Frequent post-operative monitoring of colorectal cancer using individualised ctDNA validated by multiregional molecular profiling.

BACKGROUND: Circulating tumour DNA (ctDNA) is known as a tumour-specific personalised biomarker, but the mutation-selection criteria from heterogeneous tumours remain a challenge. METHODS: We conducted multiregional sequencing of 42 specimens from 14 colorectal tumours of 12 patients, including two double-cancer cases, to identify mutational heterogeneity to develop personalised ctDNA assays using 175 plasma samples. RESULTS: "Founder" mutations, defined as a mutation that is present in all regions of the tumour in a binary manner (i.e., present or absent), were identified in 12/14 tumours. In contrast, "truncal" mutations, which are the first mutation that occurs prior to the divergence of branches in the phylogenetic tree using variant allele frequency (VAF) as continuous variables, were identified in 12/14 tumours. Two tumours without founder and truncal mutations were hypermutators. Most founder and truncal mutations exhibited higher VAFs than "non-founder" and "branch" mutations, resulting in a high chance to be detected in ctDNA. In post-operative long-term observation for 10/12 patients, early relapse prediction, treatment efficacy and non-relapse corroboration were achievable from frequent ctDNA monitoring. CONCLUSIONS: A single biopsy is sufficient to develop custom dPCR probes for monitoring tumour burden in most CRC patients. However, it may not be effective for those with hypermutated tumours.

Prognostic significance of interleukin-17A-producing colorectal tumour antigen-specific T cells.

BACKGROUND: The T cell cytokine profile is a key prognostic indicator of post-surgical outcome for colorectal cancer (CRC). Whilst TH1 (IFN-γ+) cell-mediated responses generated in CRC are well documented and are associated with improved survival, antigen-specific TH17 (IL-17A+) responses have not been similarly measured. METHODS: We sought to determine the cytokine profile of circulating tumour antigen-(5T4/CEA) specific T cells of 34 CRC patients to address whether antigen-specific IL-17A responses were detectable and whether these were distinct to IFN-γ responses. RESULTS: As with IFN-γ-producing T cells, anti-5T4/CEA TH17 responses were detectable predominantly in early stage (TNM I/II) CRC patients. Moreover, whilst IL-17A was always produced in association with IFN-γ, this release was mainly from two distinct T cell populations rather than by 'dual producing' T cells. Patients mounting both tumour-specific TH1+/TH17+ responses exhibited prolonged relapse-free survival. CONCLUSIONS: Tumour antigen-specific TH17 responses play a beneficial role in preventing post-operative colorectal tumour recurrence.

A nomogram based on pretreatment levels of serum bilirubin and total bile acid levels predicts survival in colorectal cancer patients.

BACKGROUND: Serum bilirubin and total bile acid (TBA) levels have been reported to be strongly associated with the risk and prognosis of certain cancers. Here, we aimed to investigate the effects of pretreatment levels of serum bilirubin and bile acids on the prognosis of patients with colorectal cancer (CRC). METHODS: A retrospective cohort of 1474 patients with CRC who underwent surgical resection between January 2015 and December 2017 was included in the study. Survival analysis was used to evaluate the predictive value of pretreatment levels of bilirubin and bile acids. X-Tile software was used to identify optimal cut-off values for total bilirubin (TBIL), direct bilirubin (DBIL) and TBA in terms of overall survival (OS) and disease-free survival (DFS). RESULTS: DBIL, TBIL, and TBA were validated as significant prognostic factors by univariate Cox regression analysis for both 3-year OS and DFS. Multivariate Cox regression analyses confirmed that high DBIL, TBIL and TBA levels were independent prognostic factors for both OS (HR: 0.435, 95% CI: 0.299-0.637, P < 0.001; HR: 0.436, 95% CI: 0.329-0.578, P < 0.001; HR: 0.206, 95% CI: 0.124-0.341, P < 0.001, respectively) and DFS (HR: 0.583, 95% CI: 0.391-0.871, P = 0.008; HR:0.437,95% CI: 0.292-0.655, P <0.001; HR: 0.634, 95% CI: 0.465-0.865, P = 0.004, respectively). In addition, nomograms for OS and DFS were established according to all significant factors, and the c-indexes were 0.819 (95% CI: 0.806-0.832) and 0.835 (95% CI: 0.822-0.849), respectively. CONCLUSIONS: TBIL, DBIL and TBA levels are independent prognostic factors in colorectal cancer patients. The nomograms based on OS and DFS can be used as a practical model for evaluating the prognosis of CRC patients.

