IMMUNOREACT 9: METACHRONOUS RECTAL CANCER ARE FREQUENTLY FROM PREVIOUS RECTAL OR SIGMOID CANCER AND HAVE A LOW INFILTRATION OF CD8+ T CELLS

Background:
Socioeconomic status (SES) has proven significant impact on colorectal cancer (CRC) outcomes. Lower SES has correlated with increased comorbidities, risk of postoperative complications, and inadequate adherence to treatment guidelines. Previous studies were limited in defining SES because of databases lacking sufficient socioeconomic variables. We utilized the CDC’s Social Vulnerability Index (SVI) which contains additional information that more accurately determines SES. We hypothesize that higher SVI associates with worse clinical outcomes in CRC patients undergoing surgery at a high-volume tertiary care center.

Methods:
This is a single institution retrospective study of National Surgical Quality Improvement Program (NSQIP) data for patients aged 18 and older who underwent CRC surgery from 2013-2020. Patient zip codes were used to determine SES via the SVI database. Patients were divided into quartiles from low to high SVI (Q1-Q4). Outcomes measured included NSQIP defined morbidity, surgical site infection (SSI), extended length of stay (LOS>7), 30-day readmission. Bivariate and multivariate analysis were completed.

Results:
1,242 patients underwent CRC surgery during the study period. Morbidity, LOS>7, and SSI trended higher in the third and fourth quartiles but were not statistically significant. Bivariate analysis revealed a significantly increased risk of morbidity, SSI, and readmission in the third quartile, and a significantly increased LOS>7 in the fourth quartile. Continuous bivariate analysis showed that every 10 unit increase in SVI significantly increased risk for morbidity, LOS>7, and SSI. There was also a significant risk to morbidity and LOS>7 per 10 unit increase in social vulnerability on continuous multivariate analysis.

Conclusion:
This study represents a novel application of the SVI to investigate clinical outcomes using NSQIP data. Both bivariate and multivariate analysis revealed a significantly increased risk of poor clinical outcomes with higher SVI. Future application of the SVI may reveal possible interventions to improve colorectal and other surgical outcomes.

Introduction:
Multiple randomized control trials have evaluated laparoscopic (LP) and open proctectomy (OP) for rectal cancer, with mixed results. COREAN, CLASICC and COLOR II supported the use of LP, while ALaCaRT and Z6051 did not. Additionally, there is limited data on long-term oncologic outcomes for robotic proctectomy (RP). The aim of this study is to examine the effect of surgical approach on oncologic factors and survival for patients undergoing open, laparoscopic and robotic proctectomies.

Methods:
Patients in the National Cancer Database with locally advanced rectal cancer were stratified based on surgical approach from 2010-2018. Patient demographics and tumor characteristics were compared with univariate analysis. Intent to treat multivariable analysis and survival analysis with Cox proportional hazard ratios and Kaplan-Meier method were performed. Data analysis was performed using STATA v.17 and R v.4.0.2.

8,293 patients were identified. 3,991 (48.1%) underwent OP, 2,101 (25.3%) underwent LP, 1,666 (20.1%) underwent RP. Conversion rates were 7% for RP and 20% for LP. No clinically significant difference in age or sex was noted between groups. Differences in distribution of race were noted, with those who were Black more likely to have open compared to LP or RP (p-value < 0.001). MIS approaches appear to be more common at academic and comprehensive cancer centers (p-value<0.001). And patients with private insurance are more likely to undergo LP or RP (p-value<0.001). On multivariable analysis, patients who underwent LP (OR 0.760; 95% CI 0.611-0.946; p-value=0.014) or RP (OR 0.660; 95% CI 0.511-0.853; p-value=0.002) were less likely to have positive margins compared to OP. Patients who underwent LP (OR 0.842; 95% CI 0.738-0.961; p-value=0.011) and RP (OR 0.712; 95% CI 0.615-0.825; p-value<0.001) were less likely to have positive lymph nodes compared to those who underwent OP. No difference in 30-day or 90-day mortality was noted. On adjusted survival analysis a reduction in overall survival (OS) for OP compared to LP (HR 0.811; 95% CI:0.725-0.907; p-value<0.01) and RP (HR 0.78; 95% CI:0.67-0.905; p-value=0.01) was demonstrated. There was no difference in OS between LP and RP (HR 0.96; 95% CI: 0.820-1.13; p-value=0.654).

