Publications by authors named "William E Fisher"

119 Publications

Hemoglobin A1c Is a Predictor of New Insulin Dependence After Partial Pancreatectomy: A Multi-Institutional Analysis.

J Gastrointest Surg 2021 May 4. Epub 2021 May 4.

Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Arthur G. James Cancer Hospital and Solove Research Institute, 395 W. 12th Avenue, Suite 670, Columbus, OH, 43210-1267, USA.

Background: Pancreatic diseases have long been associated with impaired glucose control. This study sought to identify the incidence of new insulin-dependent diabetes mellitus (IDDM) after pancreatectomy and the predictive accuracy of hemoglobin A1c (HbA1c) or blood glucose.

Methods: Patients who underwent partial pancreatectomy and had preoperative HbA1c available at two academic institutions were assessed for new IDDM on discharge in relation to complication rates and survival.

Results: Of the 267 patients analyzed, 67% had abnormal HbA1c levels prior to surgery (mean 6.8%, glucose 135 mg/dL). Two hundred eight (77.9%) were not insulin-dependent prior to surgery, and 35 (16.8%) developed new IDDM after resection. On multivariable regression, increasing HbA1c and preoperative glucose were the only significant predictors for new IDDM. Optimal predictive cutoffs (HbA1c of 6.25% and glucose of 121 mg/dL) were determined in a discovery group (n = 143) and confirmed in a validation group (n = 124) with a diagnostic sensitivity of 72.7% and specificity of 84.8%. Patients with new IDDM after resection had higher rates of severe complications (OR 3.39), increased TPN at discharge (OR 4.32), and increased rates of discharge to nursing facilities (OR 2.57) (all P < 0.05). New IDDM was also associated with a decreased cancer-specific survival.

Conclusion: Preoperative HbA1c ≥ 6.25% and blood glucose ≥ 121 mg/dL can accurately identify patients at increased risk of IDDM. These diagnostics may help identify patients in a preoperative setting that may benefit from interventions such as diabetes education or enhanced glucose control preoperatively.
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http://dx.doi.org/10.1007/s11605-021-05014-0DOI Listing
May 2021

The effect of high intraoperative blood loss on pancreatic fistula development after pancreatoduodenectomy: An international, multi-institutional propensity score matched analysis.

Surgery 2021 Apr 27. Epub 2021 Apr 27.

Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. Electronic address:

Background: The association between intraoperative estimated blood loss and outcomes after pancreatoduodenectomy has, thus far, been rarely explored.

Methods: In total, 7,706 pancreatoduodenectomies performed at 18 international institutions composing the Pancreas Fistula Study Group were examined (2003-2020). High estimated blood loss (>700 mL) was defined as twice the median. Propensity score matching (1:1 exact-match) was employed to adjust for variables associated with high estimated blood loss and clinically relevant pancreatic fistula occurrence. The study was powered to detect a 33% clinically relevant pancreatic fistula increase in the high estimated blood loss group, with α = 0.05 and β = 0.2.

Results: The propensity score model included 966 patients with high estimated blood loss and 966 patients with lower estimated blood loss; all covariate imbalantces were solved. Patients with high estimated blood loss patients experienced higher clinically relevant pancreatic fistula rates (19.4 vs 12.6%, odds ratio 1.66; P < .001), as well as higher severe complication rates (27.8 vs 15.6%), transfusions (50.1 vs 14.3%), reoperations (9.2 vs 4.0%), intensive care unit transfers (9.9 vs 4.8%) and 90-day mortality (4.7 vs 2.0%, all P < .001). High estimated blood loss was an independent predictor for clinically relevant pancreatic fistula (odds ratio 1.78, 95% confidence interval 1.37-2.32), as were prophylactic Octreotide administration (odds ratio 1.95, 95% confidence interval 1.46-2.61) and soft pancreatic texture (odds ratio 5.32, 95% confidence interval 3.74-5.57; all P < .001). Moreover, a second model including 1,126 pancreatoduodenectomies was derived including vascular resections as additional confounder (14.0% vascular resections performed in each group). On multivariable regression, high estimated blood loss was confirmed an independent predictor for clinically relevant pancreatic fistula reduction (odds ratio 1.80, 95% confidence interval 1.32-2.44; P < .001), whereas vascular resection was not (odds ratio 0.64, 95% confidence interval 0.34-1.88; P = .156).

Conclusion: This study better establishes the relationship between estimated blood loss and outcomes after pancreatoduodenectomy. Despite inherent contributions to blood loss, its minimization is an actionable opportunity for clinically relevant pancreatic fistula reduction and performance optimization in pancreatoduodenectomy. Accordingly, practical insights are offered to achieve this goal.
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http://dx.doi.org/10.1016/j.surg.2021.03.044DOI Listing
April 2021

A Phase 2 Randomized Placebo-Controlled Adjuvant Trial of GI-4000, a Recombinant Yeast Expressing Mutated RAS Proteins in Patients with Resected Pancreas Cancer.

J Pancreat Cancer 2021 23;7(1):8-19. Epub 2021 Mar 23.

Smuggler Mountain Group (SMG, Inc.), Aspen, Colorado, USA.

