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1.
J Surg Oncol ; 130(1): 72-82, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38726668

ABSTRACT

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.


Subject(s)
Neoadjuvant Therapy , Pancreatic Neoplasms , Pancreaticoduodenectomy , Humans , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/drug therapy , Female , Male , Retrospective Studies , Neoadjuvant Therapy/mortality , Aged , Middle Aged , Survival Rate , Carcinoma, Pancreatic Ductal/surgery , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/therapy , Chemotherapy, Adjuvant , Disease-Free Survival , Follow-Up Studies , Vascular Surgical Procedures/mortality , Vascular Surgical Procedures/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prognosis
2.
Surg Endosc ; 37(11): 8166-8177, 2023 11.
Article in English | MEDLINE | ID: mdl-37730854

ABSTRACT

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.


Subject(s)
Gastroplasty , Obesity, Morbid , Humans , Quality of Life , Treatment Outcome , Obesity/surgery , Obesity/etiology , Endoscopy/methods , Gastroplasty/methods , Weight Loss , Obesity, Morbid/surgery
3.
HPB (Oxford) ; 25(3): 301-310, 2023 03.
Article in English | MEDLINE | ID: mdl-36529625

ABSTRACT

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.


Subject(s)
Laparoscopy , Pancreatic Neoplasms , Robotic Surgical Procedures , Robotics , Humans , Aged , Pancreaticoduodenectomy/adverse effects , Robotic Surgical Procedures/adverse effects , Retrospective Studies , Prospective Studies , Propensity Score , Random Amplified Polymorphic DNA Technique , Postoperative Complications/etiology , Laparoscopy/adverse effects , Length of Stay , Pancreatic Neoplasms/surgery
4.
J Surg Res ; 279: 788-795, 2022 11.
Article in English | MEDLINE | ID: mdl-35970011

ABSTRACT

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.


Subject(s)
Hernia, Inguinal , Hernia, Ventral , Laparoscopy , Robotic Surgical Procedures , Robotics , Hernia, Inguinal/surgery , Hernia, Ventral/surgery , Herniorrhaphy/methods , Humans , Laparoscopy/methods , Retrospective Studies , Robotic Surgical Procedures/methods , United States , Veterans Health
5.
J Surg Res ; 279: 330-337, 2022 11.
Article in English | MEDLINE | ID: mdl-35810550

ABSTRACT

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.


Subject(s)
Hernia, Inguinal , Hernia, Ventral , Laparoscopy , Robotic Surgical Procedures , Robotics , Hernia, Inguinal/surgery , Hernia, Ventral/surgery , Herniorrhaphy/adverse effects , Herniorrhaphy/methods , Humans , Laparoscopy/adverse effects , Laparoscopy/methods , Retrospective Studies , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/methods , Veterans Health
6.
Ann Surg ; 274(3): e262-e268, 2021 09 01.
Article in English | MEDLINE | ID: mdl-31663967

ABSTRACT

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.


Subject(s)
Adenocarcinoma/surgery , Outcome and Process Assessment, Health Care , Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Robotic Surgical Procedures , Aged , Blood Loss, Surgical/prevention & control , Blood Transfusion/statistics & numerical data , Chemotherapy, Adjuvant , Female , Humans , Male , Postoperative Complications , Retrospective Studies
7.
J Surg Oncol ; 124(8): 1373-1380, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34406651

ABSTRACT

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.


Subject(s)
Neuroendocrine Tumors/mortality , Pancreatectomy/mortality , Pancreatic Neoplasms/mortality , SEER Program/statistics & numerical data , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Grading , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/surgery , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Survival Rate
8.
JAMA ; 325(4): 382-390, 2021 Jan 26.
Article in English | MEDLINE | ID: mdl-33496779

ABSTRACT

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.


Subject(s)
Enteral Nutrition , Fluid Therapy , Pancreatitis/therapy , APACHE , Alcohol Abstinence , Humans , Pancreatitis/diagnosis , Pancreatitis/etiology , Risk Reduction Behavior , Severity of Illness Index
9.
Surg Endosc ; 34(6): 2796-2802, 2020 06.
Article in English | MEDLINE | ID: mdl-32180000

ABSTRACT

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.


