A case of multiple hepatocellular carcinoma experiencing complete responses to sorafenib and atezolizumab-bevacizumab and developing severe, refractory venous congestive cutaneous ulcers on either regimen.

A man in his eighties presented with a history of bilateral leg congestive phlebitis, and multiple hepatocellular carcinoma (HCC) treated with sorafenib. When the dose was increased to 400 mg, ulcers appeared under both knees, which worsened, and the drug was discontinued 2 months after administration. However, the ulcers to 30 mm in diameter, requiring debridement and antibiotics. The HCC showed a complete response (CR) based on modified-RECIST criteria; however, after several rounds of locoregional therapy for recurrence, multiple HCCs and metastatic lesions in the Morrison's fossa were detected. Therefore, atezolizumab 1200 mg-bevacizumab 900 mg was started. After the first course, the patient complained of pain below both knees, and when the second course was administered, leg ulcers re-appeared and rapidly worsened. The ulcers were circular and multiple and progressed to deep digging, leading to tendon exposure. Bevacizumab-induced congestive venous ulcer was diagnosed, requiring skin grafts to heal. HCC then showed a CR based on m-RECIST criteria. Initially, the cause of the ulcer was thought to be immune-related adverse effects due to atezolizumab, but experience with sorafenib led us to conclude that the cause was stagnant venous ulcers due to vascular endothelial growth factor receptor inhibitor, which inhibited angiogenesis.

Volume-Outcome Relationship in Cancer Survival Rates: Analysis of a Regional Population-Based Cancer Registry in Japan.

BACKGROUND: There is limited data on the relationship between hospital volumes and outcomes with respect to cancer survival in Japan. The primary objective of this study was to evaluate the effect of hospital volume on cancer survival rate using a population-based cohort database. METHODS: Using the Kanagawa cancer registry, propensity score matching was employed to create a dataset for each cancer type by selecting 1:1 matches for cases from high- and other-volume hospitals. The 5-year survival rate was estimated and the hazard ratio (HR) for hospital volume was calculated using a Cox proportional hazard model. Additional analyses were performed limited to cancer patients who underwent surgical operation, chemotherapy, and other treatments in each tumor stage and at the time of diagnosis. RESULTS: The number of cases with complete data, defined as common cancers (prostate, kidney, bladder, esophagus, stomach, liver, pancreas, colon, breast, and lung), was 181,039. Adjusted HR differed significantly among hospital volume categories for the most common cancers except bladder, and the trends varied according to cancer type. The HR ranged from 0.76 (95%CI, 0.74-0.79) for stomach cancer to 0.85 (0.81-0.90) for colon cancer. CONCLUSIONS: This study revealed that a relationship may exist between hospital volume and cancer survival in Japan.

Contribution of chemotherapy to improved prognosis in stage 4 gastric cancer: trend analysis of a regional population-based cancer registry in Japan.

OBJECTIVES: Little is known about time trends in the prognosis of gastric cancer (GC), since the introduction of new chemotherapeutic agents. This study aimed to analyze how the increased number of available chemotherapeutic options affected the prognosis of GC and which patient types benefited within in a large population. METHODS: From a population-based cancer registry in Japan, 35,751 cases of GC were identified. Of these, 8214 cases were stage 4. The time trend for 3-year survival in stage 4 GC according to patient characteristics (age and tumor location) was estimated in relation to the introduction of new anticancer drugs. Multiple imputation was performed for sensitivity analysis to strengthen the missing data. In addition, we estimated the 5-year survival rate for distal-GC (DGC) and proximal-GC (PGC), and the hazard ratio (HR) was estimated by Cox proportional hazard model. RESULTS: Improvement of overall survival was accelerated in stage 4 cases over time. The prognosis was improved from 11.4% to 13.2%, subsequent to the approval of several oncologic drugs since 2009. Younger patients were more likely to have improved survival rates in response to the increase in chemotherapy options (< 60-year-old, 5.4%: 60-70, 2.2%; 70-80, 0.3%) from 2007 to 2015. The HR for DGC vs. PGC was 1.11 (95% CI 1.08-1.15), and PGC showed a higher rate of improved outcomes (2.4% vs. 0.6%). CONCLUSIONS: This analysis showed that improvement in the GC survival rate was accelerated by the introduction of new chemotherapeutic strategies and it was most evident among younger patients and in patients with PGC.