GI-4000, a series of recombinant yeast expressing four different mutated RAS proteins, was evaluated in subjects with resected -mutated pancreas cancer. Subjects ( = 176) received GI-4000 or placebo plus gemcitabine. Subjects' tumors were genotyped to identify which matched GI-4000 product to administer. Immune responses were measured by interferon-γ (IFNγ) ELISpot assay and by regulatory T cell (Treg) frequencies on treatment. Pretreatment plasma was retrospectively analyzed by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectrometry for proteomic signatures predictive of GI-4000 responsiveness. GI-4000 was well tolerated, with comparable safety findings between treatment groups. The GI-4000 group showed a similar pattern of median recurrence-free and overall survival (OS) compared with placebo. For the prospectively defined and stratified R1 resection subgroup, there was a trend in 1 year OS (72% vs. 56%), an improvement in OS (523.5 vs. 443.5 days [hazard ratio (HR) = 1.06 [confidence interval (CI): 0.53-2.13],  = 0.872), and increased frequency of immune responders (40% vs. 8%;  = 0.062) for GI-4000 versus placebo and a 159-day improvement in OS for R1 GI-4000 immune responders versus placebo ( = 0.810). For R0 resection subjects, no increases in IFNγ responses in GI-4000-treated subjects were observed. A higher frequency of R0/R1 subjects with a reduction in Tregs (CD4/CD45RA/Foxp3) was observed in GI-4000-treated subjects versus placebo ( = 0.033). A proteomic signature was identified that predicted response to GI-4000/gemcitabine regardless of resection status. These results justify continued investigation of GI-4000 in studies stratified for likely responders or in combination with immune check-point inhibitors or other immunomodulators, which may provide optimal reactivation of antitumor immunity. ClinicalTrials.gov Number: NCT00300950.
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http://dx.doi.org/10.1089/pancan.2020.0021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997807PMC
March 2021

Lactoferrin amyloid presenting as a mural nodule in a pancreatic cystic lesion prompting pancreatoduodenectomy: a case report.

BMC Gastroenterol 2021 Feb 12;21(1):66. Epub 2021 Feb 12.

Department of Pathology and Immunology, Baylor College of Medicine, 1 Baylor Plaza, MS BCM315, Houston, TX, 77030, USA.

Background: Amyloid deposition in pancreas is rare. Lactoferrin amyloid deposition has not been reported in pancreas, till date. Presence of enhancing mural nodule in a cyst on imaging is a worrisome feature for malignancy, and warrants surgical resection in a surgically fit candidate, as per Fukuoka guidelines for management of cystic lesions in pancreas.

Case Report: We report a case of localized amyloidosis presenting as a mural nodule in a 1.6 cm cyst located in the head of pancreas, which led to pancreatoduodenectomy in a 69 year old woman. Histological evaluation revealed a simple mucinous cyst with localized lactoferrin amyloid deposition corresponding to the mural nodule identified on imaging.

Conclusions: We report the first case of localized lactoferrin amyloid deposition in pancreas that presented as a mural nodule in a cystic lesion and prompted pancreatoduodenectomy. This unique case illustrates that on rare occasion mural nodule in a cyst can be benign. It adds amyloid deposition to the differential diagnosis of mural nodules in pancreatic cystic lesions seen on imaging.
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http://dx.doi.org/10.1186/s12876-021-01641-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881451PMC
February 2021

Surgeon experience contributes to improved outcomes in pancreatoduodenectomies at high risk for fistula development.

Surgery 2021 04 30;169(4):708-720. Epub 2020 Dec 30.

Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. Electronic address:

Background: Pancreatoduodenectomies at high risk for clinically relevant pancreatic fistula are uncommon, yet intimidating, situations. In such scenarios, the impact of individual surgeon experience on outcomes is poorly understood.

Methods: The fistula risk score was applied to identify high-risk patients (fistula risk score 7-10) from 7,706 pancreatoduodenectomies performed at 18 international institutions (2003-2020). For each case, surgeon pancreatoduodenectomy career volume and years of practice were linked to intraoperative fistula mitigation strategy adoption and outcomes. Consequently, best operative approaches for clinically relevant pancreatic fistula prevention and best performer profiles were identified through multivariable analysis models.

Results: Eight hundred and thirty high-risk pancreatoduodenectomies, performed by 64 surgeons, displayed an overall clinically relevant pancreatic fistula rate of 33.7%. Clinically relevant pancreatic fistula rates decreased with escalating surgeon career pancreatoduodenectomy (-49.7%) and career length (-41.2%; both P < .001), as did transfusion and reoperation rates, postoperative morbidity index, and duration of stay. Great experience (≥400 pancreatoduodenectomies performed or ≥21-year-long career) was a significant predictor of clinically relevant pancreatic fistula prevention (odds ratio 0.52, 95% confidence interval 0.35-0.76) and was more often associated with pancreatojejunostomy reconstruction and prophylactic octreotide omission, which were both independently associated with clinically relevant pancreatic fistula reduction. A risk-adjusted performance analysis also correlated with experience. Moreover, minimizing blood loss (≤400 mL) significantly contributed to clinically relevant pancreatic fistula prevention (odds ratio 0.40, 95% confidence interval 0.22-0.74).

Conclusion: Surgeon experience is a key contributor to achieve better outcomes after high-risk pancreatoduodenectomy. Surgeons can improve their performance in these challenging situations by employing pancreatojejunostomy reconstruction, omitting prophylactic octreotide, and minimizing blood loss.
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http://dx.doi.org/10.1016/j.surg.2020.11.022DOI Listing
April 2021

The Influence of Intraoperative Blood Loss on Fistula Development Following Pancreatoduodenectomy.

Ann Surg 2020 Nov 12. Epub 2020 Nov 12.

Departments of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

Objective: To investigate the role of intraoperative EBL on development of CR-POPF after pancreatoduodenectomy (PD).

Background: Minimizing EBL has been shown to decrease transfusions and provide better perioperative outcomes in PD. EBL is also felt to be influential on CR-POPF development.

