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Background: Cancers are as common in individuals with intellectual disabilities as in the general population (GP). For the subgroup of people with profound and multiple disabilities (PMD) who present with both severe intellectual disability and major motor disorders, the frequency and distribution of cancers are currently not known, preventing proper cancer surveillance. Methods: We carried out a systematic and synthetic review of the medical literature, including a focused search of Japanese data. Results: The total risk of cancer in individuals with PMD is thought to be lower than in the GP, possibly due to a shorter life expectancy. They have reduced exposure to cancer risk factors, such as alcohol, tobacco, sunlight, human papillomavirus infection, occupational toxins, and being overweight. On the other hand, individuals with PMD present a greater frequency of gastroesophageal reflux disease, Helicobacter pylori gastritis, chronic cystitis, and cryptorchidism, which increase the risk for cancer of the esophagus, stomach, urinary bladder, and testes. In addition, certain genetic disorders underlying compromised motor and cognitive functions are associated with higher risk of childhood cancers. An analysis of 135 cancers in persons with PMD in Japan suggested that they present a particular tumor profile, with certain cancers rarer than in the GP, whereas cancers of the digestive tract are frequent. Cancers of the digestive tract occurred significantly earlier than in the GP (colon: average age 48.3 years vs. 71.3 years in the GP, esophagus: 39 years vs. 72 years in the GP). An increasing number of therapeutic successes in children and adults with PMD have been reported in different countries when cancers are discovered early. Conclusion: Individuals with PMD must be appropriately monitored for cancer. Screenings for breast and colon cancer, as well as regular monitoring of the esophagus, stomach, urinary bladder, and testicles, are necessary. Population-based epidemiological studies are needed to better understand risk factors, frequency, and distribution of cancers in the PMD population. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment strategy for resectable BRAF V600E mutant colorectal oligometastases (CRM) has not been established due to the rarity and rapid progression of the disease. Since the unresectable recurrence rate is high, development of novel perioperative therapies are warranted. On December 2020, the BEACON CRC triplet regimen of encorafenib, binimetinib, and cetuximab was approved for unresectable metastatic colorectal cancer in Japan. Methods: The NEXUS trial is a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant CRM. The key inclusion criteria are as follows: histologically diagnosed with colorectal adeno/adenosquamous carcinoma; RAS wild-type and BRAF V600E mutation by tissue or blood; and previously untreated resectable distant metastases. The triplet regimen (encorafenib: 300 mg daily; binimetinib: 45 mg twice daily; cetuximab: 400 mg/m2, then 250 mg/m2 weekly, 28 days/cycle) is administered for 3 cycles each before and after curative resection. The primary endpoint of the study is the 1-year progression-free survival (PFS) rate and the secondary end points are the PFS, disease-free survival, overall survival, and objective response rate. The sample size is 32 patients. Endpoints in the NEXUS trial as well as integrated analysis with the nationwide registry data will be considered for seeking regulatory approval for the perioperative use of the triplet regimen. Discussion: The use of the triplet regimen in the perioperative period is expected to be safe and effective in patients with resectable BRAF V600E mutant CRM. Trial registration: jRCT2031220025, April. 16, 2022. [ABSTRACT FROM AUTHOR]

Background: The CARD trial was conducted in patients with metastatic castration-resistant prostate cancer (mCRPC) who had received docetaxel and experienced disease progression within 1 year on an androgen receptor-axis-targeted therapy (ARAT). Subsequent treatment with cabazitaxel had improved clinical outcomes compared with an alternative ARAT. This study aims to confirm the effectiveness of cabazitaxel in real-world patients in Japan and compare their characteristics with those of patients from the CARD trial. Methods: This was a post-hoc analysis of a nationwide post-marketing surveillance registering all patients who were prescribed cabazitaxel in Japan between September 2014 and June 2015. Included patients had received docetaxel and ≤ 1 year of an ARAT (abiraterone or enzalutamide) prior to receiving cabazitaxel or an alternative ARAT, as their third-line therapy. The primary effectiveness endpoint was the time to treatment failure (TTF) of the third-line therapy. Patients were matched (1:1) from the cabazitaxel and second ARAT arms based on propensity score (PS). Results: Of the 535 patients analysed, 247 received cabazitaxel and 288 the alternative ARAT as their third-line therapy, of which, 91.3% (n = 263/288) received abiraterone and 8.7% (n = 25/288) received enzalutamide as their second third-line ARAT. Patients in the cabazitaxel and second ARAT arms had TNM classification of M1 or MX in 73.3% and 68.1%, Gleason score of 8–10 in 78.5% and 79.2% and mean (standard deviation) serum PSA levels of 483 (1370) and 594 (1241) ng/mL, respectively. Initial cabazitaxel dose was ≤ 20 mg/m2 in 61.9% (n = 153/247) of the patients in the cabazitaxel arm. The median TTF (95% confidence interval [CI]) of the third-line therapy was 109 (94–128) days for cabazitaxel and 58 (57–66) days for the second ARAT, with a hazard ratio (95% CI) of 0.339 (0.279–0.413) favouring cabazitaxel. Similar results were obtained after PS-matching, with a hazard ratio (95% CI) of 0.323 (95% CI 0.258–0.402) favouring cabazitaxel. Conclusions: Consistent with the CARD trial, cabazitaxel demonstrated superior effectiveness over a second alternative ARAT in a real-world patient population in Japan, despite the population having more advanced disease status and a lower dose of cabazitaxel being more frequently administered, than in the CARD trial. [ABSTRACT FROM AUTHOR]

