07.11 The Negative Impact of Understaging Rectal Cancer Patients

Posted on January 25, 2017

A. M. Dinaux1,2, R. Amri1,2, L. Bordeianou1,2, H. Kunitake1,2, D. L. Berger1,2  1Massachusetts General Hospital,Surgery,Boston, MA, USA 2Harvard School Of Medicine,Surgery,Brookline, MA, USA

Introduction:
Neoadjuvant chemoradiation has been shown to reduce local recurrence in rectal cancer. It also can reduce the size of large tumors simplifying surgical resection. However, this is an expensive regimen with long-term side effects. Overstaging patients leads to unnecessary treatment. Understaging leads to delaying systemic chemotherapy as radiation therapy is usually done prior to systemic treatment postoperatively. Complicating this decision making process, is fact that we have now started to observe complete responders who have been shown to have similar outcomes with or without surgery. This abstract analyzes rectal cancer patients who were understaged and their subsequent outcomes.

Methods:
This abstract compared rectal adenocarcinoma patients who underwent surgical resection in a single center from 2004 through 2014, with either clinical stage I disease with tumor positive nodes on postoperative pathology, or neoadjuvantly treated clinical stage III patients. Patients who had a local excision were excluded.

Results:
Thirty-three clinically stage I had nodal disease on postoperative pathology (cN0 pN+). These patients had worse rates of EMVI (33.3% vs. 14.5%; P=0.008), perineural invasion (39.4% vs. 16.9%; P = 0.003), large vessel invasion (30.3% vs. 13.5%; P = 0.014), and small vessel invasion (48.5% vs. 15%; <0.001), than pathological  stage III patients  who underwent neoadjuvant therapy. Adjuvant chemotherapy rates were comparable (clinically stage I: 78.8% vs. clinically stage III: 80.7%; P = 0.800), whereas adjuvant radiotherapy rates were unsurprisingly higher in the clinically stage I group (54.5% vs. 1.4%; P<0.001). Local and distant recurrence rates were not significantly different, while rectal cancer death in clinically stage I patients was 12.1%, compared to 9.2% in the clinically stage III group (P=0.594).

Conclusion:
Clinically stage I patients who were pathologically stage III had more aggressive disease than neoadjuvantly treated clinical stage III patients. The long-term outcomes also point towards a trend with increased mortality in the understaged patients. This underlines the importance of neoadjuvant therapy and accurate staging preoperatively, which is essential to avoid understaging and therefore undertreatment of pathological stage III patients.

07.03 Surgical Strategy of Hepatic Resection with Inferior Vena Cava Resection for Liver Cancers

Posted on January 25, 2017

T. Ochiai1, D. Asano1, J. Yoshino1, S. Watanabe1, Y. Ishikawa1, N. Chiyonobu1, Y. Mizuno1, T. Sato1, H. Ueda1, Y. Iwao1, H. Ono1, Y. Mitsunori1, S. Matsumura1, D. Ban1, A. Kudo1, S. Tanaka2, M. Tanabe1  1Tokyo Medical And Dental University,Department Of Hepto-Biliary And Pancreatic Surgery,Bunkyo-ku, Tokyo, Japan 2Tokyo Medical And Dental University,Department Of Molecular Oncology,Bunkyo-ku, Tokyo, Japan

Introduction: The prognosis of patients who have liver cancer associated with inferior vena cava tumor thrombus (IVCTT) or inferior vena cava invasion (IVCI) is very poor, and effective treatment modalities are extremely limited. The objective of this study is to determine the efficacy of surgery and appropriate surgical procedures for liver malignancy with IVCTT or IVCI.

Methods: From January 2003 to December 2015, 19 patients with the liver malignancy (eight metastatic tumors, seven hepatocellular carcinomas, three intrahepatic cholangiocarcinomas and one mixed hepatocellular cholangiocarcinoma) underwent hepatectomy with concomitant IVC resection and reconstruction for eight IVCTT and eleven IVCI. We retrospectively analyzed surgical procedures and survival.