Hazard function analysis of metastatic recurrence after colorectal cancer surgery-A nationwide retrospective study.

BACKGROUND AND OBJECTIVES: An optimal postoperative surveillance protocol for colorectal cancer (CRC) is dependent on understanding the time line of recurrence. By hazard function analysis, this study aimed at evaluating the time of occurrence of metastasis. METHODS: A total of 21,671 Stage I-III colon cancer patients were retrospectively included from the Japanese study group for postoperative follow-up of colorectal cancer database. RESULTS: The 5-year incidence by metastasized organ was 6.3% for liver (right:left = 5.5%:7.0%, p = .0067), 6.0% for lung (right:left:rectum = 3.7%:4.4%:8.8%, p = 7.05E-45), and 2.0% for peritoneal (right:left:rectum = 3.1%:2.0%:1.2%, p = 1.29E-12). The peak of liver metastasis hazard rate (HR) (0.67 years) was earlier and higher than those of other metastases. The peak HR tended to be delayed in early stage CRCs (0.91, 0.76, and 0.52 years; for Stages I, II, and III, respectively). When analyzed as per the primary tumor location (right-sided, left-sided, and rectum), the peak HR for lung metastasis was twice as high for rectal cancer than for colon cancer, and peritoneal metastasis had a high HR in right-sided colon cancers. CONCLUSION: The time course for the risk of recurrence in various metastatic organs based on the primary tumor site was clearly visualized in this study. This will aid in individualizing postoperative surveillance schedules.

The interplay of KRAS mutational status with tumor laterality in non-metastatic colorectal cancer: An international, multi-institutional study in patients with known KRAS, BRAF, and MSI status.

BACKGROUND: Although the prognostic relevance of KRAS status in metastatic colorectal cancer (CRC) depends on tumor laterality, this relationship is largely unknown in non-metastatic CRC. METHODS: Patients who underwent resection for non-metastatic CRC between 2000 and 2018 were identified from institutional databases at six academic tertiary centers in Europe and Japan. The prognostic relevance of KRAS status in patients with right-sided (RS), left-sided (LS), and rectal cancers was assessed. RESULTS: Of the 1093 eligible patients, 378 had right-sided tumors and 715 had left-sided tumors. Among patients with RS tumors, the 5-year overall (OS) and recurrence-free survival (RFS) for patients with KRASmut versus wild-type tumors was not shown to differ significantly (82.2% vs. 83.2% and 72.1% vs. 76.7%, respectively, all p > .05). Among those with LS tumors, KRAS mutation was associated with shorter 5-year OS and RFS on both the univariable (OS: 79.4% vs. 86.1%, p = .004; RFS: 68.8% vs. 77.3%, p = .005) and multivariable analysis (OS: HR: 1.52, p = .019; RFS: HR: 1.32, p = .05). CONCLUSIONS: KRAS mutation status was independently prognostic among patients with LS tumors, but this association failed to reach statistical significance in RS and rectal tumors. These findings confirm reports in metastatic CRC and underline the possible biologic importance of tumor location.

Morbidity and Mortality in Patients with Perioperative COVID-19 Infection: Prospective Cohort in General, Gastroesophagic, Hepatobiliary, and Colorectal Surgery.

