Upfront laparotomy versus conversion from minimally invasive surgery to open surgery in colon cancer: Is there a difference in outcomes?

BACKGROUND: It is unclear whether conversion from minimally invasive surgery to laparotomy in patients with colon cancer contributes to worse outcomes compared with those operated by laparotomy. In this study, we aimed to assess the implications of transitioning from minimally invasive surgery to laparotomy in patients with colon cancer compared with patients undergoing upfront laparotomy. METHODS: A retrospective analysis of the National Cancer Database, including patients with stages I to III colon cancer (2010-2019). Patients who underwent either upfront laparotomy (Open Surgery Group) or minimally invasive surgery converted to open surgery (Converted Surgery Group) were included. Groups were balanced using propensity-score matching. Primary outcome was overall survival, and secondary outcomes included 30- and 90-day mortality and 30-day readmission rates. RESULTS: The study included 65,083 operated patients with stage I to III colon cancer; 57,091 patients (87.7%) were included in the Open Surgery group and 7,992 (12.3%) in the Converted Surgery group. 93.5% were converted from laparoscopy, and 6.5% were converted from robotic surgery. After propensity-score matching, 7,058 patients were included in each group. Median overall survival was significantly higher in the Converted Surgery group (107.3 months) than in the Open Surgery group (101.5 months; P = .006). A survival benefit was seen in patients >65 years of age (79.5 vs 71.9 months; P = .001), left-sided disease (129.4 vs 114.5 months; P < .001), and with a high Charlson comorbidity index score (=3; 58.9 vs 42.3 months; P = .03). Positive margin rates were similar between the groups (6.3% vs 5.6%; P = .07). Converted patients had a higher 30-day readmission rate (6.7% vs 5.6%, P = .006) and shorter duration of stay (median, 5 vs 6 days, P < .001) than patients in the Open Surgery group. In addition, 30-day mortality was comparable between the groups (2.9% vs 3.5%; P = .07). CONCLUSION: Conversion to open surgery from minimally invasive surgery was associated with better overall survival compared with upfront open surgery. A survival benefit was mainly seen in patients >65 years of age, with significant comorbidities, and with left-sided tumors. We believe these data suggest that, in the absence of an absolute contraindication to minimally invasive surgery, it should be the preferred approach in patients with colon cancer.

Short- and long-term outcome after colon cancer resections performed by male and female surgeons: A single-center retrospective cohort study.

BACKGROUND AND OBJECTIVE: To assess the effect of surgeon sex on short- and long-term outcomes after colon cancer resections. METHODS: Clinical data of patients who underwent colon cancer resections between 2010 and 2020 at Helsingborg Hospital, Sweden, were retrospectively obtained from medical records. The sex of the surgeon of each procedure was recorded. Morbidity, mortality, and long-term survival were compared in patients operated by male and female surgeons. RESULTS: Colon cancer resections were performed by 23 male and 9 female surgeons in 1113 patients (79% elective, 21% emergent). After elective surgery, there was no difference in postoperative complications, 30-day mortality, or long-term survival between patients operated by male and female surgeons. Following emergent resections, the complication rate was significantly lower in patients operated by female surgeons (41.3% vs 58.1%, p = 0.019). Similarly, the rates of R1-resections (0% vs 5.2%, p = 0.039), reoperations (3.8% vs 14.2%, p = 0.014), and intensive care unit (ICU) care (6.3% vs 17.4%, p = 0.018) were significantly lower for patients operated by female surgeons, but there was no difference in 30-day mortality (6.3% vs 5.2%, p = 0.767). Cox regression analysis showed that long-term and cancer-free survival in patients emergently operated by male surgeons was significantly shorter than that of patients operated by female surgeons (hazard ratio = 1.9 (95% confidence interval (CI) = 1.3-2.8), p = 0.001 and hazard ratio = 1.7 (95% CI = 1.1-2.7), p = 0.016). CONCLUSIONS: The short- and long-term outcome after elective colon cancer resections were similar in patients operated by male and female surgeons. The outcome following emergent resections performed by female surgeons compared favorably with that of male surgeons, with fewer complications and reoperations and better long-term survival.

Prognostic value of preoperative high-sensitivity modified Glasgow prognostic score in advanced colon cancer: a retrospective observational study.

