Catheter-Directed Hemorrhoidal Dearterialization Technique for the Management of Hemorrhoids: A Meta-Analysis of the Clinical Evidence.

PURPOSE: To assess the efficacy and safety of a catheter-directed hemorrhoidal dearterialization technique for the management of hemorrhoidal bleeding. MATERIALS AND METHODS: A systematic review and meta-analysis of pubmed, cochrane, and scopus databases was conducted according to the preferred reporting items for systematic reviews and meta-Analysis (PRISMA) guidelines. Clinical studies reporting on catheter-directed hemorrhoidal dearterialization for rectal bleeding were analyzed. RESULTS: Fourteen studies (n = 362) were identified. The mean maximum follow-up duration was 12.1 months (SD, 7.31; range, 1-28; median, 12), and the mean length of hospital stay was 1.5 days (SD, 1.1; range, 0-2.5). The mean technical success was 97.8% (SD, 3.5), and the mean clinical success was 78.9% (SD, 10.5). A statistically significant reduction in the french bleeding score before and after embolization was noted (P = .004). In subgroup analysis, when the coils-only group was compared with the coils and particles group, the average rebleeding rate was 21.5% (n = 111; SD, 18.2; range, 0%-44%) versus 10.05% (N = 108; SD, 4.8; range, 5%-15.7%), respectively (P < .0001). No bowel ischemia/necrosis or anorectal complications were reported. CONCLUSIONS: The current preliminary clinical evidence suggests that catheter-directed hemorrhoidal dearterialization is an effective and safe procedure for the treatment of hemorrhoidal bleeding. The standardization of the technique and the generation of higher level evidence will be required to compare this minimally invasive procedure with more invasive surgical options for patients with grades I-III hemorrhoids and chronic bleeding.

Sporadic colorectal cancer in adolescents and young adults: a scoping review of a growing healthcare concern.

PURPOSE: Sporadic colorectal cancer (CRC) amongst adolescents and young adults (AYA) is increasing in incidence. The reasons for this trend are not well understood. Current guidelines do not specifically address this patient cohort. A scoping review was performed to summarise the range of available evidence and identify key areas that need to be addressed in current guidelines. METHODS: A systematic literature search was conducted adhering to the PRISMA statement. All potentially eligible studies were screened, and data extraction was performed by two reviewers independently. The studies were then divided into 5 broad subgroups: (1) risk factors, (2) screening, (3) clinicopathological and molecular features, (4) presentation and (5) management. Descriptive statistics were used for data analysis. RESULTS: A total of 17 studies were included from 2010 to 2019. Overall, young adults with CRC tend to present with non-specific symptoms. The majority of these patients have a delayed diagnosis and more advanced disease at presentation, with a rise in prevalence of distal colon and rectal cancers. AYAs tend to have poorly differentiated tumours and are managed more aggressively. Overall 5-year survival varies between studies. CONCLUSION: This is, to our knowledge, the first scoping review presenting the range of available evidence on CRC in AYAs. Although the rise in incidence is recognised by specialist bodies, recommendations are limited by the sparsity of available data. We seek to highlight the need for further research, define the role of earlier screening and raise awareness to promote thorough assessment of young patients.

Long-term Survival in Esophageal Cancer After Minimally Invasive Compared to Open Esophagectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: Evaluate the existing literature comparing long-term survival after minimally invasive esophagectomy (MIE) and open esophagectomy (OE), and conduct a meta-analysis based on relevant studies. BACKGROUND: It is unknown whether the choice between MIE and OE influences the long-term survival in esophageal cancer. METHODS: A systematic electronic search for articles was performed in Medline, Embase, Web of Science, and Cochrane Library for studies comparing long-term survival after MIE and OE. Additionally, an extensive hand-search was conducted. The I test and χ test were used to test for statistical heterogeneity. Publication bias and small-study effects were assessed using Egger test. A random-effects meta-analysis was performed for all-cause 5-year (main outcome) and 3-year mortality, and disease-specific 5-year and 3-year mortality. Meta-regression was performed for the 5-year mortality outcomes with adjustment for the covariates age, physical status, tumor stage, and neoadjuvant or adjuvant therapy. The results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The review identified 55 relevant studies. Among all 14,592 patients, 7358 (50.4%) underwent MIE and 7234 (49.6%) underwent OE. The statistical heterogeneity was limited [I = 12%, 95% confidence interval (CI) 0%-41%, and χ = 0.26] and the funnel plot was symmetrical both according to visual and statistical testing (Egger test = 0.32). Pooled analysis revealed 18% lower 5-year all-cause mortality after MIE compared with OE (HR 0.82, 95% CI 0.76-0.88). The meta-regression indicated no confounding. CONCLUSIONS: The long-term survival after MIE compares well with OE and may even be better. Thus, MIE can be recommended as a standard surgical approach for esophageal cancer.

