Leveraging real-world data to predict cancer cachexia stage, quality of life, and survival in a racially and ethnically diverse multi-institutional cohort of treatment-naïve patients with pancreatic ductal adenocarcinoma.

Introduction: Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management. Objectives: The main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS). Materials and methods: A population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations. Results: CC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS. Conclusions: Using clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey.

Esophageal cancer in Hispanics: a demographic analysis of the National Cancer Database.

BACKGROUND: Hispanics are the fastest-growing minority and the second largest ethnic group in the United States, accounting for 18% of the national population. The American Cancer Society estimated 18,440 new cases of esophageal cancer (EC) in the United States in 2020. Hispanics are reported to be at high risk of EC. We sought to interrogate the demographic patterns of EC in Hispanics. Secondary objective was to examine evidence of socioeconomic disparities and differential therapy. METHODS: We identified Hispanic vs non-Hispanic patients with EC in the National Cancer Database between 2005 and 2015. Groups were statistically equated through propensity score-matched analysis. RESULTS: A total of 3205 Hispanics (3.8%) were identified among 85,004 patients with EC. We identified significant disparities between Hispanic and non-Hispanic groups. Disparities among Hispanics included higher prevalence of squamous EC, higher likelihood of stage IV cancer diagnosis, younger age, uninsured status, and income< $38,000. Hispanics were less likely to have surgical intervention or any type of treatment when compared to non-Hispanics. Multivariate analysis showed that age, ethnicity, treatment, histology, grade, stage, and Charlson-Deyo scores were independent predictors of survival. Treated Hispanics survived longer than non-Hispanics. CONCLUSION: Despite the lower prevalence of EC, there is a disproportionately higher prevalence of metastatic and untreated cases among Hispanics. This disparity may be explained by Hispanics' limited access to medical care, exacerbated by their socioeconomic and insurance status. Further study is warranted to examine these health disparities among Hispanics.

Timing After Neoadjuvant Therapy Predicts Mortality in Patients Undergoing Esophagectomy: a Propensity Score-Matched Analysis.

BACKGROUND: Currently most surgeons allow 6-12 weeks after neoadjuvant therapy prior to recommending esophagectomy. Given that complete pathologic response correlates to improved survival, some have advocated a longer interval should be entertained to increase the pathologic response. The impact of an expanded neoadjuvant therapy-surgery timing is not currently well understood. METHODS: Utilizing the National Cancer Database, we identified patients with esophageal cancer who underwent neoadjuvant therapy followed by esophagectomy. Patients were divided into 3-time intervals: < 6 weeks, 6-12 weeks, and > 3 months. RESULTS: We identified 9256 patients who received neoadjuvant therapy followed by esophagectomy. There were 7858 (84.9%) males and 1398 (15.1%) females with a median age of 62. The median lymph nodes harvested decreased as timing increased (p < 0.001) and mean lymph nodes positive decreased as timing increased, p = 0.01. The complete response rate also increased as timing increased, p < 0.001. However, this improvement in pathologic complete response did not translate into an increase in median survival. Ninety-day mortality increased as the timing from neoadjuvant therapy increased: 6.4%, 7.9%, and 10.2%, respectively, p = 0.002. CONCLUSION: Our data demonstrates that patients who have a prolonged neoadjuvant therapy- esophagectomy interval will have a substantial increase in 90-day mortality. While there was an increase in pathologic complete response rates, this did not translate into an improvement in survival. The current recommendations of a neoadjuvant therapy-surgery timing of 6-12 weeks should remain.

The use of indocyanine green (ICYG) angiography intraoperatively to evaluate gastric conduit perfusion during esophagectomy: does it impact surgical decision-making?

