The implementation status of prehabilitation during neoadjuvant chemotherapy for patients with locally advanced esophageal cancer: a questionnaire survey to the board-certified facilities in Japan.

BACKGROUND: Prehabilitation during neoadjuvant therapy has the potential to improve clinical outcomes. However, information on its global dissemination status is limited. This Japanese nationwide survey investigated the implementation status of and barriers to prehabilitation during neoadjuvant chemotherapy (NAC) for patients with locally advanced esophageal cancer in hospitals. METHODS: This multicenter nationwide survey was conducted by post. The eligible facilities were 155 Japanese hospitals that had been certified within the last 10 years as authorized institutes for board-certified esophageal surgeons by the Japan Esophageal Society. We administered an original questionnaire to investigate the current status of prehabilitation during NAC. RESULTS: The response rate was 75% (117/155 facilities). Forty-six facilities (39%) provided prehabilitation during NAC. The most frequently selected reasons for not providing or providing insufficient prehabilitation were lack of human resources, issues with the reimbursement of medical fees, difficulty in providing continuous prehabilitation during repeated inpatient and outpatient care, the lack of established standard prehabilitation programs, challenges in providing multidisciplinary prehabilitation, and difficulty in managing physical symptoms. CONCLUSION: We observed that the implementation rate of prehabilitation during NAC was low. Critical reasons were not only the lack of medical resources but also the lack of evidence-based standard prehabilitation programs during NAC and the lack of evidence for how to continuously deliver prehabilitation during NAC to patients with physical symptoms.

Priority of the basic and instrumental activities of daily living in older patients with cancer prescribed rehabilitation: a cross-sectional survey.

BACKGROUND: There is no information on whether vulnerable older patients with cancer consider basic activities of daily living (BADL) and instrumental activities of daily living (IADL) important outcomes. Our survey aimed to investigate the priority of BADL and IADL in outcomes among vulnerable older patients with cancer. METHODS: This was a single-center survey in a Japanese cancer center. Eligible patients were ≥ 65 years of age and were prescribed in-hospital rehabilitation while under cancer treatment. Using original self-administered ranking questionnaires, patients were asked to rank outcomes and subdomain of BADL and IADL. High-priority domains were defined as the highest, second-highest, and third-highest priority domains in individuals. RESULTS: A total of 169 patients were analyzed. The mean age was 74.0 years (standard deviation, 5.1 years) and the number of males was 107 (63%). The order of ranking of high-priority outcomes was BADL and IADL (n = 155), cognitive function (n = 91), mental function (n = 82), nutrition (n = 61), social function (n = 51), comorbidity (n = 39), and life span (n = 28). The top three high-priority independence subdomains of BADL and IADL were toilet use (n = 140), feeding (n = 134), and mobility (n = 69) among the BADL and shopping (n = 93), food preparation (n = 88), and ability to handle finances (n = 85) among the IADL. CONCLUSIONS: BADL and IADL can be considered the most important health outcomes in clinical trials and in practice among older patients with cancer and physical vulnerabilities.

Association of sarcopenia with relative dose intensity of neoadjuvant chemotherapy in older patients with locally advanced esophageal cancer: A retrospective cohort study.

INTRODUCTION: Sarcopenia impacts the toxicity of chemotherapy in patients with cancer, but there is little information on the association of sarcopenia with the relative dose intensity (RDI) of chemotherapy. We investigated the association of sarcopenia with RDI of neoadjuvant chemotherapy (NAC) in older patients with locally advanced esophageal cancer (LAEC). MATERIALS AND METHODS: This was a single-center retrospective cohort study of patients aged ≥65 years who underwent curative esophagectomy after NAC for LAEC between 2016 and 2020. Skeletal muscle mass index (SMI) was calculated from computed tomography images at the L3 level. Sarcopenia was defined using the Youden index of SMI. Average RDI was calculated from delivered-dose intensity and standard-dose intensity of all drugs. The cutoff point of low average RDI was defined as <85%. The multivariate logistic regression model was used for the endpoint. RESULTS: We analyzed 188 patients with a mean age of 71.3 years. The cutoff points of sarcopenia for low average RDI were defined as 42.81 cm2/m2 in males and 37.48 cm2/m2 in females. Sarcopenia significantly affected low average RDI, adjusted for age, sex, body mass index, drug regimen, clinical stage, and creatinine clearance (adjusted odds ratio: 2.195, 95% confidence interval: 1.107-4.411, p = 0.024). Compared with the non-sarcopenia patients, the sarcopenia patients with low average RDI had a higher rate of dose reduction, delayed, or discontinuation after the first cycle because of neutropenia (45% vs. 38%), and decreased performance status (11% vs. 0%). DISCUSSION: Sarcopenia predicted low average RDI (<85%) of NAC in older patients with LAEC. In the future, the information about the mechanism of association of sarcopenia with RDI will progress the development of intervention strategy and novel supportive care.