BACKGROUND: Several studies have demonstrated that the preoperative Glasgow prognostic score (GPS) and modified GPS (mGPS) reflected the prognosis in patients undergoing curative surgery for colorectal cancer. However, there are no reports on long-term prognosis prediction using high-sensitivity mGPS (HS-GPS) in colorectal cancer. Therefore, this study aimed to calculate the prognostic value of preoperative HS-GPS in patients with colon cancer. METHODS: A cohort of 595 patients with advanced resectable colon cancer managed at our institution was analysed retrospectively. HS-GPS, GPS, and mGPS were evaluated for their ability to predict prognosis based on overall survival (OS) and recurrence-free survival (RFS). RESULTS: In the univariate analysis, HS-GPS was able to predict the prognosis with significant differences in OS but was not superior in assessing RFS. In the multivariate analysis of the HS-GPS model, age, pT, pN, and HS-GPS of 2 compared to HS-GPS of 0 (2 vs 0; hazard ratio [HR], 2.638; 95% confidence interval [CI], 1.046-6.650; P = 0.04) were identified as independent prognostic predictors of OS. In the multivariate analysis of the GPS model, GPS 2 vs 0 (HR, 1.444; 95% CI, 1.018-2.048; P = 0.04) and GPS 2 vs 1 (HR, 2.933; 95% CI, 1.209-7.144; P = 0.017), and in that of the mGPS model, mGPS 2 vs 0 (HR, 1.51; 95% CI, 1.066-2.140; P = 0.02) were independent prognostic predictors of OS. In each classification, GPS outperformed HS-GPS in predicting OS with a significant difference in the area under the receiver operating characteristic curve. In the multivariate analysis of the GPS model, GPS 2 vs 0 (HR, 1.537; 95% CI, 1.190-1.987; P = 0.002), and in that of the mGPS model, pN, CEA were independent prognostic predictors of RFS. CONCLUSION: HS-GPS is useful for predicting the prognosis of resectable advanced colon cancer. However, GPS may be more useful than HS-GPS as a prognostic model for advanced colon cancer.

Anastomotic Leak is Increased With Clostridium difficile Infection After Colectomy: Machine Learning-Augmented Propensity Score Modified Analysis of 46 735 Patients.

BACKGROUND: Clostridium difficile infection (CDI) is now the most common cause of healthcare-associated infections, with increasing prevalence, severity, and mortality of nosocomial and community-acquired CDI which makes up approximately one third of all CDI. There are also increased rates of asymptomatic colonization particularly in high-risk patients. C difficile is a known collagenase-producing bacteria which may contribute to anastomotic leak (AL). METHODS: Machine learning-augmented multivariable regression and propensity score (PS)-modified analysis was performed in this nationally representative case-control study of CDI and anastomotic leak, mortality, and length of stay for colectomy patients using the ACS-NSQIP database. RESULTS: Among 46 735 colectomy patients meeting study criteria, mean age was 61.7 years (SD 14.38), 52.2% were woman, 72.5% were Caucasian, 1.5% developed CDI, 3.1% developed anastomotic leak, and 1.6% died. In machine learning (backward propagation neural network)-augmented multivariable regression, CDI significantly increases anastomotic leak (OR 2.39, 95% CI 1.70-3.36; P < .001), which is similar to the neural network results. Having CDI increased the independent likelihood of anastomotic leak by 3.8% to 6.8% overall, and in dose-dependent fashion with increasing ASA class to 4.3%, 5.7%, 7.6%, and 10.0%, respectively, for ASA class I to IV. In doubly robust augmented inverse probability weighted PS analysis, CDI significantly increases the likelihood of AL by 4.58% (95% CI 2.10-7.06; P < .001). CONCLUSIONS: This is the first known nationally representative study on CDI and AL, mortality, and length of stay among colectomy patients. Using advanced machine learning and PS analysis, we provide evidence that suggests CDI increases AL in a dose-dependent manner with increasing ASA Class.

Can the American College of Surgeons National Surgical Quality Improvement Program Risk Calculator Predict Outcomes for Urgent Colectomies?

