Effects of doxorubicin on cancer cells after two-thirds hepatectomy in rats

A rat model of liver metastases generated by intraportal injection of syngeneic tumor cells after two-thirds hepatectomy was used to determine the optimal regional chemotherapeutic modality for early hepatic metastases. WKA rats had viable tumor cells injected directly into the portal vein after two-thirds hepatectomy. Ten rats were used as a control; the remaining groups were given doxorubicin (4/3 mg/kg) injected directly into the hepatic artery at 24 hr, 72 hr, and 7 days (after liver regeneration) postoperatively. The mean survival period in each group was 21.0, 20.0, 20.5, and 20.7 days, respectively, compared with those treated with doxorubicin (4 mg/kg) injection at 24 hr, 72 hr, and 7 days postoperatively, with a mean survival period in each group of 20.0, 21.6, and 25.6 days, respectively. When a comparison was made with regard to the doses of doxorubicin administered, statistically significant differences in survival rates were recognized between the rats that had doxorubicin (4 mg/kg) injection 7 days postoperatively and the others (P < 0.01). Based on these findings, we believe that appropriate adjuvant chemotherapy should be given after the liver regeneration phase. © 1995 Wiley-Liss, Inc.     

Clinicopathologic study of patients with Borrmann type iv gastric carcinoma

Between 1979 and 1993, 665 Japanese patients with advanced gastric cancer underwent surgery at our hospital. These patients were divided into two groups, consisting of 102 patients with Borrmann type IV carcinoma, and the remaining 563 patients with all other types of gastric carcinoma, which were then compared clinicopathologically. In the patients with Borrmann type IV carcinoma, 77.4% of the lesions demonstrated poorly differentiated adenocarcinoma, and 99 patients were classified as Stage III or IV. The resection rate was 87.2% (89/102) with only 39 curative operations despite the fact that 70 total gastrectomies were performed. The incidence of peritoneal dissemination (29.4%) and serosal invasion (97.0%) was significantly higher in these patients. Microscopic lymph node metastasis was positive in 86.5%. The 5-year survival rate was 23.4% in the patients with a curative operation and 5.0% in those with a noncurative operation (p < 0.01). Peritoneal dissemination was most frequently noted in the recurrence patterns. We conclude that early detection and a curative operation are both essential to improve the prognosis of patients with Borrmann type IV gastric cancer. The addition of a potent postoperative chemotherapy regimen is also recommended. © 1995 Wiley-Liss, Inc.     

Retinal fascin: functional nature, subcellular distribution, and chromosomal localization

PURPOSE: To investigate the functional properties, subcellular localization, and chromosomal location of retinal fascin. METHODS: Recombinant retinal fascin protein was prepared by using a baculovirus-insect expression system. Actin-binding and -bundling assays were performed with chick actin purified from skeletal muscle. Western blot analysis and immunohistochemistry were performed with a polyclonal antibody raised against bovine retinal fascin. A human retinal cDNA library was screened with an expressed sequence tag cDNA fragment. Chromosomal location was determined with fluorescent in situ hybridization. RESULTS: The actin-binding and actin-bundling activities of retinal fascin were demonstrated by high- and low-speed centrifugation assays. Formation of filamentous (F)-actin bundles by retinal fascin in vitro was also morphologically confirmed by fluorescence microscopy and electron microscopy. Immunohistochemical analysis revealed that retinal fascin protein was localized specifically in the outer and inner segments of the photoreceptor cells in the retina. Two splicing variants of human retinal fascin cDNA were also located. One clone encoded 492 amino acids, and the other encoded 516 amino acids. The gene encoding retinal fascin was localized to human chromosome 17, region q24 -25. CONCLUSIONS: These results suggest that retinal fascin may play a role in formation of unique morphologic structures of the photoreceptor cells and is a candidate gene for retinal degenerative disorders.     

Fixation patterns of idiopathic macular holes after vitreous surgery

BACKGROUND: Evaluation of idiopathic macular holes with the scanning laser ophthalmoscope (SLO) has shown fixation to be located at or near the margin of the hole and above the horizontal meridian in most cases. However, changes between preoperative and postoperative fixation have not been well studied. METHOD: We used SLO microperimetry to determine scotomas and fixation points in 13 patients with idiopathic macular holes before and after vitreous surgery. The distance between preoperative and postoperative fixation points and the direction of movement were measured. RESULTS: Preoperatively, fixation was found to be at or near the margin of the macular hole in all eyes and was located above the horizontal meridian in most (84.6%) eyes. Postoperatively, there was a shift in the position of the fixation points. The distance between preoperative and postoperative fixation correlated with the degree of visual improvement (P = 0.032), but the direction of movement was variable. CONCLUSION: A shift in the position of fixation occurs after macular hole surgery, and the amount of shift correlates with visual improvement. From this observation, we define the term functional macular hole closure, characterized by centripetal movement of the neurosensory retina and improvement in vision, and the broader term anatomic macular hole closure, in which apparent hole closure may result from gliosis in the absence of movement of the neurosensory retina, not associated with visual improvement.     

