A systematic review of the impact of postoperative aerobic exercise training in patients undergoing surgery for intra-abdominal cancers.

INTRODUCTION: Enhanced recovery after surgery (ERAS) programmes which advocate early mobility after surgery have improved immediate clinical outcomes for patients undergoing abdominal cancer resections with curative intent. However, the impact of continued physical activity on patient-related outcomes and functional recovery is not well defined. The aim of this review was to assess the impact of postoperative aerobic exercise training, either alone or in conjunction with another exercise modality, on patients who have had surgery for intra-abdominal cancer. METHODS: A literature search was performed of electronic journal databases. Eligible papers needed to report an outcome of aerobic capacity in patients older than 18 years of age, who underwent cancer surgery with curative intent and participated in an exercise programme (not solely ERAS) that included an aerobic exercise component starting at any point in the postoperative pathway up to 12 weeks. RESULTS: Eleven studies were deemed eligible for inclusion consisting of two inpatient, one mixed inpatient/outpatient and eight outpatient studies. Meta-analysis of four outpatient studies, each reporting change in 6-min walk test (6MWT), showed a significant improvement in 6MWT with exercise (MD 74.92 m, 95% CI 48.52-101.31 m). The impact on health-related quality of life was variable across studies. CONCLUSION: Postoperative exercise confers benefits in improving aerobic function post surgery and can be safely delivered in various formats (home-based or group/supervised).

Long-acting PGE2 and Lisinopril Mitigate H-ARS.

Thrombocytopenia is a major complication in hematopoietic-acute radiation syndrome (H-ARS) that increases the risk of mortality from uncontrolled hemorrhage. There is a great demand for new therapies to improve survival and mitigate bleeding in H-ARS. Thrombopoiesis requires interactions between megakaryocytes (MKs) and endothelial cells. 16, 16-dimethyl prostaglandin E2 (dmPGE2), a longer-acting analogue of PGE2, promotes hematopoietic recovery after total-body irradiation (TBI), and various angiotensin-converting enzyme (ACE) inhibitors mitigate endothelial injury after radiation exposure. Here, we tested a combination therapy of dmPGE2 and lisinopril to mitigate thrombocytopenia in murine models of H-ARS following TBI. After 7.75 Gy TBI, dmPGE2 and lisinopril each increased survival relative to vehicle controls. Importantly, combined dmPGE2 and lisinopril therapy enhanced survival greater than either individual agent. Studies performed after 4 Gy TBI revealed reduced numbers of marrow MKs and circulating platelets. In addition, sublethal TBI induced abnormalities both in MK maturation and in in vitro and in vivo platelet function. dmPGE2, alone and in combination with lisinopril, improved recovery of marrow MKs and peripheral platelets. Finally, sublethal TBI transiently reduced the number of marrow Lin-CD45-CD31+Sca-1- sinusoidal endothelial cells, while combined dmPGE2 and lisinopril treatment, but not single-agent treatment, accelerated their recovery. Taken together, these data support the concept that combined dmPGE2 and lisinopril therapy improves thrombocytopenia and survival by promoting recovery of the MK lineage, as well as the MK niche, in the setting of H-ARS.

Trainee-led emergency laparotomy operating.

