7.05 Statin Use Does Not Decrease Disease Severity or Mortality among Patients with C. difficile Infection

Posted on January 18, 2018

A. S. Kulaylat1, J. S. Kim1, C. S. Hollenbeak1, D. B. Stewart1  1Penn State University College Of Medicine,Surgery,Hershey, PA, USA

Introduction:  Clostridium difficile infection (CDI) is more commonly encountered among older, comorbid patients who frequently require the use of statins for hyperlipidemia. Recent observational data has suggested that statins have pleiotropic effects which may decrease spore germination, thus decreasing the risk of developing CDI. There have been no studies, however, evaluating whether statins affect outcomes in patients who already have CDI. The aim of this study was to evaluate whether the use of statins among inpatients with CDI was associated with measurable decreases in mortality and severity of CDI. 

Methods:  All patients admitted to a single tertiary referral center with an admission diagnosis of CDI (2005 to 2015) were identified, limiting the study cohort to subjects with a positive C. difficile stool test within 24 hours of admission. Hospital records were examined to identify use of statins at the time of hospital admission. The primary study outcome was inpatient mortality; secondary outcomes included admission for recurrent CDI within 60 days, the need for admission to a monitored care setting, the need for vasopressors and the need for an emergent total abdominal colectomy. Multivariable logistic regression was used to control for underlying comorbidities and disease-related factors to isolate associations between statin usage and study outcomes. 

Results: A total of 957 patients meeting inclusion criteria were identified. Of these, 318 (33.2%) were receiving statin therapy at the time of hospital admission. After controlling for underlying patient and disease-related factors, statin therapy was not associated with differences in inpatient mortality (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.43 to 1.86), the need for admission to a monitored setting (OR 1.07, 95% CI 0.74 to 1.54), the need for vasopressors (OR 0.92, 95% CI 0.52 to 1.62) or the need for total colectomy (OR 0.51, 95% CI 0.17 to 1.53). Furthermore, statin use was not found to be a significant risk factor for admission for recurrent disease (OR 2.13, 95% CI 0.91 to 5.03). Proton pump inhibitor (PPI) therapy was observed in 447 (46.7%) study patients, and controlling for the use of PPI therapy did not reveal an association between statin use and study outcomes.

Conclusion: While prior reports suggest that statin therapy reduces the risk of developing CDI, the current study suggests that statin-pleiotropy does not influence disease mortality and severity. 

 

7.04 Black and Uninsured Patients Have Delayed and Decreased Rates of Stoma Reversal After Hartmann’s

Posted on January 18, 2018

C. R. Reed1, M. C. Turner1, M. Talbott1, Z. Sun1, K. Sherman1, C. R. Mantyh1, J. Migaly1  1Duke University Medical Center,Durham, NC, USA

Introduction:

Although stoma reversal following Hartmann’s procedure is associated with improved quality of life, existing reports suggest that reversal rates and timing to reversal are not optimal. Therefore, we aimed to evaluate the impacts of race and insurance coverage on ostomy reversal following Hartmann’s procedure for diverticulitis.

Methods:

The Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (2007-2010) were queried for patients who underwent Hartmann’s procedure in the setting of diverticulitis. Patients who died during their index hospitalization were excluded. Patients were grouped by race and insurance status. After multivariable adjustment for demographic and clinical variables, rate and timing of colostomy takedown at one year were evaluated.

Results:

Among 11,018 patients who underwent a Hartmann’s procedure, 6,900 (63%) patients underwent ostomy reversal at one year, with a median time to reversal of 18 weeks.

 Compared to white patients with private insurance, combinations of black race and non-private insurance had reduced likelihood of ostomy reversal at one year (black patients with private insurance: OR: 0.64, 95% CI: 0.44-0.93, p=0.021; white patients with Medicaid: OR: 0.79, 95% CI: 0.67-0.93, p=0.005; black patients with Medicaid: OR: 0.62, 95% CI: 0.43-0.89, p=0.009; black patients with Medicare: OR: 0.33, 95% CI: 0.18-0.59, p<0.001; white patients without insurance: OR: 0.30, 95% CI: 0.24-0.37, p<0.001; white patients with Medicare: OR: 0.29 95% CI: 0.21-0.38, p<0.001; black patients without insurance: OR: 0.24 95% CI: 0.13-0.45, p<0.001).

For patients who underwent ostomy reversal, combinations of black race and non-private insurance also had a delay to reversal compared to white patients with private insurance (white patients with Medicaid: 1.5 weeks 95% CI 0.71-2.4, p<0.001; black patients with private insurance: 1.7 weeks, 95% CI: -0.14-3.5, p=0.07; white patients with Medicare: 2.8 weeks, 95% CI: 1.2-4.4, p=0.001; black patients with Medicaid: 3.4 weeks, 95% CI: 1.3-5.6, p=0.002; white patients without insurance: 3.7 weeks, 95% CI: 2.6-4.8, p<0.001; black patients with Medicare: 3.7 weeks, 95% CI: 0.58-6.9, p=0.02; black patients without insurance: 8.0 weeks, 95% CI: 4.5-11.4, p<0.001).

Conclusion:

Race and insurance coverage have complex, significant interactions with rate and timing of ostomy reversal after Hartmann's procedure for diverticulitis. Black patients and those without private insurance receive suboptimal care compared to white patients with private insurance. These disparities are important to consider for allocation of surgical resources in marginalized communities.

7.03 Emergency Presentations for Colorectal Cancer 2008-2014: In-hospital Mortality and Discharge Status

Posted on January 18, 2018

Y. A. Zerhouni1,3, N. Melnitchouk1, E. B. Schneider2  1Brigham And Women’s Hospital,Center For Surgery And Public Health,Boston, MA, USA 2Ohio State University,Columbus, OH, USA 3UCSF- East Bay,Surgery,Oakland, CA, USA

Introduction:
Emergent presentations of colorectal cancer (CRC) are associated with worse outcomes. We examined patient factors associated with in-hospital death and discharge to continuing care.

Methods:
We queried the 2008–2013 Nationwide Emergency Department Sample, a 20% stratified sample of United States (US) ED visits, and identified all visits with a primary ICD-9-CM diagnosis of CRC. Multivariable logistic regression was used to identify factors associated with in-hospital death or discharge to continuing care (skilled nursing facility, long-term hospital, or home health care).

Results:
Approximately 312,105 ED visits were made for a primary diagnosis of CRC. 70.9% of patients were aged ≥60 years and 58.3%% were covered by Medicare. Over one-third had proximal disease (proximal 36.3%, distal 16.6%, rectum 22.7%, unspecified 24.4%). Nearly 1 in 3 patients had metastatic CRC. 89.0% of patients were admitted to the hospital. 50.5% of patients underwent a surgical procedure (colon resection, ostomy, stent, dilation). At discharge, 49.0% required continuing care. 5.6% died during the hospitalization. The average total charges for the encounter were $83,904 and average length of stay was 10.1 days. Factors associated with discharge to continuing care can be seen in Figure 1. Factors significantly associated with in-hospital death included moderate to severe liver disease (OR 4.82), metastatic CRC (OR 2.12), malnutrition (OR 1.81), mild liver disease (OR 1.78), history of myocardial infarction (OR 1.65), congestive heart failure (OR 1.59), cerebrovascular disease (OR 1.59), and chronic renal disease (1.43).