BACKGROUND: Severe acute respiratory syndrome due to coronavirus 2 has rapidly spread worldwide in an unprecedented pandemic. Patients with an ongoing COVID-19 infection requiring surgery have higher risk of mortality and complications. This study describes the mortality and morbidity in patients with perioperative COVID-19 infection undergoing elective and emergency surgeries. METHODS: Prospective cohort of consecutive patients who required a general, gastroesophageal, hepatobiliary, colorectal, or emergency surgery during COVID-19 pandemic at an academic teaching hospital. The primary outcome was 30-day mortality and major complications. Secondary outcomes were specific respiratory mortality and complications. RESULTS: A total of 701 patients underwent surgery, 39 (5.6%) with a perioperative COVID-19 infection. 30-day mortality was 12.8% and 1.4% in patients with and without COVID-19 infection, respectively (p < 0.001). Major surgical complications occurred in 25.6% and 6.8% in patients with and without COVID-19 infection, respectively (p < 0.001). Respiratory complications occurred in 30.8% and 1.4% in patients with and without COVID-19 infection, respectively (p < 0.001). Mortality due to a respiratory complication was 100% and 11.1% in patients with and without COVID-19 infection, respectively (p < 0.006). CONCLUSIONS: 30-day mortality and surgical complications are higher in patients with perioperative COVID-19 infection. Indications for elective surgery need to be reserved for non-deferrable procedures in order to avoid unnecessary risks of non-urgent procedures.

Lymphocyte-to-monocyte ratio combined with CA19-9 for predicting postoperative recurrence of colorectal cancer in patients with diabetes.

OBJECTIVE: To investigate the significance of lymphocyte-to-monocyte ratio (LMR) combined with carbohydrate antigen (CA) 19-9 for predicting postoperative recurrence of colorectal cancer (CRC) in patients with type II diabetes. METHODS: We conducted a retrospective analysis of 106 postoperative patients with stage II-III CRC and with type II diabetes. Their clinical indexes such as LMR and CA19-9 were collected, and the patients were followed up for 5 years. RESULTS: The CA19-9 level was 119.7 U/ml at baseline in the relapsed group, while this was 24.81 U/ml in non-relapsed group (p = 0.001). On the contrary, the LMR level was 5.10 and 2.57 for non-relapsed and relapsed group (p < 0.001), respectively. Kaplan-Meier survival curves stratified by CA19-9 and LMR suggested that patients with lower CA19-9 had higher survival probability (p < 0.001), while patients with high LMR level had higher survival probability (p < 0.001). The multivariable Cox proportional hazard regression analysis with CA19-9 and LMR indicated that although the baseline CA19-9 is significantly associated with increasing risk of disease recurrence, the HR (HR = 1.0, 95% CI 1.00-1.01) was small and close to 1, whereas the high baseline LMR (HR = 0.44, 95% CI 0.32-0.61) was associated with decrease in disease recurrence. Model with continuous CA19-9 and LMR was able to better predict (AUC 73.17%) the disease recurrence. CONCLUSION: LMR combined with CA19-9 may become a new index for predicting postoperative recurrence of CRC in patients with diabetes.

Influence of Muscle Mass Area and Visceral Obesity on 30-day Mortality After Colorectal Surgery with Primary Anastomosis.

BACKGROUND: Muscle mass and visceral fat may be assessed at the level of the third lumbar vertebra (L3) in computed tomography (CT). Both variables have been related with adverse surgical outcomes. OBJECTIVE: The objective of the study was to study the association of skeletal muscle index (SMI) and visceral fat area (VFA) with 30-day mortality in colorectal surgery. METHODS: This is a retrospective cohort study conducted at a tertiary referral hospital in Mexico City. Patients who underwent colorectal surgery with primary anastomosis from January 2007 to December 2018 were included in the study. Their preoperative CT scans were analyzed with the NIH ImageJ software at the level of the third lumbar vertebra to determine their SMI (L3-SMI) and the VFA. Logistic regression analysis (adjusted by surgery anatomical location) was used to determine the association between these variables and surgical 30-day mortality. RESULTS: A total of 548 patients were included; 30-day mortality was 4.18% (23 patients). On univariable analysis, L3-SMI, low SMI, anastomosis leak, pre-operative albumin, estimated blood loss, age, steroid use, Charlson comorbidity index score >2, and type of surgery were associated with 30-day mortality. On multivariable analysis, low SMI remained an independent risk factor with an odds ratio of 4.74, 95% confidence interval 1.22-18.36 (p = 0.02). CONCLUSION: Low SMI was found to be an independent risk factor for 30-day mortality in patients submitted to colorectal surgery with a primary anastomosis, whether for benign or malignant diagnosis. VFA was not associated with 30-day mortality.

