Trends in patterns of treatment and survival of colorectal cancer patients using cancer registry data in Japan: 1995-2015.

Recent advances in treating colorectal cancer (CRC) have increased the importance of multidisciplinary treatment. This study aimed to clarify trends in the treatment and survival of CRC using population-based cancer registry data in Japan. We analyzed the survival of CRC cases diagnosed from 1995 through 2015 from a population-based cancer registry of six prefectures. The year of diagnosis was classified into five periods, and the trends in the detailed categorization of treatments and survival were identified. We calculated net survival and excess hazard of death from cancer using data on 256,590 CRC patients. The use of laparoscopic surgery has been increasing since 2005 and accounts for the largest proportion of treatment types in the most recent period. Net survival of CRC patients diagnosed after 2005 remained high for laparoscopic surgery and endoscopic surgery (endoscopic mucosal resection or endoscopic submucosal dissection). There was an upward trend in treatment with chemotherapy in addition to open and laparoscopic surgery. Using the excess hazard ratio at the regional stage since 2005, there has been a significant improvement in survival in the younger age group and the rectum cancer group. By type of treatment, there was a tendency toward significant improvement in the open surgery + chemotherapy group. We clarified the trends in treating CRC and the associated trends in survival. Continuous survey based on population-based data helps monitor the impact of developments in treatment.

Subsite-specific trends in mid- and long-term survival for head and neck cancer patients in Japan: A population-based study.

Advances in diagnostic techniques and treatment modalities have impacted head and neck cancer (HNC) prognosis, but their effects on subsite-specific prognosis remain unclear. This study aimed to assess subsite-specific trends in mid- and long-term survival for HNC patients diagnosed from 1993 to 2011 using data from population-based cancer registries in Japan. We estimated the net survival (NS) for HNC by subsite using data from 13 prefectural population-based cancer registries in Japan. Changes in survival over time were assessed by multivariate excess hazard model of mortality. In total, 68,312 HNC patients were included in this analysis. We observed an overall improvement in 5-year NS for HNC patients in Japan. However, survival varied among subsites of HNC, with some, such as naso-, oro- and hypopharyngeal cancers, showing significant improvement in both 5- and 10-year NS, whereas others such as laryngeal cancer showed only a slight improvement in 5-year NS and no significant change in 10-year NS after adjustment for age, sex and stage. In conclusion, the study provides insights into changing HNC survival by site at the population level in Japan. Although advances in diagnostic techniques and treatment modalities have improved survival, these improvements are not shared equally among subsites.

Cancer incidence and type of treatment hospital among children, adolescents, and young adults in Japan, 2016-2018.

Cancer in children, adolescents, and young adults (AYAs) although rare, is the leading disease-specific cause of death in Japan. This study aims to investigate cancer incidence and type of treatment hospital among children and AYAs in Japan. Cancer incidence data (2016-2018) for those aged 0-39 years were obtained from the Japanese population-based National Cancer Registry. Cancer types were classified according to the 2017 update of the International Classification of Childhood Cancer (Third Edition), and AYA Site Recode 2020 Revision. Cases were also categorized into three groups: those treated at core hospitals for pediatric cancer treatment (pediatric cancer hospitals [PCHs]), those treated at designated cancer care hospitals, and those treated at nondesignated hospitals. The age-standardized incidence rate was 166.6 (per million-person years) for children (age 0-14 years) and 579.0 for AYAs (age 15-39 years) (including all cancers and benign or uncertain-behavior central nervous system [CNS] tumors). The type of cancer varied with age: hematological malignancies, blastomas, and CNS tumors were common in children under 10 years, malignant bone tumors and soft tissue sarcomas were relatively common in teenagers, and in young adults over 20 years, carcinomas in thyroid, testis, gastrointestinal, female cervix, and breast were common. The proportion of cases treated at PCHs ranged from 20% to 30% for children, 10% or less for AYAs, and differed according to age group and cancer type. Based on this information, the optimal system of cancer care should be discussed.

Trends in lung cancer incidence by gender, histological type and stage at diagnosis in Japan, 1993 to 2015: A multiple imputation approach.