Conclusion:
ED visits for a primary diagnosis of CRC consume substantial resources with nearly 90% of patients admitted to the hospital and over half (50.5%) requiring surgical intervention. Nearly half of the patients who survive to discharge (49.0%) require some form of additional care. Factors that increase likelihood of in-hospital death or discharge to continuing care should inform patient care.
 

7.02 Role of Process and Surgical Judgment in Incidence of Surgical Site Infection following Colectomy

Posted on January 18, 2018

A. C. Antonacci1, D. Armellino1, K. Cifu-Tursellino1, M. Schilling1, S. Dechario1, J. Nicastro1, M. Jarrett1  1North Shore University And Long Island Jewish Medical Center,Surgery,Manhasset, NY, USA

Introduction:

In addition to increased patient morbidity and mortality, the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data suggest that surgical site Infection (SSI) accounts for a 9.2% increase in hospital costs above uncomplicated colectomy cases.  This project, which included 12 acute care facilities ,  was designed to  reduce the  incidence  of post-colectomy SSI by implementing a system-wide standardized surgical bundle, monthly communication of outcome data to practitioners  and analysis of factors contributing to an organ space Infection, as defined by the National Healthcare Safety Network (NHSN),  following elective colectomy. 

Methods:

A colectomy bundle linked survey was utilized to gather information on clinical practice from 125 surgeons within our system. The data suggested specific deficiencies in bundle adherence particularly with respect to oral and mechanical bowel prep compliance. Postoperative compliance data was collected from  post-colectomy SSIs into a relational database analyzing over 50 patient, procedure, SSI and bundle compliance elements.  Data was evaluated at the system, hospital and surgeon level.  Breaches in compliance were shared to the provider level.

Results:

Two years of historical data was utilized to establish the baseline incidence of SSI and compared to six months following implementation.  A twenty-eight percent reduction in SSI was achieved in association with an 30% increase in the use of oral and mechanical bowel preparation. Elective and emergent procedures were analyzed separately with respect to organ space infection.  Despite an 80% compliance rate with oral and mechanical bowel preparation in elective cases, 62% of the cases were identified as having infection present at the time of surgery (PATOS) and 67.5% of the cases were identified as having Class III or Class IV wounds.

Conclusion:

These data suggest that bundle compliance is important in reducing SSIs, particularly with respect to oral and mechanical bowel preparation. However, the high incidence of PATOS and Class III/IV wounds found at elective colectomy suggest that surgeons may be operating on patients too early during the course of an on-going inflammatory process and that surgical judgment and decision making should be included as bundle compliance elements.

 

                                                                                                                       

7.01 Facility Variation in Upstaging and Adjuvant Chemoradiation in Clinical Stage I Rectal Cancer

Posted on January 18, 2018

D. S. Swords1,2, D. E. Skarda1,2, H. Kim2, W. T. Sause3, G. J. Stoddard4, C. L. Scaife1  1University Of Utah,Surgery,Salt Lake City, UT, USA 2Intermountain Healthcare,Surgical Services,Salt Lake City, UT, USA 3Intermountain Healthcare,Oncology Services,Salt Lake City, UT, USA 4University Of Utah,Division Of Epidemiology,Salt Lake City, UT, USA

Introduction:  The Commission-on-Cancer (CoC) rectal cancer quality measure (QM) states that patients with clinical stage I/pathologic stage II-III rectal cancer (“upstaged”) should receive adjuvant chemoradiation. Notably, the QM does not consider upstaging to be guideline discordant care. We hypothesized that there is facility variation in delivery of adjuvant chemoradiation to such patients, and that there is also variation among facilities in rates of upstaging. 

Methods:  This retrospective study of the 2009-2014 National Cancer Database examined patients < 80 years with clinical stage I rectal adenocarcinoma. Exclusion criteria included: previous cancer, no surgery, local tumor destruction/excision only, neoadjuvant therapy, surgery not at the reporting facility, and unknown clinical or pathologic stage. Outcomes were (1) being upstaged and (2) receipt of adjuvant chemoradiation among upstaged patients who survived ≥ 180 days post-diagnosis. Covariates with univariate p-values < 0.2 for each outcome were entered into multivariable poisson regression models with robust variance estimates. An imputed analysis of 50 data sets obtained through multiple imputation by chained equations was used to account for missing data. Risk- and reliability-adjusted estimates for each facility were generated to examine facility rates of outcomes.

Results: Among 6,031 patients the median age was 60 years, 57.7% were male, and 83.0% were white. Upstaging occurred in 1,607 patients (26.6%). Of pathologic stage II-III patients, 712 (67.2%) received adjuvant chemoradiation. Upstaging was independently predicted by age < 50, Hispanic ethnicity, higher grade, mucinous/signet ring histology, larger size, and elevated CEA. Treatment at > 1 CoC facility was associated with upstaging, but facility type and volume were not. Receipt of adjuvant chemoradiation among upstaged patients was independently associated with age < 70, short travel distance, pathologic stage III (vs. II), and abdominoperineal resection (vs. low anterior resection). Surprisingly, treatment at academic and high volume facilities was associated with omission of adjuvant chemoradiation. Adjusted facility rates of upstaging ranged from 15.4% to 52.7%, and adjuvant chemoradiation rates ranged from 25.3% to 84.0% (Figure).

Conclusion: There is 3-fold variation in adjusted facility rates of adjuvant chemoradiation for patients with clinical stage I/pathologic stage II-III rectal adenocarcinoma, which verifies the utility of this part of the CoC rectal cancer QM. However, there is also significant facility-level variation in rates of upstaging. Providing feedback to facilities with high outlier rates of upstaging should be considered as a quality improvement strategy.

 

69.06 Race Does Not Affect Length of Stay in Colorectal ERAS Patients with Post-Operative Complications.

Posted on January 18, 2018

P. K. Patel1, D. I. Chu1, L. Goss1, J. G. Wiener1, T. S. Wahl1, K. D. Cofer1, J. S. Richman1, M. S. Morris1, J. A. Cannon1, G. D. Kennedy1  1University Of Alabama at Birmingham,Gastrointestinal Surgery,Birmingham, Alabama, USA

Introduction:
Racial disparities have been documented in surgical outcomes. For example, recent studies have shown that black patients have longer length-of-stays (LOS) and higher rates of post-operative complications (POCs) than similar white patients.  However, it is unclear if disparities persist between black and white patients who suffer similar inpatient POCs. The primary aim of this study was to assess differences between minority status (white vs. non-white) in the LOS of patients who suffered complications for surgical patients with and without the Enhanced Recovery After Surgery (ERAS) pathway. We hypothesized that minority patients will have longer LOS if they suffer POCs.

