Aim-To clarify the incidence of choroidal neovascularisation (CNV) and predisposing findings for development of CNV in the second eye of Japanese patients with unilateral exudative age related macular degeneration (AMD). Methods-The second eyes of unilaterally aVected patients with exudative (neovascular) AMD treated in our clinic during the past 10 years (1988-97) were carefully followed up for more than a year. Evidence of CNV was confirmed by fluorescein and indocyanine green angiography. Macular lesions in patients, in whom CNV developed in the second eye, were retrospectively evaluated from patient records. Results-170 patients met the criteria. The average follow up period was 47 months (range 12-108 months). All patients were Japanese. CNV developed in the second eye in 12 (7%) of 170 patients, 30.3 months on average after the first examination. Cumulative incidence of developing CNV in the second eye using Kaplan-Meier life table analysis was: 0.6% by 1 year, 5.6% by 3 years, and 12.3% by 5 years, and was relatively low compared with that in white patients. CNV developed most frequently from serous pigment epithelial detachment (PED) in the macula (58%). Soft drusen were not prevalent and risk of developing CNV was not very high (18%). Conclusion-It was confirmed that there were some diVerences in the incidence and predisposing findings for CNV developing in AMD among Japanese and other Asian patients compared with those in white people. It is important to recognise these diVerences between the two populations to understand the pathogenesis and epidemiology of AMD. (Br J Ophthalmol 2000;84:1018-1023 Exudative (neovascular) age related macular degeneration (AMD) is a leading cause of blindness in elderly people in Western countries.1-4 Although, in Japanese as well as in other Asian people, the number of patients with exudative AMD is not as great as in Western people, the number of patients has been rapidly increasing recently and is now becoming one of the major causes of blindness in the elderly. Epidemiology and clinical features of exudative AMD have been well established in the United States and United Kingdom. In Japan, clinical manifestations of AMD have become clearer during the past 20 years.5 6 Following the increase in patients with AMD, we have recognised that Japanese patients show some diVerences from white patients with regard to epidemiological features and predisposing findings for the development of choroidal neovascularisation (CNV). In white people, soft drusen at the macula prevalent among elderly people, are commonly present in AMD, and these people show the highest risk for developing CNV. 1-4 7-17 In Japanese people, however, soft drusen are not as commonly seen among elderly people, or among patients with AMD but, rather, serous retinal pigment epithelial detachments (PED) are the most frequent predisposing lesions for developing CNV.5 18 These findings were also similar to those in other Asian patients. 19Many papers have reported a very high annual incidence of CNV in ...

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Foreign body granuloma is a tissue reaction for retained foreign bodies after skin-penetrating trauma. Detection of retained foreign bodies can be extremely difficult when the patients present with non-specific symptoms such as pain and/or swelling without recognizing a previous trauma. We report three patients of foreign body granulomas in the lower extremities with emphasis placed on their unique clinical and radiological features. The involved sites were the foot, posterior thigh, and posterior lower leg, with wooden splinters in two patients and a fragment of tile in one. Plain radiographs could not reveal the existence of foreign bodies. Magnetic resonance imaging (MRI) showed foreign bodies as low intensities on both T1- and T2-weighted images in two patients, and the surrounding reactive lesion as low to iso intensities on T1- and high intensities on T2-weighted images in all the patients. The peripheral areas of the lesion were strongly enhanced after gadolinium injection. Ultrasound sonography could clearly visualize a foreign body as an echogenic area with posterior acoustic shadowing in one patient. The surrounding ring-like reactive lesion is easily mistaken for a soft tissue neoplasm when foreign bodies are not identified. The key to arriving at the correct diagnosis is to clarify the previous trauma and to identify foreign bodies with low signal intensities on both T1- and T2-weighted images and/or the characteristic ring-like enhancement on MRI. It is also necessary to rule out a foreign body granuloma whenever we see patients with a soft tissue tumor in the extremities, irrespective of their previous trauma history.

