Port-site transversus abdominis fascia closure reduced the incidence of incisional hernia following retroperitoneal laparoscopic nephrectomy.

PURPOSE: The incidence of incisional hernia after laparoscopic surgery is reportedly 0-5.2 %; there are only a few reports of that following retroperitoneal laparoscopic nephrectomy. We evaluated the incidence of and risk factors for incisional hernia after retroperitoneal laparoscopic nephrectomy, and the efficacy of our novel prophylaxis technique. METHODS: A total of 207 renal cell carcinoma patients who underwent laparoscopic nephrectomy at Chiba University Hospital were retrospectively enrolled in this study. We compared the incidences of incisional hernia following the transperitoneal vs. retroperitoneal approaches, and, among the latter group, the incidences with vs. without use of our prophylaxis method. Also among the retroperitoneal-approach group, we evaluated selected patient characteristics as potential hernia risk factors. RESULTS: The rate of incisional hernias was 14 (8.7 %) after 161 retroperitoneal laparoscopic nephrectomies and one (2.2 %) after 46 transperitoneal laparoscopic nephrectomies (P = 0.132). For those undergoing the retroperitoneal approach, 14 (11.3 %) hernias were identified in 124 non-prophylaxed patients and none in 37 prophylaxed patients. Transversus abdominis fascia closure was a statistically significant factor for reducing the incidence of incisional hernia after retroperitoneal laparoscopic nephrectomy (P = 0.0324): rectus abdominis muscle thickness ≤7 mm and perioperative blood loss >100 ml were statistically significant independent risk factors, by multivariate analysis. CONCLUSIONS: To prevent incisional hernia after retroperitoneal laparoscopic nephrectomy in the patients with risk factors, it is useful to close the transversus abdominis fascia at the port sites from inside the surgical cavity, through the open specimen-removal trocar port site, under direct observation.

Establishment of a GIS monitoring system for schistosomiasis japonica in Kofu, Japan.

Although the incidence of human infection with Schistosoma japonicum in Japan fell to zero in 1977, the threat of the possible re-emergence of the disease caused by this trematode still exists. Surveillance of the parasite's intermediate host, Oncomelania nosophora, in Kofu basin therefore began in 1996. A simple, new method for monitoring O. nosophora in an at-risk area in Kofu, which is based on a geographical information system (GIS), was established. At each monitoring site (of which there were 120 from 1996 until 2000, and 60 from 2001 until 2003), the O. nosophora in two quadrats, each measuring 25 x 25 cm, were collected. During the study, the exact location of each site was determined using a hand-held global-positioning system (GPS). This allowed all the sites to be digitally mapped, so that anyone with a hand-held GPS could and can reach each site. The snail and location data were processed using commercial GPS/GIS software packages and used to create a risk map for schistosomiasis re-emergence. Although all snails collected between 1996 and 2003 were uninfected, the proportion of investigated sites in which O. nosophora was detected increased from 36.7% in 1996 to 56.7% in 2003. The mean number of O. nosophora collected per snail-positive site fluctuated widely, between 8.2 and 57.4, in each calendar year. Over the study period there appeared to be a shift southwards in the areas with high densities of O. nosophora. The present results indicate that it is possible to utilize a GIS-based method for the long-term monitoring of the possible re-emergence of schistosomiasis japonica in Japan.

Analysis of northern distribution of Aedes albopictus (Diptera: Culicidae) in Japan by geographical information system.

Aedes albopictus (Skuse), a mosquito vector of the dengue fever virus, is prevalent in Japan, distributed widely in Honshu Island with its northern limits between latitude 38 degrees to 40 degrees north. The factors affecting distribution of the species in the northern part of Japan were studied using the geographical information system (GIS). During 1998-2000, larval surveillance was carried out in 26 urban and rural areas in the Tohoku district, in the northern part of Honshu Island, by collecting larvae from artificial and natural habitats. Climatological analysis, using the GIS, showed that the following conditions accounted for the current distribution of Ae. albopictus: an annual mean temperature higher than 11 degrees C and a mean temperature of the coldest month, January, higher than -2 degrees C. A period with temperature above 11 degrees C in the confirmed area of the mosquito successively continues for more than 186 d per year. The accumulated temperature calculated from a temperature of 11 degrees C, which may be close to the developmental zero of Ae. albopictus, was over 1,350 degree-days. The relationship between the beginning of short-daylength, inducing egg diapause, and the monthly mean temperature during September and October necessary for successful larval development in the Tohoku district is also discussed. We also show the relationship between the current distribution of Ae. albopictus and the annual mean temperature in the United States. From these results it is predicted that Ae. albpictus will be established in some cities in northeast United States.

