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The benefit of radiation therapy for pancreatic ductal adenocarcinoma (PDAC) remains unclear. We hypothesized that a new mechanistic mathematical model of chemotherapy and radiation response could predict clinical outcomes a priori, using a previously described baseline measurement of perfusion from computed tomography scans, normalized area under the enhancement curve (nAUC).We simplified an existing mass transport model that predicted cancer cell death by replacing previously unknown variables with averaged direct measurements from randomly selected pathologic sections of untreated PDAC. This allowed using nAUC as the sole model input to approximate tumor perfusion. We then compared the predicted cancer cell death to the actual cell death measured from corresponding resected tumors treated with neoadjuvant chemoradiation in a calibration cohort (n = 80) and prospective cohort (n = 25). After calibration, we applied the model to 2 separate cohorts for pathologic and clinical associations: targeted therapy cohort (n = 101), cetuximab/bevacizumab + radiosensitizing chemotherapy, and standard chemoradiation cohort (n = 81), radiosensitizing chemotherapy to 50.4 Gy in 28 fractions.We established the relationship between pretreatment computed v nAUC to pathologically verified blood volume fraction of the tumor (r = 0.65; P = .009) and fractional tumor cell death (r = 0.97-0.99; P.0001) in the calibration and prospective cohorts. On multivariate analyses, accounting for traditional covariates, nAUC independently associated with overall survival in all cohorts (mean hazard ratios, 0.14-0.31). Receiver operator characteristic analyses revealed discrimination of good and bad prognostic groups in the cohorts with area under the curve values of 0.64 to 0.71.This work presents a new mathematical modeling approach to predict clinical response from chemotherapy and radiation for PDAC. Our findings indicate that oxygen/drug diffusion strongly influences clinical responses and that nAUC is a potential tool to select patients with PDAC for radiation therapy.

OBJECTIVES: The initial settings on an intravenous patient-controlled analgesia (IV-PCA) pump can represent a significant source of postoperative opioid exposure. The primary aim of this study was to evaluate the impact of first day IV-PCA use on total inpatient opioid use after open pancreatectomy, before and after standardization of initial dosing. METHODS: Inpatient oral morphine equivalents (OME) were reviewed for pancreatectomy patients treated with IV-PCA at a single institution before and after (3/2016–8/2017 vs. 3/2019–11/2020) implementation of a standardized initial IV-PCA dosing regimen (initial limit 0.1mg hydromorphone, or 1mg OME, every 10 min as needed). IV-PCA OME in the first 24 hours and total inpatient OME were compared between cohorts. RESULTS: Of 220 total patients, 132 were in the pre-standardization historical cohort. First-24-hour IV-PCA use was different (pre-standardization median 95mg vs. post-standardization 15mg, p

Pancreatic ductal adenocarcinoma (PDAC) has few effective treatments. Immunotherapy, an attractive alternative strategy, remains challenging with the lack of knowledge on the tumor-infiltrating lymphocyte (TIL) landscape in PDAC. To generate a reference of T-cell subpopulations, we profiled 80,000 T cells from 57 PDAC samples, 22 uninvolved/normal samples, and cultured TIL using single-cell transcriptomic and T-cell receptor analysis. These data revealed 20 cell states and heterogeneous distributions of TIL populations. The CD8+ TIL contained a putative transitional GZMK+ population based on T-cell receptor clonotype sharing, and cell-state trajectory analysis showed similarity to a GZMB+PRF1+ cytotoxic and a CXCL13+ dysfunctional population. Statistical analysis suggested that certain TIL states, such as dysfunctional and inhibitory populations, often occurred together. Finally, analysis of cultured TIL revealed that high-frequency clones from effector populations were preferentially expanded. These data provide a framework for understanding the PDAC TIL landscape for future TIL use in immunotherapy for PDAC.Significance:To improve the efficacy of immunotherapy in PDAC, there is a great need to understand the PDAC TIL landscape. This study represents a reference of PDAC TIL subpopulations and their relationships and provides a foundation upon which to base future immunotherapeutic efforts.This article is highlighted in the In This Issue feature, p. 2221

Supplementary Table from Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer

Supplementary Figure from Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer

BACKGROUND AND OBJECTIVES The impact of perioperative blood transfusion (PBT) on outcomes for pancreatic ductal adenocarcinoma (PDAC) patients given multimodality therapy (MMT) remains undefined. We sought to evaluate the association of PBT with survival after PDAC resection. METHODS Pancreatectomy patients (July 2011-December 2017) who received MMT were abstracted from a prospective database. Overall survival (OS) was compared by PBT within 30 days, 24 h (24HR-BT), or 24 h until 30 days (Postop-BT). RESULTS Most (76.6%) of 312 MMT patients underwent neoadjuvant therapy (NT). Eighty-nine patients (28.5%) received PBT; 58 (18.6%) 24HR-BT, and 31 (9.9%) Postop-BT. Compared with surgery-first, NT patients received more 24HR-BTs (22.2% vs. 6.8%, p = 0.003) and PBTs overall (32.6% vs. 15.1%, p = 0.004). Overall median OS was 45 months. The association of PBT with shorter median OS appeared limited to first 24-h transfusions (34 months 24HR-BT vs. 48 months Postop-BT vs. 53 months no-PBT, p = 0.009) and was dose-dependent, with a median OS of 52 months for 0 units 24HR-BT, 35 months for 1 unit, and 25 months for ≥2 units (p = 0.004). Independent predictors of OS included node-positivity (hazard ratio [HR]: 1.93, p