Methods: This study consists of 5534 PDs from a 17-institution collaborative (2003-2018). EBL was progressively categorized (≤150 mL; 151-400 mL; 401-1,000 mL; >1,000 mL). Impact of additive EBL was assessed using 20 3-factor fistula risk score (FRS) scenarios reflective of endogenous CR-POPF risk.

Results: CR-POPF developed in 13.6% of patients (N = 753) and median EBL was 400 mL (interquartile range 250-600 mL). CR-POPF and Grade C POPF were associated with elevated EBL (median 350 vs 400 mL, P = 0.002; 372 vs 500 mL, P < 0.001, respectively). Progressive EBL cohorts displayed incremental CR-POPF rates (8.5%, 13.4%, 15.2%, 16.9%; P < 0.001). EBL >400 mL was associated with increased CR-POPF occurrence in 13/20 endogenous risk scenarios. Moreover, 8 of 10 scenarios predicated on a soft gland demonstrated increased CR-POPF incidence. Hypothetical projections demonstrate significant reductions in CR-POPF can be obtained with 1-, 2-, and 3-point decreases in FRS points attributed to EBL risk (12.2%, 17.4%, and 20.0%; P < 0.001). This is especially pronounced in high-risk (FRS7-10) patients, who demonstrate up to a 31% reduction (P < 0.001). Surgeons in the lowest-quartile of median EBL demonstrated CR-POPF rates less than half those in the upper-quartile (7.9% vs 18.8%; P < 0.001).

Conclusion: EBL independently contributes significant biological risk to CR-POPF. Substantial reductions in CR-POPF occurrence are projected and obtainable by minimizing EBL. Decreased individual surgeon EBL is associated with improvements in CR-POPF.
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http://dx.doi.org/10.1097/SLA.0000000000004549DOI Listing
November 2020

Development and external validation of a prediction model for survival in patients with resected ampullary adenocarcinoma.

Eur J Surg Oncol 2020 09 25;46(9):1717-1726. Epub 2020 May 25.

Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.

Introduction: Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC.

Materials And Methods: An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006-2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score.

Results: Overall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73-0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73-0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival.

Conclusion: A prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.
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http://dx.doi.org/10.1016/j.ejso.2020.04.011DOI Listing
September 2020

The Fistula Risk Score Catalog: Toward Precision Medicine for Pancreatic Fistula After Pancreatoduodenectomy.

Ann Surg 2020 Jun 11. Epub 2020 Jun 11.

Departments of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

Objective: This study aims to present a full spectrum of individual patient presentations of pancreatic fistula risk, and to define the utility of mitigation strategies amongst some of the most prevalent, and vulnerable scenarios surgeons encounter.

Background: The FRS has been utilized to identify technical strategies associated with reduced CR-POPF incidence across various risk strata. However, risk-stratification using the FRS has never been investigated with greater granularity. By deriving all possible combinations of FRS elements, individualized risk assessment could be utilized for precision medicine purposes.

Methods: FRS profiles and outcomes of 5533 PDs were accrued from 17 international institutions (2003-2019). The FRS was used to derive 80 unique combinations of patient "scenarios." Risk-matched analyses were conducted using a Bonferroni adjustment to identify scenarios with increased vulnerability for CR-POPF occurrence. Subsequently, these scenarios were analyzed using multivariable regression to explore optimal mitigation approaches.

Results: The overall CR-POPF rate was 13.6%. All 80 possible scenarios were encountered, with the most frequent being scenario #1 (8.1%) - the only negligible-risk scenario (CR-POPF rate = 0.7%). The moderate-risk zone had the most scenarios (50), patients (N = 3246), CR-POPFs (65.2%), and greatest non-zero discrepancy in CR-POPF rates between scenarios (18-fold). In the risk-matched analysis, 2 scenarios (#59 and 60) displayed increased vulnerability for CR-POPF relative to the moderate-risk zone (both P < 0.001). Multivariable analysis revealed factors associated with CR-POPF in these scenarios: pancreaticogastrostomy reconstruction [odds ratio (OR) 4.67], omission of drain placement (OR 5.51), and prophylactic octreotide (OR 3.09). When comparing the utilization of best practice strategies to patients who did not have these conjointly utilized, there was a significant decrease in CR-POPF (10.7% vs 35.5%, P < 0.001; OR 0.20, 95% confidence interval 0.12-0.33).

Conclusion: Through this data, a comprehensive fistula risk catalog has been created and the most clinically-impactful scenarios have been discerned. Focusing on individual scenarios provides a practical way to approach precision medicine, allowing for more directed and efficient management of CR-POPF.
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http://dx.doi.org/10.1097/SLA.0000000000004068DOI Listing
June 2020

Long-Term Assessment of Pancreatic Function After Pancreatectomy for Cystic Neoplasms.

J Surg Res 2020 03 15;247:547-555. Epub 2019 Nov 15.

Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas. Electronic address:

Background: With advances in cross-sectional imaging, pancreatic cysts are more frequently diagnosed and have become a common indication for pancreatectomy. The impact of pancreatectomy in these patients is important. The purpose of this study was to assess short-term outcomes, long-term nutritional status, quality of life (QOL), and pancreas function after pancreatectomy for cystic neoplasms.

Materials And Methods: At a single institution, patients at least 3 y post-pancreatectomy for benign cystic neoplasms were identified. Using a validated questionnaire, short-term outcomes, long-term outcomes including endocrine and exocrine insufficiency, long-term nutritional status, and preoperative and postoperative QOL were compared based on operation and indication for resection.