Continued decrease in smoking prevalence and increasing use of sensitive diagnostic procedures necessitate updated monitoring of trends in lung cancer incidence in Japan. We analyzed histology- and stage-specific trends in 1993 to 2015 using data from 62 870 diagnosed cases from the Monitoring of Cancer Incidence in Japan project. After applying a multiple imputation approach to impute missing/unknown values of stage and histology, we estimated age-standardized incidence rates and applied joinpoint regression analyses. We observed long-term growth trends in adenocarcinoma (ADC) and localized cancer among both genders, long-term declining trends among men and leveling-off trends among women in small-cell carcinoma (SMC) and squamous cell carcinoma (SQC). Stratifying by gender, we observed an increase in localized ADC with average annual percentage changes (AAPC) of 4.5 (95% confidence interval: 3.9 to 5.0) and 5.7 (5.0 to 6.4), a decrease in regional ADC with AAPC of -1.5 (-2.5 to -0.6) and -2.3 (-4.6 to 0.0), but an increase in distant ADC with AAPC of 1.5 (1.1 to 1.9) and 1.6 (0.9 to 2.3) among males and females, respectively. Additionally, increasing trends in female-to-male incidence rate ratios were observed in localized ADC with significantly above one in the most recent diagnosis period. Our results revealed evidence for a partial shift from advanced to early cancer stage, which may suggest the modest effectiveness of nationwide organized screening programs. The observed increasing localized and distant ADC may be linked to improved diagnostic procedures, especially for metastasis detection. Further investigation is needed for more accurate quantification of these factors.

Updated Trends in Cancer in Japan: Incidence in 1985-2015 and Mortality in 1958-2018-A Sign of Decrease in Cancer Incidence.

BACKGROUND: Unlike many North American and European countries, Japan has observed a continuous increase in cancer incidence over the last few decades. We examined the most recent trends in population-based cancer incidence and mortality in Japan. METHODS: National cancer mortality data between 1958 and 2018 were obtained from published vital statistics. Cancer incidence data between 1985 and 2015 were obtained from high-quality population-based cancer registries maintained by three prefectures (Yamagata, Fukui, and Nagasaki). Trends in age-standardized rates (ASR) were examined using Joinpoint regression analysis. RESULTS: For males, all-cancer incidence increased between 1985 and 1996 (annual percent change [APC] +1.1%; 95% confidence interval [CI], 0.7-1.5%), increased again in 2000-2010 (+1.3%; 95% CI, 0.9-1.8%), and then decreased until 2015 (-1.4%; 95% CI, -2.5 to -0.3%). For females, all-cancer incidence increased until 2010 (+0.8%; 95% CI, 0.6-0.9% in 1985-2004 and +2.4%; 95% CI, 1.3-3.4% in 2004-2010), and stabilized thereafter until 2015. The post-2000 increase was mainly attributable to prostate in males and breast in females, which slowed or levelled during the first decade of the 2000s. After a sustained increase, all-cancer mortality for males decreased in 1996-2013 (-1.6%; 95% CI, -1.6 to -1.5%) and accelerated thereafter until 2018 (-2.5%; 95% CI, -2.9 to -2.0%). All-cancer mortality for females decreased intermittently throughout the observation period, with the most recent APC of -1.0% (95% CI, -1.1 to -0.9%) in 2003-2018. The recent decreases in mortality in both sexes, and in incidence in males, were mainly attributable to stomach, liver, and male lung cancers. CONCLUSION: The ASR of all-cancer incidence began decreasing significantly in males and levelled off in females in 2010.

Estimation of lifetime cumulative mortality risk of lung cancer by smoking status in Japan.

The main objective of this study was to estimate the cumulative mortality risk for lung cancer according to smoking status and exposure to secondhand smoke (SHS) in Japan. We applied a life-table method to estimate the cumulative risk. Estimated lifetime cumulative risk for 20-year-old non-smokers, former, and current smokers was 3.2%, 7.6%, and 14.9% for men and 1.9%, 5.6%, and 7.2% for women, respectively. For males, the estimated risk was 3.2% for non-smokers not exposed to SHS and 4.1% for non-smokers exposed to SHS. For females, the estimated risk was 1.9% for non-smokers not exposed to SHS and 2.4% for non-smokers exposed to SHS. Lifetime cumulative mortality risk differed greatly according to smoking status. Moreover, SHS exposure resulted in observable differences in lifetime mortality risk. This study may be useful for the development of tailored prevention programs.

