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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.

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.

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

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.

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.

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.

Objective We sought to determine whether postoperative chemotherapy after preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) prolongs survival. Background Data to support administering postoperative chemotherapy to patients who received preoperative therapy are lacking. Methods All patients with PDAC who underwent pancreatectomy after preoperative therapy between 2010 and July 2017 at The University of Texas MD Anderson Cancer Center were identified. To control for selection bias, patients who received postoperative therapy and patients who did not were matched by propensity scores based on factors associated with the use of postoperative chemotherapy. Results Among 245 patients treated with a median of 4 cycles of preoperative treatment and pancreatectomy, 155 (63%) initiated postoperative chemotherapy and 90 (37%) did not. Patients who received postoperative therapy had a higher median cancer antigen 19-9 level before surgery, larger median tumor diameter, higher rate of extrapancreatic invasion, and lower rate of pathologic major response. The propensity-matched cohort comprised 122 patients: 61 who received postoperative chemotherapy and 61 who did not. The median overall survival (OS) and recurrence free survival (RFS) for patients who received postoperative therapy were 42 and 17 months, respectively, versus 32 and 12 months for patients who did not (OS: P = 0.06; RFS: P = 0.04). Postoperative therapy was marginally associated with a longer OS (hazard ratio 0.55, 95% confidence interval 0.29-1.01; P = 0.05) and significantly associated with a longer RFS (hazard ratio 0.55, 95% confidence interval 0.29-0.96; P = 0.04). Conclusions Despite being administered more frequently to patients with poor prognostic factors, postoperative chemotherapy after preoperative therapy and pancreatectomy for PDAC was of clinical benefit.

PURPOSE Effective preoperative regimens and biomarkers for pancreatic ductal adenocarcinoma (PDAC) are lacking. We prospectively evaluated fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX)-based treatment and imaging-based biomarkers for borderline resectable PDAC. METHODS Eligible patients had treatment-naïve, histology-confirmed PDAC and one or more high-risk features: mesenteric vessel involvement, CA 19-9 level of 500 mg/dL or greater, and indeterminate metastatic lesions. Patients received modified FOLFIRINOX and chemoradiation before anticipated pancreatectomy. Tumors were classified on baseline computed tomography as high delta (well-defined interface with parenchyma) or low delta (ill-defined interface). We designated computed tomography interface response after therapy as type I (remained or became well defined) or type II (became ill defined). The study had 80% power to differentiate a 60% from 40% resection rate (α = .10). Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and subgroups were compared using log-rank tests. RESULTS Thirty-three patients initiated therapy; 45% underwent pancreatectomy. The median OS was 24 months (95% CI, 16.2 to 29.6 months). For patients who did and did not undergo pancreatectomy, the median OS was 42 months (95% CI, 17.7 months to not estimable) and 14 months (95% CI, 9.0 to 24.8 months), respectively. Patients with high-delta tumors had lower 3-year PFS (4% v 40%) and 3-year OS rates (20% v 60%) than those with low-delta tumors (both P < .05). Patients with type II interface responses had lower 3-year PFS (0% v 29%) and 3-year OS rates (16% v 47%) than those with type I responses (both P < .001). CONCLUSION Preoperative FOLFIRINOX followed by chemoradiation for high-risk borderline resectable PDAC was associated with a resection rate of 45% and median OS of approximately 2 years. Our imaging-based biomarker validation indicates that personalized treatment may be achieved using these biomarkers at baseline and post-treatment.