Results: Among 102 eligible patients, 70 had valid contact information and 51 (72.9%) agreed to participate. Median follow-up was 6 (4-8) y. Patients undergoing pancreatoduodenectomy for benign cysts had higher morbidity than a similar cohort resected for pancreatic adenocarcinoma (patients with at least 1 ≥ grade 2 complication [49.0% versus 31.6%, P = 0.038]). After long-term follow-up, pancreatectomy did not significantly affect perceived QOL. Half of patients had mild-moderate or severe malnourishment, but pancreatic enzyme replacement was reported by only 4 (7.8%) patients. New-onset diabetes was present in 15 (29.4%) patients with median time-to-diagnosis of 6 (1-12) mo after resection.

Conclusions: Pancreatectomy for benign cysts did not negatively impact patients' perceived QOL. However, after long-term follow-up, malnutrition and pancreatic insufficiency occurred in a significant percentage and may be greater than previously estimated. Consideration of short- and long-term outcomes should factor into preoperative counseling, especially in cysts with minimal risk of progression to malignancy.
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http://dx.doi.org/10.1016/j.jss.2019.09.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094044PMC
March 2020

Novel Methylated DNA Markers Discriminate Advanced Neoplasia in Pancreatic Cysts: Marker Discovery, Tissue Validation, and Cyst Fluid Testing.

Am J Gastroenterol 2019 09;114(9):1539-1549

Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Objectives: Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cyst fluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND).

Methods: From an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs.

Results: Of 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs (TBX15, BMP3) achieved sensitivity and specificity above 90%. Discrimination was significantly better by this CF-MDM panel than by mutant KRAS or carcinoembryonic antigen, with areas under the receiver operating characteristic curve of 0.93 (95% confidence interval: 0.86-0.99), 0.71 (0.57-0.85), and 0.72 (0.60-0.84), respectively. Cutoffs for the MDM panel applied to an independent CF validation set (31 cases, 56 controls) yielded similarly high discrimination, areas under the receiver operating characteristic curve = 0.86 (95% confidence interval: 0.77-0.94, P = 0.2).

Discussion: Novel MDMs discovered and validated in tissue accurately identify PCLs harboring HGD/PC. A panel of 2 MDMs assayed in CF yielded results with potential to enhance current risk prediction algorithms. Prospective studies are indicated to optimize and further evaluate CF-MDMs for clinical use.
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http://dx.doi.org/10.14309/ajg.0000000000000284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294458PMC
September 2019

Role of Adjuvant Multimodality Therapy After Curative-Intent Resection of Ampullary Carcinoma.

JAMA Surg 2019 08;154(8):706-714

Department of Surgery, University of Tennessee Health Science Center, Memphis.

Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined.

Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype.

Design, Setting, And Participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates.

Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy.

Main Outcomes And Measures: Overall survival.

Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P = .05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P = .24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P = .01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P = .53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P = .41).

Conclusions And Relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined.
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http://dx.doi.org/10.1001/jamasurg.2019.1170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547142PMC
August 2019

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery.

Clin Cancer Res 2019 07 23;25(14):4332-4342. Epub 2019 Apr 23.

The Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas.

Purpose: Clinically available intraoperative imaging tools to assist surgeons in identifying occult lesions are limited and partially responsible for the high rate of disease recurrence in patients with neuroendocrine tumors (NET). Using the established clinical efficacy of radiolabeled somatostatin analogs as a model, we demonstrate the ability of a fluorescent somatostatin analog to selectively target tumors that overexpress somatostatin receptor subtype-2 (SSTR2) and demonstrate utility for fluorescence-guided surgery (FGS).

Experimental Design: A multimodality chelator (MMC) was used as a "radioactive linker" to synthesize the fluorescently labeled somatostatin analog, Ga-MMC(IR800)-TOC. studies were performed to determine the pharmacokinetic profile, optimal imaging time point, and specificity for SSTR2-expressing tissues. Meso- and microscopic imaging of resected tissues and frozen sections were also performed to further assess specific binding, and binding to human NETs was examined using surgical biospecimens from patients with pancreatic NETs.

Results: Direct labeling with Ga/Ga provided quantitative biodistribution analysis that was in agreement with fluorescence data. Receptor-mediated uptake was observed and at the macro-, meso-, and microscopic scales. Surgical biospecimens from patients with pancreatic NETs also displayed receptor-specific agent binding, allowing clear delineation of tumor boundaries that matched pathology findings.

Conclusions: The radioactive utility of the MMC allowed us to validate the binding properties of a novel FGS agent that could have a broad impact on cancer outcomes by equipping surgeons with real-time intraoperative imaging capabilities.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-3312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675459PMC
July 2019

Evidence Versus Practice in Early Drain Removal After Pancreatectomy.

J Surg Res 2019 04 4;236:332-339. Epub 2019 Jan 4.

Baylor College of Medicine, Michael E. DeBakey Department of Surgery, Houston, TX. Electronic address:

Background: Early drain removal when postoperative day (POD) one drain fluid amylase (DFA) was ≤5000 U/L reduced complications in a previous randomized controlled trial. We hypothesized that most surgeons continue to remove drains late and this is associated with inferior outcomes.

Methods: We assessed the practice of surgeons in a prospectively maintained pancreas surgery registry to determine the association between timing of drain removal with demographics, comorbidities, and complications. We selected patients with POD1 DFA ≤5000 U/L and excluded those without drains, and subjects without data on POD1 DFA or timing of drain removal. Early drain removal was defined as ≤ POD5.