A competing-risk nomogram to predict cause-specific death in elderly patients with colorectal cancer after surgery (especially for colon cancer).

BACKGROUND: Clinically, when the diagnosis of colorectal cancer is clear, patients are more concerned about their own prognosis survival. Special population with high risk of accidental death, such as elderly patients, is more likely to die due to causes other than tumors. The main purpose of this study is to construct a prediction model of cause-specific death (CSD) in elderly patients using competing-risk approach, so as to help clinicians to predict the probability of CSD in elderly patients with colorectal cancer. METHODS: The data were extracted from Surveillance, Epidemiology, and End Results (SEER) database to include ≥ 65-year-old patients with colorectal cancer who had undergone surgical treatment from 2010 to 2016. Using competing-risk methodology, the cumulative incidence function (CIF) of CSD was calculated to select the predictors among 13 variables, and the selected variables were subsequently refined and used for the construction of the proportional subdistribution hazard model. The model was presented in the form of nomogram, and the performance of nomogram was bootstrap validated internally and externally using the concordance index (C-index). RESULTS: Dataset of 19,789 patients who met the inclusion criteria were eventually selected for analysis. The five-year cumulative incidence of CSD was 31.405% (95% confidence interval [CI] 31.402-31.408%). The identified clinically relevant variables in nomogram included marital status, pathological grade, AJCC TNM stage, CEA, perineural invasion, and chemotherapy. The nomogram was shown to have good discrimination after internal validation with a C-index of 0.801 (95% CI 0.795-0.807) as well as external validation with a C-index of 0.759 (95% CI 0.716-0.802). Both the internal and external validation calibration curve indicated good concordance between the predicted and actual outcomes. CONCLUSION: Using the large sample database and competing-risk analysis, a postoperative prediction model for elderly patients with colorectal cancer was established with satisfactory accuracy. The individualized estimates of CSD outcome for the elderly patients were realized.

Improved Disease-free Survival After Prehabilitation for Colorectal Cancer Surgery.

OBJECTIVE: The objective of this study was to investigate the effect of prehabilitation on survival after colorectal cancer surgery. SUMMARY OF BACKGROUND DATA: Preoperative multimodal exercise and nutritional programs (prehabilitation) improve functional capacity and recovery following colorectal surgery. Exercise may also affect cancer outcomes by mediating the systemic inflammatory response. The effect of prehabilitation on cancer outcomes is unknown. METHODS: Pooled data from 3 prehabilitation trials (2 randomized controlled trials, 1 cohort) in patients undergoing elective, biopsy-proven, primary non-metastatic colorectal cancer surgery from 2009 to 2014 within an enhanced recovery program were analyzed. Patients were grouped into +prehab or-prehab. The primary outcomes were 5-year disease-free (DFS) and overall survival (OS). DFS and OS were analyzed using Kaplan-Meier curves and multiple Cox regression. RESULTS: A total of 202 patients were included (+prehab 104, -prehab 98). Median prehabilitation duration was 29 days (interquartile range 20-40). Patient and tumor characteristics were well-balanced (33% stage III). Postoperative complications and time to adjuvant chemotherapy were similar. Mean duration of follow-up was 60.3 months (standard deviation 26.2). DFS was similar for the combined group of stage I-III patients (P = 0.244). For stage III patients, prehabilitation was associated with improved DFS (73.4% vs 50.9%, P = 0.044). There were no differences in OS (P = 0.226). Prehabilitation independently predicted improved DFS (hazard ratio 0.45; 95% confidence interval, 0.21-0.93), adjusting for stage and other confounders. Prehabilitation did not independently predict OS. CONCLUSION: In this report, prehabilitation is associated with improved 5-year DFS in stage III colorectal cancer. This finding should be confirmed in future trials.

Perioperative Use of Nonsteroidal Anti-inflammatory Drugs Decreases the Risk of Recurrence of Cancer After Colorectal Resection: A Cohort Study Based on Prospective Data.