Skeletal muscle mass recovery after oesophagectomy and neoadjuvant chemotherapy in oesophageal cancer: retrospective cohort study.

OBJECTIVE: Skeletal muscle mass (SMM) is an important biomarker for prognosis and health in older patients with cancer. Limited information is available on the recovery course of SMM after oesophagectomy following neoadjuvant chemotherapy (NAC) in older patients. This study was performed to investigate the recovery course of SMM after oesophagectomy following NAC and the preoperative predictors of delayed recovery in older patients with locally advanced oesophageal cancer (LAEC). METHODS: This single-centre retrospective cohort study involved older (≥65 years) and non-older (<65 years) patients with LAEC who underwent oesophagectomy following NAC. The SMM index (SMI) was calculated using CT images. One-way analysis of variance and multivariate logistic regression analysis were performed. RESULTS: In total, 110 older patients and 57 non-older patients were analysed. Loss of the SMI after NAC to 12 months postoperatively was significantly greater in older patients than in non-older patients (p<0.01). The significant preoperative predictor of delayed recovery of the SMI 12 months after surgery was loss of the SMI during NAC in older patients (per 1%: adjusted OR 1.249; 95% CI 1.131 to 1.403; p<0.001), but not in non-older patients (per 1%: OR 1.074; 95% CI 0.988 to 1.179; p=0.108). CONCLUSIONS: There is an especially large unmet need for preventing the long-term sequelae of SMM loss in older patients with LAEC after oesophagectomy following NAC. In older patients, loss of SMM during NAC is an especially useful biomarker for prescribing postoperative rehabilitation to prevent postoperative loss of SMM.

Impact of early postoperative factors on changes in skeletal muscle mass after esophagectomy in older patients with esophageal cancer.

BACKGROUND: Loss of skeletal muscle mass, measured by the skeletal muscle mass index (SMI), after esophagectomy negatively impacts prognosis. However, the information to develop novel supportive care options for preventing loss of skeletal muscle mass is limited. The purpose of this retrospective cohort study was to investigate the impact of early postoperative factors on change in SMI 4 months after curative esophagectomy in older patients with esophageal cancer. METHODS: This study included 113 subjects who underwent esophagectomy between 2015 and 2020. Preoperative and postoperative SMI (cm2/m2) were calculated from computed tomography images. The percentage change in SMI 4 months after surgery (SMI%) was calculated as follows: ([postoperative SMI - preoperative SMI] ÷ preoperative SMI) × 100. Potential factors affecting percentage change of SMI after surgery were analyzed by multiple regression. RESULTS: The mean SMI% was - 5.6%. The percentage change (per 1%) in quadriceps muscle strength in the first month after surgery (standardized ß = 0.190, p = 0.048) impacted the SMI%, which was independent of age, sex, preoperative SMI, comorbidity, pathological stage, and neoadjuvant chemotherapy. CONCLUSION: Quadriceps muscle weakness in the first month after esophagectomy impacted the SMI% in a dose-dependent relationship.

Prognostic Impact of the Loss of Skeletal Muscle Mass During Neoadjuvant Chemotherapy on Older Patients with Esophageal Cancer.

BACKGROUND: In older adults, skeletal muscle mass is an important factor for health and prognosis. The loss of SMM during neoadjuvant therapy affects the prognosis of patients with locally advanced esophageal cancer. However, information is limited regarding this possibility in older patients. This study aimed to establish the prognostic impact of SMM loss during neoadjuvant chemotherapy on older patients with locally advanced esophageal cancer. METHODS: This was a single-center retrospective cohort study. Patients age 65 years or older had undergone R0 curative esophagectomy after NAC. The skeletal muscle mass index before and after NAC was calculated from computed tomography images. The percentage change in the SMI during NAC (SMI%) was calculated from the SMI before and after NAC. RESULTS: The study analyzed 150 patients with a mean age of 71.1 ± 3.7 years. The mean value of the SMI was 42.7 ± 7.2 cm2/m2 before NAC, and the SMI% was - 6.4% ± 5.9%. The cutoff of SMI% for overall survival was defined by the log-rank test as - 12%. The Cox proportional hazard model showed that major loss of the SMI (≥ 12%) significantly influenced OS (hazard ratio, 2.490; 95% confidence interval, 1.121-5.529; p = 0.025) independently of age, sex, pathologic T and N factors, or treatment regimen. CONCLUSIONS: Major SMI loss has an impact on OS after R0 curative esophagectomy for older patients with locally advanced esophageal cancer.

Prognostic Impact of Postoperative Loss of Skeletal Muscle Mass in Patients Aged 70 Years or Older with Esophageal Cancer.