Manufacturing Industry Cancer Risk in Japan: A Multicenter Hospital-Based Case Control Study.

BACKGROUND: It is well known that specific occupations can cause harm in developing malignant neoplasms. Chemical exposure is particularly high in the manufacturing industry and workers in this sector may face a higher occupational risk for cancer. We aimed to estimate inequalities in the risk of cancers related to occupational chemical exposure in various manufacturing categories. METHODS: Using nationwide clinical inpatient data (1984-2017) in Japan, we undertook a multicenter, case-control study with regard to risks of developing cancers among various manufacturing industry categories. Using the food manufacturing industry as the reference group, odds ratios and 95% confidence intervals for each industry were estimated by conditional logistic regression, adjusted for sex, age, admission period, and the admitting hospital. Medical record summaries accounting for 89% of industrial categories with high odds ratios were collected to confirm diagnoses made on the basis of histology. We estimated industrial hazards based on the Pollutant Release and Transfer Register. RESULTS: A reduced risk for some of common cancers was observed among lumber and wood products industries. Leather tanning, leather products and fur tended to show a higher risk: 2.36 (95% CI 1.15-4.83) for pancreatic cancer, 2.85 (95% CI 1.26-6.47) for liver cancer and 2.00 (95% CI 1.01-3.99) for lung cancer. For the electronics category, observations of high risk ranged from 2.09 (95%CI 1.18-3.70) for ureter cancer, to 2.49 (95% CI 1.79-3.55) for kidney cancer. CONCLUSIONS: This study revealed industry risk inequalities in manufacturing categories were present with regard to the risk of common cancers in Japan.

A case of primary hepatic mixed neuroendocrine-non-neuroendocrine tumor (MiNEN) associated with gallbladder carcinosarcoma.

A woman in her seventies visited our hospital because of abdominal pain. Multiple hepatic tumors were detected and a liver biopsy revealed mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), which was composed of cholangiocellular carcinoma and neuroendocrine tumor (NET). Diagnostic imaging ruled out primary malignancies other than the liver and identified that the tumor originated from the liver. Because a predominant and aggressive part of the tumor was considered to be cholangiocellular carcinoma, gemcitabine and S-1 were used as first-line treatment. After the treatment, octreotide acetate was administered for the NET component, followed by transcatheter arterial embolization. Subsequently, her gallbladder (GB) rapidly swelled with biliary tract obstruction, and cholecystectomy revealed carcinosarcoma of the GB. She is still undergoing treatment at 44 months after diagnosis. Herein we report this case of primary hepatic MiNEN consisting of cholangiocarcinoma and NET, followed by GB carcinosarcoma. This is the first case illustrating that a multidisciplinary treatment approach for MiNEN accompanied with carcinosarcoma, involving assessment and treatment targeting the most aggressive component, can result in a long survival time.

The Prognosis of Hepatocellular Carcinoma Treated with Sorafenib in Combination with TACE.

OBJECTIVE: Sorafenib have been shown to be effective in the treatment of advanced HCC and has been standard therapy since its release in Japan in 2009 (Llovet et al., 2008; Cheng et al., 2009). However, due to a low response rate, more aggressive combination treatment has been utilized as a multimodal strategy. The present study aimed to determine the efficacy of sorafenib alone and in combination with transarterial chemoembolization (TACE) for the treatment of advanced HCC. METHODS: All patients with unresectable advanced HCC who were prescribed sorafenib at Kanto Rosai Hospital were included in the study. Five-year overall survival (OS) rates were estimated for patients treated with sorafenib alone or in combination with TACE. Multivariate and univariate regression analyses were performed to identify factors affecting OS. Analysis using propensity score matching and inverse-probability weights were also performed. RESULTS: A total of 46 patients were treated with sorafenib up to June 2018. The total sorafenib dose administered was higher in the TACE combination group (70900 mg vs. 24000 mg vs. with sorafenib alone), although the relative dose intensity was lower (11.7% vs. 17.6%, respectively). The 5-year survival prognosis estimated using the Kaplan-Meier method was longer in patients treated with sorafenib in combination with TACE versus sorafenib alone (36.3% vs. 7.7%). Combination with TACE was the only factor associated with improved OS in both univariate and multivariate analysis. Among cases matched by propensity scores the hazard rate for combination with TACE was 0.067 (95% CI 0.091-1.128). CONCLUSION: With an array of therapeutic options currently available, it is important to determine the efficacy of different multimodal strategies, such as sorafenib combined TACE, for patients with unresectable HCC.