Intraoperative adjunctive agents in vitrectomy: serum, cytokines, and glue

The surgical goal in the treatment of retinal breaks is to seal the edges of the break, and traditionally, photocoagulation and cryocoagulation have been used to accomplish this. However, it is sometimes difficult in complicated retinal detachments to maintain the seal against tractional forces. Adhesion is achieved through a process of cell necrosis, inflammation and subsequent fibrovascular proliferation. This strategy, however, may not be appropriate in vision-sensitive areas such as macular holes. To improve the success rate of macular hole surgery, a number of authors have advocated the use of biological modifiers, such as transforming growth factor beta, human autologous serum, tissue glue, or platelet concentrates.These materials may enhance the adhesion of the detached retina and therefore lead to a better anatomical and functional success.We have reviewed the advances of intraoperative application of synthetic or biological adhesives. However, through the improvement of surgical techniques and surgeons' skills in recent years, the anatomical success rate of macular hole surgery has increased in most institutions without adjunctive additives. Thus, many surgeons believe that adjunctive additives may not be necessary for most idiopathic macular holes.     

Clinical Usefulness of Determining the Rate of Thermal Clearance within Heated Tumors

Between June 1987 and June 1988, 28 patients (28 tumors) withliver, retroperitoneal, intrapelvic, or superficial tumors weretreated with hyperthermia combined with radiotherapy and/orchemotherapy. Hyperthermia was administered once or twice aweek for 30-60 min per session, up to a total of 2–11sessions, with an 8-MHz RF capacitive heating device. Bloodflow in the tumors was evaluated from the rate of thermal clearance(TCR) using the bio-heat transfer equation. The TCR was measuredin the middle of the first heating session and at the end ofthe last heating session by turning off the output power ofthe heating device. For 9 patients, contrast-enhanced CT scanswere taken and CT numbers at the centers of tumors were measuredbefore and after the entire course of hyperthermia. Changesin TCR were closely related to average tumor center temperature,changes in CT number, and tumor response. When smaller and moresuperficial tumors were treated by hyperthermia combined withradiotherapy and/or chemotherapy that consisted of many heatingsessions and during which a high average tumor center temperaturewas achieved, a better tumor response was obtained. The betterthe tumor response, the higher the local control rate became.The cause-specific survival rate of patients who achieved goodtumor responses was higher than that of patients who showedpoor tumor responses. Changes in TCR and CT number in heatedtumors were useful and important indicators of tumor responseto hyperthermia.     

Corneal guttata associated with the corneal dystrophy resulting from a betaig-h3 R124H mutation

AIMS: To investigate the frequency of corneal guttata in patients with a corneal dystrophy resulting from an Arg124His (R124H) mutation of betaig-h3 gene. METHODS: Slit lamp examination was performed on 30 eyes with corneal dystrophy from a genetically confirmed betaig-h3 R124H mutation and on 50 age matched control eyes. The stage of the corneal dystrophy was classified as stage 0, I, or II and the degree of guttata was classified as none, mild, or severe. Specular microscopic examinations were performed to evaluate the morphology of the corneal endothelium. RESULTS: Slit lamp examination disclosed the presence of corneal guttata in 21 eyes (70%) of the 30 eyes with the corneal dystrophy, but in only one (2%) of the 50 eyes in the age matched control group (p<0.001, chi(2) with Yates's correction). Of the 12 eyes with stage I betaig-h3 R124H corneal dystrophy, seven had no corneal guttata and five had a mild degree of guttata. Of the 18 eyes with stage II, the degree of guttata was none in two, mild in nine, and severe in seven. The degree of corneal guttata was significantly related to the stage of the corneal dystrophy (p<0.0001, Kruskul-Wallis test ANOVA on ranks). There was no significant differences between eyes with betaig-h3 R124H corneal dystrophy and normal eyes in cell density, coefficient of variation, and cell hexagonality of corneal endothelium. CONCLUSION: Corneal guttata are one of the characteristics of the corneal dystrophy resulting from betaig-h3 R124H mutation.