BACKGROUND: To achieve completion of training in general surgery, trainees are required to demonstrate competency in common procedures performed at emergency laparotomy. The aim of this study was to describe the patterns of trainee-led emergency laparotomy operating and the association between postoperative outcomes. METHODS: Data on all patients who had an emergency laparotomy between December 2013 and November 2017 were extracted from the National Emergency Laparotomy Audit database. Patients were grouped by grade of operating surgeon: trainee (specialty registrar) or consultant (including post-Certificate of Completion of Training fellows). Trends in trainee operating by deanery, hospital size and time of day of surgery were investigated. Univariable and adjusted regression analyses were performed for the outcomes 90-day mortality and return to theatre, with analysis of patients in operative subgroups segmental colectomy, Hartmann's procedure, adhesiolysis and repair of perforated peptic ulcer disease. RESULTS: The study cohort included 87 367 patients. The 90-day mortality rate was 15·1 per cent in the consultant group compared with 11·0 per cent in the trainee group. There were no increased odds of death by 90 days or of return to theatre across any of the operative groups when the operation was performed with a trainee listed as the most senior surgeon in theatre. Trainees were more likely to operate independently in high-volume centres (highest- versus lowest-volume centres: odds ratio (OR) 2·11, 95 per cent c.i. 1·91 to 2·33) and at night (00.00 to 07.59 versus 08.00 to 11.59 hours; OR 3·20, 2·95 to 3·48). CONCLUSION: There is significant variation in trainee-led operating in emergency laparotomy by geographical area, hospital size and by time of day. However, this does not appear to influence mortality or return to theatre.

ANTECEDENTES: Para completar la formación en cirugía general, se requiere que los aspirantes demuestren solvencia en la práctica de los procedimientos comunes efectuados por laparotomía de urgencia. El objetivo de este estudio fue describir los esquemas de formación de los aspirantes en laparotomía de urgencia y su asociación con los resultados postoperatorios. MÉTODOS: Todos los pacientes a los que se realizó una laparotomía de urgencia entre diciembre del 2013 y noviembre del 2017 se obtuvieron a partir de la base de datos de la Auditoría Nacional de Laparotomía de Urgencia (National Emergency Laparotomy Audit, NELA). Los pacientes se agruparon según la experiencia del cirujano; cirujanos en periodo de formación (residentes, speciality registrar) o consultores (incluyendo los que habían completado la especialidad). Se investigaron las tendencias entre los residentes por universidad, tamaño del hospital y hora del día de la cirugía. Se realizaron análisis de regresión univariable y ajustados para la mortalidad a los 90 días y la reoperación, así como análisis de subgrupos para los procedimientos quirúrgicos de colectomía segmentaria, intervención de Hartmann, liberación de bridas y la sutura de una úlcera péptica perforada. RESULTADOS: La cohorte de estudio incluyó 87.367 pacientes. La mortalidad a los 90 días en el grupo de consultores fue del 15% en comparación con el 11% en el grupo de residentes. No hubo aumento del riesgo de mortalidad a los 90 días o de reoperación en ninguno de los subgrupos de las diferentes operaciones cuando la cirugía era efectuada por el residente considerado como el más senior en las listas de quirófano. Los residentes tenían más probabilidades de operar solos en centros de alto volumen (en comparación con centros de bajo volumen; razón de oportunidades, odds ratio (OR) 2,11, i.c. del 95% 1,91-2,33) o durante la noche (00:00-07:59 horas en comparación con 08:00-11:59; OR 3,20; i.c. del 95% 2,95-3,48). CONCLUSIÓN: Existen diferencias significativas en la formación que reciben los residentes en laparotomía de urgencia según el área geográfica, el tamaño del hospital y la hora del día. Sin embargo, estas diferencias no parecen afectar a la mortalidad ni a la tasa de reoperaciones.

High-intensity interval training produces a significant improvement in fitness in less than 31 days before surgery for urological cancer: a randomised control trial.