Subject(s)
Laparoscopy/methods , Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Robotic Surgical Procedures/methods , Stents , Adult , Aged , Female , Humans , Italy , Male , Middle Aged , Pancreas/surgery , Pancreatic Ducts/surgery , Pancreatic Fistula/etiology , Pancreatic Fistula/prevention & control , Pilot Projects , Postoperative Complications/etiology , Postoperative Complications/prevention & control
11.
Ann Surg Oncol ; 25(4): 1000-1008, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29442211

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Pancreatic Ductal/secondary , Liver Neoplasms/secondary , Neoplasm Recurrence, Local/pathology , Neoplastic Cells, Circulating/pathology , Pancreatic Neoplasms/pathology , Peritoneal Neoplasms/secondary , Aged , Carcinoma, Pancreatic Ductal/blood , Carcinoma, Pancreatic Ductal/surgery , Female , Follow-Up Studies , Humans , Liver Neoplasms/blood , Liver Neoplasms/surgery , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/surgery , Pancreatectomy , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/surgery , Peritoneal Neoplasms/blood , Peritoneal Neoplasms/surgery , Prognosis , Prospective Studies , Survival Rate
12.
HPB (Oxford) ; 20(5): 418-422, 2018 05.
Article in English | MEDLINE | ID: mdl-29398424

ABSTRACT

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.


Subject(s)
Pancreatectomy/adverse effects , Pancreatic Fistula/prevention & control , Pancreaticoduodenectomy/adverse effects , Somatostatin/analogs & derivatives , Aged , Case-Control Studies , Drug Administration Schedule , Female , Humans , Injections, Subcutaneous , Male , Middle Aged , Pancreatic Fistula/diagnostic imaging , Pancreatic Fistula/etiology , Prospective Studies , Risk Factors , Somatostatin/administration & dosage , Somatostatin/adverse effects , Time Factors , Treatment Outcome
13.
HPB (Oxford) ; 19(2): 93-98, 2017 02.
Article in English | MEDLINE | ID: mdl-28038966

ABSTRACT

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.


Subject(s)
Obesity/complications , Pancreaticoduodenectomy/methods , Robotic Surgical Procedures , Aged , Body Mass Index , Chi-Square Distribution , Female , Humans , Length of Stay , Logistic Models , Male , Middle Aged , Multivariate Analysis , Obesity/diagnosis , Obesity/mortality , Odds Ratio , Pancreatic Fistula/etiology , Pancreatic Fistula/prevention & control , Pancreaticoduodenectomy/adverse effects , Pancreaticoduodenectomy/mortality , Retrospective Studies , Risk Assessment , Risk Factors , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/mortality , Surgical Wound Infection/etiology , Surgical Wound Infection/prevention & control , Time Factors , Treatment Outcome
14.
JAMA ; 325(23): 2403-2404, 2021 06 15.
Article in English | MEDLINE | ID: mdl-34129002
15.
Glycobiology ; 24(1): 62-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24150277

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/immunology , Antibodies, Neoplasm/immunology , Antibody Specificity , N-Acetylneuraminic Acid/immunology , Pancreatic Neoplasms/immunology , Animals , Cell Line, Tumor , Female , Humans , Hybridomas , Mice , Mice, Nude
16.
J Surg Res ; 185(1): 45-55, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23827791

