George Malietzis - Academia.edu (original) (raw)

Papers by George Malietzis

International journal of colorectal disease, Jan 4, 2018

This study aims to determine whether traditional risk models can accurately predict morbidity and... more This study aims to determine whether traditional risk models can accurately predict morbidity and mortality in patients undergoing major surgery by colorectal surgeons within an enhanced recovery program. One thousand three hundred eighty patients undergoing surgery performed by colorectal surgeons in a single UK hospital (2008-2013) were included. Six risk models were evaluated: (1) Physiology and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM), (2) Portsmouth POSSUM (P-POSSUM), (3) ColoRectal (CR-POSSUM), (4) Elderly POSSUM (E-POSSUM), (5) the Association of Great Britain and Ireland (ACPGBI) score, and (6) modified Estimation of Physiologic Ability and Surgical Stress Score (E-PASS). Model accuracy was assessed by observed to expected (O:E) ratios and area under Receiver Operating Characteristic curve (AUC). Eleven patients (0.8%) died and 143 patients (10.4%) had a major complication within 30 days of surgery. All models overpredicted mortality a...

Neuro-Oncology, 2014

ABSTRACT BACKGROUND AND OBJECTIVES: ATRT is a highly malignant tumour associated with grim progno... more ABSTRACT BACKGROUND AND OBJECTIVES: ATRT is a highly malignant tumour associated with grim prognosis. There is currently no consensus on optimal treatment. High dose chemotherapy with stem-cell-rescue (HD-SCR) was introduced to consolidate and improve outcome. However its benefit remains unclear and controversial. The main objective of this systematic review was to evaluate the impact of HD-SCR on Progression Free Survival (PFS) and Overall Survival (OS). METHODS: A PubMed literature review was performed with MeSH term "atypical teratoid rhabdoid tumour". Reviews and articles including non CNS-rhabdoid tumors or adult patients were excluded. Age at diagnosis, extend of surgery, staging (M0/M+), treatment with intrathecal chemotherapy (IT), use of radiotherapy, use of HD-SCR were extracted. Individual authors were contacted to complete missing data. RESULTS: Overall 359 papers were identified. Twenty-eight met inclusion criteria and were further evaluated. Three hundred and thirty two patients were analysed. Median age at diagnosis was 37 months (1 -231). Median PFS and OS for all patients were respectively 18 months and 33 months. Data on HD-SCR were available for 203 patients. Fifty eight (28.5%) underwent HD-SCR using various regimen of chemotherapy. Multivariate Cox analysis showed a significant favourable HR for OS/PFS for patients who received HD-SCR (OS: 0.529 (0.331-0.845);p = 0.008; PFS: 0.613(0.406-0.927);p = 0,02). Radiotherapy did also significantly impact OS (HR: 0.403 (0.247-0.656;p < 0.001)) and PFS (HR: 0.640 (0.438-0.935;p = 0.021). Incomplete surgical resection had significant negative impact on OS with HR of 1.665 (1.057-2.623;p = 0.028), but not PFS. The use of IT did not impact significantly on OS with HR 0.555 (0.294-1.048;p = 0.069), but a trend was observed. CONCLUSION: This systematic review allowed analysing a large dataset of children with ATRT. Data suggests that patients with newly diagnosed ATRT may benefit fromHD-SCR. Surgery and use of radiation also seem to have impact on PFS/OS. Prospective randomised trials will be needed to confirm these findings.

Background: The role of adjuvant chemotherapy [AC] is established in stage III colorectal cancer.... more Background: The role of adjuvant chemotherapy [AC] is established in stage III colorectal cancer. A significant proportion of patients are suitable for adjuvant therapy based upon clinical and histopathology stage but a proportion do not proceed with therapy. High Pre-Operative Neutrophil to lymphocyte ratio (NLR) has been showed to be an independent negative prognostic marker for disease recurrence for patients with colorectal cancer (CRC). Can preoperative NLR also be an autonomous factor for patients to receive the AC? Materials and Methods: Retrospective observational study of a prospective database of patients diagnosed with stage III CRC undergoing elective curative resection, receiving AC from 2006 to 2011. Demographics, operative factors and postoperative outcomes data were collected. Univariate analysis for predictors of succeeding to transition to AC was used, followed by multivariate analysis to determine independent predictors. Factors including sex, age, type of operati...