Recent studies defined a potentially important role of the microbiome in modulating pancreatic ductal adenocarcinoma (PDAC) and responses to therapies. We hypothesized that antibiotic usage may predict outcomes in patients with PDAC. We retrospectively analyzed clinical data of patients with resectable or metastatic PDAC seen at MD Anderson Cancer from 2003 to 2017. Demographic, chemotherapy regimen and antibiotic use, duration, type, and reason for indication were recorded. A total of 580 patients with PDAC were studied, 342 resected and 238 metastatic patients, selected retrospectively from our database. Antibiotic use, for longer than 48 hrs, was detected in 209 resected patients (61%) and 195 metastatic ones (62%). On resectable patients, we did not find differences in overall survival (OS) or progression‐free survival (PFS), based on antibiotic intake. However, in the metastatic cohort, antibiotic consumption was associated with a significantly longer OS (13.3 months vs. 9.0 months, HR 0.48, 95% CI 0.34–0.7, p = 0.0001) and PFS (4.4 months vs. 2 months, HR 0.48, 95% CI 0.34–0.68, p =, We have analyzed the effect of antibiotics’ intake on two cohorts of patients with pancreatic adenocarcinoma, resectable, and metastatic. We have found that on the metastatic cohort, antibiotics use was significantly associated with better outcomes, particularly, on patients that received gemcitabine based‐chemotherapy as the first line.

Pancreatic ductal adenocarcinoma (PDAC) has few effective treatments. Immunotherapy, an attractive alternative strategy, remains challenging with the lack of knowledge on the tumor-infiltrating lymphocyte (TIL) landscape in PDAC. To generate a reference of T-cell subpopulations, we profiled 80,000 T cells from 57 PDAC samples, 22 uninvolved/normal samples, and cultured TIL using single-cell transcriptomic and T-cell receptor analysis. These data revealed 20 cell states and heterogeneous distributions of TIL populations. The CD8+ TIL contained a putative transitional GZMK+ population based on T-cell receptor clonotype sharing, and cell-state trajectory analysis showed similarity to a GZMB+PRF1+ cytotoxic and a CXCL13+ dysfunctional population. Statistical analysis suggested that certain TIL states, such as dysfunctional and inhibitory populations, often occurred together. Finally, analysis of cultured TIL revealed that high-frequency clones from effector populations were preferentially expanded. These data provide a framework for understanding the PDAC TIL landscape for future TIL use in immunotherapy for PDAC. Significance: To improve the efficacy of immunotherapy in PDAC, there is a great need to understand the PDAC TIL landscape. This study represents a reference of PDAC TIL subpopulations and their relationships and provides a foundation upon which to base future immunotherapeutic efforts. This article is highlighted in the In This Issue feature, p. 2221

Background There remains no tool to quantify the total value of comparative processes in health care. Hospital administrative data sets are emerging as valuable sources to evaluate performance. Thus, we use a framework to simultaneously assess multiple domains of value associated with an enhanced recovery initiative using national administrative data. Materials and methods Risk-stratified clinical pathways for patients undergoing pancreatic surgery were implemented in 2016 at our institution. We used a national administrative database to characterize changes in value associated with this initiative. Value metrics assessed included in-hospital mortality, complication rates, length of stay (LOS), 30-day readmission rates, and institutional costs. We compared our performance with other hospitals both before and after implementation of the pathways. Metrics were graphed on radar charts to assess overall value. Results 22,660 cases were assessed. Comparing 75 cases at our institution and 5520 cases at all other hospitals before pathway implementation, mean in-hospital LOS was 9.6 versus 10.8 d, in-hospital mortality was 0.0% versus 1.9%, mean costs were $23,585 versus $21,387, 30-day readmission rates were 1.3% versus 7.4%, and complication rates were 8.0% versus 11.2%, respectively. Comparing 334 cases at our institution and 16,731 cases at all other hospitals after pathway implementation, mean in-hospital LOS was 7.7 versus 10.3 d, in-hospital mortality was 0.3% versus 1.6%, mean costs were $19,428 versus $22,032, 30-day readmission rates were 6.6% versus 7.5%, and complication rates were 6.3% versus 10.3%, respectively. Notably, LOS and institutional costs were reduced at our institution after implementation of the enhanced clinical care pathways. Our costs were higher than comparators before implementation, but lower than comparators after implementation. Conclusions Herein, we used an analytic framework and used national administrative data to assess the value of an enhanced care initiative as benchmarked with data from other hospitals. We thus illustrate how to identify and measure opportunities for targeted improvements in health care delivery. We also recognize the limitations of the use of administrative data in a comprehensive assessment of value in health care.

