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BACKGROUND Merkel cell polyomavirus (MCPyV) is associated with the development of Merkel cell carcinoma (MCC). Antibody (MCPyV-Ab) titers may have prognostic implications. This study evaluated the impact of the presence or absence of MCPyV-Ab on the 2-year overall survival (OS) and disease-free survival (DFS) of MCC patients. METHODS This single-center, IRB-approved, retrospective cohort study evaluated 51 adult patients with MCC from 2014 to 2021 using a prospectively maintained database. Patients were compared by MCPyV-Ab status, and Kaplan-Meier analysis was used to evaluate 2-year OS and DFS. RESULTS Of the 51 patients, 13 (25.4%) were seropositive, 41 (80.4%) underwent wide excision, 40 (80.0%) received radiotherapy, and 43 (84.3%) received multimodal therapy. The median follow-up period was 15.5 months (range 1-69.5 months). The median 2-year OS of the entire cohort was not reached. The median 2-year OS was not reached for either the seronegative or the seropositive patients. The difference in 2-year OS between the groups was not statistically significant (p = 0.37). Eight patients, all seronegative, were never rendered disease-free and were removed from recurrence analysis. The seropositive patients experienced no recurrences. Of the 30 seronegative patients, 9 (30.0%) experienced recurrence. The median 2-year DFS of the entire cohort was not reached. The median 2-year DFS of the seronegative group was 22.2 months. The 2-year DFS was not reached for the seropositive cohort. Seropositivity conferred a significantly better 2-year DFS than seronegativity (p = 0.04). CONCLUSION The MCPyV-Ab seropositive patients demonstrated improved 2-year DFS. The seropositive patients showed a strong trend toward improved 2-year OS, although the difference not statistically significant. This study substantiated the value of MCPyV-Ab assessment for MCC.

Background Enhanced recovery after surgery (ERAS) protocols are widely utilized for elective colorectal surgery to improve outcomes and decrease costs, but few studies have evaluated the impact of ERAS protocols on cost with respect to anatomic site of resection. This study evaluated the impact of ERAS protocol on elective colon resections by site and longitudinal impact over time. Methods A single-center retrospective cohort study of 598 consecutive patients undergoing elective colorectal resection before and after implementation of ERAS protocol from 2013 to 2017 was performed. The primary outcomes were length of stay (LOS) and cost. Comparative and multivariate inferential statistics were used to assess additional outcomes. Results A total of 598 patients (100 pre-ERAS vs 498 post-ERAS) were evaluated with an overall median LOS of 4 days for right and left colectomies and 3 days for transverse colectomies. When comparing type of resection before and after ERAS protocol introduction, an increased LOS for left hemicolectomies from 3.09 to 4.03 days ( P = .047) was noted, with all other comparisons failing to reach statistical significance. Over time, an initial decrease in LOS for MIS approach after protocol introduction was observed; however, this effect diminished in the ensuing years and had no significant effect overall. Total cost of care was significantly increased post-ERAS for all cohorts except transverse colectomies. No further statistically significant differences were found. Conclusion After an initial improvement in outcomes, continued utilization of ERAS protocols demonstrated no improvement in LOS compared to pre-ERAS data and increased cost overall for patients regardless of site of resection.

Background Accurate preoperative risk stratification remains elusive. Existing tools are often missing important patient-reported and functional factors. We sought to implement a novel tool, with dynamic functional data and comorbidity variables, to define factors which predict postoperative outcomes. Materials and Methods We expanded a previously validated functional questionnaire to create the Tennessee Preoperative Assessment Tool (TPAT). Unique elements included change in functional status, usual and best activity tolerance, and development of new conditions. The survey was administered to all new patients seen in several surgery clinics from July 2021 to June 2022. Results A total of 1950 patients completed the survey. Of the completed surveys, 197 patients underwent an elective, inpatient, abdominal surgery and were included in the study. Several patient-reported factors were associated with poor postoperative outcomes. For example, decrease in functional activity in the previous 60 days (n = 50; 25.4%) was a strong predictor of poor postoperative outcomes including readmission (30-day: 8.8% vs .0%; P = .034), wound dehiscence (12.0% vs 3.4%; P = .022), blood transfusion (6.0% vs .0%; P = .003), sepsis (4.0% vs .0%; P = .015), and wound infection (18.0% vs 6.8%; P = .076). Discussion In this preliminary implementation study, patients undergoing elective, inpatient, abdominal surgery, utilization of a novel, patient-reported survey tool proactively identifies patients at risk of clinically relevant postoperative outcomes. Patient-reported decreased activity in the 60 days prior to surgeon evaluation was associated with several adverse postoperative outcomes. Additionally, this study demonstrates that the TPAT can be seamlessly integrated into the usual clinical workflow and is hypothesis generating for future interventional studies.

Postoperative pain managed with opioids has contributed to the opioid crisis through over-prescribing practices. We assessed opioid-prescribing habits and their use by patients undergoing surgery for cutaneous malignancies. An Institutional Review Board–approved retrospective analysis was conducted for patients who underwent skin cancer resection between January 2018 and June 2018. Data were collected from the electronic medical record, and opioid-related data were collected from patient interviews and state registries. There were 120 study participants (42 females and 78 males) with a median age of 67 years (range, 21–94 years). All received preincision local anesthetic: 64 had liposomal bupivacaine (LB) (53%) and 56 had non-LB bupivacaine (47%). Most participants (n = 88) used 0 opioids (73%), including 43 LB-anesthetic (67%) and 45 non–LB-anesthetic (80%). No significance was seen between those with a diagnosis of chronic pain, narcotic tolerance, an area of resection, and nodal sampling groups in opioid use. Four patients (3%) requested a refill. Of 105 prescriptions written for opioids, 99 had leftover opioids for an over-prescribing rate of 94 per cent. This study suggests pain after skin cancer surgery is manageable with very limited opioid requirements. Our results support prescribing no more than five opioid tablets for postoperative pain control in patients undergoing resection for skin malignancies.

Lynch syndrome (LS) is a common genetic syndrome characterized by pathogenic mutations of DNA mismatch repair genes resulting in a hereditary predisposition to cancer. While typically associated with colonic and endometrial cancer, LS additionally influences the development of many other malignancies. The Amsterdam II and Revised Bethesda Guidelines are the established clinical criteria for diagnosing LS. These guidelines are based on the most general characteristics of LS and do not address specific characteristics of the less commonly LS-associated malignancies. For individuals that present initially with a non-colon and non-endometrial malignancy, recommendations and guidelines on when to consider screening for LS are limited. Therefore, it is essential that clinicians are familiar with distinct LS-associated patient- and tumor-specific characteristics, especially of the less common LS-associated cancers, so that LS’s diagnosis is not missed. In this review article, we focus on extra-colonic and extra-endometrial LS-associated cancers, paying particular attention to any established or currently investigated cancer features that help raise suspicion for LS and potentially lead to its earlier diagnosis. This review will also discuss current guidelines specific to each LS-associated malignancy.