Aim: Substantial treatment variation in adjuvant chemotherapy (AC) use for stage III colon cancer... more Aim: Substantial treatment variation in adjuvant chemotherapy (AC) use for stage III colon cancer exists. Myopenia is defined as clinically relevant muscle wasting due to any illness at any stage. Our objective was to evaluate the effect of myopenia upon transition to adjuvant therapy after colectomy for cancer. Method: Retrospective observational study of a prospective database of patients diagnosed with stage III CRC undergoing elective curative resection, eligible for AC from 2006 to 2013. Categories for low muscularity, normalised for stature, were based on a CT-based sarcopenic obesity study in cancer patients. Associations between myopenia, omission and delay (>8 weeks) in initiating adjuvant chemotherapy were assessed. Results: Three hundred and ninety-two patients were assessed; median age 67 years [IQR 58-77]. 64.2% (n = 251) had successful transition to AC [median 70 days [IQR 61-83]; 221 (88%) patients had a delay. Myopenic patients were much less likely to receive AC ...

Nigerian Journal of Clinical Practice, 2011

To evaluate the safety and efficacy of timolol 0.5%/travoprost 0.004% combination (duotrav) as ob... more To evaluate the safety and efficacy of timolol 0.5%/travoprost 0.004% combination (duotrav) as observed in primary open-angle glaucoma (POAG), ocular hypertension (OHT) and normal tension glaucoma (NTG) in real-life conditions. Patients with uncontrolled intraocular pressure (IOP) on other medication and no contraindication to β-blockers were switched to duotrav in 56 eyes of 28 patients. The drop in IOP was the primary outcome measured. Switch to duotrav provided an additional IOP reduction after 3-month follow-up that was statistically significant for those on latanoprost (P=0.02857), bimatoprost (P =0.04978) and travoprost (P =0.0078). Patients on latanotrost had an additional 25.9% drop 3 months after switching to duotrav while those on bimatoprost and travatan had 18.04% and 17.59% drop, respectively, after the switch. It was effective in lowering the IOP to clinically significant levels of ≤ 18.5 mmHg in POAG, NTG and OHT (12.5-17.9% drop), but not in chronic angle closure glaucoma. Duotrav was well-tolerated and produced significant additional IOP reduction when switched from other anti-glaucoma drugs in patients with uncontrolled glaucoma. It also achieved IOP of ≤ 18.5 mmHg in glaucoma patients.

British Journal of Radiology, 2013

High-intensity focused ultrasound (HIFU) is a rapidly maturing technology with diverse clinical a... more High-intensity focused ultrasound (HIFU) is a rapidly maturing technology with diverse clinical applications. In the field of oncology, the use of HIFU to non-invasively cause tissue necrosis in a defined target, a technique known as focused ultrasound surgery (FUS), has considerable potential for tumour ablation. In this article, we outline the development and underlying principles of HIFU, overview the limitations and commercially available equipment for FUS, then summarise some of the recent technological advances and experimental clinical trials that we predict will have a positive impact on extending the role of FUS in cancer therapy.

British Journal of Radiology, 2011

Interactive cardiovascular and thoracic surgery, Jan 11, 2016

Surgeons, as the consumers, must engage in commercial activity regarding medical devices since it... more Surgeons, as the consumers, must engage in commercial activity regarding medical devices since it directly has impacts on surgical practice and patient outcomes. Unique features defy traditional economic convention in this specific market partly because consumers do not usually pay directly. Greater involvement with commercial activity means better post-market surveillance of medical devices which leads to improved patient safety. The medical device industry has exhibited astonishing levels of growth and profitability reaching $398 billion on a global scale with new product development focusing on unmet clinical need. The industry has rapidly emerged within the context of an ageing population and a global surge in healthcare spending. But the market remains fragmented. The split of consumer, purchaser and payer leads to clinical need driving demand for new product development. This demand contributes to potentially large profit margins mainly contained by regulatory burden and liabi...