Background An increasing number of patients with cancer diagnoses and prior SARS-CoV-2 infection will require surgical treatment. The objective of this study was to determine whether a history of SARS-CoV-2 infection increases the risk of adverse postoperative events following surgery in patients with cancer. Methods This was a propensity-matched cohort study from April 6, 2020 to October 31, 2020 at the UT MD Anderson Cancer Center. Cancer patients were identified who underwent elective surgery after recovering from SARS-CoV-2 infection and matched to controls based on patient, disease, and surgical factors. Primary study outcome was a composite of the following adverse postoperative events that occurred within 30 days of surgery: death, unplanned readmission, pneumonia, cardiac injury, or thromboembolic event. Results A total of 5682 patients were included for study, and 114 (2.0%) had a prior SARS-CoV-2 infection. The average time from infection to surgery was 52 (range 20–202) days. Compared with matched controls, there was no difference in the rate of adverse postoperative outcome (14.3% vs. 13.4%, p = 1.0). Patients with a SARS-CoV-2-related inpatient admission before surgery had increased odds of postoperative complication (adjusted odds ratio [aOR] 7.4 [1.6–34.3], p = 0.01). Conclusions A minimal wait time of 20 days after recovering from minimally symptomatic SARS-CoV-2 infection appears to be safe for cancer patients undergoing low-risk elective surgery. Patients with SARS-CoV-2 infections requiring inpatient treatment were at increased risk for adverse events after surgery. Additional wait time may be required in those with more severe infections. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-021-10291-9.

The surgical treatment of pancreas ductal adenocarcinoma (PDAC) is plagued by high rates of distant recurrences despite complete resection, highlighting the importance of systemic therapy. Historically, patients with PDAC have been treated with postoperative therapy, but this sequencing strategy can be associated with the inability to complete therapy due to perioperative complications and prolonged recovery. In addition, a subset of patients progress early, irrespective of whether surgery is performed, highlighting the systemic nature of this disease. Preoperative therapy has increasingly been utilized in clinical practice, but studies examining its benefits are limited. In this Landmark Series, we will review seminal studies for resectable and borderline resectable PDAC.

Evaluate utility of dual energy CT iodine material density images to identify preoperatively nodal positivity in pancreatic cancer patients who underwent neoadjuvant therapy. This IRB approved retrospective study evaluated 62 patients between 2012 and 2016 with proven pancreatic ductal adenocarcinoma, who underwent neoadjuvant therapy, tumor resection and both baseline and preoperative assessment with pancreatic multiphasic rapid switching dual energy CT. Three radiologists in consensus identified on imaging nodes > 0.5 cm in short axis, evaluated nodal morphology, size and on each phase density in HU, and concentrations on iodine material density images normalized to the aorta. Of 62 patients, 33 were N0, 20 N1, and 9 N2. Total of 145 lymph nodes were evaluated, with average number of nodes per anatomic site ranging from 1.3 (body tumors) to 5 (uncinate) versus average of 24 and 30 nodes recovered respectively at surgery. Most (N = 44) were pancreatic head tumors. For all patients, regardless of site of primary tumor, the minimum measured iodine value of all of a patient’s measured nodes taken as a group on preoperative studies, as normalized to the aorta, was significant at P = 0.041 value in differentiating N0 from N1/2 and ROC analysis showed an AUC of 0.67. With a cutoff of 0.2857, sensitivity was 0.78 and specificity was 0.58, with values

ObjectivesTumor size measurement is critical for accurate tumor staging in patients with pancreatic ductal adenocarcinoma (PDAC). However, accurate tumor size measurement is challenging in patients who received neoadjuvant therapy before resection, due to treatment-induced fibrosis and tumor invasion beyond the grossly identified tumor area. In this study, we evaluated the correlation between the tumor size and tumor volume measured on post-therapy computed tomography (CT) scans and the pathological measurement. Also, we investigated the correlation between these measurements and clinicopathological parameters and survival.Materials and methodsRetrospectively, we evaluated 343 patients with PDAC who received neoadjuvant therapy, followed by pancreaticoduodenectomy and had pre-operative pancreatic protocol CT imaging. We measured the longest tumor diameter (RadL) and the radiological tumor volume (RadV) on the post-therapy CT scan, then we categorized RadL into four radiologic tumor stages (RTS) based on the current AJCC staging (8th edition) protocol and RadV based on the median. Pearson correlation or Spearman's coefficient (δ), T-test and ANOVA was used to test the correlation between the radiological and pathological measurement. Chi-square analysis was used to test the correlation with the tumor pathological response, lymph-node metastasis and margin status and Kaplan-Meier and Cox-proportional hazard for survival analysis. P-value < 0.05 was considered significant.ResultsAs a continuous variable, RadL showed a positive linear correlation with the post-therapy pathologic tumor size in the overall patient population (Pearson correlation coefficient: 0.72, P&nbsp

