The consecutive impact of COVID-19 on thoracic surgical procedures in Japan: an analysis of data from the National Clinical Database.

PURPOSE: The current study was designed to analyze the impact of the COVID-19 pandemic on general thoracic surgeries in Japan. METHODS: Changes in surgeries for lung cancer and metastatic lung tumors were evaluated based on National Clinical Database data regarding cancer screening. RESULTS: In 2021, surgeries for primary lung cancer increased by 3.4% compared to 2020, which, given the increase from 2014 to 2019, indicates an overall 11.1% decrease. In contrast, surgeries for metastatic lung tumors in 2021 decreased by 5.8% compared to 2020, which, given the increase from 2014 to 2020, indicates an overall 9.2% decrease. Half of the primary diseases for metastatic lung tumor were cases of colorectal cancer. Low anterior resection procedures in 2020 decreased by 5.5% compared to 2019. Lung and colon cancer screening examinees in 2021 were increased compared to 2020; however, they still showed respective decreases of 11% and 9.0% compared to 2019. CONCLUSIONS: Surgeries for primary lung cancer still decreased substantially during the COVID-19 pandemic. The continued stagnation of screening was responsible for this decrease. Surgeries for metastatic lung tumors decreased profoundly, and the decrease in screening for primary tumors was responsible for this reduction. Our findings emphasize the significance of maintaining cancer screening efforts, even during a pandemic.

Impact of coronavirus disease 2019 on the number of newly diagnosed cancer patients and examinations and surgeries performed for cancer in Japan: a nationwide study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has rapidly and dramatically influenced healthcare across Japan. However, the influence of the COVID-19 pandemic on the number of newly diagnosed cancer, surgical treatment, and diagnostic examination for cancer types have not been completely investigated all over Japan. This study aimed to analyze the number of cases before and during the COVID-19 pandemic. METHODS: This retrospective study was a survey that asked to provide the number of cases diagnosed with gastric, colorectal, lung, breast, and cervical cancer between January 2019 and December 2020. The survey was sent to tertiary healthcare hospitals, including national cancer institutions, university hospitals, and general hospitals, all over Japan. Data obtained from 105 of 486 surveyed hospitals were evaluated, and the number of cases in each quarter in 2020 was compared with that in the equivalent quarter in 2019. RESULTS: In the second quarter (Q2), significant reductions were observed in the median number of newly diagnosed cases from 2019 to 2020: gastric cancer, 26.7% (43 vs. 32, p <  0.001); colorectal cancer, 17.9% (52 vs. 40, p <  0.001); lung cancer, 12.3% (53.5 vs. 47, p <  0.001); and breast cancer, 13.1% (43 vs. 35.5, p <  0.001). A significant reduction of 11.4% (9 vs. 8, p = 0.03) was observed in the third quarter (Q3) for cervical cancer. In Q2, the number of cases decreased by 30.9% (25 vs. 15, p <  0.001) for stage I gastric cancer, by 27.3% (12 vs. 9, p <  0.001) for stage I colorectal cancer, and by 17.6% (13 vs. 10, p <  0.001) for stage II breast cancer. The magnitude of reduction was significant for the localized stages of gastric, colorectal, and breast cancer according to diagnostic examinations in Q2 and surgical and endoscopic treatment in Q3 rather than that for lung or cervical cancer. CONCLUSIONS: COVID-19 has prolonged collateral effects on cancer care, including examination, diagnosis, and surgery, with significant effects on gastric cancer, followed by colorectal, lung, breast, and cervical cancer in Japan.

Human papillomavirus vaccine to prevent cervical intraepithelial neoplasia in Japan: A nationwide case-control study.

Cervical cancer remains among the most common cancers in women worldwide and can be prevented by vaccination. The Ministry of Health, Labour and Welfare of Japan suspended active recommendation of regular human papillomavirus (HPV) vaccines in 2013 because of various symptoms including chronic pain and motor impairment. This nationwide case-control study from April 2013 to March 2017 targeted women aged 20-24 years old at cervical screening. We compared HPV vaccination exposure between those with abnormal and normal cytology. Abnormal cytology was classified based on the results of histological test and we calculated the odds ratio (OR) and 95% confidence interval (CI) of the above endpoints and vaccination exposure using the conditional logistic regression model and estimated vaccine effectiveness using the formula (1 - OR) × 100. A total of 2483 cases and 12 296 controls (one-to-five matching) were eligible in 31 municipalities in Japan. The distribution of histological abnormalities among cases was 797 CIN1 (including dysplasia) (32.1%), 165 CIN2 (6.7%), 44 CIN3 (1.8%), and eight squamous cell carcinoma (SCC) (0.3%). The OR of HPV vaccination compared with no vaccination for abnormal cytology, CIN1+, CIN2+, and CIN3+ versus controls was 0.42 (95% CI, 0.34-0.50), 0.42 (95% CI, 0.31-0.58), 0.25 (95% CI, 0.12-0.54), and 0.19 (95% CI, 0.03-1.15), respectively, equating to a vaccine effectiveness of 58.5%, 57.9%, 74.8%, and 80.9%, respectively. Eight patients had SCC, none was vaccinated. This nationwide case-control study in Japan demonstrated a substantial risk reduction in abnormal cytology and CIN among women who did versus those who did not receive HPV vaccination.

