Neoadjuvant chemotherapy is associated with improved disease-free survival in pancreatic cancer patients undergoing pancreaticoduodenectomy with vascular resection.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (NAC) is becoming favored for all pancreatic adenocarcinoma (PDAC). Patients with seemingly resectable disease infrequently still display vascular involvement intraoperatively. Outcomes following NAC versus upfront surgery in patients undergoing pancreaticoduodenectomy (PD) with vascular resection are unknown. METHODS: We performed a retrospective cohort study of PDAC patients who underwent PD with vascular resection between January 1, 2013, to December 31, 2020, within a single academic center. Clinicopathologic characteristics and disease-free survival (DFS) were compared between NAC versus upfront surgery cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. RESULTS: Eighty-one patients who underwent PD with vascular resection for PDAC were included. Forty-six patients (56%) received NAC. The NAC cohort more often had pathologic N0 status (47.8% vs. 8.6%, p < 0.001), had decreased vascular invasion (11% vs. 40%, p = 0.002), and completed chemotherapy (80% vs. 40%, p < 0.01). The NAC cohort demonstrated improved DFS (40.5 vs. 14.3 months, p = 0.007). In multivariable analysis, NAC remained independently associated with increased DFS (HR = 0.48, p = 0.02). CONCLUSIONS: NAC was associated with improved clinicopathologic outcomes and DFS in PD with vascular resection. These findings demonstrate the advantage of NAC in PDAC patients undergoing PD with vascular resection.

Endoscopic therapies for patients with obesity: a systematic review and meta-analysis.

BACKGROUND: Obesity is a major threat to public health and traditional bariatric surgery continues to have low utilization. Endoscopic treatments for obesity have emerged that offer less risk, but questions remain regarding efficacy, durability, and safety. We compared the efficacy of endoscopic bariatric procedures as compared to other existing treatments. METHODS: A literature search of Embase, Cochrane Central, and Pubmed was conducted from January 1, 2014 to December 7, 2021, including endoscopic bariatric therapies that were FDA or CE approved at the time of search to non-endoscopic treatments. Thirty-seven studies involving 15,639 patients were included. Primary outcomes included % total body weight loss (%TBWL), % excess body weight loss (%EBWL), and adverse events. Secondary outcomes included quality of life data and differences in hemoglobin A1C levels. Strength of clinical trial and observational data were graded according to the Cochrane methods. RESULTS: Intragastric balloons achieved greater %TBWL with a range of 7.6-14.1% compared to 3.3-6.7% with lifestyle modification at 6 months, and 7.5-14.0% compared to 3.1-7.9%, respectively, at 12 months. When endoscopic sleeve gastroplasty (ESG) was compared to laparoscopic sleeve gastrectomy (LSG), ESG had less %TBWL at 4.7-14.4% compared to 18.8-26.5% after LSG at 6 months, and 4.5-18.6% as compared to 28.4-29.3%, respectively, at 12 months. For the AspireAssist, there was greater %TBWL with aspiration therapy compared to lifestyle modification at 12 months, 12.1-18.3% TBWL versus 3.5-5.9% TBWL, respectively. All endoscopic interventions had higher adverse events rates compared to lifestyle modification. CONCLUSION: This review is the first to evaluate various endoscopic bariatric therapies using only RCTs and observational studies for evaluation of weight loss compared with conservative management, lifestyle modification, and bariatric surgery. Endoscopic therapies result in greater weight loss compared to lifestyle modification, but not as much as bariatric surgery. Endoscopic therapies may be beneficial as an alternative to bariatric surgery.

Robotic versus open pancreaticoduodenectomy in elderly patients: a propensity score-matched analysis.