International journal of colorectal disease, Jan 26, 2016

Enhanced recovery after surgery (ERAS) is a well-established and accepted practice following colo... more Enhanced recovery after surgery (ERAS) is a well-established and accepted practice following colorectal surgery and has been demonstrated to reduce hospital length of stay (LOS) and 30-day morbidity. Despite evidence to support the individual elements on which the programme is based, there remains uncertainty as to how many and which of these are required to realise its benefits. Furthermore, elements of an ERAS programme might either precipitate or reflect recovery, in which case compliance could have a role in the improvement or prediction of outcome. A multidimensional prospective database of 799 consecutive patients undergoing colorectal surgery within an established ERAS programme at a single institution was interrogated. After application of exclusion criteria, 614 patients were studied. The novel concept of 'active compliance' is introduced. An ERAS element is classified as 'active' if the participation of the patient is required to achieve its compliance. Thi...

Annals of surgical oncology, Jan 22, 2016

Muscle depletion is a poor prognostic indicator in colorectal cancer (CRC) patients, but there we... more Muscle depletion is a poor prognostic indicator in colorectal cancer (CRC) patients, but there were no data assessing comparative temporal body composition changes following elective CRC surgery. We examined patient skeletal muscle index trajectories over time after surgery and determined factors that may contribute to those alterations. Patients diagnosed with CRC undergoing elective surgical resection between 2006 and 2013 were included in this study. Image analysis of serial computed tomography (CT) scans was used to calculate lumbar skeletal muscle index (LSMI). A multilevel mixed-effect linear regression model was applied using STATA (version 12.0) using the xtmixed command to fit growth curve models (GCM) for LSMI and time. In 856 patients, a total of 2136 CT images were analyzed; 856 (38.2 %) were preoperative. A quadratic GCM with random intercept and random slope for patients' LSMI was identified that demonstrated laparoscopy produces a positive change on the LSMI curve...

European Radiology, 2016

To review primary research evidence investigating performance of CT colonography for colorectal c... more To review primary research evidence investigating performance of CT colonography for colorectal cancer surveillance. The financial impact of using CT colonography for surveillance was also estimated. We identified primary studies of CT colonography for surveillance of colorectal cancer patients. A summary ROC curve was constructed. Inter-study heterogeneity was explored using the I2 value. Financial impact was estimated for a theoretical cohort of patients, based on Cancer Research UK statistics. Seven studies provided data on 880 patients. Five of seven studies (765 patients) were included for qualitative analysis. Sensitivity of CT colonography for detection of anastomotic recurrence was 95 % (95 % CI 62 - 100), specificity 100 % (95 % CI 75 - 100) and sensitivity for metachronous cancers was 100 %. No statistical heterogeneity was detected (I2 = 0 %). We estimated that CT colonography as a 'single test' alternative to colonoscopy and standard CT for surveillance would potentially save €20,785,232 (£14,803,404) for an annual cohort of UK patients. CT colonography compares favourably to colonoscopy for detection of anastomotic recurrence and metachronous colorectal cancer, and appears financially beneficial. These findings should be considered alongside limitations of small patient numbers and high clinical heterogeneity between studies. • CT colonography compares favourably to colonoscopy/standard CT for colorectal cancer surveillance. • CT colonography offers single-test luminal, serosal and extra-colonic assessment. • CT colonography is a potentially cost-saving alternative to standard surveillance protocols.

Tumor Biology, 2016

Dendritic cells (DCs) are antigen-presenting cells that can acquire tumour antigens and initiate ... more Dendritic cells (DCs) are antigen-presenting cells that can acquire tumour antigens and initiate cytotoxic T cell reactions. Obesity has been proposed as a cause for tumours escaping immune surveillance, but few studies investigate the impact of other body composition parameters. We examined the relationship of DC phenotype with computer tomography (CT)-defined parameters in patients with colorectal cancer (CRC). DCs were identified within peripheral blood mononuclear cells by flow cytometry as HLA-DR positive and negative for markers of other cell lineages in 21 patients. Analysis of CT scans was used to calculate lumbar skeletal muscle index (LSMI) and mean muscle attenuation (MA). Positive correlation between the LSMI and expression of CD40 in all DCs (r = 0.45; p = 0.04) was demonstrated. The MA was positively correlated with scavenger receptor CD36 [all DCs (r = 0.60; p = 0.01) and myeloid DCs (r = 0.63; p < 0.01)]. However, the MA was negatively correlated with CCR7 expression in all DCs (r = -0.46, p = 0.03.) and with CD83 [all DCs (r = -0.63; p = 0.01) and myeloid DCs (r = -0.75; p < 0.01)]. There were no relationships between the fat indexes and the DC phenotype. These results highlight a direct relationship between muscle depletion and changes in stimulatory, migratory and fatty acid-processing potential of DC in patients with CRC.

