Factors contributing to tourism demand at major Japanese hot springs.

Hot springs are a major tourism resource in nature-based tourism, and the hot springs market is one of the biggest sectors in wellness tourism markets. In the present study, we examine factors contributing to tourism demand for major hot spring resorts in Japan using ordinary least squares regression models and generalized linear mixed models, and compare the estimation results. The results show that significant factors in most of our models are quality of accommodations and the degree of dependence on inbound demand. Furthermore, the number of non-Japanese languages supported on websites of hot spring resorts has a significant impact on inbound demand. Since the results of the present study cover more than 80 hot spring sites, the results highlight common important factors for hot spring resorts. Such widely applicable factors have been missing in previous studies, and the present study fills this research gap.

Qualitative analysis of cancer telephone consultations: Differences in the counseling needs of Japanese men and women.

OBJECTIVE: To analyze large-scale data obtained from telephone cancer consultations and clarify sex differences in the information sought by callers to guide future cancer survivor support. METHODS: We qualitatively analyzed 10,534 cases of telephone consultations with cancer patients. The relationships between callers' words and sex were visualized through a correspondence analysis, and the keywords extracted were visualized with a dependency relationship to the words "worry" and "anxiety," which had a high prevalence in the text data. RESULTS: Most of the male callers sought consultation about stomach cancer (11.8%), the consultations were predominantly about "suspicion of having cancer" (25.2%), and males indicated that the goal was to gather accurate information. Female callers mostly sought consultation about breast cancer (18.4%) were mainly interested in learning about "treatment" (31.0%), and mostly used the keywords "worry" and "anxiety." The total number of callers without a definitive diagnosis accounted for 20% of all consultations. CONCLUSIONS: Healthcare providers need to understand unique sex-based coping styles and perform regular follow-ups. There is also a need for online platforms that provide information from the patient's perspective. PRACTICAL IMPLICATIONS: Providing a cancer consultation support system and easy-to-understand medical information will improve communication between survivors, their families, and medical staff.

Autonomic nervous system function in adolescent migraineurs.

BACKGROUND: Migraine is a common and disabling neurological disorder. Studies on the relationship between migraine and the autonomic nervous system (ANS) have been inconclusive. Moreover, pediatric studies are extremely limited. Therefore, the present study investigated interictal ANS function in adolescent migraineurs. METHODS: We studied 21 patients with migraine and 26 healthy controls. Beat-to-beat blood pressure (BP) and heart rate (HR) were non-invasively and continuously measured in the supine and standing positions. ANS function was evaluated on power spectral analysis of HR variability and diastolic BP (DBP) variability. RESULTS: Heart rate and systolic BP were not different between the two groups in either the supine or standing position. DBP did not differ between groups in the standing position, but was significantly higher in migraineurs in the supine position. The vasoconstrictor index was significantly higher in migraineurs. High-frequency (HF) RR interval variability (RR-HF) and the ratio of the low-frequency (LF) to HF component of RR interval variability (RR-LF/HF) were not different between the two groups in both positions. The LF component of DBP variability (DBP-LF) in the supine position was significantly lower in migraineurs, while DBP-LF during standing in migraineurs was significantly higher than in controls. CONCLUSION: Migraineurs have significantly lower sympathetic vasomotor activity in the supine position, while sympathetic vasomotor activity was hyperresponsive during standing.

Increasing trends in cervical cancer mortality among young Japanese women below the age of 50 years: an analysis using the Kanagawa population-based Cancer Registry, 1975-2012.

