Circulating myostatin as a biomarker of muscle mass and strength in individuals with cancer or obesity.

BACKGROUND & AIMS: Our study aims to determine whether myostatin (MSTN) is associated with muscle mass and strength in individuals with cancer or obesity, as well as with cancer cachexia (CC) or sarcopenic obesity (SO). METHODS: The ACTICA study included individuals with CC (n = 70) or without CC (NC, n = 73). The MYDIASECRET study included individuals with obesity evaluated before (T0) and 3 months (T3) after bariatric surgery (n = 62). Body composition was assessed using bioelectrical impedance analysis (BIA). Skeletal muscle mass (SMM) and appendicular SMM (ASMM) were calculated from Janssen's and Sergi's equations, respectively, and expressed as indexes (SMMI and ASMMI). Handgrip strength (HGS) was assessed using a Jamar hand-held dynamometer. MSTN plasma levels were measured using ELISA. Spearman's coefficient was used to correlate MSTN with muscle mass and strength. Receiver operating characteristic (ROC) curve analysis was performed to identify an optimal MSTN cutoff level for the prediction of CC or SO. RESULTS: In the ACTICA study, muscle mass and strength were lower in CC individuals than in NC individuals (SMMI: 8.0 kg/m2vs 9.0 kg/m2, p = 0.004; ASMMI: 6.2 kg/m2vs 7.2 kg/m2, p < 0.001; HGS: 28 kg vs 38 kg, p < 0.001). MSTN was also lower in CC individuals than in NC individuals (1434 pg/mL vs 2149 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN (SMMI: R = 0.500, p < 0.001; ASMMI: R = 0.479, p < 0.001; HGS: R = 0.495, p < 0.001). ROC curve analysis showed a MSTN cutoff level of 1548 pg/mL (AUC 0.684, sensitivity 57%, specificity 75%, p < 0.001) for the prediction of CC. In the MYDIASECRET study, muscle mass and strength were reduced at T3 (SMMI: -8%, p < 0.001; ASMMI: -12%, p < 0.001; HGS: -6%, p = 0.005). MSTN was also reduced at T3 (1773 pg/mL vs 2582 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN at T0 and T3 (SMMI-T0: R = 0.388, p = 0.002; SMMI-T3: R = 0.435, p < 0.001; HGS-T0: R = 0.337, p = 0.007; HGS-T3: R = 0.313, p = 0.013). ROC curve analysis showed a MSTN cutoff level of 4225 pg/mL (AUC 0.835, sensitivity 98%, specificity 100%, p = 0.014) for the prediction of SO at T3. CONCLUSIONS: MSTN is positively correlated with muscle mass and strength in individuals with cancer or obesity, suggesting its potential use as a biomarker of muscle mass and strength. The ROC curve analysis suggests the potential use of MSTN as a screening tool for CC and SO.

Long-term follow-up after retrosternal ileocolic esophagoplasty in two cases of long-gap esophageal atresia: why it is still a valid option as a rescue strategy.

Introduction: Esophageal replacement surgery in children is sometimes necessary for long-gap esophageal atresia. Ileocolic esophagoplasty in the retrosternal space can serve as a good alternative technique in case of hostile posterior mediastinum. We present two cases of successful ileocolic transposition performed at 6 months of age. Methods: Esophageal replacement was performed through a midline laparotomy incision associated with a left cervical approach. The ileocolic transplant was pediculized on the right superior colic artery after ligating the right colic and ileocolic vessels. A retrosternal tunnel was created, and the ileocolic transplant pulled through it to reach the cervical region. Proximally, esophageal-ileal anastomosis and, distally, colonic-gastric anastomosis were performed. Ileocolic continuity was repaired. Results: There were no early postoperative complications. In both cases, the patients presented oral feeding difficulties during the first 6 postoperative months. Thereafter, full oral feeding was achieved, and both patients were clinically asymptomatic during the following 18 and 20 years, respectively, with satisfactory oral radiological assessments, showing no redundancy or inappropriate growth of the graft and no anastomotic stricture. Currently, these patients do not complain of dysphagia, pathological reflux, or respiratory symptoms. Conclusion: When native esophagus preservation in long-gap esophageal atresia is estimated unfeasible, ileocolic transposition in the retrosternal space might be considered a good and safe option, particularly in those difficult cases after multiple previous surgical attempts and mediastinitis. This technique is putatively associated with a beneficial anti-reflux effect, thanks to the presence of the ileocecal valve, in preventing cervical peptic esophagitis. Long-term follow-up confirms that the transposed colon in the retrosternal space did not suffer any abnormal modification in size and growth.