Oncological outcomes for patients with locally advanced prostate cancer treated with neoadjuvant endocrine and external-beam radiation therapy followed by adjuvant continuous/intermittent endocrine therapy in an open-label, randomized, phase 3 trial.

BACKGROUND: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT). METHODS: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death. RESULTS: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722). CONCLUSIONS: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.

Effectiveness of HPV vaccination against the development of high-grade cervical lesions in young Japanese women.

BACKGROUND: Although more than 10 years have passed since HPV vaccination was implemented, first as an interim programme (Emergent vaccine promotion programme) in November 2010, followed by incorporating into the National Immunization Programme in April, 2013 and suspended in June 2013, limited studies have investigated the HPV vaccine effectiveness against high-grade cervical lesions in Japan. METHODS: We collected the matched data of the results of cervical biopsy and history of vaccination from the Japan Cancer Society database. The subjects were women aged 20 to 29 years screened for cervical cancer between April, 2015 and March, 2017, and with information on HPV vaccination status. We estimated the relative risk of developing high-grade cervical lesions in vaccinated subjects using Poisson regression as compared to unvaccinated subjects. RESULTS: Among the 34,281 women screened, 3770 (11.0%) were vaccinated. The prevalence of CIN2+ was statistically significantly lower in the vaccinated women as compared to the unvaccinated women (Vaccine Effectiveness (VE) =76%; RR = 0.24, 95% CI:0.10-0.60). High VE against CIN3+ was also observed (91%; RR = 0.09, 95% CI:0.00-0.42). CONCLUSION: Women aged 20-29 years who received at least one dose of HPV vaccine had a significantly lower risk of high-grade cervical lesions than those not vaccinated. In Japan, HPV vaccination should be resumed in order to reduce the incidence of cervical cancer.

Impact of reduced smoking rates on lung cancer screening programs in Japan.

BACKGROUND: In Japan, lung cancer screening by annual chest radiography has been performed for the past 30 years. However, changes in risk factor status may have influenced the efficiency of current organized lung cancer screening program. The purpose of this study was to clarify whether the reduced smoking rate in younger Japanese affects the efficiency and effectiveness of lung cancer screening. METHODS: We investigated chronological changes in epidemiological indicators, which support lung cancer screening programs offered by the Japan Cancer Society, such as gender- and age-specific numbers of participants and lung cancers detected by the screening by clinical stage, in relation to smoking rates from 1991 to 2016. RESULTS: Participant age at the time of screening and age at the time of cancer detection have both increased over time. The lung cancer detection rate (LCDR) in younger age cohorts tended to decrease from 1991 to 2016 in both genders, particularly men aged <55 years. Age-adjusted LCDR significantly decreased from 1991 to 2016 in both genders. After 2001, ~45% of overall detected cases in men and 70% in women were found in stage I. Although trends differed between men and women, smoking rate decreased from 1991 to 2016 in most age cohorts in both genders. CONCLUSIONS: These results suggest that organized lung cancer screening in Japan should be limited to higher-risk populations.

A comparison of liquid-based and conventional cytology using data for cervical cancer screening from the Japan Cancer Society.

OBJECTIVE: Liquid-based cytology has replaced conventional cytology in cervical cancer screening in many countries. However, a detailed comparison of liquid-based cytology with conventional cytology has not been reported in Japan. Therefore, the aim of the study is to evaluate efficacy of liquid-based cytology in Japan. METHODS: We first evaluated the prevalence of use of liquid-based cytology and then examined the efficacy of liquid-based cytology and conventional cytology for detecting CIN and the rate of unsatisfactory specimens using data from cancer screening collected by the Japanese Cancer Society from FY2011 to FY2014. A Poisson regression model with random effects analyses was used to classify histological outcomes and unsatisfactory specimens using liquid-based cytology compared to conventional cytology. RESULTS: A total of 3 815 131 women were analyzed in the study. The rate of liquid-based cytology increased from approximately 8% in FY2011 to 37% in FY2014. Compared to conventional cytology, the detection rates with liquid-based cytology were significantly higher (1.42 times) for CIN1+ [detection rate ratio (DRR) = 1.42, 95% confidence interval (CI) 1.35-1.48, P < 0.001] and CIN2+ (DRR = 1.16, 95% CI 1.08-1.25, P < 0.001). Positive predictive value ratios of CIN1+ and CIN2+ were also significantly higher for liquid-based cytology than for conventional cytology. However, there was no significant difference between liquid-based cytology and conventional cytology for detection rates and positive predictive values of CIN3+ and cancer. The rate of unsatisfactory specimens was significantly lower with liquid-based cytology compared to conventional cytology (DRR = 0.07, 95% CI 0.05-0.09, P < 0.001). CONCLUSIONS: In order to avoid the unsatisfactory specimens in cervical cancer screening, the results of this study did indicate that liquid-based cytology was more useful than conventional cytology in practical standpoints.

