ABSTRACT
AIM: Surgery for complex colorectal cancer is elaborate: preoperative assessment, patient selection, radiological interpretation, operative strategy, operative technical skills, operative standardization, postoperative care and management of complications are all critical components. Given this complexity, training that encompasses all these crucial aspects to generate suitably edified surgeons is essential. To date, no curriculum exists to guide training in advanced and recurrent pelvic malignancy, particularly for complex colorectal cancer. Such a curriculum would potentially offer numerous advantages, not only for individual surgeons but also for research, governance, international collaboration and benchmarking. The aim of this study was to design and develop a framework for a curriculum for fellowship training in complex colorectal cancer that encompasses pelvic exenteration surgery. METHOD: Kern described a six-step method for curriculum design that is now widely adopted in medical education. Our study utilizes steps 1-4 of Kern's method to develop a syllabus and assessment framework for curriculum development for fellowship training in complex colorectal cancer encompassing pelvic exenteration. A literature review was conducted to address step 1, followed by targeted needs assessment in step 2 by conducting focus groups with trainees, fellows and experts to identify learning needs and goals with objective setting for step 3. An expert consensus group then voted on these recommendations and developed educational strategy recommendations as step 4. For the purposes of brevity, 'pelvic exenteration' in the text is taken to also encompass extended and multivisceral resections that fall under the remit of complex [colorectal] cancer. RESULTS: Step 1 of Kern's method identified a gap in the literature on curricula in complex cancer surgery. Step 2 identified key areas regarded as learning needs by trainees, including anatomy, hands-on experience and case volume. Step 3 defined the goals and objectives of a fellowship curriculum, defined in six domains including theoretical knowledge, decision-making, technical skills, postoperative management and continuing professional development. Finally, as a prelude to stages 5 and 6, a strategy for implementation and for feedback and assessment was agreed by an expert consensus meeting that defined case volume (a minimum of 20 pelvic exenteration operations within a fellowship period) and coverage of this syllabus with derived metrics. CONCLUSIONS: Our working group has developed a curriculum framework for advanced fellowship training in complex cancer in the UK. Validation is needed through implementation, and affirmation of its utility, both nationally and internationally, must be sought.
Subject(s)
Clinical Competence , Colorectal Neoplasms , Curriculum , Fellowships and Scholarships , Pelvic Exenteration , Humans , Pelvic Exenteration/education , United Kingdom , Colorectal Neoplasms/surgery , Education, Medical, Graduate/methods , Colorectal Surgery/education , Needs Assessment , Focus GroupsABSTRACT
BACKGROUND: Accurate preoperative risk assessment for major colorectal cancer (CRC) surgery remains challenging. Body composition (BC) and cardiopulmonary exercise testing (CPET) can be used to evaluate risk. The relationship between BC and CPET in patients undergoing curative CRC surgery is unclear. METHODS: Consecutive patients undergoing CPET prior to CRC surgery between 2010 and 2020 were identified between two different UK hospitals. Body composition phenotypes such as sarcopenia, myosteatosis, and visceral obesity were defined using widely accepted thresholds using preoperative single axial slice CT image at L3 vertebrae. Relationships between clinicopathological, BC, and CPET variables were investigated using linear regression analysis. RESULTS: Two hundred eighteen patients with stage I-III CRC were included. The prevalence of sarcopenia, myosteatosis, and visceral obesity was 62%, 33%, and 64%, respectively. The median oxygen uptake at anaerobic threshold (VO2 at AT) was 12.2 mL/kg/min (IQR 10.6-14.2), and oxygen uptake at peak exercise (VO2 peak) was 18.8 mL/kg/min (IQR 15.4-23). On univariate linear regression analysis, male sex (P < 0.001) was positively associated with VO2 at AT. While ASA grade (P < 0.001) and BMI (P = 0.007) were negatively associated with VO2 at AT, on multivariate linear regression analysis, these variables remained significant (P < 0.05). On univariate linear regression analysis, male sex (P < 0.001) was positively associated with VO2 peak, whereas age (P < 0.001), ASA grade (P < 0.001), BMI (P = 0.003), sarcopenia (P = 0.015), and myosteatosis (P < 0.001) were negatively associated with VO2 peak. On multivariate linear regression analysis age (P < 0.001), ASA grade (P < 0.001), BMI (P < 0.001), and sarcopenia (P = 0.006) were independently and negatively associated with VO2 peak. CONCLUSIONS: The novel finding that sarcopenia is independently associated with reduced VO2 peak performance in CPET supports the supposition that reduced muscle mass relates to poor physical function in CRC patients. Further work should be undertaken to assess whether sarcopenia diagnosed on CT can act as suitable surrogate for CPET to further enhance personalized risk stratification.