Merkel cell polyomavirus (MCPyV) is associated with the development of Merkel cell carcinoma (MCC). Antibody (MCPyV-Ab) titers may have prognostic implications. This study evaluated the impact of the presence or absence of MCPyV-Ab on the 2-year overall survival (OS) and disease-free survival (DFS) of MCC patients.This single-center, IRB-approved, retrospective cohort study evaluated 51 adult patients with MCC from 2014 to 2021 using a prospectively maintained database. Patients were compared by MCPyV-Ab status, and Kaplan-Meier analysis was used to evaluate 2-year OS and DFS.Of the 51 patients, 13 (25.4%) were seropositive, 41 (80.4%) underwent wide excision, 40 (80.0%) received radiotherapy, and 43 (84.3%) received multimodal therapy. The median follow-up period was 15.5 months (range 1-69.5 months). The median 2-year OS of the entire cohort was not reached. The median 2-year OS was not reached for either the seronegative or the seropositive patients. The difference in 2-year OS between the groups was not statistically significant (p = 0.37). Eight patients, all seronegative, were never rendered disease-free and were removed from recurrence analysis. The seropositive patients experienced no recurrences. Of the 30 seronegative patients, 9 (30.0%) experienced recurrence. The median 2-year DFS of the entire cohort was not reached. The median 2-year DFS of the seronegative group was 22.2 months. The 2-year DFS was not reached for the seropositive cohort. Seropositivity conferred a significantly better 2-year DFS than seronegativity (p = 0.04).The MCPyV-Ab seropositive patients demonstrated improved 2-year DFS. The seropositive patients showed a strong trend toward improved 2-year OS, although the difference not statistically significant. This study substantiated the value of MCPyV-Ab assessment for MCC.

Background Early ambulation after surgery is demonstrated to reduce complications and decreases patient length of stay (LOS) as part of an enhanced recovery after surgery (ERAS) program. This study hypothesizes that missed and refused ambulation attempts prolong patient LOS. Methods From January 2014 to December 2016, all patients admitted to one ward who had undergone bowel resection surgery were assigned a dedicated ambulation team with the goal of ambulating 3 times per day. Clinical data was collected prospectively. Statistical analysis of ambulation frequency, percentage of ambulation sessions completed and overall LOS was performed to test the hypothesis. Results A total of 127 patients were analyzed for mean age, breakdown of laparoscopic/open procedures/pre-surgery ambulation status. The median LOS (mLOS) for all patients was 4.3 days. When ambulation was not offered for a 24-hour period, the mLOS increased from 3.6 to 6.6 days (P

Postoperative pain managed with opioids has contributed to the opioid crisis through overprescribing practices. We assessed opioid-prescribing habits and their use by patients undergoing surgery for cutaneous malignancies. An Institutional Review Board-approved retrospective analysis was conducted for patients who underwent skin cancer resection between January 2018 and June 2018. Data were collected from the electronic medical record, and opioid-related data were collected from patient interviews and state registries. There were 120 study participants (42 females and 78 males) with a median age of 67 years (range, 21-94 years). All received preincision local anesthetic: 64 had liposomal bupivacaine (LB) (53%) and 56 had non-LB bupivacaine (47%). Most participants (n = 88) used 0 opioids (73%), including 43 LB-anesthetic (67%) and 45 non-LB-anesthetic (80%). No significance was seen between those with a diagnosis of chronic pain, narcotic tolerance, an area of resection, and nodal sampling groups in opioid use. Four patients (3%) requested a refill. Of 105 prescriptions written for opioids, 99 had leftover opioids for an overprescribing rate of 94 per cent. This study suggests pain after skin cancer surgery is manageable with very limited opioid requirements. Our results support prescribing no more than five opioid tablets for postoperative pain control in patients undergoing resection for skin malignancies.

Skin substitutes have shown success in complex wound reconstruction. We evaluate the use of a human acellular dermal matrix (ADM) as a viable alternative to autologous skin grafting for defects secondary to skin cancer excision. An institutional review board-approved, retrospective review of ADM-reconstructed defects secondary to skin cancer excision between 2012 and 2018 was conducted. ADM was indicated in patients with preclusive factors for general anesthesia, protracted procedure time, reluctance for additional donor site wound, and personal choice. We reviewed defect characteristics, healing time, postoperative outcomes, and patient demographics. The 228 participants (151 males, 77 females) had a median age of 72 years (range, 29-95 years), with melanoma diagnosed in 113 (49.6%), squamous cell carcinoma in 61 (26.8%), and basal cell carcinoma in 28 (12.2%) patients. The median interval to complete epidermal coverage was 42 days, with graft failure evident in six patients (2.6%). ADM is a viable, low-morbid alternative for reconstruction of defects secondary to skin cancer excision, with no donor site morbidity. With exception to complete healing time, outcomes are similar to those of autologous grafting.

A multimodality approach to enhance recovery after bowel surgery is demonstrated to reduce complications and decrease patient length of stay (LOS). This study evaluates the factors that influence patient LOS within a formal enhanced recovery protocol. From January 2014 to December 2016, all consecutive patients admitted to one ward, who had undergone bowel resection and were enrolled in an enhanced recovery protocol, were evaluated prospectively. We entered every patient's data into the American College of Surgeons Risk Calculator (ACSRC) to compare predicted versus actual outcomes. Statistical analysis of clinical factors, patient participation, and outcomes compared with the overall LOS was performed. Of 670 bowel resections performed during the study period, a total of 127 (19%) patients met the criteria and were analyzed for comorbidities, type of surgery, complications, and participation in recovery protocols. The median length of stay (mLOS) for all patients was 4.0 days (1.8-24.6 days). Factors influencing mLOS included laparoscopic versus open surgery (P = 0.006), COPD (P = 0.003), missing 24 hours of ambulation (P0.001), use of patient-controlled analgesia (P = 0.011), and diagnosis of insulin-dependent diabetes mellitus (P = 0.041). Increasing the use of morphine equivalents (MEs) increased mLOS beyond the ACSRC estimate (P = 0.003). Developing a major complication increased mLOS by 8.5 times the ACSRC estimate.A multimodality approach to enhance surgical recovery after bowel surgery decreases the LOS. The surgical approach, participation in ambulation, insulin-dependent diabetes mellitus, and COPD influenced the overall LOS. Increasing use of morphine equivalents and developing a complication increased mLOS beyond the ACSRC preoperative risk estimates.