Results:Of the 19 patients, 2 underwent trisegmentectomy, 6 underwent bisegmentectomy, 5 underwent segmentectomy and 6 underwent partial hepatectomy. As IVC reconstruction, 13 underwent primary closure, 4 required 20-mm expansive polytetrafluoroethylene (ePTFE) graft and 2 required patch graft using round ligament and epicardium, respectively. During the IVC cross-clamping, 6 required infrarenal abdominal aortic cross-clamping without cardiopulmonary bypass or venous bypass, 3 required extracorporeal circulation assisting device to maintain stable hemodynamics. Median operation time was 515 minutes (range 256 to 918 minutes) and median intraoperative bleeding was 2353 ml (range 740 to 44000 ml). No hospital death was recognized. The median survival time of hepatocellular carcinoma was 27 months (range 4 to 89 months) and of colorectal liver metastases was 22 months (range 2 to 48 months). One out of 3 in intrahepatic cholangiocarcinoma is still alive 60 months after surgery. 

Conclusion:Hepatic resection with IVC resection and reconstruction for liver tumors provided acceptable outcomes in 19 patients. Considering morphology of the tumor and intraoperative hemodynamics, appropriate surgical procedures should be selected.

 

06.16 Survival of Rectal Carcinoids by Extent of Surgery: A National Analysis of 1,900 Patients

Posted on January 25, 2017

B. Ezekian1, M. A. Adam1, B. F. Gilmore1, Z. Sun1, M. L. Cox1, M. C. Turner1, C. R. Mantyh1, J. Migaly1  1Duke University Medical Center,Department Of Surgery,Durham, NC, USA

Introduction:
Current National Comprehensive Cancer Network (NCCN) guidelines recommend local resection for rectal carcinoids ≤2 cm and radical resection for tumors >2 cm. However, given the limited data examining the appropriate extent of surgery for these lesions, we queried a national database to determine the impact of extent of resection on pathologic lymph node positivity and survival.

Methods:
Patients undergoing surgical treatment for non-metastatic, clinically-node negative rectal carcinoid were identified from the National Cancer Data Base (1998-2012). The association between extent of surgery, tumor size, and the likelihood of lymph node positivity was examined. Kaplan-Meier analysis was used to compare overall survival between patients undergoing local vs. radical resection.

Results:
In total, 1,900 patients were identified, of whom 1,644 (86.5%) were treated with a local resection and 256 (13.5%) were treated with a radical resection. Patient age, race, co-morbidities, and 30-day mortality were not different between groups (all p > 0.05). A vast majority of patients with tumors ≤2 cm received a local excision (88.96%), whereas most patients with tumors 2.1-4 cm (55.17%) or >4 cm (54.17%) received radical surgery. In patients who underwent radical resection, those with larger tumor size were more likely to have lymph node metastases (7.0% of patients with ≤2 cm tumors, 31.3% with 2.1-4 cm tumors, and 50.0% with >4 cm tumors). 5-year survival was not different in patients receiving local vs. radical surgery for tumors <4 cm (93% vs 93%, p = 0.67 for tumors ≤2 cm and 76% vs. 76%, p = 0.77 for tumors 2.1-4 cm).

Conclusion:
In this large cohort of patients with rectal carcinoids, we show that while survival appears to be equivalent between local vs. radical resection for rectal carcinoids up to 4 cm, the likelihood of lymph node metastases significantly increases with tumor size >2 cm. Thereby, current guidelines recommending radical resection for tumors >2 cm seem appropriate.
 

06.12 Use Of Suprahepatic Occlusion Of The IVCFor Resection Of HCC With Tumor Thrombus In The Hepatic Vein

Posted on January 25, 2017

A. Li1, M. Wu1  1Eastern Hepatobiliary Surgery Hospital,SMMU,Shanghai, SHANGHAI, China

Introduction: To investigate the differences in the surgical approaches for resection of hepatocellular carcinoma (HCC) with tumor thrombus was extending into the hepatic vein using occlusion of the suprahepatic inferior vena cava (IVC) with occlusion forceps.

Methods: Between January 2011 and December 2013, 21 patients diagnosed with advanced HCC with tumor thrombi in the hepatic vein underwent hepatectomy and thrombectomy. Peri- and postoperative morbidity and mortality rates were evaluated prospectively and analyzed.