BACKGROUND: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Risk Calculator (RC) predicts postoperative outcomes using 19 risk factors, including operative acuity. Acuity is defined by the calculator as emergent or elective only. The objective of this study is to evaluate the RC's accuracy in urgent (nonelective/nonemergent) cases. METHODS: This is a retrospective review of the NSQIP data for patients who underwent urgent colectomies at a single tertiary care center over a 4-year period. Each urgent case was entered into the RC as both elective and emergent, and predicted outcomes were compared to actual postoperative outcomes. Receiver operating characteristic (ROC) curves were used when sufficient statistical power was present and the area under the curve (AUC) was calculated. RESULTS: A total of 301 urgent colectomy patients were evaluated, representing 19% of all colectomies performed at our institution during the study period. Of the 15 possible postoperative outcomes, the RC showed high predictive value only for mortality (AUC elective .8467; emergent .8451) and discharge to a nursing/rehabilitation facility (AUC elective .8089; emergent .8105). The RC showed no predictive value for 6 outcomes and the remainder lacked statistical power to draw conclusions. DISCUSSION: While the calculator predicted mortality and discharge to a nursing/rehabilitation facility, it did not accurately predict complications for urgent colectomies. Future versions of the calculator should focus on improving the predictive value by including urgent cases as a separate category.

Sequential Minimally Invasive Treatment of Concomitant Abdominal Aortic Aneurysm and Colorectal Cancer: A Single-Center Experience.

BACKGROUND: The surgical management of concomitant occurrence of abdominal aortic aneurysm (AAA) and colorectal cancer (CRC) is still controversial. Conversely, benefits from a minimally invasive approach are well known concerning the treatment of both AAA and CRC. The aim of this study is to assess safety and feasibility of a sequential 2-staged minimally invasive during the same recovery by endovascular aneurysm repair (EVAR) technique and laparoscopic colorectal resection. METHODS: From January 2008 to December 2020, all patients with concomitant AAA and CRC were consecutively treated by EVAR and laparoscopic colorectal resection. Perioperative data were retrospectively collected in order to evaluate short- and long-term outcomes following the sequential 2-staged procedures. RESULTS: A total of 24 patients were included. The localization of the aneurysm was infrarenal abdominal aortic in 23 cases and in one case of common iliac artery. EVAR procedure has always been performed first. In 18 patients, a percutaneous access has been used while in 6 patients a surgical access has been adopted. Twelve patients had cancer in the left colon, 9 in the right colon, and 3 patients had rectal cancer. No conversions or intraoperative complications had occurred during laparoscopic surgery. The major complications rate after EVAR and CRC surgery was 8.3% and 12.5%, respectively. The mean interval between EVAR and CRC treatment was 7.8 ± 1 and the mean length of stay was 15.4 ± 3.6. No deaths occurred during hospitalization and between the procedures. Overall mortality was 20.8% with a mean follow-up of 39.41 ± 19.2 months. CONCLUSION: Elective sequential 2-staged minimally invasive treatment is a safe and feasible approach with acceptable morbidity and mortality rates and it should be adopted in current clinical practice to manage concomitant AAA and CRC.

Immune Dysfunction as Measured by the Systemic Immune-Inflammation Index is Associated with the Sub-Type of Minimal Residual Disease and Outcome in Stage II Colon Cancer Treated with Surgery alone.

OBJECTIVE: Within 5 years after curative surgery for stage II colon cancer 25% of patients will relapse due to minimal residual disease (MRD). MRD is the net result of the biological properties of subpopulations of primary tumour cells which enable them to disseminate, implant in distant tissues and survive and the immune system's ability to eliminate them. We hypothesize that markers of immune dysfunction such as the systemic inflammation index (SII) are associated with the sub-type of MRD defined by bone marrow micro-metastasis (mM) and circulating tumour cells (CTCs). A higher immune dysfunction being associated with a more aggressive MRD and worse prognosis. METHODS AND PATIENTS: Blood and bone marrow samples were taken to detect CTCs and mM using immunocytochemistry with anti-CEA one month after surgery. The SII, absolute neutrophil, platelet and lymphocyte counts (ANC, APC, ALC) were determined immediately pre-surgery and one month post-surgery. These were compared with the sub-types of MRD; Group I MRD (-); Group II mM positive and Group III CTC positive; cut-off values of SII of >700 and >900 were used. Follow-up was for up to 5 years or relapse and survival curves using Kaplan-Meier (KM) were calculated. RESULTS: One hundred and eighty one patients (99 women) participated, mean age 68 years, median follow up 4.04 years; I: = 105 patients, II: N= 36 patients, III: N=40 patients. The SII significantly decreased post-surgery only in Group I patients. The frequency of SII >700 and >900 was significantly higher in Group III, between Groups I and II there was no significant difference.  The SII was significantly associated with the number of CTCs detected. The 5-year KM was 98% Group I, 68% Group II and 7% Group III. CONCLUSIONS: The results of the study suggest that the severity of immune dysfunction as determined by the SII is associated with differing sub-types of MRD and a worse prognosis; increasing immune dysfunction is associated with a more aggressive CTC positive MRD sub-type; a more severe immune dysfunction is associated with a higher number of CTCs detected.
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Intersection of social vulnerability and residential diversity: Postoperative outcomes following resection of lung and colon cancer.