We have previously demonstrated that TNM status and age were significant predictors of overall survival (OS) in our study population of Caucasian patients with invasive breast carcinoma (2000-2004 study period). However, estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) biomarker expression was not predictive of OS when using the five-group ER/PR/HER2 subtype classification system recommended by St. Gallen International Consensus Panel in 2011. The current study reassessed the relevance of tumor biomarkers (ER/PR/HER2) in our study population using a recently proposed biologic TNM (bTNM) classification system in which the inclusion of triple negative ER/PR/HER2 phenotype (TNP) could improve the prognostic accuracy of TNM for staging, prognosis and treatment of breast cancer patients. Seven hundred eighty-two Caucasian women diagnosed with invasive ductal carcinoma from 1998 to 2008 were grouped according to their TNM stage and TNP versus non-TNP ER/PR/HER2 phenotype. OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis. TNM stage (Stage II = HR 1.41, 95% CI 1.01-1.97; Stage III = HR 3.96, 95% CI 2.68-5.88; Stage IV = HR 27.25, 95% CI 16.84-44.08), and age (HR 1.05, 95% CI 1.04-1.06) were significant predictors of OS. TNP significantly worsened prognosis/survival only in higher TNM stages (Stage III = HR 3.08, 95% CI 1.88-5.04, Stage IV = HR 24.36, 95% CI 13.81-42.99), but not in lower stages (I and II). Our data support the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes and show that biomarkers primarily improve the accuracy of TNM staging in advanced stages of breast cancer. We suspect that type of ER/PR/HER2 classification system(s) (St. Gallen, TNP, etc.), characteristics of populations studied (Caucasians, minorities, etc.), and the time period chosen for a study are major factors that determine impact of biomarkers on the prognostic accuracy of TNM. We propose systematic analyses of these factors before biomarkers are fully incorporated into the TNM staging system (bTNM).

Pneumatosis intestinalis (PI) identified on computed tomography (CT) suggests an underlying pathology including bowel ischemia. Patients receiving tube feeds can develop PI, potentially requiring surgical intervention. We identify clinical factors in PI to predict those that may be safe to observe versus those that need immediate intervention. We retrospectively reviewed patients from a single institution from 2008 to 2016 with CT findings of PI and an enteric feeding tube. Patients who had not received tube feeds within one week of the CT were excluded. We analyzed clinical, operative, and outcome data to differentiate benign from pathologic outcomes. P values0.05 were set as significant. Forty patients were identified. We classified 24 as benign (no intervention) and 16 as pathologic (requiring intervention). A pathologic outcome was demonstrated for free fluid on CT [odds ratio (OR) = 5.00, confidence interval (CI) 1.23-20.30, P = 0.03)], blood urea nitrogen (BUN) elevation (OR = 8.27, CI 1.53-44.62, P = 0.01), creatinine (Cr) elevation (OR = 5.00, CI 1.27-19.62, P = 0.02), BUN/Cr ratio30 (OR = 8.57, CI 1.79-40.98, P = 0.006), and vomiting/feeding intolerance (OR = 9.38, CI 1.64-53.62, P = 0.01). Bowel function within 24 hours of the CT, bowel dilatation (small ≥ 3 cm; large ≥6 cm), and lactic acidemia were not significant. Peritonitis was only seen in pathologic states, but this did not reach statistical significance (P = 0.06). This represents the largest single-center retrospective analysis of tube feeding-induced PI to date. The presence of free fluid on CT, BUN and Cr elevation, BUN/Cr30, vomiting/feeding intolerance and peritonitis were predictive of a pathologic etiology of PI.

Background A significant increase in industry support of professional medical associations coupled with data suggesting that gifts from industry have significant clinical influence have prompted calls from the Institute of Medicine and physician leaders to identify and manage conflicts of interest that stem from financial support of professional medical associations by industry. Study Design A joint task force of members appointed by the Association for Academic Surgery and the Society of University Surgeons was convened in July 2009. Recommendations were developed regarding management of all potential conflicts of interest that can arise within the context of an academic surgical society, with specific focus on relationships with industry. Task force members reached consensus around each recommendation and the guidelines were subsequently adopted by the Executive Councils of both societies. Results The committee identified 4 primary areas of need for transparent and definitive management of conflict of interest: 1) individual society activities, including general budget support, society endorsements, and journal affiliation; 2) individual personnel conflicts such as society leadership and standards for disclosure of conflict; 3) meeting activities including budgetary support, program committee associations, and abstract review process; and 4) foundation support and research and travel awards. The resulting guidelines aim to protect the societies and their membership from undue bias that may undermine the credibility and mission of these associations. Conclusions Policy guidelines to mitigate conflict of interest are necessary to protect the integrity of the work of academic surgical societies and their fiduciary duty to members and patients. Guidelines created and adopted by the Association for Academic Surgery and Society of University Surgeons form an effective model for academic surgical societies and their members.

PURPOSE: Although mucinous adenocarcinomas represent 6% to 19% of all colorectal adenocarcinomas, little is known about the genome-wide alterations associated with this malignancy. We have sought to characterize both the gene expression profiles of mucinous adenocarcinomas and their clinicopathologic features. METHODS: Tumors from 171 patients with primary colorectal cancer were profiled using the Affymetrix HG-U133Plus 2.0 GeneChip with characterization of clinicopathologic data. Gene ontology software was used to identify altered biologic pathways. RESULTS: Twenty (11.7%) mucinous adenocarcinomas and 151 (89.3%) nonmucinous adenocarcinomas were identified. Mucinous adenocarcinomas were more likely to be diagnosed with lymph node (LN) metastases (75% vs 51%, P = .04) and at a more advanced stage (85% vs 54%, P = .006) but long-term survival (5-y survival 58.9% vs 58.7%, P = NS) was similar. Mucinous adenocarcinomas displayed 182 upregulated and 135 downregulated genes. The most upregulated genes included those involved in cellular differentiation and mucin metabolism (eg, AQP3 + 4.6, MUC5AC +4.2, MUC2 + 2.8). Altered biologic pathways included those associated with mucin substrate metabolism (P = .002 and .02), amino acid metabolism (P = .02), and the mitogen-activated protein kinase cascade (P = .02). DISCUSSION: Using gene expression profiling of mucinous adenocarcinomas, we have identified the differential upregulation of genes involved in differentiation and mucin metabolism, as well as specific biologic pathways. These findings suggest that mucinous adenocarcinomas represent a genetically distinct variant of colorectal adencarcinoma and have implications for the development of targeted therapies.