BACKGROUND: The number of patients with esophageal cancer aged ≥ 70 years with a poor prognosis is increasing. In general patients with esophageal cancer, postoperative loss of skeletal muscle mass (SMM) is a prognostic factor. This study was designed to investigate the prognostic impact of postoperative loss of SMM in patients aged ≥ 70 years with esophageal cancer. METHODS: This study was a single-center, retrospective cohort study. Patients with esophageal cancer who underwent R0 esophagectomy between 2016 and 2020 were included. The percentage postoperative loss of skeletal muscle mass index (SMI%) was calculated using computed tomography images before and at 4 ± 2 months after surgery. RESULTS: The number of subjects in the ≥ 70-year and < 70-year age groups was 166 and 218, respectively. The median SMI% was 5% in all patients; thus, 5% was defined as the cutoff point to define major loss of SMI. Major loss of SMI impacted 3-year overall survival (OS) in the ≥ 70-year age group, independent of age, sex, clinical stage, pathological T and N factors, Charlson comorbidity index, and length of hospital stay (adjusted hazard ratio [HR]: 4.400; 95% confidence interval: 1.202-16.105; P = 0.025). The adjusted HR of major loss of SMI in the ≥ 70-year age group was higher than in the < 70-year age group (adjusted HR: 4.400 vs. 2.388, respectively). CONCLUSIONS: Postoperative loss of SMI in patients with esophageal cancer aged ≥ 70 years more strongly impacted 3-year OS than in patients aged < 70 years.

Comparison of Lipoprotein Cholesterol Levels in Golden Syrian Hamster Administrated trans-Octadecenoic Acid Positional Isomers.

We previously conducted a study using HepG2 cells to compare the effect on the secreted apolipoprotein B-100 and apolipoprotein A-1 ratio (B-100/A-1) corresponding to the ratio of low-density to high-density lipoprotein cholesterol (LDL/HDL) among 13 types of trans-octadecenoic acid (t-18:1) positional isomers. The results revealed that trans-5-18:1 (t5) significantly increased B-100/A-1. In this study, 1% of t5 in the diet, corresponding to 2.08 energy%, was administrated golden Syrian hamsters for 4 weeks to reveal the effects on lipid profiles, including LDL/HDL, by comparing cis-9-octadecenoic acid (OA, oleic acid), trans-9-octadecenoic acid (EA), trans-11-octadecenoic acid (VA), and trans-9,trans-12- octadecadienoic acid (TT). LDL/HDL was not significantly different among the groups. However, the cholesterol concentration of medium very low-density lipoprotein (VLDL) was significantly lower in the TT diet than in the OA and t5 diets. The cholesterol concentration of small VLDL was significantly lower in the TT diet than in the OA, t5, and EA diets. The cholesterol concentration of large LDL was significantly lower in the TT diet than in the t5 and EA diets. However, no significant difference was detected between the TT and OA diets. In contrast, the cholesterol concentration of very small HDL was significantly higher in the TT diet than in the t5 diet. These results would support that lipid metabolism is affected by the structure of TFA in animals. However, t5-18:1 did not significantly change any lipid profile compared to OA existing in nature, and the previous result from the cell experiment showing that t5 increased B-100/A-1 (LDL/HDL) was not confirmed in this animal experiment.

Development and evaluation of an "Interdisciplinary Postoperative Support Program" in outpatient clinics after thoracic esophagectomy.

BACKGROUND: To support patients discharged from the hospital after surgery, we launched an "Interdisciplinary Postoperative Support Program" in outpatient clinics for patients who were discharged within 1 month after thoracic esophagectomy and their families. We introduce our program and clarify the patient's physical and psychologic status by analyzing the questionnaire provided from this program. MATERIALS AND METHODS: From August 2014 to January 2015, we conducted the Interdisciplinary Postoperative Support Program every month. Thus, questionnaires regarding physical and psychologic symptoms as well as the meaningfulness of the program were obtained from 59 patients and prospectively analyzed. RESULTS: We obtained valid responses from 48 patients (81.4%). Frequent postoperative difficulties included dysphagia (50%) and decreased physical strength (39.5%). Oral intake decreased to half (55.3%) and one-fourth (25.5%) of that before esophagectomy. Frequent requests made by patients to medical staff included explanations of the postoperative symptoms (97.9%), further information on the treatments of esophageal cancer (93.8%), and the typical postoperative course experienced by other patients (76.6%). A higher percentage of positive comments were obtained regarding the management of symptoms (87.8%) and optimal access to the consultations (78.9%). The incidences of unscheduled outpatient visits were 4.1% and 14.0%, respectively, under conditions with and without this postoperative program (P = 0.03). CONCLUSION: We found that our program could provide appropriate information with higher levels of satisfaction after thoracic esophagectomy. Further investigations regarding longer periods of physical and psychologic symptoms, as well as the needs of patients and their families should be conducted to augment our program.