BACKGROUND: In Japan, cervical cancer (CC) deaths among women aged <50 years have doubled over the last three decades. Obtaining age-specific CC mortality rates among young women is important for taking measures against CC. Age-adjusted CC mortality rates for all ages are inadequate because of the classification of 'uterine cancer, not otherwise specified' (NOS uterine cancer) and CC mortality rates among elderly women. The aim of the present study was to calculate exact age-specific CC mortality rates in women aged <50 years in Kanagawa, taking into account the impact of NOS uterine cancer. METHODS: Using the Kanagawa Cancer Registry, CC deaths (1975-2012) were analyzed and CC mortality rates (age-adjusted, 20-29, 30-49, and ≥50 years) were calculated. In addition, hospitals were surveyed to reclassify cases of NOS uterine cancer. After reclassification, chronological trends were also analyzed. RESULTS: Age-specific CC mortality rates in Kanagawa and Japan overall showed increasing trends for ages 20-29 (P for trend<0.001) and 30-49 (P for trend<0.001). Rates of NOS uterine cancer death were significantly lower in Kanagawa than in Japan overall (P<0.05), except for patients aged <50 years in 2005-2009 (P=0.159). CONCLUSIONS: The present study revealed concern for CC among Japanese women younger than 50 years. Well-organized CC screening and HPV vaccination should be provided to reduce CC mortality rates for these young women.

Systematic review and meta-analysis of histopathological predictive factors for lymph node metastasis in T1 colorectal cancer.

BACKGROUND: In this study we examined whether histopathological findings, specifically lymphatic vessel invasion identified by an anti-human podoplanin antibody, and several other factors are associated with lymph node metastasis in T1 colorectal cancer. METHODS: We searched PubMed and Cochrane Library, and also handsearched relevant journals, for reports written in English and published between 1998 and 2012, utilizing combination headings, such as 'colorectal cancer,' 'lymph node metastasis,' and 'risk factors.' For the report to be included in our study, the following criteria had to be met: (1) data on the frequency of lymph node metastasis in T1 colorectal cancer in relation to histopathological factors were reported; (2) patients had undergone bowel resection and had histologically diagnosed T1 colorectal cancer; (3) lymphatic vessel invasion was identified by immunohistochemistry with an anti-human podoplanin antibody rather than by hematoxylin and eosin staining; (4) univariate and multivariate analyses were conducted. Studies investigating molecular markers were excluded. The independent predictive factors were confirmed in at least one study included in the meta-analysis in the present systematic review. Microsoft Excel 2013 for Windows was used for the statistical analysis. RESULTS: Initially, 369 publications were identified in the database searches and handsearches, of which five ultimately met all of the inclusion criteria and selected for this systematic review. The meta-analysis revealed that only two factors were significantly associated with T1 colorectal cancer lymph node metastasis: (1) lymphatic vessel invasion identified by an anti-human podoplanin antibody [Mantel-Haenszel odds ratio (OR) 5.19; (95% confidence interval (CI) 3.31-8.15; P = 0.01]; (2) tumor budding (OR 7.45; 95 % CI 4.27-13.02; P = 0.0077). CONCLUSION: Our meta-analysis revealed that lymphatic vessel invasion identified by an anti-human podoplanin antibody and tumor budding were significantly associated with T1 colorectal cancer lymph node metastasis.

Comprehensive assessment of cancer patients' concerns and the association with quality of life.

OBJECTIVE: Comprehensive assessment of perceived concerns can be used to guide supportive care appropriate to individual cancer patients. This study sought to determine the prevalence of cancer patients' concerns and the degree to which these concerns contribute to patients' quality of life. METHODS: Participants were patients with all types of cancer, who completed an Internet survey questionnaire regarding comprehensive concerns about physical, psychological, psychosocial and economic aspects of having cancer. The questionnaire was based on the newly developed Comprehensive Concerns Assessment Tool and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. RESULTS: We obtained complete data from 807 patients. Factors related to 'self-management' concerns were the most common (61.2%), followed by concerns about 'psychological symptoms' (48.5%), 'medical information' (46.2%), 'daily living' (29.9%), 'pain' (17.6%), 'constipation' (15.6%) and other 'physical symptoms' (15.2%). Multiple regression analysis revealed that all concerns except those about 'medical information' significantly contributed to quality of life. CONCLUSIONS: Cancer patients' concerns were shown to be multidimensional and significantly associated with quality of life. Thus, assessment of patients' concerns should be multidimensional in nature, and a multidisciplinary care team should help patients improve their quality of life.

Characteristics of elderly cancer patients' concerns and their quality of life in Japan: a Web-based survey.