Annals of Surgery, 2016

The objectives of this systematic review and pooled analysis were to examine long-term survival, ... more The objectives of this systematic review and pooled analysis were to examine long-term survival, morbidity, and mortality following surgical resection of gastric cancer hepatic metastases and to identify prognostic factors that improve survival. Patients with hepatic metastases from gastric cancer are traditionally treated with palliative chemotherapy. A systematic literature search was undertaken (1990 to 2015). Publications were included if they studied more than 10 patients undergoing hepatectomy for hepatic metastasis from gastric adenocarcinoma in the absence of peritoneal disease or other distant organ involvement. The primary outcome was the hazard ratio (HR) for overall survival. The influence of liver metastasis related factors; multiple vs single and metachronous vs synchronous upon survival was also assessed. The median number of resections for the 39 studies included was 21 (range 10 to 64). Procedures were associated with a median 30-day morbidity of 24% (0% to 47%) and mortality of 0% (0% to 30%). The median 1-year, 3-year, and 5-year survival were 68%, 31%, and 27%, respectively. Survival was improved in Far Eastern compared with Western studies; 1-year (73% vs 59%), 3-year (34% vs 24.5%), and 5-year (27.3% vs 16.5%). Surgical resection of hepatic metastases was associated with a significantly improved overall survival (HR = 0.50; P < 0.001). Meta-analysis confirmed the additional survival benefit of solitary compared with multiple hepatic metastases (odds ratio = 0.31; P = 0.011). The observed improved survival rates following the resection of hepatic metastasis from gastric adenocarcinoma in selected patients merit a prospective study to formally address the survival benefits and the influence on quality of life of such approach.

European Journal of Cancer, 2014

ABSTRACT Background: Loss of lean muscle mass is a poor indicator in patients with cancer but the... more ABSTRACT Background: Loss of lean muscle mass is a poor indicator in patients with cancer but the underlying factors of myopenia remain unclear. Dendritic cells (DCs) are antigen presenting cells, can acquire tumour antigens and initiate cytotoxic T-cells reactions against tumour. Fat has been proposed as a cause for tumours escaping immune surveillance but very few studies investigates the impact of skeletal muscle mass. Our aim was to examine the relationship of skeletal muscle mass index on DC phenotype in patients with CRC. Materials and Methods: Peripheral blood mononuclear cells were obtained from CRC patients before surgical bowel resection. DC identified as HLADR positive and lineage (anti-CD3, CD14, CD16, CD19, CD34 and CD56) negative cells. DCs were further classified as CD11c+ myeloid (mDC) or CD11c− putative plasmacytoid. CD40, CD86 and CCR7 expression was determined on DC by flow-cytometry. Image analysis of CT scans was used to measure skeletal muscle area (cm2) and after normalisation for stature the corresponding index where calculated (cm2/m2). Relationships between variables were examined using Pearson correlation coefficients (r) as appropriate. P values of less than 0.05 were considered statistically significant. Results: 19 patients (12 males) were recruited for this study with median age of 69 (IQR 65−74) and 11 of them were sarcopenic. There were no relationships between the muscle mass index and markers of maturation (CD86) or migration (CCR7). However a significant positive correlation between the skeletal muscle index and both the expression of CD40 in all DCS (r = 0.115; p = 0.038) and mDCs (r = 0.200; p < 0.001) was demonstrated. Conclusion: These results highlight a direct relationship between low levels of skeletal muscle and the presence of reduced DCs activation expressed as CD40 in patients with operable colorectal cancer. Understanding what factors contribute to these may lead to novel and more effective interventions that support optimal body composition and metabolism, improving clinical and metabolic outcomes in cancer patients.

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland, Jan 11, 2015

Perineal sinus is a complication of radical pelvic surgery and excision of the tracks can lead to... more Perineal sinus is a complication of radical pelvic surgery and excision of the tracks can lead to substantial tissue loss[1]. Previous methods of providing tissue coverage used myofascial flaps 2], but these carried the risk of late incisional hernia formation. In this video, we describe some technical considerations in the use of a newer fasciocutaneous flap including the inferior gluteal artery perforator (IGAP) flap to cover tissue defects following colorectal surgery[3]. This article is protected by copyright. All rights reserved.