BACKGROUND: Ischemia is known to be a major contributor for anastomotic leaks and indocyanine green (ICYG) fluorescence angiography has been utilized to assess perfusion. Experienced esophageal surgeons have clinically assessed the gastric conduit with acceptable outcomes for years. We sought to examine the impact of ICYG in a surgeon's decision-making during esophagectomy. METHODS: We queried a prospectively maintained database to identify patients who underwent robotic esophagectomy. Time to initial perfusion, time to maximum perfusion, and residual ischemia were measured and used as a guide to resection of residual stomach. During esophagectomy the surgeon identified the anticipated line of ischemic demarcation (LOD) prior to ICYG injection. The distance between the surgeon's LOD and ICYG LOD was measured. RESULTS: We identified 312 patients who underwent robotic esophagectomy, 251 without ICYG and 61 with ICGY. There were no differences in age, sex, race, body mass index, histology, stage, or neoadjuvant therapy use between groups. The incidence of anastomotic leak did not differ between groups (non-ICYG, 5.2% vs. ICYG, 6.6%), p = 0.67. The initial perfusion time was ≥ 10 s and max perfusion was > 25 s in all the patients in the ICYG that developed anastomotic leaks. All patients were noted to have at least 1 cm of residual gastric ischemia. Fifteen patients underwent independent surgeon evaluation of the ischemic LOD prior to ICYG. Differential distances were noted in 12 (80%) patients with a mean distance between surgical line of demarcation and ICYG LOD of 0.77 cm. CONCLUSION: While the implementation of ICYG during esophagectomy demonstrates no significant improvements in anastomotic leak rates compared to historical controls, surgeon's decision-making is impacted in 80% of cases resulting in additional resection of the gastric conduit. Elevated times to initial perfusion and maximum perfusion were associated with increased gastric ischemia and anastomotic leaks.

The effects of the tumor suppressor gene PTEN on the proliferation and apoptosis of breast cancer cells via AKT phosphorylation.

Background: The proliferation and apoptosis of cancer cells play important roles in breast carcinomas. However, to date, there have been few reports on the correlation between the expression of PTEN and AKT phosphorylation in breast cancer. This present study investigated the effects of the phosphatase and tensin homology deleted from chromosome 10 (PTEN) gene on the proliferation and apoptosis of breast cancer cells through protein kinase B (AKT) phosphorylation. Methods: Human breast cancer MDA-MB-231 cells were transfected with the pcDNA3.0 control vector or the pcDNA3.0-PTEN vector for 48 hours. The Cell Counting Kit 8 (CCK-8) was used to detect cell survival rates, double staining was performed to detect apoptosis, and Western blot (WB) analysis was conducted to detect protein expression. The effects of PTEN expression on the cell cycle and apoptosis of human breast cancer cell line MDA-MB-231, and on the levels of phosphorylated AKT protein were further analyzed. Moreover, the relationship between the PTEN gene and clinical features were also analyzed. Results: The cell survival rate of cells transfected with pcDNA3.0-PTEN was significantly lower than that of cells transfected with the control pcDNA3.0 vector (55.65%±12.18% vs. 97.32%±12.45%, P=0.004). Compared with the pcDNA3.0 group, the apoptosis rate of the pcDNA3.0-PTEN group was significantly increased (20.65±2.18 vs. 2.32±0.45, P=0.001). The expression of PTEN protein in pcDNA3.0-PTEN group was higher than that in the pcDNA3.0 group, and the expression of the AKT and mTOR proteins was significantly lower than that in pcDNA3.0 group (P<0.05). The expression of PTEN in the lymph node metastasis positive group was significantly higher than that in the lymph node metastasis negative group (P<0.05). The expression of the AKT protein in breast cancer was higher than that in normal breast tissue, and the difference was statistically significant (P<0.01). Conclusions: Overexpression of the PTEN gene can promote AKT phosphorylation, increase the apoptotic index of breast cancer cells, and reduce the proliferative activity of breast cancer cells. This provided a new direction for the next treatment of breast cancer, but further clinical research is needed.

Comparative outcomes of laparoscopic and robotic approaches to gastrectomy: a National Cancer Database study.

BACKGROUND: Gastric cancer is associated with significant mortality worldwide. Radical gastrectomy with lymphadenectomy is considered the only curative option. Traditionally, these operations are associated with significant morbidity. Laparoscopic gastrectomy (LG) and more recently robotic gastrectomy (RG) techniques have been developed to potentially decrease the perioperative morbidity. We sought to compare oncologic outcomes with laparoscopic and robotic techniques for gastrectomy. METHODS: Utilizing the National Cancer Database we identified patients who underwent gastrectomy for adenocarcinoma. Patients were stratified by open, robotic or laparoscopic surgical technique. Open gastrectomy patients were excluded. RESULTS: We identified 1,301 patients who underwent RG and 4,892 LG with median ages of 65 (20-90) and 66 (18-90) respectively, p = 0.02. The mean number of positive lymph nodes were higher in the LG 2.2 ± 4.4 vs RG 1.9 ± 3.8, p = 0.01. The R0 resections were higher in the RG at 94.5% vs 91.9% in LG, p = 0.001. Conversions to open were 7.1% in the RG and 16% in the LG group, p < 0.001. The median length of hospitalization was 8 (6-11) in both groups. There was no difference in the 30-day readmission (p = 0.65), 30-day mortality (p = 0.85) and 90-day mortality (p = 0.34) between groups. The median and overall 5-year survival was 71.3 mo and 56% in the RG and 66.1 mo and 52% in the LG, p = 0.03. Multivariate analysis revealed that age, Charlson-Deyo comorbidity scores, location of gastric cancer, histology grade, pathologic T-stage, pathologic N-stage, surgical margins, and facility volume were all predictors of survival. CONCLUSIONS: Robotic and laparoscopic techniques are both acceptable approaches to gastrectomy. However, conversions to open are higher and R0 resections rates are lower in the laparoscopic group. Additionally, a survival benefit is demonstrated in those undergoing robotic gastrectomy.