OBJECTIVE: Cancer incidence and the number of cancer patients are increasing in today's aging society. The purpose of this study was to investigate the characteristics of elderly cancer patients' concerns and examine the association between their concerns and quality of life. METHODS: This was a cross-sectional web-based survey completed by ambulatory cancer patients aged 20 years or older. The questionnaire on cancer patients' concerns, comprehensive concerns assessment tool and the European Organization for Research and Treatment of Cancer QLQ-C30 were distributed to the subjects. Multiple regression analysis was conducted to determine which patients' concerns significantly contributed to their quality of life. RESULTS: The final study population consisted of 807 cancer patients, among whom 243 (30%) were elderly (65 years or older). Elderly cancer patients had particular difficulty with self-management, psychological symptoms and medical information, and the prevalence of their concerns was generally lower than that of younger patients, with the exception of physical symptoms. Multiple types of elderly patients' concerns were independently associated with quality of life. CONCLUSIONS: We found that elderly cancer patients suffered from various concerns, thus multidisciplinary intervention is important for providing them with optimal care. The results of this study suggest that elderly cancer patients' quality of life will improve if their concerns are properly handled.

Breast cancer clustering in Kanagawa, Japan: a geographic analysis.

BACKGROUND: The purpose of the present study was to determine geographic clustering of breast cancer incidence in Kanagawa Prefecture, using cancer registry data. The study also aimed at examining the association between socio-economic factors and any identified cluster. MATERIALS AND METHODS: Incidence data were collected for women who were first diagnosed with breast cancer during the period from January to December 2006 in Kanagawa. The data consisted of 2,326 incidence cases extracted from the total of 34,323 Kanagawa Cancer Registration data issued in 2011. To adjust for differences in age distribution, the standardized mortality ratio (SMR) and the standardized incidence ratio (SIR) of breast cancer were calculated for each of 56 municipalities (e.g., city, special ward, town, and village) in Kanagawa by an indirect method using Kanagawa female population data. Spatial scan statistics were used to detect any area of elevated risk as a cluster for breast cancer deaths and/ or incidences. The Student t-test was performed to examine differences in socio-economic variables, viz, persons per household, total fertility rate, age at first marriage for women, and marriage rate, between cluster and other regions. RESULTS: There was a statistically significant cluster of breast cancer incidence (p=0.001) composed of 11 municipalities in southeastern area of Kanagawa Prefecture, whose SIR was 35 percent higher than that of the remainder of Kanagawa Prefecture. In this cluster, average value of age at first-marriage for women was significantly higher than in the rest of Kanagawa (p=0.017). No statistically significant clusters of breast cancer deaths were detected (p=0.53). CONCLUSIONS: There was a statistically significant cluster of high breast cancer incidence in southeastern area of Kanagawa Prefecture. It was suggested that the cluster region was related to the tendency to marry later. This study methodology will be helpful in the analysis of geographical disparities in cancer deaths and incidence.

Variant cardiovascular regulation in children with postural tachycardia syndrome.

BACKGROUND: Postural tachycardia syndrome (POTS) manifests as marked tachycardia while standing. We noticed two forms of circulatory response to orthostatic stress in POTS. We investigated cardiovascular and autonomic nervous response to orthostatic stress in the two forms. METHODS: We studied 79 patients with POTS and 38 healthy control subjects (Ct). Beat-to-beat blood pressure (BP) and heart rate (HR) were non-invasively and continuously measured in the supine and standing positions. Autonomic nervous function was evaluated on power spectral analysis of HR variability and diastolic BP variability. We divided the subjects into two groups: standing-induced tachycardia (SI group; increase in HR ≥35 beats/min) and supine tachycardia (Su group; standing HR ≥115 beats/min with standing-induced HR increase <35 beats/min). RESULTS: The Su group had higher supine BP and HR compared with the other groups, indicating dominant sympathetic control of the heart in the supine position. While rising, the SI group had a higher increase in HR than the Ct group, indicating excessive withdrawal of vagal tone. The Su group had a smaller increase in HR and a greater decrease of systolic BP and cardiac index by standing compared with the SI group. These results suggest that compensatory mechanisms of sympathetic function during standing failed in the Su group, probably because of exhaustion by the nearly maximum effort to generate sympathetic drive even in the supine position with low central blood volume. CONCLUSION: There is a difference between the two types of POTS, in the balance of resting autonomic function and hemodynamic response to standing.