181 Background: The University of Tennessee Medical Center in Knoxville, Tennessee is the regions only academic medical center. This includes the Cancer Institute, where in 2013 a division dedicated to melanoma and soft tissue tumors (MASTT) was created. Since 2013, the number of melanoma cases treated at UTMCK treated has increased in excess of 300%. One critical aspect of the MASTT service was to provide survivorship care to all patients treated. This has given MASTT a unique opportunity to determine how survivorship care has impacted detection of recurrence in melanoma. Methods: Tumor registry data was retrospectively reviewed from a prospectively maintained database. All melanoma patients treated from 2011 to 2015 were identified. This cohort was selected because all of these patients would have been eligible for survivorship care. These patients were then stratified into stage and sub-stage, recurrence status, stage at recurrence, and whether alive or dead. Median and range of time to recurrence were calculated as well. Results: A total of 758 patients were treated for melanoma between 2011 and 2015 at UTMCK by the MASTT service. From this overall sample, a total of 37 patients demonstrated recurrence (4.88% overall). Local recurrence was noted in 9 cases (1.2%), regional recurrence in 4 cases (0.53%) and distant in 15 cases (2.0%). Seven of the recurrent cases were not specified. Median time to recurrence was 12 months (6-40 months). Overall mortality rate for patients with recurrent melanoma was 18/37 (48.6%). Nationally, local recurrence rates are reported between 3 – 5%. Conclusions: A retrospective analysis of tumor registry data for melanoma patients treated at UTMCK CI by the MASTT service line shows that offering survivorship care to this population is beneficial in detecting recurrence. This is key in getting patients evaluated and established for immunotherapy and/or other treatment options at the earliest time of recurrence, which can potentially improve their response to treatment by.

Background On occasion, patients followed with positron emission tomographic (PET)/computed tomographic (CT) imaging for nonbreast malignancies will have incidental breast findings concerning for second primary breast cancers. The aim of this study was to determine the predictive value of PET/CT imaging to identify breast cancers in these patients. Methods Patients with primary nonbreast malignancies and findings concerning for second primary breast cancers were identified from a prospectively acquired nuclear medicine database from January 2005 to July 2008. Chart reviews were then performed. Results Nine hundred two women underwent PET/CT imaging to evaluate nonbreast malignancies. Nine women (1%) had concerning breast findings, and 5 (56%) had subsequent breast cancer diagnoses. The positive predictive value of PET/CT imaging in these patients was 63%. Evidence of compliance with current screening guidelines was present in only 22% of these patients. Conclusions The data suggest that findings concerning for an additional primary breast cancer should be evaluated and that age-appropriate screening tools should not be abandoned.

Background Despite a paucity of evidence-based guidelines, the use of PET/CT (positron emission tomography/computed tomography) in the management of cancer patients is increasing. As widespread clinical application increases, unexpected radiographic findings are occasionally identified. These incidental findings are often suspicious for a second primary malignancy. The purpose of this study was to determine the clinical impact of these incidental PET/CT findings. Methods A query of our prospectively acquired Nuclear Medicine database was performed to identify patients with a known malignancy being staged or serially imaged with PET/CT. Patients with incidental findings suggestive of a second primary malignancy were selected. Statistical analysis was performed to determine the ability of PET/CT to identify a second primary malignancy. All PET/CT were interpreted by board certified nuclear radiologists. Results Of 3,814 PET/CT scans performed on 2,219 cancer patients at our institution from January 1, 2005, to December 29, 2008, 272 patients (12% of all patients) had findings concerning for a second primary malignancy. An invasive work-up was performed on 49% (133/272) of these patients, while 15% (40/272) had no further evaluation due to an advanced primary malignancy. The remaining 36% (99/272) had no further evaluation secondary to a low clinical suspicion determined by the treating team, a clinical plan of observation, or patients lost to follow-up. Of the 133 patients evaluated further, clinicians identified a second primary malignancy in 41 patients (31%), benign disease in 62 patients (47%), and metastatic disease from their known malignancy in 30 patients (23%). The most common sites for a proven second primary malignancy were: lung (N = 10), breast (N = 7), and colon (N = 5). Investigation of these lesions was performed using several techniques, including 24 endoscopies (6 malignant). A surgical procedure was performed in 74 patients (29 malignant), and a percutaneous biopsy was performed on 34 patients (12 malignant). The overall positive predictive value for PET/CT to detect a second primary malignancy was 31% in this subgroup. At a median follow-up of 22 months, 9 of 41 patients with a second primary were dead of a malignancy, 20 were alive with disease, and 12 had no evidence of disease. Conclusion Incidental PET/CT findings consistent with a second primary are occasionally encountered in cancer patients. In our data, approximately half of these findings were benign, a third were consistent with a second primary malignancy or a metastatic focus, and the remainder were never evaluated due to physician and patient decision. Advanced primary tumors are unlikely to be impacted by a second primary tumor suggesting that this subset of patients will not benefit from further investigation. Our data suggests that, despite the high rate of false positivity, incidental PET/CT findings should be investigated when the results will impact treatment algorithms. The timing and route of investigation should be dictated by clinical judgment and the status of the primary tumor. Further investigation will need to be performed to determine the long-term clinical impact of incidentally identified second primary malignancies.

The influence of preoperative hemoglobin levels on outcomes of patients undergoing esophagectomy for cancer is not clearly defined. The goal of this article was to explore the association between combined modality therapy, preoperative anemia status, and perioperative blood transfusion and risk of postoperative complications among patients undergoing esophageal resection.From a retrospective esophageal database, 413 patients were identified. Anemia was defined according to the World Health Organization classification of13 g/dL or12 g/dL for men or women, respectively. Statistical analysis was performed with analysis of variance, Pearson's chi(2), or Fisher exact test as appropriate. The independent association of anemia, blood transfusion, and combined modality treatment on risk of postoperative complications were examined using multiple logistic regression.Information on combined modality treatment, preoperative hemoglobin levels, and blood transfusion was available for 413 patients, of whom 57% received combined modality treatment. Overall 197 (47.6%) patients were preoperatively found to be anemic, and those who had received combined modality treatment were more likely to be anemic (60.6% versus 30.7%, P0.001). Anemic patients required more blood transfusions than nonanemic patients (46.7% versus 29.6%, P0.001). Seventy-five percent of patients who required transfusion during the hospital stay had received combined modality treatment (P = 0.01). Combined modality treatment and anemia were not associated with increased risk of complications. Patients with any perioperative complication and surgical site infections were more likely to have received blood transfusion compared to patients without complications (OR = 1.73; 95% CI 1.04-2.87 and OR = 2.98; 95% CI 1.04-8.55; respectively).Overall, we determined that administration of neoadjuvant treatment to esophageal cancer patients was not associated with an increased rate of perioperative complications. Preoperative anemia did not predict worsened short-term outcomes, but increased the chances of red blood cell transfusion, which were significantly associated with higher overall complications and increased risk of surgical site infections. These data confirm previous studies that allogenic red blood cell transfusions are independent risk factors for increased morbidity and mortality and should be minimized during surgery for esophageal cancer.