Outcomes of adjuvant radiation therapy after chemotherapy in resected extrahepatic cholangiocarcinoma: A National Cancer Database analysis.

BACKGROUND: Adjuvant capecitabine is considered a standard of care for resected cholangiocarcinoma per the BILCAP trial. The role of adjuvant radiation therapy in that trial was not addressed. This study was designed to examine the outcomes of adjuvant radiation in patients who received chemotherapy for resected cholangiocarcinoma. METHODS: Using the National Cancer Database, the authors identified high-risk patients with resected extrahepatic cholangiocarcinoma with either positive nodes (N+) or margins (R1) who received adjuvant chemotherapy between 2006 and 2014. Overall survival (OS) was determined with the Kaplan-Meier method. Propensity score matching (PSM) and multivariate analysis (MVA) were performed to identify prognostic factors for survival. RESULTS: The authors identified 1478 patients after PSM who were included in the analysis. There was no difference in OS between patients receiving single-agent chemotherapy and patients receiving multiagent chemotherapy (p = .69). There was a significant OS benefit associated with radiation therapy. The median OS and the 5-year OS rate for radiated patients versus nonradiated patients were 34 months and 33% versus 27 months and 24% (p < .001) for the whole group, 30 months and 29% versus 24 months and 19% (p = .007) for the N+ subgroup, and 25 months and 23% versus 20 months and 12% (p = .03) for the R1 subgroup. MVA demonstrated that age, N stage, T stage, R1, and grade were associated with increased mortality, whereas adjuvant radiation was associated with decreased mortality (p < .001). CONCLUSIONS: This is the first study showing that adjuvant radiation therapy after chemotherapy resulted in a significant OS benefit for patients with resected high-risk extrahepatic cholangiocarcinoma. Trials are needed to address the role of radiation therapy in this population.

Efficacy and safety of esophagectomy via left thoracic approach versus via right thoracic approach for middle and lower thoracic esophageal cancer: a multicenter randomized clinical trial (NST1501).

Background: Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC). Methods: Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test. Results: A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92 vs. 205.34±51.47 min, P<0.001); had more complications (33.8% vs. 26.3% P=0.016); harvested more lymph nodes (LNs) (23.61±10.09 vs. 21.92±10.26, P=0.015); achieved a significantly improved OS in stage IIIa patients (67.8% vs. 51.8%, P=0.022). The 3-year OS and DFS were 68.7% and 64.3% in LTA arm versus 71.3% and 63.7% in RTA arm (P=0.20; P=0.96). Conclusions: Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy. Trial Registration: ClinicalTrials.gov NCT02448979.

Adjuvant therapy for margin positive pancreatic cancer: A propensity score matched analysis.

BACKGROUND: Adjuvant chemotherapy or chemoradiation is often recommended for resected pancreatic adenocarcinoma. We sought to examine the impact of these therapies on R1 resected pancreatic cancer. METHODS: Utilizing the National Cancer Database we identified patients who underwent pancreatic resection for adenocarcinoma. Patients were stratified by resection status and adjuvant therapy. RESULTS: We identified 28,440 patients who underwent pancreatic resection. Patients with tumor size >2 cm were more likely to undergo R1 resections, p < 0.001. Adjuvant therapy improved survival in all patients with median and 5-year survival: adjuvant chemotherapy (21.7 months, 17.45%), chemoradiation (23.3 months, 20.9%) vs no adjuvant therapy (19.5 months, 19.1%), p < 0.001. In the R1 resection cohort survival was also improved with adjuvant therapy with chemoradiation demonstrating the most significant improvement: adjuvant chemotherapy (15.9 months, 6.5%), chemoradiation (18.7 months, 11.2%) vs no adjuvant therapy (12.5 months, 8.7%), p < 0.001. Chemoradiation but not adjuvant chemotherapy improved survival in the R1 node negative, p < 0.004, and node positive, p < 0.001. Adjuvant chemotherapy benefited survival in R1 node positive patients, p < 0.001. CONCLUSIONS: Patients with pancreatic cancer who undergo R1 resection have significant improvement in survival when treated with adjuvant chemoradiation and adjuvant chemotherapy. However, benefits were greater in those receiving adjuvant chemoradiation.