OBJECTIVES: To assess the efficacy of high-intensity interval training (HIIT) for improving cardiorespiratory fitness (CRF) in patients awaiting resection for urological malignancy within four weeks. SUBJECTS/PATIENTS AND METHODS: A randomised control trial of consecutive patients aged (>65 years) scheduled for major urological surgery in a large secondary referral centre in a UK hospital. The primary outcome is change in anaerobic threshold (VO2AT) following HIIT vs. standard care. RESULTS: Forty patients were recruited (mean age 72 years, male (39): female (1)) with 34 completing the protocol. Intention to treat analysis showed significant improvements in anaerobic threshold (VO2AT; mean difference (MD) 2.26 ml/kg/min (95% CI 1.25-3.26)) following HIIT. Blood pressure (BP) also significantly reduced in following: HIIT (SBP: -8.2 mmHg (95% CI -16.09 to -0.29) and DBP: -6.47 mmHg (95% CI -12.56 to -0.38)). No reportable adverse safety events occurred during HIIT and all participants achieved >85% predicted maximum heart rate during sessions, with protocol adherence of 84%. CONCLUSIONS: HIIT can improve CRF and cardiovascular health, representing clinically meaningful and achievable pre-operative improvements. Larger randomised trials are required to investigate the efficacy of prehabilitation HIIT upon different cancer types, post-operative complications, socio-economic impact and long-term survival.

Delay in Source Control in Perforated Peptic Ulcer Leads to 6% Increased Risk of Death Per Hour: A Nationwide Cohort Study.

BACKGROUND: Delay to theatre for patients with intra-abdominal sepsis is cited as a particular risk factor for death. Our aim was to evaluate the potential relationship between hourly delay from admission to surgery and post-operative mortality in patients with perforated peptic ulcer (PPU). METHODS: All patients entered in the National Emergency Laparotomy Audit who had an emergency laparotomy for PPU within 24 h of admission from December 2013 to November 2017 were included. Time to theatre from admission was modelled as a continuous variable in hours. Outcome was 90-day mortality. Logistic regression adjusting for confounding factors was performed. RESULTS: 3809 patients were included, and 90-day mortality rate was 10.61%. Median time to theatre was 7.5 h (IQR 5-11.6 h). The odds of death increased with time to operation once adjustment for confounding variables was performed (per hour after admission adjusted OR 1.04 95% CI 1.02-1.07). In patients who were physiologically shocked (N = 334), there was an increase of 6% in risk-adjusted odds of mortality for every hour Em Lap was delayed after admission (OR 1.06 95% CI 1.01-1.11). CONCLUSION: Hourly delay to theatre in patients with PPU is independently associated with risk of death by 90 days. Therefore, we suggest that surgical source control should occur as soon as possible after admission regardless of time of day.

Long-term outcomes of biological mesh repair following extra levator abdominoperineal excision of the rectum: an observational study of 100 patients.

BACKGROUND: Current evidence suggests that pelvic floor reconstruction following extralevator abdominoperineal excision of rectum (ELAPER) may reduce the risk of perineal herniation of intra-abdominal contents. Options for reconstruction include mesh and myocutaneous flaps, for which long-term follow-up data is lacking. The aim of this study was to evaluate the long-term outcomes of biological mesh (Surgisis®, Biodesign™) reconstruction following ELAPER. METHODS: A retrospective review of all patients having ELAPER in a single institution between 2008 and 2018 was perfomed. Clinic letters were scrutinised for wound complications and all available cross sectional imaging was reviewed to identify evidence of perineal herniation (defined as presence of intra-abdominal content below a line between the coccyx and the lower margin of the pubic symphysis on sagittal view). RESULTS: One hundred patients were identified (median age 66, IQR 59-72 years, 70% male). Median length of follow-up was 4.9 years (IQR 2.3-6.7 years). One, 2- and 5-year mortality rates were 3, 8 and 12%, respectively. Thirty three perineal wounds had not healed by 1 month, but no mesh was infected and no mesh needed to be removed. Only one patient developed a symptomatic perineal hernia requiring repair. On review of imaging a further 7 asymptomatic perineal hernias were detected. At 4 years the cumulative radiologically detected perineal hernia rate was 8%. CONCLUSIONS: This study demonstrates that pelvic floor reconstruction using biological mesh following ELAPER is both safe and effective as a long-term solution, with low major complication rates. Symptomatic perineal herniation is rare following mesh reconstruction, but may develop sub clinically and be detectable on cross-sectional imaging.