Background: Soft tissue sarcomas (STS) are a rare type of malignancy comprising a variety of histological diagnoses. Chemotherapy constitutes the standard treatment for advanced STS. Doxorubicin-based regimens, which include the administration of doxorubicin alone or in combination with ifosfamide or dacarbazine, are widely accepted as first-line chemotherapy for advanced STS. Trabectedin, eribulin, pazopanib, and gemcitabine plus docetaxel (GD), which is the empirical standard therapy in Japan, are major candidates for second-line chemotherapy for advanced STS, although clear evidence of the superiority of any one regimen is lacking. The Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group (JCOG) conducts this trial to select the most promising regimen among trabectedin, eribulin, and pazopanib for comparison with GD as the test arm regimen in a future phase III trial of second-line treatment for patients with advanced STS. Methods: The JCOG1802 study is a multicenter, selection design, randomized phase II trial comparing trabectedin (1.2 mg/m2 intravenously, every 3 weeks), eribulin (1.4 mg/m2 intravenously, days 1 and 8, every 3 weeks), and pazopanib (800 mg orally, every day) in patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. The principal eligibility criteria are patients aged 16 years or above; unresectable and/or metastatic STS; exacerbation within 6 months prior to registration; histopathological diagnosis of STS other than Ewing sarcoma, embryonal/alveolar rhabdomyosarcoma, well-differentiated liposarcoma and myxoid liposarcoma; prior doxorubicin-based chemotherapy for STS, and Eastern Cooperative Oncology Group performance status 0 to 2. The primary endpoint is progression-free survival, and the secondary endpoints include overall survival, disease-control rate, response rate, and adverse events. The total planned sample size to correctly select the most promising regimen with a probability of > 80% is 120. Thirty-seven institutions in Japan will participate at the start of this trial. Discussion: This is the first randomized trial to evaluate trabectedin, eribulin, and pazopanib as second-line therapies for advanced STS. We endeavor to perform a subsequent phase III trial comparing the best regimen selected by this study (JCOG1802) with GD. Trial registration: This study was registered with the Japan Registry of Clinical Trials (jRCTs031190152) on December 5, 2019. [ABSTRACT FROM AUTHOR]

Background: Bronchoscopy can be a distress for the patient. There have been few studies on the combination of sedatives and opioids. The aim of this study was to demonstrate the usefulness and safety of administration of the combination of midazolam and pethidine during bronchoscopy.Methods: In this prospective randomized single (patient)-blind study, we randomly assigned 100 patients who were scheduled to undergo bronchoscopy biopsy to receive treatment with either the midazolam/pethidine combination (combination group) or midazolam alone (midazolam group) during examinations. After the end of bronchoscopy, patients completed a questionnaire and the visual analogue scale was measured. The primary outcome was the patients' acceptance of re-examination assessed by visual analogue scale. We also assessed pain levels, vital signs, midazolam use, xylocaine use, and adverse events. Univariate analyses were performed using Fisher's exact test for categorical data, and the t-test or Mann-Whitney test was carried out for analysis of numeric data. All P-values were two-sided, and values < 0.05 were considered statistically significant.Results: We analyzed 47 patients in the combination group and 49 patients in the midazolam group. The primary outcome was a good trend in the combination group, but not significantly different (3.82 ± 2.3 in combination group versus 4.17 ± 2.75 in midazolam alone, P = 0.400). In the combination group, the visual analog scale score for pain during bronchoscopy was significantly lower (1.10 ± 1.88 versus 2.13 ± 2.42, P = 0.022), and the sedation level score per the modified observer's assessment of alertness/sedation scale was significantly deeper (3.49 ± 0.98 versus 3.94 ± 1.03, P = 0.031). Maximal systolic blood pressure during testing was significantly lower (162.39 ± 23.45 mmHg versus 178.24 ± 30.24 mmHg, P = 0.005), and the number of additional administrations of midazolam was significantly lower (2.06 ± 1.45 versus 2.63 ± 1.35, P = 0.049). There were also significantly fewer adverse events (30 versus 41, P = 0.036).Conclusions: The combination uses of midazolam and pethidine for sedation resulted in significant improvements in the pain, blood pressure, additional use of midazolam, and safety during bronchoscopy among patients.Trial Registration: This study was registered in the University Medical Hospital Information Network in Japan (UMINCTR Registration number: UMIN000032230 , Registered: 13/April/2018). [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of paclitaxel (PTX). There is no known prophylactic measure, although there are some reports of prevention with compression therapy using surgical gloves. On account of its predominantly subjective symptoms, it is difficult to exclude bias when assessing for CIPN. In this study, we assessed the effectiveness of the same procedure for the prevention of paclitaxel-induced PN based on a double-blind study design.Methods: The patients with early and recurrent breast cancer (with no prior PTX exposure) initiating weekly chemotherapy with PTX 80 mg/m2 were enrolled. Each patient donned two gloves on each hand at every PTX infusion. Two one-size-smaller gloves were donned on one hand (study side) and two normal-size gloves were donned on the other hand (control side) during 90 min from 30 min before the infusion to 30 min after the end of the infusion. Study side are blind for both patients and assessing physicians according to determination of the study side by research nurses in the chemotherapy unit. The primary outcome was the difference in the frequency of CIPN (motor/sensory) determined by the physician using the common terminology criteria for adverse events (CTCAE v4.0), with an evaluation at each cycle of PTX infusion. McNemar test was used to assess the primary outcome.Results: Between July 2017 and November 2018, 56 patients were enrolled and 49 patients were evaluated. Overall, Grade ≥ 2 PN (sensory) was observed in 30.6 and 36.7% in the study and control sides, respectively (McNemar p = 0.25). PN (motor) was observed in 4.1 and 6.1% in the study and control sides, respectively (McNemar p = 1.0).Conclusion: Surgical glove compression therapy showed no statistically significant effect on the incidence of PTX-induced PN.Trial Registrations: This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry managed by the National University Hospital Council of Japan ( UMIN000027944 ). Registered 26 June 2017. [ABSTRACT FROM AUTHOR]

Background: Young adult cancer patients often face unique challenges and have potential unmet needs. This study aimed (1) to describe unmet supportive care needs among young adults with cancer in Japan, and (2) to identify its associated factors.Methods: In a cross-sectional web-based survey, 206 young adults with cancer were assessed for supportive care needs. Multiple regression analysis examined whether demographics, clinical variables and social support were associated with unmet supportive care needs.Results: A total of 206 patients (180 female) with a mean age of 33.7 years (SD = 4.3, range: 22-39) participated. One hundred and fifty-eight participants (76.7%) reported at least one unmet supportive care needs. The top 20 unmet needs included 9 of the 10 psychological needs, 3 of the 5 physical and daily living needs, 8 of the 11 health system and information needs and 1 of the 5 sexuality needs. Multiple regression analysis revealed that perceived poorer PS, experience of change in work/school after a cancer diagnosis and poor social support were significantly associated with higher supportive care needs. The total score of supportive care needs was significantly associated with both psychological distress and QOL.Conclusions: More than 70% of young adult cancer patients reported unmet supportive care needs and most of those were psychological needs. The findings suggest potential opportunities for intervention in addressing psychological needs rather than physical and information needs. [ABSTRACT FROM AUTHOR]