Conclusion:
MIS proctectomy is associated with improved survival compared to open technique. Importantly, there was no difference in survival between a robotic and laparoscopic approach. This suggests that robotic assisted proctectomies are a safe option.

Background: Extremity deep venous thromboses (DVTs) and portomesenteric venous thromboses (PMVTs) differ in their etiology, potential sequelae, and the efficacy of pharmacologic prophylaxis in preventing their occurrence. However, the National Surgical Quality Improvement Program (NSQIP) tracks the occurrence of both extremity DVTs and PMVTs within 30 days of surgery together under its “vein thrombosis requiring therapy” variable without distinguishing the two. We therefore aimed to determine the incidence of extremity DVTs and PMVTs in patients undergoing surgery for colorectal, pancreatic, and splenic malignancies to clarify the specific complications captured under the “vein thrombosis requiring therapy” variable in NSQIP and whether further division of this variable is warranted.

Methods: Patients undergoing operations for colorectal, pancreatic, and splenic malignancies at a single institution between January 1, 2006 and March 1, 2021 were identified. Patients who experienced a new onset upper or lower extremity DVT or a PMVT within 30 days of surgery were considered cases for the study (NSQIP DVT). Patients were then stratified by cancer type, and the anatomic location of each patient’s DVT (extremity or portomesenteric) was recorded. Univariate comparisons between cancer types and venous thromboembolism types were performed.

Results: A total of 8,491 operations for colorectal (n=6,003), pancreatic (n=1,496), or splenic malignancies (n=992). The overall incidence of NSQIP DVTs was 1.7%; 52% of NSQIP DVTs were PMVTs. The overall NSQIP DVT rate was highest in operations for a splenic malignancy (3.3%), followed by operations for pancreatic (2.7%) and colorectal (1.1%) malignancies (p < 0.01). After operations for pancreatic and splenic malignancies, the majority of NSQIP DVTs were either PMVTs alone or combined PMVTs plus extremity DVTs (pancreatic: 70%, splenic: 58%), while PMVTs comprised over a third of the NSQIP DVTs after surgery for colorectal malignancies (38%) (FIGURE). Of patients with an extremity DVT, 17% were also diagnosed with a pulmonary embolism (PE), compared to patients with a PMVT where a pulmonary embolism was diagnosed in only 4% of patients (p = 0.01). Lastly, PMVTs were diagnosed at a later postoperative day (median, [interquartile range]) than extremity DVTs for colorectal (19, [10-28] vs 15, [8-22]; p = 0.23) and pancreatic (21, [12-27] vs 15.5, [7-20]; p = 0.07) malignancies, but not for splenic malignancies (15 [9-22] vs 18 [12-28]); p = 0.16)

Conclusion: The current NSQIP DVT variable does not represent the full clinical picture of venous thromboembolic events after operations for colorectal, pancreatic, and splenic malignancies. The variable should be redesigned into separate “extremity DVT” and “PMVT” variables to better reflect postoperative outcomes and strengthen future research utilizing NSQIP datasets.

Background
Colorectal cancer is the 4th most commonly diagnosed malignancy and the 3rd leading cause of mortality worldwide. A positive resection margin following surgery for colon cancer is linked with higher rates of recurrence and worse survival. The aim of this study was to use a developed diffuse reflectance spectroscopy (DRS) probe and tracking system to distinguish cancer and non-cancer colorectal tissue live on-screen intraoperatively in order to aid margin assessment.

Methods

Patients undergoing elective colorectal cancer resection surgery at a tertiary hospital in London were prospectively recruited between April 2021 and July 2022. A hand-held DRS probe was used on the surface of freshly resected ex-vivo colorectal tissue. Spectral data was acquired for normal and cancerous tissue. Binary classification was achieved using supervised machine learning classifiers, which were evaluated in terms of sensitivity, specificity, accuracy and the area under the curve.