Association between surgeon special interest and mortality after emergency laparotomy.

BACKGROUND: Approximately 30 000 emergency laparotomies are performed each year in England and Wales. Patients with pathology of the gastrointestinal tract requiring emergency laparotomy are managed by general surgeons with an elective special interest focused on either the upper or lower gastrointestinal tract. This study investigated the impact of special interest on mortality after emergency laparotomy. METHODS: Adult patients having emergency laparotomy with either colorectal or gastroduodenal pathology were identified from the National Emergency Laparotomy Audit database and grouped according to operative procedure. Outcomes included all-cause 30-day mortality, length of hospital stay and return to theatre. Logistic and Poisson regression were used to analyse the association between consultant special interest and the three outcomes. RESULTS: A total of 33 819 patients (28 546 colorectal, 5273 upper gastrointestinal (UGI)) were included. Patients who had colorectal procedures performed by a consultant without a special interest in colorectal surgery had an increased adjusted 30-day mortality risk (odds ratio (OR) 1·23, 95 per cent c.i. 1·13 to 1·33). Return to theatre also increased in this group (OR 1·13, 1·05 to 1·20). UGI procedures performed by non-UGI special interest surgeons carried an increased adjusted risk of 30-day mortality (OR 1·24, 1·02 to 1·53). The risk of return to theatre was not increased (OR 0·89, 0·70 to 1·12). CONCLUSION: Emergency laparotomy performed by a surgeon whose special interest is not in the area of the pathology carries an increased risk of death at 30 days. This finding potentially has significant implications for emergency service configuration, training and workforce provision, and should stimulate discussion among all stakeholders.

Quick and simple; psoas density measurement is an independent predictor of anastomotic leak and other complications after colorectal resection.

BACKGROUND: Radiologically defined sarcopenia has been shown to predict negative outcomes after cancer surgery, however radiological assessment of sarcopenia often requires additional software and standardisation against anthropomorphic data. Measuring psoas density using hospital Picture Archiving and Communication Systems (PACS), universally available in the UK, may have advantages over methods requiring the use of additional specialist and often costly software. The aim of this study was to assess the association between radiologically defined sarcopenia measured by psoas density and postoperative outcome in patients having a colorectal cancer resection. METHODS: All patients having a resection for colorectal cancer, discussed by the colorectal multi-disciplinary team in one institution between 1/1/15 and 31/12/15, were retrospectively identified. Mean psoas density at the level of the L3 vertebra was analysed from preoperative computed tomography (CT) scans to define sarcopenia using the Picture Archiving and Communication Systems (PACS). Postoperative complications and mortality were recorded. RESULTS: One hundred and sixty-nine patients had a colorectal resection for cancer and 140 of these had a primary anastomosis. Ninety-day mortality and 1-year mortality were 1.1% and 7.1%, respectively. Eighteen (10.7%) patients suffered a Clavien-Dindo grade 3 or 4 complication of which 6 (33%) were anastomotic leaks. In the whole cohort, sarcopenia was associated with an increased risk of Clavien-Dindo grade 3 or 4 complications [adjusted OR 6.33 (1.65-24.23) p = 0.007]. In those who had an anastomosis, sarcopenia was associated with an increased risk of anastomotic leak [adjusted OR 14.37 (1.37-150.04) p = 0.026]. CONCLUSIONS: A quick and easy radiological assessment of sarcopenia by measuring psoas density on preoperative CT scan using software universally available in the UK is highly predictive of postoperative morbidity in colorectal cancer patients.

EGFR-Stat3 signalling in nerve glial cells modifies neurofibroma initiation.