Identification of myokines susceptible to improve glucose homeostasis after bariatric surgery.

IMPORTANCE AND OBJECTIVE: The identification of myokines susceptible to improve glucose homeostasis following bariatric surgery could lead to new therapeutic approaches for type 2 diabetes. METHODS: Changes in the homeostasis model assessment (HOMA) test were assessed in patients before and 3 months after bariatric surgery. Changes in myokines expression and circulating levels were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Myokines known to regulate glucose homeostasis were identified using literature (targeted study) and putative myokines using RNA-sequencing (untargeted study). A linear regression analysis adjusted for age and sex was used to search for associations between changes in the HOMA test and changes in myokines. RESULTS: In the targeted study, brain-derived neurotrophic factor (BDNF) expression was upregulated (+30%, P = .006) while BDNF circulating levels were decreased (-12%, P = .001). Upregulated BDNF expression was associated with decreased HOMA of insulin resistance (HOMA-IR) (adjusted estimate [95% confidence interval {CI}]: -0.51 [-0.88 to -0.13], P = .010). Decreased BDNF serum levels were associated with decreased HOMA of beta-cell function (HOMA-B) (adjusted estimate [95% CI] = 0.002 [0.00002-0.0031], P = .046). In the untargeted study, upregulated putative myokines included XYLT1 (+64%, P < .001), LGR5 (+57, P< .001), and SPINK5 (+46%, P < .001). Upregulated LGR5 was associated with decreased HOMA-IR (adjusted estimate [95% CI] = -0.50 [-0.86 to -0.13], P = .009). Upregulated XYLT1 and SPINK5 were associated with increased HOMA of insulin sensitivity (HOMA-S) (respectively, adjusted estimate [95% CI] = 109.1 [28.5-189.8], P = .009 and 16.5 [0.87-32.19], P = .039). CONCLUSIONS: Improved glucose homeostasis following bariatric surgery is associated with changes in myokines expression and circulating levels. In particular, upregulation of BDNF, XYLT1, SPINK5, and LGR5 is associated with improved insulin sensitivity. These results suggest that these myokines could contribute to improved glucose homeostasis following bariatric surgery. STUDY REGISTRATION: NCT03341793 on ClinicalTrials.gov (https://clinicaltrials.gov/).

Distalization of Standard Roux-en-Y Gastric Bypass: Indications, Technique, and Long-Term Results.

INTRODUCTION: Weight loss failure or weight regain after primary Roux-en-Y gastric bypass (RYGB) is a challenge for bariatric surgeons. Failure to achieve a body mass index (BMI) <35 kg/m2 after RYGB occurs in up to 40.0%. The aim of this study was to evaluate long-term results of a novel technique for distalization of Roux-en-Y gastric bypass (DRYGB) as a revisional procedure. METHODS: Retrospective data were reviewed for 22 patients who had undergone RYGB and failed to achieve an excess weight loss (EWL) >50% or BMI <35 kg/m2 and underwent limb distalization between 2013 and 2022. For this DRYGB procedure, the length of the common channel was 100 cm, and the lengths of the biliopancreatic limb and the alimentary limb were 1/3 and 2/3 of the remaining bowel, respectively. RESULTS: The mean BMI values before and after DRYGB were 43.7 kg/m2 and 33.5 kg/m2, respectively. Five years after DRYGB, mean % EWL was 74.3% and mean % total weight loss (TWL) was 28.8%. Mean % EWL and mean % TWL of the two procedures (RYGB and DRYGB) after 5 years were 80.9% and 44.7%, respectively. Three patients experienced protein calorie malnutrition. One was reproximalized and the others were treated with parenteral nutrition with no recurrence. There was a significant decrease in the incidence of diabetes type 2 and dyslipidemia after DRYGB. CONCLUSION: The DRYGB procedure results in substantial and sustained long-term weight loss. Due to the risk of malnutrition, patients must be strictly followed for life after the procedure.

A Population-Based Study Using Belgian Cancer Registry Data Supports Centralization of Esophageal Cancer Surgery in Belgium.