Risk of cancer and longest-held occupations in Japanese workers: A multicenter hospital-based case-control study.

OBJECTIVES: Little is known about the risk of developing various cancers according to occupation and occupational physical activity. METHODS: Using nationwide clinical inpatient data (1984-2017) in Japan, we undertook a multicentered, matched case-control study with regard to the risk of developing various cancers according to occupation and using patients admitted with fractures as controls. Using standardized national occupation and industrial classifications, we first identified the longest-held job for each patient. Using sales workers as the reference group, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by conditional logistic regression, adjusted for age, admission period, and the admitting hospital, with smoking, alcohol consumption, and lifestyle diseases as covariates. The risk of high and low occupational physical activity was also estimated. RESULTS: Across all occupations, a reduced risk for all common cancers among males was observed among those occupations associated with high physical activities, such as agriculture. People in these occupations tended to show a lower risk for most cancers, including, for example, prostate cancer (OR 0.58, 95% CI 0.45-0.75) and lung cancer (OR 0.63, 95% CI 0.51-0.76). For females, the breast cancer risk was low in women engaged in agriculture (OR 0.58, 95% CI 0.45-0.75) and in those occupations with high levels of occupational physical activity (OR 0.58, 95% CI 0.52-0.66). CONCLUSIONS: This study revealed differences in cancer risk among diverse occupations in Japan. Specifically, those occupations associated with high levels of physical activity may be associated with a decreased risk of cancer.

Occupational class and male cancer incidence: Nationwide, multicenter, hospital-based case-control study in Japan.

Little is known about socioeconomic inequalities in male cancer incidence in nonwestern settings. Using the nationwide clinical and occupational inpatient data (1984-2016) in Japan, we performed a multicentered, matched case-control study with 214 123 male cancer cases and 1 026 247 inpatient controls. Based on the standardized national classifications, we grouped patients' longest-held occupational class (blue-collar, service, professional, manager), cross-classified by industrial cluster (blue-collar, service, white-collar). Using blue-collar workers in blue-collar industries as the referent group, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by conditional logistic regression with multiple imputation, matched for age, admission date, and admitting hospital. Smoking and alcohol consumption were additionally adjusted. Across all industries, a reduced risk with higher occupational class (professionals and managers) was observed for stomach and lung cancer. Even after controlling for smoking and alcohol consumption, the reduced odds persisted: OR of managers in white-collar industries was 0.80 (95% CI 0.72-0.90) for stomach cancer, and OR of managers in white-collar industries was 0.66 (95% CI 0.55-0.79) for lung cancer. In white-collar industries, higher occupational class men tended to have lower a reduced risk for most common types of cancer, with the exception of professionals who showed an excess risk for prostate cancer. We documented socioeconomic inequalities in male cancer incidence in Japan, which could not be explained by smoking and alcohol consumption.

Occupational inequalities in female cancer incidence in Japan: Hospital-based matched case-control study with occupational class.