BACKGROUND: Perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to reduce inflammatory response in relation to surgery. Inflammation may promote recurrence of cancer, thus inhibition by use of NSAIDs could reduce recurrence after surgery. OBJECTIVE: The aim of this study was to examine the association between perioperative use of NSAIDs and cancer recurrence, as well as disease-free survival (DFS) and mortality after colorectal cancer surgery. METHODS: This was a cohort study based on data from a prospective clinical database, electronic medical records, and nationwide registers, and included patients from six major colorectal centers in Denmark. The primary outcome was cancer recurrence, while secondary outcomes included 5-year mortality and DFS. RESULTS: Overall, 2308 patients undergoing colorectal cancer surgery between 1 January 2006 and 31 December 2009 were included. A total of 909 patients received at least 2 days of treatment with NSAIDs, of whom 702 (77.2%) received ibuprofen and 204 (22.4%) received diclofenac. Cox regression analysis adjusting for NSAIDs resulted in decreased recurrence risk (adjusted hazard ratio [HRadjusted] 0.84, 95% confidence interval [CI] 0.72-0.99; p = 0.042). Competing risk analysis confirmed the finding, with an HRadjusted of 0.76 (95% CI 0.60-0.97; p = 0.026). There was no significant effect on mortality or DFS. Sensitivity analysis of the effect of ibuprofen reported an HRadjusted of 0.83 (95% CI 0.70-1.00; p = 0.047). In restricted analyses of localized disease only (Union for International Cancer Control [UICC] I-II) and elective surgery only, no effect was found (localized: HRadjusted 0.81, 95% CI 0.62-1.06, p = 0.12; elective: HRadjusted 0.85, 95% CI 0.72-1.01, p = 0.063). CONCLUSIONS: Perioperative use of NSAIDs was associated with a reduced risk of cancer recurrence after resection for colorectal cancer. No effect on 5-year mortality or DFS was found.

Survival in Patients with High-Grade Colorectal Neuroendocrine Carcinomas: The Role of Surgery and Chemotherapy.

BACKGROUND: Colorectal neuroendocrine tumors are a rare malignancy, yet their incidence appears to be increasing. The optimal treatment for the high-grade subset of these tumors remains unclear. We aimed to examine the relationship between different treatment modalities and outcomes for patients with high-grade neuroendocrine carcinomas (HGNECs) of the colon and rectum. METHODS: The National Cancer Database (2004-2015) was used to identify patients diagnosed with colorectal HGNECs. The primary outcome was overall survival. A Cox Proportional hazard model was used to identify risk factors for survival. RESULTS: Overall, 1208 patients had HGNECs; 452 (37.4%) patients had primary tumors of the rectum, and 756 (62.5%) patients had primary tumors of the colon. A total of 564 (46.7%) patients presented with stage IV disease. The median survival was 9.0 months [95% confidence interval (CI) 8.2-9.8]. In multivariable analysis, surgical resection [hazard ratio (HR) 0.54, 95% CI 0.44-0.66; p < 0.001], chemotherapy (HR 0.74, 95% CI 0.69-0.79; p < 0.001), and rectum as the primary site of tumor (HR 0.62, 95% CI 0.51-0.76; p < 0.001) were associated with better overall survival, while older age (HR 1.01, 95% CI 1.00-1.01; p = 0.02) and the presence of metastatic disease (HR 3.34, 95% CI 2.69-4.15; p < 0.001) were associated with worse survival. CONCLUSIONS: Patients with colorectal HGNECs selected for chemotherapy and surgical resection of the primary tumor demonstrated better overall survival than those managed without resection. Patients who were able to undergo systemic chemotherapy may benefit from potentially curative resection of the primary tumor.

Meta-analysis of medial-to-lateral versus lateral-to-medial colorectal mobilisation during laparoscopic colorectal surgery.