Delayed gastric emptying (DGE) is a frequent complication after pancreaticoduodenectomy (PD) that impairs recovery and quality of life. The purpose of this study was to assess the impact risk-stratified pancreatectomy clinical pathways (RSPCPs) had on delayed gastric emptying (DGE) and identify factors associated with DGE in a contemporary period. A single-institution, prospective database was queried for consecutive PDs during July 2011–November 2019. Using international definitions, DGE rates were compared between periods before and after RSPCPs were implemented in 2016, classifying patients according to their postoperative pancreatic fistula (POPF) risk. Risk factors were analyzed to identify modifiable targets. Among 724 elective PDs, 552 (76%) were for adenocarcinoma and 172 (24%) for other diagnoses. Of the 197 (27%) patients with DGE, 119 (16%) had type A, 41 (6%) type B, and 38 (5%) type C. In the overall cohort, DGE rates were higher with pylorus-preserving vs. classic hand-sewn reconstruction (odds ratio [OR] − 1.84; p < 0.001), postoperative abscess (OR − 2.54; p = 0.003), and non-white patients (p = 0.007), but lower after implementation of RSPCPs (OR − 0.34, p < 0.001). In the 374 patients treated with RSPCPs, only 17% (n = 65/374) developed DGE. Patients with protocol-compliant NGT removal ≤ 48 h were less likely to experience DGE (OR − 1.46, p = 0.042). Our data suggest that implementation of preoperatively assigned RSPCPs as a care bundle was the most important factor in decreasing DGE. These gains were accentuated in patients who underwent early nasogastric tube removal and had a classic hand-sewn gastro-jejunostomy reconstruction. Application of these modifiable factors is generalizable with low implementation barriers.

The role of (chemo) radiation in the perioperative management of patients with resectable and borderline resectable pancreatic ductal adenocarcinoma is controversial. Herein, we review and interpret existing data relating to the ability of (chemo) radiation to "downstage" pancreatic tumors, delay recurrence, and prolong patients' survival. In sum, the evidence suggests that while neoadjuvant (chemo) radiation may impact pathologic metrics favorably, it rarely converts anatomically unresectable tumors to resectable ones. And while data do support the ability of (chemo)radiation to delay cancer progression, its ability to prolong longevity has not been confirmed. It is possible that (chemo)radiation is effective in prolonging the survival of select patients, but to date, this cohort remains undefined due to heterogeneity in both the populations studied and the regimens used to treat them. Based on our interpretation of existing data, we currently administer neoadjuvant and adjuvant (chemo)radiation selectively to patients with localized pancreatic cancer who we consider at highest risk for local progression. We may also use it as an alternative to pancreatectomy in patients who are poor candidates for surgery. Ultimately, the role of (chemo)radiation in these settings is evolving. Better studies of patients most likely to benefit from its local effects are necessary to clearly define its place within the perioperative treatment algorithms used for patients with localized pancreatic cancer.

We previously demonstrated associations between exercise during pancreatic cancer treatment and quality of life and physical fitness prior to pancreatectomy. In this study, we quantified exercise among survivors following pancreatic tumor resection and characterized concordance with established guidelines. We quantified exercise frequency, duration, and intensity among survivors who underwent pancreatectomy for adenocarcinoma or a neuroendocrine tumor at our center from 2000 to 2017 and compared them with American College of Sports Medicine Guidelines for Cancer Survivors. Additional surveys measured motivation to exercise, barrier self-efficacy, quality of life, and fatigue. Multivariable models were constructed to evaluate associations between clinicodemographic and psychosocial variables and guideline concordance, and between guideline concordance and quality of life and fatigue. Of 504 eligible survivors, 262 (52%) returned surveys. Only 62 participants (24%) reported meeting both aerobic and strengthening guidelines; 103 (39%) reported meeting neither. Adjusted analyses demonstrated that higher autonomous motivation was associated with higher aerobic and strengthening guideline concordance (both p 0.05). We found favorable associations between aerobic guideline concordance and both quality of life and fatigue (both p

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, governmental agencies, state medical boards, and healthcare organizations have called for restricting “elective” operations to mitigate the risk of transmission of the virus amongst patients and healthcare providers and to preserve essential resources for potential regional surges of COVID patients. While the fear of delaying surgical care for many of our patients is deeply challenging for us as cancer care providers, we must balance our personal commitment to providing timely and appropriate oncologic care to our cancer patients with our societal responsibility to protect our patients (including those on whom we are operating), co-workers, trainees, families, and community, from undue risks of contracting and propagating COVID-19. Herein, we present guidelines for surgical decision-making and case prioritization developed among all adult disease specialties in the MD Anderson Cancer Center Departments of Surgical Oncology and Breast Surgical Oncology in Houston, Texas.