OBJECTIVE: We sought to identify potential radiologic and serologic markers of pancreatic tumor response to therapy, using pathologic major response (pMR) as the objective endpoint. BACKGROUND: We previously demonstrated that a pMR to preoperative therapy, defined as detection of

OBJECTIVES: Neoadjuvant therapy (NT) is used for advanced pancreatic ductal adenocarcinoma (PDAC). No clear guidelines exist for switching therapies when patients do not respond to initial NT. We sought to characterize patients who underwent early switch from FOLFIRINOX to gemcitabine/nab-paclitaxel (GA) as NT for PDAC. METHODS: We identified patients at a single institution switched from FFX to GA within the first 4 months of NT for PDAC during 2012–2017. We compared clinicopathologic data and oncologic outcomes. RESULTS: Of 25 patients who met criteria, 21 showed a serologic or radiographic response to GA; 11 (52%) reached resection. Responders had decreased carbohydrate antigen (CA) 19-9 levels from pre-treatment to post-GA (P = 0.036). Resected responders had significantly decreased CA 19-9 comparing pre-switch to post-GA (P = 0.048). The only predictor of GA response was pre-chemotherapy CA 19-9

Background With the increasing use of biliary stents for neoadjuvant therapy (NT) for pancreatic adenocarcinoma (PDAC), the risk of post-pancreaticoduodenectomy (PD) infection remains relevant. This study documents the contemporary incidence of stent-related complications (SRC) during NT and to analyze their impact on surgical infections. Methods Consecutive patients from a single institution (2011–15) with resected PDAC treated with biliary decompression, NT, and PD were analyzed. Stent-related complications (SRC) were compared among patients with/without prospectively documented composite pre- and post-operative infections (surgical site infection [SSI], organ space infection [OSI], and cholangitis). Results Of 114 total patients, (median 164 days, initial stent to surgery), 95% had initial endoscopic (vs. percutaneous) stenting. Initial stents were often plastic (80/114, 70%), with 43/114 (38%) undergoing routine exchange to metal stent before NT. Fifteen (13%) patients had stent cholangitis during NT requiring antibiotics and/or stent exchange. There were 33/114 (29%) patients with SRC, requiring 66 exchanges. Post-PD rates of SSI, OSI, and cholangitis were 23%, 5%, and 4%, respectively [composite rate 30%]. On multivariate analysis, SRC were not associated with composite surgical infections (p > 0.05). Conclusions Although SRC occurred in almost one-third of PDAC patients during NT, with appropriate intervention, there was no association with increased surgical infections.

BackgroundGlucose-regulated protein 78 (GRP78) plays an essential role in protein folding, transportation, and degradation, thus regulates ER homeostasis and promotes cell survival, proliferation and invasion. GRP78 expression in PDAC patients who received neoadjuvant therapy has not been reported.MethodsThis retrospective study of resected PDAC patients included 125 patients treated with neoadjuvant therapy (NAT) and 140 patients treated with surgery first (SF). The expression of GRP78 was evaluated by immunohistochemistry on tissue microarrays and the results were correlated with clinicopathologic parameters and survival.ResultsGRP78 expression was higher in SF patients compared to NAT patients (P&nbsp

BACKGROUND: CD73, a newly recognized immune checkpoint mediator, is expressed in several types of malignancies. However, CD73 expression and its impact on tumor microenvironment and clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) remain unclear. METHODS: This study included two cohorts: 138 patients from our institution (MDA) and 176 patients from TCGA dataset. CD73 expression, CD4+, CD8+, CD21+ and CD45RO+ tumor infiltrating lymphocytes (TILs) were evaluated by immunohistochemistry using tissue microarrays. The results of CD73 expression were correlated with clinicopathologic parameters, survival and TILs. RESULTS: CD73 overexpression correlated with poorly differentiation (P = 0.002) and tumor size (P = 0.049). For CD73-low group, median overall survival (OS) and recurrence-free survival (RFS) were 26.9 ± 3.8 months and 12.6 ± 2.6 months, respectively, compared to 16.9 ± 4.4 months (P = 0.01) and 7.9 ± 1.2 months (P = 0.01), respectively, in CD73-high group. CD73 was an independent predictor for both RFS (P = 0.015) and OS (P = 0.01) by multivariate variate analysis. Similarly, CD73-high tumors had significantly shorter OS than CD73-low tumors in TCGA dataset (P < 0.0001). CD73-high correlated with decreased CD4+ TILs in MDA cohort and decreased CD8A and CR2 (CD21) expression in TCGA cohort. CONCLUSIONS: CD73 overexpression is associated with poor differentiation, tumor size, and shorter survival, and is an independent prognostic factor in PDAC patients. CD73 overexpression is associated with decreased CD4+, CD8+ and CD21+ TILs. Our data support that CD73 plays an important role in immunosuppressive tumor microenvironment and promote tumor progression in PDAC.

Patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) should receive preoperative chemotherapy with or without radiation therapy, with the intent to eradicate occult metastatic cancer cells, to select patients with a "locally dominant cancer phenotype" for whom local therapies might be most effective, and to reduce the anatomic extent of tumors to facilitate surgical resection. The administration of preoperative therapy may also be a useful strategy to deliver the maximum load of chemotherapy to patients with BR PDAC, since as many as half of patients will never qualify for adjuvant treatments following pancreatectomy due to postoperative morbidity or disease progression. Patients with BR PDAC should be categorized at diagnosis on the basis of anatomical, biological, and conditional criteria and should be offered induction systemic chemotherapy with close monitoring for toxicity, followed by administration of (chemo)radiation in selected cases. Patients should be restaged after systemic therapy and, if used, (chemo)radiation. Patients who continue to show disease response or disease stability without signs of progression should be considered for pancreatectomy; better measures of response to therapy are needed.

IMPORTANCE: Fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and gemcitabine plus nanoparticle albumin-bound (nab)–paclitaxel (GA) are first-line chemotherapy regimens for pancreatic cancer. Their relative efficacy in the setting of localized disease is unknown. OBJECTIVE: To evaluate radiographic and serologic measures of responses associated with first-line chemotherapy with FOLFIRINOX or GA, and to determine the association between these drug regimens, putative measures of response, and survival. DESIGN, SETTING, AND PARTICIPANTS: This case series assessed 485 consecutive patients who were diagnosed as having previously untreated localized pancreatic ductal adenocarcinoma at The University of Texas MD Anderson Cancer Center between January 1, 2010, and December 31, 2017, and who received at least 3 cycles of first-line chemotherapy with FOLFIRINOX or GA. The median (range) follow-up duration was 33 (2-28) months. EXPOSURES: Administration of FOLFIRINOX (285 patients [59%]) or GA (200 patients [41%]) as first-line chemotherapy. MAIN OUTCOMES AND MEASURES: Resection rate, radiographic metrics (Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1, and change in tumor volume or anatomic staging), a serologic metric (serum cancer antigen 19-9 level), and overall survival after administration of first-line chemotherapy. RESULTS: In total, 485 patients (266 [55%] male) were included in the analysis. Patients treated with FOLFIRINOX were generally younger (median [range] age at diagnosis: 61 [30-81] vs 71 [36-89] years; P = .001) and had better performance status as indicated by the Eastern Cooperative Oncology Group scale (range 0-4, with lower numbers representing better performance) score of 2 or lower (274 patients [96%] vs 165 patients [82%] P = .001) but more invasive tumors than patients who received GA (91 [32%] vs 90 [45%] resectable tumors; P = .01). After propensity score matching to control for these biases, many objective serologic and radiographic metrics of response associated with administration of FOLFIRINOX or GA—including low rates of local tumor downstaging—did not differ. However, RECIST partial response was more common among patients treated with FOLFIRINOX (27 of 140 patients [19%]) than with GA (8 of 140 patients [6%]; P = .001). Moreover, (chemo)radiation (50% vs 34%; P = .001) was more commonly administered to and pancreatectomy (27% vs 16%; P = .01) was subsequently performed more frequently for patients initially treated with FOLFIRINOX. The overall survival duration of patients treated with either regimen was similar (hazard ratio, 1.48; 95% CI, 0.97-2.26; P = .07). CONCLUSIONS AND RELEVANCE: In this cohort of patients with localized pancreatic adenocarcinoma who received FOLFIRINOX or GA as their first line of therapy, FOLFIRINOX was associated with higher rates of RECIST partial response and subsequent pancreatectomy than GA, but the overall survival associated with these regimens was similar.