Background Esophageal cancer continues to increase in incidence. Many patients are presenting with stage II or greater disease and proceeding to neoadjuvant chemoradiation therapy before resection. Approximately 30% of patients will achieve a complete response and might not benefit from proceeding to resection. This study will examine the ability of PET to predict patients with a complete pathologic response. Study Design A query of our IRB-approved esophageal database revealed 81 patients who underwent a pre- and postchemoradiation PET scan and then proceeded to esophageal resection. Statistical analysis was performed to determine the ability of PET to predict a complete pathologic response. Results When comparing posttherapy PET with final pathology, it was determined that PET could not consistently differentiate a complete pathologic response from patients who still had persistent disease. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 61.8%, 43.8%, 70%, 35%, and 56%, respectively, for patients with a complete PET response after neoadjuvant therapy. Conclusions A complete PET response after neoadjuvant chemoradiation is not substantially predictive of a complete pathologic response. Patients should still be referred for resection unless distant metastases are identified.

Given the increasing rate of obesity, the effects of excessive body weight on surgical outcomes constitute a relevant quality of care concern. Our aim was to determine the relationship between preoperative body mass index (BMI) on perioperative complications after esophagectomy for cancer.From our comprehensive esophageal cancer database consisting of 510 patients, we identified 166 obese (BMI ≥30), 176 overweight (BMI 25-29), and 148 normal-weight (BMI 20-24) patients. Malnourished patients (BMI of20) were excluded. Incidence of preoperative risk factors and perioperative complications in each group were analyzed.The patient group consists of 420 men and 70 women with a mean age at time of surgery were 64 years (range 28-86 years). The categories of patients (obese, overweight, and normal-weight) were similar in terms of demographics and comorbidities, with the exception of a younger age (62.5 years vs 66.2 years vs 65.3 years, P = 0.002), and a higher incidence of diabetes (23.5% vs 11.4% vs 10.1%, P = 0.001) and hiatal hernia (28.3% vs 14.8% vs 20.3%, P = 0.01) for obese patients. More patients with BMI24 were found with adenocarcinoma, compared with the normal-weight group (90.8% vs 90.9% vs 82.5%, P = 0.03). Despite similar preoperative stage, obese patients were less likely to receive neoadjuvant treatment (47.6% vs 54.5% vs 66.2%, P = 0.004). The type of surgery performed, overall blood loss, extent of lymphadenectomy, rate of resections with negative margins, and postoperative complications were not influenced by BMI on univariate and multivariate analysis.In our experience, BMI did not affect number of harvested lymph-nodes, rates of negative margins, and morbidity and mortality after esophagectomy for cancer. In our experience, esophagectomy could be performed safely and efficiently in mildly obese patients.

There is still a paucity of data on how breast cancer (BC) biology influences outcomes in elderly patients. We evaluated whether ER/PR/HER2 subtype and TNM stage of invasive BC had a significant impact on overall survival (OS) in a cohort of 232 elderly Caucasian female patients (≥70 year old (y/o)) from our institution over a ten-year interval (January 1998–July 2008). Five ER/PR/HER2 BC subtypes classified per 2011 St. Gallen International Expert Consensus recommendations were further subclassified into three subtypes (traditionally considered “favorable” subtype-ER+/PR+/HER2-, and traditionally considered “unfavorable” BC subtypes: HER2+ and triple negative). OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis, when controlled for TNM stage. The majority of our patients (178/232 = 76.8%) were of the “favorable” BC subtype, 23.2% patients were with “unfavorable” subtype (HER2+ = 12% (28/232) and triple negative = 11.2% (26/232)). Although a trend for better OS was noted in HER2+ patients (68%) vs. 56% in ER+/PR+ HER2- or 58% in triple negative patients, “favorable” BC subtype was not significantly predictive of better OS (p = 0.285). TNM stage was predictive of OS (p &lt, 0.001). These results are similar to our published studies on Caucasian BC patients of all ages in which ER/PR/HER2 status was not predictive of OS, irrespective of classification system used.

Background Approximately 15% of gastrointestinal stromal tumors (GISTs) will not respond to tyrosine kinase inhibitors and drug resistance can develop over time. For refractory tumors, additional therapies are needed. Odontogenic ameloblast–associated protein (ODAM) is expressed in some epithelial malignancies and can correlate with clinical outcomes. This study evaluated ODAM and its relationship to phosphatase and tensin homolog on chromosome 10 (PTEN) and phosphorylation of AKT to an activated state (pAKT) in GISTs. Materials and methods Ninety-five distinct tumor specimens from 79 patients were identified. Morphologic features and clinical data were recorded for all tumors. Risk of recurrence was calculated using the Memorial Sloan-Kettering nomogram. Immunohistochemistry was performed using antibodies to ODAM, PTEN, and pAKT. Immunoreactivity was assessed for both cytoplasmic and nuclear expression. Staining patterns were correlated with clinical outcomes. Results Increasing cytoplasmic ODAM staining correlated with a lower recurrence score (P = 0.002), a lower mitotic rate (P = 0.0001), and smaller tumor size (P = 0.038). Increasing pAKT cytoplasmic staining correlated with a higher recurrence score (P = 0.037) and a higher mitotic rate (P = 0.036). ODAM and pAKT expression in the nucleus was associated with tumor origin. PTEN nuclear expression increased with increasing mitotic rate. pAKT expression increased in the cytoplasm and nucleus in high-risk tumors. Conclusions Risk of recurrence correlated with cytoplasmic expression of ODAM and pAKT, whereas nuclear expression did not predict recurrence. The staining pattern for ODAM and pAKT in the cytoplasm may further clarify the risk of recurrence beyond the available nomograms. The increased expression of pAKT in the cytoplasm and nucleus of high-risk tumors suggests a potential target for systemic therapy.