A transgenic rat line carrying three copies of the human c-Ha-ras proto-oncogene, including its own promoter region, has been established in our laboratory (Hras128 rats), and shown to be highly susceptible to induction of mammary and urinary bladder tumors. Mutation analysis of induced lesions indicated the majority to contain some but not all cells with transgene mutation. In the present study, the susceptibility of Hras128 rats to N-nitrosomethylbenzylamine (NMBA) induction of esophageal tumors was examined with a similar mutation analysis of the transgenes. Male 6-week-old Hras128 and wild littermate rats were treated with NMBA, 0.5 mg/kg subcutaneously, 3 times a week for 5 weeks and then maintained for 5 weeks without any further treatment. Multiple esophageal tumors, squamous cell papillomas and carcinomas, rapidly developed within this 10-week experimental period in Hras128 rats (11.05 ± ± ± ±7.83/rat). In contrast, wild-type littermates had only small numbers of mostly benign tumors (1.67 ± ± ± ±2.06/rat). The Hras128 rats had no other tumors or abnormalities. In their esophageal lesions, codon 12 GGC to GAC mutations of the transgene were frequently detected by restriction fragment length polymorphisms (RFLP) and subsequent direct sequencing analysis (19/25, 76%). In the endogenous rat c-Ha-ras gene they were less frequent (2/25, 8%), than in wild-type rats (8/14, 57.1%). The densities of mutated bands in the RFLP analysis indicated that mutated cells were major populations in tumors, in contrast to the case with mammary and urinary bladder lesions. Furthermore, activated ras protein, detected by binding to raf protein, was clearly increased in tumors as compared to surrounding epithelium or the normal esophagus of untreated rats. The results show that Hras128 rats are highly susceptible to NMBA esophageal carcinogenesis, as well as induction of mammary and urinary bladder tumors, but that tissue-specific characteristics exist for the roles of transgene ras mutations.Key words: Transgenic rats -c-Ha-ras -Esophageal tumors -N-Nitrosomethylbenzylamine Transgenic mice are widely used for analysis of gene function and as animal models for various diseases. In the field of chemical carcinogenesis, transgenic mice harboring a human c-Ha-ras proto-oncogene, 1, 2) v-Ha-ras transgenic mice (Tg.AC mice),3) pim-1 transgenic mice 4) and p53 knockout mice 5) have been shown to be highly susceptible to tumor induction by certain carcinogens, with indication that the transgene is actively involved. However, for studies of chemical carcinogenesis, 6) rats have been more frequently used, so that abundant information has accumulated regarding various biological characteristics of preneoplasias. 7,8) Therefore the Hras128 rats generated in our laboratory have great potential for studies of neoplasia. 9,10) For esophageal tumors, rats are preferable to mice 11,12) due to the availability of the organotropic carcinogens and the larger size of the organ.Human esophageal squamous cell carcinomas are presumed to be caused by ...

Granulocyte colony-stimulating factor (G-CSF)-producing nonhematopoietic malignancies have been reported in various organs and are associated with a poor clinical outcome. Moreover, carcinoma of unknown primary site (CUP) is an uncommon malignancy that occurs in about 2-6% of cancer patients. CUP also has a poor prognosis due to its missing profile. Since both G-CSF-producing carcinoma and CUP are rare, G-CSF-producing CUP (GCSF-CUP) is considered to have an even poorer prognosis and is seldom encountered. Herein, we report the case of a GCSF-CUP patient. A 75-year-old man was admitted to our hospital complaining of cervical lymphadenopathy. Multiple bulky lymph nodes without a primary site were revealed by image analysis. His complete blood count showed leukocytosis, and his blood chemistry panel indicated highly elevated levels of G-CSF. Although the patient was treated with combination chemotherapy of carboplatin, paclitaxel, bevacizumab and erlotinib, he died of intestinal perforation due to tumor invasion 23 days after the start of the therapy. An autopsy confirmed that the tumor was positive for anti-G-CSF antibody, but the primary site was still not detected.