[Occurrence of alveolar hydatid disease (multilocular echinococcosis) outside of Hokkaido and a proposal for its prevention].

Alveolar hydatid disease (AHD), had been endemic only in Rebun Island prior to 1945, it is now prevalent throughout the mainland Hokkaido. AHD cases have been reported also in 21 prefectures outside of Hokkaido, e.g. Aomori, Tokyo, Miyagi, etc. Case reports of AHD (n = 135) were reviewed and 76 cases were identified in 21 prefectures outside of Hokkaido in 1926-96. These cases were classified in 4 groups: 1) cases supposedly infected where they lived (n = 19), 2) cases that were infected in Hokkaido (n = 23), 3) cases that were infected in foreign countries (n = 30), 4) cases infected in unidentified places (n = 4). Prefectural distribution and sex ratios were characteristic according to the groups. The first group was supposedly infected were they lived, but it was suggested that this group had some relationship with the epidemics of AHD in Hokkaido. Cases of the 1st and 2nd group were estimated to have been infected prior to early 1970, and it was suggested that these 2 groups will increase the number hereafter in the prefectures outside of Hokkaido because the number of AHD cases has been increasing in the mainland Hokkaido since late 1980.

[Epidemiology of alveolar hydatid disease (AHD) and estimation of infected period of AHD in Rebun Island, Hokkaido].

An epidemiological study was performed of endemic alveolar hydatid disease (AHD, multilocular echinococcosis), Rebun Island, Hokkaido and the period of AHD infection of patients was estimated. Death certificates of the residents of the island were analyzed, and 74 deaths (43 males and 31 females) by AHD were found out of the 3,126 deaths that occurred during the period from 1948 to 1990. The red fox population of the island was estimated on the basis of past researchs. The deaths due to AHD distributed around a major peak (n = 67) between 1948-1975 and there were 7 sporadic cases between 1976-90. The red fox population on the island had been estimated to be largest in 1935. The mean infection period from initial AHD infection to death was estimated to be 26 +/- 7 years (x +/- SD) on the basis of the period between the year in which the peak red fox population was observed (1935) and the major peak of patient death (1962). The mean symptomatic period was 5 +/- 5 years, and the mean latent period from infection to the onset of AHD was 21 +/- 7 years. Sex ratio (M/F = 28/13 = 2.15) was higher (P < 0.05) at the age groups below 10 and 26-45 years than the other age groups (15/18 = 0.83), and playing outdoors during childhood and working outdoors in the prime of life were assumed to be the causes of infection.

The insulin-like growth factor-1 elevates urokinase-type plasminogen activator-1 in human breast cancer cells: a new avenue for breast cancer therapy.

Tumor recurrence is a common problem in the treatment of breast cancer. In breast cancer, the expression of high protein levels of the insulin-like growth factor-1 receptor (IGF-1R) and urokinase-type plasminogen activator-1 (uPA) is strongly associated with breast cancer recurrence and decreased survival. The expression of uPA by tumors is thought to not only stimulate tumor invasion but also facilitate angiogenesis. In this study, our goal was to address whether IGF-1R could influence the expression of the extracell ular matrix proteases, matrix metalloproteinase (MMP), or uPA thus allowing a selective advantage for tumor invasion and concomitant neovascularization. Initially, we determined whether or not insulin-like growth factor (IGF)-1 regulated the production MMP or uPA in the human breast cancer MDA-MB-231 cells. There was no increase in MMP activity when the cells were treated with IGF-1 (10 ng/mL) for 24 h. In contrast, uPA mRNA and protein were induced in a time-dependent manner. Furthermore, clones expressi ng a dominant negative inhibitor of IGF-1R termed 486stop had less uPA mRNA, and the clones were less invasive through Matrigel. Taken together, these data illustrate that IGF-1R stimulates uPA production. Hence, these two prognostic indicators may be interrelated, suggesting they may function in a synergistic manner to facilitate local tumor invasion as well as angiogenesis. Our data suggest that disruption of IGF-1 signaling in breast cancer may lead to breast cancer prevention and intervention by decreasing uPA expression.

Mapping of metastasis suppressor genes for prostate cancer by microcell-mediated chromosome transfer.