Comparative outcomes of transthoracic versus transhiatal esophagectomy.

BACKGROUND: Surgical resection has become a mainstay of therapy for locally advanced esophageal cancer and can increase survival significantly. With the advancement of minimally invasive surgery, there is still debate on the best approach for esophagectomy. We report a modern analysis of outcomes with transthoracic versus transhiatal esophagectomy. METHODS: A prospectively managed esophagectomy database was queried for patients undergoing transthoracic or transhiatal esophagectomy between 1996 and 2016. Continuous variables were compared using the Kruskal-Wallis or the analysis of variance tests as appropriate. Pearson χ2 test was used to compare categorical variables. All statistical tests were 2-sided and an α (type I) error < .05 was considered statistically significant. RESULTS: A total of 846 patients underwent esophagectomy with a median age of 66 (28-86) years. There was no difference in estimated blood loss for transthoracic and transhiatal, but mean operating room times were longer for transthoracic versus transhiatal (P < .001), and the number of retrieved lymph nodes was higher for transthoracic versus transhiatal (P < .002). Postoperative complications occurred in 207 (29%) transthoracic patients vs 59 (44.7%) transhiatal patients, (P < .001). The most common complications in transthoracic versus transhiatal techniques, respectively, were anastomotic leaks: 4.3% vs 9.8%; (P = .01), anastomotic stricture 7% vs 26.5%; (P < .001), and pneumonia 12.6% vs 22.7%; (P < .002). Median survival significantly improved in patients undergoing transthoracic (62 months) vs transhiatal (39 months) P = .03. CONCLUSION: We found that a transthoracic approach was associated with lower pneumonias, anastomotic leaks, wound infections, and strictures, with an improvement in nodal harvest. Survival was also significantly improved in patients who underwent transthoracic esophagectomy.

The Florida Pancreas Collaborative Next-Generation Biobank: Infrastructure to Reduce Disparities and Improve Survival for a Diverse Cohort of Patients with Pancreatic Cancer.

Background: Well-annotated, high-quality biorepositories provide a valuable platform to support translational research. However, most biorepositories have poor representation of minority groups, limiting the ability to address health disparities. Methods: We describe the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective cohort study and biorepository designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L). We provide an overview of stakeholders; study eligibility and design; recruitment strategies; standard operating procedures to collect, process, store, and transfer biospecimens, medical images, and data; our cloud-based data management platform; and progress regarding recruitment and biobanking. Results: The FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and questionnaires (62%). Conclusions: This biorepository addresses a critical gap in PaCa research and has potential to advance translational studies intended to minimize disparities and reduce PaCa-related morbidity and mortality.

Multi-agent neoadjuvant chemotherapy improves response and survival in patients with resectable pancreatic cancer.

BACKGROUND: We sought to examine the impact of neoadjuvant chemotherapy (NCT), single agent (SA) or multi-agent (MA) chemotherapy, and chemoradiation (NCRT) on response and survival in pancreatic cancer. METHODS: Utilizing the National Cancer Database, we identified patients who underwent resection of the pancreatic head for adenocarcinoma [2006-2013]. Overall survival (OS) analysis was performed using the Kaplan-Meier method. Multivariable cox proportional hazard models (MVA) and propensity score matching (PSM) were developed to identify predictors of survival. For upfront surgery (UFS), OS was limited to receipt of adjuvant treatment. RESULTS: We identified 26,563 patients who underwent pancreatic head resection: UFS =23,877, NCRT =1,482, and NCT =1,204. MA-NCT was utilized in 77% and after PSM, 52%. There was improved R0 resections and 30-day mortality associated with neoadjuvant therapy compared to UFS. Overall response rate to neoadjuvant therapy was 24%. The highest response rate seen with MA-NCRT. Response rates for SA-NCT, MA-NCT, SA-NCRT, and MA-NCRT were 11.5%, 18.1%, 27.5%, and 33.1% (P=0.01). However, OS was improved with neoadjuvant therapy regardless of response compared to UFS (P=0.03). After PSM, the median OS for UFS, SA-NCT, MA-NCT, SA-NCRT, and MA-NCRT was 21.9, 21.5, 29.8, 25.3, and 25.8 months in all patients (P=0.001). MVA after PSM demonstrated that only MA-NCT was associated with decreased mortality while increasing age, higher Charlson-Deyo index, N1, higher grade, tumor size, and positive margins were associated with higher mortality. CONCLUSIONS: There was improved OS associated with MA-NCT in pancreatic cancer patients compared to UFS with adjuvant therapy. OS was improved regardless of response to therapy.