Background: Terminal-stage solid tumors are one of the main causes of disseminated intravascular coagulation (DIC); effective therapeutic strategies are therefore warranted. This study aimed to investigate the association between mortality and antithrombin therapy in patients with stage IV solid tumor-associated DIC using a large nationwide inpatient database.Methods: From July 2010 to March 2018, patients with stage IV solid tumor-associated DIC in the general wards, intensive care unit, or high care unit were identified using the Japanese Diagnosis Procedure Combination Inpatient Database. Patients who received antithrombin within 3 days of admission were allocated to the antithrombin group, while the remaining patients were allocated to the control group. One-to-four propensity score matching analyses were applied to compare outcomes. The primary outcome was the 28-day in-hospital mortality.Results: Of the 25,299 eligible patients, 919 patients had received antithrombin within 3 days of admission and were matched with 3676 patients in the control group. There were no significant differences in the 28-day mortality between the two groups (control vs. antithrombin: 28.9% vs. 30.3%; hazard ratio, 1.08; 95% confidence interval, 0.95-1.23). There were no significant differences in the organ failure score and the proportion of critical bleeding between the two groups. Subgroup analyses showed that the effects of antithrombin were not significantly different among different tumor types.Conclusion: Using a nationwide Japanese inpatient database, this study showed that there is no association between antithrombin administration and 28-day mortality in patients with stage IV solid tumor-associated DIC. Therefore, establishing other therapeutic strategies for solid tumor-associated DIC is required. [ABSTRACT FROM AUTHOR]

Background: The recommended starting dose of cabazitaxel for castration-resistant prostate cancer (CRPC) is 25 mg/m2 in Japan and Europe. Although lower doses are established alternatives based on randomized controlled trials, the safety and efficacy of 25 and 20 mg/m2 in real-world settings are not well established. Therefore, we investigated the safety and efficacy of cabazitaxel at the recommended starting dose or a lower dose (20 mg/m2) in real-world clinical practice.Methods: We compared the safety and efficacy of cabazitaxel between patients who received cabazitaxel at starting doses of 25 and 20 mg/m2 (C25 and C20, respectively) in a Japanese post-marketing surveillance study of 662 patients with docetaxel-refractory CRPC. Safety was assessed in terms of adverse drug reactions (ADRs). Prostate-specific antigen (PSA) response rate, overall survival (OS), and time-to-treatment failure (TTF) were compared between the C25 and C20 groups in unmatched patients and after applying propensity score matching.Results: The C20 and C25 groups comprised 190 and 159 patients without matching and 112 patients per group after matching. In unmatched patients, any-grade (C25 vs C20: 89.3% vs 78.4%, Fisher's p < 0.01) and grade ≥ 3 (81.1% vs 61.1%) ADRs were more frequent in the C25 group. Neutropenia (any grade: 61.6% vs 54.2%; grade ≥ 3: 55.3% vs 42.6%) and febrile neutropenia (grade ≥ 3: 30.2% vs 14.7%) were more frequent in the C25 group. In matched patients, the PSA response rate (reduction in PSA ≥30% from a baseline ≥5 ng/mL) was 26.4 and 32.0% in the C20 and C25 groups, respectively, median OS was 291 days (95% CI 230-not reached) versus not reached (hazard ratio 0.73, 95% CI 0.50-1.08), and TTF favored C25 (hazard ratio 0.75, 95% CI 0.57-0.99).Conclusions: Clinicians should consider the patient's risk of clinically significant ADRs and prophylactic granulocyte colony stimulating factor when selecting the starting dose of cabazitaxel for CRPC. Some patients at high risk of ADRs or unfit patients may benefit from a lower starting dose of 20 mg/m2, whereas fit patients may be candidates for a starting dose of 25 mg/m2.Trial Registration: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Prophylactic cranial irradiation (PCI) is a current standard of care after confirmed response to radical chemoradiotherapy for limited disease small cell lung cancer (LD-SCLC). This standard is mostly based on results of old randomized studies when brain imaging with magnetic resonance (MRI) was not available. Survival benefit of PCI in extended disease SCLC was recently challenged by the results of randomized phase III study from Japan.Methods: Eighty patients with LD-SCLC after response to chest chemoradiotherapy will be enrolled. Patients will be followed up by brain MRI every 3 to 6 months up to 3 years. Neurocognitive function tests will be performed at baseline and after 12 and 24 months. Patients who develop brain metastases will be irradiated with stereotactic (SRT) or whole brain RT (WBRT). The primary endpoint is overall survival. The secondary endpoints are: response rate to radiotherapy of early detected brain metastases, analysis of efficacy of SRT and WBRT; assessment and analysis of neurocognitive functions and QoL in the studied cohorts: QLQ-C30 questionnaire and the California Verbal Learning Test, Color connection test, Benton visual retention test, and verbal fluency test will be carried out.Discussion: The results of this trial may contribute to changing of LD-SCLC clinical management by deescalating the treatment. There is a lack of prospective, recent studies in LD-SCLC patients with omission of PCI and modern radiation therapy technologies for developed brain metastases. The comprehensive neurocognitive function testing will help to assess the impact of modern radiotherapy (SRT) compared with WBRT and no-PCI in SCLC patients. A subgroup of long-term survivors, who will not develop brain metastases, will not be exposed to unnecessary brain irradiation with its deleterious consequences. The limitation of our study is a lack of parallel randomized control arm. This is a potential source of bias; however, randomized study will be difficult to complete for two major reasons: (1) limited population of LD-SCLC eligible for the study and (2) opinions of our patients, who after information and discussion about benefits and potential harms of PCI, often choose to omit PCI in our practice.Trial Registration: ClinicalTrials.gov Identifier: NCT04168281, 19 Nov. 2019. [ABSTRACT FROM AUTHOR]