AIM: To identify the metastasis suppressor genes for prostate cancer. METHODS: A copy of human chromosomes was introduced into the highly metastatic Dunning R-3327 rat prostate cancer cells by the use of microcell-mediated chromosome transfer. Relationships between the size of human chromosomes introduced into microcell hybrid clones and the number of lung metastases produced by the clones were analyzed to determine which part of human chromosomes contained the metastasis suppressor gene(s) for prostate cancer. To determine portions of human chromosomes introduced, G-banding chromosomal analysis, fluorescence in situ hybridization analysis, and polymerase chain reaction analysis were performed. RESULTS: Each of microcell hybrid clones containing human chromosomes 7, 8, 10, 11, 12, or 17 showed decreased ability to metastasize to the lung without any loss of tumorigenicity. This demonstrates that these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portions of human chromosomes was observed in the human chromosome 7, 10, 11, 12, and 17 studies. In the human chromosome 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletions of human chromosome 8. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasis suppressor genes on human chromosomes were located on 7q21-22, 7q31.2-32, 8p21-12, 10q11-22, 11p13-11.2, 12p11-q13, 12q24-ter, and 17pter-q23. KAI1 and MKK4/SEKI were identified as metastasis suppressor genes from 11p11.2 and 17p12, respectively. CONCLUSION: This assay system is useful to identify metastasis suppressor gene (s) for prostate cancer.

Metastasis suppressor gene(s) for rat prostate cancer on the long arm of human chromosome 7.

Allelotype analyses of human prostate cancer indicate that allelic losses on human chromosome arms 7q, 8p, 10q, 13q, 16q, 17q, and 18q are observed frequently. For the study of the possible biological significance of the frequently observed deletions on chromosome arm 7q in human prostate cancer, human chromosome 7 was introduced into highly metastatic rat prostate cancer cells by use of a microcell-mediated chromosome transfer technique. The introduction of human chromosome 7 resulted in the suppression of metastatic ability of the microcell hybrids, whereas no suppression of tumorigenicity was observed. To identify the portion of chromosome 7 containing the metastasis-suppressive function gene, the derivative chromosome 7 that was generated with the initial transfer was retransferred into rat prostate cancer cells. Human chromosome 7-containing rat prostate cancer cells could be used as the donor cells, because rodent cells produced a sufficient number of microcells with colchicine treatment. Cytogenetic and molecular analyses of these clones demonstrated that loss of segments on 7q was related to the reexpression of the metastatic phenotype. These results show that human 7q contains a metastasis suppressor gene or genes for rat prostate cancer. The findings also suggest that this gene may play an important role in the progression of human prostate cancer.

Soil factors influencing the distribution of Oncomelania quadrasi, the intermediate host of Schistosoma japonicum, on Bohol Island, Philippines.

Soil conditions essential to the survival of Oncomelania quadrasi on Bohol Island in the Philippines were examined to clarify the factors limiting distribution of the snail and to develop a method for breeding large numbers of the snail in the laboratory. Soil samples in and around snail habitats were analysed and used for breeding experiments in the laboratory. Experiments using paddy soil derived from different parent materials revealed that the numbers of juvenile snails hatched varied widely between several soil samples. The best soils for reproduction generally had a pH of 5.6-7.9 and > 200 mg of available CaO/100 g. These soil factors, in addition to shade and moisture, determine the optimum conditions for the breeding of O. quadrasi in the field as well as in the laboratory. The determination of the optimum conditions for laboratory breeding of O. quadrasi and other intermediate snail hosts should facilitate detailed study of the hosts and the development of better methods to control or eradicate schistosomiasis and other snail-transmitted diseases.

Location of KAI1 on the short arm of human chromosome 11 and frequency of allelic loss in advanced human prostate cancer.

BACKGROUND: We recently isolated the KAI1 gene, a metastasis suppressor gene for prostate cancer, from human chromosome region 11p13-cen-containing rat prostate cancer cells. The present study was performed to further locate the region of the KAI1 gene on the short arm of chromosome 11, and to examine whether loss of this region is significant during progression of human prostate cancer. METHODS: The small portion of human chromosome 11 (i.e., 11p13-cen) was reintroduced into highly metastatic rat prostate cancer cells by using microcell-mediated chromosome transfer. Loss of heterozygosity (LOH) at polymorphic microsatellite loci on the human chromosome 11 was examined in human prostate cancer tissues. RESULTS: The minimum region of human chromosome 11 that contained the KAI1 gene was located on the proximal region of 11p11.2 divided by the D11S554 locus. The percentage of LOH or allelic imbalance at the D11S1344 locus, which is located on the same region as the KAI1 locus, in metastasis tissues from autopsy cases who died from metastatic prostate cancer was 70% (7 of 10 informative cases), whereas the percentages in primary tumors from the same cases and from cases with clinically localized prostate cancer were 33% (3 of 9 informative cases) and 8% (1 of 12 informative cases), respectively. CONCLUSIONS: These findings demonstrate a high frequency of LOH or allelic imbalance at the centromeric region of 11p, which contains the KAI1 gene in advanced prostate cancer.