OBJECTIVES: To evaluate comparative outcomes of medial-to-lateral and lateral-to-medial colorectal mobilisation in patients undergoing laparoscopic colorectal surgery. METHODS: We conducted a systematic search of electronic databases and bibliographic reference lists. Perioperative mortality and morbidity, procedure time, length of hospital stay, rate of conversion to open procedure, and number of harvested lymph nodes were the outcome parameters. Combined overall effect sizes were calculated using fixed-effects or random-effects models. RESULTS: We identified eight comparative studies reporting a total of 1477 patients evaluating outcomes of medial-to-lateral (n = 626) and lateral-to-medial (n = 851) approaches in laparoscopic colorectal resection. The medial-to-lateral approach was associated with significantly lower rate of conversion to open (odds ratio (OR) 0.43, P = 0.001), shorter procedure time (mean difference (MD) - 32.25, P = 0.003) and length of hospital stay (MD - 1.54, P = 0.02) compared to the lateral-to-medial approach. However, there was no significant difference in mortality (risk difference (RD) 0.00, P = 0.96), overall complications (OR 0.78, P = 0.11), wound infection (OR 0.84, P = 0.60), anastomotic leak (OR 0.70, P = 0.26), bleeding (OR 0.60, P = 0.50), and number of harvested lymph nodes (MD - 1.54, P = 0.02) between two groups. Sub-group analysis demonstrated that the lateral-to-medial approach may harvest more lymph nodes in left-sided colectomy (MD - 1.29, P = 0.0009). The sensitivity analysis showed that overall complications were lower in the medial-to-lateral group (OR 0.72, P = 0.49). CONCLUSIONS: Our meta-analysis (level 2 evidence) showed that medial-to-lateral approach during laparoscopic colorectal resection may reduce procedure time, length of hospital stay and conversion to open procedure rate. Moreover, it may probably reduce overall perioperative morbidity. However, both approaches carry similar risk of mortality, and have comparable ability to harvest lymph nodes. Future high-quality randomised trials are required.

Screening and systematic follow-up for cardiopulmonary comorbidity in elective surgery for colorectal cancer: a randomised feasibility study.

BACKGROUND: One third of patients with colorectal cancer (CRC) have comorbidity, which impairs their postoperative outcomes. Scoring systems may predict mortality, but there is limited evidence of effective interventions in high-risk patients. Our aim was to test a trial setup to assess the effect of extra postoperative medical visits and follow-up on 1-year mortality and other outcomes in patients with cardiopulmonary risk factors undergoing elective surgery for colorectal tumours. METHODS: Patients preoperatively screened positive for cardiopulmonary comorbidity were eligible. On postoperative day 4, they were randomised to either routine follow-up (RFU) or RFU with one extra medical visit and additional visits to the Cardiology and Respiratory Medicine Clinics 1 and 3 months postoperatively. The primary outcome measure was 1-year mortality; secondary outcome measures were length of stay (LOS), complications, and readmissions. RESULTS: Of 673 screened patients 326 (48%) were found eligible, 108 declined participation, and 198 were randomised. Postoperative medical problems and/or need for intervention were found in 15-23% of the patients at the extra medical visits. The 90-day mortality was 0 and the 1-year mortality only 2.6% with no differences between the two groups. LOS and complication rates did not differ, but there were significantly fewer readmissions in the intervention group. CONCLUSIONS: The 1-year mortality after elective CRC surgery was low, even in the presence of cardiopulmonary risk factors. There was no evidence of reduced mortality with additional medical follow-up in these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02328365 registered 31 December 2014 (retrospectively registered).

Treatment and Outcome of Synchronous Colorectal Carcinomas: A Nationwide Study.

BACKGROUND: Synchronous colorectal carcinomas (CRC) occur in 1-8% of patients diagnosed with CRC. This study evaluated treatment patterns and patient outcomes in synchronous CRCs compared with solitary CRC patients. METHODS: All patients diagnosed with primary CRC between 2008 and 2013, who underwent elective surgery, were selected from the Netherlands Cancer Registry. Using multivariable regressions, the effects of synchronous CRC were assessed for both short-term outcomes (prolonged postoperative hospital admission, anastomotic leakage, postoperative 30-day mortality, administration of neoadjuvant or adjuvant treatment), and 5-year relative survival (RS). RESULTS: Of 41,060 CRC patients, 1969 patients (5%) had synchronous CRC. Patients with synchronous CRC were older (mean age 71 ± 10.6 vs. 69 ± 11.4 years), more often male (61 vs. 54%), and diagnosed with more advanced tumour stage (stage III-IV 54 vs. 49%) compared with solitary CRC (all p < 0.0001). In 50% of the synchronous CRCs, an extended surgery was conducted (n = 934). Synchronous CRCs with at least one stage II-III rectal tumour less likely received neoadjuvant (chemo)radiation [78 vs. 86%; adjusted OR 0.6 (0.48-0.84)], and synchronous CRCs with at least one stage III colon tumour less likely received adjuvant chemotherapy [49 vs. 63%; adjusted OR 0.7 (0.55-0.89)]. Synchronous CRCs were independently associated with decreased survival [RS 77 vs. 71%; adjusted RER 1.1 (1.01-1.23)]. CONCLUSIONS: The incidence of synchronous CRCs in the Dutch population is 5%. Synchronous CRCs were associated with decreased survival compared with solitary CRC. The results emphasize the importance of identifying synchronous tumours, preferably before surgery to provide optimal treatment.

