The impact of goal-directed prehabilitation therapy on functional capacity in patients undergoing hepatobiliary and pancreatic surgery: A randomized clinical trial.

BACKGROUND: Emerging evidence has supported the idea that goal-directed prehabilitation is a promising approach to boost functional capacity in preoperative patients. However, its usefulness has not been tested in the hepatobiliary and pancreatic fields. The objective of this trial was to investigate the efficacy of goal-directed prehabilitation for improving functional capacity in patients who were planned to undergo major hepatobiliary and pancreatic operations. METHODS: This assessor-blinded, parallel-arm, randomized clinical trial recruited patients who were scheduled for major hepatobiliary and pancreatic surgeries for malignancy. Patients were randomly allocated into the step goal-directed prehabilitation group as the test group and into the conventional prehabilitation group as the control group. Patients in the goal-directed prehabilitation group participated in a walking prehabilitation program with an intergrading goal of the step count. Patients in the conventional prehabilitation group received standard physical and nutritional prehabilitation. The primary outcome was change in the 6-minute walking distance, which ranged from the time before starting prehabilitation (baseline) to the time after completing prehabilitation (immediately before surgery). RESULTS: Among 180 randomized patients, 144 patients were included in the primary analysis (73 patients in the conventional prehabilitation group and 71 patients in the goal-directed prehabilitation group). The mean change in the 6-minute walking distance was 27 meters in the conventional prehabilitation group and 31 meters in the goal-directed prehabilitation group (P = .633). CONCLUSION: In patients undergoing major hepatobiliary and pancreatic surgeries for malignancies, a goal-directed prehabilitation program did not result in a significantly greater increase in functional capacity than did conventional prehabilitation. REGISTRATION NUMBER: UMIN000038791 (https://www.umin.ac.jp/).

Efficacy of rehabilitation initiated in the early phase after simultaneous deceased donor liver and kidney transplantation: A case report.

RATIONALE: The purpose of this case report is to describe a case of successful early rehabilitation intervention for simultaneous liver and kidney transplantation (SLKT). PATIENT CONCERNS: A 51-year-old Japanese man was diagnosed with Caroli disease 27 years ago. Hemodialysis was introduced due to end-stage renal disease 17 years ago. DIAGNOSES: After successful SLKT, the patient was extubated on postoperative day (POD) 1, liberated from dialysis on POD 4, and discharged from the intensive care unit on POD 9. INTERVENTIONS: Supervised rehabilitation was started on POD 2, and the patient was able to walk 100 m on POD 9. Electrical muscle stimulation therapy was started to improve muscle weakness in both legs on POD 16, and aerobic exercise using a cycle-ergometer was started on POD 24. OUTCOMES: The 6-minute walking distance improved from 324 m on POD 14 to 501 m on POD 28. The patient could walk 4000 to 5000 steps per day at hospital discharge, and was discharged home on POD 32. There were no adverse events, including worsening hepatic or renal function, during the rehabilitation period. One month after discharge, the patient was able to perform 30 to 40 minutes of aerobic exercise every day, and returned to work 5 months after discharge. LESSONS: This case shows that early rehabilitation intervention immediately after SLKT safely and rapidly improved physical performance without adverse events. The results in the present case suggest that regular physical assessment and appropriate interventions with a variety of exercise modalities can contribute to improved physical performance in SLKT patients.

Chest three-dimensional-computed tomography imaging data analysis for the variation of exercise capacity after lung lobectomy.

BACKGROUND: Postoperative loss of exercise capacity and pulmonary function is a major concern among lung cancer patients. In this study, the time for a stair-climbing to 12-m height was used to investigate whether preoperative chest 3D-computed tomography (CT) could be a useful tool for predicting postoperative variations in exercise capacity and pulmonary function. METHODS: Seventy-eight patients undergoing lobectomy for suspected stage I lung cancer were prospectively enroled. Preoperatively, lobe volume and low attenuation volume (LAV) were evaluated using the SYNAPSE VINCENT system. Preoperative data on stair-climbing time, spirometry and diffusing capacity of the lung for carbon monoxide (DLCO ) at baseline and 6-month postoperative data were used to evaluate variations in exercise capacity and pulmonary function. Maximal oxygen uptake (VO2 t) was evaluated based on the stair-climbing time. RESULTS: Significant differences in the variation of exercise capacity at 6 months postoperatively were found between the groups categorized by target lobe volume and LAV status: The large volume/LAV (+) group had a greater decline in VO2 t. Mean loss of VO2 t was -6.2%, -1.4%, -1.6% and -0.1% in the large volume/LAV (+), large volume/LAV (-), small volume/LAV (+) and small volume/LAV (-) groups, respectively. The large volume/LAV (-) group had a greater decline in forced expiratory volume in 1 s. The small volume/LAV (+) group showed a reduced decline in the DLCO . CONCLUSIONS: Analysis of chest 3D-CT scans is a potential tool for predicting the loss of exercise capacity and pulmonary function after lung lobectomy.