Amino acid profile index for early detection of endometrial cancer: verification as a novel diagnostic marker.

BACKGROUND: Plasma amino acid profiles (PAAPs) vary in individual cancer patients, and it has been suggested that they may be useful for early detection of several types of cancer. We evaluated the diagnostic performance of a profile index for endometrial cancer composed of multiple plasma amino acids as a novel biomarker and compared its diagnostic performance with that of CA125. METHODS: Plasma amino acid levels of 80 patients with endometrial cancer, 122 with benign gynecological diseases, and 240 age- and body mass index-matched control subjects were measured using liquid chromatography and mass spectrometry. After univariate analysis, we applied a multiplex model based on the PAAP multivariate analysis to distinguish patients with endometrial cancer from control subjects. We compared the diagnostic performance of the multiple PAAP index (API) with that of CA125. RESULTS: The levels of several plasma amino acids were significantly different in patients with endometrial cancer. The area under the receiver operating characteristic curves (AUC) used to distinguish endometrial cancer patients from control subjects was 0.94. The AUC for API was significantly larger than that for CA125 (P = 0.0068). For the same specificity of 98.3 %, API showed a significantly higher sensitivity (60.0 %, 95 % CI, 43.3-75.1) than that of CA125 (22.5 %, 95 % CI, 10.1-38.5). In stage I cases, API showed significantly higher positivity than that of CA125 (P = 0.0002). CONCLUSIONS: The sensitivity and disease specificity of API for early-stage detection of endometrial cancer was superior to CA125. This novel plasma biomarker has the potential to become a diagnostic and screening marker for endometrial cancer.

Body mass index and weight change during adulthood are associated with increased mortality from liver cancer: the JACC Study.

BACKGROUND: We investigated the association of baseline body mass index (BMI) and weight change since age 20 years with liver cancer mortality among Japanese. METHODS: The data were obtained from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). A total of 31 018 Japanese men and 41 455 Japanese women aged 40 to 79 years who had no history of cancer were followed from 1988 through 2009. RESULTS: During a median 19-year follow-up, 527 deaths from liver cancer (338 men, 189 women) were documented. There was no association between baseline BMI and liver cancer mortality among men or men with history of liver disease. Men without history of liver disease had multivariable hazard ratios (HR) of 1.95 (95%CI, 1.07-3.54) for BMI less than 18.5 kg/m(2) and 1.65 (1.05-2.60) for BMI of 25 kg/m(2) or higher, as compared with a BMI of 21.0 to 22.9 kg/m(2). BMI was positively associated with liver cancer mortality among women and women with history of liver disease. Weight change since age 20 years was positively associated with liver cancer mortality among women regardless of history of liver disease. Women with history of liver disease had a multivariable HRs of 1.96 (1.05-3.66) for weight gain of 5.0 to 9.9 kg and 2.31 (1.18-4.49) for weight gain of 10 kg or more, as compared with weight change of -4.9 to 4.9 kg. CONCLUSIONS: Both underweight (BMI <18.5 kg/m(2)) and overweight (BMI ≥25 kg/m(2)) among men without history of liver disease, and weight gain after age 20 (weight change ≥5 kg) among women with history of liver disease, were associated with increased mortality from liver cancer.

Cohort profile of the Japan Collaborative Cohort Study at final follow-up.

The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) was established in the late 1980s to evaluate the risk impact of lifestyle factors and levels of serum components on human health. During the 20-year follow-up period, the results of the study have been published in almost 200 original articles in peer-reviewed English-language journals. However, continued follow-up of the study subjects became difficult because of the retirements of principal researchers, city mergers throughout Japan in the year 2000, and reduced funding. Thus, we decided to terminate the JACC Study follow-up at the end of 2009. As a final point of interest, we reviewed the population registry information of survivors. A total of 207 (0.19%) subjects were ineligible, leaving 110 585 eligible participants (46 395 men and 64 190 women). Moreover, errors in coding date of birth and sex were found in 356 (0.32%) and 59 (0.05%) cases, respectively, during routine follow-up and final review. Although such errors were unexpected, their impact is believed to be negligible because of the small numbers relative to the large total study population. Here, we describe the final cohort profile at the end of the JACC Study along with selected characteristics of the participants and their status at the final follow-up. Although follow-up of the JACC Study participants is finished, we will continue to analyze and publish study results.