BACKGROUND: Socioeconomic inequalities in female cancer incidence have previously been undocumented in Japan. METHODS: Using a nationwide inpatient dataset (1984-2016) in Japan, we identified 143,806 female cancer cases and 703,157 controls matched for sex, age, admission date, and admitting hospital, and performed a hospital-based matched case-control study. Based on standardized national classification, we categorized patients' socioeconomic status (SES) by occupational class (blue-collar, service, professional, manager), cross-classified by industry sector (blue-collar, service, white-collar). Using blue-collar workers in blue-collar industries as the reference group, we estimated the odds ratio (OR) for each cancer incidence using conditional logistic regression with multiple imputation, adjusted for major modifiable risk factors (smoking, alcohol consumption). RESULTS: We identified lower risks among higher-SES women for common and overall cancers: e.g., ORs for managers in blue-collar industries were 0.67 (95% confidence interval [CI], 0.46-0.98) for stomach cancer and 0.40 (95% CI, 0.19-0.86) for lung cancer. Higher risks with higher SES were evident for breast cancer: the OR for professionals in service industries was 1.60 (95% CI, 1.29-1.98). With some cancers, homemakers showed a similar trend to subjects with higher SES; however, the magnitude of the OR was weaker than those with higher SES. CONCLUSIONS: Even after controlling for major modifiable risk factors, socioeconomic inequalities were evident for female cancer incidence in Japan.

Cholangiocarcinoma Prognosis Varies over Time Depending on Tumor Site and Pathology.

BACKGROUND: Cholangiocarcinoma is a relatively rare cancer that is difficult to diagnose and has a poor prognosis. Currently, knowledge concerning its etiology, tumor localization, and pathological features remains limited. The present study aimed to clarify the clinico-epidemiologic nature of cholangiocarcinoma with its clinical subtypes using the largest regional cancer registry in Japan. METHODS: Using a regional cancer registry in Kanagawa prefecture, Japan, we estimated three-year and five-year survival rates of cholangiocarcinoma patients, who were classified into two groups: intrahepatic (i-CCA) and extrahepatic cholangiocarcinoma (e-CCA) cases. The hazard ratio for each subtype, including pathological tissue type and tumor site, was calculated. RESULTS: During the period from 1976 to 2013, 14,287 cases of cholangiocarcinoma were identified. The prognosis markedly improved after 2006, when a new type of chemotherapy for cholangiocarcinoma was introduced in Japan. Patients with i-CCA were more likely to be younger, and less likely to undergo surgery than those with e-CCA. The prognosis of cases with i-CCA was poor compared to that of patients with e-CCA. CONCLUSION: In Japan, i-CCA was more likely to develop in younger people and to have a poor prognosis. The prognosis of both i-CCA and e-CCA cases markedly improved after 2006. The present study describes clinico-epidemiological features of cholangiocarcinoma that may be useful for determining therapeutic strategies for this disease.

Efficacy of ledipasvir/sofosbuvir with or without ribavirin for 12 weeks in genotype 1b HCV patients previously treated with a nonstructural protein 5A inhibitor-containing regimen.

AIM: The therapeutic benefit of adding ribavirin (RBV) to 12 weeks of ledipasvir/sofosbuvir (LDV/SOF) for patients who experienced failure of a previous nonstructural protein (NS) 5A inhibitor-containing regimen is unclear. METHODS: A total of 29 genotype 1b HCV patients who had failed prior daclatasvir (DCV) plus asunaprevir (ASV) treatment were retreated for 12 weeks of LDV/SOF, with or without RBV. Antiviral efficacy and predictive factors associating with a sustained virological response at 24 weeks (SVR24) were evaluated retrospectively. RESULTS: SVR24 was achieved in 67% (10/15) of patients who received LDV/SOF with, and 64% (9/14) without, RBV. The SVR24 rates were 80% in patients with, and 58% without, mild fibrosis (FIB-4 < 3.25). The SVR24 rate was lower with unfavorable IL28B rs8099917 SNP genotypes; specifically, the TT, TG and GG had SVR24 rates of 78%, 50% and 40%. The SVR24 rate was lower with a poor response to prior DCV plus ASV, where relapse, viral breakthrough and no response had SVR24 rates 71%, 58% and 0%. The SVR24 rate was lower with the number of NS5A resistance-associated substitutions (RAS), where 2, 3, 4 and 5 RAS had SVR24 rates of 78%, 67%, 50% and 0%. A patient with an NS5A-P32 deletion, which shows resistance to next-generation NS5A inhibitors, was retreated with LDV/SOF with RBV and achieved SVR24. CONCLUSIONS: The addition of RBV to 12 weeks of LDV/SOF has little therapeutic benefit when retreating patients in whom a prior NS5A inhibitor-containing regimen had failed.