Effects of Neuromuscular Electrical Stimulation on Lower Limb Muscle Strength After Living Donor Liver Transplant: A Case-Control Study.

BACKGROUND: Early mobilization after liver transplant (LT) plays an important role in postoperative recovery and complication prevention; however, patients undergoing LT cannot achieve early mobilization because of mechanical ventilation and poor preoperative physical performance. We investigated the effect of neuromuscular electrical stimulation (NMES) on lower limb muscle strength after living donor liver transplant (LDLT). METHODS: Adult patients who underwent LDLT between December 2016 and January 2019 at a university hospital were recruited. A consecutive series of patients who underwent LDLT without NMES therapy before the clinical trial (April 2014-May 2016) were enrolled as the non-NMES (control) group. Patients in the NMES group received NMES on the quadriceps muscles starting 1 day post LDLT for 4 weeks. The study was conducted in accordance with the Declaration of Helsinki, and all patients provided informed consent. RESULTS: Twenty-four patients in the NMES group and 16 patients in the non-NMES group were analyzed. There was no significant difference between groups regarding changes in any outcome. CONCLUSIONS: The application of NMES in patients with LDLT did not yield greater improvement of muscle strength, functional capacity, activities of daily living, or length of hospital stay 4 weeks postoperatively compared with the control group. However, developing a novel NMES device and confirming whether additional NMES is effective for other body areas may yield different results.

Risk Assessment for Loss-of-Exercise Capacity After Lung Cancer Surgery: Current Advances in Surgery and Systemic Treatment.

BACKGROUND: Considering advances in current post-recurrence treatment, we examined the prognostic significance of the number of risk factors for loss-of-exercise capacity (LEC) after lung cancer surgery, which were identified by our previous prospective observational study. METHODS: Risk factors for LEC were defined as a short baseline 6-min walk distance (<400 m), older age (≥75 years), and low predicted postoperative diffusing capacity for carbon monoxide (<60%). Patients were classified as Risk 0/I/II/III according to the number of risk factors. The survival data were retrospectively analyzed. RESULTS: Between 2014 and 2017, 564 patients (n = 307, 193, 57, 7; Risk 0/I/II/III) who underwent lung cancer surgery were included in the study. The number of risk factors was associated with smoking status, predicted postoperative forced expiratory volume in 1 s, histology, pathological stage, and adjuvant therapy. In a multivariate Cox regression analysis, compared to Risk 0, Risk I/II/III showed significant associations with overall survival (hazard ratios: 1.92, 3.35, 9.21; 95% confidence interval: 1.27-2.92, 2.01-5.58, 3.64-23.35; Risk I/II/III, respectively). In 141 patients with recurrence, molecular targeted therapies (MTTs) or immune checkpoint inhibitors (ICIs) were included in 58%, 47%, 32%, and 0% (Risk 0/I/II/III) during the course of treatment. In patients with MTT/ICI treatment, the estimated 1-year and 3-year post-recurrence survival rates were 88% and 58%, respectively. CONCLUSIONS: Risk classification for LEC was associated with survival after lung cancer surgery, as well as post-recurrence treatment. The concept of physical performance-preserving surgery may contribute to improving the outcomes of current lung cancer treatment.

Simultaneous Treatment of Long-chain Monounsaturated Fatty Acid and n-3 Polyunsaturated Fatty Acid Decreases Lipid and Cholesterol Levels in HepG2 Cell.