BACKGROUND: Pancreaticoduodenectomy (PD) is complex procedure with high morbidity in the elderly. This retrospective study aimed to compare post-operative outcomes in patients ≥75 years of age who underwent robot-assisted (RA)PD and open PD. METHODS: We analyzed 2502 patients ≥75 years of age who underwent PD from 2015 to 2018 in the National Surgical Quality Improvement Program (NSQIP) database. RAPD and open PD patients were propensity score matched 1:5 to assess the 30-day outcomes of interest: postoperative complications, length of stay, discharge destination, and readmissions. RESULTS: Of 725 matched patients, 110 underwent RAPD, 615 OPD, and 12 were converted to an open operation. Post-operative outcomes were largely similar between cohorts. RAPD was associated a shorter length of stay (median 8 days, interquartile range [IQR] 6 to 11) than OPD (median 8 days, IQR 7 to 13) (p = 0.003). However, RAPD was associated with more readmissions (28.1% vs. 17.7%; p = 0.02). CONCLUSIONS: RAPD in patients ≥75 years of age appears to be safe and has a similar complication profile to open PD. Randomized or well-designed prospective matched studies are needed to confirm these findings.

Disparities in Utilization and Outcomes of Minimally Invasive Techniques for Gastric Cancer Surgery in the United States.

BACKGROUND: This study investigated national implementation patterns and perioperative outcomes of minimally invasive gastrectomy (MIG) in gastric cancer surgery in the United States. METHODS: The National Inpatient Sample (NIS) was queried for patients who underwent elective gastrectomy for gastric cancer from 2008-2018. The MIG versus open gastrectomy approach was correlated with hospital factors, patient characteristics, and complications. RESULTS: There was more than a fivefold increase in MIG from 5.8% in 2008 to 32.9% in 2018 (nptrend < 0.001). Patients undergoing MIG had a lower Elixhauser Comorbidity Index (p = 0.001). On risk adjusted analysis, black patients (AOR = 0.77, p = 0.024) and patients with income below 25th percentile (AOR = 0.80, p = 0.018) were less likely to undergo MIG. When these analyses were limited to minimally invasive capable centers only, these differences were not observed. Hospitals in the upper tertile of gastrectomy case volume, Northeast, and urban teaching centers were more likely to perform MIG. Overall, MIG was associated with a 0.7-day decrease in length of stay, reduced risk adjusted mortality rates (AOR = 0.58, p = 0.05), and a $4,700 increase in total cost. CONCLUSIONS: In this national retrospective study, we observe socioeconomic differences in patients undergoing MIG, which is explained by hospital level factors in MIG utilization. We demonstrate that MIG is associated with a lower mortality compared with open gastrectomy. Establishing MIG as a safe approach to gastric cancers and understanding regional differences in implementation patterns can inform delivery of equitable high-quality health care.

Trends in Robot-Assisted Procedures for General Surgery in the Veterans Health Administration.

INTRODUCTION: Implementation of robot-assisted procedures is growing. Utilization within the country's largest healthcare network, the Veterans Health Administration, is unclear. METHODS: A retrospective cohort study using data from the Department of Veterans Affairs Corporate Data Warehouse from January 2015 through December 2019. Trends in robot utilization for cholecystectomy, ventral hernia repair, and inguinal hernia repair were characterized nationally and regionally by Veterans Integrated Services Network. Patients, who underwent laparoscopic repairs for these procedures and open hernia repairs, were included to determine proportion performed robotically. RESULTS: We identified 119,191 patients, of which 5689 (4.77%) received a robotic operation. The proportion of operations performed robotically increased from 1.49% to 10.55% (7.08-fold change; slope, 2.14% per year; 95% confidence interval [0.79%, 3.49%]). Ventral hernia repair had the largest growth in robotic procedures (1.51% to 13.94%; 9.23-fold change; slope, 2.86% per year; 95% confidence interval [1.04%, 4.68%]). Regions with the largest increase in robotic utilization were primarily along the Northeast, Midwest, and West Coast. CONCLUSIONS: Robot utilization in general surgery is increasing at different rates across the United States in the Veterans Health Administration. Future studies should investigate the regional disparities and drivers of this approach.