Neurofibromatosis type 1 (NF1) is an inherited disease in which affected patients are predisposed to develop benign Schwann cell (SC) tumours called neurofibromas. In the mouse, loss of Nf1 in the SC lineage causes neurofibroma formation. The tyrosine kinase receptor EGFR is expressed in Schwann cell precursors (SCP), which have been implicated in plexiform neurofibroma initiation. To test if EGFR activity affects neurofibroma initiation, size, and/or number, we studied mice expressing human EGFR in SCs and SCP in the context of mice that form neurofibromas. Neurofibroma number increased in homozygous CNP-hEGFR mice versus heterozygous littermates, and neurofibroma number and size increased when CNP-hEGFR was crossed to Nf1fl/fl;DhhCre mice. Conversely, diminished EGFR signalling in Nf1fl/fl;DhhCre;Wa2/+ mice decreased neurofibroma number. In vivo transplantation verified the correlation between EGFR activity and neurofibroma formation. Mechanistically, expression of CNP-hEGFR increased SCP/neurofibroma-initiating cell self-renewal, a surrogate for tumour initiation, and activated P-Stat3. Further, Il-6 reinforced Jak2/Stat3 activation in SCPs and SCs. These gain- and loss-of function assays show that levels of tyrosine kinase expression in SCPs modify neurofibroma initiation.

A 31-day time to surgery compliant exercise training programme improves aerobic health in the elderly.

BACKGROUND: Over 41,000 people were diagnosed with colorectal cancer (CRC) in the UK in 2011. The incidence of CRC increases with age. Many elderly patients undergo surgery for CRC, the only curative treatment. Such patients are exposed to risks, which increase with age and reduced physical fitness. Endurance-based exercise training programmes can improve physical fitness, but such programmes do not comply with the UK, National Cancer Action Team 31-day time-to-treatment target. High-intensity interval training (HIT) can improve physical performance within 2-4 weeks, but few studies have shown HIT to be effective in elderly individuals, and those who do employ programmes longer than 31 days. Therefore, we investigated whether HIT could improve cardiorespiratory fitness in elderly volunteers, age-matched to a CRC population, within 31 days. METHODS: This observational cohort study recruited 21 healthy elderly participants (8 male and 13 female; age 67 years (range 62-73 years)) who undertook cardiopulmonary exercise testing before and after completing 12 sessions of HIT within a 31-day period. RESULTS: Peak oxygen consumption (VO2 peak) (23.9 ± 4.7 vs. 26.2 ± 5.4 ml/kg/min, p = 0.0014) and oxygen consumption at anaerobic threshold (17.86 ± 4.45 vs. 20.21 ± 4.11 ml/kg/min, p = 0.008) increased after HIT. CONCLUSIONS: It is possible to improve cardiorespiratory fitness in 31 days in individuals of comparable age to those presenting for CRC surgery.

Systematic review of pre-operative exercise in colorectal cancer patients.

The aim of this systematic review was to evaluate the evidence for exercise interventions prior to surgery for colorectal cancer resection. The evidence for use of exercise to improve physical fitness and surgical outcomes is as yet unknown. A systematic search was performed of MEDLINE, EMBASE, CINAHL, AMED and BNI databases for studies involving pre-operative exercise in colorectal cancer patients. Eight studies were included in the review. There is evidence that pre-operative exercise improves functional fitness, and to a lesser extent objectively measurable cardio-respiratory fitness prior to colorectal cancer resection. There is no clear evidence at present that this improvement in fitness translates into reduced peri-operative risk or improved post-operative outcomes. Current studies are limited by risk of bias. This review highlights the common difficulty in transferring promising results in a research setting, into significant improvements in the clinical arena. Future research should focus on which type of exercise is most likely to maximise patient adherence and improvements in cardio-respiratory fitness. Ultimately, adequately powered, randomised controlled trials are needed to investigate whether pre-operative exercise improves post-operative morbidity and mortality.

A systematic review and meta-regression analysis of prophylactic gabapentin for postoperative pain.