Results:Mean age of the patients was 47 years. Median primary tumor size was 12.0±4.0cm. All HVTT were removed using occlusion of the suprahepatic IVC with Satinsky vascular clamp. Pringle’s maneuver time was 19 minutes (range 15 to 24 minutes). Mean time of occlusion of the suprahepatic IVC was 10 minutes (range 8 to 20 minutes). Mean intraoperative blood loss was 600 mL (range 300 to 2,000 mL). Postoperative complications were seen in 10% of patients (n=2), included pleural effusion (n=2). Median follow-up was 38 months (range 2 to 72 months). The 1- and 2-year overall survival (OS) rates were 57% and 4%, respectively, while the 1- and 2-year recurrence rates were 94% and 96%.

Conclusion: This study showed that using occlusion of the suprahepatic IVC, resection for HCC with tumor thrombi in the hepatic vein can be performed safely and thereby avoid embolus rupture of tumor thrombus and air embolism, and may improve the prognosis of these patients. This method is especially suitable for unexpected, intraoperatively detected hepatic vein tumor thrombus.
 

04.17 Surgical patients with infection have suppressed monocyte function and increased IRAK-M expression

Posted on January 25, 2017

N. J. Galbraith1, S. P. Walker1, S. A. Gardner1, J. V. Carter1, S. Manek1, S. Galandiuk1, H. C. Polk1  1University Of Louisville,Department Of Surgery,Louisville, KY, USA

Introduction:
Some patients who suffer major infection or trauma respond with an exaggerated compensatory anti-inflammatory response. The purpose of this study was to study monocyte function of patients with surgical infection, and determine the expression of negative regulators of toll-like receptor signaling. . 

Methods:

Monocytes were isolated following phlebotomy after written informed consent in colon and rectal surgery patients diagnosed with deep surgical site infection. Samples were studied for baseline parameters of monocyte function, including HLA-DR, and immune response was studied by ex-vivo lipopolysaccharide (LPS) stimulation (100 ng/mL) for 4h. At 4 h, levels of HLA-DR and cytokine responses determined by flow cytometry (FACS) and ELISA, respectively. Monocyte gene expression of negative regulators including suppressor of cytokine signaling 3 (SOCS3),  interleukin-1 receptor-associated kinase M (IRAK-M), Src homology region 2 domain-containing phosphatase-1 (SHP-1), and A20 (TNFAIP3, Tumor Necrosis Factor, Alpha-Induced Protein 3) were measured by qRT-PCR. Follow-up samples from the same patients were obtained after resolution of the infection where possible. Healthy controls were studied for comparison. 

Results:

Sixteen patients with deep surgical site infection were studied, the majority of which were diagnosed with intra-abdominal abscesses and who were hemodynamically stable at the time of sampling. Ten healthy controls were included for comparison. Baseline monocyte HLA-DR expression was similar between patients and healthy controls, but patients with deep surgical site infection had a lower HLA-DR expression in response to LPS (p<0.05). Infected patients had a suppressed TNF-α production when compared against healthy volunteers (p<0.05). In contrast, infected patients had higher levels of circuiting plasma IL-10 levels (p<0.05).

Of the negative regulators studied, IRAK-M was the most consistently up-regulated in infected patients as compared to healthy controls (p<0.05). Interestingly, the expression of IRAK-M partially returned to the levels of healthy controls following clinical recovery from infection. 

Conclusion:

In this study, patients with deep surgical site infection have lower levels of HLA-DR and TNF-α following LPS stimulation, suggestive of impaired cytokine responses and antigen presenting function. IRAK-M, a negative regulator of TLR signaling, was up-regulated in patients during infection, with a partial return to normal levels following clinical recovery. IRAK-M may play a role as a biomarker in identifying “high risk” patients.