International journal of colorectal disease, Jan 4, 2018

This study aims to determine whether traditional risk models can accurately predict morbidity and... more This study aims to determine whether traditional risk models can accurately predict morbidity and mortality in patients undergoing major surgery by colorectal surgeons within an enhanced recovery program. One thousand three hundred eighty patients undergoing surgery performed by colorectal surgeons in a single UK hospital (2008-2013) were included. Six risk models were evaluated: (1) Physiology and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM), (2) Portsmouth POSSUM (P-POSSUM), (3) ColoRectal (CR-POSSUM), (4) Elderly POSSUM (E-POSSUM), (5) the Association of Great Britain and Ireland (ACPGBI) score, and (6) modified Estimation of Physiologic Ability and Surgical Stress Score (E-PASS). Model accuracy was assessed by observed to expected (O:E) ratios and area under Receiver Operating Characteristic curve (AUC). Eleven patients (0.8%) died and 143 patients (10.4%) had a major complication within 30 days of surgery. All models overpredicted mortality a...

Neuro-Oncology, 2014

ABSTRACT BACKGROUND AND OBJECTIVES: ATRT is a highly malignant tumour associated with grim progno... more ABSTRACT BACKGROUND AND OBJECTIVES: ATRT is a highly malignant tumour associated with grim prognosis. There is currently no consensus on optimal treatment. High dose chemotherapy with stem-cell-rescue (HD-SCR) was introduced to consolidate and improve outcome. However its benefit remains unclear and controversial. The main objective of this systematic review was to evaluate the impact of HD-SCR on Progression Free Survival (PFS) and Overall Survival (OS). METHODS: A PubMed literature review was performed with MeSH term "atypical teratoid rhabdoid tumour". Reviews and articles including non CNS-rhabdoid tumors or adult patients were excluded. Age at diagnosis, extend of surgery, staging (M0/M+), treatment with intrathecal chemotherapy (IT), use of radiotherapy, use of HD-SCR were extracted. Individual authors were contacted to complete missing data. RESULTS: Overall 359 papers were identified. Twenty-eight met inclusion criteria and were further evaluated. Three hundred and thirty two patients were analysed. Median age at diagnosis was 37 months (1 -231). Median PFS and OS for all patients were respectively 18 months and 33 months. Data on HD-SCR were available for 203 patients. Fifty eight (28.5%) underwent HD-SCR using various regimen of chemotherapy. Multivariate Cox analysis showed a significant favourable HR for OS/PFS for patients who received HD-SCR (OS: 0.529 (0.331-0.845);p = 0.008; PFS: 0.613(0.406-0.927);p = 0,02). Radiotherapy did also significantly impact OS (HR: 0.403 (0.247-0.656;p < 0.001)) and PFS (HR: 0.640 (0.438-0.935;p = 0.021). Incomplete surgical resection had significant negative impact on OS with HR of 1.665 (1.057-2.623;p = 0.028), but not PFS. The use of IT did not impact significantly on OS with HR 0.555 (0.294-1.048;p = 0.069), but a trend was observed. CONCLUSION: This systematic review allowed analysing a large dataset of children with ATRT. Data suggests that patients with newly diagnosed ATRT may benefit fromHD-SCR. Surgery and use of radiation also seem to have impact on PFS/OS. Prospective randomised trials will be needed to confirm these findings.

Background: The role of adjuvant chemotherapy [AC] is established in stage III colorectal cancer.... more Background: The role of adjuvant chemotherapy [AC] is established in stage III colorectal cancer. A significant proportion of patients are suitable for adjuvant therapy based upon clinical and histopathology stage but a proportion do not proceed with therapy. High Pre-Operative Neutrophil to lymphocyte ratio (NLR) has been showed to be an independent negative prognostic marker for disease recurrence for patients with colorectal cancer (CRC). Can preoperative NLR also be an autonomous factor for patients to receive the AC? Materials and Methods: Retrospective observational study of a prospective database of patients diagnosed with stage III CRC undergoing elective curative resection, receiving AC from 2006 to 2011. Demographics, operative factors and postoperative outcomes data were collected. Univariate analysis for predictors of succeeding to transition to AC was used, followed by multivariate analysis to determine independent predictors. Factors including sex, age, type of operati...