Background: CYP2A6 is an enzyme involved in oxidation of a number of environmental chemicals, including nicotine, pro-carcinogenic nitrosamines and polycyclic aromatic hydrocarbons (PAHs). The whole gene deletion of CYP2A6 (CYP2A6*4) is prevalent in East Asian population. Whether or not CYP2A6*4 associates with cancer is still controversial.Methods: We undertook an association study to determine whether deletion of CYP2A6 gene associates with total cancer and major cancer types employing data of consecutive autopsy cases registered in the Japanese single-nucleotide polymorphisms for geriatric research (JG-SNP) database. The presence of cancer were inspected at the time of autopsy and pathologically confirmed. Genotyping for CYP2A6 wild type (W) and deletion (D) was done by allele specific RT-PCR method.Results: Among 1373 subjects, 826 subjects (60.2%) were cancer positive and 547 subjects (39.8%) were cancer negative. The genotype frequency in the whole study group for WW, WD and DD were 65.0, 30.6 and 4.4%, respectively, which obeyed the Hardy-Weinberg equilibrium (p = 0.20). Total cancer presence, as well as major cancers including gastric, lung, colorectal, and blood cancers did not show any positive association with CYP2A6 deletion. When male and female were separately analyzed, CYP2A6 deletion associated with decreased gastric cancer risk in female (OR = 0.49, 95%CI: 0.25-0.95, p = 0.021, after adjustment for age, smoking and drinking). When smoker and non-smoker were separately analyzed, CYP2A6 deletion associated with decreased total cancer in female nonsmokers (OR = 0.67, 95%CI: 0.45-0.99, p = 0.041 after adjustment). On the other hand, CYP2A6 deletion associated increase blood cancers in smokers (OR = 2.05, 95%CI: 1.19-3.53, p = 0.01 after adjustment).Conclusion: The CYP2A6 deletion may not grossly affect total cancer. It may associate with individual cancers in sex and smoking dependent manner. Further studies with larger sample size are warranted to confirm our results. [ABSTRACT FROM AUTHOR]

Background: Assessment of preoperative general condition to predict postoperative outcomes is important, particularly in older patients who typically suffer from various comorbidities and exhibit impaired functional status. In addition to various indices such as Charlson Comorbidity Index (CCI), National Institute on Aging and National Cancer Institute Comorbidity Index (NIA/NCI), Adult Comorbidity Evaluation-27 (ACE-27), and American Society of Anesthesiologists Physical Status classification (ASA-PS), controlling nutritional status (CONUT) score is recently gaining attention as a tool to evaluate the general condition of patients from a nutritional perspective. However, the utility of these indices in older patients with colorectal cancer has not been compared.Methods: The study population comprised 830 patients with Stage I - IV colorectal cancer aged 75 years or older who underwent surgery at the National Cancer Center Hospital from January 2000 to December 2014. Associations of each index with overall survival (OS) (long-term outcome) and postoperative complications (short-term outcome) were examined.Results: For the three indices with the highest Akaike information criterion values (i.e., CONUT score, CCI and ACE-27), but not the remaining indices (NIA/NCI and ASA-PS), OS significantly worsened as general condition scores decreased, after adjusting for known prognostic factors. In contrast, for postoperative complications, only CONUT score was identified as a predictive factor (≥4 versus 0-3; odds ratio: 1.90; 95% CI: 1.13-3.13; P = 0.016).Conclusion: For older patients with colorectal cancer, only CONUT score was a predictive factor of both long-term and short-term outcomes after surgery, suggesting that CONUT score is a useful preoperative risk assessment index. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Carbohydrate antigen (CA) 19-9 levels after resection are considered to predict prognosis; however, the significance of decreased CA19-9 levels after neoadjuvant therapy has not been clarified. This study aimed to define the prognostic significance of decreased CA19-9 levels after neoadjuvant therapy in patients with pancreatic adenocarcinoma.Methods: Between 2001 and 2012, 240 consecutive patients received neoadjuvant therapy and subsequent resection at seven high-volume institutions in Japan. These patients were divided into three groups: Normal group (no elevation [≤37 U/ml] before and after neoadjuvant therapy), Responder group (elevated levels [> 37 U/ml] before neoadjuvant therapy but decreased levels [≤37 U/ml] afterwards), and Non-responder group (elevated levels [> 37 U/ml] after neoadjuvant therapy). Analyses of overall survival and recurrence patterns were performed. Uni- and multivariate analyses were performed to clarify the clinicopathological factors influencing overall survival. The initial metastasis sites were also evaluated in these groups.Results: The Responder group received a better prognosis than the Non-responder group (3-year overall survival: 50.6 and 41.6%, respectively, P = 0.026), but the prognosis was comparable to the Normal group (3-year overall survival: 54.2%, P = 0.934). According to the analysis of the receiver operating characteristic curve, the CA19-9 cut-off level defined as no elevation after neoadjuvant therapy was ≤103 U/ml. The multivariate analysis revealed that a CA19-9 level ≤ 103 U/ml, (P = 0.010, hazard ratio: 1.711; 95% confidence interval: 1.133-2.639), tumor size ≤27 mm (P = 0.040, 1.517; (1.018-2.278)), a lack of lymph node metastasis (P = 0.002, 1.905; (1.276-2.875)), and R0 status (P = 0.045, 1.659; 1.012-2.627) were significant predictors of overall survival. Moreover, the Responder group showed a lower risk of hepatic recurrence (18%) compared to the Non-responder group (31%), though no significant difference in loco-regional, peritoneal or other distant recurrence were observed between groups (P = 0.058, P = 0.700 and P = 0.350, respectively).Conclusions: Decreased CA19-9 levels after neoadjuvant therapy predicts a better prognosis, with low incidence of hepatic recurrence after surgery. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the cost-effectiveness of replacing standard intravenous therapy (taxane) with oral S-1 therapy for first-line metastatic breast cancer treatment.Methods: This cost-effectiveness analysis was based on data from a randomized phase III trial (SELECT BC). As cost-effectiveness was a secondary endpoint of the SELECT BC trial, some of the randomized patients participated in an EQ-5D survey (N = 391) and health economic survey (N = 146). The EQ-5D responses, claims, and prescription data were collected for as long as possible until death. The expected quality-adjusted life years (QALY) obtained from each treatment were calculated using patient-level EQ-5D data, and the expected cost was calculated using patient-level claim data. The analysis was performed from the perspective of public healthcare payers.Results: The estimated EQ-5D least-square means and 95% CI up to 48 months were 0.764 (95% CI, 0.741-0.782) and 0.742 (95% CI, 0.720-0.764) in the S-1 and taxane arms, respectively. The expected QALY was 2.11 for the S-1 arm and 2.04 for the taxane arm, with expected costs of JPY 5.13 million (USD 46,600) and JPY 5.56 million (USD 50,500), respectively. These results show that S-1 is cost-saving. According to probabilistic sensitivity analysis, S-1 was dominant with a probability of 63%. When the willingness to pay (WTP) value was JPY 5 million (USD 45,500) per QALY, the probability of being cost-effective was 92%.Conclusions: Our results show that the introduction of oral S-1 therapy for metastatic breast cancer is highly likely to be cost-effective.Trial Registration: UMIN CTR C000000416 . Registered on May 10, 2006. [ABSTRACT FROM AUTHOR]