Systematic Review and Meta-analysis of Objective Assessment of Physical Fitness in Patients Undergoing Colorectal Cancer Surgery.

BACKGROUND: Gas exchange-derived variables obtained from cardiopulmonary exercise testing allow objective assessment of functional capacity and hence physiological reserve to withstand the stressors of major surgery. Field walk tests provide an alternate means for objective assessment of functional capacity that may be cheaper and have greater acceptability, in particular, in elderly patients. OBJECTIVE: This systematic review evaluated the predictive value of cardiopulmonary exercise testing and field walk tests in surgical outcomes after colorectal surgery. DATA SOURCE: A systematic search was undertaken using Medline, PubMed, Embase, CINAHL, and PEDro. STUDY SELECTION: Adult patients who had cardiopulmonary exercise testing and/or field walk test before colorectal surgery were included. MAIN OUTCOME MEASURE: The primary outcomes measured were hospital length of stay and postoperative morbidity and mortality. RESULTS: A total of 7 studies with a cohort of 1418 patients who underwent colorectal surgery were identified for inclusion in a qualitative analysis. Both pooled oxygen consumption at anaerobic threshold (range, 10.1-11.1 mL·kg·min) and peak oxygen consumption (range, 16.7-18.6 mL·kg·min) were predictive of complications (OR for anaerobic threshold, 0.76; 95% CI, 0.66-0.85, p<0.0001; OR for peak oxygen consumption, 0.76; 95% CI, 0.67-0.85, p<0.0001). Patients had significant increased risk of developing postoperative complications if their anaerobic threshold was below this cut point (p<0.001). However, it was not predictive of anastomotic leak (p = 0.644). Shorter distance (<250 m) walked in incremental shuttle walk test, lower anaerobic threshold, and lower peak oxygen consumption were associated with prolonged hospital length of stay, which was closely related to the development of complications. CONCLUSIONS: Variables derived from cardiopulmonary exercise testing are predictive of postoperative complications and hospital length of stay. Currently, there are insufficient data to support the predictive role of the field walk test in colorectal surgery.

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.

Predictors of Anastomotic Leak in Elderly Patients After Colectomy: Nomogram-Based Assessment From the American College of Surgeons National Surgical Quality Program Procedure-Targeted Cohort.