Suppression of invasive ability of highly metastatic rat prostate cancer by introduction of human chromosome 8.

BACKGROUND: Introduction of human chromosome 8 to a highly metastatic subline (AT6.2) from the Dunning R-3327 rat prostate cancer resulted in suppression of metastatic ability of the resultant microcell hybrids (AT6.2-8 clones) [12]. The present study has been performed to clarify which step of metastasis was suppressed in the microcell hybrids. METHODS: Northern blot analysis of E-cadherin and alpha-catenin, in vitro invasion assay, and intra-venous metastasis assay by injection of tumor cells into the lateral tail vein of nude mice were performed. RESULTS: No detectable expressions of either E-cadherin or alpha-catenin were found in either AT6.2 parental or AT6.2-8 microcell hybrid clones. In the invasion assay, invasiveness of AT6.2-8 hybrid clones was less than that of the AT6.2 parental clone. In the intravenous metastasis assay, no significant differences in the number of lung metastases were observed among these cell lines. CONCLUSIONS: Introduction of human chromosome 8 to AT6.2 cells shows suppression of invasiveness and no suppression of cell dissociation or process after entry into blood circulation. This suggests that human chromosome 8 contains suppressor gene(s) for the invasive ability of prostate cancer.

Mapping of metastasis suppressor gene(s) for rat prostate cancer on the short arm of human chromosome 8 by irradiated microcell-mediated chromosome transfer.

Our previous studies demonstrated that human chromosome 8 contains metastasis suppressor gene(s) for rat prostate cancer. However, it is still unknown which portion of human chromosome 8 is associated with suppression of metastatic ability, because all of the clones in which metastatic ability is suppressed contain at least one copy of intact human chromosome 8. In the present study, we used the irradiated microcell-mediated chromosome transfer technique to enrich for specific chromosomal arm deletions of selected chromosomes. The resultant series of human chromosomes 8 with a variety of chromosomal deletions was introduced into highly metastatic Dunning rat prostate cancer cells. All of the resultant microcell hybrids showed reduced metastatic ability. To obtain a smaller size of human chromosome 8 and to locate further the region of metastasis suppressor gene(s), the most reduced size of human chromosome 8 that was generated with the initial irradiated chromosome transfer was retransferred into the Dunning cancer cells without irradiation. The resultant microcell hybrids were analyzed to determine which portion of human chromosome 8 suppressed the metastatic ability of the recipient cells. This analysis demonstrates that the portion of human chromosome 8 containing metastasis suppressor gene(s) for rat prostate cancer cells lies on human chromosome segment 8p21-p12, where frequent allelic losses have been detected in allelotype analyses of human prostate cancer. This suggests that one of the metastasis suppressor genes for rat prostate cancer on human chromosome 8 may also play an important role in the progression of human prostate cancer.

Metastasis suppressor genes for prostate cancer.

To examine the role of human chromosomes in the development of metastatic prostate cancer, we introduced a copy of human chromosomes into highly metastatic Dunning R-3327 rat prostatic cancer cells by microcell-mediated chromosome transfer. Each microcell hybrid clones containing human chromosomes 8, 10, 11, and 17, respectively, showed decreased ability to metastasize to the lung, without any loss of tumorigenicity. This finding demonstrates that these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portions of human chromosomes was observed in human chromosome 10, 11, and 17 studies. In the human chromosome 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletions of human chromosome 8. Relationships between the size of human chromosomes introduced into microcell hybrid clones and the number of lung metastases produced by the clones were analyzed to determine which part of human chromosomes contained metastasis suppressor gene(s) for prostate cancer. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasis suppressor genes on human chromosomes 8, 10, and 11 were located on 8p23-q12, 10q, 11p13-11.2, respectively. Further analyses are proposed to confirm the potentially useful advantage of this assay system to identify metastasis suppressor gene(s) for prostate cancer.

Localization of metastasis suppressor gene(s) for rat prostatic cancer to the long arm of human chromosome 10.

To examine the role of human chromosome 10 in development of prostatic cancer, we introduced human chromosome 10 into highly metastatic rat prostatic cancer cells by microcell-mediated chromosome transfer. Microcell hybrid cells introduced with human chromosome 10 showed suppression of the metastatic ability to the lung to some extent without any suppression of tumorigenicity, although the tumor growth rate decreased slightly. To minimize the region that contains metastasis suppressive activity, the hybrid cells in metastasis foci of lung were established in culture and reanalyzed for portions of human chromosome 10 retained in the metastasis tissues. Cytogenetic and molecular analyses demonstrated that loss of the region between 10cen and D10S215 on human chromosome arm 10q was related to expression of the metastatic phenotype. These results demonstrate that the region between 10cen and D10S215 on human chromosome arm 10q contains at least one of the metastasis suppressor genes for rat prostatic cancer.