The n-3 type polyunsaturated fatty acids (n-3PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), from fish oil exhibit health benefits such as triacylglycerol- and cholesterol-lowering effects. Some pelagic fishes contain long-chain monounsaturated fatty acids (LC-MUFAs) such as eicosenoic acid (C20:1), which exert health-promoting effects. However, no study has evaluated beneficial effects of n-3PUFA and LC-MUFA combination. Here, we investigated effects of simultaneous treatment with n-3PUFA (EPA and DHA) and LC-MUFA (cis-5-C20:1 and cis-7-C20:1) and found that n-3PUFA and LC-MUFA combination significantly decreased lipid accumulation and reduced total cholesterol in HepG2 cells. Cholesterol level was significantly lower in DHA + cis-7-C20:1 group than in DHA + EPA group. These results suggest the importance of LC-MUFA as a functional molecule in fish oil.

Preoperative paraspinous muscle sarcopenia and physical performance as prognostic indicators in non-small-cell lung cancer.

BACKGROUND: Despite the associations of both preoperative sarcopenia and physical performance with post-operative mortality in non-small-cell lung cancer (NSCLC), there have been no comprehensive studies of the impact of physical status on prognosis. This study was performed to investigate the prognostic significance of preoperative sarcopenia and physical performance in NSCLC. METHODS: This retrospective cohort study was performed in NSCLS patients undergoing curative lung resection at a university hospital between January 2014 and December 2017. The patients were divided into four groups according to the skeletal muscle index [sarcopenia (lowest sex-specific tertile) and non-sarcopenia] and 6 min walking distance (6MWD) [short distance (<400 m) and long distance (≥400 m)]. Sarcopenia was assessed by preoperative cross-sectional areas of right and left paraspinous muscles at the level of the 12th thoracic vertebra from computed tomography images, and physical performance was determined by preoperative 6MWD. The primary and secondary endpoints were post-operative overall survival (OS) and disease-free survival (DFS). RESULTS: The 587 patients [mean age: 68.5 ± 8.8 years, 399 men (68%)] included in the study were divided into the non-sarcopenia/long-distance group (58%), sarcopenia/long-distance group (26%), non-sarcopenia/short-distance group (9%), and sarcopenia/short-distance group (7%). A total of 109 (18.6%) deaths and 209 (35.6%) combined endpoints were observed over a mean follow-up of 3.1 ± 1.3 years. After adjusting for other covariates, the sarcopenia/short-distance group showed significant associations with shorter OS (hazard ratio, 3.38; 95% confidence interval, 1.79-6.37; P < 0.001) and DFS (hazard ratio, 2.11; 95% confidence, 1.27-3.51; P = 0.004) compared with the non-sarcopenia/long-distance group on multivariate analyses. Although not significant, adding skeletal muscle index and 6MWD to the pre-existing risk model increased the area under the curve on time-dependent receiver operating characteristic curve analysis for OS and DFS, except within 2 years of surgery. CONCLUSIONS: The presence of both preoperative paraspinous muscle sarcopenia and short distance in 6MWD had an adverse effect on post-operative prognosis in patients with NSCLC, suggesting that preoperative assessment of thoracic sarcopenia and physical performance may be useful for risk stratification of surgical candidates with potential for targeted interventions.

Factors associated with changes in the 12-m stair-climbing time after lung lobectomy.

OBJECTIVE: Postoperative loss-of-exercise capacity is one of the main concerns for patients undergoing lung cancer surgery. This study was designed to identify the factors associated with loss-of-exercise capacity after lobectomy, using an easy surrogate measure: the 12-m stair-climbing time (SCt). METHODS: Ninety-eight patients undergoing lobectomy for suspected stage I lung cancer were prospectively enrolled. SCt and pulmonary function test were evaluated preoperatively as baseline and at 6 months postoperatively. At 6 months postoperatively, 20 patients dropped out. Loss-of-exercise capacity was defined as at least a 3.3% decline (lower quartile) in the estimated maximal oxygen uptake (VO2t: 43.06 - 0.4 × SCt). Factors associated with loss-of-exercise capacity were analyzed. RESULTS: Median (interquartile range) baseline SCt was 31.5 (28.2-36.7) s. Baseline SCt was not significantly associated with complications. At 6 months postoperatively, SCt increased by + 4.4 (+ 3.2, + 6.8) s in patients with loss-of-exercise capacity. Sex, smoking status, lobe, procedure, and forced expiratory volume in 1 s showed no significant association with loss-of-exercise capacity. In the multivariable logistic regression, older age (≥ 73 years) (odds ratio: 5.25, 95% confidence interval: 1.50-18.43, p = 0.010) and lower baseline diffusing capacity of the lung for carbon monoxide (< 75%) (odds ratio: 9.23, 95% confidence interval: 1.94-43.93, p = 0.005) were significantly associated with loss-of-exercise capacity. CONCLUSION: Age and the baseline diffusing capacity of the lung for carbon monoxide were identified as significant variables associated with variation of exercise capacity after lung cancer surgery, using pre- and postoperative SCt.