The critical roles of oxygen homeostasis in metabolism are indisputable and hypoxic responses are correlated with the pathogenesis of gastrointestinal, pulmonary, renal diseases and cancers. Evaluating tissue hypoxia to predict treatment outcome is challenging, however, due to the lack of rapid, accurate and non-invasive methods. Hypoxia enhances prolyl-4-hydroxylase α1 (P4HA1) expression, which can convert bradykinin (BK) to hydroxyprolyl-BK (Hyp-BK), leading us to hypothesize that circulating Hyp-BK/BK ratios may reflect tissue hypoxia and predict treatment outcomes. Direct quantification of Hyp-BK peptides in serum or plasma by conventional MALDI-TOF MS analysis is technically challenging. In our study, a nanopore-based fractionation and enrichment protocol was utilized to allow the simple workflow for circulating Hyp-BK/BK analysis. Hypoxia is linked to poor prognosis due to its role in promoting pancreatic cancer progression and metastasis. Here we show that P4HA1 expression was increased in pancreatic tumors versus adjacent tissue, associated with poor survival, and corresponded with tumor expression of the hypoxia inducible factor 1α (HIF-1α) and carbonic anhydrase 9 (CA9). Hypoxia-induced P4HA1 expression and BK conversion to Hyp-BK were found to be HIF-1α dependent, pre-treatment serum Hyp-BK/BK ratios corresponded with tissue HIF-1α and P4HA1 expression, and high Hyp-BK/BK levels corresponded with poor response to therapy. These results suggest that pre-treatment circulating Hyp-BK/BK ratios may have value as a non-invasive, surrogate indicator of tissue hypoxia and tumor responses to therapy.

Administration of dexamethasone to mitigate postoperative nausea and vomiting has been suggested to improve short- and long-term outcomes after pancreatic ductal adenocarcinoma (PDAC) resection. This study aimed primarily to evaluate these hypotheses in a contemporary patient cohort treated with multimodality therapy. The clinicopathologic and perioperative characteristics of consecutive resected PDAC patients (July 2011 to October 2018) were analyzed from a prospectively maintained database. Intraoperative administration of dexamethasone (4–10 mg) was retrospectively abstracted from the electronic medical record. The majority of 373 patients (59.8%) received intraoperative dexamethasone. Most of these patients underwent neoadjuvant therapy (75.3%), were potentially resectable at presentation (69.7%), and underwent pancreaticoduodenectomy (79.9%). Women were more likely to receive dexamethasone than men (69.9 vs 30.1%; p

The PanNET Working Group of the 16th International Multiple Endocrine Neoplasia Workshop (MEN2019) convened in Houston, TX, USA, 27–29 March 2019 to discuss key unmet clinical needs related to PanNET in the context of MEN1, with a special focus on non-functioning (nf)-PanNETs. The participants represented a broad range of medical scientists as well as representatives from patient organizations, pharmaceutical industry and research societies. In a case-based approach, participants addressed early detection, surveillance, prognostic factors and management of localized and advanced disease. For each topic, after a review of current evidence, key unmet clinical needs and future research directives to make meaningful progress for MEN1 patients with nf-PanNETs were identified. International multi-institutional collaboration is needed for adequately sized studies and validation of findings in independent datasets. Collaboration between basic, translational and clinical scientists is paramount to establishing a translational science approach. In addition, bringing clinicians, scientists and patients together improves the prioritization of research goals, assures a patient-centered approach and maximizes patient involvement. It was concluded that collaboration, research infrastructure, methodologic and reporting rigor are essential to any translational science effort. The highest priority for nf-PanNETs in MEN1 syndrome are (1) the development of a data and biospecimen collection architecture that is uniform across all MEN1 centers, (2) unified strategies for diagnosis and follow-up of incident and prevalent nf-PanNETs, (3) non-invasive detection of individual nf-PanNETs that have an increased risk of metastasis, (4) chemoprevention clinical trials driven by basic research studies and (5) therapeutic targets for advanced disease based on biologically plausible mechanisms.

Background The objective of this study was to assess current perceptions surrounding opioid prescribing in surgical oncology to inform perioperative quality improvement initiatives. Methods After the Society of Surgical Oncology (SSO) approval, a survey was distributed to its membership. Five sample procedures were used to assess provider perceptions and prescribing habits. Data were summarized and compared by self-reported demographics. Results One hundred and seventy-five participants completed the survey: 149 (85%) faculty, 24 (14%) trainees, and 2 (1%) advanced practice providers. Most participants (76%) practiced in academic programs and 21% practiced in non-US locations. Few differences were identified based on clinical role, academic rank, or practice years. Compared with non-US providers, US providers expected higher pain scores at discharge, recommended greater opioid prescriptions, and estimated more days of opioid use for almost every procedure. More non-US providers believed discharge opioids should not be distributed to patients who are opioid-free in their last 24 inpatient hours (80% vs 50%, P = .001). All providers ranked education as "very important" for reducing opioid prescriptions. Conclusions Compared with their international counterparts, US surgical oncology providers expected greater opioid needs and recommended higher prescription numbers. Educating providers on multimodal opioid-sparing bundles, accelerated weaning protocols, and standardized discharge prescribing habits could have a positive impact the US opioid epidemic.

