Targeting Mitochondria and Oxidative Stress in Cancer- and Chemotherapy-Induced Muscle Wasting.

Significance: Cancer is frequently associated with the early appearance of cachexia, a multifactorial wasting syndrome. If not present at diagnosis, cachexia develops either as a result of tumor progression or as a side effect of anticancer treatments, especially of standard chemotherapy, eventually representing the direct cause of death in up to one-third of all cancer patients. Cachexia, within its multiorgan affection, is characterized by severe loss of muscle mass and function, representing the most relevant subject of preclinical and clinical investigation. Recent Advances: The pathogenesis of muscle wasting in cancer- and chemotherapy-induced cachexia is complex, and encompasses heightened protein catabolism and reduced anabolism, disrupted mitochondria and energy metabolism, and even neuromuscular junction dismantling. The mechanisms underlying these alterations are still controversial, especially concerning the molecular drivers that could be targeted for anticachexia therapies. Inflammation and mitochondrial oxidative stress are among the principal candidates; the latter being extensively discussed in the present review. Critical Issues: Several approaches have been tested to modulate the redox homeostasis in tumor hosts, and to counteract cancer- and chemotherapy-induced muscle wasting, from exercise training to distinct classes of direct or indirect antioxidants. We herein report the most relevant results obtained from both preclinical and clinical trials. Future Directions: Including the assessment and the treatment of altered redox balance in the clinical management of cancer patients is still a big challenge. The available evidence suggests that fortifying the antioxidant defenses by either pharmacological or nonpharmacological strategies will likely improve cachexia and eventually the outcome of a broad cancer patient population. Antioxid. Redox Signal. 38, 352-370.

The Italian version of the LARS score: cross-cultural adaptation and validation. An Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CCN) collaborative study.

PURPOSE: The LARS score is an internationally well-accepted questionnaire to assess low anterior resection syndrome, but currently there is no formally validated Italian version. The purpose of this study was to test the reliability and validity of the Italian version among Italian patients submitted to sphincter-sparing surgery for rectal cancer. METHODS: The English version of the LARS score was translated into Italian following the forward-and-back translation process. A total of 147 patients filled out our version. Among them, 40 patients answered the questionnaire twice for the test-retest reliability phase. The validity of the LARS score was tested using convergent and discriminant validity indicators by correlating the EORTC QLQ-C30 and QLQ-CR29 questionnaires. The LARS score capability to differentiate groups of patients with different demographic or clinical features was also assessed. RESULTS: The test-retest reliability was excellent in 87.5% of patients, remained in the same LARS category in both tests. The convergent validity phase showed a relevant relationship of the LARS score with the EORTC domains, which was significant for 7 of 15 EORTC QLQ-C30 subscales, and for 14 of 29 EORTC QLQ-CR29 subscales. The LARS score was able to discriminate patients who received radiotherapy (p = 0.0026), TME vs. PME (p = 0.0060), tumour site at < 10 cm from the anal verge (p = 0.0030) and history of protective stoma (p < 0.0001). CONCLUSION: The Italian version of the LARS score is a valid and reliable tool for measuring LARS in Italian patients after SSS for rectal cancer.

Upper GI training of young surgeons: a reality full of hurdles. An international survey.

OBJECTIVE: Anecdotal evidence suggests that the training of young surgeons in Upper GI is not homogeneous across the world. This survey aimed to investigate the different training programs and the level of satisfaction of young surgeons with their surgical and scientific education pathway. DESIGN: A multiple-choice and single best answer format questionnaire was sent to 36 Upper GI chairs from international referral centres and then forwarded to young surgeons (attending physician less than 40 years old). The same questionnaire containing 5 main topics (demographics, residency, fellowship, academic research and activities, manual skill improvement) was posted online on a Surveymonkey website. SETTING: San Luigi University Hospital, Orbassano (Turin), Italy; Tertiary University Hospital. RESULTS: Fourteen replies were received from colleagues in 36 referral centres (39% response rate) and 65 voluntary answers from the survey monkey platform. During residency training, only 43% of residents had a specific training in upper GI tract surgery, which was characterized by a small number of interventions performed both with trainer scrubbed and unscrubbed. Fellowship programmes were undertaken by 49% of participants and 64% spent this training period abroad. Operative experience was reported by nearly all respondents with only 27% performing > 10 gastrectomies and only 11% performing > 10 oesophagectomies with the trainer scrubbed. The majority attended less than 10 meetings (58%), and 70% of them published less than 5 papers. CONCLUSIONS: The present survey reveals that the young surgeons of the twenty-first century face many hurdles during their surgical training. Overall, the surgical education settings are limited for both practical and scientific training for upper GI trainees. As a result, it is not possible to train in upper GI surgery to a level of competent independent practice.