Results

A total of 2702 mean spectra were obtained for normal and cancerous colorectal tissue. The Light Gradient Boosting Model was the best performing machine learning algorithm for differentiating normal and cancerous colorectal tissue, with an overall diagnostic accuracy of 90.7% and area under the curve of 96.7%. Live on-screen classification of tissue type was achieved using a graduated colourmap.

Conclusion

Real-time classification of tissue type was achieved using a DRS system, with high diagnostic accuracy, allowing differentiation of cancerous and normal colorectal tissue. This is a promising step towards an in-vivo classification system that is able to aid surgeons with accurate resection margin assessment for colorectal cancer intra-operatively.

Introduction
Recently, the use of minimally invasive surgery has been identified as a surrogate for quality of surgical care, while rates of emergent surgery are a surrogate for access to care. It has been demonstrated that health care outcomes may be more dependent on socioeconomic status and access to care than biologic factors. While significant advancements have been made in the management of patients with inflammatory bowel disease (IBD), it seems that the presence of disparate outcomes between black and white patients has not changed. We utilized the American College of Surgeons National Surgery Quality Improvement Program (NSQIP) database to evaluate trends in the rates of emergent operations, use of laparoscopic surgery and surgical outcomes comparing black and white patients.
Materials and Methods
The NSQIP database from the year 2012 to 2020 was used to evaluate trends in emergency surgery, laparoscopy and outcomes in IBD patients undergoing colectomy. IBD patients were identified using ICD codes for Crohn’s disease (ICD9: 555.x; ICD10 K50.x) and ulcerative colitis (ICD9: 556.x; ICD10 K51.x). The primary outcomes were rates of emergent and laparoscopic surgery over time. Secondary outcomes were length of stay and complication rates. Categorical variables were analyzed using Chi-square test, continuous variables using the Student’s t-test or Wilcoxon rank sums test, and proportions of laparoscopic and emergent surgeries using logistic regression modeling.
Results
There were 18,979 patients with IBD with race of either white (17,220) or black (1759) in the study period. The utilization of laparoscopic surgery is increasing at a greater rate in white patients compared to black patients (Figure 1), while emergent surgeries are remaining similar (Figure 2). The rates of any complication (25.7% vs 21.1%, p <0.0001) and major complication (23.2% vs 17.9%, p <0.0001) were higher in black patients. In subgroup analysis of patients undergoing laparoscopic surgery, rates of any complication were similar (17.9% vs 15.7%, p = 0.07), while major complications were more frequent in black patients (16.1% vs 13.2%, p = 0.01). Median post-operative length of stay was higher in black patients (6 days vs 5, p <0.0001).
Conclusion
There was an overall increase in the rate of laparoscopic surgery between 2012 and 2020 in IBD patients undergoing colectomy, however this disproportionately represented white patients. Additionally, black patients experienced greater post operative length of stay and increased complications compared to white patients, a disparity which is attenuated in the laparoscopic surgery group. These results raise concerns that while access to care is improving based on the declining rate of emergent surgeries, quality of surgical care is not improving. Further research is required to explore the underlying factors contributing to this disparity.

Introduction: Patients with fulminant Clostridioides difficile infection (CDI) may require surgical intervention. If surgery is required, total abdominal colectomy (TAC) is the most common approach. Diverting loop ileostomy (DLI) with antegrade colonic lavage has been introduced as a colon-sparing surgical approach to fulminant CDI. Prior analyses of National Inpatient Sample (NIS) data suggested equivalent postoperative outcomes between groups but did not evaluate healthcare resource utilization. As such, we aimed to analyze a more recent NIS cohort to compare these two approaches in terms of both postoperative outcomes and healthcare resource utilization.

Methods: A retrospective analysis of the NIS from 2016 to 2019 was conducted. Adult patients who underwent either a TAC or DLI with antegrade colonic lavage for fulminant CDI were identified using the relevant International Classification of Diseases, 10^th revision codes. The primary outcome was postoperative in-hospital morbidity. Secondary outcomes included postoperative in-hospital mortality, specific postoperative complications, total admission healthcare cost, and length of stay (LOS). Univariable and multivariable regressions were utilized to compare the two operative approaches. Subgroup analyses were performed for patients undergoing early intervention (i.e., intervention within three days of admission).