Efficacy of direct-acting antiviral treatment for chronic hepatitis C: A single hospital experience.

AIM: To evaluate the efficacy of direct-acting antivirals (DAAs) in Kanto Rosai Hospital. METHODS: All patients with hepatitis C virus (HCV) who underwent DAA prescription were enrolled in this study. The present study was a single center retrospective analysis using patients infected with HCV genotype 1 or 2. Resistance analysis was performed by using direct sequencing and cycleave PCR in genotype 1 patients treated with interferon (IFN)-free DAA. The primary endpoint was sustained virologic response at 12 wk after therapy (SVR12). RESULTS: A total of 117 patients participated in the study, including 135 with genotype 1 and 42 with genotype 2. Of the 135 patients with genotype 1, 16 received protease inhibitor + IFN + ribavirin and all achieved SVR. Of the 119 patients who received IFN-free DAA (in different combinations), 102 achieved SVR and 9 failed (7/9 were on daclatasvir/asunaprevir and 2/9 on ledipasvir/sofosbuvir). Efficacy analysis was done only for 43 patients who received daclatasvir/asunaprevir. From this analysis, Y93 resistance-associated substitutions were significantly correlated with SVR. CONCLUSION: The SVR rate was 98% for genotype 1 and 100% for genotype 2. However, caution is needed for HCV NS5A resistance-associated substitutions that are selected by HCV NS5A inhibitors because cerebrovascular adverse events are induced by some DAA drugs.

Primary Hepatic Lymphoma Complicated by a Hepatic Inflammatory Pseudotumor and Tumor-Forming Pancreatitis.

BACKGROUND: Hepatic inflammatory pseudotumor (IPT) is considered to be benign in biological behavior, and its malignant transformation is extremely rare. There has only been one published case of primary hepatic lymphoma complicated by hepatic IPT. CASE PRESENTATION: A 73-year-old man presented with obstructive jaundice and a pancreatic head mass. Histology of the mass revealed chronic pancreatitis with lymphoid follicle formation, leading to a diagnosis of a suspicion of follicular pancreatitis. After a choledochojejunostomy, a hepatic tumor was detected, and a biopsy revealed lymphoplasmacytic infiltration. Immunohistochemistry confirmed the polyclonal nature of lymphoplasma cells, indicative of an IPT. The hepatic tumor disappeared during follow-up, but the patient exhibited a high fever related to tumor recurrence. A biopsy revealed the co-existence of a diffuse large B-cell lymphoma and an IPT. IgG4-related disease was excluded because storiform fibrosis, obliterative phlebitis, and a significant increase in IgG4-immunoreactive cells were absent in all investigated tissues. The tumor completely disappeared after chemotherapy. CONCLUSION: Careful observation is necessary in this kind of situation because the presence of a hepatic IPT may represent an increased risk of malignant transformation.

The Effect of New Therapeutic and Diagnostic Agents on the Prognosis of Hepatocellular Carcinoma in Japan ­ An Analysis of Data from the Kanagawa Cancer Registry

Objective: Notable advances in diagnostic imaging modalities and therapeutic agents have contributed to improvement in the prognosis of hepatocellular carcinoma (HCC) over the past decade. However, knowledge concerning their epidemiological contribution remains limited. The present study investigated the effect of emerging diagnostic and therapeutic agents on HCC prognosis, using the largest regional cancer registry in Japan. Methods: Using data from the Kanagawa Cancer Registry, the five-year survival rate of patients with liver cancer was estimated according to the International Statistical Classification of Diseases and Related Health Problems (10th Edition). Result: A total of 40,276 cases of HCC (from 1976 to 2013) were identified. The prognosis markedly improved after the introduction of new devices into the diagnosis and treatment of HCC (p<0.01). The trend of survival rate varied significantly between institutions with many registered patients (high-volume centers) (p<0.01). Conclusion: The five-year survival rate of patients with HCC in Kanagawa has markedly improved in recent years. This improvement in survival may be attributed to the advances in surveillance and intervention for the treatment of HCC.