Results: Two hundred and forty four patients met inclusion criteria. Only 90 (37%) had drains removed early. Estimated blood loss was greater in the late removal group (190 mL versus 100 mL, P = 0.005) and pathological findings associated with soft gland texture were more frequent (97 [63%] versus 35 [39%], P < 0.0001). Patients in the late drain removal group had more complications (84 [55%] versus 30 [33%], P = 0.001) including pancreatic fistula (55 [36%] versus 4 [4%], P < 0.0001), delayed gastric emptying (27 [18%] versus 3 [3%], P = 0.002), and longer length of stay (7 d versus 5 d, P < 0.0001). In subset analysis for procedure type, complications and pancreatic fistula remained significant for both pancreatoduodenectomy and distal pancreatectomy.

Conclusions: Despite level one data suggesting improved outcomes with early removal when POD1 DFA is ≤ 5000 U/L, experienced pancreas surgeons more frequently removed drains late. This practice was associated with known risk factors (estimated blood loss, soft pancreas) and may be associated with inferior outcomes suggesting potential for improvement.
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http://dx.doi.org/10.1016/j.jss.2018.11.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377814PMC
April 2019

Pancreatic Incidentalomas: A Management Algorithm for Identifying Ectopic Spleens.

J Surg Res 2019 04 17;236:144-152. Epub 2018 Dec 17.

Elkins Pancreas Center, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas. Electronic address:

Background: Identification of incidental pancreatic lesions is increasing because of advancements in imaging. Diagnosis remains a challenge for clinicians, with intrapancreatic accessory spleens (IPAS) posing a unique dilemma. IPAS are frequently resected because of inability to exclude alternate diagnoses, subjecting patients to unnecessary risk. The purpose of this study was to examine our institutional experience with IPAS and develop a multidisciplinary algorithm to improve preoperative diagnosis.

Materials And Methods: Patients who underwent a distal pancreatectomy at a single institution from 2005 to 2018 were identified from a prospectively maintained database. Examination of final pathology for a diagnosis of IPAS yielded the final cohort. Demographics, preoperative workup, and operative course were reviewed and analyzed. A diagnostic algorithm was composed based on the consensus of a panel of expert pancreatic surgeons, a radiologist, and a pathologist.

Results: Ten patients of 303 patients who underwent a distal pancreatectomy were identified with a final pathology of IPAS. The average age was 54 y, 80% were white, and 60% were male. Lesions ranged in size from 7 mm to 5.1 cm in largest diameter (mean 2.2 cm). Lesions were described as round, well-marginated, and enhancing masses within the pancreatic tail. Preoperative workup was variable in terms of imaging and laboratory testing. Diagnostic workups were examined and combined with multidisciplinary input to create a diagnostic algorithm.

Conclusions: Incidental pancreatic lesions like IPAS remain a diagnostic challenge for clinicians. Employing a diagnostic algorithm as proposed may aid in the distinction of malignant and premalignant pathology and prevent unwarranted pancreatic resections.
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http://dx.doi.org/10.1016/j.jss.2018.11.032DOI Listing
April 2019

In Reply.

Obstet Gynecol 2018 12;132(6):1506

Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, Texas.

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http://dx.doi.org/10.1097/AOG.0000000000002994DOI Listing
December 2018

SRC-3 inhibition blocks tumor growth of pancreatic ductal adenocarcinoma.

Cancer Lett 2019 02 10;442:310-319. Epub 2018 Nov 10.

Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX, 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant and lethal disease with few treatment options. Steroid receptor coactivator-3 (SRC-3, also known as NCOA3, AIB1, pCIP, ACTR, RAC3, TRAM1) sits at the nexus of many growth signaling pathways and has been pursued as a therapeutic target for breast, prostate and lung cancers. In this study, we find that SRC-3 is overexpressed in PDAC and inversely correlates with patient overall survival. Knockdown of SRC-3 reduces pancreatic cancer cell proliferation, migration and invasion in vitro. Additionally, inhibition of SRC-3 using either shRNA or a small molecule inhibitor can significantly inhibit tumor growth in orthotopic pancreatic cancer mouse models. Collectively, this study establishes SRC-3 as a promising therapeutic target for pancreatic cancer treatment.
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http://dx.doi.org/10.1016/j.canlet.2018.11.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311429PMC
February 2019

Initiating Telehealth in a Complex Organization.

Semin Plast Surg 2018 Nov 22;32(4):159-161. Epub 2018 Oct 22.

Division of Plastic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas.

Medicine has been praised for breakthroughs that improve the quality and longevity of human life. In the setting of today's fast-paced, tech-savvy society in combination with increased patient volume entering hospital doors, telemedicine proves an effective tool to enable the industry to adapt to the changing world around us. A review of the current literature and legislative laws was conducted along with knowledge from the experience gathered at starting a telehealth platform at Texas Children's Hospital to find the necessary steps for starting a telehealth program. Through digital platform, telemedicine offers remote delivery of medical services to all parts of the country, urban and rural, while enhancing interprofessional referral patterns in the local setting. Telemedicine sets to preemptively triage and guide patients through their appropriate phases of care all the meanwhile, bringing the patient and physician closer together. This discussion delves into the further added benefits to large hospital systems, breaks down the basics of the technological platform, and addresses current barriers to entry in the telehealth industry. This article serves as an introduction to a series regarding effective implementation of telemedicine into the hospital system.
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http://dx.doi.org/10.1055/s-0038-1672132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197881PMC
November 2018

A Prospective Study to Establish a New-Onset Diabetes Cohort: From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer.

Pancreas 2018 Nov/Dec;47(10):1244-1248

Division of Gastroenterology, Department of Medicine, Mayo Clinic, Rochester, MN.