Induced Bias Due to Crossover Within Randomized Controlled Trials in Surgical Oncology: A Meta-regression Analysis of Minimally Invasive versus Open Surgery for the Treatment of Gastrointestinal Cancer.

BACKGROUND: Randomized controlled trials (RCTs) inform clinical practice and have provided the evidence base for introducing minimally invasive surgery (MIS) in surgical oncology. Crossover (unplanned intraoperative conversion of MIS to open surgery) may affect clinical outcomes and the effect size generated from RCTs with homogenization of randomized groups. OBJECTIVES: Our aims were to identify modifiable factors associated with crossover and assess the impact of crossover on clinical endpoints. METHODS: A systematic review was performed to identify all RCTs comparing MIS with open surgery for gastrointestinal cancer (1990-2017). Meta-regression analysis was performed to analyze factors associated with crossover and the influence of crossover on endpoints, including 30-day mortality, anastomotic leak rate, and early complications. RESULTS: Forty RCTs were included, reporting on 11,625 patients from 320 centers. Crossover was shown to affect one in eight patients (mean 12.6%, range 0-45%) and increased with American Society of Anesthesiologists score (ß = + 0.895; p = 0.050). Pretrial surgeon volume (ß = - 2.344; p = 0.037), composite RCT quality score (ß = - 7.594; p = 0.014), and site of tumor (ß = - 12.031; p = 0.021, favoring lower over upper gastrointestinal tumors) showed an inverse relationship with crossover. Importantly, multivariate weighted linear regression revealed a statistically significant positive correlation between crossover and 30-day mortality (ß = + 0.125; p = 0.033), anastomotic leak rate (ß = + 0.550; p = 0.004), and early complications (ß = + 1.255; p = 0.001), based on intention-to-treat analysis. CONCLUSIONS: Crossover in trials was associated with an increase in 30-day mortality, anastomotic leak rate, and early complications within the MIS group based on intention-to-treat analysis, although our analysis did not assess causation. Credentialing surgeons by procedural volume and excluding high comorbidity patients from initial trials are important in minimizing crossover and optimizing RCT validity.

Prognostic significance of peritoneal lavage cytology in staging gastric cancer: systematic review and meta-analysis.

BACKGROUND: Peritoneal cytology has been used as a part of the cancer staging of gastric cancer patients. The primary aim of this systematic review was to evaluate the value of peritoneal cytology as part of the staging of gastric cancer and survival prediction. The second aim was to establish if positive cytology may be modified by neoadjuvant therapy, to improve prognosis. METHODS: An electronic literature search was performed using Embase, Medline, Web of Science, and Cochrane library databases up to January 2016. The logarithm of the hazard ratio (HR) with 95% confidence intervals (CI) was used as the primary summary statistic. Comparative studies were used, and the outcome measure was survival in three groups: (1) positive versus negative cytology at staging laparoscopy immediately preceding surgery; (2) effect of neoadjuvant therapy on cytology and survival; and (3) positive cytology in the absence of macroscopic peritoneal disease was compared with obvious macroscopic peritoneal disease. RESULTS: Pooled analysis demonstrated that positive cytology was associated with significantly reduced overall survival (HR, 3.46; 95% CI, 2.77-4.31; P < 0.0001). Interestingly, negative cytology following neoadjuvant chemotherapy was associated with significantly improved overall survival (HR, 0.42; 95% CI, 0.31-0.57; P < 0.0001). The absence of macroscopic peritoneal disease with positive cytology was associated with significantly improved overall survival (HR, 0.64; 95% CI, 0.56-0.73; P < 0.0001). CONCLUSION: This study suggests that patients with initial positive cytology may have a good prognosis following neoadjuvant treatment if the cytology results change to negative after treatment.

Perioperative risk prediction in the era of enhanced recovery: a comparison of POSSUM, ACPGBI, and E-PASS scoring systems in major surgical procedures of the colorectal surgeon.