Down-regulation of apoptosis genes has been implicated in the development and progression of malignant melanoma. We used cDNA microarray to evaluate pro-apoptotic gene expression comparing normal skin to melanoma (thin and thick), nodal disease and distant metastases. Twenty-eight specimens including skin (n = 1), thin melanoma (n = 6), thick melanoma (n = 7), nodal disease (n = 6), and distant metastases (n = 8), were harvested at the time of resection from 16 individuals. RNA was isolated and microarray analysis utilizing the Affymetrix GeneChip (54,000 genetic elements, U133A+B... levels) was performed. Mean level of expression was calculated for each gene within a sample group. Expression profiles were then compared between tissue groups. Student’s t-test was used to determine variance in expression between groups. We reviewed the expression of 54,000 genetic elements, of which 2,015 were found to have significantly altered expression. This represents 1,602 genes. Twenty-two pro-apoptotic genes were found to be down-regulated when compared to normal skin. Overall reduction was evaluated comparing normal skin to metastases with a range of 3.31–64.04-fold-decrease. When comparing the tissue types sequentially, the greatest fold-decrease in gene expression occurred when comparing skin to all melanomas (thin and thick) (p = 0.011). Subset analysis comparing normal skin to thin melanoma or thick melanoma, revealed the greatest component of overall reduction at the transition from thin to thick lesions (p = 0.003). Sequential down-regulation of pro-apoptotic genes is associated with the progression of malignant melanoma. The greatest fold-decrease occurs in the transformation from thin to thick lesions.

Cytoreductive therapy for metastatic carcinoid provides symptomatic relief and improvement in overall survival. We evaluated whether CgA and 5HIAA could predict symptomatic relief and control of disease progression after cytoreductive surgery.We retrospectively reviewed 70 patients who underwent cytoreductive surgery for neuroendocrine hepatic metastases between 1996 and 2005. Twenty-two patients had pre and post-operative CgA and/or 5HIAA levels measured. Reduction of biomarkers following cytoreduction was correlated with patient symptoms and progression of disease following surgery.Our study consisted of 14 males and 8 females with a mean age of 55 (+/-12 years). Median follow-up was 18 months (range 5-64 months). Six patients (26.1%) had complete (R0) cytoreduction, while 4 (17.4%) and 13 (56.5%) had microscopic (R1) and gross (R2) disease remaining. All patients reported improvements in their symptoms, with 12 (54.5%) reporting complete resolution (CR) and 10 (45.5%) reporting partial resolution (PR). Reduction of CgA ofor= 80% was highly predictive of complete resolution of symptoms (P = 0.007) and stabilization of disease (P = 0.034). Reduction of 5HIAA levels ofor= 80% (or normalization) was predictive of symptomatic relief, but not progression of disease (P = 0.026 and P = 0.725). Five of six patients who had R0 resections had CR and were free of disease at last follow-up (median 24.5 months, range: 11-48, P = 0.002).We conclude thator= 80% reduction in CgA level following cytoreductive surgery for carcinoid tumors is predictive of subsequent symptom relief and disease control. Substantial reduction in CgA is associated with improved patient outcomes, even after incomplete cytoreduction.

PURPOSE OF REVIEW: Molecular profiling has proven to be an invaluable tool in cancer research. Although only in its infancy, microarray technology and gene arrays have led to substantial advances in tumor identification, staging and prediction of response. This review outlines some of the more recent advances in the use of microarrays as a novel means to advance the standard of care for patients with gastrointestinal cancers. RECENT FINDINGS: Recent investigations have shown that gene expression profiles can be used to identify, stage, and guide therapeutic intervention in many gastrointestinal cancers. In cases of unknown primary disease, genetic fingerprints can be used to define the origin of the tumor in the majority of cases. Similarly, gene expression has been shown to allow for more accurate staging of patients with a variety of tumor types. Perhaps most exciting is early data that support the potential for microarray to guide therapeutic intervention by providing specific gene fingerprints which correlate with sensitivity to specific chemotherapy, biologic therapy, or other cancer treatments. SUMMARY: Gene microarrays have become a powerful resource in cancer investigations. Individualized cancer care based on specific gene profiles is on the horizon for patients with gastrointestinal cancers.

Metastases to the liver is the leading cause of death in patients with colorectal cancer.The authors review the data on diagnosis and management of this clinical problem, and they discuss management options that can be considered.Complete surgical resection of metastases from colorectal cancer that are localized to the liver results in 5-year survival rates ranging from 26% to 40%.By adding modalities such as targeted systemic therapy and other "local" treatments for liver metastases, further gains in survival are anticipated.

Over the last several years, attempts have been made to use the tumoricidal effects of tumor necrosis factor (TNF)-alpha to treat cancer. Many of these studies demonstrated dose-limiting systemic side effects from high concentrations of TNF-alpha. The recent focus has been on developing a local delivery system for TNF-alpha to minimize the systemic response.This study was part of a phase I open-label multi-institutional trial using TNFerade. We focus on the patients treated at Baylor University Medical Center and provide postoperative and long-term follow-up. TNFerade uses a second-generation nonreplicating adenovirus as the vector for delivery of the human transgene TNF-alpha. An early growth response 1 promoter was placed upstream from the TNF-alpha gene. This promoter is activated by ionizing radiation, thus allowing for temporal and spatial control of TNF-alpha release. Tumors were injected over 5 weeks with ionizing radiation given 3 days after injections for 6 weeks. Tumor response was measured by computed tomographic imaging and physical examination.As described in our original experience, no patients experienced dose-limiting toxicities up to doses of 4 x 10(11) particles per injection. Tumors injected demonstrated a response independently of histology. Four patients had complete regression of the tumor injected. Three patients with complete regression have survivedor = 2 years from the time of treatment.Both short-term and long-term safety are observed with TNFerade. These data demonstrate the need for phase II trials.