04.11 Psychological Stress During Pregnancy Alters Immune Function in Maternal and Neonatal Mice

Posted on January 25, 2017

S. Deas1, M. Melendez-Ferro1, V. Yeramilli4, C. Culbreath2, R. Lorenz5, C. Martin1,3  1University Of Alabama at Birmingham,Surgery,Birmingham, Alabama, USA 2Inova Fairfax Hospital,Surgery,Falls Church, VA, USA 3Children’s Of Alabama,Surgery,Birmingham, ALABAMA, USA 4University Of Alabama at Birmingham,Microbiology,Birmingham, Alabama, USA 5University Of Alabama at Birmingham,Pathology,Birmingham, Alabama, USA

Introduction:  Psychological and environmental stress have been linked to several health conditions. During pregnancy, stress can negatively affect both the mother and child. Potential psychological stressors include a challenging home environment or life event, substance abuse, or chronic health problems. The impact of maternal psychological stress on the neonatal immune system remains unknown. A key element of immune development in neonates is the transfer of protective antibodies from the mother to the newborn. Specifically, the presence of immunoglobulin A (IgA) and early bacterial colonization are key processes in the development of passive immunity in neonates. IgA protects the mucosal surface of the gut by binding to pathogenic bacteria and preventing colonization; in the early stages of development, it is passed from mother to child in breast milk. The gut microbiome further protects mucosa, and it is primarily transmitted from the vaginal microbiome during passage through the birth canal and feeding. We hypothesize that prenatal psychological stress depresses immune function in the mother, thereby impairing transmission of passive immunity to neonates. 

Methods:  8-week-old C57BL/6 littermates underwent timed breeding. The females of three mating pairs were subjected to daily psychological stress by using a well-established restraint model during days 7-14 of the gestational period. The control group experienced no stress. Maternal vaginal microbiome was sampled two days prior to delivery via vaginal lavage; samples were then cultured on Schaedler agar in aerobic conditions for 24 hours at 37°C. Enzyme-linked immunosorbent assay (ELISA) was used to measure fecal IgA levels in in 2-week-old pups.  

Results: Two-week-old mice from the stressed group had significantly less fecal IgA compared with the control group; stress group mean = 51658.51 ng/mL, standard error = 11982.92; control group mean = 200320.22 ng/mL, standard error = 57674.83 (P value = 0.0033). Microbial culture of vaginal microbiome from the mother revealed 98 colony forming units (CFUs) for the stressed group, compared to 187 CFUs for the control group (see figure).

Conclusion: Maternal gestational stress results in significantly less fecal IgA in offspring compared to controls. Additionally, stressed dams had lower vaginal bacterial colonization compared to controls, which could explain this finding. Future experiments will further elucidate this mechanism by analyzing serum IgA levels in the pups and stress hormones in dams and pups.  

 

04.07 Interferon-gamma enhances monocyte function and increases PD-L1 expression.

Posted on January 25, 2017

S. P. Walker1, N. Galbraith1, C. Bishop1, M. Reid1, S. Gardner1, H. Polk1  1University Of Louisville,Department Of Surgery,Louisville, KY, USA

Introduction:

Major infection and trauma lead to poorly understood pro-inflammatory and compensatory anti-inflammatory immunological responses. Some patients have resulting monocyte impairment which is predictive of nosocomial infection and death. Attempts to augment host defenses in surgical patients, such as interferon-gamma (IFN-γ), have thus far failed to improve mortality. An incomplete understanding exists of the underlying immunological mechanisms, including the role of programmed cell death-ligand 1 (PD-L1), a negative co-stimulatory molecule. The purpose of this study was to determine the effects of IFN-γ on monocyte function and PD-L1 expression.        

Methods:

Venous blood was taken using EDTA tubes from healthy volunteers and stimulated ex-vivo with 100 ng/mL of lipopolysaccharide (LPS) for 18 hours in the presence or absence of recombinant IFN-γ (100 ng/mL).  The monocyte inflammatory response was measured using quantitative measurements of surface protein expression of human leukocyte antigen-DR (HLA-DR) and PD-L1 on CD14 positive monocytes using flow cytometry.  Cytokine responses including tumor necrosis factor-alpha (TNF-α) were measured by ELISA. Statistical analyses was determined using Paired T-test or Wilcoxon signed-rank test as appropriate, with significance set at 0.05. Six donors were used for each experiment.     