GNB3 C825T polymorphism is associated with postural tachycardia syndrome in children.

AIM: Postural tachycardia syndrome (POTS) is one of the most frequent forms of chronic orthostatic intolerance in children and adolescents. The aim of the present study was to examine the influence of a genetic background on POTS. METHODS: A total of 96 children and adolescents with orthostatic dysregulation were studied. The polymorphism of the G protein ß3 subunit (GNB3) C825T and G protein α subunit (GNAS1) T131C of genes encoding components of the autonomic nervous system were determined and compared with circulatory responses to active standing. RESULTS: In the GNB3 gene C825T polymorphism, the CT and TT genotype had a significant lower supine heart rate and a larger increase of heart rate by standing than the CC, associated with evaluated power of the high-frequency component of heart rate variability. According to the criteria of the Japanese clinical guidelines, 48 children were diagnosed as POTS and 30 were as normal responder with somatoform disorder (SD). In GNB3 C825T polymorphism, the TT genotype was more frequently found in the POTS group (45.8%) than in the SD group (20.0%; P = 0.036) [corrected]. In the GNAS1 T393C, the genotype frequencies for the T393C polymorphisms of GNA1 did not differ significantly between the groups. CONCLUSION: The gene polymorphisms GNB3 C825T might be a risk factor for POTS through the enhanced vagal withdrawal of the heart in children and adolescents.

The associations between RAS mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort.

BACKGROUND: Many studies on thyroid follicular tumors have reported the presence of somatic mutations to three forms of RAS: HRAS, KRAS, and NRAS. However, the frequency and clinical significance of these RAS mutations remain unclear, in large part due to the different methodologies being used for mutation analysis and the limited number of cases featured in studies. To clarify the significance of RAS mutations, we examined a large number of follicular adenomas and carcinomas obtained from a single institute using established methods for the analysis of RAS. METHODS: Tumor samples from 40 follicular adenoma and 58 follicular carcinoma patients treated at the Kanagawa Cancer Center Hospital were analyzed. The three RAS mutations at codons 12 and 61 were assessed with a polymerase chain reaction-based loop-hybrid mobility shift assay followed by confirmation with direct sequencing. The relationships between mutation status and clinicopathological features at the time of the initial operation and the prognosis of the patients were also analyzed. RESULTS: Twelve out of 40 (30%) adenomas harbored RAS mutations. In contrast, 33 out of 58 (57%) follicular carcinomas harbored RAS mutations, and the mutation was predominantly found in the NRAS codon 61 (22/33, 67%, p<0.01). The rate of gene mutations was significantly higher in the carcinomas than in the adenomas (p<0.01). The NRAS codon 61 mutation in follicular carcinomas was positively associated with distant metastases through the entire clinical course of the patients (p<0.05), and RAS mutations were associated with poor overall patient survival (p<0.05). CONCLUSIONS: We investigated the frequency of RAS mutations in follicular thyroid tumors from a large number of cases obtained from a single institute. The predominance of NRAS codon 61 mutations as a feature of carcinomas indicates that the diagnosis of adenoma alongside the presence of this mutation should be made cautiously. Our study raises the possibility that follicular adenomas with the RAS mutations have an inherent malignant potential; however, the clinical significance of this finding should be further investigated in more patients and over a longer follow-up period.

Stromal micropapillary component as a novel unfavorable prognostic factor of lung adenocarcinoma.