We searched MEDLINE, Embase, CINAHL, AMED and CENTRAL databases until December 2014 and included 133 randomised controlled trials of peri-operative gabapentin vs placebo. Gabapentin reduced mean (95% CI) 24-h morphine-equivalent consumption by 8.44 (7.26-9.62) mg, p < 0.001, whereas more specific reductions in morphine equivalents were predicted (R(2)  = 90%, p < 0.001) by the meta-regression equation: 3.73 + (-0.378 × control morphine consumption (mg)) + (-0.0023 × gabapentin dose (mg)) + (-1.917 × anaesthetic type), where 'anaesthetic type' is '1' for general anaesthesia and '0' for spinal anaesthesia. The type of surgery was not independently associated with gabapentin effect. Gabapentin reduced postoperative pain scores on a 10-point scale at 1 h, 2 h, 6 h, 12 h and 24 h by a mean (95% CI) of: 1.68 (1.35-2.01); 1.21 (0.88-1.55); 1.28 (0.98-1.57); 1.12 (0.91-1.33); and 0.71 (0.56-0.87), respectively, p < 0.001 for all. The risk ratios (95% CI) for postoperative nausea, vomiting, pruritus and sedation with gabapentin were: 0.78 (0.69-0.87), 0.67 (0.59-0.76), 0.64 (0.51-0.80) and 1.18 (1.09-1.28), respectively, p < 0.001 for all. Gabapentin reduced pre-operative anxiety and increased patient satisfaction on a 10-point scale by a mean (95% CI) of 1.52 (0.78-2.26) points and 0.89 (0.22-1.57) points, p < 0.001 and p = 0.01, respectively. All the effects of gabapentin may have been overestimated by statistically significant small study effects.

Ionizing radiation induces myofibroblast differentiation via lactate dehydrogenase.

Pulmonary fibrosis is a common and dose-limiting side-effect of ionizing radiation used to treat cancers of the thoracic region. Few effective therapies are available for this disease. Pulmonary fibrosis is characterized by an accumulation of myofibroblasts and excess deposition of extracellular matrix proteins. Although prior studies have reported that ionizing radiation induces fibroblast to myofibroblast differentiation and collagen production, the mechanism remains unclear. Transforming growth factor-ß (TGF-ß) is a key profibrotic cytokine that drives myofibroblast differentiation and extracellular matrix production. However, its activation and precise role in radiation-induced fibrosis are poorly understood. Recently, we reported that lactate activates latent TGF-ß through a pH-dependent mechanism. Here, we wanted to test the hypothesis that ionizing radiation leads to excessive lactate production via expression of the enzyme lactate dehydrogenase-A (LDHA) to promote myofibroblast differentiation. We found that LDHA expression is increased in human and animal lung tissue exposed to ionizing radiation. We demonstrate that ionizing radiation induces LDHA, lactate production, and extracellular acidification in primary human lung fibroblasts in a dose-dependent manner. We also demonstrate that genetic and pharmacologic inhibition of LDHA protects against radiation-induced myofibroblast differentiation. Furthermore, LDHA inhibition protects from radiation-induced activation of TGF-ß. We propose a profibrotic feed forward loop, in which radiation induces LDHA expression and lactate production, which can lead to further activation of TGF-ß to drive the fibrotic process. These studies support the concept of LDHA as an important therapeutic target in radiation-induced pulmonary fibrosis.

Forming a consensus opinion on exercise prehabilitation in elderly colorectal cancer patients: a Delphi study.