PURPOSE: 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. METHODS: 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). RESULTS: Eleven patients (0.8%) died and 143 patients (10.4%) had a major complication within 30 days of surgery. All models overpredicted mortality and had poor discrimination: POSSUM 8.5% (O:E 0.09, AUC 0.56), P-POSSUM 2.2% (O:E 0.37, AUC 0.56), CR-POSSUM 7.1% (O:E 0.11, AUC 0.61), and E-PASS 3.0% (O:E 0.27, AUC 0.46). ACPGBI overestimated mortality in patients undergoing surgery for cancer 4.4% (O:E = 0.28, AUC = 0.41). Predicted morbidity was also overestimated by POSSUM 32.7% (O:E = 0.32, AUC = 0.51). E-POSSUM overestimated mortality (3.25%, O:E 0.57 AUC = 0.54) and morbidity (37.4%, O:E 0.30 AUC = 0.53) in patients aged ≥ 70 years and over. CONCLUSION: All models overestimated mortality and morbidity. New models are required to accurately predict the risk of adverse outcome in patients undergoing major abdominal surgery taking into account the reduced physiological and operative insult of laparoscopic surgery and enhanced recovery care.

"The Longest Way Round Is The Shortest Way Home": An Overhaul of Surgical Ward Rounds.

BACKGROUND: Ward rounds, a keystone of hospital surgical practice, have recently been under the spotlight. Poor-quality ward rounds can lead to a greater number of adverse events, thereby cascading to an increased financial strain on our already burdened healthcare systems. Faced with mounting pressures from both outside and inside health organizations, concerted efforts are required to restore it back into prominence where it can no longer take a backseat to the other duties of a surgeon. METHODS: The nucleus of this narrative review is derived from an extensive literature search on surgical ward rounds. RESULTS: In this review, we focus on the need for reforms, current characteristics of surgical ward rounds, obstacles encountered by competing interests and proposed solutions in delivery of effective ward rounds that can meet with newly laid guidelines. CONCLUSION: Ward rounds should be standardized and prioritized to improve patient care.

CT colonography for surveillance of patients with colorectal cancer: Systematic review and meta-analysis of diagnostic efficacy.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. KEY POINTS: • 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.

The value of adding sub-valvular procedures for chronic ischemic mitral regurgitation surgery: a meta-analysis.

BACKGROUND: The most performed repair technique for the treatment of chronic ischemic mitral regurgitation in patients referred for bypass grafting remains restricted annuloplasty. However, it is associated with a high rate of failure, especially if severe tenting exists. OBJECTIVES: To understand if adjunctive sub-valvular mitral procedures may provide better repair performance. METHODS: A systematic literature review identified six studies of which five fulfilled the criteria for meta-analysis. Outcomes for a total of 404 patients (214 had adjunctive sub-valvular procedures and 190 restricted annuloplasty) were meta-analyzed using random effects modeling. Heterogeneity and subgroup sensitivity analysis were assessed. Primary endpoints were: late recurrence of moderate mitral regurgitation, left ventricle remodeling and coaptation depth at follow-up. Secondary endpoints were: early mortality, mid-term survival and operative outcomes. RESULTS: Sub-valvular procedure technique was associated with a significantly lower late recurrence of mitral regurgitation (Odds ratio (OR) 0.34, 95% Confidence Interval (CI) [0.18, 0.65], p=0.0009), smaller left ventricle end-systolic diameter (Weighted Mean Difference (WMD) -4.06, 95% CI [-6.10, -2.03], p=0.0001) and reduced coaptation depth (WMD -2.36, 95% CI [-5.01, -0.71], p=0.009). These findings were consistent, even in studies that included patients at high risk for repair failure (coaptation depth >10 mm and tenting area >2.5 cm2). A low degree of heterogeneity was observed. There was no difference in terms of early mortality and mid-term survival; sub-valvular technique was associated with prolonged cardiopulmonary and cross-clamp time. CONCLUSIONS: Adding sub-valvular procedures when repairing ischemic chronic mitral valve regurgitation may be associated with better durability, even in the case of the presence of predictors for late failure. PERSPECTIVE: Surgical sub-valvular adjunctive procedures have to be considered in the case of the presence of echocardiographic predictors for late failure.

Influence of Surgical Resection of Hepatic Metastases From Gastric Adenocarcinoma on Long-term Survival: Systematic Review and Pooled Analysis.

OBJECTIVES: 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. BACKGROUND: Patients with hepatic metastases from gastric cancer are traditionally treated with palliative chemotherapy. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Low Muscularity and Myosteatosis Is Related to the Host Systemic Inflammatory Response in Patients Undergoing Surgery for Colorectal Cancer.