INTRODUCTION: While the impact of demographic factors on postoperative outcomes has been examined, little is known about the intersection between social vulnerability and residential diversity on postoperative outcomes following cancer surgery. METHODS: Individuals who underwent a lung or colon resection for cancer were identified in the 2016-2017 Medicare database. Data were merged with the Centers for Disease Control and Prevention social vulnerability index and a residential diversity index was calculated. Logistic regression models were utilized to estimate the probability of postoperative outcomes. RESULTS: Among 55 742 Medicare beneficiaries who underwent lung (39.4%) or colon (60.6%) resection, most were male (46.6%), White (90.2%) and had a mean age of 75.3 years. After adjustment for competing risk factors, both social vulnerability and residential diversity were associated with mortality and other postoperative outcomes. In assessing the intersection of social vulnerability and residential diversity, synergistic effects were noted as patients from counties with low social vulnerability and high residential diversity had the lowest probability of 30-day mortality (3.2%, 95% confidence interval [CI]: 3.0-3.5) while patients from counties with high social vulnerability and low diversity had a higher probability of 30-day postoperative death (5.2%, 95% CI: 4.6-5.8; odds ratio: 1.02, 95% CI: 1.01-1.03). CONCLUSION: Social vulnerability and residential diversity were independently associated with postoperative outcomes. The intersection of these two social health determinants demonstrated a synergistic effect on the risk of adverse outcomes following lung and colon cancer surgery.

Differential Perioperative Outcomes in Patients With Obstructive Sleep Apnea, Obesity, or a Combination of Both Undergoing Open Colectomy: A Population-Based Observational Study.

BACKGROUND: An increasing body of evidence demonstrates an association between obstructive sleep apnea (OSA) and adverse perioperative outcomes. However, large-scale data on open colectomies are lacking. Moreover, the interaction of obesity with OSA is unknown. This study examines the impact of OSA, obesity, or a combination of both, on perioperative complications in patients undergoing open colectomy. We hypothesized that while both obesity and OSA individually increase the likelihood for perioperative complications, the overlap of the 2 conditions is associated with the highest risk. METHODS: Patients undergoing open colectomies were identified using the national Premier Healthcare claims-based Database (2006-2016; n = 340,047). Multilevel multivariable models and relative excess risk due to interaction (RERI) analysis quantified the impact of OSA, obesity, or both on length and cost of hospitalization, respiratory and cardiac complications, intensive care unit (ICU) admission, mechanical ventilation, and inhospital mortality. RESULTS: Nine thousand twenty-eight (2.7%) patients had both OSA and obesity diagnoses; 10,137 (3.0%) had OSA without obesity; and 33,692 (9.9%) had obesity without OSA. Although there were overlapping confidence intervals in the binary outcomes, the risk increase was found highest for OSA with obesity, intermediate for obesity without OSA, and lowest for OSA without obesity. The strongest effects were seen for respiratory complications: odds ratio (OR), 2.41 (2.28-2.56), OR, 1.40 (1.31-1.49), and OR, 1.50 (1.45-1.56), for OSA with obesity, OSA without obesity, and obesity without OSA, respectively (all P < .0001). RERI analysis revealed a supraadditive effect of 0.51 (95% confidence interval [CI], 0.34-0.68) for respiratory complications, 0.11 (-0.04 to 0.26) for cardiac complications, 0.30 (0.14-0.45) for ICU utilization, 0.34 (0.21-0.47) for mechanical ventilation utilization, and 0.26 (0.15-0.37) for mortality in patients with both OSA and obesity, compared to the sum of the conditions' individual risks. Inhospital mortality was significantly higher in patients with both OSA and obesity (OR [CI], 1.21 [1.07-1.38]) but not in the other groups. CONCLUSIONS: Both OSA and obesity are individually associated with adverse perioperative outcomes, with a supraadditive effect if both OSA and obesity are present. Interventions, screening, and perioperative precautionary measures should be tailored to the respective risk profile. Moreover, both conditions appear to be underreported compared to the general population, highlighting the need for stringent perioperative screening, documentation, and reporting.