Prognostic impact of tumor location in colon cancer: the Monitoring of Cancer Incidence in Japan (MCIJ) project.

BACKGROUND: Colorectal cancer (CRC) is globally one of the most common cancers. Although studies have found a significant prognostic impact of cancer location for right-sided colon cancers compared with those of the left-side, evidence is lacking in a Japanese population. Therefore, we investigated 5-year net survival in colon cancer by tumor site in a Japanese population. METHODS: Diagnoses obtained between 2006 and 2008 in 21 population-based cancer registries from the Monitoring of Cancer Incidence in Japan (MCIJ) project were used. Colon cancer patients were categorized as having right-sided (C18.0-18.4) or left-sided colon cancer (C18.5-C18.7). We calculated the 5-year net survival for subjects diagnosed from 2006 until 2008 by anatomical subsite according to sex, age groups, tumor stage at diagnosis. We applied the excess mortality model to calculate excess hazard ratios (EHRs) and 95% confidential intervals (CIs) with and without adjustment for age, sex and cancer stages to evaluate the effect of location of colon cancer. RESULTS: This study analyzed a total of 62,350 colon cancer subjects. Five-year net survivals for subjects with left- and right-sided colon cancer were 74.0% (95% CI, 73.4-74.7%) and 70.4% (95% CI, 69.7-71.0%), respectively. Compared with left-sided colon cancers, the EHR for right-sided colon cancers was 1.20 (95% CI, 1.16-1.25) after adjustment for age, sex and stage. CONCLUSION: Our study found that the net survival for right-sided colon cancer was significantly lower than that for left-sided colon cancer. The anatomical site of cancer in the colon might be an important stratification factor in future studies of colon cancer.

Development of a Novel Platform of Proteome Profiling Based on an Easy-to-Handle and Informative 2D-DIGE System.

Proteome profiling based on two-dimensional (2D)-DIGE might be a useful tool for investigating drug-like compounds and the mode of action of drugs. However, obtaining data for profiling requires high labor costs, and it is difficult to control the reproducibility of spot positions because 2D-DIGE usually requires large-size glass plates and spot alignments are greatly affected by the quality of DryStrips and polyacrylamide gels (PAGs). Therefore, we have developed a novel platform by employing small size DryStrips and PAGs, and an image analysis strategy based on dual correction of spot alignment and volume. Our system can automatically detect a large number of consistent spots through all images. Cytosol fractions of HeLa cells treated with dimethyl sulfoxide (DMSO) or bortezomib were analyzed, 1697 consistent spots were detected, and 775 of them were significantly changed with the treatment. Deviations between different days and lot sets of DryStrips and PAGs were investigated by calculating the correlation coefficients. The mean values of the correlation between days and lot sets were 0.96 and 0.94, respectively. Clustering analysis of all the treatment data clearly separated the DMSO or bortezomib treated groups beyond day deviations. Thus, we have succeeded in developing an easy-to-handle 2D-DIGE system that can be a novel proteome profiling platform.

Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.

Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.

Estimation of lifetime cumulative incidence and mortality risk of gastric cancer.

