Faculty Bibliography

PURPOSE/OBJECTIVE:Pancreatic ductal adenocarcinoma (PDA) is a common, deadly cancer that is challenging both to diagnose and to manage. Its hallmark is an expansive, desmoplastic stroma characterized by high mechanical stiffness. In this study, we sought to leverage this feature of PDA for two purposes: differential diagnosis and monitoring of response to treatment. EXPERIMENTAL DESIGN/METHODS:Harmonic Motion Imaging is a functional ultrasound technique that yields a quantitative relative measurement of stiffness suitable for comparisons between individuals and over time. We used HMI to quantify pancreatic stiffness in mouse models of pancreatitis and PDA as well as in a series of freshly resected human pancreatic cancer specimens. RESULTS:In mice, we learned that stiffness increased during progression from pre-neoplasia to adenocarcinoma, and also effectively distinguished PDA from several forms of pancreatitis. In human specimens, the distinction of tumors versus adjacent pancreatitis or normal pancreas tissue was even more stark. Moreover, in both mice and humans, stiffness increased in proportion to tumor size, indicating that tuning of mechanical stiffness is an ongoing process during tumor progression. Finally, using a brca2-mutant mouse model of PDA that is sensitive to cisplatin, we found that tissue stiffness decreases when tumors respond successfully to chemotherapy. Consistent with this observation, we found that tumor tissues from patients who had undergone neoadjuvant therapy were less stiff than those of untreated patients. CONCLUSIONS:These findings support further development of HMI for clinical applications in disease staging and treatment response assessment in pancreatic ductal adenocarcinoma.

Background/Aims/UNASSIGNED:The management of small, incidentally discovered nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has been a matter of debate. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a tool used to identify and risk-stratify PNETs. This study investigates the concordance rate of Ki67 grading between EUS-FNA and surgical pathology specimens in NFPNETs and whether certain NF-PNET characteristics are associated with disease recurrence and disease-related death. Methods/UNASSIGNED:: We retrospectively reviewed the clinical history, imaging, endoscopic findings, and pathology records of 37 cases of NFPNETs that underwent pre-operative EUS-FNA and surgical resection at a single academic medical center. Results/UNASSIGNED:: There was 73% concordance between Ki67 obtained from EUS-FNA cytology and surgical pathology specimens; concordance was the highest for low- and high-grade NF-PNETs. High-grade Ki67 NF-PNETs based on cytology (p=0.028) and histology (p=0.028) were associated with disease recurrence and disease-related death. Additionally, tumors with high-grade mitotic rate (p=0.005), tumor size >22.5 mm (p=0.104), and lymphovascular invasion (p=0.103) were more likely to have poor prognosis. Conclusions/UNASSIGNED:: NF-PNETs with high-grade Ki67 on EUS-FNA have poor prognosis despite surgical resection. NF-PNETs with intermediate-grade Ki67 on EUS-FNA should be strongly considered for surgical resection. NF-PNETs with low-grade Ki67 on EUSFNA can be monitored without surgical intervention, up to tumor size 20 mm.

BACKGROUND:The American College of Chest Physicians and American Hepato-Pancreato-Biliary Association recommend using low-molecular-weight heparin for 28 days postoperatively for venous thromboembolism prophylaxis after cancer surgery. Dabigatran is a once daily oral anticoagulant that is FDA approved for venous thromboembolism prophylaxis after orthopedic surgery, uses fixed dosing, and has an antidote. METHODS:Patients undergoing surgery for malignant pancreatic tumors (neuroendocrine excluded) from January 2017 to January 2018 were converted to dabigatran 220 mg daily on discharge until postoperative day 28; patients with medical or insurance contraindications were converted to enoxaparin or another direct oral anticoagulant. The primary endpoint was bleeding complications through 90 days. RESULTS:A total of 134 patients were considered for this study (median age 67 ± 10; 58.9% male). Eighty-seven (82.9%) patients received dabigatran and 18 (17.1%) received another form of anticoagulation. There were 19 (4.2%) patients not prescribed dabigatran due to medical or inpatient contraindications. Four patients experienced bleeding complications after discharge while on dabigatran. Two (2%) were major bleeds (Clavien-Dindo IV and V), and 2 (2%) were minor (Clavien-Dindo I). Patient compliance was excellent, with 93% of prescribed patients fully completing their prophylaxis. There were 2 patients that developed symptomatic deep vein thrombosis. CONCLUSION:The use of a direct oral anticoagulant as extended venous thromboembolism prophylaxis after major gastrointestinal surgery has not been studied to date. These results show dabigatran to be a safe alternative to low-molecular-weight heparin for extended venous thromboembolism prophylaxis with regard to bleeding complications.

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Staggering statistics regarding the global burden of disease due to lack of surgical care worldwide has been gaining attention in the global health literature over the last 10 years. The Lancet Commission on Global Surgery reported that 16.9 million lives were lost due to an absence of surgical care in 2010, equivalent to 33% of all deaths worldwide. Although data from low- and middle-income countries (LMICs) are limited, recent investigations, such as the African Surgical Outcomes Study, highlight that despite operating on low risk patients, there is increased postoperative mortality in LMICs versus higher-resource settings, a majority of which occur secondary to seemingly preventable complications like surgical site infections. We propose that implementing creative, low-cost surgical outcomes monitoring and select quality improvement systems proven effective in high-income countries, such as surgical infection prevention programs and safety checklists, can enhance the delivery of safe surgical care in existing LMIC surgical systems. While efforts to initiate and expand surgical access and capacity continues to deserve attention in the global health community, here we advocate for creative modifications to current service structures, such as promoting a culture of safety, employing technology and mobile health (mHealth) for patient data collection and follow-up, and harnessing partnerships for information sharing, to create a framework for improving morbidity and mortality in responsible, scalable, and sustainable ways.