BACKGROUND: Elderly patients undergoing colorectal surgery have increasingly become under scrutiny by accounting for the largest fraction of geriatric postoperative deaths and a significant proportion of all postoperative complications, including anastomotic leak. OBJECTIVE: This study aimed to determine predictors of anastomotic leak in elderly patients undergoing colectomy by creating a novel nomogram for simplistic prediction of anastomotic leak risk in a given patient. DESIGN: This study was a retrospective review. SETTINGS: The database review of the American College of Surgeons National Surgical Quality Improvement Program was conducted at a single institution. PATIENTS: Patients aged ≥65 years who underwent elective segmental colectomy with an anastomosis at different levels (abdominal or low pelvic) in 2012-2013 were identified from the multi-institutional procedure-targeted database. MAIN OUTCOME MEASURES: We constructed a stepwise multiple logistic regression model for anastomotic leak as an outcome; predictors were selected in a stepwise fashion using the Akaike information criterion. The validity of the nomogram was externally tested on elderly patients (≥65 years of age) from the 2014 American College of Surgeons National Surgical Quality Improvement Program colectomy-targeted database. RESULTS: A total of 10,392 patients were analyzed, and anastomotic leak occurred in 332 (3.2%). Of the patients who developed anastomotic leak, 192 (57.8%) were men (p < 0.001). Based on unadjusted analysis, factors associated with an increased risk of anastomotic leak were ASA score III and IV (p < 0.001), chronic obstructive pulmonary disease (p = 0.004), diabetes mellitus (p = 0.003), smoking history (p = 0.014), weight loss (p = 0.013), previously infected wound (p = 0.005), omitting mechanical bowel preparation (p = 0.005) and/or preoperative oral antibiotic use (p < 0.001), and wounds classified as contaminated or dirty/infected (p = 0.008). Patients who developed anastomotic leak had a longer length of hospital stay (17 vs 7 d; p < 0.001) and operative time (191 vs 162 min; p < 0.001). A multivariate model and nomogram were created. LIMITATIONS: This study was limited by its retrospective nature and short-term follow-up (30 d). CONCLUSIONS: An accurate prediction of anastomotic leak affecting morbidity and mortality after colorectal surgery using the proposed nomogram may facilitate decision making in elderly patients for healthcare providers.

Factors affecting the postoperative morbidity and survival of patients with liver cirrhosis following colorectal cancer surgery.

PURPOSE: Data are lacking on the appropriate risk stratification of patients undergoing surgery for colorectal cancer (CRC). This study aimed to evaluate the predictive factors for perioperative morbidity and oncological outcomes in CRC patients with liver cirrhosis (LC). METHODS: A retrospective analysis of prospectively collected data was conducted. A total of 161 LC patients who underwent surgery for CRC were identified between January 2001 and December 2010. RESULTS: The mean patient age was 60 ± 10 years, and the median follow-up period was 54.0 months (range 0.5-170.0). The proportions of patients with Child-Pugh classifications for LC were as follows: A (n = 118; 73.3%), B (n = 39; 24.2%), and C (n = 4; 2.5%). The median model for end-stage liver disease (MELD) score was 8 (range 6-21). The postoperative morbidity rate was 37.3% (60/161). Hyperbilirubinemia (p = 0.002), prothrombin time (PT) prolongation (p = 0.020), and intraoperative transfusion (p = 0.003) were the significant factors for postoperative morbidity in multivariate analysis. The postoperative mortality rate was 3.1% (5/161), and the 5-year cancer-specific and 5-year overall survival rates were 86.1 and 59.9%, respectively. The significant clinical risk factors by multivariate analysis that influenced overall survival were the TNM stage of CRC (p = 0.035), MELD score (>8 points) (p < 0.001), and the coexistence of hepatocellular carcinoma (HCC) (p = 0.012). CONCLUSIONS: Hyperbilirubinemia, PT prolongation, and intraoperative transfusion are significant risk factors for postoperative morbidity in LC patients who undergo surgery for CRC. Additionally, not only advanced TNM stage but also a high MELD score and the coexistence of HCC are associated with poor overall survival in CRC patients with LC.

Outcomes after non-cardiac surgery: mortality, complications, disability, and rehospitalization.

In the last 25 years, the number of patients aged ≥75 years undergoing non-cardiac surgery has greatly increased. In elderly patients, frailty is significantly associated with an increased risk of adverse events, functional decline, procedural complications, prolonged hospitalization, and mortality. The relationship between frailty and increased mortality and morbidity requires an appropriate tool of assessment to accurately quantify the patient's clinical and perioperative conditions. The preoperative evaluation of elderly patients candidate for non-cardiac surgery should include assessment of frailty, sarcopenia and malnutrition, as these are related to high surgical risk. For colon-rectal surgery as also for gastric cancer surgery, especially early gastric cancer, the introduction of laparoscopy has yielded considerable benefits in terms of short-term postsurgical outcomes, e.g. lower rate of intraprocedural bleeding and reduced length of hospital stay. Despite the progress made in preoperative assessment, surgical procedures and postoperative management, the improvement of outcomes after non-cardiac surgery in elderly patients remains a challenge and calls for future, well-designed clinical studies.