Background In patients with esophageal cancer, treatment decisions often involve a balance between a high-risk procedure and the chance for long-term benefit. The decision can be additionally challenging for elderly patients since some studies have reported an increased incidence of morbidity and mortality in this age group, and data are not clear on the overall benefit of multimodality therapy. Methods To investigate the management and outcomes associated with esophagectomy in elderly patients with esophageal cancer, we performed a review of the literature as well as an analysis of our own institutional data, with a focus on the impact of age on surgical outcomes. We examined type of surgery, neoadjuvant and adjuvant therapy, postoperative complications, length of hospitalization, and mortality as variables in elderly patients with esophageal cancer. Results When assessing the impact of age on the success of esophagectomy, several studies have concluded that advanced age itself is not a predictor of outcomes as much as associated comorbidities are. Our own experience suggests that age is not associated with adverse outcomes when controlling for patient comorbidities. This finding is similar to data reported elsewhere. Conclusions When considering treatment for patients of advanced age, the risks of treatment should be compared with the survival benefits of the therapy prescribed, taking into account additional factors such as poor performance status, existing comorbidities, and residual tumor following neoadjuvant therapy. Many reports, as well as our own experience, have concluded that when adjusted for comorbidities, patient age does not significantly affect outcomes.

Neoadjuvant chemoradiation (NCRT) has become the preferred treatment for patients with locally advanced esophageal cancer. Survival often is correlated to degree of pathologic response; however, outcomes in patients who are found to be pathologic nonresponders (pNR) remain uninvestigated. This study was designed to evaluate survival in pNR to NCRT compared with patients treated with primary esophagectomy (PE). Using our comprehensive esophageal cancer database, we identified patients treated with NCRT and deemed pNR along with patients who proceeded to PE. Clinical and pathologic data were compared using Fisher’s exact and χ2, whereas Kaplan–Meier estimates were used for survival analysis. We identified 63 patients treated with NCRT and were found to have a pNR, and 81 patients who underwent PE. Disease-free (DFS) and overall survival (OS) were significantly decreased in the pNR group compared with those treated with PE (10 vs. 50 months (0–152), P

Pancreatic Adenocarcinoma (PDAC), the fourth highest cause of cancer related deaths in the United States, has the most aggressive presentation resulting in a very short median survival time for the affected patients. Early detection of PDAC is confounded by lack of specific markers that has motivated the use of high throughput molecular approaches to delineate potential biomarkers. To pursue identification of a distinct marker, this study profiled the secretory proteome in 16 PDAC, 2 carcinoma in situ (CIS) and 7 benign patients using label-free mass spectrometry coupled to 1D-SDS-PAGE and Strong Cation-Exchange Chromatography (SCX). A total of 431 proteins were detected of which 56 were found to be significantly elevated in PDAC. Included in this differential set were Parkinson disease autosomal recessive, early onset 7 (PARK 7) and Alpha Synuclein (aSyn), both of which are known to be pathognomonic to Parkinson's disease as well as metabolic enzymes like Purine Nucleoside Phosphorylase (NP) which has been exploited as therapeutic target in cancers. Tissue Microarray analysis confirmed higher expression of aSyn and NP in ductal epithelia of pancreatic tumors compared to benign ducts. Furthermore, extent of both aSyn and NP staining positively correlated with tumor stage and perineural invasion while their intensity of staining correlated with the existence of metastatic lesions in the PDAC tissues. From the biomarker perspective, NP protein levels were higher in PDAC sera and furthermore serum levels of its downstream metabolites guanosine and adenosine were able to distinguish PDAC from benign in an unsupervised hierarchical classification model. Overall, this study for the first time describes elevated levels of aSyn in PDAC as well as highlights the potential of evaluating NP protein expression and levels of its downstream metabolites to develop a multiplex panel for non-invasive detection of PDAC.

Incidences of esophageal cancer and obesity are both rising in the United States. The aim of this study was to determine the influence of elevated body mass index on outcomes after esophagectomy for cancer.Overall and disease-free survivals in obese (BMI ≥ 30), overweight (BMI 25-29), and normal-weight (BMI 20-24) patients undergoing esophagectomy constituted the study end points. Survivals were calculated by the Kaplan-Meier method, and differences were analyzed by log rank method.The study included 166 obese, 176 overweight, and 148 normal-weight patients. These three groups were similar in terms of demographics and comorbidities, with the exception of younger age (62.5 vs. 66.2 vs. 65.3 years, P = 0.002), and higher incidence of diabetes (23.5 vs. 11.4 vs. 10.1%, P = 0.001) and hiatal hernia (28.3 vs. 14.8 vs. 20.3%, P = 0.01) in obese patients. Rates of adenocarcinoma histology were higher in obese patients (90.8 vs. 90.9 vs. 82.5%, P = 0.03). Despite similar preoperative stage, obese patients were less likely to receive neoadjuvant treatment (47.6 vs. 54.5 vs. 66.2%, P = 0.004). Response to neoadjuvant treatment, type of surgery performed, extent of lymphadenectomy, rate of R0 resections, perioperative complications, and administration of adjuvant chemotherapy were not influenced by BMI. At a median follow-up of 25 months, 5-year overall and disease-free survivals were longer in obese patients (respectively, 48, 41, 34%, P = 0.01 and 48, 44, 34%, P = 0.01).In our experience, an elevated BMI did not reduce overall and disease-free survivals after esophagectomy for cancer.

Esophageal cancer remains a malignancy with high morbidity and mortality despite improvements to diagnosis, staging, chemotherapy, radiation, and surgery. Neoadjuvant therapy (NT) may improve oncologic outcome in many patients, however the degree to which patients benefit remains unclear. We examined the relationship between pathologic response to NT and magnitude of benefit in patients with esophageal cancer.Using a comprehensive esophageal cancer database, we identified patients who underwent esophagectomy between 1994 and 2008. Pathologic response was denoted as complete (pCR), partial (pPR), and nonresponse (NR). Clinical and pathologic data were compared using Fisher's exact and chi-square when appropriate, while Kaplan-Meier estimates were used for survival analysis.We identified 347 patients who underwent esophagectomy, and 262 (75.5%) were treated with NT. The median age was 66 years (28-86 years) with median follow-up of 20 months (1-177 months). There were 106 (40.5%) patients exhibiting pCR, 95 (36.3%) with pPR, and 61 (23.3%) with NR. The rate of R0 resections was higher amongst pCR (100%) compared with 94.7% in pPR (P = 0.02) and 87.5% in NR (P = 0.0007). There were 15 (14.2%) recurrences in pCR, 22 (23.7%) in pPR, and 17 (28.8%) in NR (P = 0.04). Patients achieving pCR had 5-year disease-free survival (DFS) and overall survival (OS) of 52% and 52%, respectively, compared with 36% and 38% in pPR and 22% and 19% in NR (P0.0001, P0.0001).Esophageal cancer patients frequently succumb to their disease. However, patients treated with neoadjuvant therapy who achieve pCR have a higher rate of R0 resections, fewer recurrences, and improved 5-year OS and DFS.