The National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases initiated the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) in 2015 (the CPDPC's origin, structure, governance, and research objectives are described in another article in this journal). One of the key objectives of CPDPC is to assemble a cohort of 10,000 subjects 50 years or older with new-onset diabetes, called the NOD cohort. Using a define, enrich, and find early detection approach, the aims of the NOD study are to (a) estimate the 3-year probability of pancreatic ductal adenocarcinoma (PDAC) in NOD (define), (b) establish a biobank of clinically annotated biospecimens from presymptomatic PDAC and control new-onset type 2 diabetes mellitus subjects, (c) conduct phase 3 validation studies of promising biomarkers for identification of incident PDAC in NOD patients (enrich), and (d) provide a platform for development of a future interventional screening protocol for early detection of PDAC in patients with NOD that incorporates imaging studies and/or clinical algorithms (find). It is expected that 85 to 100 incidences of PDAC will be diagnosed during the study period in this cohort of 10,000 patients.
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http://dx.doi.org/10.1097/MPA.0000000000001169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6432934PMC
March 2019

PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies: Rationale and Study Design for PROCEED From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer.

Pancreas 2018 Nov/Dec;47(10):1229-1238

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH.

Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) is the first prospective, observational cohort study of chronic pancreatitis (CP) in the United States. The primary goals of PROCEED are to define disease progression, test the predictive capability of candidate biomarkers, and develop a platform to conduct translational and mechanistic studies in CP. Using objective and consensus-driven criteria, PROCEED will enroll adults at different stages of CP-controls, suspected CP, and definite CP. In addition to collecting detailed information using structured case report forms and protocol-mandated evaluations at baseline and during follow-up, PROCEED will establish a linked biorepository of blood, urine, saliva, stool, pancreatic fluid, and pancreatic tissue. Enrollment for PROCEED began in June 2017. As of July 1, 2018, nine clinical centers of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer are enrolling, and 350 subjects have completed baseline evaluation. In conclusion, PROCEED will provide the most accurate and reliable estimates to date on progression of CP. The established cohort and biorepository will facilitate numerous analyses, leading to new strategies for diagnosis, methods to monitor disease progression, and treatment of CP.
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http://dx.doi.org/10.1097/MPA.0000000000001170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619499PMC
March 2019

Standard Operating Procedures for Biospecimen Collection, Processing, and Storage: From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer.

Pancreas 2018 Nov/Dec;47(10):1213-1221

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH.

High-quality and well-annotated biorepositories are needed to better understand the pathophysiology and biologic mechanisms of chronic pancreatitis (CP) and its consequences. We report a methodology for the development of a robust standard operating procedure (SOP) for a biorepository based on the experience of the clinical centers within the consortium to study Chronic Pancreatitis, Diabetes and Pancreas Cancer Clinical Centers (CPDPC), supported by the National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases as a unique multidisciplinary model to study CP, diabetes, and pancreatic cancer in both children and adults. Standard operating procedures from the CPDPC centers were evaluated and consolidated. The literature was reviewed for standard biorepository operating procedures that facilitated downstream molecular analysis. The existing literature on biobanking practices was harmonized with the SOPs from the clinical centers to produce a biorepository for pancreatic research. This article reports the methods and basic principles behind the creation of SOPs to develop a biorepository for the CPDPC. These will serve as a guide for investigators developing biorepositories in pancreas research. Rigorous and meticulous adherence to standardized biospecimen collection will facilitate investigations to better understand the pathophysiology and biologic mechanisms of CP, diabetes, and pancreatic cancer.
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http://dx.doi.org/10.1097/MPA.0000000000001171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197069PMC
March 2019

Understaging of clinical stage I pancreatic cancer and the impact of multimodality therapy.

Surgery 2019 02 20;165(2):307-314. Epub 2018 Sep 20.

Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX; Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, TX. Electronic address:

Background: Although current guidelines recommend multimodal therapy for all patients with pancreatic ductal adenocarcinoma, it is unclear the extent to which clinical stage I patients are accurately staged and how this may affect management.

Methods: In this retrospective cohort study of 4,404 patients aged 18-79 years with clinical stage 1 (ie, T1N0 or T2N0) pancreatic ductal adenocarcinoma treated with upfront resection in the National Cancer Database (2004-2014), understaging was ascertained by comparing pretreatment clinical stage with pathologic stage. The association between adjuvant treatment and overall risk of death among true stage I and understaged patients was evaluated using multivariable Cox regression.

Results: Upstaging was identified in 72.6% of patients (62.8% T3/4, 53.9% N1) of whom 69.7% received adjuvant therapy compared with 47.0% with true stage I disease. Overall survival at 5 years among those with true stage I disease was significantly higher than those who had been clinically understaged (42.9% vs 16.6%; log-rank, p < 0.001). For true stage I patients, adjuvant therapy was not associated with risk of death (hazard ratio: 1.07, 95% confidence interval: 0.89-1.29). For understaged patients, adjuvant therapy significantly decreased risk of death (hazard ratio: 0.64, 95% confidence interval: 0.55-0.74).

Conclusion: The majority of clinical stage I pancreatic ductal adenocarcinoma patients actually have higher-stage disease and benefit from multimodal therapy; however, one third of understaged patients do not receive any adjuvant treatment. Clinicians should discuss all potential treatment strategies with patients (in the context of the acknowledged risks and benefits), including the utilization of neoadjuvant approaches in those presenting with potentially resectable disease.
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http://dx.doi.org/10.1016/j.surg.2018.08.003DOI Listing
February 2019

Intraperitoneal Drainage and Pancreatic Resection.

Authors:
William E Fisher

Adv Surg 2018 09 19;52(1):205-222. Epub 2018 Jun 19.

Division of General Surgery, Michael E. DeBakey Department of Surgery, Elkins Pancreas Center, Baylor College of Medicine, 6620 Main Street, Suite 1425, Houston, TX 77030, USA. Electronic address:

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http://dx.doi.org/10.1016/j.yasu.2018.03.013DOI Listing
September 2018

An Academic Relative Value Unit System for Incentivizing the Academic Productivity of Surgery Faculty Members.