Robot-Assisted General Surgery Procedures at the Veterans Health Administration: A Comparison of Surgical Techniques.

INTRODUCTION: The use of the robot in general surgery has exploded in the last decade. The Veterans Health Administration presents a unique opportunity to study differences between surgical approaches due to the ability to control for health system and insurance variability. This study compares clinical outcomes between robot-assisted and laparoscopic or open techniques for three general surgery procedures. METHODS: A retrospective observational study using the Veterans Affair Surgical Quality Improvement Program database. Operative time, length of stay, and complications were compared for cholecystectomy (robot-assisted versus laparoscopic), ventral, and inguinal hernia repair (robot-assisted versus laparoscopic or open) from 2015 to 2019. RESULTS: More than 80,000 cases were analyzed (21,652 cholecystectomy, 9214 ventral hernia repairs, and 51,324 inguinal hernia repairs). Median operative time was longer for all robot-assisted approaches as compared to laparoscopic or open techniques with the largest difference seen between open and robot-assisted primary ventral hernia repair (unadjusted difference of 93 min, P < 0.001). Median length of stay was between 1 and 4 d and significantly for robot-assisted ventral hernia repairs (versus open, P < 0.01; versus lap for recurrent hernia, P < 0.05). Specific postoperative outcomes of interest were overall low with few differences between techniques. CONCLUSIONS: While the robotic platform was associated with longer operative time, these findings must be interpreted in the context of a learning curve and indications for use (i.e., use of the robot for technically challenging cases). Our findings suggest that at the Veterans Health Administration, the robot is as safe a platform for common general surgery procedures as traditional approaches. Future studies should focus on patient-centered outcomes including pain and cosmesis.

Oncologic Outcomes After Robotic Pancreatic Resections Are Not Inferior to Open Surgery.

OBJECTIVE: Compare oncologic outcomes after open and robotic pancreatic resections for pancreatic adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: Receipt of adjuvant chemotherapy improves survival after resected PDAC. Complications after pancreatectomy have been shown to prohibit the administration of adjuvant chemotherapy and survival. We examined the effect of surgical approach on receipt of adjuvant chemotherapy, complications, and overall survival after pancreatectomy. METHODS: A single-institution retrospective review of all patients with PDAC who underwent robotic or open pancreatectomy from 2011 to 2016 with 24-month follow-up. RESULTS: Four hundred fifty-six patients underwent resection: 226 robotic and 230 open. No significant difference was identified in major complications or receipt of adjuvant chemotherapy between robotic and open pancreatectomy, nor was approach an independent predictor of these outcomes. Robotic pancreatectomy patients had a shorter length of stay than patients who underwent open pancreatectomy (7 days vs 9 days; P < 0.001). Additionally, wound infection rate (32.3% vs 12.4%, P < 0.0001) and transfusion (39.6% vs 12.4%, P < 0.0001) was improved in robotic pancreatectomy group with no differences in perioperative mortality. Improved median overall survival approached statistical significance for the robotic cohort (25.6 months vs 23.9 months; P = 0.055); however, on multivariable analysis the robotic approach predicted overall survival, (hazard ratio 0.77, P = 0.041). Robotic approach was an independent predictor of decreased blood loss and less transfusions than the open approach. CONCLUSIONS: Robotic pancreatectomy was not inferior compared to open pancreatectomy in a high-volume experienced center for oncologic outcomes and due to decreased blood loss and transfusion may have improved survival.

Phase II Trial of Adjuvant Dendritic Cell Vaccine in Combination with Celecoxib, Interferon-α, and Rintatolimod in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases.