ABSTRACT
BACKGROUND & AIMS: Patients with colorectal cancer who are more socio-economically deprived have worse outcomes; deprivation is also associated with higher obesity rates, defined as a body mass index (BMI) of greater than thirty. Body composition (BC) factors such as sarcopenia and myosteatosis are also known to predispose to poorer outcomes following colorectal cancer surgery. There is limited evidence to date to relate the effect of deprivation upon these host characteristics that are linked to prognosis. We aimed to examine the relationship between deprivation and body composition in colorectal cancer. METHODS: Analysis was performed on a prospectively collected database of preoperative primary colorectal cancer patients at St Mark's - The National Bowel Hospital, UK. Body composition characteristics were identified by analysing the L3 axial slices of Computer Tomogram (CT) slices of preoperative staging using Slice-O-Matic software with Automatic Body composition Analyser using Computed tomography image Segmentation (ABACS) L3 plug-in. Deprivation status for each patient was determined using their postal code which was linked to the Index of Multiple Deprivation (IMD). Each domain of the IMD was examined individually in relation to BC characteristics. Binary logistic regression analysis was performed on the data using a model developed from previous published analyses of this dataset. RESULTS: Four hundred and nineteen patients were included in the final analysis, the median age was 69 years and 57% of the patient population was male. Patients who were more deprived were significantly more likely to be sarcopenic [OR 1.56 (95% CI 1.01-2.41, p = 0.045)] and myosteatotic [OR 1.69 (95% CI 1.019-2.81, p = 0.042)]. More deprived patients were also more likely to have a lower BMI [OR 0.60 (95% CI 0.38-0.94, p = 0.026)] despite no significant difference in visceral obesity between the most and least deprived. CONCLUSIONS: Deprivation is an important independent determinant of sarcopenia in the colorectal cancer population. Identifying these patients early and addressing reversible factors may help improve post-operative surgical outcomes in this poor prognostic group. Sarcopenia may be a premorbid state in the deprived colorectal cancer patient that may not be wholly driven by tumour characteristics.
Subject(s)
Colonic Diseases , Rectal Neoplasms , Surgeons , Humans , Rectal Neoplasms/surgery , Rectum/surgery , Hospitals , Retrospective StudiesABSTRACT
Automated computed tomography (CT) scan segmentation (labelling of pixels according to tissue type) is now possible. This technique is being adapted to achieve three-dimensional (3D) segmentation of CT scans, opposed to single L3-slice alone. This systematic review evaluates feasibility and accuracy of automated segmentation of 3D CT scans for volumetric body composition (BC) analysis, as well as current limitations and pitfalls clinicians and researchers should be aware of. OVID Medline, Embase and grey literature databases up to October 2021 were searched. Original studies investigating automated skeletal muscle, visceral and subcutaneous AT segmentation from CT were included. Seven of the 92 studies met inclusion criteria. Variation existed in expertise and numbers of humans performing ground-truth segmentations used to train algorithms. There was heterogeneity in patient characteristics, pathology and CT phases that segmentation algorithms were developed upon. Reporting of anatomical CT coverage varied, with confusing terminology. Six studies covered volumetric regional slabs rather than the whole body. One study stated the use of whole-body CT, but it was not clear whether this truly meant head-to-fingertip-to-toe. Two studies used conventional computer algorithms. The latter five used deep learning (DL), an artificial intelligence technique where algorithms are similarly organized to brain neuronal pathways. Six of seven reported excellent segmentation performance (Dice similarity coefficients > 0.9 per tissue). Internal testing on unseen scans was performed for only four of seven algorithms, whilst only three were tested externally. Trained DL algorithms achieved full CT segmentation in 12 to 75 s versus 25 min for non-DL techniques. DL enables opportunistic, rapid and automated volumetric BC analysis of CT performed for clinical indications. However, most CT scans do not cover head-to-fingertip-to-toe; further research must validate using common CT regions to estimate true whole-body BC, with direct comparison to single lumbar slice. Due to successes of DL, we expect progressive numbers of algorithms to materialize in addition to the seven discussed in this paper. Researchers and clinicians in the field of BC must therefore be aware of pitfalls. High Dice similarity coefficients do not inform the degree to which BC tissues may be under- or overestimated and nor does it inform on algorithm precision. Consensus is needed to define accuracy and precision standards for ground-truth labelling. Creation of a large international, multicentre common CT dataset with BC ground-truth labels from multiple experts could be a robust solution.