Inhibition of growth and increase of acid phosphatase by testosterone on androgen-independent murine prostatic cancer cells transfected with androgen receptor cDNA.

Most androgen-unresponsive prostatic cancer cells are found to lack androgen receptor (AR). To clarify the role of AR in the process of the progression from androgen-dependent to androgen-unresponsive tumor, the AR gene was transfected into an AR-negative rat prostatic cancer cell line CUB-II. AR-transfectant cells expressed AR mRNA and showed binding to R1881. AR was found in nuclei of AR-transfectant cells by histochemical examination. Therefore, AR-transfectant cells were considered to contain functional AR. The growth of AR-transfectant cells was markedly inhibited in culture in the presence of testosterone, and the effect of testosterone was reduced by simultaneous addition of flutamide. Moreover, tumors inoculated with AR-transfectant cells in male mice showed much slower growth than those in females. The tumors of AR-transfectant cells in mice consisted of slightly larger spindle-shaped cells when compared to those of CUB-II cells. Moreover, AR-transfectant cells contained a few polynuclear giant cells. Since CUB-II cells contained acid phosphatase (AcP) activity, the addition of testosterone in culture increased AcP activity of AR-transfectant cells. It is concluded that resumption of androgen-dependent processes reduces the growth rate accompanying changes of phenotype.

Suppression of metastasis of rat prostatic cancer by introducing human chromosome 8.

In previous allelotype analyses of human prostatic cancer specimens, allelic loss on the short arm of chromosome 8 is frequently observed. However, it is still unclear whether this allelic loss is an initial event or a later one in development of prostatic cancer. Our previous studies demonstrate that introduction of human chromosome 11 into highly metastatic rat prostatic cancer cells results in suppression of metastatic ability without suppression of the in vivo growth rate or tumorigenicity of the hybrid cells (T. Ichikawa et al. Cancer Res., 52: 3486-3490, 1992). To clarify the role of human chromosome 8 in prostatic cancer, this chromosome was introduced into highly metastatic rat prostatic cancer cells using microcell-mediated chromosome transfer. Introduction of human chromosome 8 resulted in suppression of metastatic ability of the microcell hybrids, whereas no suppression of the in vivo growth rate or tumorigenicity was observed. These results demonstrate that human chromosome 8 contains metastasis suppressor gene(s) for prostatic cancer derived from a rat. These also suggest that human chromosome 8 has an important role in development of prostatic cancer.

Studies on thyrotropin releasing hormone in cerebellar ataxia mutant mouse brain.

The effects of cathecholamine on the regional TRH distribution in the brain was studied in rolling mouse Nagoya (RMN) and non-affected C3H mice. TRH was extracted from the hypothalamus, brain stem, cerebellum, and cerebrum one hour after i.p. injection of the precursor or inhibitors of cathecholamine. TRH was distributed throughout the brain of both affected and non-affected mice; however, in RMN, TRH levels were lower in the hypothalamus and higher in other areas. 1-Dopa caused a decrease of TRH in the brain stem but no change in other regions in the RMN brain, whereas it caused an increase in TRH levels in all areas of the C3H brain. Fusaric acid increased TRH in the hypothalamus of RMN and decreased it in the cerebellum; alpha-MPT also caused a decrease in the TRH level in the cerebellum. Reserpine increased the TRH level in the hypothalamus and decreased it in the cerebrum. From these results, it appears that cerebellar ataxia in RMN does not result from a decrease in the TRH, which is actually increased in the cerebellum. Catecholamine had different effects on TRH levels in RMN and the controls; this might be due to the excess accumulation of noradrenaline in the RMN brain.

Gigantism associated with McCune-Albright's syndrome.

The case of a 16 year-old boy with McCune-Albright's syndrome which is rarely accompanied by gigantism was studied endocrinologically. The stimulation of growth hormone (GH) release by hypoglycemia, the decline of elevated GH by hyperglycemia and a little lower somatostatin like immunoreactivity (SLI) may support abnormalities of hypothalamic function, but the existence of pituitary microadenoma cannot be ruled out because of the paradoxical suppression of GH release by oral administration of bromocriptine (CB-154) and L-DOPA and the stimulation of GH release by intravenous administration of TRH.