OBJECTIVE: We examined the relationships between computed tomography (CT)-defined skeletal muscle parameters and the systemic inflammatory response (SIR) in patients with operable primary colorectal cancer (CRC). BACKGROUND: Muscle depletion is characterized by a reduced muscle mass (myopenia) and increased infiltration by inter- and intramuscular fat (myosteatosis). It is recognized as a poor prognostic indicator in patients with cancer, but the underlying factors remain unclear. METHODS: A total of 763 patients diagnosed with CRC undergoing elective surgical resection between 2006 and 2013 were included. Image analysis of CT scans was used to calculate Lumbar skeletal muscle index (LSMI), and mean muscle attenuation (MA). The SIR was quantified by the preoperative neutrophil to lymphocyte ratio (NLR) and albumin levels. Correlation and multivariate regression analysis was performed to identify independent relationships between patient SIR and muscle characteristics. RESULTS: Patients with NLR > 3 had significantly lower LSMI and lower MA than those with NLR < 3 [LSMI = 42.07 cmm vs 44.27 cmm (P = 0.002) and MA = 30.04 Hounsfield unit (HU) vs 28.36 HU (P = 0.016)]. Multivariate logistic regression analysis showed that high NLR [odds ratio (OR) = 1.78 (95% confidence interval [CI]: 1.29-2.45), P < 0.001] and low albumin [OR = 1.80 (95% CI: 1.17-2.74), P = 0.007] were independent predictors of reduced muscle mass. High NLR was significantly related with a low mean MA and hence myosteatosis [OR = 1.60 (95% CI: 1.03-2.49), P = 0.038]. CONCLUSIONS: These results highlight a direct association between myopenia, myosteatosis, and the host SIR in patients with operable CRC. A better understanding of factors that regulate muscle changes such as myopenia and myosteatosis may lead to the development of novel therapies that influence a more metabolically "healthy" skeletal muscle and potentially alter cancer outcomes.

Skeletal Muscle Changes After Elective Colorectal Cancer Resection: A Longitudinal Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 [estimate = 0.17 cm(2)/m(2), standard error (SE) 0.06 cm(2)/m(2); p = 0.03], whereas Union for International Cancer Control (UICC) stage III + IV disease contributed to a negative curve change (estimate = -0.19 cm(2)/m(2), SE 0.09 cm(2)/m(2); p = 0.03). Older age (p < 0.01), female gender (p < 0.01), higher American Society of Anesthesiologists (ASA) score (p < 0.01), and altered systemic inflammatory response [SIR] (p = 0.03) were factors significantly associated with lower values of LSMI over time. CONCLUSION: In patients undergoing CRC surgery, laparoscopy and the absence of a significantly elevated SIR favored preservation and restoration of skeletal muscle, postoperatively. These emerging data may permit the development of new treatment protocols whereby monitoring and modification of body composition has therapeutic potential.

Body composition of the host influences dendritic cell phenotype in patients treated for colorectal cancer.

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.

The emerging role of microdialysis in diabetic patients undergoing amputation for limb ischemia.

Lower limb ischemia in diabetic patients is a result of macro- and microcirculation dysfunction. Diabetic patients undergoing limb amputation carry high mortality and morbidity rates, and decision making concerning the level of amputation is critical. Aim of this study is to evaluate a novel microdialysis technique to monitor tissue microcirculation preoperatively and predict the success of limb amputation in such patients. Overall, 165 patients with type 2 diabetes mellitus undergoing lower limb amputation were enrolled. A microdialysis catheter was placed preoperatively at the level of the intended flap for the stump reconstruction, and the levels of glucose, glycerol, lactate and pyruvate were measured for 24 consecutive hours. Patients were then amputated and monitored for 30 days regarding the outcome of amputation. Failure of amputation was defined as delayed healing or stump ischemia. Patients were divided into two groups based on the success of amputation. There was no difference between the two groups regarding gender, ASA score, body mass index, comorbidities, diagnostic modality used, level of amputation, as well as glucose, glycerol, and pyruvate levels. However, local concentrations of lactate were significantly different between the two groups and lactate/pyruvate (L/P) ratio was independently associated with failed amputation (threshold defined at 25.35). Elevated preoperative tissue L/P ratio is independently associated with worse outcomes in diabetic patients undergoing limb amputation. Therefore, preoperative tissue L/P ratio could be used as a predicting tool for limb amputation's outcome, although more clinical data are needed to provide safer conclusions.