Background: The rates of thoracoscopic esophagectomy performed in the prone and left lateral decubitus positions are similar in Japan. We retrospectively reviewed short- and long-term outcomes of thoracoscopic esophagectomy for esophageal cancer performed in the left lateral decubitus position.Methods: Between 1996 and 2015, 654 patients with esophageal cancer underwent thoracoscopic esophagectomy in the left lateral decubitus position. Patients were divided into early (1996-2008) and late groups (2009-2015, with standardization of the procedure and formalized training), and their clinical outcomes reviewed.Results: The completion rate of thoracoscopic esophagectomy was 99.5%, and the procedure was converted to thoracotomy in three patients, due to hemorrhage. The mean intrathoracic operative time, intrathoracic blood loss, and number of dissected mediastinal lymph nodes were 205.0 min, 127.3 mL, and 24.7, respectively. Postoperative complications included pneumonia (8.5%), anastomotic leakage (7.5%), and recurrent nerve paralysis (3.5%). Postoperative (30d) mortality was 4/654 (0.61%) due to anastomotic leak and pneumonia. The five year overall survival rate was 70%. A comparison of the 289 early- and 365 late-study period cases revealed significant differences in mean intrathoracic blood loss (174.0 vs. 94.2 mL), number of mediastinal lymph nodes dissected (20.0 vs. 28.4), hospital length of stay (33.4 vs. 20.0 days, p < 0.001), and postoperative anastomotic leakage (14% vs. 1.6%, p < 0.0001).Conclusions: Standardization of the procedure for thoracoscopic esophagectomy in the left lateral decubitus position, with a standardized clinical pathway for perioperative care led to significant improvements in surgical outcomes. [ABSTRACT FROM AUTHOR]

Background: A high incidence of severe hematological adverse events during sunitinib treatment complicates decision making on dose and treatment cycle. We identified the characteristics of early-onset hematotoxicity of sunitinib in Japanese patients with renal cell carcinoma (RCC).Methods: Seventy-nine patients were treated with sunitinib as 6-week cycles of "4-week on 2-week off" schedule. To evaluate early-onset hematotoxicity, we compared patients with dose reduction during the first cycle (dose-reduced group, n = 57) and those who maintained the initial dose (dose-maintained group, n = 22). ABCG2 and FLT3 genotypes were analyzed for association between hematotoxicity and reported gene polymorphisms.Results: Mean relative dose intensity (RDI) was similar in the two groups during the first 2 weeks of dosing in the first cycle, but was significantly lower in the dose-reduced group during the last 2 weeks. Lymphocytopenia and thrombocytopenia were observed in the dose-reduced group within the first 2 weeks. Genetic analysis indicated a significantly higher frequency of FLT3 738 T/C polymorphism in the dose-reduced group, but no significant difference in the ABCG2 421 C/A polymorphism.Conclusions: This study showed a high incidence of sunitinib-induced hematotoxicity in Japanese patients with RCC, many of whom need dose adjustment during the first cycle. Further studies should verify whether dose adjustment based on early-onset thrombocytopenia prolongs sunitinib treatment. [ABSTRACT FROM AUTHOR]

Background: TAS-102 (trifluridine and tipiracil hydrochloride; a novel combination oral nucleoside anti-tumor agent) has recently received regulatory approval for patients with refractory metastatic colorectal cancer (mCRC). Internal review of data at a single-institution showed a trend towards better overall survival (OS) for patients who experienced chemotherapy-induced neutropenia at 1-month (CIN-1-month). To explore this finding further, a cohort study was designed based on outcome data from three centers in United States and one from Japan.Methods: CIN-1-month after starting TAS-102 was defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03 as a neutrophil count decrease of ≥ grade 2 (absolute neutrophil count < 1500/mm(3)). Patients had confirmed mCRC that was refractory to standard therapies. Patient demographics and clinical characteristics were compared between patients with CIN-1-month (CIN-1-month positive) versus those who did not have CIN-1-month (CIN-1-month negative); with the median progression-free survival (PFS) and OS were calculated using the Kaplan-Meier method, and differences evaluated using the Log-rank test.Results: Our cohort study had a total of 149 patients with data regarding their neutrophil assessment at 1-month mark. Patients who developed ≥ grade 2 CIN-1-month had a both longer PFS (median 3.0 months versus 2.4 months; Log-rank P-value = 0.01), as well as OS (14.0 versus 5.6 months; Log-rank P-value < 0.0001). Only CIN-1-month (adjusted HR: 0.21 (95 % CI: 0.11-0.38) and higher baseline CEA levels (adjusted HR: 2.00 (95 % CI: 1.22-3.35) were noted to be independent predictors of OS. Furthermore, the CIN-1-month was noted to be a statistically significantly predictor of OS over a wide range of cutoffs.Conclusions: Our observations are novel and hypothesis generating. Neutropenia after starting TAS-102 was associated with better prognosis in patients with refractory mCRC. It can be postulated that the dosage of TAS-102 potentially may need to be increased to achieve better outcomes in patients not experiencing any neutropenia. Further pharmacologic investigations should help elucidate these issues. [ABSTRACT FROM AUTHOR]