Aim: Substantial treatment variation in adjuvant chemotherapy (AC) use for stage III colon cancer... more Aim: Substantial treatment variation in adjuvant chemotherapy (AC) use for stage III colon cancer exists. Myopenia is defined as clinically relevant muscle wasting due to any illness at any stage. Our objective was to evaluate the effect of myopenia upon transition to adjuvant therapy after colectomy for cancer. Method: Retrospective observational study of a prospective database of patients diagnosed with stage III CRC undergoing elective curative resection, eligible for AC from 2006 to 2013. Categories for low muscularity, normalised for stature, were based on a CT-based sarcopenic obesity study in cancer patients. Associations between myopenia, omission and delay (>8 weeks) in initiating adjuvant chemotherapy were assessed. Results: Three hundred and ninety-two patients were assessed; median age 67 years [IQR 58-77]. 64.2% (n = 251) had successful transition to AC [median 70 days [IQR 61-83]; 221 (88%) patients had a delay. Myopenic patients were much less likely to receive AC ...

Nigerian Journal of Clinical Practice, 2011

To evaluate the safety and efficacy of timolol 0.5%/travoprost 0.004% combination (duotrav) as ob... more To evaluate the safety and efficacy of timolol 0.5%/travoprost 0.004% combination (duotrav) as observed in primary open-angle glaucoma (POAG), ocular hypertension (OHT) and normal tension glaucoma (NTG) in real-life conditions. Patients with uncontrolled intraocular pressure (IOP) on other medication and no contraindication to β-blockers were switched to duotrav in 56 eyes of 28 patients. The drop in IOP was the primary outcome measured. Switch to duotrav provided an additional IOP reduction after 3-month follow-up that was statistically significant for those on latanoprost (P=0.02857), bimatoprost (P =0.04978) and travoprost (P =0.0078). Patients on latanotrost had an additional 25.9% drop 3 months after switching to duotrav while those on bimatoprost and travatan had 18.04% and 17.59% drop, respectively, after the switch. It was effective in lowering the IOP to clinically significant levels of ≤ 18.5 mmHg in POAG, NTG and OHT (12.5-17.9% drop), but not in chronic angle closure glaucoma. Duotrav was well-tolerated and produced significant additional IOP reduction when switched from other anti-glaucoma drugs in patients with uncontrolled glaucoma. It also achieved IOP of ≤ 18.5 mmHg in glaucoma patients.

British Journal of Radiology, 2013

High-intensity focused ultrasound (HIFU) is a rapidly maturing technology with diverse clinical a... more High-intensity focused ultrasound (HIFU) is a rapidly maturing technology with diverse clinical applications. In the field of oncology, the use of HIFU to non-invasively cause tissue necrosis in a defined target, a technique known as focused ultrasound surgery (FUS), has considerable potential for tumour ablation. In this article, we outline the development and underlying principles of HIFU, overview the limitations and commercially available equipment for FUS, then summarise some of the recent technological advances and experimental clinical trials that we predict will have a positive impact on extending the role of FUS in cancer therapy.

British Journal of Radiology, 2011

Interactive cardiovascular and thoracic surgery, Jan 11, 2016

Surgeons, as the consumers, must engage in commercial activity regarding medical devices since it... more Surgeons, as the consumers, must engage in commercial activity regarding medical devices since it directly has impacts on surgical practice and patient outcomes. Unique features defy traditional economic convention in this specific market partly because consumers do not usually pay directly. Greater involvement with commercial activity means better post-market surveillance of medical devices which leads to improved patient safety. The medical device industry has exhibited astonishing levels of growth and profitability reaching $398 billion on a global scale with new product development focusing on unmet clinical need. The industry has rapidly emerged within the context of an ageing population and a global surge in healthcare spending. But the market remains fragmented. The split of consumer, purchaser and payer leads to clinical need driving demand for new product development. This demand contributes to potentially large profit margins mainly contained by regulatory burden and liabi...