ABSTRACT
This article adopts a multidisciplinary approach, including surgery, oncology, radiology and patient perspectives, to discuss the key points of debate surrounding a watch and wait approach. In an era of shared decision-making, discussion of watch and wait as an option in the context of complete clinical response is appropriate, although it is not the gold standard treatment. Key challenges are the difficulty in assessing for a complete clinical response, prediction of recurrence and access to timely diagnostics for surveillance. Salvage surgery has good results if regrowth is detected early but does have imperfect outcomes, with only a 90% salvage rate. Good communication with patients about the risks and alternatives is essential. Patients undergoing watch and wait should ideally be enrolled in prospective registries or clinical trials.
Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Prospective Studies , Watchful Waiting , Neoplasm Recurrence, Local/drug therapy , Rectal Neoplasms/surgery , Chemoradiotherapy/methods , Chemoradiotherapy, Adjuvant , Patient Care Team , Treatment OutcomeABSTRACT
INTRODUCTION: Pathological factors that influence and predict survival following pelvic exenteration (PE) for locally advanced (LARC) or locally recurrent rectal cancer (LRRC), especially LRRC, remain poorly understood. A clear resection margin has previously been demonstrated to be of most significance. MATERIALS AND METHODS: A retrospective cohort study was performed for all patients undergoing a curative PE for LARC or LRRC between 2008 and 2021 at a tertiary referral UK specialist colorectal hospital. Cox regression analysis was planned to identify pathological factors associated with overall (OS), disease free (DFS) and local recurrence free survival (LRFS). RESULTS: 388 patients were included in the analysis with 256 resections for LARC and 132 for LRRC. 62.4% of patients were male with a median age of 59 years (IQR 49-67). 247 (64%) partial pelvic exenterations and 141 (36%) total pelvic exenterations performed. Overall R0 rate 86.6%. Poorly differentiated tumours and a positive resection margin independently influenced OS, DFS and LRFS on multivariate analysis in LARC. On multivariate analysis venous invasion negatively influenced DFS and poorly differentiated lesions negatively influenced LRFS in LRRC. CONCLUSIONS: A positive resection margin and poorly differentiated tumours are significant negative prognostic markers for survival and recurrence in LARC. The results of this study support the need to look for alternative prognostic markers beyond that in the existing standard reporting dataset for rectal cancers. With increasing R0 rates, novel prognostic pathological markers are required to help guide treatment and surveillance for patients with LRRC.
Subject(s)
Pelvic Exenteration , Rectal Neoplasms , Humans , Male , Middle Aged , Aged , Female , Retrospective Studies , Margins of Excision , Neoplasm Recurrence, Local/pathology , Rectal Neoplasms/pathology , Rectum/surgery , Rectum/pathology , Treatment OutcomeABSTRACT
AIM: The choice of whether to perform protective ileostomy (PI) after anterior resection (AR) is mainly guided by risk factors (RFs) responsible for the development of anastomotic leakage (AL). However, clear guidelines about PI creation are still lacking in the literature and this is often decided according to the surgeon's preferences, experiences or feelings. This qualitative study aims to investigate, by an open-ended question survey, the individual surgeon's decision-making process regarding PI creation after elective AR. METHOD: Fifty four colorectal surgeons took part in an electronic survey to answer the questions and describe what usually led their decision to perform PI. A content analysis was used to code the answers. To classify answers, five dichotomous categories (In favour/Against PI, Listed/Unlisted RFs, Typical/Atypical, Emotions/Non-emotions, Personal experience/No personal experience) have been developed. RESULTS: Overall, 76% of surgeons were in favour of PI creation and 88% considered listed RFs in the question of whether to perform PI. Atypical answers were reported in 10% of cases. Emotions and personal experience influenced surgeons' decision-making process in 22% and 49% of cases, respectively. The most frequently considered RFs were the distance of the anastomosis from the anal verge (96%), neoadjuvant chemoradiotherapy (88%), a positive intraoperative leak test (65%), blood loss (37%) and immunosuppression therapy (35%). CONCLUSION: The indications to perform PI following rectal cancer surgery lack standardization and evidence-based guidelines are required to inform practice. Until then, expert opinion can be helpful to assist the decision-making process in patients who have undergone AR for adenocarcinoma.