Active and passive compliance in an enhanced recovery programme.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. This contrasts with 'passive' compliance, where an intervention is delivered to the patient without their direct contribution. The short-term surgical outcomes of this cohort are reported with reference to ERAS protocol compliance. RESULTS: Compliance with the passive elements of the programme was higher than with the active elements. Univariate and multivariate analyses demonstrate that poor compliance with active but not passive elements of the programme was significantly associated with major morbidity. Receiver operator characteristic curve analysis demonstrated active compliance to be a stronger predictor of both major morbidity (AUC 0.71 vs. AUC 0.56) and length of stay (AUC 0.83 vs. 0.57) when compared with passive compliance. CONCLUSION: The results suggest that poor active compliance may be a surrogate marker of morbidity which can be recognised in the early post-operative period. This implies the potential for timely diagnosis and intervention. This aspect of ERAS compliance is clinically relevant yet has achieved scant attention. Independent validation of our observations is required.

Factors Implicated for Delay of Adjuvant Chemotherapy in Colorectal Cancer: A Meta-analysis of Observational Studies.

BACKGROUND: The survival benefit of administering adjuvant chemotherapy (AC) in colorectal cancer is well established, as is the impact of its timing. Although various factors have been associated with treatment delay, their implications remain controversial. We determined clinicopathological factors associated with delay in transition to AC via systematic review and meta-analysis. METHODS: Studies assessing factors for delay in initiating AC were identified from MEDLINE, EMBASE, and Cochrane Databases. Studies were included only if relevant clinicopathological factors were adequately described and appropriate comparative groups were balanced. For each study, the odds ratio (OR) and 95 % confidence interval (CI) were estimated, regarding response to early versus delayed AC initiation. RESULTS: We identified 15 eligible studies involving 67,537 patients. Twelve studies were multicentre studies and three were single-center cohort studies. Meta-analysis demonstrated age >75 years [4 studies, OR = 1.44 (95 % CI 1.32-1.58)], marital status-single [3 studies, OR = 1.32 (95 % CI 1.20-1.44)], low socioeconomic status (SES) [7 studies, OR = 1.67 (95 % CI 1.32-2.12)], worse comorbidity status [5 studies, OR = 1.47 (95 % CI 1.14-1.90)], low tumour grade [7 studies, OR = 1.06 (95 % CI 1.02-1.11)], prolonged length of stay [3 studies, OR 2.37 (95 % CI 2.10-2.68)], and readmission [3 studies, OR = 3.23 (95 % CI 1.66-6.26)] were significant predictors of delayed initiation of AC. Laparoscopy compared to an open surgical approach was a significant predictor of earlier AC initiation [5 studies, OR = 0.70 (95 % CI 0.51-0.97)]. CONCLUSIONS: Laparoscopy is associated with earlier initiation of AC, encouraging its increased adoption. Social isolation and low SES merit consideration of approaches that counter the lack of social support and deprivation to improve cancer outcomes.

The prognostic significance and relationship with body composition of CCR7-positive cells in colorectal cancer.

BACKGROUND AND OBJECTIVES: The host local immune response (LIR) to cancer is a determinant of cancer outcome. Regulation of this local response is largely achieved through chemokine synthesis from the tumor microenvironment such as C-Chemokine-Receptor-7 (CCR7). We examined the LIR measured as CCR7 expression, in colorectal cancers (CRC) and explored relationships with body composition (BC) and survival. METHODS: A study of paraffin-embedded tissue specimens was carried out in 116 patients with non-metastatic CRC. CCR7 expression was determined by immunohistochemistry. Analysis of computer tomography scans was used to calculate BC parameters. Survival analyses and multivariate regression models were used. RESULTS: High CCR7(+) cell density within the tumor stroma and at the margin was significantly associated with increased age, the presence of lymphovascular invasion, higher tumor stage, lymph node metastasis, high Klintrup-Makinen immune score, and myosteatosis. High CCR7(+) cell density in the tumor margin was significantly associated with shorter disease-free (DFS) and overall survival (OS) (P < 0.001). This was also significantly associated with shorter survival in multivariate analysis (HR = 8.87; 95%CI [2.51-31.3]; P < 0.01 for OS and HR = 4.72; 95%CI (1.24-12.9); P = 0.02 for DFS). CONCLUSIONS: Our results suggest that a specific immune microenvironment may be associated with altered host's BC and tumor behavior, and that CCR7 may serve as a novel prognostic biomarker.

Defining characteristics of patients with colorectal cancer requiring emergency surgery.