International journal of colorectal disease, Jan 26, 2016

Enhanced recovery after surgery (ERAS) is a well-established and accepted practice following colo... more Enhanced recovery after surgery (ERAS) is a well-established and accepted practice following colorectal surgery and has been demonstrated to reduce hospital length of stay (LOS) and 30-day morbidity. Despite evidence to support the individual elements on which the programme is based, there remains uncertainty as to how many and which of these are required to realise its benefits. Furthermore, elements of an ERAS programme might either precipitate or reflect recovery, in which case compliance could have a role in the improvement or prediction of outcome. A multidimensional prospective database of 799 consecutive patients undergoing colorectal surgery within an established ERAS programme at a single institution was interrogated. After application of exclusion criteria, 614 patients were studied. The novel concept of 'active compliance' is introduced. An ERAS element is classified as 'active' if the participation of the patient is required to achieve its compliance. Thi...

Annals of surgical oncology, Jan 22, 2016

Muscle depletion is a poor prognostic indicator in colorectal cancer (CRC) patients, but there we... more Muscle depletion is a poor prognostic indicator in colorectal cancer (CRC) patients, but there were no data assessing comparative temporal body composition changes following elective CRC surgery. We examined patient skeletal muscle index trajectories over time after surgery and determined factors that may contribute to those alterations. Patients diagnosed with CRC undergoing elective surgical resection between 2006 and 2013 were included in this study. Image analysis of serial computed tomography (CT) scans was used to calculate lumbar skeletal muscle index (LSMI). A multilevel mixed-effect linear regression model was applied using STATA (version 12.0) using the xtmixed command to fit growth curve models (GCM) for LSMI and time. In 856 patients, a total of 2136 CT images were analyzed; 856 (38.2 %) were preoperative. A quadratic GCM with random intercept and random slope for patients' LSMI was identified that demonstrated laparoscopy produces a positive change on the LSMI curve...

European Radiology, 2016

To review primary research evidence investigating performance of CT colonography for colorectal c... more To review primary research evidence investigating performance of CT colonography for colorectal cancer surveillance. The financial impact of using CT colonography for surveillance was also estimated. We identified primary studies of CT colonography for surveillance of colorectal cancer patients. A summary ROC curve was constructed. Inter-study heterogeneity was explored using the I2 value. Financial impact was estimated for a theoretical cohort of patients, based on Cancer Research UK statistics. Seven studies provided data on 880 patients. Five of seven studies (765 patients) were included for qualitative analysis. Sensitivity of CT colonography for detection of anastomotic recurrence was 95 % (95 % CI 62 - 100), specificity 100 % (95 % CI 75 - 100) and sensitivity for metachronous cancers was 100 %. No statistical heterogeneity was detected (I2 = 0 %). We estimated that CT colonography as a 'single test' alternative to colonoscopy and standard CT for surveillance would potentially save €20,785,232 (£14,803,404) for an annual cohort of UK patients. CT colonography compares favourably to colonoscopy for detection of anastomotic recurrence and metachronous colorectal cancer, and appears financially beneficial. These findings should be considered alongside limitations of small patient numbers and high clinical heterogeneity between studies. • CT colonography compares favourably to colonoscopy/standard CT for colorectal cancer surveillance. • CT colonography offers single-test luminal, serosal and extra-colonic assessment. • CT colonography is a potentially cost-saving alternative to standard surveillance protocols.

Tumor Biology, 2016

Dendritic cells (DCs) are antigen-presenting cells that can acquire tumour antigens and initiate ... more Dendritic cells (DCs) are antigen-presenting cells that can acquire tumour antigens and initiate cytotoxic T cell reactions. Obesity has been proposed as a cause for tumours escaping immune surveillance, but few studies investigate the impact of other body composition parameters. We examined the relationship of DC phenotype with computer tomography (CT)-defined parameters in patients with colorectal cancer (CRC). DCs were identified within peripheral blood mononuclear cells by flow cytometry as HLA-DR positive and negative for markers of other cell lineages in 21 patients. Analysis of CT scans was used to calculate lumbar skeletal muscle index (LSMI) and mean muscle attenuation (MA). Positive correlation between the LSMI and expression of CD40 in all DCs (r = 0.45; p = 0.04) was demonstrated. The MA was positively correlated with scavenger receptor CD36 [all DCs (r = 0.60; p = 0.01) and myeloid DCs (r = 0.63; p < 0.01)]. However, the MA was negatively correlated with CCR7 expression in all DCs (r = -0.46, p = 0.03.) and with CD83 [all DCs (r = -0.63; p = 0.01) and myeloid DCs (r = -0.75; p < 0.01)]. There were no relationships between the fat indexes and the DC phenotype. These results highlight a direct relationship between muscle depletion and changes in stimulatory, migratory and fatty acid-processing potential of DC in patients with CRC.