Impact of Frailty on Clinical Outcomes and Hospitalization Costs Following Elective Colectomy.

BACKGROUND: Frailty has been increasingly recognized as a risk factor for inferior surgical outcomes and greater resource use. The present study evaluated the impact of a coding-based frailty tool on outcomes of elective colectomy in a national cohort. STUDY DESIGN: Adults undergoing elective colectomy were identified in the 2016-17 Nationwide Readmissions Database. Frailty was defined using the Johns Hopkins 10-domain coding-based binary tool. Generalized linear models were used to examine the association of frailty with in-hospital mortality, nonhome discharge, hospitalization duration (LOS), and inflation-adjusted costs. Kaplan-Meier survival analysis and log-rank test was used to compare readmissions up to 1-year. RESULTS: Of 133 175 patients, 10.6% were considered frail. The most common resections were sigmoid (43.9%) and right (34.7%) while total colectomy was least common (2.8%). After adjustment, frailty was associated with greater odds of mortality (3.2, 95% CI 2.8-3.8) and nonhome discharge (6.0, 95% CI 5.5-6.4) as well as a $13,400-increment (95% CI 12,400-14,400) in costs and 4.4-day (95% CI 4.1-4.6) increase in LOS. Nonelective readmissions at 30 days were greater in frail than non-frail groups (14.7% vs. 10.4%, P < .001). CONCLUSION: Frailty is associated with inferior clinical outcomes and increased resource use following elective colectomy. Inclusion of frailty in risk models may facilitate risk stratification and shared decision-making.

Impact of laparoscopy on oncological outcomes after colectomy for stage III colon cancer: A post-hoc multivariate analysis from PETACC8 European randomized clinical trial.

BACKGROUND: In colon cancer (CC), surgery remains the mainstay of treatment with curative intent. Despite several clinical trials comparing open and laparoscopic approaches, data on long-term outcomes for stage III CC are lacking. METHODS: This post-hoc analysis of the European PETACC8 randomized phase 3 trial included patients from 340 sites between December 2005 and November 2009, with long follow-up (median 7.56 years). Patients were randomly assigned to FOLFOX or FOLFOX+cetuximab after colonic resection. The surgical approach was left to the referring surgeon's discretion. RESULTS: Among 2555 patients included, 1796 (70.29%) were operated on by open surgery and 759 (29.71%) by laparoscopy. The 5-year OS rate was better after laparoscopic resection (85.4%, 95%CI 82.5-87.7) than after open surgery (80.2%, 95%CI 78.2-82.0; p = 0.002). The 5-year DFS rate was also better after laparoscopy (p = 0.016). However, in multivariate analysis using a propensity matching, the surgical approach was not found to be an independent prognostic factor for OS or DFS. OS (p = 0.0243) and DFS (p = 0.035) were increased after laparoscopic surgery in KRAS/BRAF WT sub-group CONCLUSION: We showed that laparoscopic resection has comparable long-term outcomes to open surgery in patients with stage III CC. For those with RAS and BRAF WT CC, laparoscopic colectomy may favorably impact survival.

Short-term outcomes of complete mesocolic excision versus D2 dissection in patients undergoing laparoscopic colectomy for right colon cancer (RELARC): a randomised, controlled, phase 3, superiority trial.