Orthotopic neobladder after cystectomy for bladder cancer.

More than 90% of bladder cancer is composed of transitional cell carcinoma (TCC), being characterized by the development of multiple tumors in the entire urinary tract over time. When cystectomy is conducted, the urinary tract must be reconstructed by various procedures, which can include an orthotopic neobladder using the patient's own intestine formed into a spherical shape anastomosed to the urethra. Using this procedure, patients can void urine from their own urethra even after cystectomy. The incidence of subsequent urethral cancer arising after cystectomy is known to be relatively high; however, if patients with a high risk of urethral recurrence are appropriately excluded, a neobladder can be safely provided for patients. Orthotopic neobladder use is reviewed from an oncological viewpoint and the patient's quality of life after cystectomy for bladder cancer.

[Ten Years after Implementation of Cancer Control Act].

A brief description of the history of Cancer Control in Japan was presented for the first time. The establishment of the National Cancer Center and Comprehensive 10-year Strategy for Cancer Control Program, which has been implemented for 30 years, is most important. In response to the concerns raised by cancer patients, their families, and lay people, such as elimination of disparity arising from where they live or which hospital they attend, and asymmetrical cancer information, the Cancer Control Act was established in 2006 and executed in 2007. The Basic Plan to Promote Cancer Control Programs was started in 2007 as a 10-year plan. Hospitals that specialize in cancer treatment, nearly 400 in total, were appointed all over Japan. Hospitals that specialize in pediatric cancer were also appointed all over Japan. Cancer education for children and special issues, including employment of cancer patients, were stressed. Since the establishment of the Cancer Control Act, the Cancer Control Strategy in this country has been achieved remarkably as a frame. Henceforth, all items should be elucidated by giving importance to the opinion of patients, their families, and lay people.

[Cancer Education from Childhood].

Cancer education from childhood should include important issues such as lifestyle and time-determined human life. It should be established as a continuing education targeting not only junior and senior high school but also elementary school students. A compassionate newmovement is desirable between children and their parents concerning lifestyle, including tobacco use and cancer screening.

Inhibition of intestinal polyp growth by oral ingestion of bovine lactoferrin and immune cells in the large intestine.

Studies using animal models have demonstrated that ingestion of bovine lactoferrin (bLF) inhibits carcinogenesis in the colon and other organs of experimental animals. As a result of these studies, a blinded, randomized, controlled clinical trial was conducted in the National Cancer Center Hospital, Tokyo, Japan to determine whether ingestion of bLF had an effect on the growth of colorectal polyps in humans. Patients with colorectal polyps ≤5 mm diameter and likely to be adenomas ingested 0, 1.5, or 3.0 g bLF daily for 1 year. Ingestion of 3.0 g bLF suppressed the growth of colorectal polyps and increased the level of serum human lactoferrin in trial participants 63 years old or younger. The purpose of the present study was to investigate correlations between immune parameters and changes in polyp size. Trial participants with regressing polyps had increased NK cell activity, increased serum hLF levels (indicating increased neutrophil activity), and increased numbers of CD4+ cells in the polyps. These findings are consistent with a correlation between higher immune activity and suppression of colorectal polyps. In addition, participants with regressing polyps had lower numbers of PMNs and increased numbers of S100A8+ cells in the polyps, consistent with a correlation between lower inflammatory potential in the colon and suppression of colorectal polyps. Trial participants ingesting bLF had increased serum hLF levels, a possible increase in systemic NK cell activity, and increased numbers of CD4+ and CD161+ cells in the polyps. Taken together, our findings suggest that bLF suppressed colorectal polyps by enhancing immune responsiveness.

[Cancer screening in Japan and prostate cancer screening].

National cancer control programs are structured to include four main areas: prevention, screening, diagnosis and treatment, and palliative care. Cancer screening is particularly important because it helps to reduce medical costs and achieve maximum benefits for both patients and the country. There are many issues with cancer screening in Japan that need a solution, such as low participation rate and lack of sufficient quality control. Prostate cancer screening frequently leads to over-diagnosis and over-treatment, and therefore it should not be part of the 6th national screening program in Japan.