INTRODUCTION: Emergency surgery for colorectal cancer has been associated with high mortality. The aim of this study is to determine factors predictive of undergoing emergency surgery, of 30-day mortality, and explore the role of screening in patients undergoing emergency surgery. METHODS: All patients at our unit, undergoing surgery for colorectal cancer between 2004 and 2014 were included. Data on patient demographics, tumour staging, admission type, comorbidity score, mortality data, and screening data were analysed. Multivariable analyses were carried out to determine predictors of undergoing emergency surgery as well as mortality postoperatively. RESULTS: A total of 1911 consecutive patients underwent elective and emergency surgery for colorectal cancer. Of the 263 patients who underwent emergency surgery for CRC, 37.3 % (n = 98) had right-sided colonic cancers. Multivariable analyses determined right-sided cancers (OR 2.92, 95 % CI 2.03-4.20, p < 0.001) and stage IV tumours to be independently associated with undergoing emergency surgery (OR 6.64, 95 % CI 2.86-15.42, p < 0.001). Undergoing emergency surgery was an independent predictor of 30-day mortality (OR 9.62, 95 % CI 5.96-15.54, p < 0.001). Of the 50 patients that died within 30 days in the emergency surgery group, 32 % were in patients with right-sided colon cancers. Cancer detection through guaiac faecal occult blood testing (gFOBT) amongst this group is low with six out of nine patients having a false negative gFOBT test. CONCLUSION: Emergency CRC surgery is associated with high mortality. Alternative screening strategies that improve detection of proximal colon cancers may reduce the number of patients undergoing emergency surgery for right-sided cancers.

The impact of anastomotic leak and its treatment on cancer recurrence and survival following elective colorectal cancer resection.

AIM: Anastomotic leakage is a serious complication in restorative colorectal surgery. Anastomotic leakage and its subsequent management may have long-term impact on survival. This study aims to assess the impact of colorectal anastomotic leak (AL) on overall survival (OS) and disease-free survival (DFS). METHODS: A prospective database of 1,048 patients undergoing restorative colorectal cancer resections at St Mark's hospital between October 2004 and October 2013 was examined. RESULTS: The overall leak rate was 99/1,048 (9.4%). 43 ALs were managed conservatively with antibiotics or radiological drainage and 56 with reoperations. OS was significantly reduced in the AL group treated with a reoperation (HR 2.74, 95% CI 1.67-4.52, p < 0.001). AL was not significantly associated with worse DFS [conservatively managed AL's vs. no AL-HR 2.07 (95% CI 1.05-4.10); reoperated AL's vs. no AL-HR 1.56 (95% CI 0.81-2.99), overall p value = 0.058]. CONCLUSION: Patients who suffer anastomotic leaks requiring reoperations have worse OS compared to patients who do not leak, but there were no significant differences in DFS between patients who leaked and those who did not.

A preoperative neutrophil to lymphocyte ratio of 3 predicts disease-free survival after curative elective colorectal cancer surgery.

OBJECTIVE: This study aims to determine the role of the neutrophil to lymphocyte ratio (NLR) as a prognostic marker for patients with nonmetastatic colorectal cancer undergoing curative resection. BACKGROUND: An NLR reflects a systematic inflammatory response, with some evidence suggesting that an elevated preoperative NLR of more than 5.0 is associated with poorer survival in patients with colorectal cancer. METHODS: Data from 506 consecutive patients with a diagnosis of nonmetastatic colorectal adenocarcinoma undergoing surgical resection between 2006 and 2011 were included. Receiver operating characteristic curve analysis was used to identify the optimal value for NLR in relation to disease-free and overall survival. Univariate and multivariate Cox regression models were used to determine the role of NLR after stratification by several clinicopathological factors. Patients were followed by a standardized protocol until February 2013. RESULTS: Median follow-up was 45 months [interquartile range, 21-65]. Multivariate Cox regression analysis identified an NLR of more than 3 as an independent prognostic factor for disease-free survival (odds ratio = 2.41; 95% confidence interval = 1.12-5.15; P = 0.024) but not for overall survival (odds ratio = 1.23; 95% confidence interval = 0.80-1.90; P = 0.347). A high NLR was significantly associated with older age, higher T and N stages, the presence of microvascular invasion, low preoperative albumin levels, and higher ASA (American Society of Anesthesiologists) status of the patient. CONCLUSIONS: For patients with colorectal cancer, a preoperative NLR of more than 3.0 may be an independent prognostic factor for disease-free survival. Considering this in addition to well-established prognostic variables may improve the processes of identifying patients at higher risk of recurrence who would benefit from adjuvant therapies or more frequent surveillance, thereby providing more personalized cancer care.