Results:

Exposure to LPS led to an increase in HLA-DR expression and increased TNF-α production. IFN-γ alone offered minimal effects on HLA-DR or TNF-α levels.  The addition of the immunoadjuvant IFN-γ augmented HLA-DR expression and TNF-α levels at 18 h (p<0.05). Monocyte PD-L1 expression was low at baseline (0 h) in healthy volunteers, but increased in the presence of either LPS or IFN-γ alone (p<0.05). IFN-γ treatment in combination with LPS led to a synergistic increase in PD-L1 expression at 6 h and 18 h after stimulation (p<0.05).

Conclusion:

In this study we found that IFN-γ acts to increase monocyte responsiveness as measured by increased HLA-DR expression and TNF-α production in the presence of LPS. Monocyte PD-L1, a negative co-stimulatory molecule, increased in the presence of LPS. Adjuvant IFN-γ treatment further increased PD-L1 expression. These results suggest that IFN-γ therapy stimulates a negative feedback loop through the PD-1-PD-L1 axis, which could have therapeutic implications in approaching immunoadjuvant therapy in the “high risk” patient. 

04.02 The inflammatory environment of the gut in the surgical Crohn’s patient

Posted on January 25, 2017

M. Laffin2, T. Perry2, B. Dicken2, R. Fedorak3, K. Madsen3  1University Of Alberta,Edmonton, AB, Canada 2University Of Alberta,Department Of Surgery,Edmonton, AB, Canada 3University Of Alberta,Department Of Medicine,Edmonton, AB, Canada

Introduction: Crohn’s disease (CD), is a type of inflammatory bowel disease, defined by transmural inflammation of the alimentary tract. Complications of CD leads to intestinal resection in the majority of patients during their lifetime. While CD can affect any segment of the intestinal tract, it is most often found in the ileocecal region, making Ileocolic resection the most common procedure performed.  Unfortunately, after resection of the diseased segment, inflammation almost inevitably returns proximal to the surgical anastomosis in the neo-terminal ileum. Studying this recurrence may offer a glimpse into the pathophysiology and development of the disease. To date, few published results examine the inflammatory milieu of the peri-operative CD patient and how that profile relates to recurrence.

The objective of our study is to define the immunologic environment of the gut at the time of surgery which and identified how it is associated with post-operative recurrence.

Methods: 26 CD patients were recruited at the time of Ileocolic resection and followed prospectively. Mesenteric lymph node (MLN) and mucosal samples from the terminal ileum were snap frozen in the operating theatre. All patients received follow-up ileocolonoscopy six months post-operatively, at which time recurrence scores in the neo-terminal ileum were recorded using the Rutgeert’s scale. Endoscopic recurrence was defined as a score ≥ 2. A comprehensive multiplex immune assay utilizing the MesoScale Discovery platform measured tissue concentrations of 31 cytokines and chemokines. Known clinical characteristics associated with recurrence were tested using the Fisher’s exact test. Individual analytes were compared using the Mann-Whitney-U test.

Results: 30% of patients had endoscopic disease recurrence at follow up. Mean time to ileocolonoscopy was 209 days in the recurrence group vs. 176 days in the remission group. Clinical parameters including fistulizing disease, previous surgery, and smoking were not significantly associated with recurrence after 6 months in our cohort. When patients were stratified based on these clinical parameters mucosal IL-6 was associated with stricturing disease, smoking was associated with elevated mucosal IL-6 and IL-1α, and perianal disease was associated with elevated mucosal TNF-α, IL-6, IL-1β, and IFN-γ.

When analytes were evaluated by post-operative recurrence, elevated MCP-1 in the mucosa of surgical specimens was associated with disease recurrence. An elevated level of IL-5 and IL-16 was seen in the MLN of patients who recurred.

Conclusion: Results from this study suggest that chemokines are a factor in post-operative recurrence as MCP-1, IL-5 and IL-16 all act as prominent chemoattractants to various immune cell types. These observations highlight the need for further study in cell recruitment to the gut, and its relationship to post-operative recurrence.
 