Comparison of Clinical Characteristics between Occupational and Sporadic Young-Onset Cholangiocarcinoma.

BACKGROUND: Since seventeen employees of an offset printing company in Osaka, Japan developed cholangiocarcinoma it has become recognized as an occupational cancer. This study investigated the differences of clinical features between occupational cholangiocarcinoma and sporadic young-onset cholangiocarcinoma. MATERIALS AND METHODS: Thirty-four young adults (<50 years old) with sporadic cholangiocarcinoma were extracted from the Rosai Hospital Group database (sporadic group) and their clinical features were compared with those of 17 patients with occupational cholangiocarcinoma (occupational group). RESULTS: The 34 patients in the sporadic group were treated for cholangiocarcinoma at 16 different Rosai hospitals. There were significant differences of age (p<0.01), gender (p<0.01), abnormal laboratory tests (p<0.01), and tumor location (p<0.01) between the two groups. The percentage of patients with abnormal laboratory tests was significantly higher in the occupational group than in the sporadic group (p<0.001). Regional dilation of bile ducts, which is a characteristic of occupational cholangiocarcinoma, was not observed in the sporadic group. CONCLUSIONS: No cluster of cholangiocarcinoma cases was identified in the Rosai Hospital database. There were differences of clinical features between occupational and sporadic cholangiocarcinoma, which might be helpful for diagnosing occupational cholangiocarcinoma in the future.

A new index of abdominal obesity which effectively predicts risk of colon tumor development in female Japanese.

BACKGROUND: A relation between abdominal obesity and colorectal tumor development has been reported repeatedly, and is believed to be more remarkable in man than in women. However, the details vary depending on scientific reports. This may be due at least partly to the selected surface anthropometric index in addition to the influence of gender and ethnic groups. To cope with this, we considered a new index of abdominal obesity and evaluated its risk prediction potential. MATERIALS AND METHODS: Six hundred ninety five Japanese (262 women and 433 men) who had a colonoscopy were studied. The new index was named as waist circumference to height index (WHI) and was calculated by the formula of waist circumference (cm)/height (m)/height (m). Biochemical and lifestyle factors were investigated preceding the colonoscopy. Statistical analysis was performed using SPSS for Windows. RESULTS: Increase of WHI was associated with altered metabolism of carbohydrate and lipid in both women and men. WHI was positively related with the development of colon tumor of women, while not with that of men. Logistic regression analysis performed for stratified age groups (45-54, 55-64 and 65-74 years) showed that WHI significantly increased odds ratio to 1.31 (CI 1.05-1.64 p=0.01) in women of 55-65 years. In contrast, in men this index WHI reduced the odds ratio insignificantly, while low density lipoprotein and triglyceride significantly increased the odds ratio to 1.01 (CI 1.00-1.03 p=0.02) in the 55-65 year group and to 1.02 (CI 1.00-1.03 p=0.02) in the 45-55 year group. CONCLUSIONS: In Japanese the risk factors for colon tumor development are different between women and men. WHI is a simple and efficient predictor of colon tumor risk in Japanese women and may be used to select those who should have colonoscopy.

Two cases of food additive-induced severe liver damage associated with positive results on lymphocyte stimulation test and for antinuclear antibodies.