BACKGROUND:Intraductal papillary mucinous neoplasm (IPMN) is premalignant pancreatic lesion. International guidelines offer limited predictors of individual risk. A nomogram to predict individual IPMN malignancy risk was released, with good diagnostic performance based on a large cohort of Asian patients with IPMN. The present study validated a nomogram to predict malignancy risk and invasiveness of IPMN using both Eastern and Western cohorts. METHODS:Clinicopathological and radiological data from patients who underwent pancreatic resection for IPMN at four centres each in Eastern and Western countries were collected. After excluding patients with missing data for at least one malignancy predictor in the nomogram (main pancreatic duct diameter, cyst size, presence of mural nodule, serum carcinoembryonic antigen and carbohydrate antigen (CA) 19-9 levels, and age). RESULTS:In total, data from 393 patients who fit the criteria were analysed, of whom 265 were from Eastern and 128 from Western institutions. Although mean age, sex, log value of serum CA19-9 level, tumour location, main duct diameter, cyst size and presence of mural nodule differed between the Korean/Japanese, Eastern and Western cohorts, rates of malignancy and invasive cancer did not differ significantly. Areas under the receiver operating characteristic (ROC) curve values for the nomogram predicting malignancy were 0·745 for Eastern, 0·856 for Western and 0·776 for combined cohorts; respective values for the nomogram predicting invasiveness were 0·736, 0·891 and 0·788. CONCLUSIONS:External validation of the nomogram showed good performance in predicting cancer in both Eastern and Western patients with IPMN lesions.

OBJECTIVE:To identify a clinical fistula risk score following distal pancreatectomy. BACKGROUND:Clinically relevant pancreatic fistula (CR-POPF) following distal pancreatectomy (DP) is a dominant contributor to procedural morbidity, yet risk factors attributable to CR-POPF and effective practices to reduce its occurrence remain elusive. METHODS:This multinational, retrospective study of 2026 DPs involved 52 surgeons at 10 institutions (2001-2016). CR-POPFs were defined by 2016 International Study Group criteria, and risk models generated using stepwise logistic regression analysis were evaluated by c-statistic. Mitigation strategies were assessed by regression modeling while controlling for identified risk factors and treating institution. RESULTS:CR-POPF occurred following 306 (15.1%) DPs. Risk factors independently associated with CR-POPF included: age (<60 yrs: OR 1.42, 95% CI 1.05-1.82), obesity (OR 1.54, 95% CI 1.19-2.12), hypoalbuminenia (OR 1.63, 95% CI 1.06-2.51), the absence of epidural anesthesia (OR 1.59, 95% CI 1.17-2.16), neuroendocrine or nonmalignant pathology (OR 1.56, 95% CI 1.18-2.06), concomitant splenectomy (OR 1.99, 95% CI 1.25-3.17), and vascular resection (OR 2.29, 95% CI 1.25-3.17). After adjusting for inherent risk between cases by multivariable regression, the following were not independently associated with CR-POPF: method of transection, suture ligation of the pancreatic duct, staple size, the use of staple line reinforcement, tissue patches, biologic sealants, or prophylactic octreotide. Intraoperative drainage was associated with a greater fistula rate (OR 2.09, 95% CI 1.51-3.78) but reduced fistula severity (P < 0.001). CONCLUSIONS:From this large analysis of pancreatic fistula following DP, CR-POPF occurrence cannot be reliably predicted. Opportunities for developing a risk score model are limited for performing risk-adjusted analyses of mitigation strategies and surgeon performance.

BACKGROUND:The Association of Perioperative Registered Nurses (AORN) released new guidelines for operating room attire in 2015 in an attempt to reduce surgical site infections (SSIs). These guidelines have been adopted by the Centers for Medicare and Medicaid Services. We aimed to assess the relationships among operating room attire, SSIs, and healthcare costs. STUDY DESIGN:In March 2016, our center introduced the AORN attire policy. National Health Safety Network data from our hospital were collected on general surgery, cardiac, neurosurgery, orthopaedic, and gynecology procedures from January 2014 to November 2017. The SSI rates and microbiological culture data for 30,493 procedures before and after policy implementation were compared using propensity score matching. The associated costs of the AORN policy were analyzed. RESULTS:After 1:1 propensity score matching, 12,585 matched pairs spanning the policy change were included (25,170 patients total); before policy change (BC group) and after policy change (AC group). The rate of SSIs did not differ between groups (1.0% AC group vs 1.1% BC group; p = 0.7). There was no difference in the incidence of Staphylococcal species cultured from wounds (19.3% AC group vs 16.8% BC group; p = 0.6). Multivariable analyses demonstrated that wound classification and emergent procedures were the strongest independent predictors of SSIs. The cost of attire for 1 person entering the operating room increased from $0.07 to $0.12 before policy change to $1.11 to $1.38 after policy change. Use of the mandated operating room long-sleeved jackets alone in our institution was associated with an added cost of $1,128,078 annually, which translates to an estimated $540 million per year for all US hospitals combined. CONCLUSIONS:Implementation of the AORN guidelines has not decreased SSIs and has increased healthcare costs.