BACKGROUND: Peritoneal metastases portend poor prognosis in the setting of standard chemotherapy. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves outcomes, but relapse is common. We report a phase II trial evaluating the safety and efficacy of adjuvant αDC1 vaccination with chemokine modulation (CKM) after CRS/HIPEC. METHODS: Patients undergoing CRS/HIPEC for appendiceal cancer, colorectal cancer, or peritoneal mesothelioma were enrolled. In addition to standard adjuvant chemotherapy, patients received intranodal and intradermal injections of autologous tumor-loaded αDC1 vaccine. After each vaccine booster, patients received CKM over 4 days, consisting of celecoxib, interferon (IFN)-α, and rintatolimod. RESULTS: Forty-six patients underwent CRS/HIPEC followed by αDC1 treatment, including 24 appendiceal primaries, 20 colorectal, and 2 mesotheliomas. DC maturation was successful, with 97% expressing HLA-DR and CD86. Tumor cell recovery from peritoneal tumors was challenging, resulting in only 17% of patients receiving the target dose of αDC1. The αDC1 and CKM regimen was well tolerated. CKM successfully modulated serum inflammatory cytokine and chemokine levels. Median progression-free survival (PFS) for appendiceal primaries was 50.4, 34.2, and 8.9 months for grade 1, 2, and 3 tumors, respectively, while median PFS for colorectal cancer was 20.5 and 8.9 months for moderately and poorly differentiated tumors, respectively. CONCLUSIONS: Adjuvant autologous tumor antigen-loaded αDC1 vaccine and CKM is well tolerated. The mucinous nature of peritoneal metastases limits the feasibility of obtaining adequate autologous tumor cells. The improvement in median PFS did not meet our predefined thresholds, leading us to conclude that αDC1 vaccination is not appropriate for patients undergoing CRS/HIPEC for peritoneal metastases.

Surgical resection of high-grade nonfunctional pancreatic neuroendocrine carcinoma is associated with improved survival.

BACKGROUND AND OBJECTIVES: The role of surgery in the treatment of nonfunctional pancreatic neuroendocrine carcinomas (PNEC) is not well defined. This study investigated the effect of surgical resection on cause-specific survival compared with nonoperative management. METHODS: The Surveillance, Epidemiology, and End Results Program (SEER) database was utilized to identify patients with nonfunctional pancreatic neuroendocrine carcinoma diagnosed between January 1, 2004 and December 31, 2015. Survival was modeled using Kaplan-Meier analysis and multivariable Cox proportional hazards models. RESULTS: Of the 488 patients identified, 137 (29%) underwent surgical resection of the primary site. Patients who underwent surgery had a median CSS of 31 months compared with 5 months in those who did not (p < 0.01). A survival benefit was observed when the cohort was stratified into local, nodal, and metastatic disease. CONCLUSION: Resection of the primary site in the cohort of PNEC patients compiled by SEER is associated with improved survival. Further consideration be placed on primary surgical resection for PNEC while additional studies that can select specifically for high-grade, poorly differentiated carcinomas need to be undertaken.

Poorly differentiated histologic grade correlates with worse survival in SMAD4 negative pancreatic adenocarcinoma patients.

BACKGROUND AND OBJECTIVES: This study investigated the influence of the transcription factor SMAD4 on overall patient survival following surgical resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: The SMAD4 status of 125 surgically resected PDAC specimens at a large academic center from 2014 to 2017 was routinely determined prospectively and correlated with clinicopathologic characteristics and overall survival. RESULTS: SMAD4 loss was identified in 62% of patients and was not associated with overall survival (OS). On multivariate Cox proportional hazards survival analysis, histologic grade was the best predictor of survival in the SMAD4(-) population (adjusted hazard ratio = 4.8, p < .0001). In the SMAD4(+) population, histologic grade was not associated with survival on multivariate analysis. In the SMAD4(-) population, median OS for well/moderately differentiated patients and poorly differentiated patients was 39.6 and 8.6 months, respectively. CONCLUSION: In this large cohort of resected PDAC, routine SMAD4 assessment identified a subpopulation of patients with SMAD4(-) and histologically poorly differentiated tumors that had significantly poor prognosis with median OS of 8.6 months. Characterization of the role of SMAD4 within the context of poorly differentiated tumors may help settle the controversy regarding SMAD4 in PDAC and lead to identification of personalized therapeutic strategies for subgroups of PDAC.