Introduction Short-term outcomes after distal pancreatectomy (DP) for retroperitoneal (RP) tumors are unknown. We sought to identify rates of postoperative pancreatic fistula (POPF) and morbidity after en bloc DP with RP tumor resection. Methods A retrospective review of 43 patients who underwent DP with RP tumor resection (1/2011–12/2017) was performed. Results Seventeen patients had RP sarcoma, 12 renal cell carcinoma, 11 gastrointestinal stromal tumor, and 3 adrenocortical carcinoma. Grade III-IV complications occurred in 7 patients. Grade B POPF occurred in 14 patients, grade C POPF in none, and biochemical leak in 6. Of 22 patients who developed radiographically evident peri-pancreatic fluid collections, 7 required percutaneous drainage. The 90-day readmission rate was 33%. Conclusions DP with RP tumor resection is associated with high rates of clinically relevant POPF compared to historical results for DP for primary pancreatic tumors. Multi-center studies to identify targetable predictors and risk mitigation strategies for POPF in this rare high-risk population are needed.

Objective To summarize the multi-specialty strategy and initial guidelines of a Case Review Committee in triaging oncologic surgery procedures in a large Comprehensive Cancer Center and to outline current steps moving forward after the initial wave. Summary of background data The impetus for strategic rescheduling of operations is multifactorial and includes our societal responsibility to minimize COVID-19 exposure risk and propagation among patients, the healthcare workforce, and our community at large. Strategic rescheduling is also driven by the need to preserve limited resources. As many states have already or are considering to re-open and relax stay-at-home orders, there remains a continued need for careful surgical scheduling because we must face the reality that we will need to co-exist with COVID-19 for months, if not years. Methods The quality officers, chairs, and leadership of the 9 surgical departments in our Division of Surgery provide specialty-specific approaches to appropriately triage patients. Results We present the strategic approach for surgical rescheduling during and immediately after the COVID-19 first wave for the 9 departments in the Division of Surgery at The University of Texas MD Anderson Cancer Center in Houston, Texas. Conclusions Cancer surgeons should continue to use their oncologic knowledge to determine the window of opportunity for each surgical procedure, based on tumor biology, preoperative treatment sequencing, and response to systemic therapy, to safely guide patients through this cautious recovery phase.

Background The incidence and magnitude of indicators of radiographic response of pancreatic cancer to systemic chemotherapy and (chemo)radiation administered prior to anticipated pancreatectomy are unclear. Methods Sequential computed tomography scans of 226 patients with localized pancreatic cancer who received chemotherapy consisting of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) or gemcitabine and nanoparticle albumin-bound paclitaxel (GA) with or without (chemo)radiation and who subsequently underwent surgery with curative intent from January 2010 to December 2018 at The University of Texas MD Anderson Cancer Center and Verona University Hospital were re-reviewed and compared. Results Overall, 141 patients (62%) received FOLFIRINOX, 70 (31%) received GA, and 15 (7%) received both; 164 patients (73%) received preoperative (chemo)radiation following chemotherapy and prior to surgery; and 151 (67%), 70 (31%), and 5 (2%) patients had Response Evaluation Criteria in Solid Tumors (RECIST) stable disease, partial response, and progressive disease, respectively. The tumors of 29% of patients with borderline resectable or locally advanced cancer were downstaged after preoperative therapy. Radiographic downstaging was more common with chemotherapy than with (chemo)radiation (24% vs. 6%; p = 0.04), and the median tumor volume loss after chemotherapy was significantly greater than that after (chemo)radiation (28% vs. 17%; p Conclusions Less than one-third of patients treated with FOLFIRINOX or GA with or without (chemo)radiation experienced either RECIST partial response or radiographic downstaging prior to surgery. The incidence of tumor downstaging was higher and the magnitude of tumor volume loss was greater following chemotherapy than after (chemo)radiation.