Methods:
Using a prospectively maintained database of patients undergoing colorectal surgery before and after the implementation of ERAS at a single institution, we identified patients who suffered a POC using NSQIP variables. The primary outcome was LOS. Bivariate comparisons were made between races and ERAS status using chi square tests, one-way analysis of variances, and the Kruskal-Wallis test.

Results:
Out of a total of 1121 patients, 718 (64%) were pre-ERAS and 403 (36%) underwent ERAS. Of the 718 pre-ERAS patients, 191 (26.6%) were members of a minority group and 527 (73.4%) were white.  A total of 201 (28.0%) patients had post-operative complications with rates of 36.1% for minorities and 25.1% for whites (p<0.01). Overall there was a significant difference in LOS between minorities and whites (median 7 days vs. 5 days, p<0.01). Among those without POCs, minorities had a longer LOS (median 6 days vs. 5 days, p=0.01), but there was no difference in LOS for those with a POC (median 8 days vs. 8 days, p=0.95). Of the 403 ERAS patients, 221 (28.9%) were members of minority groups and 543 (71.1%) were white. A total of 106 (26.3%) individuals experienced a POC with rates of 28.6% for minorities and 25.4% for whites (p=0.50). Top complications in ERAS patients were organ space SSI (4.7%), superficial incisional SSI (3.4%), and UTI (2.5%). There was no significant difference in POCs by minority status (p=0.93). LOS did not differ by minority status overall (minority median 3 days vs. 3 days, p=0.50), for patients without complications (3 days vs. 3 days, p=0.58), or for patients with POCs (minority median 6 days vs. 5 days, p=0.26).

Conclusion:
In the pre-ERAS era, racial disparities existed with longer LOS and higher rates of POCs among minority patients. These disparities in LOS, however, appeared to be driven by patients without POCs. Under ERAS, there were no observed racial disparities in LOS, with or without POCs. The effect of ERAS on reducing disparities in LOS may therefore occur through its standardization of recovery pathways for patients without complications.

60.05 The contribution of Enterococcus-mediated plasmin(ogen) activation in anastomotic leak pathogenesis

Posted on January 18, 2018

R. A. Jacobson1,2, O. Zaborina1, J. C. Alverdy1  1The University Of Chicago,Surgery,Chicago, IL, USA 2Rush University/Cook County,Surgery,Chicago, IL, USA

Introduction:  Recent work in our lab has demonstrated that Enterococcus faecalis (E. faecalis) alone can cause anastomotic leak (AL) in rodents by activating tissue associated pro-matrix metalloprotease 9 (pro-MMP9) leading to pathologic degradation of submucosal collagen in the anastomotic wound. However the fibrinolytic protease plasminogen (PLG) 1) is concentrated and cleaved to active plasmin at sites of tissue injury 2) activates pro-MMP9 and 3) directly cleaves collagen, therefore its role in AL pathogenesis needs to be clarified. Here we hypothesized that PLG is also activated by E. faecalis and acts synergistically with MMP9 leading to further enhancement of collagen degradation. Therefore, the aim of this study was to define the relative contribution of PLG in the molecular pathogenesis of AL via its effect on collagen degradation.

 

Methods:  A collagenolytic E. faecalis strain (E44), previously identified to play a putative role in AL was used in these experiments. Plasmin(ogen) activation was assessed with a fluorogenic substrate specific to plasmin. Fluorescein-tagged gelatin, type 1 collagen and type 4 collagen assays were employed to assess E. faecalis-mediated collagenolylsis in the presence of PLG, the known plasminogen activator urokinase (uPA), and pro-MMP9. All purified enzymes were purified recombinant human forms Tranexamic acid (TXA) was used to inhibit plasmin(ogen) activation. 

Results:

Plasmin(ogen) activation: E. faecalis alone activated PLG in a concentration-dependent fashion (reaction velocity increased by 0.32 RFU/s per E. faecalis colony forming unit, R2 = 0.99 ). The effect was amplified in the presence of uPA (1.57 RFU/s per CFU, R2 = 0.96). This process was inhibited by TXA in a concentration-dependent fashion. 

 

Collagenolysis/gelatinolysis: E. faecalis-mediated cleavage of type 4 collagen was unchanged by the addition of pro-MMP9, but was significantly increased in the presence of PLG with and without its activator uPA. In the presence of PLG and uPA, addition of pro-MMP9 appeared to synergistically increase collagenolytic activity (Panel A). TXA diminished overall gelatinolytic activity in a dose dependent manner (1.16 AU 10mM TXA vs 3.50 AU E.faecalis + PLG/uPA/proMMP9, p<0.05, panel B). Results were redemonstrated in gelatin and type 1 collagen cleavage assays.

Conclusion: Our data suggest that the molecular pathogenesis of anastomotic leak may involve synergistic activation of plasmin(ogen) and pro-MMP9 in a manner that drives collagenolytic activity to supraphysiologic levels. That this process can be suppressed by the use of TXA, offers a novel therapeutic role to apply this FDA approved agent to high risk anastomotic surgery. 

 

60.04 Synergistic Apoptosis Following Endoplasmic Reticulum Stress Aggravation in Mucinous Colon Cancer

Posted on January 18, 2018

B. D. Honick1, A. K. Dilly1, S. Hong1, Y. J. Lee1,2, H. J. Zeh1, D. L. Bartlett1, H. A. Choudry1  2University Of Pittsburg,Department Of Pharmacology & Chemical Biology,Pittsburgh, PA, USA 1University Of Pittsburg,Department Of Surgery,Pittsburgh, PA, USA

Introduction: Cancer cells up-regulate endoplasmic reticulum (ER) stress response related molecular signaling pathways, known as unfolded protein response (UPR), in order to accommodate high protein turnover associated with rapidly proliferating cells. We hypothesized that mucinous colon cancers would have higher basal ER stress owing to high mucin 2 (MUC2) protein production, and that ER stress aggravation in these tumors would overwhelm cytoprotective capacity of UPR and induce apoptosis.  

Methods:  In vitro studies were conducted using explant tissue from mucinous and non-mucinous colon cancers, normal colon, LS174T cells (MUC2-secreting human colon cancer cells), and stably transfected LS174T cells expressing dominant negative TCF4 (differentiated goblet-like cells controlled by Tet-on system that express higher MUC2 levels than wild-type LS174T cells). ER stress aggravators included ER calcium pump inhibitor celecoxib and fatty acid synthase inhibitor orlistat.