Comparative outcomes of minimally invasive and robotic-assisted esophagectomy.

OBJECTIVE: Minimally invasive esophagectomy (MIE) has demonstrated superior outcomes compared to open approaches. The myriad of techniques has precluded the recommendation of a standard approach. The addition of robotics to esophageal resection has potential benefits. We sought to examine the outcomes with MIE to include robotics. METHODS: Utilizing a prospective esophagectomy database, we identified patients who underwent (MIE) Ivor Lewis via thoracoscopic/laparoscopic (TL), transhiatal (TH), or robotic-assisted Ivor Lewis (RAIL). Patient demographics, tumor characteristics, and complications were analyzed via ANOVA, χ2, and Fisher exact where appropriate. RESULTS: We identified 302 patients who underwent MIE: TL 95 (31.5%), TH 63 (20.8%), and RAIL 144 (47.7%) with a mean age of 65 ± 9.6. The length of operation was longer in the RAIL: TL (299 ± 87), TH (231 ± 65), RAIL (409 ± 104 min), p < 0.001. However, the EBL was lower in the patients undergoing transthoracic approaches (RAIL + TL): TL (189 ± 188 ml), TH (242 ± 380 ml), RAIL (155 ± 107 ml), p = 0.03. Conversion to open was also lower in these patients: TL 7 (7.4%), TH 8 (12.7%), RAIL 0, p < 0.001. The R0 resection rate and lymph node (LN) harvest also favored the RAIL cohort: TL 86 (93.5%), TH 60 (96.8%), and RAIL 144 (100%), p = 0.01; LN: TL 14 ± 7, TH 9 ± 6, and RAIL 20 ± 9, p < 0.001. The overall morbidity was lower in MIE patients that underwent a transthoracic approach vs. transhiatal: TL 29 (30.5%), TH 39 (61.9%), RAIL 34 (23.6%), p < 0.001. CONCLUSIONS: Patients undergoing MIE via thoracoscopic/laparoscopic and robotic transthoracic approaches demonstrated lower EBL, morbidity, and conversion to open compared to the transhiatal approach. Additionally the oncologic outcomes measured by R0 resections and LN harvest also favored the patients who underwent a transthoracic approach.

Comparative Perioperative Outcomes by Esophagectomy Surgical Technique.

INTRODUCTION: Surgical resection is vital in the curative management of patients with esophageal cancer. However, a myriad of surgical procedures exists based on surgeon preference and training. We report on the perioperative outcomes based on esophagectomy surgical technique. METHODS: A prospectively managed esophagectomy database was queried for patients undergoing esophagectomy from 1996 and 2016. Basic demographics, tumor characteristics, operative details, and post-operative outcomes were recorded and analyzed by comparison of transhiatal vs Ivor-lewis and minimally invasive (MIE) vs open procedures. RESULTS: We identified 856 patients who underwent esophagectomy. Neoadjuvant therapy was administered in 543 patients (63.4%). There were 504 (58.8%) open esophagectomies and 302 (35.2%) MIE. There were 13 (1.5%) mortalities and this did not differ among techniques (p = 0.6). While there was no difference in overall complications between MIE and open, complications occurred less frequently in patients undergoing RAIL and MIE IVL compared to other techniques (p = 0.003). Pulmonary complications also occurred less frequently in RAIL and MIE IVL (p < 0.001). Anastomotic leaks were less common in patients who underwent IVL compared to trans-hiatal approaches (p = 0.03). MIE patients were more likely to receive neoadjuvant therapy (p = 0.001), have lower blood loss (p < 0.001), have longer operations (p < 0.001), and higher lymph node harvests (p < 0.001) compared to open patients. CONCLUSION: Minimally invasive and robotic Ivor Lewis techniques demonstrated substantial benefits in post-operative complications. Oncologic outcomes similarly favor MIE IVL and RAIL.