PURPOSE The combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has provided clinically meaningful improvement for pancreatic ductal adenocarcinoma (PDAC). We previously uncovered a role for the serine hydrolase carboxylesterase 2 (CES2) in mediating intratumoral activation of the prodrug irinotecan, a constituent of FOLFIRINOX. We aimed to further test the predictive value of CES2 for response to irinotecan using patient-derived xenograft (PDX) models and to elucidate the determinants of CES2 expression and response to FOLFIRINOX treatment among patients with PDAC. METHODS PDXs were engrafted subcutaneously into nude mice and treated for 4 weeks with either saline control or irinotecan. CES2 and hepatocyte nuclear factor 4 alpha (HNF4A) expression in PDAC tissues was evaluated by immunohistochemical and Western blot analysis. Kaplan-Meier and Cox regression analyses were applied to assess the association between overall survival and hemoglobin A1C (HbA1C) levels in patients who underwent neoadjuvant FOLFIRINOX treatment. RESULTS High CES2 activity in PDAC PDXs was associated with increased sensitivity to irinotecan. Integrated gene expression, proteomic analyses, and in vitro genetic experiments revealed that nuclear receptor HNF4A, which is upregulated in diabetes, is the upstream transcriptional regulator of CES2 expression. Elevated CES2 protein expression in PDAC tissues was positively associated with a history of type 2 diabetes (odds ratio, 4.84; P = .02). High HbA1C levels were associated with longer overall survival in patients who received neoadjuvant FOLFIRINOX treatment ( P = .04). CONCLUSION To our knowledge, we provide, for the first time, evidence that CES2 expression is associated with a history of type 2 diabetes in PDAC and that elevated HbA1C, by predicting tumor CES2 expression, may represent a novel marker for stratifying patients most likely to respond to FOLFIRINOX therapy.

As inpatient stays become shorter, one concern with standardizing discharge opioid prescriptions is the potential risk of "rebound refills." We sought to compare opioid prescription refill rates and volumes for surgical patients discharged on postoperative day (POD) 2-3, 4-7, and 8+.In a prospective quality improvement protocol, faculty volunteered to use either a 5x-multiplier (5x) or usual care (UC) for discharge prescriptions after inpatient (≥48 h stay) surgery from Sep-Dec 2019. The 5x-multiplier is 5-times the patient's last 24-h opioid use (by oral morphine equivalents, OME). Cohorts were compared by POD of discharge: POD 2-3 ("SHORT"), POD 4-7 ("INTERMEDIATE"), and POD 8+ ("LONG"). The primary endpoint was 30-d refill rates. Secondary endpoints included 30-d refill OME and inpatient opioid weaning/discharge metrics.From 22 faculty, 409 patients were included. When stratified by POD, 154 (37.7%) were discharged SHORT, 176 (43.0%) INTERMEDIATE, and 79 (19.3%) LONG. SHORT stay patients had a median last 24-h OME of 10 mg (versus 5 mg INTERMEDIATE, 5 mg LONG; P = 0.268), and a median discharge OME of 55 mg (versus 75 mg INTERMEDIATE, 100 mg LONG; P = 0.221). Patients with SHORT stays did not have higher refill rates (11.7% versus 18.2% INTERMEDIATE, 19.0% LONG; P = 0.193) or higher median refill OME (150 mg versus 300 mg INTERMEDAITE, 339 mg LONG; P = 0.154).Despite concerns of increased refills, patients discharged by POD 2-3 were not associated with "rebound refills." A patient-centered 5x-multiplier standardization of discharge opioid prescriptions is feasible in all inpatient surgery patients, even those discharged following a short inpatient stay.

Purpose Patients with pancreatic cancer often receive radiation therapy before undergoing surgical resection. We compared the clinical outcomes differences between stereotactic body radiation therapy (SBRT) and 3-dimensional (3D)/intensity-modulated radiation therapy (IMRT). Methods and Materials We retrospectively collected data from the University of Texas MD Anderson Cancer Center. Patients with borderline resectable/potentially resectable or locally advanced pancreatic cancer receiving neoadjuvant SBRT (median, 36.0 Gy/5fx), 3D conformal radiation (median, 50.4 Gy/28 fx) or IMRT (median, 50.4 Gy/28 fx) were included. Overall survival (OS) and progression-free survival were analyzed using Cox regression. Results In total, 104 patients were included in our study. Fifty-seven patients (54.8%) were treated with SBRT, and 47 patients (45.2%) were treated with 3D/IMRT. Patients in the SBRT group were slightly older (median age: 70.3 vs 62.7 in the 3D/IMRT group). Both groups had similar proportions of patients with locally advanced pancreatic cancer (SBRT: 30, 52.6%; 3D/IMRT: 24, 51.1%). All patients were treated with chemotherapy. Patients in the SBRT group underwent more surgical resection compared with the 3D/IMRT group (38.6% vs 23.4%, respectively). At a median follow-up of 22 months, a total of 60 patients (57.7%) died: 25 (25/57, 43.9%) in the SBRT group, and 35 (35/47, 74.5%) in the 3D/IMRT group. Median OS was slightly higher in the SBRT group (29.6 months vs 24.1 months in the 3D/IMRT group). On multivariable Cox regression, the choice of radiation therapy technique was not associated with differences in OS (adjusted hazard ratios [aHR] = 0.5; 95% confidence interval [CI], 0.2%-1.3%, P = .18). Moreover, patients that underwent surgical resection had better OS (aHR = 0.3, 95% CI, 0.1%-0.8%, P = .01). Furthermore, progression-free survival was also similar between patients treated with SBRT and those treated with 3D/IMRT (aHR = 0.9, 95% CI, 0.5%-1.8%, P = .81) Conclusions SBRT was associated with similar clinical outcomes compared with conventional radiation techniques, despite being delivered over a shorter period of time which would spare patients prolonged treatment burden. Future prospective data are still needed to better assess the role of SBRT in patients with pancreatic cancer.