BACKGROUND: Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This trial aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. This article reports the early safety results from the trial. METHODS: This randomised, controlled, phase 3, superiority, trial was done at 17 hospitals in nine provinces of China. Eligible patients were aged 18-75 years with histologically confirmed primary adenocarcinoma located between the caecum and the right third of the transverse colon, without evidence of distant metastases. Central randomisation was done by means of the Clinical Information Management-Central Randomisation System via block randomisation (block size of four). Patients were randomly assigned (1:1) to CME or D2 dissection during laparoscopic right colectomy. Central lymph nodes were dissected in the CME but not in the D2 procedure. Neither investigators nor patients were masked to their group assignment but the quality control committee were masked to group assignment. The primary endpoint was 3-year disease-free survival, but the data for this endpoint are not yet mature; thus, only the secondary outcomes-intraoperative surgical complications and postoperative complications within 30 days of surgery, graded according to the Clavien-Dindo classification, mortality (death from any cause within 30 days of surgery), and central lymph node metastasis rate in the CME group only-are reported in this Article. This early analysis of safety was preplanned. The outcomes were analysed according to a modified intention-to-treat principle (excluding patients who no longer met inclusion criteria after surgery or who did not have surgery). This study is registered with ClinicalTrials.gov, NCT02619942. Study recruitment is complete, and follow-up is ongoing. FINDINGS: Between Jan 11, 2016, and Dec 26, 2019, 1072 patients were enrolled and randomly assigned. After exclusion of 77 patients, 995 patients were included in the modified intention-to-treat population (495 in the CME group and 500 in the D2 dissection group). The postoperative surgical complication rate was 20% (97 of 495 patients) in the CME group versus 22% (109 of 500 patients) in the D2 group (difference, -2·2% [95% CI -7·2 to 2·8]; p=0·39); the frequency of Clavien-Dindo grade I-II complications were similar between groups (91 [18%] vs 92 [18%], difference, -0·0% [95% CI -4·8 to 4·8]; p=1·0) but Clavien-Dindo grade III-IV complications were significantly less frequent in the CME group than in the D2 group (six [1%] vs 17 [3%], -2·2% [-4·1 to -0·3]; p=0·022); no deaths occurred in either group. Of the intraoperative complications, vascular injury was significantly more common in the CME group than in the D2 group (15 [3%] vs six [1%], difference, 1·8 [95% CI 0·04 to 3·6]; p=0·045). Metastases in the central lymph nodes were detected in 13 (3%) of 394 patients who underwent central lymph node biopsy in the CME group; no patient had isolated metastases to central lymph nodes. INTERPRETATION: Although the CME procedure might increase the risk of intraoperative vascular injury, it generally seems to be safe and feasible for experienced surgeons. FUNDING: The Capital Characteristic Clinical Project of Beijing and the Chinese Academy of Medical Sciences.

Comparison of open and minimally invasive approaches to colon cancer resection in compliance with 12 regional lymph node harvest quality measure.

BACKGROUND: There has been a growing trend toward minimally invasive surgery (MIS) for colon cancer. Pathological analysis of a minimum of 12 lymph nodes (LNs) is a benchmark for adequate resection. Here, we present a comparison of surgical techniques in achieving a full oncologic resection. METHODS: Patients undergoing surgery for Stage I-III colon cancer (2010-2016) were identified from the National Cancer Database. Cases were stratified by surgical approach. Trends in approach were assessed, including whether the 12-LN benchmark was met. Uni- and multivariate regression was used to assess overall survival (OS). RESULTS: A total of 290,776 colectomies were analyzed. MIS increased from 32.8% to 57.2% from 2010 to 2016 (p < .001). An overall median of 18 LNs were harvested and compliance with the 12-LN benchmark increased (84.6%-91.6%, p < .001); there were no difference between open and MIS. A subset analysis comparing hospital type revealed that regardless of approach, compliance was lower at community hospitals (p < .001). OS was better for patients treated at academic or National Cancer Institute centers, underwent MIS, and in those meeting the 12-LN benchmark (all p ≤ .002). CONCLUSION: As MIS colon resections continue to increase, we demonstrate that there is no difference in the ability to achieve the 12-LN benchmark with open and MIS approaches.

Clinical Calculator Based on Molecular and Clinicopathologic Characteristics Predicts Recurrence Following Resection of Stage I-III Colon Cancer.