Results: In total, 886 patients underwent TAC and 409 patients underwent DLI with antegrade colonic lavage. Adjusted analyses demonstrated no difference between groups in terms of postoperative in-hospital morbidity (aOR 0.96, 95%CI 0.64-1.44, p=0.85) or postoperative in-hospital mortality (aOR 1.15, 95%CI 0.81-1.64, p=0.436). On adjusted analyses, patients undergoing TAC experienced significantly decreased total admission healthcare cost (MD 79,715.34, 95%CI 133,841-25,588, p=0.004) and shorter postoperative LOS (MD 4.06, 95%CI 6.96-1.15, p=0.006). Findings were similar in the subgroup of patients undergoing early intervention. Younger patients (aOR 0.98, 95%CI 0.97-0.99, p=0.003) and patients being managed at teaching hospitals (aOR 3.38, 95%CI 1.15-9.97, p=0.027) were significantly more likely to undergo DLI with antegrade colonic lavage.

Conclusions: There are minimal differences between TAC and DLI with antegrade colonic lavage for fulminant CDI in terms of postoperative morbidity and mortality. Healthcare resource utilization, however, is significantly improved when patients undergo TAC as evidenced by clinically important decreases in total admission healthcare cost and postoperative LOS. Future prospective comparative studies reporting long-term outcomes are required to determine whether one approach is more favourable in this setting.

Introduction:
The incidence of diverticulitis has a well-documented cyclic variation, with the highest incidence in the summer months (quarter 3: July- September). Previous studies have not evaluated the severity of the disease by season. We hypothesize that there may be differences in severity based on the time of year; that perhaps patients presenting in the “off-season” may have more severe disease. The aim of this study was to identify differences in severity of diverticulitis based on the time of year.


Methods: A retrospective cohort study of patients admitted with CT-confirmation of diverticulitis in one health system (2006-2021) was performed. Outcomes reflecting disease severity, including operation within 24 hours of admission, operation during index admission (>24hrs), length of stay, and 30-day readmission were obtained. Univariate and multivariate analyses were performed to compare outcomes based on the admission months according to quarter of the year: Q1 (Jan 1-March 31), Q2 (April 1-June 30), Q3 (July 1-Sept 30), Q4 (Oct 1-Dec 31). A secondary analysis was performed using just admissions in the summer months (May-Aug) vs winter months (Nov-Feb).


Results:
A total of 8,622 patients were included; 55.4% female (n=4,777), 20.5% smokers (1,768), and 92.2% with uncomplicated disease (7,950), with a mean age of 60.6 years (SD15.4). Rates of admission were highest in Q3 (2497, 29.0%), followed by Q2 (2226, 25.8%), Q4 (2077, 24.1%) and Q1 (1822, 21.1%). Although not significant, admissions for complicated diverticulitis were highest in Q1 (165, 9.1%) and lowest in Q3 (171, 6.9 %; p=0.07), rates of emergent operation were highest in Q1 (180, 2.1%) and lowest in Q3 (42, 1.7%), rates of operative intervention during index admission were highest in Q1 (n=30, 1.7) and lowest in Q3 (n=28, 1.1%; p=0.48), and readmission rates were highest in Q1 (n=220, 12.1%) and lowest in Q3 (n=249, 10.0%; p=0.18). On multivariate regression, patients in Q3 had a significantly decreased odds of presenting with complicated disease (OR 0.73, 95%CI0.59-0.92) compared to Q1, a significantly lower risk of emergent operation (OR0.65; 95%CI 0.42-0.98), and a significantly lower rate of 30 day readmission (OR 0.81, 95%CI 0.67-0.98). When just comparing summer to winter, patients in the winter were significantly more likely to require an emergent operation (OR 1.48, 95%CI 1.03-2.14).


Conclusion:
While diverticulitis admissions have a slightly higher incidence in the summer months, the severity of disease is significantly worse in the winter months with regard to complicated disease, needing an emergent operation, or being readmitted within 30 days. This suggests that disease severity overall might be worse for patients presenting in the “off-season,” allowing clinicians to better manage expectations and anticipate possible hospital resource utilization.