Subject(s)
Rectal Neoplasms , Rectum , Humans , Rectum/surgery , Rectum/pathology , Ileostomy/adverse effects , Rectal Neoplasms/pathology , Anastomotic Leak/etiology , Anastomosis, Surgical/adverse effects , Retrospective StudiesABSTRACT
AIM: Locally advanced intestinal neoplasms including colon cancer may require radical en bloc pancreaticoduodenectomy and right hemicolectomy (PD-RC) to achieve curative, margin-negative resection, but the safety and benefit of this uncommon procedure has not been established. The Association of Coloproctology of Great Britain and Ireland IMPACT initiative has also highlighted a lack of awareness about current services available within the UK for patients with advanced colorectal cancer and concerns about low-volume centres managing complex cases. Thus, we aimed to review the feasibility, safety and long-term outcomes of this procedure at a single high-volume hepatopancreaticobiliary surgery unit in the UK. METHOD: A retrospective cohort study was performed using a database of all consecutive patients with intestinal cancer who had been referred to our regional advanced multidisciplinary team and undergone PD-RC in a 7-year period (2013-2020). Clinico-pathological and outcome data were reviewed. RESULTS: Ten patients (mean age 54 ± 13, 8/10 men) were identified. Final histology revealed the primary tumour sites were colon (n = 7) and duodenum (n = 3). R0 resection was achieved in all cases. The major complication rate (Clavien-Dindo ≥ 3) was 10% (1/10) with no deaths within 90 days of surgery. The Kaplan-Meier estimated 5-year overall survival was 83.3% (95% CI 58.3%-100%). Univariate survival analysis identified perineural invasion and extra-colonic origin as predictors of poor survival (log-rank P < 0.05). CONCLUSION: En bloc PD-RC for locally advanced intestinal cancer can be performed safely with a high proportion of margin-negative resections and resultant long-term survival in carefully selected patients.
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Male , Humans , Pancreaticoduodenectomy/methods , Retrospective Studies , Colonic Neoplasms/pathology , Colorectal Neoplasms/surgery , Colectomy/methodsABSTRACT
BACKGROUND: Benchmark comparisons in surgery allow identification of gaps in the quality of care provided. The aim of this study was to determine quality thresholds for high (HAR) and low (LAR) anterior resections in colorectal cancer surgery by applying the concept of benchmarking. METHODS: This 5-year multinational retrospective study included patients who underwent anterior resection for cancer in 19 high-volume centres on five continents. Benchmarks were defined for 11 relevant postoperative variables at discharge, 3 months, and 6 months (for LAR). Benchmarks were calculated for two separate cohorts: patients without (ideal) and those with (non-ideal) outcome-relevant co-morbidities. Benchmark cut-offs were defined as the 75th percentile of each centre's median value. RESULTS: A total of 3903 patients who underwent HAR and 3726 who had LAR for cancer were analysed. After 3 months' follow-up, the mortality benchmark in HAR for ideal and non-ideal patients was 0.0 versus 3.0 per cent, and in LAR it was 0.0 versus 2.2 per cent. Benchmark results for anastomotic leakage were 5.0 versus 6.9 per cent for HAR, and 13.6 versus 11.8 per cent for LAR. The overall morbidity benchmark in HAR was a Comprehensive Complication Index (CCI®) score of 8.6 versus 14.7, and that for LAR was CCI® score 11.9 versus 18.3. CONCLUSION: Regular comparison of individual-surgeon or -unit outcome data against benchmark thresholds may identify gaps in care quality that can improve patient outcome.