BACKGROUND: Pulmonary adenocarcinomas with a micropapillary component having small papillary tufts and lacking a central fibrovascular core are thought to result in poor prognosis. However, the component consists of tumor cells often floating within alveolar spaces (aerogenous micropapillary component [AMPC]) rather than invading fibrotic stroma observed in other organs like breast (stromal invasive micropapillary component [SMPC]). We previously observed cases of lung adenocarcinoma with predominant SMPC that was associated with micropapillary growth of tumors in fibrotic stroma observed in other organs. We evaluated the incidence and clinicopathological characteristics of SMPC in lung adenocarcinoma cases. PATIENTS AND METHODS: We investigated the clinicopathological characteristics and prognostic significance of SMPC in lung adenocarcinoma cases by reviewing 559 patients who had undergone surgical resection. We examined the SMPC by performing immunohistochemical analysis with 17 antibodies and by genetic analysis with epidermal growth factor receptor (EGFR) and KRAS mutations. RESULTS: SMPC-positive (SMPC(+)) tumors were observed in 19 cases (3.4%). The presence of SMPC was significantly associated with tumor size, advanced-stage disease, lymph node metastasis, pleural invasion, lymphatic invasion, and vascular invasion. Patients with SMPC(+) tumors had significantly poorer outcomes than those with SMPC-negative tumors. Multivariate analysis revealed that SMPC was a significant independent prognostic factor of lung adenocarcinoma, especially for disease-free survival of pathological stage I patients (p = 0.035). SMPC showed significantly higher expression of E-cadherin and lower expression of CD44 than the corresponding expression levels shown by AMPC and showed lower surfactant apoprotein A and phospho-c-Met expression level than corresponding expression levels shown by tumor cell components without a micropapillary component. Fourteen cases with SMPC(+) tumors (74%) showed EGFR mutations, and none of them showed KRAS mutations. CONCLUSIONS: SMPC(+) tumors are rare, but they may be associated with a poor prognosis and have different phenotypic and genotypic characteristics from those of AMPC(+) tumors.

Plasma free amino acid profiling of five types of cancer patients and its application for early detection.

BACKGROUND: Recently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs) is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection. METHODS AND FINDINGS: Plasma samples were collected from approximately 200 patients from multiple institutes, each diagnosed with one of the following five types of cancer: lung, gastric, colorectal, breast, or prostate cancer. Patients were compared to gender- and age- matched controls also used in this study. The PFAA levels were measured using high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS). Univariate analysis revealed significant differences in the PFAA profiles between the controls and the patients with any of the five types of cancer listed above, even those with asymptomatic early-stage disease. Furthermore, multivariate analysis clearly discriminated the cancer patients from the controls in terms of the area under the receiver-operator characteristics curve (AUC of ROC >0.75 for each cancer), regardless of cancer stage. Because this study was designed as case-control study, further investigations, including model construction and validation using cohorts with larger sample sizes, are necessary to determine the usefulness of PFAA profiling. CONCLUSIONS: These findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis. PFAA profiles can also be used to determine various disease diagnoses from a single blood sample, which involves a relatively simple plasma assay and imposes a lower physical burden on subjects when compared to existing screening methods.

Simple and precise detection of UGT1A1 polymorphisms with a modified loop-hybrid mobility shift assay using Cy5-labeled loop probes.

BACKGROUND: Irinotecan, an inhibitor of topoisomerase I, has been widely used as an important anti-cancer therapeutic drug. Deleterious effects of the drug in hypersensitive patients are known to be associated with genetic polymorphisms of the UGT1A1 gene, namely the polymorphic variants, *28 and *6. METHODS: A modified form of loop-hybrid mobility shift assay using a Cy5-tagged loop-hybrid probe was proposed as a precise and easy method of determining TA repeat polymorphisms at the *28 locus. RESULTS: In this modified method, only loop-hybrid bands were detected by a Cy5-fluorescent signal, despite several irregular electrophoretic bands due to TA repeats in the PCR product. CONCLUSIONS: When a loop-hybrid using a Cy5-tagged probe for the *28 locus and *6 locus were combined and used for mobility shift assay, simultaneous typing of the *28 and *6 variants was achieved in a single lane.

High serum alanine aminotransferase levels for the first three successive years can predict very high incidence of hepatocellular carcinoma in patients with Child Stage A HCV-associated liver cirrhosis.