How Many Steps Per Day are Necessary to Prevent Postoperative Complications Following Hepato-Pancreato-Biliary Surgeries for Malignancy?

PURPOSE: The current study was designed to investigate the association between the average preoperative physical activity and postoperative outcomes in patients undergoing surgeries for hepato-pancreato-biliary (HPB) malignancy. METHODS: Patients who were scheduled to undergo open abdominal surgeries for HPB malignancies (major hepatectomy, pancreatoduodenectomy, or hepato-pancreatoduodenectomy) between 2016 and 2017 were included. The average steps per day were recorded by a pedometer and calculated for each patient during the preoperative waiting period. Physical activity levels were classified according to the average number of daily steps as poor (< 5000 steps/day) and good (≥ 5000 steps/day). RESULTS: Of the 105 eligible patients, 78 met the inclusion criteria. The median number of steps per day was 6174. There were 48 patients (62%) with good physical activity and 30 patients (38%) with poor physical activity. Patients with poor physical activity revealed a significantly higher rate of major complications with Clavien grade ≥ 3 (63% vs. 35%, p = 0.016), a higher rate of infectious complications (53% vs. 23%, p = 0.006), and a longer postoperative hospital stay (median, 30 vs. 21 days, p < 0.001) compared with those with good physical activity. After a multivariate analysis, poor physical activity was identified as an independent risk factor for the development of major complications (odds ratio, 2.842, p = 0.042) and infectious complications (odds ratio, 3.844, p = 0.007). CONCLUSIONS: The current study demonstrated that preoperative physical activity levels are associated with the incidence of major postoperative complications following HPB surgery for malignancy.

Evaluating the Content and Distribution of Trans Fatty Acid Isomers in Foods Consumed in Japan.

Trans fatty acids (TFA) are considered risk factors for cardiovascular disease. However, detailed information on total content of TFA and TFA isomers and distribution of trans-octadecenoic acid positional isomers in foods consumed in Japan is not available till date. In this study, 250 foods, 169 processed foods and 81 foods derived from ruminant meat or milk, were analyzed. According to the results, most foods contained less than 1.0 g TFA / 100 g food. However, almost all foods containing butter had more than 1.0 g TFA / 100 g food. TFA isomers in foods were classified into two categories, monoene-rich type and polyenerich type. We hypothesized that these differences were attributed to diverse TFA formation mechanisms. Furthermore, we observed that trans-10-18:1 was also the dominant trans-18:1 positional isomer in foods consumed in Japan. These results are valuable for future analysis of the role of TFA in epidemiological studies in Japan.

Clinical Benefit of Preoperative Exercise and Nutritional Therapy for Patients Undergoing Hepato-Pancreato-Biliary Surgeries for Malignancy.

BACKGROUND: The impact of prehabilitation on physical fitness and postoperative course after hepato-pancreato-biliary (HPB) surgeries for malignancy is unknown. The current study aimed to investigate the effect of preoperative exercise and nutritional therapies on nutritional status, physical fitness, and postoperative outcomes of patients undergoing an invasive HPB surgery for malignancy. METHODS: Patients who underwent open abdominal surgeries for HPB malignancies (major hepatectomy, pancreatoduodenectomy, or hepato-pancreatoduodenectomy) between 2016 and 2017 were subjected to prehabilitation. Patients before the introduction of prehabilitation were included as historical control subjects for 1:1 propensity score-matching (no-prehabilitation group). The preoperative nutritional status and postoperative course were compared between the two groups. RESULTS: The prehabilitation group consisted of 76 patients scheduled to undergo HPB surgeries for malignancy. An identical number of patients were selected as the no-prehabilitation group after propensity score-matching. During the waiting period, serum albumin levels were significantly deteriorated in the no-prehabilitation group, whereas this index did not deteriorate or even improved in the prehabilitation group. By performing prehabilitation, a 6-min walk distance and total muscle/fat ratio were significantly increased during the waiting period. Although the overall incidence of postoperative complications did not differ between the two groups, the postoperative hospital stay was shorter in the prehabilitation group than in the no-prehabilitation group (median, 23 vs 30 days; p = 0.045). CONCLUSION: The introduction of prehabilitation prevented nutritional deterioration, improved physical fitness before surgery, and shortened the postoperative hospital stay for the patients undergoing HPB surgeries for malignancy.