Resección hepática mayor: una cirugía segura y eficaz / Hepatic resection: a safe and effective surgery

Introducción: Se analizan las resecciones hepáticas mayores realizadas en 10 años, con el objetivo principal de evaluar los resultados perioperatorios. Como objetivos secundarios, se evalúan los factores relacionados con las complicaciones mayores y el análisis comparativo de 2 periodos de 5 años. Métodos: Análisis retrospectivo de pacientes intervenidos mediante una resección hepática mayor (3 o más segmentos) desde enero de 2005 hasta diciembre de 2014, de los datos pre-, intra- y postoperatorios. Se utiliza la clasificación de Clavien para el análisis de la morbilidad postoperatoria. Resultados: Se realizaron 416 hepatectomías mayores, con necesidad de transfusión en 38 pacientes (9,1%) y maniobra de Pringle en el 47,7% de los casos. La mitad de los pacientes no presentaron ninguna complicación y únicamente 96 pacientes (23%) presentaron una complicación mayor. La fuga biliar fue la complicación más frecuente (n = 72; 17,3% de los pacientes), sobre todo, por enfermedad maligna y derivación biliar, con ASA elevado (III-IV) y tiempo quirúrgico prolongado. Trece pacientes cumplían criterios de insuficiencia hepática, de los cuales 7 murieron (5 asociaban sobreinfección bacteriana). La estancia hospitalaria media fue de 12,5 días, con una tasa de reingreso del 11,8%. Al comparar 2 periodos de 5 años, se operan pacientes más complejos, con menor incidencia de transfusiones y de complicaciones (ns). Conclusiones: La cirugía hepática ha aumentado de forma significativa en los últimos años. El manejo quirúrgico del hígado permite en la actualidad ofrecer una cirugía segura y eficaz, con un índice de complicaciones muy bajo. El límite de la resecabilidad viene marcado por el volumen hepático residual (AU)

Introduction: We analyze major liver resections performed in 10 years, with the objective of evaluating perioperative results. As secondary objectives, factors related to major complications and comparative analyses of 2 5-year periods are evaluated. Methods: Retrospective analysis of patients undergoing major hepatic resection (3 or more segments) from January 2005 to December 2014, from pre, intra and postoperative data. The Clavien classification is used for postoperative morbidity. Results: A total of 416 major hepatectomies were performed. Transfusions were performed in 38 patients (9.1%). A Pringle maneuver was used in 47.7% of the cases. Half of the patients had no complications, and only 96 patients (23%) had a major complication. Bile leakage was the most frequent complication (n = 72, 17.3% of patients), especially due to malignant disease and biliary reconstruction, high risk ASA (III-IV) and prolonged surgical time. Thirteen patients met criteria for liver failure, of which 7died (5 associated a bacterial infection). The mean hospital stay was 12.5 days, with an 11,8% readmission rate. When comparing 25-year periods, at present more complex patients are operated on, with a lower incidence of transfusions and complications (ns). Conclusions: Liver surgery has increased significantly in recent years. Surgical management of the liver now allows safe and effective surgery, with a very low complication rate. The limit of resectability depends on the residual hepatic volume (AU)

Hepatic resection: a safe and effective surgery. / Resección hepática mayor: una cirugía segura y eficaz.

INTRODUCTION: We analyze major liver resections performed in 10 years, with the objective of evaluating perioperative results. As secondary objectives, factors related to major complications and comparative analyses of 25-year periods are evaluated. METHODS: Retrospective analysis of patients undergoing major hepatic resection (3 or more segments) from January 2005 to December 2014, from pre, intra and postoperative data. The Clavien classification is used for postoperative morbidity. RESULTS: A total of 416 major hepatectomies were performed. Transfusions were performed in 38 patients (9.1%). A Pringle maneuver was used in 47.7% of the cases. Half of the patients had no complications, and only 96 patients (23%) had a major complication. Bile leakage was the most frequent complication (n=72, 17.3% of patients), especially due to malignant disease and biliary reconstruction, high risk ASA (III-IV) and prolonged surgical time. Thirteen patients met criteria for liver failure, of which 7died (5 associated a bacterial infection). The mean hospital stay was 12.5 days, with an 11,8% readmission rate. When comparing 25-year periods, at present more complex patients are operated on, with a lower incidence of transfusions and complications (ns). CONCLUSIONS: Liver surgery has increased significantly in recent years. Surgical management of the liver now allows safe and effective surgery, with a very low complication rate. The limit of resectability depends on the residual hepatic volume.