OBJECTIVE: To estimate cumulative incidence and mortality risk for gastric cancer by risk category. METHODS: Risk was classified into four types according to the presence/absence of Helicobacter pylori infection and chronic atrophic gastritis: in order of lowest to highest risk, Group A: H. pylori(-) and atrophic gastritis(-); Group B: H. pylori(+) and atrophic gastritis(-); Group C:H. pylori(+) and atrophic gastritis(+); and, Group D: H. pylori(-) and atrophic gastritis(+). We used vital statistics for the crude all-cause and crude gastric cancer mortality rates in 2011 and data from population-based cancer registries (the Monitoring of Cancer Incidence in Japan) for gastric cancer incidence in 2011. For relative risk and prevalence, we used the results of a meta-analysis integrating previous studies and data from the Japan Public Health Center-based Prospective Study for the Next Generation, respectively (baseline survey 2011-16). We calculated the crude incidence and mortality rates and estimated the cumulative risk using a life-table method. RESULTS: The estimated lifetime cumulative incidence risk was 11.4% for men and 5.7% for women. The estimated risk for Groups A, B, C and D was 2.4%, 10.8%, 26.7% and 35.5% for men, and 1.2%, 5.5%, 13.5% and 18.0% for women, respectively. Similarly, the estimated lifetime cumulative mortality risk was 3.9% for men and 1.8% for women. The estimated risk of mortality for Groups A, B, C and D was 0.8%, 3.6%, 9.0% and 12.0% for men, and 0.4%, 1.7%, 4.2% and 5.7% for women, respectively. CONCLUSIONS: Our results may be useful for designing individually tailored prevention programs.

Childhood, adolescent and young adult cancer incidence in Japan in 2009-2011.

Little is known about cancer incidence among children and youths in Japan. We aimed to describe cancer incidence in Japan focusing on childhood, adolescence and young adulthood (AYA). Cancer incidence data were obtained from the Monitoring of Cancer Incidence in Japan project. For the 2009-2011 incidence, the data were collected from 40 prefectures, of which data from 27 prefectures meeting quality standards were analyzed (population coverage: 38.6%). Cancers diagnosed in 0-39 years of age were classified according to the International Classification of Childhood Cancer (version 3). Crude incidence rates of cancer (including benign or behavior-unknown brain tumors) were 122.7, 142.2, 310.7, and 910.6 for the 0-14, 15-19, 20-29, and 30-39 age groups, respectively (per million population). Using the sex- and age-specific incidence rates, the national estimates of cancer incidence were 2055 for 0-14 years (1118 males and 937 females), 864 for 15-19 years (450 males and 414 females), 4246 for 20-29 years (1699 males and 2547 females), and 16 295 for 30-39 years of age (5101 males and 11 194 females). The five leading cancers were leukemia, cancer of the central nervous system (CNS), lymphoma, malignant germ cell and other gonadal tumors, and neuroblastoma in childhood cases (0-14 years old); leukemia, malignant germ cell and other gonadal tumors, lymphoma, CNS, and malignant bone tumors in adolescence (15-19 years old). The leading cancer in 20-29 years of age was malignant germ cell other gonadal tumors (mainly testis and ovary), whereas female breast cancer was most frequent in 30-39 years of age. These results provide an overall picture of childhood and AYA cancer in Japan.

Secondhand smoke exposure and risk of lung cancer in Japan: a systematic review and meta-analysis of epidemiologic studies.

OBJECTIVE: Systematic evaluation of the association between secondhand smoke exposure and lung cancer in Japan has yet to be conducted. Here, we performed a systematic review and meta-analysis of the relationship between secondhand smoke and lung cancer in Japanese non-smokers. METHODS: Relevant studies were collected from the MEDLINE and Ichushi Web databases using a combination of search terms and Medical Subject Headings. Eligible studies were identified, and relative risks or odds ratios were extracted to calculate pooled risk estimates. This procedure was performed independently by at least two authors. Stratified analyses were carried out according to study design, publication year, and whether or not potential confounding variables were accounted for. The presence of publication bias was assessed via funnel plots. RESULTS: We identified four cohort studies and five case-control studies. Quantitative synthesis was conducted only for secondhand smoke exposure in the home during adulthood. Of the 12 populations included in meta-analysis, positive secondhand smoke exposure-lung cancer associations were observed in 11, whereas an inverse association was found in the remaining 1. The pooled relative risk of lung cancer associated with secondhand smoke exposure was 1.28 (95% confidence interval: 1.10-1.48). We found no evidence of publication bias, and a significant association remained even when potentially missing studies were included (pooled relative risk: 1.26; 95% confidence interval: 1.09-1.46). The results were stable across different subgroup analyses, including by study design, publication year, and when adjusting for confounding variables. CONCLUSIONS: Secondhand smoke exposure in the home during adulthood results in a statistically significant increase in the risk of lung cancer.