With the completion of the human genome project, a multitude of techniques have been invented to evaluate large portions of the human genome simultaneously. Investigations are typically focused on the genome, transcriptome or proteome to identify unique characteristics that may explain the origin of human disease and potentially predict future outcomes. The goal of these investigative pursuits is to eventually individualize treatment for each patient based on their unique gene expression patterns.

Background Patients who develop metastatic melanoma often have limited effective treatment options. However, a select group of patients will benefit from aggressive surgery or a multidisciplinary approach, depending on the site of metastasis. Methods The current literature was reviewed and summarized regarding the collective recommendations for staging and treating patients with metastatic melanoma. Results A thorough preoperative staging includes positron-emission tomography, MRI of the brain, and CT of the chest, abdomen, and pelvis. Tumor biology ultimately determines the success of intervention. A long disease-free interval is a good indicator of potential benefit from resection of metastatic disease. If surgery is performed, no less than a complete resection will affect the overall survival of the patient. Surgery and other multimodality treatment options can be used for symptomatic palliation but will not affect survival. Chemotherapy and radiation are often used to control the symptoms of brain and bony metastases but have limited if any impact on survival. Conclusions A select group of patients with metastatic melanoma will benefit from aggressive surgery. Identifying which patients will benefit from treatment requires good clinical judgment and a thorough radiologic evaluation to identify the true extent of disease.

Cytoreductive surgery represents a therapeutic attempt to improve patient outcomes by reducing overall tumor burden to render postsurgical therapy effective or at least increase its effectiveness. The intent of cytoreduction differs from palliative or curative-intent surgery for oligometastatic melanoma. Both palliative surgery and attempted curative resection have important roles to play in the management of patients with melanoma that has spread beyond the regional nodes or recurred "in transit" between the primary and the regional nodal basin. To date, however, no evidence shows that cytoreductive surgery offers any meaningful benefit to patients with metastatic melanoma, and, outside of a clinical trial, there is no role for cytoreductive surgery in melanoma. To date, adjuvant vaccine therapy after complete resection of metastatic melanoma has not proved to be efficacious in clinical trials, so there is little reason to believe that the use of currently available immunotherapy strategies will be enhanced after incomplete tumor resections.

CONTEXT Patients with peritoneal carcinomatosis have a dismal prognosis despite systemic chemotherapy or palliative surgery. A novel strategy of complete tumor debulking with intraoperative hyperthermia with chemotherapy has been proposed to provide prolonged survival. OBJECTIVE To retrospectively analyze the preliminary experience with this technique at Baylor University Medical Center. METHODS All patients underwent attempted tumor debulking followed by intraperitoneal hyperthermia with 40 mg mitomycin-C over 2 hours. RESULTS Patient diagnoses included nonmucinous colorectal carcinomatosis (n = 9), diffuse peritoneal adenomucinosis (n = 1), peritoneal mucinous carcinomatosis (n = 2), and gastric carcinomatosis (n = 3). Tumors in most patients (13/15) were resected to < or = 5 mm, and those in 10 of 15 were resected to no gross disease. Complications included ileus (n = 9), bowel leak (n = 2), infection (n = 1), and fistula (n = 1). One patient died of progressive gastric cancer at 1 month. Within a median follow-up of 4 months, 8 patients had no tumor by radiologic or tumor marker analysis. CONCLUSION Intraoperative hyperthermia with chemotherapy is a viable treatment for patients with isolated peritoneal carcinomatosis from colorectal or gastric origin.

On January 29, 1881, in Vienna, Austria, Dr. Theodor Billroth performed the first successful operation for gastric cancer. Two previous attempts by other surgeons had resulted in early postoperative deaths; Dr. Billroth's patient survived the surgery but died a few months later from metastatic disease (1). Today surgeons are still challenged by similar obstacles in gastric cancer, notably the dismal result of incomplete resection.

Neuroendocrine tumors (NETs) are rare tumors of the endocrine pancreas that require a high degree of suspicion for timely diagnosis. Diagnosis is often delayed due to the nonspecific and intermittent presentation of symptoms. As many as 45% to 55% of tumors are nonfunctional and are typically diagnosed secondary to mass effect related symptoms or found incidentally. Functional tumors often are symptom specific and are diagnosed at an earlier stage than nonfunctional tumors. The challenging aspects of treating NETs are localizing the tumors, treating extensive or metastatic disease, and palliating symptoms. Most NETs have an indolent course, and aggressive multimodality treatment is often indicated and encouraged.

130 Background: Esophageal cancer often presents as locally advanced disease with 15% of patients having T4 tumors upon diagnosis. Esophagectomy was often reserved for palliation given the dismal survival rates and high rates of R1/R2 resections. However, neoadjuvant therapy (NT) has the potential to significantly downstage esophageal cancers and thus increase complete resection rates. We report our experience with surgically resected T4 cancers of the esophagus. Methods: Using a comprehensive esophageal cancer database, we identified patients who underwent an esophagectomy for T4 tumors between 1994 and 2008. Neoadjuvant therapy and pathologic response were recorded and denoted as complete (pCR), partial (pPR), and non-response (NR). Clinical and pathologic data were compared using Fisher's exact and chi-square when appropriate while Kaplan Meier estimates were used for survival analysis. Results: We identified 39 patients with T4 tumors who underwent esophagectomy of which 38 (97%) underwent NT. The median age was 61 (31-79) years with a median follow-up of 32 (5-97) months. There were 3 (7.9%) pCR, 17 (44.7%) pPR, and 18 (47.4%) NR. R0 resections were accomplished in 37 (94.9%). Two patients had incomplete resections. One patient had a R2 resection after NT and was deemed as NR. An additional patient had a R1 resection after NT and was a pPR with a residual 0.2 cm tumor on permanent pathology. There were 14 (35.9%) recurrences with a median time to recurrence of 19.5 (4-71) months. Complete pathologic response represented 1 (7.1%), whereas pPR and NR represented 6 (42.9%), and 7 (50%) respectively of all recurrences. The overall and disease free survival for all patients with T4 tumors was 28% and 34% respectively. Patients achieving a pCR had a 5-year overall and disease free survival of (43% and 47%), compared to pPR (30% and 21%) while there were no 5-year survivors in the NR cohort. Conclusions: T4 esophageal cancer often portends a dismal prognosis even after surgical resection. Historical incomplete resections and dismal survival rates often make surgery palliative rather then curative. However, we have demonstrated that neoadjuvant therapy and down staging of T4 tumors leads to increased R0 resections and improvements in overall and disease free survival. No significant financial relationships to disclose.