Two cases of severe liver injury and positive result for antinuclear antibodies induced by food additives are reported. The first patient reported long-term intake of Mabo Ramen(®) noodle soup, nutritional supplements, and over-the-counter drugs. Total bilirubin, aspartate aminotransferase, and alanine aminotransferase were 9.6 mg/dL, 1,048, and 1,574 IU/L, respectively. Antinuclear antibody was 80×. The drug-induced lymphocyte stimulation test (DLST) was positive for Mabo Ramen(®) and its additives such as Xanthan gum, guar gum, and Doubanjiang. Histologic examination of a liver biopsy specimen showed lymphocyte infiltration and necrosis. The autoimmune hepatitis score was 3. The second patient reported intake of dietary supplements, including Bimore C(®) and Chokora BB(®). Laboratory tests revealed that total bilirubin was 9.8 mg/dL, aspartate aminotransferase was 1,130 IU/L, and alanine aminotransferase was 1,094 IU/L. Antinuclear antibody was 320×. Co-existing pancreatic damage was confirmed by the findings on abdominal CT and elevation of serum lipase, span-1, and DUPAN-2. DLSTs were positive for both supplements. These two supplements contained additives such as titanium oxide, magnesium stearate, and hydroxypropylcellulose. DLSTs for all three additives were positive. Histologic examination revealed periportal necrosis and lymphocyte infiltration of lobular and portal areas. These two cases demonstrate that repeating DLSTs is useful for identifying causative constituents in foods and supplements.

Clinico-epidemiologic study of the metabolic syndrome and lifestyle factors associated with the risk of colon adenoma and adenocarcinoma.

BACKGROUND: The numbers of patients with colorectal cancer and associated deaths have been increasing in Japan, probably due to rapid lifestyle changes. Prevention is clearly important and the present study aimed to clarify risk factors and to promote colon cancer screening. METHODS: We investigated lifestyle factors, biochemical data, and pathological features of 727 individuals who underwent colonoscopy. Data were subjected to statistical analysis using SPSS software. RESULTS: Low-grade adenoma was more frequent among the elderly and in men. All of the men and 87.5% of the women with high-grade adenoma or adenocarcinoma were aged≥45 and≥50 years, respectively. In women, a larger waist circumference (=80 cm) increased the odds ratio for colon adenoma or adenocarcinoma (colon tumors) by 1.033 (95% confidence index (CI), 1.001-1.066; p=0.040). Metabolic syndrome significantly increased the odds ratio of colon tumors in men, but not in women. Cigarette smoking, drinking alcohol, and increased physical activity were significant risk factors for colon tumors in men, with odds ratios of 1.001 (95% CI, 1.000-1.002; p=0.001), 1.001 (95% CI, 1.000-1.003; p=0.047), and 1.406 (95% CI 1.038-1.904; p=0.028), respectively. CONCLUSIONS: Colon tumors have a high prevalence in the elderly. A larger waist circumference in women and metabolic syndrome in both men and women elevate the risk of colon tumors. In addition, smoking, drinking, and excessive physical activity are risk factors for adenoma and adenocarcinoma in men. For early detection of colorectal cancer, men older than 45 years and women older than 50 years with these risk factors are recommended to undergo colonoscopy.

Ursodeoxycholic acid exacerbates peginterferon-induced interstitial pneumonia in a patient with hepatitis C.

Pegylated interferon alpha combined with ribavirin is currently the standard treatment for hepatitis C virus (HCV) infection. Ursodeoxycholic acid (UDCA) is used as a complementary treatment in patients who are non-responders or who develop severe side effects of this combined therapy. UDCA is generally considered to be a relatively safe drug. However, we recently encountered a patient with chronic hepatitis C in whom interferon-induced interstitial pneumonia was exacerbated by UDCA. This patient responded to initial antiviral therapy with non-pegylated interferon alpha-2b and ribavirin, but hepatitis recurred soon after the end of treatment. A second course of antiviral therapy using peginterferon alpha-2b and ribavirin achieved normalization of serum transaminases and HCV-RNA, but also caused interstitial pneumonia. After discontinuing peginterferon, this side effect was ameliorated. On the other hand, hepatitis relapsed four months later. UDCA treatment was started and serum transaminase levels decreased, but exacerbation of interstitial pneumonia occurred with marked elevation of the serum KL-6 level. To our knowledge, this is the first reported case of peginterferon-induced interstitial pneumonia showing exacerbation due to UDCA therapy.