 1925 jours): le taux de survie a 3 ans était de 28.5%. Les lésions avaient diminué de façon notable chez 7 (50%) de 14 patients. L'ascite a disparu dans 7 des 9 cas. Une survie à long terme (3 ans) a été notée dans 4 cas. Les effets secondaires ont été une insuffisance rénale dans 2 cas (5%), une leucopénie dans 2 cas (5%) et une perforation de l'intestin grêle dans un cas (2%). Les résultats suggèrent que la PPCH est efficace dans le traitement du cancer gastrique avec dissémination péritonéale.

     

The endoscopic evaluation of gastritis,gastric remnant residue,and the incidence of secondary cancer after pylorus-preserving and transverse gastrectomies

Background Pylorus-preserving gastrectomy (PPG) and transverse gastrectomy (TrG) have been accepted as function-preserving procedures for node-negative early gastric cancer. It is believed that a better quality of life is guaranteed after PPG or TrG compared to that after distal subtotal gastrectomy (DSG) with Billroth type-I reconstruction. However, objective evaluations of the gastric remnant following gastrectomy have not been widely reported, and the real advantages and disadvantages of PPG or TrG over DSG remain unclear. Moreover, the risk of secondary cancer after PPG or TrG is uncertain.Methods Between 1991 and 2000, 834 DSGs were carried out in our institute for preoperatively diagnosed patients with early gastric cancer. The degree of residual gastritis and the amount of diet residue in the gastric remnant were evaluated by annual gastrointestinal endoscopic investigations prospectively for 72 patients after PPG, 95 patients after TrG, and 60 patients after DSG. These analyses were performed using the RGB classification (residue, gastritis, bile). The incidence of disease greater than or equal to grade 2 was calculated, and the time trends of the incidence for each procedure were also studied for 3 years after gastrectomy. In addition, secondary cancer cases in the gastric remnant mucosa were checked for each procedure during this period, and the incidence of secondary cancer after each operation was calculated.Results The incidence of gastritis, of grade 2 or more, found in the gastric remnant was significantly lower after PPG (1.4%) and TrG (2.1%) than after DSG (43.3%). However, the incidence of moderate or greater residue in the gastric remnant, grade 2 or more, was significantly higher after PPG (45.8%) and TrG (40.0%) than after DSG (11.7%). The analysis of time trends of gastritis and diet residue reflected the significant advantage or disadvantage for each procedure 1 year after surgery. The analysis also included these factors without consideration of elapsed time following surgery. Two patients after PPG (2.8%) and three patients after TrG (3.2%) developed secondary cancer in the gastric remnant. No DSG-treated patient showed new cancer genesis in the remaining stomach.Conclusion PPG and TrG have the advantage over DSG in preventing postoperative gastritis in the gastric remnant. On the other hand, moderate or greater diet residue in the gastric remnant is more common after PPG or TrG than after DSG. For the risk of carcinogenesis in the remnant gastric mucosa, we could not conclude that there was any apparent difference between these range-limited gastrectomies and conventional DSG. Further study is necessary to determine the significant advantages and disadvantages of using PPG or TrG.     

Transitional cell carcinoma of the ovary: Report of three cases

Background We investigated retrospectively the records and tissue samples of patients with primary ovarian transitional cell carcinoma to determine clinical and pathologic features. Methods The records of 3 patients with ovarian transitional cell carcinoma were reviewed using data from several imaging techniques: transvaginal ultrasound, computed tomography, and magnetic resonance imaging. We also determined levels of several tumor marker molecules; and the level of carbohydrate antigen 125 (CA 125), was examined by means of immunohistochemistry. Results The tumors of 2 patients were classified as pure trnasitional cell carcinoma; in the remaining patient, as predominantly transitional cell carcinoma. All tumors were bilateral, and 2 of the 3 tumors formed solid masses. Areas of irregular high intensity signals were seen in magnetic resonance images of the solid parts of the tumors. All 3 tumors tested positive for CA 125; histochemical expression was confined to the tumor cell membrane and/or the cytoplasm in all cases. The tumors of all 3 patients tested negative for carcinoembryonic antigen (CEA), and second-look laparotomies did not reveal any residual neoplasms in any of the patients. The patients have been in a disease-free state for 34, 42, and 14 months, respectively. Conclusion Our results suggest that transitional cell carcinomas tend to arise bilaterally and to form solid tumors. Magnetic resonance imaging was a useful diagnostic modality in these cases. Transitional cell carcinoma was characterized by the presence of CA 125 and the absence of CEA.     

Spontaneous regression of malignant pleural mesothelioma

We describe the spontaneous regression of a malignant pleural mesothelioma with left pleural effusion, chest pain, and a high fever (38° to 39°C) in a 37-year-old man. The patient was referred to us because multiple nodules were seen on his chest radiograph after he was successfully treated with thoracocentesis and conventional antibiotic therapy for pleural effusion. Our diagnosis was malignant pleural mesothelioma, based on histologic findings in a biopsy specimen obtained during thoracoscopy. Interestingly, the tumors markedly regressed without treatment, and the patient was doing well more than 5 months after the cancer was diagnosed. The spontaneous regression of malignant pleural mesothelioma is rare, and this may represent the first case report.     

Metastasis to the iris in squamous cell lung cancer

A 72-year-old Japanese woman, suffering from squamous cell lung cancer with brain metastasis, underwent 2 courses of combination chemotherapy, consisting of cisplatin and vindesine. Although both the primary tumor and the brain metastasis regressed markedly, she developed left ocular pain with blurred vision. An abnormal mass was found in the left iris, and cytologic examination of the aqueous aspirate revealed a few malignant cells, which, when examined by electron microscopy, were considered to be derived from squamous cell carcinoma of the lung.