Results: Higher levels of ER stress response proteins, including GRP78/BiP (immunoglobulin heavy chain-binding protein), ATF4 (activating transcription factor 4), CHOP (C/EBP homologous protein) assessed by real-time PCR and immunofluorescence, were detected in mucinous colon cancer explant tissue and MUC2 over-expressing LS174T-dnTCF4 cells as compared to non-mucinous cancer explant tissue, normal colon epithelium and wild-type LS174T cells. These data suggest a correlation between MUC2 protein production and basal ER stress levels. Treatment of LS174T cells with ER stress inducers celecoxib or orlistat alone decreased cell viability (assessed by MTS assay and phase-contrast microscopy) and induced apoptosis (measured by flow cytometry with annexin-V and propidium iodide staining) and ER stress response proteins (BiP, ATF4, CHOP evaluated by western blot) in a dose-dependent fashion, with doses > 75 µM (celecoxib) and > 200 µM (orlistat) required to achieve > 50% cell death. Combination treatment of LS174T cells with celecoxib (50 µM) and orlistat (100 µM) demonstrated synergistic loss of cell viability (> 50% cell death by MTS assay) and induction of apoptosis (flow cytometry) and ER stress response proteins (western blot). Western blot demonstrated synergistic induction of PUMA (p53 upregulated modulator of apoptosis), cleaved caspases 9 and 3, and cleaved PARP (poly ADP-ribose polymerase) as the downstream mechanism for apoptosis following combination therapy in LS174T cells.

Conclusion: Mucinous cancers have higher basal ER stress than non-mucinous cancers, perhaps due to the higher protein turnover associated with abundant MUC2 production. These tumors may be especially vulnerable to drugs that overwhelm the ER stress response through disrupting protein homeostasis. Ongoing studies will determine whether ER stress aggravation by this combination therapy triggers a switch from autophagy to apoptosis.

 

60.06 Topical application of a Dual PI3K/mTOR Inhibitor for the Prevention of Anal Carcinogenesis In Vivo

Posted on January 18, 2018

B. L. Rademacher1, L. M. Meske1, K. A. Matkowskyj2, E. D. LaCount1, E. H. Carchman1  1University Of Wisconsin,Department Of Surgery, Division Of General Surgery,Madison, WI, USA 2University Of Wisconsin,Department Of Pathology And Laboratory Medicine,Madison, WI, USA

Introduction:  Patients with anogenital human papilloma virus (HPV) infection are at high risk of developing squamous cell dysplasia that can progress to squamous cell carcinoma of the anal canal (SCCA). We have previously shown that dual PI3K/mTOR inhibition results in decreased dysplasia and SCCA with systemic drug administration in our HPV mouse model of anal carcinogenesis. Here we sought to investigate the effect of local, topical application of a dual PI3K/mTOR inhibitor, BEZ235, on tumor free survival, histopathologic changes and autophagy.

Methods:  K14E6/E7 mice were given no treatment (Control), topical BEZ235 (BEZ), the carcinogen DMBA (DMBA), or both DMBA and BEZ for a total of 20 weeks. Mice were assessed weekly for tumor development. At 20 weeks they were euthanized and their anal samples examined for histopathologic changes at the anal transition zone (ATZ). Slide sections of the ATZ were assessed for mTOR and PI3K activity by staining for pS6 and pAKT expression (immunohistochemistry), respectively, and evidence of autophagic function via LC3β and p62 expression (immunofluorescence). Tumor free survival analysis was conducted used Kaplan Meier statistics, and all comparisons of mean differences in histopathologic score or protein signal were conducted using a one-way ANOVA.

Results: Regarding tumor free survival, mice receiving DMBA alone survived, on average, 16.9 weeks prior to tumor onset, whereas mice receiving both DMBA and BEZ survived, on average, 19.3 weeks (P<0.000001). Histopathological analysis revealed a significant decrease in mean score comparing DMBA with DMBA plus BEZ (P<0.000001). Comparing DMBA versus DMBA plus BEZ, IF revealed efficacy of topically applied dual PI3K/mTOR inhibitor, via significant decreases in both pS6 and pAKT (P<0.001 for both comparisons). Compared to Control mice, both BEZ and DMBA plus BEZ treated mice had significantly higher LC3β expression, signifying autophagic induction (P<0.005 for both comparisons), whereas DMBA, BEZ, and DMBA plus BEZ treated mice had significantly lower p62 expression, signifying increased autophagic function (P<0.0005 for all comparisons).

Conclusion: Consistent with systemic delivery of a dual PI3K/mTOR inhibitor, topical application of BEZ235 shows prolonged tumor free survival. Furthermore, this finding is confirmed via targeted inhibition of the PI3K/mTOR pathway resulting in activation of autophagy and decreased carcinogenesis.

 

60.01 A Tumor Infiltrating Nanoparticle Delivery Platform for In Vivo KRAS Knockdown

Posted on January 18, 2018

B. A. Krasnick1, M. S. Strand1, N. Sankpal1, Y. Bi1, P. Goedegebuure1, S. Wickline2, H. Pan2, R. C. Fields1  1Washington University,Surgery,St. Louis, MO, USA 2University Of South Florida College Of Medicine,Cardiology,Tampa, FL, USA

Introduction: For patients with metastatic colorectal cancer (CRC), 5 year survival is ~10%. Unlike conventional chemotherapy, where treatment is not targeted and often inefficient, nanoparticles (NPs) have the potential to allow precise delivery of cargo (such as siRNA or other small molecule inhibitors) directly to sites of disease. The cargo being delivered can theoretically target multiple different pathways simultaneously, including those not “druggable” by other means (such as KRAS).  Here, we describe our peptide based, endosomolytic NP system designed to deliver siRNA against KRAS to several model CRC tumor systems.
 

Methods: Quasar 705 (Q705) tagged siRNA NPs (Fluorescent NP) were given via IV injection to mice, and in vivo uptake was assessed. To assess Fluorescent NP uptake we utilized confocal microscopy, in vivo and ex vivo imaging systems, as well as multi-color flow cytometry. CT26 murine CRC cells, which harbor a KRAS mutation are used throughout. For patient derived xenografts (PDXs), a unique KRAS mutant CRC cell line, 322, was derived. Subcutaneous (SQ) CT26 ± GFP/Luciferase labelled murine CRC tumors were created by injecting tumor cells into the right flank of BALB/C mice. For liver tumors, a hemi-splenectomy liver metastasis model was used, with CT26 GFP/luciferase labelled CRC cells injected into the BALB/C hemispleen. A KRAS specific siRNA was used create our KRAS siRNA NP (KRAS NP) for IV treatment, and KRAS RNA level was assessed via RT-PCR.