Neoadjuvant therapy and pancreatic cancer: a national cancer database analysis.

BACKGROUND: We sought to examine the impact of neoadjuvant chemotherapy (NCT), single agent or multiagent chemotherapy, and neoadjuvant chemoradiation (NCRT) on survival in pancreatic cancer. METHODS: Utilizing the National Cancer Database, we identified patients who underwent pancreatic resection for adenocarcinoma (2006 to 2013). Overall survival (OS) analysis was performed using the Kaplan-Meier method. Multivariable cox proportional hazard models (MVA) and propensity score matching (PSM) were developed to identify predictors of survival. For upfront surgery (UFS), OS was limited to receipt of adjuvant treatment. RESULTS: We identified 26,563 patients who underwent pancreatic resection: UFS =23,877, NCRT =1,482, and NCT =1,204. Multiagent chemotherapy was utilized in 77% of NCT and 42% of NCRT. There was improved R0 resections associated with neoadjuvant therapy compared to UFS, however, there was no difference between NCT and NCRT. In addition, the was improved R0 with MA-NCT (P<0.001) but not for single agent NCT (P=0.26). After PSM, the median OS for UFS, SA-NCT, MA-NCT, SA-NCRT, and MA-NCRT was 21.9, 21.5, 29.8, 25.3, and 25.8 months in all patients (P=0.001), and 23.6, 23.9, 31.6, 25.9, and 26.6 months in R0 patients (P=0.03), respectively. There was no difference in OS in patients with R1/2 resection. MVA after PSM demonstrated that only MA-NCT was associated with decreased mortality while increasing age, higher Charlson-Deyo index, N1, higher grade, tumor size, and positive margins were associated with higher mortality. CONCLUSIONS: There was improved OS associated with MA-NCT in pancreatic cancer patients compared to UFS with adjuvant therapy.

Clinical fate of T0N1 esophageal cancer: results from the National Cancer Database.

The long-term survival for patients with locally advanced esophageal cancer (EC) remains poor despite improvements in multi-modality care. Neoadjuvant chemoradiation (NCR) followed by surgical resection remains pivotal in the management of patients with EC. However, the outcome of patients whose primary tumor exhibits a complete response with residual regional nodal disease (T0N1) remains unclear as well as the role for adjuvant therapy.Utilizing the National Cancer Database we identified patients with EC who underwent NCR followed by esophagectomy who had subsequent pathology of T0N1. Baseline univariate comparisons of patient characteristics were made for continuous variables using both the Mann-Whitney U and Kruskal Wallis tests as appropriate. Pearson's Chi-square test was used to compare categorical variables. Unadjusted survival analyses were performed using the Kaplan-Meier method comparing survival curves with the log-rank test. All statistical tests were two-sided and α (type I) error <0.05 was considered statistically significant.We identified 7,116 patients diagnosed with EC; 6,235 (87.6%) adenocarcinoma (AC), 881 (12.4%) squamous cell carcinoma (SCC) with a median age of 62 [21-88] years. There were 6,031 (84.8%) males and 1,085 (15.2%) females. R0 resections were achieved in 6,668 (93.7%) patients and this correlated to improved median survival 39.5 (R0) and 20.1 (R1) months respectively, P<0.001. The median nodes harvested were 13 [0-83] with a mean positive LN's of 1.4±2.9. Pathologic complete response (pCR) was achieved in 1,334 (18.7%), partial response (pPR) 2,812 (39.5%) and non-response (pNR) 2,970 (41.7%). There were 230 (3.2%) patients deemed as pathologic T0N1. The median survival of patients with pCR was 61.7 months compared to 32.1 months in the T0N1 patients P<0.001. T0N1 patients did not demonstrate an improved survival over T1/2 patients who had a median survival of 30.5 months, P=0.79. However, T0N1 did reveal an improved survival over T3/4 patients who had a median survival of 24.6 months, P=0.02. Adjuvant chemotherapy in T0N1 did not provide a benefit in survival, median survival adjuvant versus no adjuvant 30.8 vs. 32.1 months respectively, P=0.08. Multivariate analysis in T0N1 patients demonstrated only number of LN's positive, and histology SCC vs. ACC as predictive of survival, HR, 1.22, 95% CI: 1.10-1.36, P<0.001; HR, 0.43, 95% CI: 0.24-0.75, P=0.003, respectively.Patients with EC who exhibit a pathologic T0N1 after NCR have oncologic fates similar to node positive patients. Patients with pCR of the primary tumor and regional lymph nodes continue to demonstrate significant survival benefits over all remaining pathologic cohorts.