Changes in exercise capacity, muscle strength, and health-related quality of life in esophageal cancer patients undergoing esophagectomy.

BACKGROUND: Surgery for cancer of the thoracic esophagus is a challenging procedure associated with high morbidity and mortality. Perioperative rehabilitation has been introduced to promote early mobilization of the patients and to prevent postoperative pulmonary complications. The purpose of the present study was to characterize the preoperative functional exercise capacity, muscle strength, anxiety, depression, and health-related quality of life (QOL) in patients with esophageal cancer, and to evaluate the impact of radical esophagectomy on these parameters. METHODS: We performed a retrospective review of 34 consecutive patients with newly diagnosed resectable esophageal cancer who underwent esophagectomy followed by postoperative rehabilitation from January to December 2014. Patients were tested for 6-min walk distance (6MWD), knee-extensor muscle strength, hand grip strength, the Hospital Anxiety and Depression Scale (HADS), and the chronic obstructive pulmonary disease (COPD) assessment test (CAT) before and two weeks after the surgery. Before surgery, the pulmonary function test, and components of the MOS 36-item Short-Form Health Survey (SF-36) Questionnaire for general health were assessed. RESULTS: The mean age was 67.3 ± 8.1 years. The patients were predominantly male (76.4 %), had high rates of smoking history (91.2 %), and squamous cell carcinoma (97.1 %). The predicted value for forced expiratory volume in 1 s was 94.0 ± 15.9 %, and 12 patients (35.3 %) had COPD. The clinical stage was 0-I in 12 patients, II in 4 patients, III in 16 patients, and IV in 2 patients. Thirty-one patients (91.2 %) underwent open surgery. At the baseline, components of the SF-36 scores significantly correlated with CAT and HADS scores, and the physical status was significantly poorer in patients with COPD than those without. Comparisons between the preoperative and postoperative values revealed significant decreases in 6MWD, hand grip strength, isometric knee extensor muscle strength, and a significant increase in CAT scores but not in HADS scores after surgery. In multiple regression analysis, decreases in 6MWD after the surgery significantly correlated with the preoperative physical component summary of SF-36. CONCLUSIONS: Our results indicate that surgery remained detrimental to health outcomes at two weeks. Further research should investigate whether prehabilitation would improve the postoperative outcomes, QOL, and physical fitness.

Switching of actin isoforms in skeletal muscle differentiation using mouse ES cells.

Among six actin isoforms, alpha-skeletal and alpha-cardiac actins have similar amino acid components and are highly conserved. Although skeletal muscles essentially express alpha-skeletal actins in the adult tissue, alpha-cardiac isoform actin is prominent in the embryonic muscle tissue. Switching of actin isoforms from alpha-cardiac to alpha-skeletal actin occurs during skeletal muscle differentiation. The cardiac type alpha-actin is expressed in the regeneration and patho-physiological states of the skeletal muscles as well. In the present study, we demonstrate the morphological switching of alpha-type actin isoforms from alpha-cardiac to alpha-skeletal actin in vitro using mouse ES cells for the first time. Immunofluorescent double staining with two specific antibodies revealed that alpha-cardiac actin appeared first in myoblasts. After cell fusion to form myotubes, the cardiac type actin decreased and alpha-skeletal actin conversely increased. Finally, the alpha-skeletal isoform remained as a main actin component in the fully mature skeletal muscle fibers. The exchange of isoforms is not directly linked to the sarcomere formation. As a result, ES cells provide a useful in vitro system for exploring skeletal muscle differentiation.