 

Results: Our Fluorescent NP localizes to SQ murine CRC tumors (Figure Part A, N=5 per group—Fluorescent NP or Control NP treated) with minimal non-tumor uptake, as well as 322 PDX CRC tumors (not shown). Our Fluorescent NP localizes specifically to GFP positive murine CRC tumor cells and not to non-tumor cells in a SQ tumor model (Figure Part B, N=3 per group—Fluorescent NP and Control NP treated). In our liver metastasis model, Fluorescent NP is delivered specifically to GFP+ tumor cells in the liver (Figure Part C). Mice harboring CT26 SQ tumors were then treated with KRAS NP, which leads to a 50% knockdown in tumor KRAS RNA expression as compared to Control NP treated mice (p<0.0001).

 

Conclusion: Our peptide based nanoparticle localizes to in vivo CRC cells in metastatic and heterotopic model systems. This system can be used to specifically target KRAS expression. We are currently exploring the therapeutic potential of this system in multiple pre-clinical systems as a novel platform for targeted delivery of precision therapeutics. 

 

57.03 Silicone-rubber as a Viable, Cheaper Alternative to Current Commercial Simulated Bowels

Posted on January 18, 2018

K. M. Bell1, B. Wise1, C. Kwan1, A. Witt1, C. M. Pugh1  1University Of Wisconsin,Surgery,Madison, WI, USA

Introduction:
Surgical residency programs have relied on cadaveric animal tissue, to practice and teach surgical procedures and techniques. The drawbacks to using animal tissue are short shelf life, sporadic availability, and costs of manpower and management needs. For training purposes, commercial synthetic tissue and virtual reality simulators are also used, but can be very expensive. The aim of this study is to determine if our fabricated silicone-based bowels are valuable for surgical education and competitive with commercial products. We hypothesize that silicone-based bowels can be a useful training tool for general surgery residents and can be more cost effective than commercial products.

Methods:
General Surgery residents (N=6) evaluated three synthetic bowel prototypes. Two synthetic small bowels (Model B and C) were fabricated using cellulose fiber sheets, cotton fiber mesh, and silicone rubbers in different concentrations, to replicate the serosa, muscularis and mucosa. Cost for these models is $5. A third, commercial small bowel was purchased (Model A) for $60. Participants blindly selected what they felt to be most realistic from a covered basin and those choices were documented. Next, participants performed a suturing task on all three samples and evaluated the bowel’s realism using a Likert based survey. Favorable responses were denoted as ‘average’, ‘accurate’, or ‘highly accurate’. Unfavorable responses included ‘highly inaccurate’ and ‘inaccurate’.

Results:
83% of participants had previously used synthetic bowel for learning purposes, and 50% of participants reported performing 1 to 5 bowel Enterotomy repairs per month in the operating room. During the blind identification test, 66% of participants selected one of the silicone-based rubber bowels (B or C), over the commercial bowel (A) as feeling the most realistic. Model A tended to have more favorable responses regarding mechanical functionality of the bowel, with ten-out-of-ten of the favorable survey responses. Model B had seven-out of ten favorable responses, and Model C had a five-out-of-ten favorable responses. All the participants answered ‘accurate’ or ‘highly accurate’ in response to the survey statements confirming that simulation could highlight the strengths or weaknesses in their technical skill.

Conclusion:
The silicone-based bowels, models B and C, were more likely to be selected in the blind identification test. When the favorable properties of model B and C are combined, we will be able to produce a prototype that is financially, tactically, and mechanically competitive to the current commercial products. This study shows that silicone based rubber bowels have value for surgical education, and that with advancement; they can be a viable replacement to cadaveric animal tissue, commercial prototypes, and other, more costly training products.

56.02 Is Solo Surgery the Goal of the Laparoscopic Colorectal Surgeries?

Posted on January 18, 2018

J. Yasutomi1, K. Kusashio1, M. Matsumoto1, T. Suzuki1, A. Iida1, K. Fushimi1, S. Irabu2, T. Komura2, N. Yamamoto2, N. Imamura1, R. Harano1, A. Yoshizumi1, R. Takayanagi1, N. Matsuyama1, I. Udagawa1  1Chiba Rosai Hospital,Department Of Surgery,Ichihara-city, CHIBA, Japan 2Chiba Rosai Hospital,Department Of Emergency And Intensive Care,Ichihara-city, CHIBA, Japan

Introduction : The technical qualification of the Japanese Society for Endoscopic Surgery requires the operator to lead every operative procedure with initiative throughout the operation. Since leadership and initiative of the operator is regarded as important, relatively high score is given to solo surgery.  However, in order to let young surgeons experience laparoscopic colorectal surgeries as operators, the expert support and guiding performed by the assistant should be necessary. The presenting author experienced more than 600 cases as an assistant (mentor). The aim of this study is to justify our educational system of laparoscopic surgery.

Method : ?We analyzed the current status of laparoscopic surgeries. Sigmoid colon resections (n=172) and right hemicolectomies (n=184) were performed from 2011 to 2016 in our institution, in which 87 of the former and 106 of the latter were performed  by surgeons in training. The operative data were compared. ?We also classified our laparoscopic colorectal surgeries by the achievement level of the operator. Step 0: A beginner-level surgeon, even if the mentor provides a complete operative field, it is still necessary to assist, or to be replaced by the senior scope holder.  Step 1: At the level where the operator can understand and practice the standardized procedure. Step 2: The operator is at the level of the mentor (or the certified surgeon) and leads the entire operation.

Result : ?In recent 8 years, we performed 998 colorectal surgeries including 722 laparoscopic surgeries in our institution. The average number of laparoscopic colorectal surgeries performed by surgeons in training (N=17) was 13 cases per year, and that of laparoscopic cholecystectomies was 38 cases per year. Compared to staff surgeons, we found no significant difference in operative time in sigmoid colon resections—Surgeons in Training ;170min.(SD:37, N=87) , Staff (senior) surgeons:160min.(SD:35,N=85). We could find no significant difference in blood loss either. The surgeons in training performed almost satisfying number of surgeries as operators and no severe complications were experienced.?Among 104/116 laparoscopic colorectal surgeries performed in our hospital in 2015/2016, the number of Step 0 operations were 32/30 cases, whereas Step 1 were 42/57 cases, and Step 2 were 12/11 cases.
Conclusion : Is "Solo Surgery" the Goal of the Laparoscopic Colorectal Surgeries? The answer is "No".  An ideal form of the laparoscopic colorectal surgery that we still think is almost the same as traditional open surgery, in which the operator should lead the whole operative procedures and at the same time the assistant should perform a role of harmonious movement with the operator. In order to allow surgeons in training perform laparoscopic colorectal surgeries, our educational system was seemed to be feasible and thought to be the first step for an ideal form of the operation.

48.12 Racial Disparities in Incidence of Rectal Cancer in Patients with IBD

Posted on January 18, 2018

D. Sessinou1, D. Chen1, V. Pandit1, C. Charlton1, A. Cruz1, P. Vij1, V. N. Nfonsam1, V. N. Nfonsam1  1University Of Arizona,Medicine,Tucson, AZ, USA

 

Introduction: Rectal cancer (RC) continues to be prevalent among patients with inflammatory bowel disease (IBD). Disparities in patients with RC are well known however there is paucity of data on patient with IBD developing RC. The aim of this study was to assess racial disparities in patients with IBD developing RC.