BACKGROUND: There is no consensus amongst colorectal surgeons as to whether preoperative exercise is beneficial in the management of colorectal cancer patients. Research has shown higher rates of postoperative complications in patients who are less fit. Agreement needs to be sought on whether improving fitness via exercise should be a part of preoperative care. The Delphi process is an iterative process designed to refine opinions on a subject, until consensus agreement is reached within an expert group. METHODS: We performed a Delphi survey with a group of consultant colorectal surgeons. Statements achieving >80% agreement were taken as consensus, those achieving >80% disagreement were removed, and those in between were revised in the following round. The process ended with a group of statements which achieved consensus. RESULTS: Thirty-two statements were included in the first round of the survey. After three rounds of the survey, 21 statements were accepted as consensus, six statements were rejected, and seven statements did not reach consensus. It was agreed that exercise training should form part of preoperative care and would be supported by surgeons. That suitable programmes pose significant risk to patients was rejected. There was no consensus reached on the strength of current available evidence or whether it would be possible to deliver exercise programmes. CONCLUSIONS: This work is the first to produce a set of statements on which expert consensus opinion has been agreed regarding preoperative exercise in colorectal cancer patients. Future work, informed by this study, will design interventions to produce rapid improvements in fitness before surgery.

Day-case closure of ileostomy: feasible, safe and efficient.

AIM: Over 5000 loop ileostomy closures were performed in the UK in 2013 with a median inpatient stay of 5 days. Previously we have successfully implemented a 23-h protocol for loop ileostomy closure which was modified for same-day discharge. We present our early experience of day-case loop ileostomy closure. METHOD: A specific patient pathway for day-case discharge following loop ileostomy closure was implemented with inclusion criteria to conform with British Association of Day Surgery guidelines. Exclusion criteria included postoperative chemoradiotherapy, multiple comorbidities and social care needs. Follow-up consisted of telephone contact (24 and 72 h after discharge) and a routine outpatient appointment. Patients were provided with a 24-h contact point in case of emergency. RESULTS: Fifteen (12 male) patients were enrolled of median age 67 (39-80) years. The median operating time was 41 (23-80) min. The indication for ileostomy formation was to cover a low anterior resection for adenocarcinoma (13), reversal of Hartmann's procedure (1) and functional bowel disorder (1). The median interval from the primary procedure to day-case loop ileostomy closure was 8 (3-14) months. Every patient was discharged on the day of surgery. There were no complications related to the surgery and there was one readmission due to a urinary tract infection. The median length of follow-up was 4 (2-16) months. CONCLUSION: Our early experience shows that day-case loop ileostomy closure is feasible, safe and efficient. This protocol will become standard within our institution for suitable patients, saving on average five inpatient bed days per patient.

Simple psoas cross-sectional area measurement is a quick and easy method to assess sarcopenia and predicts major surgical complications.

AIM: Radiologically assessed muscle mass has been suggested as a surrogate marker of functional status and frailty and may predict patients at risk of postoperative complications. We hypothesize that sarcopenia negatively impacts on postoperative recovery and is predictive of complications. METHOD: One hundred patients undergoing elective resection for colorectal carcinoma were included in this study. Lean muscle mass was estimated by measuring the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra identified on a preoperative CT scan, normalizing for patient height. Perioperative morbidity was scored according to the Clavien-Dindo classification. All statistical data analyses were carried out using the Statistical Package for the Social Sciences (SPSS) version 20.0. RESULTS: Fifteen per cent of patients were identified as sarcopenic. There were no deaths in the study group. Sarcopenia was associated with a significantly increased risk of developing major complications (Grade 3 or greater, OR = 5.41, 95% CI: 1.45-20.15, P = 0.01). Sarcopenia did not predict length of stay, critical care dependency or time to mobilization. CONCLUSION: Sarcopenia, as a marker of frailty, is an important risk factor in surgical patients but difficult to estimate using bedside testing. CT scans, performed for preoperative staging, provide an opportunity to quantify lean muscle mass without additional cost or exposure to radiation and eliminate the inconvenience of further investigations.

Assessing surgeon stress when operating using heart rate variability and the State Trait Anxiety Inventory: will surgery be the death of us?