Simple Summary Renal medullary carcinoma (RMC) is a rare but highly aggressive malignancy that affects individuals of African descent with sickle cell trait (SCT). The driver of RMC pathogenesis is thought to be renal medullary ischemia from red blood cell sickling in the setting of SCT. Currently, no modifiable risk factors for RMC have been identified that explain why certain individuals with SCT develop RMC. Prior studies have demonstrated that high-intensity exercise increases adverse events related to red blood cell sickling. We hypothesized that high-intensity exercise may increase the risk of RMC. We used multiple sources of evidence including retrospective and prospective review of RMC patient exercise activity, objective measurements of skeletal muscle surface area, and measurement of hypoxia levels in the renal medulla of mice with SCT following high or moderate-intensity exercise. Our results suggest that high but not moderate-intensity exercise may be associated with the development of RMC among individuals with SCT. Abstract Renal medullary carcinoma (RMC) is a lethal malignancy affecting individuals with sickle hemoglobinopathies. Currently, no modifiable risk factors are known. We aimed to determine whether high-intensity exercise is a risk factor for RMC in individuals with sickle cell trait (SCT). We used multiple approaches to triangulate our conclusion. First, a case-control study was conducted at a single tertiary-care facility. Consecutive patients with RMC were compared to matched controls with similarly advanced genitourinary malignancies in a 1:2 ratio and compared on rates of physical activity and anthropometric measures, including skeletal muscle surface area. Next, we compared the rate of military service among our RMC patients to a similarly aged population of black individuals with SCT in the U.S. Further, we used genetically engineered mouse models of SCT to study the impact of exercise on renal medullary hypoxia. Compared with matched controls, patients with RMC reported higher physical activity and had higher skeletal muscle surface area. A higher proportion of patients with RMC reported military service than expected compared to the similarly-aged population of black individuals with SCT. When exposed to high-intensity exercise, mice with SCT demonstrated significantly higher renal medulla hypoxia compared to wild-type controls. These data suggest high-intensity exercise is the first modifiable risk factor for RMC in individuals with SCT.

Surgeon-led clinical trials have defined the standard of care for locoregional pancreatic cancer to date. The infrastructure and collaborative nature of cooperative oncology groups offer many advantages, such as providing an ideal mechanism through which multidisciplinary pancreatic cancer trials are performed. As key members of the treatment team, surgeons bring experience and expertise to the design of surgical and multidisciplinary trials and are uniquely poised to be leaders of future pancreatic cancer trials.

Aerobic exercise is associated with decreased cancer incidence and cancer-associated mortality. However, little is known about the effects of exercise on pancreatic ductal adenocarcinoma (PDA), a disease for which current therapeutic options are limited. Herein, we show that aerobic exercise reduces PDA tumor growth, by modulating systemic and intra-tumoral immunity. Mechanistically, exercise promotes immune mobilization and accumulation of tumor-infiltrating IL15Rα

To explore whether body composition and/or sarcopenia are associated with liver hypertrophy following portal vein embolization (PVE) in patients with colorectal liver metastases (CLM). Patients with CLM who underwent right PVE prior to a planned right hepatectomy were identified from the institutional liver database from 2004 to 2014. Patients were excluded due to previous liver-directed therapy/hepatectomy, right PVE + segment IV embolization, or planned 2-stage hepatectomy. Advanced imaging software was used to measure body compartment volumes (cm2), which were standardized to height (m2) to create an index: skeletal muscle index (SMI), subcutaneous adipose index (SAI), and visceral adipose index (VAI). SMI, gender, and body mass index (BMI) were used to define sarcopenia. The main outcome of interest was hypertrophy of the future liver remnant (FLR) following PVE, which was reported as degree of hypertrophy (DH) and kinetic growth rate (KGR). Patients were evenly divided into three KGR groups: lower third (KGR:0.7–2.0%), middle third (KGR:2.0–4.1%), and upper third (KGR:4.2–12.3%). Patients in the lower third KGR group had a lower VAI (31.0 vs 53.0 vs 54.5 cm2/m2, p = 0.042) and were more commonly sarcopenic (60%) compared to the upper third (20%, p = 0.025). Eighteen patients (40%) met criteria for sarcopenia. Sarcopenic patients had a lower VAI (29.1 vs 57.4 cm2/m2, p = 0.004), lesser degree of hypertrophy (8.3% vs 15.2%, p = 0.009), and lower KGR (2.0% vs 4.0%, p = 0.012). Sarcopenia and associated body composition indices are strongly associated with clinically relevant impaired liver regeneration, which may result in increased liver-specific complications following hepatectomy for CLM.