Background: This study aimed to provide an updated analysis of childhood cancer mortality rates and long-term trends to 2013 to describe the current level of deaths and identify changes in recent decades. Methods: Data on number of deaths from cancer in children aged under 15 years were derived from Vital Statistics in Japan and the World Health Organization (WHO) mortality database for comparison countries. Trends in mortality were examined by fitting a joinpoint regression model. Results: For all cancers combined, the mortality rate during 2010-2013 was 19.9 per 1,000,000 population for boys and 17.5 for girls in Japan. Mortality from all cancers combined decreased significantly from 1980 to 2003 for boys and from 1980 to 2001 for girls. Afterwards, the rates remained stable for both sexes. Mortality from leukemia declined over the entire study period by 4.6 % per year (p <0.05) in boys and 4.3 % per year (p <0.05) in girls. For central nervous system (CNS) tumors, a slight increase in mortality was observed for both sexes, with a statistically significant annual percent change (APC) of 0.5 % (p <0.05) for boys and 0.6 % (p <0.05) for girls. Conclusions: We provided updated information on recent trends of childhood cancer death. The establishment of a nationwide, childhood cancer registry is required in Japan. Moreover, trends in cancer mortality should be monitored continuously. [ABSTRACT FROM AUTHOR]

Background: We usually report five-year survival from population-based cancer registries in Japan; however these survival estimates may be pessimistic for cancer survivors, because many patients with unfavourable prognosis die shortly after diagnosis. Conditional survival can provide relevant information for cancer survivors, their family and oncologists.Methods: We used the period approach to estimate the latest 10-year survival of 38,439 patients with stomach, colorectal, lung, breast and prostate cancer diagnosed between 1990 and 2004 and followed-up from 2000-04 in Osaka, Japan. Conditional survival is an estimate, with the pre-condition of having already survived a certain length of time. Conditional five-year relative survival of one to five years after diagnosis was calculated by site, age and stage for survivors under the age of 70.Results: Five-year relative survival for stomach cancer was 60%. Conditional five-year relative survival was 77% one year after diagnosis and 97% five years after diagnosis. This means that 97% of patients who survive five years after diagnosis can survive a further five years. Conditional five-year relative survival improved successively with each additional year that patients lived after diagnosis for stomach, colorectal and lung cancer. These figures for breast and prostate cancer were stable at high survival. Liver cancer did not show an increase in conditional five-year survival.Conclusion: Conditional five-year survival is a relevant figure for long-term cancer survivors in Japan. It is important for population-based cancer registries to provide figures which cancer patients and oncologists really need. [ABSTRACT FROM AUTHOR]

Background: To assess the trends of risk classification and primary therapy in Japanese patients who were diagnosed with prostate cancer between 2004-2006 and 2007-2009.Methods: A total of 4752 patients who were newly diagnosed with prostate cancer at Nara Medical University and its 23 affiliated hospitals between 2004 and 2009 were enrolled. The differences in risk classification and primary therapy were compared in patients who were newly diagnosed between 2004-2006 (prior period) and 2007-2009 (latter period).Results: The proportion of patients with a high or greater risk significantly decreased in the latter period compared to the prior period (p < 0.001). The proportion of primary androgen deprivation therapy (PADT) was 50% in the prior period, and 40% in the latter period. On the other hand, the proportion of radiation therapy was 14% in the prior period, but 24% in the latter period. The proportion of radical prostatectomy was the same in the two periods (30%). The primary therapy was significantly different between the two periods (p < 0.001).Conclusions: Higher risk patients significantly decreased in the latter period compared to the prior period. The use of PADT also significantly decreased in the latter period. However, there were still higher risk patients in Japan, and the use of PADT was still common in patients with localized prostate cancer or locally advanced prostate cancer in Japan. [ABSTRACT FROM AUTHOR]

Background: The financial burden of medical expenses has been increasing for cancer patients. We investigated the relationship between household income and financial burden among patients with chronic myelogenous leukaemia (CML) who have been treated with imatinib. Methods: A questionnaire was distributed to 1200 patients between May and August 2009. We retrospectively surveyed their household incomes, out-of-pocket medical expenses, final co-payments after refunds, and the perceived financial burden of their medical expenses in 2000, 2005 and 2008. Results: A total of 577 patients completed the questionnaire. Their median age was 61 years (range, 15–94). A financial burden was felt by 41.2 % (28 of 68) of the patients treated with imatinib in 2000, 70.8 % (201 of 284) in 2005, and 75.8 % (400 of 528) in 2008. Overall, 182 patients (31.7 %) considered its discontinuation because of the financial burden and 15 (2.6 %) temporarily stopped their imatinib prescription. In 2000, 2005 and 2008, the patients’ median annual household incomes were 49,615 US Dollars (USD), 38,510 USD and 36,731 USD, respectively, with an average currency exchange rate of 104 Yen/USD in 2008. Their median annual out-of-pocket expenses were 11,548, 12,067 and 11,538 USD and their median final annual co-payments were 4,375, 4,327 and 3,558 USD, respectively. Older patients (OR = 0.96, 95 % CI: 0.95–0.98, p<0.0001 for 1-year increments), and patients with higher household incomes (OR = 0.92, 95 % CI: 0.85–0.99, p = 0.03 for 10,000 USD-increments) were less likely to have considered discontinuing their imatinib treatment. Conversely, patients with higher annual final co payments (OR = 2.21, 95 % CI: 1.28–4.28, p = 0.004 for 10,000 USD-increments) were more likely to have considered discontinuing their imatinib treatment. Conclusions: The proportion of CML patients who sensed a financial burden increased between 2000 and 2008. During this period, their annual incomes fell by 13,000 USD, although their medical expenses did not change. Financial support for patients being treated with expensive drugs remains a major problem in Japan. [ABSTRACT FROM AUTHOR]

The article presents a research which examines the genome sequences of circulating hepatitis B virus DNA (HBV-DNA) from the sera of hepatocellular carcinoma (HCC) patients who were infected with HBV genotype C in the western part of Japan between 1988 and 2004 to identify the G1613A and C1653T mutations from HBV. It is reported that, the researchers used polymerase chain reaction (PCR) on serum samples.