Subject(s)
Colorectal Surgery , Proctectomy , Rectal Neoplasms , Humans , Benchmarking , Retrospective Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Rectal Neoplasms/surgeryABSTRACT
BACKGROUND: Shared decision-making in pelvic exenteration is a complex and detailed process, which must balance clinical, oncological and patient-reported outcomes (PROs), whilst addressing and valuing the patient priorities. Communicating patient-centred information on quality of life (QoL) and functional outcomes is an essential component of this. The aim of this systematic review was to understand the impact of pelvic exenteration on QoL PROs over a longitudinal period and to develop QoL trajectories to support decision-making in this context. METHODS: MEDLINE, Embase and Web of Science databases were searched between 1st January 2000 and 20th December 2021 Studies reporting on PROs, including QoL, in adults undergoing pelvic exenteration were included. Risk of bias was assessed using the ROBINS-I assessment tool. Data from studies reporting QoL using the same outcome measure at the same candidate timepoint were extracted and synthesised to develop a longitudinal QoL trajectory. RESULTS: Fourteen studies consisting of 1370 patients were included in this review. QoL trajectories were constructed in the domains of physical function, psychological function, role function, sexual function, body image and general and specific symptoms. Decision-making was only assessed by one study, with satisfaction with decision-making reported to be high. There is an initial decline in QoL scores in the domains of physical function, role function, sexual function, body image and general health and symptoms deteriorating during the first 3-6 months post-operatively. Psychological function is the only QoL domain that remains stable throughout the post-operative period. CONCLUSION: Mapping QoL trajectories provides a visual representation of post-operative progress, highlighting the enduring impact of pelvic exenteration on patients and can be used to inform pre-operative shared decision-making.
Subject(s)
Pelvic Exenteration , Adult , Humans , Pelvic Exenteration/methods , Quality of Life , Patient Reported Outcome Measures , Body Image , Decision MakingABSTRACT
BACKGROUND: Despite multimodal therapy 5-15% of patients who undergo resection for advanced rectal cancer (LARC) will develop local recurrence. Management of locally recurrent rectal cancer (LRRC) presents a significant therapeutic challenge and even with modern exenterative surgery, 5-year survival rates are poor at 25-50%. High rates of local and systemic recurrence in this cohort are reflective of the likely biological aggressiveness of these tumour types. This review aims to appraise the current literature identifying pathological factors associated with survival and tumour recurrence in patients undergoing exenterative surgery. METHODS: A systematic review was carried out searching MEDLINE, EMBASE and COCHRANE Trials database for all studies assessing pathological factors influencing survival following pelvic exenteration for LARC or LRRC from 2010 to July 2021 following PRISMA guidelines. Risk of bias was assessed using QUIPS tool. RESULTS: Nine cohort studies met inclusion criteria, reporting outcomes for 2864 patients. Meta-analysis was not possible due to significant heterogeneity of reported outcomes. Resection margin status and nodal disease were the most commonly reported factors. A positive resection margin was demonstrated to be a negative prognostic marker in six studies. Involved lymph nodes and lymphovascular invasion also appear to be negative prognostic markers with tumour stage to be of lesser importance. No studies assessed other adverse tumour features that would not otherwise be included in a standard histopathology report. CONCLUSION: Pathological resection margin status is widely demonstrated to influence disease free and overall survival following pelvic exenteration for rectal cancer. With increasing R0 rates, other adverse tumour features must be explored to help elucidate differences in survival and potentially guide tailored oncological treatment.