Ann Surg 2018 09;268(3):526-533

Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX.

Objective: The objective of this study was to evaluate a new academic relative-value unit (aRVU) scoring system linked to faculty compensation and analyze its association with overall departmental academic productivity.

Summary Background Data: Faculty are often not incentivized or financially compensated for educational and research activities crucial to the academic mission.

Methods: We launched an online, self-reporting aRVU system in 2015 to document and incentivize the academic productivity of our faculty. The system captured 65 specific weighted scores in 5 major categories of research, education, innovation, academic service, and peer review activities. The aRVU scores were rank-aggregated annually, and bonuses were distributed to faculty members in 3 tiers: top 10%, top third, and top half. We compared pre-aRVU (academic year 2015) to post-aRVU (academic year 2017) departmental achievement metrics.

Results: Since 2015, annual aRVU bonuses totaling $493,900 were awarded to 59 faculty members (58% of eligible department faculty). Implementing aRVUs was associated with significant increases in several key departmental academic achievement metrics: presentations (579 to 862; P = 0.02; 49% increase), publications (390 to 446; P = 0.02; 14%), total research funding ($4.6 M to $8.4 M; P < 0.001; 83%), NIH funding ($0.6 M to $3.4 M; P < 0.001; 467%), industry-sponsored clinical trials (8 to 23; P = 0.002; 188%), academic society committee positions (226 to 298; P < 0.001; 32%), and editorial leadership positions (50 to 74; P = 0.01; 48%).

Conclusions: Implementing an aRVU system was associated with increases in departmental academic productivity. Although other factors undoubtedly contributed to these increases, an aRVU program may represent an important mechanism for tracking and rewarding academic productivity in surgery departments.
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http://dx.doi.org/10.1097/SLA.0000000000002921DOI Listing
September 2018

Nonobstetric Surgery During Pregnancy.

Obstet Gynecol 2018 08;132(2):395-403

Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, and the Department of Surgery, Baylor College of Medicine, Houston, Texas.

One percent to 2% of pregnant women undergo nonobstetric surgery during pregnancy. Historically, there has been a reluctance to operate on pregnant women based on concerns for teratogenesis, pregnancy loss, or preterm birth. However, a careful review of published data suggests four major flaws affecting much of the available literature. Many studies contain outcomes data from past years in which diagnostic testing, surgical technique, and perioperative maternal-fetal care were so different from current experience as to make these data of limited utility today. This issue is further compounded by a tendency to combine experience from vastly disparate types of surgery into a single report. In addition, reports in nonobstetric journals often focus on maternal outcomes and contain insufficient detail regarding perinatal outcomes to allow distinction between complications associated with surgical disease and those attributable to surgery itself. Finally, most series are either uncontrolled or use the general population of pregnant women as controls rather than women with surgical disease who are managed nonsurgically. Consideration of these factors as well as our own extensive experience suggests that when the risks of maternal hypotension or hypoxia are minimal, or can be adequately mitigated, indicated surgery during any trimester does not appear to subject either the mother or fetus to risks significantly beyond those associated with the disease itself or the complications of surgery in nonpregnant individuals. In some cases, reluctance to operate during pregnancy becomes a self-fulfilling prophecy in which delay in surgery contributes to adverse perinatal outcomes traditionally attributed to surgery itself.
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http://dx.doi.org/10.1097/AOG.0000000000002748DOI Listing
August 2018

Venous thrombosis following pancreaticoduodenectomy with venous resection.

J Surg Res 2018 08 13;228:271-280. Epub 2018 Apr 13.

Baylor College of Medicine, The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, Houston, Texas. Electronic address:

Background: Addition of en bloc segmental venous reconstruction (VR) to pancreaticoduodenectomy (PD) for venous involvement of pancreatic tumors increases the complexity of the operation and may increase complications. The long-term mesenteric venous patency rate and oncologic outcome has not been well defined.

Methods: Our prospective database was reviewed to assess 90-day postoperative outcomes for patients who underwent PD or PD + VR (September 2004-June 2016). Two independent observers reviewed CT scans to determine long-term vein patency. In patients with pancreatic ductal adenocarcinoma, the impact of VR on 5-year overall survival was assessed using multivariate Cox proportional hazards regression. Student's t-test was used to evaluate continuous variables and the chi-square test for categorical variables.

Results: Three hundred ninety-three patients underwent PD (51 PD + VR). Patients undergoing PD + VR had longer operations (561 ± 119 versus 433 ± 89 min, P < 0.00001) and greater blood loss (768 ± 812 versus 327 ± 423 cc, P < 0.00001). There was no difference in 90-day mortality, overall postoperative complication rates, complication severity grades, reoperation, readmission, or length of stay. 26.7% experienced venous thrombosis. Most thromboses occurred in the first year after surgery, but we also observed late thrombosis in 1 patient after 89-month follow-up. Among 135 patients with pancreatic ductal adenocarcinoma, survival was significantly longer in the PD-alone group (31.3 months [95% confidence interval: 22.9-40.0] versus 17.0 [95% confidence interval: 13.0-19.1], p = 0.013).

Conclusions: PD + VR does not increase short-term morbidity, but venous thrombosis is frequent and can occur long after surgery. Survival is inferior when VR is required especially in the absence of neoadjuvant chemotherapy.
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http://dx.doi.org/10.1016/j.jss.2018.02.006DOI Listing
August 2018

Enhancing the Potency and Specificity of Engineered T Cells for Cancer Treatment.