Methods: Using the National Inpatient Sample (NIS) from the year 2011, we included patients with age ≥ 18 with IBD. Patients with RC were assessed. Patients were stratified by race. Statistical analysis was performed to assess difference in groups.

Results:: A total number of 57,358 patients with IBD were assessed of which 172 had RC.
79.9% were white and 11.3% were black. Patients with IBD were more likely to develop RC (p=0.001). Among patient developing RC, they were more likely to be Whites and Asians/Pacific Islanders. Out of the patients with both IBD and RC, there were more males (65.1%) than females (34.9%) (p=0.0001). 

Conclusion:The results of this study suggest that people with a history of IBD are at an increased risk of developing RC, which is supported by the literature. We also see that Whites have the highest incidence of IBD and RC, followed by Asians/Pacific Islanders. These differences may be due to healthcare disparities and lower utilization of screening tests observed among racial groups. Future studies in other years could establish whether there is a trend in incidence. 

35.08 Clinical Impact of Genetic Alterations According to Primary Tumor Sidedness in Colorectal Cancer

Posted on January 18, 2018

Y. Shimada1, Y. Tajima1, M. Nagahashi1, H. Ichikawa1, M. Nakano1, H. Kameyama1, J. Sakata1, T. Kobayashi1, Y. Takii2, S. Okuda3, K. Takabe4,5, T. Wakai1  1Niigata University Graduate School Of Medical And Dental Sciences,Division Of Digestive And General Surgery,Niigata, , Japan 2Niigata Cancer Center Hospital,Department Of Surgery,Niigata, , Japan 3Niigata University Graduate School Of Medical And Dental Sciences,Division Of Bioinformatics,Niigata, , Japan 4Roswell Park Cancer Institute,Breast Surgery,Buffalo, NY, USA 5University At Buffalo Jacobs School Of Medicine And Biomedical Sciences,Department Of Surgery,Buffalo, NY, USA

Introduction: Right-sided colorectal cancer (RCRC), which is derived from midgut, has different molecular and biological characteristics compared with left-sided colorectal cancer (LCRC) which is derived from hindgut. Recently, several unplanned retrospective analyses revealed the differences between RCRC and LCRC in prognosis and response to targeted therapy. We hypothesized that primary tumor sidedness is a surrogate for non-random distribution of genetic alterations, and is a simple and useful biomarker in patients with Stage IV CRC. To teste this hypothesis, we investigated the genetic alterations using comprehensive genomic sequencing (CGS), and analyzed the clinical impact of primary tumor sidedness in patients with Stage IV CRC.

Methods:  One-hundred-eleven Stage IV CRC patients with either RCRC or LCRC were analyzed. We investigated genetic alterations using 415-gene panel, which includes the genetic alterations associated with resistance to anti-EGFR therapy. The differences of clinicopathological characteristics and genetic alterations were analyzed between RCRC and LCRC using Fisher’s exact test. The differences in response to targeted therapies, and clinical significance of residual tumor status were analyzed between RCRC and LCRC using log-rank test. 

Results: Thirty-four patients (31%) and 77 patients (69%) had RCRC and LCRC, respectively. Histopathological grade 3 was significantly associated with RCRC (P = 0.042). Pulmonary metastasis was significantly associated with LCRC (P = 0.012), and peritoneal metastasis was significantly associated with RCRC (P = 0.002). Regarding residual tumor status, R0 resection of both primary and metastatic lesions showed significantly better overall survival compared with R2 resection in both RCRC and LCRC (P = 0.026 and 0.002, respectively). Regarding genetic alterations, RCRC has more genetic alterations associated with resistance to anti-EGFR therapy (BRAF, ERBB2, FGFR1, KRAS, PIK3CA, PTEN) compared with LCRC (P = 0.040). In 73 patients with anti-VEGF therapy, there was no significant difference on progression-free survival (PFS) between RCRC and LCRC (P = 0.866). Conversely, in 47 patients with anti-EGFR therapy, RCRC showed significantly worse PFS than LCRC (P = 0.019).

Conclusion: RCRC is more likely to have the genetic alterations associated with resistance to anti-EGFR therapy compared with LCRC, and shows resistance to anti-EGFR therapy. Primary tumor sidedness is a surrogate for non-random distribution of molecular subtypes in CRC.
 

35.04 Adequacy of Daily Enoxaparin After Colorectal Surgery: An Examination of Anti-Factor Xa Levels

Posted on January 18, 2018

C. J. Pannucci1, K. I. Fleming1, A. Prazak2, C. Bertolaccini2, B. Pickron3  1University Of Utah,Division Of Plastic Surgery,Salt Lake City, UT, USA 2University Of Utah,Department Of Pharmacy,Salt Lake City, UT, USA 3University Of Utah,Department Of Surgery,Salt Lake City, UT, USA

Introduction:
Colorectal surgery patients, particularly those with malignancy, are known to be at increased risk for post-operative venous thromboembolism (VTE).  Current recommendations support that enoxaparin prophylaxis minimizes risk for peri-operative VTE.  While enoxaparin 40mg once daily is a commonly prescribed prophylactic dose, whether this dose adequately thins the blood remains unknown—this is relevant because inadequate enoxaparin dose has been associated with downstream VTE events in other surgical populations.  We examined anti-Factor Xa (aFXa) levels, a marker of blood thin-ness, in response to enoxaparin 40mg once daily among a prospectively recruited cohort of colorectal surgery patients. 

Methods:
Colorectal surgery patients were prospectively enrolled into this clinical trial (NCT02704052).  Patients received enoxaparin 40mg once daily, initiated at 6-18 hours after their surgical procedure.  Peak and trough aFXa levels were drawn, with goals of 0.3-0.5 IU/mL and 0.1-0.2 IU/mL, respectively; these ranges have been shown to maximize VTE risk reduction while minimizing bleeding risk.  We examined the proportion of patients with in and out of range aFXa in response to enoxaparin 40mg once daily and the impact of patient weight on rapidity of enoxaparin metabolism.

Results:
To date, 39 colorectal surgery patients who received enoxaparin 40mg once daily have been enrolled.  One patient had post-operative rectal bleeding requiring enoxaparin cessation prior to aFXa lab draws.  63.2% of patients (n=24) had inadequate peak aFXa levels (<0.3 IU/mL) in response to enoxaparin 40mg once daily.  28.9% of patients (n=11) had in range peak aFXa levels (0.3-0.5 IU/mL) and 7.9% of patients (n=3) were over-anticoagulated (>0.5 IU/mL).  Patient weight was associated with rapidity of enoxaparin metabolism (r2=0.41).  Among 22 patients who had trough levels drawn, 81.8% (n=18) had an undetectable trough level at 12 hours—thus the majority of patients actually receive no chemical prophylaxis for 12 hours per day. 