Subject(s)
Pelvic Exenteration , Rectal Neoplasms , Humans , Margins of Excision , Neoplasm Recurrence, Local , Rectum , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Selection of patients for preoperative treatment in rectal cancer is controversial. The new 2020 National Institute for Health and Care Excellence (NICE) guidelines, consistent with the National Comprehensive Cancer Network guidelines, recommend preoperative radiotherapy for all patients except for those with radiologically staged T1-T2, N0 tumours. We aimed to assess outcomes in non-irradiated patients with rectal cancer and to stratify results on the basis of NICE criteria, compared with known MRI prognostic factors now omitted by NICE. METHODS: For this retrospective cohort study, we identified patients undergoing primary resectional surgery for rectal cancer, without preoperative radiotherapy, at Basingstoke Hospital (Basingstoke, UK) between Jan 1, 2011, and Dec 31, 2016, and at St Marks Hospital (London, UK) between Jan 1, 2007, and Dec 31, 2017. Patients with MRI-detected extramural venous invasion, MRI-detected tumour deposits, and MRI-detected circumferential resection margin involvement were categorised as MRI high-risk for recurrence (local or distant), and their outcomes (disease-free survival, overall survival, and recurrence) were compared with patients defined as high-risk according to NICE criteria (MRI-detected T3+ or MRI-detected N+ status). Kaplan-Meier and Cox proportional hazards analyses were used to compare the groups. FINDINGS: 378 patients were evaluated, with a median of 66 months (IQR 44-95) of follow up. 22 (6%) of 378 patients had local recurrence and 68 (18%) of 378 patients had distant recurrence. 248 (66%) of 378 were classified as high-risk according to NICE criteria, compared with 121 (32%) of 378 according to MRI criteria. On Kaplan-Meier analysis, NICE high-risk patients had poorer 5-year disease-free survival compared with NICE low-risk patients (76% [95% CI 70-81] vs 87% [80-92]; hazard ratio [HR] 1·91 [95% CI 1·20-3·03]; p=0·0051) but not 5-year overall survival (80% [74-84] vs 88% [81-92]; 1·55 [0·94-2·53]; p=0·077). MRI criteria separated patients into high-risk versus low-risk groups that predicted 5-year disease-free survival (66% [95% CI 57-74] vs 88% [83-91]; HR 3·01 [95% CI 2·02-4·47]; p<0·0001) and 5-year overall survival (71% [62-78] vs 89% [84-92]; 2·59 [1·62-3·88]; p<0·0001). On multivariable analysis, NICE risk assessment was not associated with either disease-free survival or overall survival, whereas MRI criteria predicted disease-free survival (HR 2·74 [95% CI 1·80-4·17]; p<0·0001) and overall survival (HR 2·44 [95% CI 1·51-3·95]; p=0·00027). 139 NICE high-risk patients who were defined as low-risk based on MRI criteria had similar disease-free survival as 118 NICE low-risk patients; therefore, 37% (139 of 378) of patients in this study cohort would have been overtreated with NICE 2020 guidelines. Of the 130 patients defined as low-risk by NICE guidelines, 12 were defined as high-risk on MRI risk stratification and would have potentially been missed for treatment. INTERPRETATION: Compared to previous guidelines, implementation of the 2020 NICE guidelines will result in significantly more patients receiving preoperative radiotherapy. High-quality MRI selects patients with good outcomes (particularly low local recurrence) without radiotherapy, with little margin for improvement. Overuse of radiotherapy could occur with this unselective approach. The high-risk group, with the most chance of benefiting from preoperative radiotherapy, is not well selected on the basis of NICE 2020 criteria and is better identified with proven MRI prognostic factors (extramural venous invasion, tumour deposits, and circumferential resection margin). FUNDING: None.
Subject(s)
Margins of Excision , Rectal Neoplasms , Cohort Studies , Extranodal Extension , Humans , Magnetic Resonance Imaging , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery , Retrospective StudiesABSTRACT
The role of microbiota:immune system dysregulation in the etiology of colorectal cancer (CRC) is poorly understood. CRC develops in gut epithelium, accompanied by low level inflammatory signaling, intestinal microbial dysbiosis and immune dysfunction. We examined populations of intraepithelial lymphocytes in non-affected colonic mucosa of CRC and healthy donors and circulating immune memory to commensal bacterial species and yeasts. γδ T cells and resident memory T cells, populations with a regulatory CD39-expressing phenotype, were found at lower frequencies in the colonic tissue of CRC donors compared to healthy controls. Patterns of T cell proliferative responses to a panel of commensal bacteria were distinct in CRC, while B cell memory responses to several bacteria/yeast were significantly increased, accompanied by increased proportions of effector memory B cells, transitional B cells and plasmablasts in blood. IgA responses to mucosal microbes were unchanged. Our data describe a novel immune signature with similarities to and differences from that of inflammatory bowel disease. They implicate B cell dysregulation as a potential contributor to parainflammation and identify pathways of weakened barrier function and tumor surveillance in CRC-susceptible individuals.