Acute Pancreatitis: A Review.

IMPORTANCE: In the United States, acute pancreatitis is one of the leading causes of hospital admission from gastrointestinal diseases, with approximately 300 000 emergency department visits each year. Outcomes from acute pancreatitis are influenced by risk stratification, fluid and nutritional management, and follow-up care and risk-reduction strategies, which are the subject of this review. OBSERVATIONS: MEDLINE was searched via PubMed as was the Cochrane databases for English-language studies published between January 2009 and August 2020 for current recommendations for predictive scoring tools, fluid management and nutrition, and follow-up and risk-reduction strategies for acute pancreatitis. Several scoring systems, such as the Bedside Index of Severity in Acute Pancreatitis (BISAP) and the Acute Physiology and Chronic Health Evaluation (APACHE) II tools, have good predictive capabilities for disease severity (mild, moderately severe, and severe per the revised Atlanta classification) and mortality, but no one tool works well for all forms of acute pancreatitis. Early and aggressive fluid resuscitation and early enteral nutrition are associated with lower rates of mortality and infectious complications, yet the optimal type and rate of fluid resuscitation have yet to be determined. The underlying etiology of acute pancreatitis should be sought in all patients, and risk-reduction strategies, such as cholecystectomy and alcohol cessation counseling, should be used during and after hospitalization for acute pancreatitis. CONCLUSIONS AND RELEVANCE: Acute pancreatitis is a complex disease that varies in severity and course. Prompt diagnosis and stratification of severity influence proper management. Scoring systems are useful adjuncts but should not supersede clinical judgment. Fluid management and nutrition are very important aspects of care for acute pancreatitis.

Endoscopic placement of pancreatic stent for "Deep" pancreatic enucleations operative technique and preliminary experience at two high-volume centers.

BACKGROUND: Pancreatic enucleation (PE) is a viable option for the removal of non-malignant pancreatic masses leading to complete preservation of organ function. Nevertheless, PE is associated with substantial rates of post-operative pancreatic fistula (POPF), particularly when the mass is close to the main pancreatic duct (MPD). Preoperative stenting of the MPD may prevent its injury when performing PE. This paper describes a novel technique of "deep" PE preceded by endoscopic stenting of the MPD. METHODS: From January 2017 to May 2019, patients with small pancreatic neuroendocrine tumors proximal to the MPD were candidates for PE with previous stenting of the MPD at the University of Verona, Italy, and at the UCLA Medical Center, Los Angeles, California. The endoscopic stenting was scheduled either the day before or 3 weeks before surgery, depending on the participating institute. RESULTS: Ten patients were included in this pilot study. The endoscopic procedure was successful and well tolerated in all cases. Open, laparoscopic and robotic PE were performed. Seven patients had surgical complications. Among these, six developed a post-operative pancreatic fistula (POPF), but neither grade C fistulas nor disruptions of the MPD were detected. At pathology, a low grade pancreatic neuroendocrine tumor was confirmed in all cases. CONCLUSION: In the setting of high-volume centers, this procedure is safe, and it is associated with acceptable short-term surgical morbidity. The preoperative stenting of the MPD might extend the surgical indications for PE.

Splenic artery pseudoaneurysm with hemosuccus pancreaticus requiring multimodal treatment.

Termed hemosuccus pancreaticus by Sandblom in 1970, hemorrhage from the pancreatic duct into the gastrointestinal tract represents a rare and challenging problem. Patients present with repeated upper gastrointestinal bleeding that is intermittent but often self-limited. In most cases, this pathophysiologic process is secondary to pancreatitis, chronic inflammation, and subsequent splenic artery pseudoaneurysm bleeding. Previously treated with open splenectomy and distal pancreatectomy, hemosuccus pancreaticus is now often managed with minimally invasive endovascular means. We describe an uncommon presentation of hemosuccus pancreaticus in the absence of prior pancreatitis, requiring open splenectomy, distal pancreatectomy, and celiac artery ligation after failed endovascular intervention.

Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer.

BACKGROUND: Occult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients. EXPERIMENTAL DESIGN: A total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay. CTC enumeration was correlated with clinicopathologic variables and outcomes following both surgical and systemic therapies. RESULTS: CTCs were identified in 78% of PDAC patients and CTC counts correlated with increasing stage (ρ = 0.42, p < 0.001). Of the 53 patients taken for potentially curative surgery, 13 (24.5%) had occult metastatic disease intraoperatively. Patients with occult disease had significantly more CTCs than patients with local disease only (median 7 vs. 1 CTC, p < 0.0001). At a cut-off of three or more CTCs/4 mL, CTCs correctly identified patients with occult metastatic disease preoperatively (area under the receiver operating characteristic curve 0.82, 95% confidence interval (CI) 0.76-0.98, p < 0.0001). CTCs were a univariate predictor of recurrence-free survival following surgery [hazard ratio (HR) 2.36, 95% CI 1.17-4.78, p = 0.017], as well as an independent predictor of overall survival on multivariate analysis (HR 1.38, 95% CI 1.01-1.88, p = 0.040). CONCLUSIONS: CTCs show promise as a prognostic biomarker for PDAC patients at all stages of disease being treated both medically and surgically. Furthermore, CTCs demonstrate potential as a preoperative biomarker for identifying patients at high risk of occult metastatic disease.

Pasireotide does not prevent postoperative pancreatic fistula: a prospective study.

BACKGROUND: Pancreatic fistula is a major cause of morbidity after pancreas surgery. In 2014, a single-center, randomized-controlled trial found pasireotide decreased pancreatic fistula rates. However, this finding has not been validated, nor has pasireotide been widely adopted. METHODS: A single-arm study in 111 consecutive patients undergoing pancreatic resection April 2015-October 2016 was conducted. Beginning immediately before surgery, patients received 900 µg subcutaneous pasireotide twice daily for up to seven days. Fistula rates were compared to 168 historical controls from July 2013 to March 2015. The primary outcome was Grade B/C fistula, as defined by the International Study Group on Pancreatic Fistula (ISGPF). RESULTS: There were no significant differences between the pasireotide group and historical controls in demographics, comorbidities, operation type, malignancy, gland texture, or pancreatic duct size. Pasireotide did not reduce fistula rate (15.5% control versus 17.1% pasireotide, p = 0.72). In subgroup analyses of pancreaticoduodenectomy or distal pancreatectomy, or patients with soft gland texture and/or small duct size, there was no decrease in fistulas. Thirty-nine patients (38%) experienced dose-limiting nausea. CONCLUSIONS: In an appropriately-powered, single-institution prospective study, pasireotide was not validated as a preventive measure for pancreatic fistula.

Robotic approach mitigates perioperative morbidity in obese patients following pancreaticoduodenectomy.