Abstract Objective. To assess retrospectively whether continuously high serum alanine aminotransferase (ALAT) levels (<80 IU) in the first three successive years after the diagnosis of liver cirrhosis (LC) are predictive of a subsequent high incidence of hepatocellular carcinoma (HCC) in patients with Child Stage A hepatitis C virus (HCV)-LC. Material and methods. The study comprised 132 HCV-LC (Child Stage A) patients who had not received interferon therapy but had been treated with anti-inflammatory agents. At the end of a 3-year follow-up after the diagnosis of LC, the patients were subdivided into three groups according to their serum ALAT levels and the subsequent incidence of HCC was assessed. Results. The cumulative incidence of HCC starting from 3 years after the diagnosis of LC in the continuously high ALAT group (annual average over 3 years always > or =80 IU; n=41; Group A) was markedly higher than that in the continuously low ALAT group (always <80 IU; n=48; Group B) (p<0.005) during an observation period of 7.9+/-3.7 years. The incidence of HCC in Group A was 11.8%/year. The odds ratios of developing HCC in Group A and Group C (mixed high and low ALAT levels; n=43) were 5.1-fold and 1.5-fold that of Group B, respectively. A multivariate analysis revealed that the ALAT group was independently associated with HCC development. Conclusions. Continuously high ALAT levels for three successive years following the diagnosis of LC can be predictive of a very high incidence of HCC in Child A HCV-LC patients. Prospective trials using therapeutic approaches aimed at decreasing ALAT levels are necessary in order to confirm a positive impact of ALAT reduction on the incidence of HCC in patients with HCV-LC.

Analysis of stage IVB endometrial carcinoma patients with distant metastasis: a review of prognoses in 55 patients.

BACKGROUND: Adequate treatment for extremely advanced endometrial cancer is unknown. The purpose of this study was to clarify the prognosis of patients with stage IVB endometrial carcinoma and the validity of treatment. Furthermore, we evaluated whether there was a connection between the prognosis and the site of metastasis. METHODS: The prognoses of 55 patients with stage IVB endometrial carcinoma were studied with reference to the initial treatment method and the metastatic site at the time of the initial treatment. RESULTS: The median survivals of the group of 35 patients who were initially treated with surgery and the group of 10 patients who underwent radiotherapy or chemotherapy as their initial treatment followed by surgery were 11.5 months and 9.5 months, respectively. The residual tumor diameter after surgery was precisely measured in 40 of these 45 patients. The prognosis was significantly better in the patients with a residual tumor diameter of less than 2 cm compared to those with a tumor diameter of 2 cm or greater, and the median survival periods in these two groups were 23.5 months and 11.5 months, respectively (P = 0.027). Furthermore, the prognosis of patients with lung metastasis was significantly better than that of patients with non-lung hematogenous metastasis; the median survival periods of these two groups were 18.5 months and 10.5 months, respectively (P = 0.014). CONCLUSION: For operable patients, surgery as an initial treatment and reduction of the residual tumor size to less than 2 cm appeared to contribute to a better prognosis. In addition, conservative initial treatment and the presence of non-lung hematogenous metastasis were poor prognostic factors.

Reproductive and menstrual factors and thyroid cancer among Japanese women: the Japan Collaborative Cohort Study.

AIM: Thyroid cancer is more frequent in women than in men, suggesting the potential role of reproductive and menstrual factors in this cancer. To investigate the association with these factors, we examined 37,986 women involved in the Japan Collaborative Cohort (JACC) Study from 1988 to 1997. METHODS: Reproductive and menstrual factors were assessed with a self-administered questionnaire at baseline. Hazard ratios (HR) and 95% confidence intervals (95% CI) of thyroid cancer incidence were estimated using Cox proportional hazards regression. RESULTS: Eighty-six new cases of thyroid cancer were recorded during 379,281 person-years of follow-up. Overall incidence rate was 22.7 per 100,000 person-years, with a diagnosed peak of 38.2 per 100,000 at 55-59 years old. Multivariate HRs of 0.56 (95% CI 0.25-1.24) and 0.52 (95% CI 0.24-1.16) were observed for women who had experienced pregnancy or a live birth, respectively, but without statistical significance. Further, we saw no associations with other factors, such as age at menarche, age at menopause, age at first birth, or hormone use. CONCLUSIONS: There was no significant association between thyroid cancer and reproductive and menstrual factors in the present study. Additional cohort studies should further examine this possible relationship among Japanese women.