Subject(s)
Colorectal Neoplasms , Microbiota , Bacteria , Colorectal Neoplasms/pathology , Dysbiosis/microbiology , Humans , Immunoglobulin A , Intestinal Mucosa , Memory T CellsABSTRACT
BACKGROUND: Sarcopenia, myosteatosis and visceral obesity (VO) are known to negatively impact on outcomes from colorectal cancer (CRC). Little is known about tumour factors associated with these body composition (BC) phenotypes. We aimed to identify whether histopathological tumour characteristics were associated with various BC phenotypes. METHODS: A prospectively collected database of patients undergoing surgery for primary CRC at a tertiary referral unit in the United Kingdom was analysed. Sarcopenia, myosteatosis and VO were identified on preoperative CT. Binary logistic regression modelling was performed to determine significant associations between tumour stage, grade and BC phenotype. RESULTS: Final analysis included 795 patients; median age 69, 56% male, 65% were sarcopenic, 72% myosteatotic, 52% VO and 20% had sarcopenic obesity (SO). VO patients were significantly less likely to have advanced T Stage (T3-4) OR0.62(95%CI 0.44-0.86, p = 0.005); nodal metastases OR0.60(95%CI 0.44-0.82, p = 0.001); vascular invasion OR0.63(95%CI 0.46-0.88, p = 0.006) and poor tumour differentiation OR0.49(95%CI 0.28-0.86, p = 0.012). Myosteatotic patients were more likely to have metastatic disease OR2.31(95%CI 1.15-4.63, p = 0.018) but less likely to have poorly differentiated tumours OR0.48(95%CI 0.27-0.86, p = 0.013). SO patients were significantly more likely to have poorly differentiated tumours OR2.01(95%CI 1.04-3.87, p = 0.037). CONCLUSION: VO predisposes to earlier stage tumours with a less aggressive tumour phenotype. The SO group have adverse tumour characteristics which may be explained by differences in fat distribution. Myosteatosis relates to increased likelihood of distant metastasis that may be related to a systemic inflammatory response, despite the association with better differentiated tumours.
Subject(s)
Colorectal Neoplasms , Sarcopenia , Body Composition , Colorectal Neoplasms/pathology , Female , Humans , Male , Muscle, Skeletal/pathology , Obesity/complications , Obesity, Abdominal/complications , Obesity, Abdominal/pathology , Phenotype , Retrospective Studies , Sarcopenia/complications , Tomography, X-Ray ComputedABSTRACT
BACKGROUND AND AIMS: Alterations in body composition are common in inflammatory bowel disease [IBD] and have been associated with differences in patient outcomes. We sought to consolidate knowledge on the impact and importance of body composition in IBD. METHODS: We performed a systematic search of MEDLINE, EMBASE and conference proceedings by combining two key research themes: inflammatory bowel disease and body composition. RESULTS: Fifty-five studies were included in this review. Thirty-one focused on the impact of IBD on body composition with a total of 2279 patients with a mean age 38.4 years. Of these, 1071 [47%] were male. In total, 1470 [64.5%] patients had Crohn's disease and 809 [35.5%] had ulcerative colitis. Notably, fat mass and fat-free mass were reduced, and higher rates of sarcopaenia were observed in those with active IBD compared with those in clinical remission and healthy controls. Twenty-four additional studies focused on the impact of derangements in body composition on IBD outcomes. Alterations in body composition in IBD are associated with poorer prognoses including higher rates of surgical intervention, post-operative complications and reduced muscle strength. In addition, higher rates of early treatment failure and primary non-response are seen in patients with myopaenia. CONCLUSIONS: Patients with IBD have alterations in body composition parameters in active disease and clinical remission. The impacts of body composition on disease outcome and therapy are broad and require further investigation. The augmentation of body composition parameters in the clinical setting has the potential to improve IBD outcomes in the future.