Evaluation of response to preoperative therapy for patients with pancreatic adenocarcinoma has been historically difficult. Therefore, preoperative regimens have generally been selected on the basis of baseline data such as radiographic stage and serum CA 19-9 level and then typically administered for a pre-specified duration as long as 6 months or more. The decision to proceed with resection following preoperative therapy likewise has rested upon the absence of disease progression rather than evidence for tumor response. This article reviews the basis for the evaluation of therapeutic response after preoperative therapy for pancreatic cancer in the existing scientific literature, and providing updates and new perspectives.

Preoperative chemotherapy provides early treatment of micro-metastases and guaranteed delivery of all components of multimodality therapy for localized pancreatic ductal adenocarcinoma (PDAC). For locally advanced (LA) PDAC, induction chemotherapy is the standard of care. This study evaluated the use of gemcitabine and nab-paclitaxel (Gem/nab-P) as first-line therapy for localized PDAC. Clinicopathologic features, treatment, and outcomes were evaluated for 99 patients with localized PDAC. The patients were staged using previously published criteria as follows: potentially resectable (PR), borderline type A (BR-A) (anatomy amenable to vascular resection), BR-B (biology suspicious for metastatic disease including high CA19-9), BR–C (comorbidities requiring medical optimization), and LA. The 99 patients (PR/BR/LA: 45/14/40) were treated with Gem/nab-P. Clinical staging showed that 20 patients had PR or BR-A disease, whereas 39 patients had BR-B or BR-C disease. The BR-B+C cases included one or more of the following: age of 80 years or older (13%), Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 or more (13%), moderate to severe comorbidities (55%), CA19-9 of 1000 or higher (28%), and suspicion for metastases (21%). The majority of the patients received biweekly Gem/nab-P dosing, which was well tolerated. Pancreatectomy was performed for 12 (60%) of 20 patients with PR+BR-A, 2 (5%) of 39 patients with BR-B+C, and 1 (3%) of 40 patients with LA disease. During a median follow-up period of 26 months, the median overall survival (OS) period was 18 months (95% confidence interval [CI], 15.6–20.5 months) for all the patients, 17 months (95% CI, 14.6–19.5 months) for the unresected patients, and not reached for the resected patients (p = 0.028 for resected vs unresected patients). A significant number of patients with radiographically resectable PDAC albeit aggressive biology (BR-B), medically inoperable conditions (BR-C), or both received biweekly first-line Gem/nab-P. The resection rates were lower for the BR-B/BR-C patients than for the PR/BR-A patients (hazard ratio [HR], 0.43; 95% CI, 0.19–1.00; p = 0.05).

BACKGROUND AND OBJECTIVES Venous patency rates after pancreaticoduodenectomy (PD) with portal vein (PV) resection are not well established, and the oncologic impact of portal vein thrombosis (PVT) is unknown. The primary aim of this study was to determine rates and predictors of PVT after PD with PV resection for pancreatic adenocarcinoma (PDAC). METHODS A retrospective cohort study was performed on PDAC patients treated with preoperative therapy and PD with PV resection at a high-volume institution (2008-15). Primary outcomes were early and late PVT (≤ or >90 days of surgery). Secondary outcomes included major complications and OS. RESULTS Patients undergoing vein resection (N = 120) included 41.7% (N = 50) primary repair or patch venoplasty, 29.2% (N = 35) primary anastomosis, and 29.2% (N = 35) interposition graft. Thirty-four (28.3%) patients developed PVT (early 7.5% [N = 9]; late 20.8% [N = 25]). Late PVT was often detected concurrently with local recurrence (76.0%; N = 19). There was no association of PVT with vascular resection extent or complications (P > 0.05). On multivariable analysis, PVT was associated with worse OS (HR 2.2 [95% CI 1.34-3.5], P