PURPOSE: Clinical calculators and nomograms have been endorsed by the American Joint Committee on Cancer (AJCC), as they provide the most individualized and accurate estimate of patient outcome. Using molecular and clinicopathologic variables, a third-generation clinical calculator was built to predict recurrence following resection of stage I-III colon cancer. METHODS: Prospectively collected data from 1,095 patients who underwent colectomy between 2007 and 2014 at Memorial Sloan Kettering Cancer Center were used to develop a clinical calculator. Discrimination was measured with concordance index, and variability in individual predictions was assessed with calibration curves. The clinical calculator was externally validated with a patient cohort from Washington University's Siteman Cancer Center in St Louis. RESULTS: The clinical calculator incorporated six variables: microsatellite genomic phenotype; AJCC T category; number of tumor-involved lymph nodes; presence of high-risk pathologic features such as venous, lymphatic, or perineural invasion; presence of tumor-infiltrating lymphocytes; and use of adjuvant chemotherapy. The concordance index was 0.792 (95% CI, 0.749 to 0.837) for the clinical calculator, compared with 0.708 (95% CI, 0.671 to 0.745) and 0.757 (0.715 to 0.799) for the staging schemes of the AJCC manual's 5th and 8th editions, respectively. External validation confirmed robust performance, with a concordance index of 0.738 (95% CI, 0.703 to 0.811) and calibration plots of predicted probability and observed events approaching a 45° diagonal. CONCLUSION: This third-generation clinical calculator for predicting cancer recurrence following curative colectomy successfully incorporates microsatellite genomic phenotype and the presence of tumor-infiltrating lymphocytes, resulting in improved discrimination and predictive accuracy. This exemplifies an evolution of a clinical calculator to maintain relevance by incorporating emerging variables as they become validated and accepted in the oncologic community.

Quantitative analysis of CDX2 protein expression improves its clinical utility as a prognostic biomarker in stage II and III colon cancer.

AIM: Better stratification of patients with stage II and stage III colon cancer for risk of recurrence is urgently needed. The present study aimed to validate the prognostic value of CDX2 protein expression in colon cancer tissue by routine immunohistochemistry and to evaluate its performance in a head-to-head comparison with tandem mass spectrometry-based proteomics. PATIENT AND METHODS: CDX2 protein expression was evaluated in 386 stage II and III primary colon cancers by immunohistochemical staining of tissue microarrays and by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis using formalin-fixed paraffin-embedded tissue sections of a matched subset of 23 recurrent and 23 non-recurrent colon cancers. Association between CDX2 expression and disease-specific survival (DSS) was investigated. RESULTS: Low levels of CDX2 protein expression in stage II and III colon cancer as determined by immunohistochemistry was associated with poor DSS (hazard ratio [HR] = 1.97 (95% confidence interval [CI]: 1.26-3.06); p = 0.002). Based on analysis of a selected sample subset, CDX2 prognostic value was more pronounced when detected by LC-MS/MS (HR = 7.56 (95% CI: 2.49-22.95); p < 0.001) compared to detection by immunohistochemistry (HR = 1.60 (95% CI: 0.61-4.22); p = 0.34). CONCLUSION: This study validated CDX2 protein expression as a prognostic biomarker in stage II and III colon cancer, conform previous publications. CDX2 prognostic value appeared to be underestimated when detected by routine immunohistochemistry, probably due to the semiquantitative and subjective nature of this methodology. Quantitative analysis of CDX2 substantially improved its clinical utility as a prognostic biomarker. Therefore, development of routinely applicable quantitative assays for CDX2 expression is needed to facilitate its clinical implementation.

Is Initial Board Certification Associated With Better Early Career Surgical Outcomes?