Conclusion:
Based on pharmacodynamics, enoxaparin 40mg once daily is inadequate for the majority of colorectal surgery patients.  For a medication that is administered daily, four out of five colorectal surgery patients receive no detectable anticoagulation for 12 hours per day.  This study plans to continue patient accrual for one year, with the goal of correlating aFXa with clinically relevant endpoints including 90-day VTE and 90-day bleeding.  As patient weight predicts rapidity of enoxaparin metabolism, a weight-based enoxaparin dosing strategy might be more appropriate.
 

33.04 Resection for Anal Melanoma: Is There an Optimal Approach?

Posted on January 18, 2018

A. T. Hawkins1, T. Geiger1, R. Muldoon1, B. Hopkins1, M. Ford1  1Vanderbilt University Medical Center,Colon & Rectal Surgery,Nashville, TN, USA

Introduction:
Anal melanoma is a lethal disease but its rarity makes understanding the behavior and effects of intervention challenging.  Local resection (LR) and abdominal perineal resection (APR) are the proposed treatments for non-metastatic disease and have each gone in and out of favor over the years. We hypothesize that there will be no difference in overall survival between the two types of resection. 

Methods:
The National Cancer Database (NCDB 2004-2014) was queried for adults with a diagnosis of anal melanoma who underwent curative resection. Patients with metastatic disease were excluded.  Patients were divided into two groups – those who underwent local resection (LR) and those who underwent abdominal perineal resection (APR).  Bivariate and multivariable analyses were used to examine the association between resection type and R0 resection rate, short term survival and overall survival.  

Results:
570 patients with anal melanoma who underwent resection were identified over the study period.  The median age was 68 and 59% of patients were female.  383 (67%) underwent LR.  Rate of LR did not change significantly by year. Factors associated with the use of LR included older age, government insurance, and treatment at a high volume center. LR was associated with lower rates of R0 resection rates (LR 73% vs. APR 91%; p<0.001). Overall five year survival for the entire cohort was 20%. There was no significant difference in five-year overall survival (LR 17% vs. APR 21%; p=0.31). (SEE FIGURE)  Even when adjusting for confounding variables including age, gender, comorbidity, and R0 resection in a Cox proportional hazard multivariable model there was no significant survival difference between resection methods (OR 0.84; 95%CI 0.66-1.06; p=0.15).  In addition, there was no improvement in overall survival for patients who underwent R0 resection (OR 1.18; 95%CI 0.90-1.56; p=0.22). 

Conclusion:
Anal melanoma has an abysmal prognosis, with only 1 out of 5 patients alive at five years.  Older age, government insurance, and treatment at a high volume center were associated with local resection. Although local resection was associated with lower rates of R0 resection, there was no discernable difference in overall survival in both unadjusted and adjusted analysis. Given the known morbidity of APR resection, local resection should be considered in cases of anal melanoma.  

Figure- Kaplan-Meier Curve for Overall Survival Comparing Method of Resection

 

31.01 Functional Assessment of TILs in Rectal Cancer

Posted on January 18, 2018

J. C. Kong1,2, G. R. Guerra1,2, R. M. Millen1,2, S. K. Warrier1,2, W. Phillips1,2, A. C. Lynch1,2, R. Ramsay1,2, A. G. Heriot1,2  1Peter MacCallum Cancer Centre,Division Of Cancer Surgery,Melbourne, VIC, Australia 2The University Of Melbourne,Sir Peter MacCallum Department Oncology,Melbourne, VIC, Australia

Introduction

 

Currently there are no reliable methods that can adequately predict response to neoadjuvant chemoradiotherapy (NACRT) in locally advanced rectal cancer. However tumour infiltrating lymphocytes (TIL) have gained significant prominence in predicting response and survival outcome in rectal cancer. The aim of this study was to assess whether a novel functional cytotoxic immune assay measuring the kinetics of TIL killing predicts pathological tumour response after NACRT accurately.

 

Methods

 

Treatment naïve fresh rectal cancer biopsies from each patient was processed to cultivate organoids and TIL. An immune cytotoxic assay comprising of patient-matched TIL and organoids were co-cultured for 48 hours. A fluorescence microscope was utilitised to measure organoid death, by an automated computer algorithm that calculates the mean fluorescence intensity.

 

Results

 

A total of 17 consecutive rectal cancer patients were recruited. In each cytotoxic assay, a total of 15,000 organoids were measured, with organoid to TIL ratio of 1:10,000. The mean fluorescence intensity for each response group were; complete response=27982 (n=6), partial response=16663 (n=5) and no response=8933 (n=6) (p-value<0.001). This demonstrates that by measuring the kinetics of TIL killing, it can predict response to NACRT accurately before surgery. This was further validated by measuring the IFN-Y production of cytotoxic (CD8+) T cell, which was significantly higher in complete/partial response TIL compared to no response TIL (mean 1969 pg/ml and 76 pg/ml respectively, p-value=0.02).

 

Conclusion
 

A functional immune assay can predict rectal cancer response to NACRT. This has the potential both to modify clinical management and opens the door for novel therapeutic approaches. 

28.08 Bowel Preparation with Antibiotics Decreases Surgical-Site Infection for Both Left & Right Colectomy

Posted on January 18, 2018

A. J. Hjelmaas1, A. Kanters1, R. Anand1, J. Cedarbaum1, Y. Chen1, L. Ly1, N. Kamdar1, D. Campbell1, S. Hendren1, S. Regenbogen1  1University Of Michigan,Michigan Medicine,Ann Arbor, MI, USA

Introduction:
Despite recent studies demonstrating the effectiveness of mechanical bowel preparation with oral antibiotics for decreasing rates of surgical site infections (SSI) after colectomy, there remains inconsistency in practice with particular controversy over the role of bowel preparation in right-sided resections. Generally, bacterial concentration and stool solidity increases with progression through the colon, and there persists a belief that bowel preparation is needed only for left-sided resections. To understand whether there is heterogeneity in the efficacy of bowel preparation, we evaluate rates of SSI by the anatomy of resection and type of bowel preparation.

Methods:
We conducted a retrospective cohort study of patients who underwent elective colorectal resection with anastomosis and without stoma between 2012 and 2015, using prospectively-collected data from the Michigan Surgical Quality Collaborative, a state-wide consortium encompassing 73 community, academic, and tertiary hospitals. MSQC nurse reviewers collect a variety of colectomy-specific processes of care, including the type of bowel preparation – mechanical preparation with antibiotics, mechanical preparation without antibiotics, and no bowel preparation. We categorized resections by type of anastomosis according to CPT code – ileocolic (IC), colo-colonic (CC), or colorectal (CR); then compared the incidence of SSI between bowel preparation subtypes. We compared adjusted rates of SSI using logistic regression, including known patient-specific risk factors for SSI.