Background: Although gangliocytic paraganglioma (GP) has generally been regarded as a neuroendocrine tumor, its origin remains unclear. We therefore aimed to investigate the details of this disease by carefully analyzing and extracting common features of the disease as presented in selected publications. Methods: We searched for English and Japanese cases of GP using the PubMed and IgakuChuoZasshi databases on August 2010. We then extracted and sampled raw data from the selected publications and performed appropriate statistical analyses. Additionally, we evaluated the expression of hormone receptors based on our previously reported case. Results: 192 patients with GP were retrieved from the databases. Patient ages ranged from 15 y to 84 y (mean: 52.3 y). The gender ratio was 114:76 (male to female, 2 not reported). Maximum diameter of the tumors ranged from 5.5 mm to 100 mm (mean: 25.0 mm). The duodenum (90.1%, 173/192) was found to be the most common site of the disease. In 173 patients with duodenal GP, gastrointestinal bleeding (45.1%, 78/173) was found to be the most common symptom of the disease, followed by abdominal pain (42.8%, 74/173), and anemia (14.5%, 25/173). Rate of lymph node metastasis was 6.9% (12/173). Our statistical analysis indicated that significant differences were found for gender between GP within the submucosal layer and exceeding the submucosal layer. Furthermore, our immunohistochemical evaluation showed that both epithelioid and pancreatic islet cells showed positive reactivity for progesterone receptors. Conclusions: Our literature survey revealed that there were many more cases of GP exceeding the submucosal layer than were expected. Meanwhile, our statistical analyses and immunohistochemical evaluation supported the following two hypotheses. First, vertical growth of GP might be affected by progesterone exposure. Second, the origin of GP might be pancreatic islet cells. However, it is strongly suspected that our data have been affected by publication bias and to confirm these hypotheses, further investigation is required. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether individualized treatments based on biological factors have improved the prognosis of recurrent breast cancer. The purpose of this study is to evaluate the survival improvement of patients with recurrent breast cancer after the introduction of third generation aromatase inhibitors (AIs) and trastuzumab. Methods: A total of 407 patients who received first diagnosis of recurrent breast cancer and treatment at National Kyushu Cancer Center between 1992 and 2008 were retrospectively evaluated. As AIs and trastuzumab were approved for clinical use in Japan in 2001, the patients were divided into two time cohorts depending on whether the cancer recurred before or after 2001. Cohort A: 170 patients who were diagnosed between 1992 and 2000. Cohort B: 237 patients who were diagnosed between 2001 and 2008. Tumor characteristics, treatments, and outcome were compared. Results: Fourteen percent of cohort A and 76% of cohort B received AIs and/or trastuzumab (P < 0.001). The median overall survival (OS) times after breast cancer recurrence were 1.7 years and 4.2 years for these respective cohorts (P < 0.001). Both the time period and treatment of AIs and/or trastuzumab for recurrent disease were significant prognostic factors in multivariate analysis (cohort B vs. cohort A: HR = 0.70, P = 0.01; AIs and/or trastuzumab for recurrent disease: yes vs. no: HR = 0.46, P < 0.001). When patients were categorized into 4 subgroups by the expression of hormone receptor (HR) and HER-2 status, the median OS times of the HR-positive/ HER-2-negative, HR-positive/HER-2-positive, HR-negative/HER-2-positive, and HR-negative/HER-2-negative subtypes were 2.2, 2.4, 1.6, and 1.0 years in cohort A and 4.5, 5.1, 5.0, and 1.4 years in cohort B. Conclusions: The prognosis of patients with recurrent breast cancer was improved over time following the introduction of AIs and trastuzumab and the survival improvement was apparent in HR- and/or HER-2-positive tumors. [ABSTRACT FROM AUTHOR]

Background: Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine with anti-tumor activity. The objective of this study was to determine whether LTA polymorphisms influence the presence of cancer. Methods: LTA polymorphisms C804A (rs1041981, T60N) and T495C (rs2229094, C13R) were determined in 1,536 consecutive autopsy cases and were registered in the Japanese singlenucleotide polymorphisms (SNPs) for geriatric research (JG-SNP) Internet database. Tumors were systematically reviewed, pathologically confirmed, and assessed in relation to LTA genotype. Results: The study population consisted of 827 males and 709 females, with a mean age of 80 years. Altogether, we studied 606 subjects without cancer and 930 subjects with cancer of the stomach (n = 183), lung (n = 164), colon or rectum (n = 143), or other sites. The presence of cancer was higher in males than in females. The C804A and T495C polymorphisms were associated with cancer in males (CA + AA: CC, adjusted OR = 0.72, 95% CI = 0.53 -- 0.99; TC + CC: TT, adjusted OR = 1.45, 95% CI = 1.04 -- 2.02; respectively) but not in females. In males, the C804A polymorphism was associated with lung cancer (CA + AA: CC, adjusted OR = 0.60, 95% CI = 0.37 -- 0.97), whereas the T495C polymorphism was associated with gastric cancer (TC + CC: TT, adjusted OR = 1.68, 95% CI = 1.06 -- 2.65). Conclusion: We found some evidence of an association between LTA polymorphisms and cancer risk in elderly Japanese men. Further studies in larger populations should examine this hypothesis. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the role of osteoprotegerin gene (OPG) polymorphisms as genetic modifiers in the etiology of prostate cancer (PCa) and disease progression. Methods: Three hundred and sixty one patients with PCa and 195 normal controls were enrolled in the study, and two genetic polymorphisms, 149 T/C and 950 T/C in the putative promoter region of OPG, were genotyped. Results: There was no significant difference in the genotype frequencies between PCa patients and controls (P = 0.939 and 0.294 for 149 T/C and 950 T/C polymorphisms, respectively). However, those patients with TC and TT genotypes in the 950 T/C polymorphism had a significantly increased risk of extraprostatic (age-adjusted odds ratio; aOR = 1.74 and 2.03 for TC and TT genotypes compared with the CC genotype, P = 0.028) and metastatic disease (aOR = 1.72 and 2.76 for TC and TT genotypes compared with the CC genotype, P = 0.009) compared with those with the CC genotype. In addition, analysis of the metastatic PCa patients (Stage D) showed that the presence of the T allele of the OPG 950 T/C polymorphism was an independent risk factor predicting survival by Cox proportional hazard regression analyses (P = 0.031). Conclusion: Progression of PCa may be influenced by an intrinsic genetic factor of the host's bone metabolism. The variant C allele of 950 T/C in the OPG promoter may play a major role as a genetic safe guard against progression in patients with PCa. [ABSTRACT FROM AUTHOR]