Annals of Surgery, 2016

The objectives of this systematic review and pooled analysis were to examine long-term survival, ... more The objectives of this systematic review and pooled analysis were to examine long-term survival, morbidity, and mortality following surgical resection of gastric cancer hepatic metastases and to identify prognostic factors that improve survival. Patients with hepatic metastases from gastric cancer are traditionally treated with palliative chemotherapy. A systematic literature search was undertaken (1990 to 2015). Publications were included if they studied more than 10 patients undergoing hepatectomy for hepatic metastasis from gastric adenocarcinoma in the absence of peritoneal disease or other distant organ involvement. The primary outcome was the hazard ratio (HR) for overall survival. The influence of liver metastasis related factors; multiple vs single and metachronous vs synchronous upon survival was also assessed. The median number of resections for the 39 studies included was 21 (range 10 to 64). Procedures were associated with a median 30-day morbidity of 24% (0% to 47%) and mortality of 0% (0% to 30%). The median 1-year, 3-year, and 5-year survival were 68%, 31%, and 27%, respectively. Survival was improved in Far Eastern compared with Western studies; 1-year (73% vs 59%), 3-year (34% vs 24.5%), and 5-year (27.3% vs 16.5%). Surgical resection of hepatic metastases was associated with a significantly improved overall survival (HR = 0.50; P < 0.001). Meta-analysis confirmed the additional survival benefit of solitary compared with multiple hepatic metastases (odds ratio = 0.31; P = 0.011). The observed improved survival rates following the resection of hepatic metastasis from gastric adenocarcinoma in selected patients merit a prospective study to formally address the survival benefits and the influence on quality of life of such approach.

European Journal of Cancer, 2014

ABSTRACT Background: Loss of lean muscle mass is a poor indicator in patients with cancer but the... more ABSTRACT Background: Loss of lean muscle mass is a poor indicator in patients with cancer but the underlying factors of myopenia remain unclear. Dendritic cells (DCs) are antigen presenting cells, can acquire tumour antigens and initiate cytotoxic T-cells reactions against tumour. Fat has been proposed as a cause for tumours escaping immune surveillance but very few studies investigates the impact of skeletal muscle mass. Our aim was to examine the relationship of skeletal muscle mass index on DC phenotype in patients with CRC. Materials and Methods: Peripheral blood mononuclear cells were obtained from CRC patients before surgical bowel resection. DC identified as HLADR positive and lineage (anti-CD3, CD14, CD16, CD19, CD34 and CD56) negative cells. DCs were further classified as CD11c+ myeloid (mDC) or CD11c− putative plasmacytoid. CD40, CD86 and CCR7 expression was determined on DC by flow-cytometry. Image analysis of CT scans was used to measure skeletal muscle area (cm2) and after normalisation for stature the corresponding index where calculated (cm2/m2). Relationships between variables were examined using Pearson correlation coefficients (r) as appropriate. P values of less than 0.05 were considered statistically significant. Results: 19 patients (12 males) were recruited for this study with median age of 69 (IQR 65−74) and 11 of them were sarcopenic. There were no relationships between the muscle mass index and markers of maturation (CD86) or migration (CCR7). However a significant positive correlation between the skeletal muscle index and both the expression of CD40 in all DCS (r = 0.115; p = 0.038) and mDCs (r = 0.200; p < 0.001) was demonstrated. Conclusion: These results highlight a direct relationship between low levels of skeletal muscle and the presence of reduced DCs activation expressed as CD40 in patients with operable colorectal cancer. Understanding what factors contribute to these may lead to novel and more effective interventions that support optimal body composition and metabolism, improving clinical and metabolic outcomes in cancer patients.

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland, Jan 11, 2015

Perineal sinus is a complication of radical pelvic surgery and excision of the tracks can lead to... more Perineal sinus is a complication of radical pelvic surgery and excision of the tracks can lead to substantial tissue loss[1]. Previous methods of providing tissue coverage used myofascial flaps 2], but these carried the risk of late incisional hernia formation. In this video, we describe some technical considerations in the use of a newer fasciocutaneous flap including the inferior gluteal artery perforator (IGAP) flap to cover tissue defects following colorectal surgery[3]. This article is protected by copyright. All rights reserved.