Results:
A total of 6192 patients were included in the study. 1134 underwent IC anastomosis, 3537 underwent CC anastomosis, and 1521 underwent CR anastomosis. Adjusted comparisons are shown in the Figure. For all cases, adjusted rates of SSI were 8.3% for no bowel preparation, 7.1% for mechanical preparation, and 4.6% for mechanical preparation with antibiotics (p<0.001). For right-sided colectomy, the adjusted rates of postoperative SSI were 11.1%, 5.4%, and 5.1% for no prep, mechanical prep, and mechanical prep with antibiotics, respectively (p=0.005).

Conclusion:
As in previous studies, we find overall rates of SSI are lowest when mechanical preparation is used in conjunction with oral antibiotics. Contrary to the assumption that bowel preparation is unnecessary for right colectomy, we found that bowel preparation led to significantly fewer SSIs even among resections with ileocolic anastomosis. This finding will reinvigorate efforts in our statewide collaborative to encourage bowel preparation with antibiotics for all colorectal resections. 
 

28.02 A Comparison of Operative Approaches in Diverticulitis Requiring Urgent Intervention

Posted on January 18, 2018

C. E. Cauley1, Z. Fong1,2, D. Chang2, H. Kunitake1, R. Ricciardi1, L. Bordeianou1  1Massachusetts General Hospital,Department Of Surgery,Boston, MA, USA 2Massachusetts General Hospital,Codman Center For Clinical Effectiveness In Surgery,Boston, MA, USA

Introduction: Guidelines from the American Society of Colon and Rectal Surgeons support the use of sigmoid resection and primary anastomosis with proximal diversion as a safe option for hemodynamically stable patients with perforated diverticulitis (including feculent peritonitis) at the surgeon’s discretion.  However, there are concerns regarding the broad implementation of these guidelines across hospitals with varying expertise. This study evaluates and compares the outcomes of primary anastomosis with proximal diversion versus end colostomy and Hartmann’s pouch for patients with perforated diverticulitis at National Surgical Quality Improvement Program facilities.

Methods:   We abstracted data from the National Surgical Quality Improvement Program participant user file. Patients who underwent emergent colectomy for perforated diverticulitis between 1/1/2005 through 12/31/2015 were identified. To confirm purulent or feculent diverticulitis, we excluded patients with wound classification of 1 or 2. Outcomes of patients who underwent primary anastomosis with proximal diversion were compared to those treated with end colostomy before and after propensity score matching (caliber width 0.03). Factors associated with mortality, reoperation, and infection were also determined using logistic regression modeling.

Results: 5,254 patients requiring emergent colectomy for perforated diverticulitis were selected: 4,261 (81%) with end colostomy and 993 (18.9%) with primary anastomosis and proximal diversion.  The rate of primary anastomosis with proximal diversion was 10.3% in 2005 and 19.2% in 2015.  Median hospital stay was the same (10 [7-15] days for primary anastomosis with diversion vs. 10 [7-14] days for end colostomy, p=0.8). The reoperation rate was statistically similar (8.7% for end colostomy vs. 7.1% for primary anastomosis with diversion, p=0.1), and mortality rate was statistically equivalent (8.1% end colostomy vs. 6.5% for primary anastomosis with diversion p=0.08).   After propensity score matching, surgical outcomes remained similar with equivalent mortality (8.2% vs 7.0%).  Multivariable logistic regression analysis revealed that operation type (primary anastomosis or Hartmann resection) was not associated with the outcomes of reoperation, postoperative infection, or mortality. (Figure)

Conclusions: Our data demonstrate no difference in surgical outcomes for perforated diverticulitis patients treated with primary anastomosis and proximal diversion as compared to traditional Hartmann resection. These findings indicate that guidelines for perforated diverticulitis in hemodynamically stable patients may be safely and broadly applied to institutions participating in the National Surgical Quality Improvement Program.

27.10 Postoperative Morbidity Independently Predicts Cancer-Related Survival in Peritoneal Metastases

Posted on January 18, 2018

H. A. Choudry1, Y. Shuai2, J. F. Pingpank1, M. P. Holtzman1, S. S. Ahrendt1, H. L. Jones1, L. Ramalingam1, A. H. Zureikat1, H. J. Zeh1, D. L. Bartlett1  1University Of Pittsburgh Medical Center,Surgical Oncology,Pittsburgh, PA, USA 2University Of Pittsburgh Cancer Institute,Biostatistics Facility,Pittsburgh, PA, USA

Introduction: Postoperative morbidity may negatively impact cancer-related outcomes by inducing a pro-tumorigenic environment and preventing the timely initiation of postoperative systemic therapy. We hypothesized that postoperative morbidity would predict cancer-related survival, independent of tumor histology, grade, extent of disease, and other comorbidities. 

Methods: We addressed our hypothesis by using a prospective database of 1296 patients with peritoneal metastases undergoing complex surgical resection with high postoperative morbidity and long-term cancer-related mortality rates. We graded all postoperative morbidity using the Clavien-Dindo grading system. Kaplan-Meier method was used to estimate survival.  Multivariate analyses identified associations with survival and postoperative morbidity.

Results: Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion was performed for peritoneal metastases from cancers of the appendix (50%), colorectum (30%), ovary (8%) and mesothelioma (12%). Tumor burden assessed by median peritoneal carcinomatosis index (PCI) was 16 and optimal cytoreduction (residual tumor < 2.5mm) was achieved in 93% of patients. Major postoperative morbidity (Clavien-Dindo grades 3-5) occurred in 24% of patients and long-term cancer-related mortality was 53%, after a median follow-up of 55 months. Median progression-free survival and overall survival calculated from surgery were 15 and 39 months, respectively. In a multivariate Cox proportional hazards model, major postoperative morbidity (Clavien-Dindo grades 3/4) was an independent negative predictor of survival (HR 1.4) along with non-appendiceal primary histology, higher tumor grade, higher PCI, incomplete cytoreduction, higher age-adjusted Charlson comorbidity index, and recurrent symptomatic disease at presentation. Patients with grades 3/4 postoperative morbidity were 1.6/2.5 times more likely to die of their cancer than those with no post-operative complications. Using multivariate logistic regression model, independent predictors of major postoperative morbidity included higher preoperative ASA (American Society of Anesthesiologists) physical status classification, longer operative time, higher PCI, and non-appendiceal primary histology. 

Conclusion: In our experience, postoperative morbidity independently predicted cancer-related survival, regardless of comorbidities, tumor type, extent, grade, and completeness of surgery. Future work will focus on mechanism underlying this phenomenon. Moreover, the extent of surgical resection required to clear the disease played a dominant role in predicting occurrence of postoperative morbidity. Ongoing studies will address optimization of selection criteria and perioperative management strategies that may reduce postoperative morbidity in such patients that frequently require lengthy procedures and multi-visceral resections. 

 

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