Background: In general, human papillomavirus (HPV) vaccines have demonstrated efficacy in young women worldwide, but there is limited evidence on the efficacy of the quadrivalent HPV6/11/16/18 vaccine in adult women and no evidence of its effectiveness in Japanese adult women in particular. This study aims to evaluate the efficacy of the quadrivalent HPV6/11/16/18 vaccine for persistent HPV16/18 infection in Japanese women aged 27-45 years.Methods: This is an interventional, nonrandomized, non-double-blind prospective cohort study designed to compare the rates of persistent HPV16/18 infection between the vaccinated arm and unvaccinated arm. The subjects will consist of all women aged 27-45 years who have normal cytology results confirmed by cervical cancer screening from May 2019 to March 2021. The follow-up time is two years. The subjects will be divided into two groups: the vaccinated group and the unvaccinated group. The study will need to enroll 600 vaccinated participants (experimental arm) and 2200 unvaccinated participants (control arm).Discussion: The findings of this trial (HAKUOH study) might provide the first local evidence on the subject and be significantly useful not only to medical academia but also to the Japanese Ministry of Health, Labour and Welfare. The findings could contribute to public health improvement by providing local supportive knowledge on the prevention of HPV infection through HPV vaccination in young adult women in Japan, where active recommendations have been suspended for a long time due to adverse effects.Trial Registration: Trial registration number: NCT04022148 . Registration began on December 1, 2019. [ABSTRACT FROM AUTHOR]

Background: Myxoid liposarcoma (MLS) has the tendency to metastasize extrapulmonary. Although prognostic factors at the initial diagnosis of MLS have been reported, those at diagnosis of metastasis remain unclear. The purpose of this study was to investigate the prognostic factors for disease-specific survival at the initial diagnosis of metastasis.Methods: This retrospective observational study was conducted at three cancer centers and two university hospitals in Japan. Of 274 MLS patients pathologically diagnosed between 2001 and 2015, 48 metastatic patients were examined.Results: Lung metastases were detected in nine patients (18.8%) and extrapulmonary metastases in 45 (93.8%). Interval from primary diagnosis to the first metastasis was significantly shorter in patients with lung metastases than without (p = 0.007). Median disease-specific survival after diagnosis of metastases was 52.5 months in all patients. In multivariable analysis, liver metastasis (hazard ratio (HR), 2.71 [95% confidence interval (CI), 1.00-7.09]) and no evidence of disease (NED) achieved by radical treatment (resection with or without radiation therapy, or radiation therapy ≥60 Gy) or semi-radical (radiation therapy ≥40 Gy) treatment were significantly related to survival (HR, 0.36; 95%CI [0.13-0.95]). The number of metastases (odds ratio (OR), 0.44; 95%CI [0.25-0.78]) and abdominal/retroperitoneal metastases (OR, 0.09; 95%CI [0.008-0.95]) were the significant inhibitory factors of achieving NED.Conclusions: This is the first study to statistically demonstrate the importance of achieving NED with surgical resection or radiation therapy for longer survival in metastatic MLS patients. As number of metastases was a significant factor for achieving NED, early detection of metastases might be important. [ABSTRACT FROM AUTHOR]

Background: Paclitaxel is used in second-line conventional chemotherapies to manage patients with unresectable advanced gastric cancer (GC). Paclitaxel-induced peripheral neuropathy is a known adverse event leading to treatment discontinuation. Additionally, oxaliplatin which causes irreversible peripheral neuropathy is now commonly used in first-line chemotherapy for advanced GC in Japan. Thus, examining the incidence of peripheral neuropathy with paclitaxel after oxaliplatin is necessary to improve the quality of life and outcomes of patients with advanced GC in the second-line treatment setting.Methods: This prospective observational multicenter study, (which we named IVY study), will evaluate the degree of chemotherapy-induced peripheral neuropathy (CIPN) and the efficacy of second-line chemotherapy for unresectable advanced GC. A patient neurotoxicity questionnaire (PNQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) will be used to assess CIPN during the second-line treatment. The key eligibility criteria are as follows: 1) unresectable or recurrent GC histologically confirmed to be primary adenocarcinoma of the stomach, 2) age over 20 years, 3) Eastern Cooperative Oncology Group performance status score of 0-2, 4) written informed consent following full study information is provided to the patient, 5) progression or intolerance for first-line chemotherapy comprising fluorinated pyrimidine and platinum anticancer drugs (cisplatin or oxaliplatin) for advanced GC. 6) presence of evaluable lesions as confirmed using a computed tomography (CT) or magnetic resonance imaging. A total of 200 patients is considered to be appropriate for inclusion in this study.Discussion: The results of this study will provide some information on CIPN with the sequential usage of oxaliplatin as first-line chemotherapy to paclitaxel as second-line chemotherapy in clinical practice.Trial Registration: This trial is registered in the University Hospital Medical Information Network's Clinical Trials Registry with the registration number UMIN000033376 (Registered 11 July 2018). [ABSTRACT FROM AUTHOR]

Background: Since Fuchs' report in 1999, the reported protective effect of dietary fiber from colorectal carcinogenesis has led many researchers to question its real benefit. The aim of this study is to evaluate the association between diet, especially dietary fiber and fat and colorectal cancer in Japan.Methods: A multiple regression analysis (using the stepwise variable selection method) was performed using the standardized mortality ratios (SMRs) of colon and rectal cancer in 23 Japanese prefectures as objective variables and dietary fiber, nutrients and food groups as explanatory variables.Results: As for colon cancer, the standardized partial correlation coefficients were positively significant for fat (1,13, P = 0.000), seaweeds (0.41, P = 0.026) and beans (0.45, P = 0.017) and were negatively significant for vitamin A (-0.63, P = 0.003), vitamin C (-0.42, P = 0.019) and yellow-green vegetables (-0.37, P = 0.046). For rectal cancer, the standardized partial correlation coefficient in fat (0.60, P = 0.002) was positively significant. Dietary fiber was not found to have a significant relationship with either colon or rectal cancers.Conclusions: This study failed to show any protective effect of dietary fiber in subjects with a low fat intake (Japanese) in this analysis, which supports Fuchs' findings in subjects with a high fat intake (US Americans). [ABSTRACT FROM AUTHOR]