Cancer Discov 2018 08 7;8(8):972-987. Epub 2018 Jun 7.

Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas.

The adoptive transfer of chimeric antigen receptor (CAR)-modified T cells has produced tumor responses even in patients with refractory diseases. However, the paucity of antigens that are tumor selective has resulted, on occasion, in "on-target, off-tumor" toxicities. To address this issue, we developed an approach to render T cells responsive to an expression pattern present exclusively at the tumor by using a trio of novel chimeric receptors. Using pancreatic cancer as a model, we demonstrate how T cells engineered with receptors that recognize prostate stem cell antigen, TGFβ, and IL4, and whose endodomains recapitulate physiologic T-cell signaling by providing signals for activation, costimulation, and cytokine support, produce potent antitumor effects selectively at the tumor site. In addition, this strategy has the benefit of rendering our cells resistant to otherwise immunosuppressive cytokines (TGFβ and IL4) and can be readily extended to other inhibitory molecules present at the tumor site (e.g., PD-L1, IL10, and IL13). This proof-of-concept study demonstrates how sophisticated engineering approaches can be utilized to both enhance the antitumor efficacy and increase the safety profile of transgenic T cells by incorporating a combination of receptors that ensure that cells are active exclusively at the tumor site. .
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http://dx.doi.org/10.1158/2159-8290.CD-17-1298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428579PMC
August 2018

The Interface of Pancreatic Cancer With Diabetes, Obesity, and Inflammation: Research Gaps and Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

Pancreas 2018 May/Jun;47(5):516-525

A workshop on "The Interface of Pancreatic Cancer with Diabetes, Obesity, and Inflammation: Research Gaps and Opportunities" was held by the National Institute of Diabetes and Digestive and Kidney Diseases on October 12, 2017. The purpose of the workshop was to explore the relationship and possible mechanisms of the increased risk of pancreatic ductal adenocarcinoma (PDAC) related to diabetes, the role of altered intracellular energy metabolism in PDAC, the mechanisms and biomarkers of diabetes caused by PDAC, the mechanisms of the increased risk of PDAC associated with obesity, and the role of inflammatory events and mediators as contributing causes of the development of PDAC. Workshop faculty reviewed the state of the current knowledge in these areas and made recommendations for future research efforts. Further knowledge is needed to elucidate the basic mechanisms contributing to the role of hyperinsulinemia, hyperglycemia, adipokines, and acute and chronic inflammatory events on the development of PDAC.
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http://dx.doi.org/10.1097/MPA.0000000000001037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361376PMC
October 2018

Sequential drain amylase to guide drain removal following pancreatectomy.

HPB (Oxford) 2018 06 23;20(6):514-520. Epub 2018 Feb 23.

Baylor College of Medicine, Michael E. DeBakey Department of Surgery, One Baylor Plaza Suite 404D, Houston, TX 77030, USA. Electronic address:

Background: Although used as criterion for early drain removal, postoperative day (POD) 1 drain fluid amylase (DFA) ≤ 5000 U/L has low negative predictive value for clinically relevant postoperative pancreatic fistula (CR-POPF). It was hypothesized that POD3 DFA ≤ 350 could provide further information to guide early drain removal.

Methods: Data from a pancreas surgery consortium database for pancreatoduodenectomy and distal pancreatectomy patients were analyzed retrospectively. Those patients without drains or POD 1 and 3 DFA data were excluded. Patients with POD1 DFA ≤ 5000 were divided into groups based on POD3 DFA: Group A (≤350) and Group B (>350). Operative characteristics and 60-day outcomes were compared using chi-square test.

Results: Among 687 patients in the database, all data were available for 380. Fifty-five (14.5%) had a POD1 DFA > 5000. Among 325 with POD1 DFA ≤ 5000, 254 (78.2%) were in Group A and 71 (21.8%) in Group B. Complications (35 (49.3%) vs 87 (34.4%); p = 0.021) and CR-POPF (13 (18.3%) vs 10 (3.9%); p < 0.001) were more frequent in Group B.

Conclusions: In patients with POD1 DFA ≤ 5000, POD3 DFA ≤ 350 may be a practical test to guide safe early drain removal. Further prospective testing may be useful.
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http://dx.doi.org/10.1016/j.hpb.2017.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995628PMC
June 2018

Evidence-Based Management of Drains Following Pancreatic Resection: A Systematic Review.

Pancreas 2018 01;47(1):12-17

From the Elkins Pancreas Center and the Department of Surgery at Baylor College of Medicine, Houston TX.

Many pancreatic surgeons continue to use intraperitoneal drains, but others have limited or avoided their use, believing this improves outcomes. We conducted a systematic review and meta-analysis of the literature assessing outcomes in pancreatectomy without drains, selective drainage, and early drain removal. We searched PubMed, Embase, and the Cochrane Library databases and conducted a systematic review of randomized and nonrandomized studies comparing routine intra-abdominal drainage versus no drainage, selective drain use, and early versus late drain removal after pancreatectomy, with major complications as the primary outcome. A meta-analysis of the literature assessing routine use of drains was conducted using the random-effects model. A total of 461 articles met search criteria from PubMed (168 articles), Embase (263 articles), and the Cochrane Library (30 articles). After case reports and articles without primary data on complications were excluded, 14 studies were identified for systematic review. Definitive evidence-based recommendations cannot be made regarding the management of drains following pancreatectomy because of limitations in the available literature. Based on available evidence, the most conservative approach, pending further data, is routine placement of a drain and early removal unless the patient's clinical course or drain fluid amylase concentration suggests a developing fistula.
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http://dx.doi.org/10.1097/MPA.0000000000000961DOI Listing
January 2018