Introduction: Rectal cancer is a leading cancer diagnosis in the US, and the number of older patients diagnosed with this disease is expected to rise. Locally advanced rectal cancer (LARC) is commonly treated with consolidation neoadjuvant chemoradiation with the goal of organ preservation. However, frailty is not often recognized or considered in the treatment algorithm for rectal cancer. The prevalence of frailty in Medicare beneficiaries with cancer has been reported to approach 50% and the treatment of frail older cancer patients is complex and challenging. In the current study, we assessed the impact of frailty on the early postoperative outcomes of frailty among rectal cancer patients.

Methods
This retrospective, propensity score-matched study was conducted by extracting patients from the institutional’s rectal cancer database and merging with the institutional’s NSQIP registry. Patient characteristics included demographics, neoadjuvant therapy, time on neoadjuvant therapy, time to surgery, surgical approach, and oncological staging. Frailty was assessed using the Modified Frailty Index (mFI). Outcomes include loss of independence (LOI) or need for increased support outside the home, length of stay, and major complications (Clavien-Dindo II-IV). For analysis, patients were matched for frailty status, contingent on sex, race, chemoradiation, and procedure approach.

Results
129 patients operated on due to LARC from 2010 to 2021 were identified and in this group, 27 (21%) were frail. Neoadjuvant chemoradiotherapy was given at a similar rate in frail and non-frail patients (70% vs. 70.6%). No significant differences were observed in the surgical approach (Robotic 22% vs. 35%, p=0.25), the R0 resection rate (85% vs. 92%, p=0.29), and complete pathologic response rate (22% vs. 27%, p=0.81) in frail and non-frail patients, respectively. On propensity matched analysis, rectal cancer treatment outcomes in frail patients were associated with longer hospitalization time (OR=1.67; 95%CI 1.5-1.9; p<0.001) and a higher rate of major complications (OR=3.21; 95%CI 1.4-7.5, p=0.007). Frail patients had a significant increase in LOI (OR=2.14; 95%CI 1.4-3.2; p<0.001)

Conclusions
Frail patients undergo similar multimodal treatment for rectal cancer as non-frail patients and have poor postoperative outcomes. Further studies are necessary to examine the effect of this treatment paradigm on long-term cancer specific outcomes in the frail older patient so that properly balanced treatment strategies can be established.

Background
In a previous study, we demonstrated that the frequency of mismatch repair genes defect was similar in metachronous and sporadic colorectal cancer while an altered immune microenvironment may be a crucial factor for the occurrence of metachronous ones. The density of tumor-infiltrating lymphocytes (TIL) is an independent predictor of outcome in patients with colorectal cancer, and our hypothesis is that they can be involved in the onset of metachronous rectal cancer. The aim of this study was to analyze the tumor microenvironment in sporadic and metachronous rectal cancer.
Methods
This study is a sub-analysis of data from the IMMUNOREACT 1 and 2 (NCT04915326 and NCT04917263) including all the patients whose records had information about the past medical history. We defined as metachronous cancer a rectal cancer arising after a previous colorectal cancer at least 6 months after the first surgery. In this multicentric study, we collected healthy mucosa surrounding the rectal cancer. A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8beta, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Immune markers within the healthy rectal mucosa were compared between patients with metachronous rectal cancer and those with a sporadic one. Sporadic rectal cancer and metachronous rectal cancer were compared. Nonparametric tests were used for small sample size comparison.
Results
A total of 412 patients with rectal cancer included in the retrospective cohort of IMMUNOREACT 1 and 2 cohorts were analyzed and 18 of them had a metachronous rectal cancer. Previously, only 4 of them had a right colon cancer while the other 14 had a previous left or sigmoid colon cancer. No mismatch repair gene deficiencies were observed in the two cohorts. In therapy-naïve patients with metachronous cancer, CD8+ T-cells infiltration was lower than that in patients with sporadic cancer (p=0.021). Moreover, in the whole cohort of patients, metachronous cancer had less frequently aa high level of CD8+ T cell infiltration than sporadic cancers (p=0.047).
Conclusion
Our study showed that, metachronous rectal cancer occurs frequently in the same site of the primitive ones suggesting a role for the cancerization field. Moreover, our data suggest that a constitutive weak cytotoxic T-cell activity may be a crucial factor, permitting the occurrence of metachronous CRC.