More than Means to an End: Assessing Surgical Provider Familiarity with Palliative Care.

BACKGROUND: As palliative medicine concepts emerge as essential surgical education, there has been a resulting spike in surgical palliative care research. Historic surgical dogma viewed mortality and comfort-focused care as a failure of the providers' endurance, knowledge base, or technical skill. Therefore, many providers avoided consultation to a palliative medicine service until it became evident a patient could not survive or was actively dying. As the need for surgical palliative care grows, the identification of deficits in surgical providers' understanding of the scope of palliative medicine is necessary to direct further training and development efforts. METHOD: A ten-question survey was emailed to all residents, physician assistants, nurse practitioners, and attending physicians in the general surgery and subspecialty surgical departments within the Einstein Healthcare Network. RESULTS: 30 non-trainees (attending surgeons, nurse practitioners, and physician assistants) and 26 trainees (PGY-1 to PGY-5) completed the survey. Less than half of participants reported training in conversations regarding withdrawal of life-prolonging treatments in the setting of expected poor outcomes, 55% reported receiving training in pain management, and 64% reported receiving training in delivery of bad news. 54% report being involved in five or more end-of-life discussions in the last year with trainees reporting fewer end-of-life discussions than non-trainees; 67% of trainees reported zero to four discussions while 23% of non-trainees reported over twenty discussions (P = .009). CONCLUSIONS: Despite many participants training in intensive care settings, providers lack the training to carry out major discussions regarding life-limiting illness, goals of care, and end-of-life independently.

Impact of Repeat Head Computed Tomography on Mild Traumatic Brain Injury Patients With Abbreviated Injury Score 1-2 Injuries.

BACKGROUND: Patients presenting with traumatic intracranial hemorrhage (ICH) routinely undergo repeat head Computed Tomography (CT) scans with the goal of identifying progressing hemorrhage early and providing timely intervention. Glasgow Coma Scale (GCS) score and Abbreviated Injury Score (AIS) are typically used to grade the severity of traumatic brain injury (TBI) and triage subsequent management. However, most patients receive a repeat head CT scan within 6 hours of the initial insult, regardless of these clinical scores. We investigated the yield of a repeat CT scan for mild blunt TBI (GCS 13-15, AIS 1-2). METHODS: This was a single-center retrospective chart review at a level 1 trauma center between 2009 and 2019. Our primary outcome was medical or surgical intervention directly resulted from change in CT head findings. We used multivariate regression to identify predictors of surgical and medical intervention. RESULTS: 234 mild TBI patients met inclusion criteria. 33.7% of all patients had worsening ICH. 7.7% of patients required a surgical intervention, and 27.4% received a medical intervention. Multivariate analysis found that a decline in GCS (OR 8.64), and polytrauma (Injury Severity Score >15; OR 3.32) predicted surgical intervention. Worsening ICH did not predict surgical or medical intervention. Patients requiring medical intervention were more likely to have a decline in GCS (OR 2.53, P = .02) and be older (age >65, OR 2.06, P = .02). CONCLUSION: In the population of blunt traumatic injury, worsening ICH did not predict surgical or medical intervention. Routine repeat imaging for this population is low yield, and clinical exam should guide the decision to reimage.

A step towards personalizing next line therapy for resected pancreatic and related cancer patients: A single institution's experience.

BACKGROUND: There is a lack of precision medicine in pancreatic ductal adenocarcinoma (PDA) and related cancers, and outcomes for patients with this diagnosis remain poor despite decades of research investigating this disease. Therefore, it is necessary to explore novel therapeutic options for these patients who may benefit from personalized therapies. OBJECTIVE: Molecular profiling of hepatopancreaticobiliary malignancies at our institution, including but not limited to PDA, was initiated to assess the feasibility of incorporating molecular profiling results into patient oncological therapy planning. METHODS: All eligible patients from Thomas Jefferson University (TJU) with hepatopancreaticobiliary tumors including PDA, who agreed to molecular testing profiling, were prospectively enrolled in a registry study from December 2014 to September 2017 and their tumor samples were tested to identify molecular markers that can be used to guide therapy options in the future. Next generation sequencing (NGS) and protein expression in tumor samples were tested at CLIA-certified laboratories. Prospective clinicopathologic data were extracted from medical records and compiled in a de-identified fashion. RESULTS: Seventy eight (78) patients were enrolled in the study, which included 65/78 patients with PDA (local and metastatic) and out of that subset, 52/65 patients had surgically resected PDA. Therapy recommendations were generated based on molecular and clinicopathologic data for all enrolled patients. NGS uncovered actionable alterations in 25/52 surgically resected PDAs (48%) which could be used to guide therapy options in the future. High expression of three proteins, TS (p = 0.005), ERCC1 (p = 0.001), and PD-1 (p = 0.04), was associated with reduced recurrence-free survival (RFS), while TP53 mutations were correlated with longer RFS (p = 0.01). CONCLUSIONS: The goal of this study was to implement a stepwise strategy to identify and profile resected PDAs at our institution. Consistent with previous studies, approximately half of patients with resected PDA harbor actionable mutations with possible targeted therapeutic implications. Ongoing studies will determine the clinical value of identifying these mutations in patients with resected PDA.

Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer.

Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.Significance: New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. Cancer Discov; 8(9); 1112-29. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047.

Genetic Drivers of Pancreatic Cancer Are Identical Between the Primary Tumor and a Secondary Lesion in a Long-Term (>5 Years) Survivor After a Whipple Procedure.

Background: A new mass in the remnant pancreas of a patient with previously resected pancreatic ductal adenocarcinoma (PDA) typically represents either a recurrence of the initial primary tumor or a second primary tumor. Recent advances in next-generation sequencing (NGS) strategies allow us to compare the genetic makeup of primary and secondary lesions. Case presentation: A 50-year-old Caucasian female presented for a surgical evaluation of a new biopsy-proven PDA at the junction of the body and tail of the pancreas. Six years prior, in 2011, the patient was found to have a T3N0M0 PDA of the pancreatic head, which was surgically resected with a classic Whipple procedure and concurrent hemicolectomy. Pathology showed pancreatic intraepithelial neoplasia grade 2 and PDA with negative surgical margins, positive perineural spread, and negative lymphovascular spread, and the patient received adjuvant chemotherapy and local radiation. In 2017, she was diagnosed with a new PDA lesion in the remaining pancreatic body far from the previous anastomosis site and was taken to surgery for a completion pancreatectomy and revision of the gastrojejunostomy. NGS was performed on both specimens. Both lesions shared identical mutations in KRAS, TP53, and CDKN2A genes. Amplifications of MYC and mutant KRAS were identified in the 2017 tumor and an ACVR1B mutation was identified in the 2011 tumor, but was not found in the 2017 tumor. Conclusions: This case demonstrates the ability to evaluate similarities between key genetic drivers from a resected primary tumor and a PDA lesion that presented in the same patient 6 years later. Histological analysis and NGS can be used to understand potential differences and similarities between lesions and may be useful in future studies as predictive markers or to provide insight into resistance mechanisms (e.g., MYC amplification).