Accuracy of endoscopic ultrasound staging for T2N0 esophageal cancer: a National Cancer Database analysis.

BACKGROUND: To determine accuracy of clinical staging of T2N0 esophageal cancer from the National Cancer Database (NCDB). METHODS: The NCDB was accessed to identify patients with T2N0M0 esophageal cancer (adenocarcinoma or squamous cell carcinoma) treated between 2004-2013 that underwent esophagectomy. Pathologic staging was compared to clinical stage. Univariate (UVA) and multivariate analysis (MVA) was performed to identify factors related to pathologic upstaging using Cox proportional hazard ratio. RESULTS: We identified 1,840 patients with T2N0 esophageal cancer who underwent esophagectomy as first line therapy. The median age was 67 years. The vast majority of patients were male and had distal adenocarcinomas. Clinical staging in was accurate pathologically in 30.7% of patients. While there was a trend for worse accuracy with increasing year of diagnosis, there rate of pT0-2N0 was stable. Tumor length >3 cm was significantly associated with tumor upstaging, while poor differentiation was significantly associated with nodal upstaging. UVA and MVA identified younger age, tumor length >3 cm, and poor differentiation were significantly associated with overall upstaging. Gender, tumor location, and tumor histology were not prognostic. CONCLUSIONS: Clinical staging for T2N0M0 esophageal cancer continues to remain highly inaccurate, however, rates of pT0-2N0 have steadily remained over 50%. Tumor length >3 cm and poor differentiation are strongly associated with pathologic upstaging.

Anastomotic leak and neoadjuvant chemoradiotherapy in esophageal cancer.

BACKGROUND: Anastomotic leaks (AL) cause significant morbidity after esophagectomy. Most patients receive neoadjuvant chemoradiation (NCR) prior to esophagectomy which has been associated with increase perioperative complications and mortality. We report on a comparison of AL rates in upfront surgical (UFS) and NCR patients. METHODS: An esophagectomy database was queried for UFS and NCR patients treated between 1996 and 2015. Predictors of AL rate were identified using univariate and multivariate (MVA) analysis and propensity score matching (PSM). RESULTS: We identified 820 patients (UFS, 288; NCR, 532). Overall AL rate was 5.4%. Decreased AL rate was observed in NCR patients on MVA (8.0% vs. 4.1%; P=0.02) but no difference was seen after PSM (7.7% vs. 4.2%; P=0.14). MVA of factors associated with decreased AL in UFS patients included distal esophageal tumors and body mass index (BMI) >25. Age, gender, year of surgery, histology, anastomotic location, and diabetes were not prognostic. Before PSM, MVA of NCR patients of factors associated with decreased AL revealed that only thoracic anastomosis was prognostic. However, this was not observed after PSM. MVA of factors associated with decreased AL in all patients revealed thoracic anastomosis, NCR, and BMI 25-30. After PSM, only distal esophageal tumors and thoracic anastomosis were prognostic for decreased AL. CONCLUSIONS: There is no difference in the AL rate between UFS and NCR patients. Decreased AL rate was observed in patients with distal esophageal tumors and thoracic anastomosis.

Esophagectomy from then to now.

We have come a long way from the onset of surgery for esophageal cancer. Surgical resection is pivotal for the long-term survival in patients with locally advanced esophageal cancer. Moreover, advancements in post-operative care and surgical techniques have contributed to reductions in morbidity. More recently minimally invasive esophagectomy has been increasingly used in patients undergoing esophageal cancer resection. Potential advantages of MIE include: the decreased pulmonary complications, lower post-operative wound infection, decreased post-operative pain, and decreased length of hospitalization. The application of robotics to esophageal surgery is becoming more widespread. Robotic esophageal surgery has potential advantages over the known limitations of laparoscopic and thoracoscopic approaches to esophagectomy while adhering to the benefits of the minimally invasive approach. This paper is a review of the evolution from open esophagectomy to the most recent robotic approach.