The impact of COVID-19 on thoracic surgical procedures in Japan: Analysis of data from the National Clinical Database.

OBJECTIVE: The COVID-19 pandemic has far-reaching collateral health impacts on the ongoing delivery of surgical care worldwide. The current study was designed to analyze the impact of the COVID-19 pandemic on the number of surgeries of general thoracic surgery in Japan. METHODS: Changes in the number of surgeries for total and three representative tumors were analyzed using the National Clinical Database data with reference to the pandemic infection rate and lung cancer screening. RESULTS: In 2020, the number of surgeries in total and for primary lung cancer and mediastinal lung tumor decreased by 4.9, 5.1, and 5.0 %, respectively. Considering the five-year trend towards a 5 % annual increase, there was a potential 10 % decrease in the number of primary lung cancer surgeries. The number of primary lung cancer surgeries bottomed in July 2020 but recovered towards the end of the year. In contrast, the number of metastatic lung tumor surgeries in 2020 increased by 3.2 %, following a similar trend observed over the previous five years. The number of lung cancer screening examinees decreased markedly with the lowest number in May. Our findings indicate that surgical triage had a limited impact on the decrease in primary lung cancer surgeries during the pandemic; rather, the decrease in lung cancer screening, which was a few months preceding, is most likely responsible. CONCLUSIONS: The decrease in primary lung cancer was mainly caused by the decrease in lung cancer screening, indicating that continuing screening is vital even during a pandemic.

Patient-reported outcomes following neoadjuvant endocrine therapy, external beam radiation, and adjuvant continuous/intermittent endocrine therapy for locally advanced prostate cancer: A randomized phase III trial.

BACKGROUND: We evaluated patient-reported outcomes (PRO) during neoadjuvant androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) followed by either adjuvant continuous ADT (CADT) or intermittent ADT (IADT) for patients with locally advanced prostate cancer (Pca). METHODS: A multicenter, randomized phase III trial enrolled 303 patients with locally advanced Pca. The patients were treated with 6 months (M) of ADT followed by 72 Gy of EBRT, and were randomly assigned to CADT or IADT after 14 M. The PROs were evaluated at sic points: baseline, 6 M, 8 M, 14 M, 20 M, and 38 M using FACT-P questionnaires and EPIC urinary, bowel, and sexual bother subscales. RESULTS: The FACT-P total scores were significantly better (p < 0.05) in IADT versus CADT at 20 M (121.6 vs.115.4) and at 38 M (119.9 vs. 115.2). The physical well-being scores (PWB) were significantly better (p < 0.05) in IADT versus CADT at 38 M (25.4 vs. 24.0). The functional scores were significantly better in IADT than those in CADT at 14 M (20.2 vs18.7, p < 0.05) and at 20 M (21.0 vs.18.9, p < 0.05). CONCLUSION: The PRO was significantly favorable in IADT on FACT-P total score at 20 M and 38 M, PWB and functional scores at 38 M.

Fibroblast growth factor receptor 3 mutation in voided urine is a useful diagnostic marker and significant indicator of tumor recurrence in non-muscle invasive bladder cancer.

The fibroblast growth factor receptor (FGFR)-3 gene encodes a receptor tyrosine kinase that is frequently mutated in non-muscle invasive bladder cancer (NMIBC). A sensitive and quantitative assay using peptide nucleic acid-mediated real-time PCR was developed for detecting FGFR3 mutations in the urine samples and evaluated as a molecular marker for detecting intravesical recurrence of NMIBC in patients undergoing transurethral resection of bladder tumor. FGFR3 mutation was examined in tumor tissues and serially taken pre- and postoperative urine sediments in 45 NMIBC patients with a median follow up of 32 months. FGFR3 mutations were detected in 53.3% (24/45) of primary tumor tissues, among which intravesical recurrence developed in 37.5% (9/24) of cases. FGFR3 mutation in the primary tumor was not a significant prognostic indicator for recurrence, while the proportion of FGFR3 mutation (i.e. tumor cellularity was >or=11%) in the preoperative urine sediments was a significant indicator for recurrence in patients with FGFR3 mutations in the primary tumors. FGFR3 mutations were detected in 78% (7/9) of postoperative urine samples from recurrent cases with FGFR3 mutations in the tumor, while no mutations were detected in the urine of 15 non-recurrent cases. Urine cytology was negative in all cases with FGFR3 mutations in the primary tumors, while the sensitivity of cytological examination was as high as 56% (5/9) in cases showing wild-type FGFR3 in the primary tumors. Urine FGFR3 mutation assay and cytological examination may be available in the future as complementary diagnostic modalities in postoperative management of NMIBC.