BACKGROUND: Esophageal cancer surgery outcomes benefit from higher hospital volumes. Despite the evidence, organization of national health care often is complex and depends on various factors. The volume-outcome results of this population-based study supported national health policy measures regarding concentration of esophageal resections in Belgium. METHODS: The Belgian Cancer Registry (BCR) database was linked to administrative data on cancer treatment. All Belgian patients with newly diagnosed esophageal cancer in 2008-2018 undergoing resection were allocated to the hospital at which surgery was performed. The study assessed hospital volume association with 90-day mortality and 5-year overall survival, classifying average annual hospital volume of resections as low (LV, <6), medium (MV, 6-19), or high (HV, ≥20) and as a continuous covariate in the regression models. RESULTS: The study included 4156 patients who had surgery in 79 hospitals (2 HV hospitals [37% of all surgeries], 12 MV hospitals [30% of all surgeries], and 65 LV hospitals [33% of all surgeries]). Adjusted 90-day mortality in HV hospitals was lower than in LV hospitals (odds ratio [OR], 0.37; 95% CI, 0.21-0.65; p = 0.001). Case-mix adjusted 5-year survival was superior in HV versus LV (hazard ratio [HR], 0.43; 95% CI, 0.31-0.60; p < 0.001). The continuous model demonstrated a lower 90-day mortality (OR, 0.40; 95% CI, 0.23-0.71; p = 0.002) and a superior 5-year survival (HR, 0.45; 95% CI, 0.33-0.63; p < 0.001) in hospitals with volumes of 40 or more resections annually. CONCLUSION: Population-based data from the BCR confirmed a strong volume-outcome association for esophageal resections. Improved 5-year survival in centers with annual volumes of 20 or more resections was driven mainly by the achievement of superior 90-day mortality. These findings supported centralization of esophageal resections in Belgium.

Esophageal Cancer in Elderly Patients, Current Treatment Options and Outcomes; A Systematic Review and Pooled Analysis.

Esophageal cancer, despite its tendency to increase among younger patients, remains a disease of the elderly, with the peak incidence between 70-79 years. In spite of that, elderly patients are still excluded from major clinical trials and they are frequently offered suboptimal treatment even for curable stages of the disease. In this review, a clear survival benefit is demonstrated for elderly patients treated with neoadjuvant treatment, surgery, and even definitive chemoradiation compared to palliative or no treatment. Surgery in elderly patients is often associated with higher morbidity and mortality compared to younger patients and may put older frail patients at increased risk of autonomy loss. Definitive chemoradiation is the predominant modality offered to elderly patients, with very promising results especially for squamous cell cancer, although higher rates of acute toxicity might be encountered. Based on the all the above, and although the best available evidence comes from retrospective studies, it is not justified to refrain from curative treatment for elderly patients based on their age alone. Thorough assessment and an adapted treatment plan as well as inclusion of elderly patients in ongoing clinical trials will allow better understanding and management of esophageal cancer in this heterogeneous and often frail population.

What are the impact and the optimal design of a physical prehabilitation program in patients with esophagogastric cancer awaiting surgery? A systematic review.

BACKGROUND: Substantial postoperative complications occur after tumor resection for esophagogastric cancers. Physical prehabilitation programs aim to prepare patients for surgery by improving their functional status with the aim of reducing postoperative complications. This systematic review aims to summarize the effects of physical prehabilitation programs on exercise capacity, muscle strength, respiratory muscle function, postoperative outcomes, and health-related quality of life and to determine the optimal design of such a program to improve these outcomes in esophagogastric cancer patients undergoing tumor resection. METHODS: A systematic literature review was conducted using PubMed, The Cochrane Library, Scopus, and PEDro databases to identify studies evaluating the effects of physical prehabilitation program on exercise capacity, muscle strength, respiratory muscle function, postoperative complications, length of hospital stay, mortality, and health-related quality of life in patients with esophagogastric cancer awaiting surgery. Data from all studies meeting the inclusion criteria were extracted. The quality of each selected study was determined using the Downs and Black checklist. RESULTS: Seven studies with 645 participants were included. The preoperative exercise program consisted of respiratory training alone in three studies, a combination of aerobic and resistance training in two studies, and a combination of respiratory, aerobic, and resistance training in two studies. Training frequency ranged from three times a day to twice a week and each session lasted between 20 and 75 min. Four studies were of fair quality and three of good quality. Some studies reported improvements in maximal inspiratory pressure, inspiratory muscle endurance, postoperative (pulmonary) complications, and length of hospital stay in the preoperative exercise group compared to the control group. CONCLUSION: This systematic review reports the current evidence for physical prehabilitation programs in patients with esophagogastric cancer awaiting surgery. However, due to the limited number of randomized controlled trials, the significant heterogeneity of exercise programs, and the questionable quality of the studies, higher quality randomized controlled trials are needed. TRIAL REGISTRATION: PROSPERO Registration Number: CRD42020176353 .