INTRODUCTION: The aim was to evaluate the impact of obesity on perioperative outcomes in patients undergoing robotic pancreaticoduodenectomy (RPD) compared to open pancreaticoduodenectomy (OPD). METHODS: A retrospective review of all pancreaticoduodenectomies from 9/2011 to 4/2015 was performed. Obesity was defined as body mass index (BMI) > 30 kg/m2. RESULTS: Of 474 pancreaticoduodenectomies performed: RPD = 213 (45%) and OPD = 261 (55%). A total of 145 (31%) patients were obese (70 RPD, 75 OPD). Obese patients had increased EBL (p = 0.03), pancreatic fistula (B&C; p = 0.077), and wound infection (p = 0.068) compared to the non-obese. For obese patients, RPD had decreased OR time (p = 0.0003), EBL (p < 0.001), and wound infection (p = 0.001) with no difference in Clavien ≥3 complications, margins, LOS or 30-day mortality compared with OPD. In multivariate analysis, obesity was the strongest predictor of Clavien ≥3 (OR 1.6; p = 0.041) and wound infection if BMI > 35 (OR 2.6; p = 0.03). The robotic approach was protective of Clavien ≥3 (OR 0.6; p = 0.03) on univariate analysis and wound infection (OR 0.3; p < 0.001) and grade B/C pancreatic fistula (OR 0.34; p < 0.001) on multivariate analysis. CONCLUSIONS: Obese patients are at risk for increased postoperative complications regardless of approach. However, the robotic approach mitigates some of the increased complication rate, while preserving other perioperative outcomes.

Breast cancer-related lymphedema after axillary lymph node dissection: does early postoperative prediction model work?

PURPOSE: Early detection and timely intervention demonstrate the greatest promise of reducing the incidence of late-stage lymphedema in breast cancer patients undergoing axillary lymph node dissection (ALND). A nomogram was developed for predicting the risk of lymphedema (LE) in patients with ALND. This study's aim was to test the early postoperative prediction model for the diagnosis of clinical and subclinical LE after ALND. METHODS: Patients requiring ALND were identified preoperatively through our LE program database. Measurements using metered tape with bioimpedance spectroscopy (L-Dex U400) were obtained preoperatively (n = 180) and at 3-6-month intervals postoperatively. The 5-year probability of LE after ALND was calculated using the Cleveland Clinic Risk Calculator. The discrimination of the nomogram was assessed by calculating the area under (AUC) the receiver operating characteristic curve. RESULTS: LE was present in 36.1% (n = 65) of 180 patients with ALND. Of these 65 patients, 22 (12.2%) had clinical LE and 43 (23.9%) had subclinical LE. Statistical analyses showed significant differences in BMI and receipt of radiotherapy between patients with and without LE (p = 0.03 and p = 0.01, respectively). AUC was 0.601, 0.614, and 0.600 for the nomogram using any LE, clinical LE, and subclinical LE patients, respectively. CONCLUSIONS: The recently created prediction model for the diagnosis of LE in ALND is not accurate in predicting who will develop clinical or subclinical LE. Periodic monitoring of women with ALND is the most effective method to aid in reducing clinical LE incidence through early detection and timely intervention of LE.

Metabolic exploitation of the sialic acid biosynthetic pathway to generate site-specifically labeled antibodies.

Lack of a universal site-specific conjugation methodology for antibodies limits their potential to be developed as tumor-specific imaging agents or targeted therapeutics. A potential mechanism for site-specific conjugation involves utilization of the conserved N-glycosylation site in the CH2 domain. We sought to develop an antibody with an altered azido-sugar at this site whereby site-specific label could be added. The HB8059 hybridoma was cultured with peracetylated N-azidoacetlymannosamine (Ac4ManNAz). The resulting azido-sugar antibody was conjugated to phosphine-polyethylene glycol (PEG3)-biotin via a modified Staudinger reaction. Biochemical and functional characterization of the biotinylated antibody was performed. The azido-sugar antibody was also labeled with DyLight-650-Phosphine and injected into mice harboring pancreatic cancer xenografts. The tumors were dissected and imaged utilizing an IVIS fluorescent camera. The antibody was successfully produced in 100 µM Ac4ManNAz. The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. Treatment with a N-linked glycosidase extinguished the band. Flow cytometry demonstrated antigen-specific binding of CA19-9-positive cells and the antibody localized to the antigen-positive tumor in vivo. We successfully produced an antibody with an azido-sugar at the conserved CH2 glycosylation site. We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. Finally, we demonstrated functionality of our antibody for in vitro and in vivo targeting of pancreatic cancer cells.