ABSTRACT

BACKGROUND: Antibody-based therapeutics is a rapidly growing field. Small engineered antibody fragments demonstrate similar antigen affinity compared with the parental antibody but have a shorter serum half-life and possess the ability to be conjugated to nanoparticles. The goal of this study was to engineer an anti-carbohydrate antigen 19-9 (CA19-9) cys-diabody fragment in hopes of targeting nanoparticles to pancreatic cancer. METHODS: The anti-CA19-9 cys-diabody was created by engineering a C-terminal cysteine residue into the DNA single-chain Fv construct of the anti-CA19-9 diabody and expressed in NS0 cells. Maleimide chemistry was used to conjugate the cys-diabody to polymerized liposomal nanoparticles (PLNs) through the cysteine residues. Flow cytometry was used to evaluate targeting of cys-diabody and cys-diabody-PLN conjugate to human pancreatic cancer cell lines. The cys-diabody was radiolabeled with a positron emitter ((124)I) and evaluated in a mouse model of CA19-9-positive and CA19-9-negative xenografts with micro-positron emission tomography/micro-computed tomography at successive time intervals after injection. Percentage of injected dose per gram of radioactivity was measured in blood and tumor to provide objective confirmation of the micro-positron emission tomographic images. RESULTS: Tumor xenograft imaging of the anti-CA19-9 cys-diabody demonstrated an average tumor-to-blood ratio of 3.0 and positive-to-negative tumor ratio of 7.4. Successful conjugation of the cys-diabody to PLNs was indicated by flow cytometry showing specific binding of cys-diabody-PLN conjugate to human pancreatic cancer cells in vitro. CONCLUSIONS: Our results show that the anti-CA19-9 cys-diabody targets pancreatic cancer providing specific molecular imaging in tumor xenograft models. Furthermore, the cys-diabody-PLN conjugate demonstrates target-specific binding of human pancreatic cancer cells with the potential to deliver targeted treatment.


Subject(s)
Antibodies, Bispecific/pharmacology , CA-19-9 Antigen/immunology , Nanoparticles/therapeutic use , Pancreatic Neoplasms/therapy , Positron-Emission Tomography/methods , Single-Chain Antibodies/pharmacology , Animals , Antibodies, Bispecific/chemistry , Cell Line, Tumor , Cystine/chemistry , Cystine/pharmacology , Female , Humans , Immunotherapy/methods , Liposomes/pharmacology , Mice , Mice, Nude , Multiple Myeloma , Pancreatic Neoplasms/diagnostic imaging , Protein Engineering , Single-Chain Antibodies/chemistry , Xenograft Model Antitumor Assays
18.
J Gastrointest Surg ; 27(11): 2365-2372, 2023 11.
Article in English | MEDLINE | ID: mdl-37552388

ABSTRACT

BACKGROUND: Duodenal neuroendocrine tumors (dNETs) are rare, and their management is not well-defined. National Comprehensive Cancer Network (NCCN) guidelines recommend surgical resection of large dNETs (> 2 cm) and endoscopic resection of small tumors (< 2 cm). We compared the survival outcomes between surgical and endoscopic resection in various dNET sizes. METHODS: A retrospective cohort study was conducted using patient data from Surveillance, Epidemiology, and End Results Program (SEER) database. Variables analyzed included age, tumor size, grade, stage, and lymph node status. Disease-specific survival (DSS) was compared for endoscopic and surgical groups in dNET size strata: 0-0.5, 0.5-1, 1-2, 2-3, and > 3 cm. Kaplan-Meier and multivariable Cox proportional hazards models were used for survival analysis. RESULTS: The study included 465 patients, with 124 (26.7%) undergoing surgical resection. The average age was 61.9 years, and tumor sizes ranged from 0.1 to 10.5 cm. Endoscopic resection had 40.5% of tumors between 0 and 0.5 cm, while surgery had only 21% (p < 0.001). In the surgical cohort, 79.8% had grade 1 tumors compared to 88.3% in the endoscopy group (P = 0.024). Among surgically resected cases, 48.4% (60 patients) had lymph node involvement. Age, tumor size, grade, and stage did not significantly predict survival after surgical resection. Stratified by tumor size, no difference in DSS was observed between surgery and endoscopy groups. CONCLUSIONS: Endoscopic resection demonstrated similar survival outcomes to surgical resection across dNET sizes in this national analysis. Given the risks and the lack of survival benefits for surgery, endoscopic resection may be beneficial for both small and large tumors. Further studies are warranted to validate the current NCCN guidelines.