OBJECTIVE: To determine if initial American Board of Surgery certification in general surgery is associated with better risk-adjusted patient outcomes for Medicare patients undergoing partial colectomy by an early career surgeon. BACKGROUND: Board certification is a voluntary commitment to professionalism, continued learning, and delivery of high-quality patient care. Not all surgeons are certified, and some have questioned the value of certification due to limited evidence that board-certified surgeons have better patient outcomes. In response, we examined the outcomes of certified versus noncertified early career general surgeons. METHODS: We identified Medicare patients who underwent a partial colectomy between 2008 and 2016 and were operated on by a non-subspecialty trained surgeon within their first 5 years of practice. Surgeon certification status was determined using the American Board of Surgery data. Generalized linear mixed models were used to control for patient-, procedure-, and hospital-level effects. Primary outcomes were the occurrence of severe complications and occurrence of death within 30 days. RESULTS: We identified 69,325 patients who underwent a partial colectomy by an early career general surgeon. The adjusted rate of severe complications after partial colectomy by certified (n = 4239) versus noncertified (n = 191) early-career general surgeons was 9.1% versus 10.7% (odds ratio 0.83, P = 0.03). Adjusted mortality rate for certified versus noncertified early-career general surgeons was 4.9% versus 6.1% (odds ratio 0.79, P = 0.01). CONCLUSION: Patients undergoing partial colectomy by an early career general surgeon have decreased odds of severe complications and death when their surgeon is board certified.

Thirty-day outcomes in the operative management of intestinal-cutaneous fistulas: A NSQIP analysis.

INTRODUCTION: Intestinal-cutaneous fistulas (ICFs) constitute a major surgical challenge. Definitive surgical treatment of ICFs continues to be associated with significant morbidity. The purpose of this study was to utilize a nationwide database to define the morbidity associated with current treatment strategies in the surgical management of ICFs. METHODS: The 2006-2017 American College of Surgeon National Surgical Quality Improvement datasets (ACS-NSQIP) were used to assess 30-day morbidity and mortality after surgical repair of ICFs. Outcomes for emergent repair were compared to elective repair of ICFs. RESULTS: Overall, 4197 patients undergoing ICF-repair were identified. Mean age was 55.9 (SD 15.3). Patients were generally comorbid (62.9% were in ASA class III). The observed in-hospital mortality was 2.3%. However, the observed morbidity rate was 47.3%. Of the observed morbidity, 35.6% was due to post-operative infectious complications (superficial surgical site infections (SSI), deep SSI, organ/space SSI, wound disruption, pneumonia, urinary tract infection (UTI) sepsis or septic shock). The most common infectious complication was sepsis (13.1%). 30-day readmission rate was 15.3% and the 30-day reoperation rate was 11.0%. Emergent repair was associated with a sevenfold increase in mortality (11.9% vs 1.8%, P < 0.001) CONCLUSION: The management of patients with ICFs is complex and is associated with significant morbidity. Half of patients undergoing surgical management of ICFs developed in-hospital complications.

Trends in Morbidity and Mortality Following Colectomy Among Patients with Ulcerative Colitis in the Biologic Era (2002-2013): A Study Using the National Inpatient Sample.

BACKGROUND: Total abdominal colectomy (TAC) is a treatment modality of last recourse for patients with severe and/or refractory ulcerative colitis (UC). The goal of this study is to evaluate temporal trends and treatment outcomes following TAC among hospitalized UC patients in the biologic era. METHODS: We queried the National Inpatient Sample (NIS) to identify patients older than 18 years with a primary diagnosis of ulcerative colitis (UC) who underwent TAC between 2002 and 2013. We evaluated postoperative morbidity and mortality as outcomes of interest. Logistic regression was used to explore factors associated with postoperative morbidity and mortality after TAC. RESULTS: A weighted total of 307,799 UC hospitalizations were identified. Of these, 27,853 (9%) resulted in TAC. Between 2002 and 2013, hospitalizations for UC increased by over 70%; however, TAC rates dropped significantly from 111.1 to 77.1 colectomies per 1000 UC admissions. Overall, 2.2% of patients died after TAC. Mortality rates after TAC decreased from 3.5% in 2002 to 1.4% in 2013. Conversely, morbidity rates were stable throughout the study period. UC patients with emergent admissions, higher comorbidity scores and who had TAC in low volume colectomy hospitals had poorer outcomes. Regardless of admission type, outcomes were worse if TAC was performed more than 24 h after admission. CONCLUSIONS: Despite increased hospitalizations for UC, rates of TAC have declined during the post-biologic era. For UC patients who undergo TAC, mortality has declined significantly while morbidity remains stable. Older age, race, emergent admissions and delayed surgery are predictive factors of both postoperative morbidity and mortality.