04.01 Evidence for Botulinum Toxin in Management of Ventral Hernia: A Systematic Review and Meta-Analysis

Posted on January 25, 2017

J. M. Weissler1, M. A. Lanni1, M. G. Tecce1, M. J. Carney1, V. Shubinets1, J. P. Fischer1  1University Of Pennsylvania,Plastic Surgery,Philadelphia, PA, USA

Introduction:  Incisional hernia (IH) remains a challenging and costly surgical complication with high morbidity and exceptionally high recurrence rates. With nearly 350,000 repairs and a cost burden of $3.2 billion annually, there is a clear need for reparative strategies to thwart recurrence and the dramatic physiologic changes to the abdominal wall musculature after hernia. Botulinum toxin (Botox) injections have recently been identified as a potential preoperative means to counteract abdominal wall tension, reduce hernia size, and facilitate ultimate fascial closure. This systematic review and meta-analysis reviews outcomes after Botox injections in the setting of ventral hernia, and demonstrates the applicability of Botox in abdominal wall reconstruction. 

Methods:  A systematic review of the literature was conducted in accordance with PRISMA guidelines using MeSH terms “ventral hernia”, “herniorrhaphy”, “hernia repair”, and “botulinum toxins.” Relevant studies reporting pre- and post-injection data were included. Outcomes of interest included changes in hernia defect width and lateral abdominal muscle length, recurrence, complications, and patient follow-up. Qualitative findings were also considered to help demonstrate valuable themes across the literature.  

Results: Overall, 164 titles were identified following the initial database search from which 11 articles were reviewed. 3 titles were ultimately included in the quantitative analysis, with a total of 56 patients. The remaining articles were considered qualitative in nature and analyzed the subjective effects of Botox. Meta-analysis revealed significant hernia width reduction (mean= 5.79cm; n=29; p<0.001) and lateral abdominal wall muscular lengthening (mean= 3.33cm; n=44; p<0.001) following Botox injections (Table 1). Mean length of follow-up was 24.7 months (range 9-49). The specific metrics before and after Botox injections for each hemi-abdomen were also included in the analysis. 

Conclusion: While traditional abdominal wall reconstruction approaches have unquestionable benefits, Botox injections of the abdominal wall also offer tremendous potential in managing complex ventral hernias. This minimally invasive “chemical component separation” technique may provide crucial tissue mobility, minimize undue abdominal wall tension, and decrease abdominal muscle contractile force facilitating fascial closure, with a potentially easier postoperative recovery for the patient. Although further studies are needed, there is a significant opportunity to bridge the knowledge gap in preoperative practice measures for ventral hernia risk reduction. 

 

95.20 An Imperfect Effort at Week #1 Education for Surgical Trainees: Have Them Drink From the FIRE Hose

Posted on January 25, 2017

Y. N. AlJamal1, B. Gas1, S. Heller1, D. Farley1  1Mayo Clinic,General Surgery,Rochester, MN, USA

Introduction: Converting recent medical school graduates from timid, incompetent, and bewildered learners to a trusted, skillful, and savvy surgical intern takes more than a one-week Boot Camp. Programs pour hundreds of hours and extensive resources into creating a diverse learning opportunity for incoming interns. We ponder how effective this effort has been in our institution.

Methods: We tabulated our work effort in creating and administering our weeklong boot camp and assessed intern pre- and post-test performance. Trainees were asked for candid feedback the week of the boot camp and anonymously 4 months later.

Results: June of 2015, thirty incoming interns participated in our boot camp. Over 7 days of education and orientation, delivery included 16 hours of lecture, 20 hours of ATLS, 4 hours of simulation, 12 hours of computer training, and 8 hours of team building. Over 1000 man-hours of effort was involved (1 PD, 3 PC, 5 STAFF, and 10 others used prep, delivery, and post-camp time) in course creation and delivery. Posttest scores of necessary intern skills (72 vs. 43, p = 0.01) exceeded pre-test performance. Immediate intern feedback was positive (grateful 100%, useful 100%, engaging 100%) but not without critique (overwhelming 100%, too much computer training 100%, and not enough clinical vignettes 65%). Anonymous feedback 4 months into internship from 22 interns revealed different feedback: too little computer training 31%, not enough time for surgical skills 25%, and more desire to engage with senior trainees 30% and discussing surgical scenarios 30%.

Conclusion: The true value of a surgical boot camp is elusive to obtain. Data and feedback from our orientation effort suggests we deliver a message that interns retain, but we need to dial back the water pressure from the fire hose and focus more time on bonding interns with peers and upper level trainees especially with hands on training.

 

« Previous Page