AIM: Performance in the operating room is affected by a combination of individual, patient and environmental factors amongst others. Stress has a potential negative impact on performance with the quality of surgical practice and patient safety being affected as a result. In order to appreciate the level of stress encountered during surgical procedures both objective and subjective methods can be used. This study reports the use of a combined objective (physiological) and subjective (psychological) method for evaluating stress experienced by the operating surgeon. METHOD: Six consultant colorectal surgeons were evaluated performing eighteen anterior resections. Heart rate was recorded using a wireless chest strap at eight pre-determined operative steps. Heart Rate Variability indices were calculated offline using computerized software. Surgeon reported stress was collected using the State Trait Anxiety Inventory, a validated clinical stress scale. RESULTS: A significant increase in stress was demonstrated in all surgeons whilst operating as indicated by sympathetic tone (control: 4.02 ± 2.28 vs operative: 11.42 ± 4.63; P < 0.0001). Peaks in stress according to operative step were comparable across procedures and surgeons. There was a significant positive correlation with subjective reporting of stress across procedures (r = 0.766; P = 0.0005). CONCLUSION: This study demonstrates a significant increase in sympathetic tone in consultant surgeons measured using heart rate variability during elective colorectal resections. A significant correlation can be demonstrated between HRV measurements and perceived stress using the State Trait Anxiety Inventory. A combined approach to assessing operative stress is required to evaluate any effect on performance and outcomes.

One-third of patients fail to return to work 1 year after surgery for colorectal cancer.

BACKGROUND: Achieving full recovery after colorectal cancer surgery means a return to normal physical and psychological health and to a normal social life. Recovery data focusses on time to discharge rather than longer term functionality including return to work (RTW). We aim to assess return to normal holistic function at 1 year after colorectal cancer surgery. METHOD: Questionnaires were created and dispatched to 204 patients who had undergone surgery with curative intent for colorectal cancer, in 2011-2012, in a single teaching hospital. RESULTS: Response rate was 75 % (153/204), 82 % (129/157) for open surgery (OS) and 51 % (24/47) for laparoscopic surgery (LS). Median age was 68 (48-91) years for OS and 65 (36-84) for LS. Eighty-four per cent of patients felt 'ready' and 95 % had adequate pain control upon discharge (no difference between groups). LS reported earlier 'return to full fitness' (1-3 months) than OS (>6 months; Mann-Whitney U, p < 0.05). Recovery from LS was 'better than expected' compared to OS 'worse than expected' (Mann-Whitney U test, p < 0.05). Forty-nine patients were employed preoperatively and 61 % (n = 30) returned to work. RTW was more frequent after LS (Chi-square test, p < 0.05). Length of time to RTW was significantly less after LS [44 (6-84) days] than OS [71 (14-252) days] (t test, p < 0.05). Levels of self-employment were equal between groups. CONCLUSIONS: One-third of patients failed to RTW at 1 year post-surgery. Patients having LS returned to full fitness faster, felt recovery was shorter and returned to work earlier than OS. We must invest more in managing expectations and provide better post-discharge support to improve RTW.

MAF mediates crosstalk between Ras-MAPK and mTOR signaling in NF1.

Mutations in the neurofibromatosis type 1 (NF1) tumor suppressor gene are common in cancer and can cause resistance to therapy. Using transcriptome analysis we identified MAF as an NF1- regulated transcription factor and verified MAF regulation through RAS/MAPK/AP-1 signaling in malignant peripheral nerve sheath tumor (MPNST) cell lines. MAF was also downregulated in human MPNST. Acute re-expression of MAF promoted expression of glial differentiation markers in MPNST cells in vitro, decreased self-renewal of embryonic precursors and transiently affected tumor cell phenotypes in vitro by increasing MPNST cell death and reducing metabolic activity and anchorage-independent growth. Paradoxically, chronic MAF overexpression enhanced MPNST cell tumor growth in vivo, correlating with elevated pS6 in vitro and in vivo. RAD001 blocked MAF-mediated tumor growth, and MAF regulated the mTOR pathway through DEPTOR. MAPK inhibition with NF1 loss of function is predicted to show limited efficacy due to reactivation of mTOR signaling via MAF.