Feasibility and Preliminary Effectiveness of a Tele-Prehabilitation Program in Esophagogastric Cancer Patients.

Tele-rehabilitation provides better access to healthcare services and optimizes exercise adherence. However, its feasibility and effectiveness are unknown in the preoperative period in esophagogastric cancer patients. We aimed to assess the feasibility and the preliminary effects of a "tele-prehabilitation" program in esophagogastric cancer patients requiring surgery. Enrolled participants performed an internet-based tele-prehabilitation including aerobic, resistance and inspiratory muscle training over 2-4 weeks. The primary outcome was feasibility, measured in terms of recruitment, retention and attendance rates, adverse events and patient satisfaction. Secondary outcomes (functional exercise capacity, fatigue, quality of life, anxiety and depression) were assessed at baseline, presurgery, and 4 and 12 weeks postsurgery. Among the 24 eligible subjects, 23 were enrolled, 22 performed the intervention and 15 completed the study. Recruitment and retention rates were both 96%. Attendances to aerobic and resistance sessions and inspiratory muscle training were 77% and 68%, respectively. No adverse events occurred, and the satisfaction was excellent. After prehabilitation, participants significantly improved fatigue (p = 0.039), quality of life (p = 0.009), physical well-being (p = 0.034), emotional well-being (p = 0.005) and anxiety (p = 0.044). This study demonstrated the feasibility of a tele-prehabilitation in esophagogastric cancer patients undergoing surgery, with a high recruitment rate, retention rate and satisfaction, a good attendance to exercise sessions and no exercise-related adverse events.

Unusual Management of Thoracic Aortic Injury After Spinal Instrumentation: Just Glue It!

We report the cases of two patients who presented with screw misplacement following spinal surgery. Both benefited from unusual vascular surgical management with removal of the material and injection of biological glue facing the injury, with uneventful postoperative courses.

Herniation of an abdominal antireflux fundoplication into the chest: what does it mean?

OBJECTIVES: The specific contribution of the herniation of an abdominal antireflux fundoplication into the chest to symptomatic and therefore surgical failure remains unclear. METHODS: The study was conducted in 189 consecutive fundoplication patients, categorized as patients reoperated on for chest herniation of either an abdominal 360° (Group 1; n = 95) or a partial (Group 2; n = 10) fundoplication, and patients having undergone an intrathoracic 360° fundoplication for short oesophagus (Group 3; n = 84; reference group). There were four subgroups in Group 1: 1A: wrap still complete and perioesophageal; 1B: wrap still complete but perigastric; 1C: wrap still perioesophageal but partially disrupted and 1D: wrap perigastric and partially disrupted. RESULTS: The prevalence of defective symptoms (heartburn and regurgitation) was significantly lower (P < 0.0001) in Group 3 (0.0%) and Subgroup 1A (3.7%) than in Subgroups 1B (84.4%), 1C (86.7%) and 1D (100%) and Group 2 (100%). The prevalence of obstructive symptoms (dysphagia, chest pain, necrosis and perforation) was significantly higher (P < 0.0001) in Subgroup 1A (100%) than in Subgroups 1B (57.8%), 1C (60.0%) and 1D (25.0%). The prevalence of a short oesophagus, an abdominal wall hernia repair and high abdominal pressure episodes in reoperated patients were 13.7, 36.2 and 67.2%, respectively. CONCLUSIONS: Unlike perigastric or partial fundoplication, a 360° perioesophageal abdominal fundoplication, when herniated into the chest, is still effective against reflux. Obstructive symptoms are due to either diaphragmatic strangulation or perigastric migration of the wrap (slipknot effect). Short oesophagus, weakness of the abdominal wall and high abdominal pressure episodes favour the herniation process.