Subject(s)
Duodenal Neoplasms , Neuroendocrine Tumors , Humans , Child , Middle Aged , Neuroendocrine Tumors/pathology , Retrospective Studies , Duodenal Neoplasms/pathology , Endoscopy, Gastrointestinal
19.
Int J Surg Case Rep ; 105: 107974, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36933407

ABSTRACT

INTRODUCTION AND IMPORTANCE: Heterotopic Pancreas (HP) is defined by the presence of pancreatic tissue in an anatomically distinct location from the main pancreas. While often clinically silent, it may present symptomatically. If located in the gastric antrum, HP may cause gastric outlet obstruction (GOO). The objective of this paper is to present a rare case of HP in the gastric antrum causing GOO. CASE PRESENTATION: Herein, we report a 43-year-old man who presented with abdominal pain and non-bilious emesis in the setting of COVID-19 infection and alcohol consumption. During the initial workup, computed-tomography (CT) was non-specific but demonstrated GOO, concerning for cancer. Cold forceps biopsies taken during esophagogastroduodenoscopy (EGD) confirmed benign HP. Since the patient was symptomatic from gastric outlet compression, he underwent resection via laparoscopic distal gastrectomy and Billroth II gastrojejunostomy. At 1-month postoperative follow-up, the patient recovered uneventfully. We hypothesized that GOO by HP in this case may have been associated with cumulative effects of alcohol consumption and COVID-19 infection on the ectopic tissue. CLINICAL DISCUSSION: HP is rare and difficult to diagnose preoperatively. When located in gastric antrum, HP can cause GOO, mimicking gastric malignancy. Combination of EGD/EUS, biopsy/FNA, and surgical resection are necessary to definitively make the diagnosis. Finally, it is important to consider that heterotopic pancreatitis or structural changes in HP may occur due to classic pancreatic stressors like alcohol and viral infections. CONCLUSION: HP may cause GOO presenting with non-bilious emesis and abdominal pain, mistaken for malignancy on CT imaging.

20.
Syst Rev ; 12(1): 197, 2023 10 14.
Article in English | MEDLINE | ID: mdl-37838696

ABSTRACT

BACKGROUND: Antiplatelet agents are central in the management of vascular disease. The use of dual antiplatelet therapy (DAPT) for the management of thromboembolic complications must be weighed against bleeding risk in the perioperative setting. This balance is critical in patients undergoing cardiac or non-cardiac surgery. The management of patients on DAPT for any indication (including stents) is not clear and there is limited evidence to guide decision-making. This review summarizes current evidence since 2015 regarding the occurrence of major adverse events associated with continuing, suspending, or varying DAPT in the perioperative period. METHODS: A research librarian searched PubMed and Cochrane from November 30, 2015 to May 17, 2022, for relevant terms regarding adult patients on DAPT for any reason undergoing surgery, with a perioperative variation in DAPT strategy. Outcomes of interest included the occurrence of major adverse cardiac events, major adverse limb events, all-cause death, major bleeding, and reoperation. We considered withdrawal or discontinuation of DAPT as stopping either aspirin or a P2Y12 inhibitor or both agents; continuation of DAPT indicates that both drugs were given in the specified timeframe. RESULTS: Eighteen observational studies met the inclusion criteria. No RCTs were identified, and no studies were judged to be at low risk of bias. Twelve studies reported on CABG. Withholding DAPT therapy for more than 2 days was associated with less blood loss and a slight trend favoring less transfusion and surgical re-exploration. Among five observational CABG studies, there were no statistically significant differences in patient death across DAPT management strategies. Few studies reported cardiac outcomes. The remaining studies, which were about procedures other than exclusively CABG, demonstrated mixed findings with respect to DAPT strategy, bleeding, and ischemic outcomes. CONCLUSION: The evidence base on the benefits and risks of different perioperative DAPT strategies for patients with stents is extremely limited. The strongest signal, which was still judged as low certainty evidence, is that suspension of DAPT for greater than 2 days prior to CABG surgery is associated with less bleeding, transfusions, and re-explorations. Different DAPT strategies' association with other outcomes of interest, such as MACE, remains uncertain. SYSTEMATIC REVIEW REGISTRATION: A preregistered protocol for this review can be found on the PROSPERO International Prospective Register of systematic reviews ( http://www.crd.york.ac.uk/PROSPERO/ ; registration number: CRD42022371032).


Subject(s)
Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Adult , Humans , Aspirin/therapeutic use , Hemorrhage/chemically induced , Platelet Aggregation Inhibitors/therapeutic use , Stents , Systematic Reviews as Topic
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