The changes in body composition that occur in response to therapy for localized pancreatic ductal adenocarcinoma (PDAC) and during the early survivorship period, as well as their clinical significance, are poorly understood. One hundred twenty-seven consecutive patients with PDAC who received preoperative therapy followed by pancreatoduodenectomy (PD) at a single institution between 2009 and 2012 were longitudinally evaluated. Changes in skeletal muscle (SKM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured on serial computed tomography images obtained upon presentation, prior to pancreatectomy, and approximately 3 and 12 months after surgery. Prior to therapy, patients’ mean baseline BMI was 26.5 ± 4.7 kg/m2 and 63.0% met radiographic criteria for sarcopenia. During a mean 5.4 ± 2.3 months of preoperative therapy, minimal changes in SKM (− 0.5 ± 7.8%, p > 0.05), VAT (− 1.8 ± 62.6%, p

PURPOSE OF REVIEW Pancreatic neuroendocrine tumors (pNETs) are a rare, heterogeneous group of pancreatic neoplasms with a wide range of malignant potential. They may manifest as noninfiltrative, slow-growing tumors, locally invasive masses, or even swiftly metastasizing cancers. RECENT FINDINGS In recent years, because of the increasing amount of scientific literature available for pNETs, the classification, prognostic stratification criteria, and available consensus guidelines for diagnosis and therapy have been revised and updated. SUMMARY The vast majority of new pNET diagnoses consist of incidentally discovered lesions on cross-sectional imaging. The biologic behavior of pNETs is defined by the grade and stage of the tumor. Surgery is the only curative treatment and it, therefore, represents the first therapeutic choice for any localized pNET; however, recent evidence suggests that patients with small (

Although preoperative therapy is increasingly administered to patients with pancreatic adenocarcinoma, the role of preoperative therapy for patients with adenocarcinoma of the ampulla of Vater is undefined. All patients with ampullary cancer who were evaluated between 1999 and 2014 were retrospectively reviewed. Differences in clinicopathologic characteristics, perioperative complications, and overall survival were compared between patients who underwent surgery de novo and those who received preoperative therapy before pancreatoduodenectomy. A total of 142 patients underwent pancreatoduodenectomy: 43 (30.3%) who received preoperative therapy and 99 (69.7%) who did not. Preoperative therapy consisted of chemoradiation (65%), chemotherapy (7%), or both (28%). Patients who underwent surgery first had a lower comorbidity index (p

In a randomized trial, pasireotide significantly decreased the incidence and severity of postoperative pancreatic fistula (POPF). Subsequent analyses concluded that its routine use is cost-effective. We hypothesized that selective administration of the drug to patients at high risk for POPF would be more cost-effective. Consecutive patients who did not receive pasireotide and underwent pancreatoduodenectomy (PD) or distal pancreatectomy (DP) between July 2011 and January 2014 were distributed into groups based on their risk of POPF using a multivariate recursive partitioning regression tree analysis (RPA) of preoperative clinical factors. The costs of treating hypothetical patients in each risk group were then computed based upon actual institutional hospital costs and previously published relative risk values associated with pasireotide. Among 315 patients who underwent pancreatectomy, grade B/C POPF occurred in 64 (20%). RPA allocated patients who underwent PD into four groups with a risk for grade B/C POPF of 0, 10, 29, or 60% (P

5-Fluorouracil, doxorubicin, and streptozocin (FAS) leads to a 39 % response rate in advanced pancreatic neuroendocrine tumors (pNETs). We sought to validate our hypothesis that preoperative FAS may facilitate resection of locoregionally advanced pNETs by reducing the anatomic extent of the primary tumor. All patients who received FAS between 2000 and 2012 as initial therapy for a localized pNET were reviewed. Tumor size and vascular relationships were compared on pretreatment and posttreatment imaging studies to quantify treatment response. Twenty-nine patients received a median 4 cycles of FAS (range 2–15). Rates of RECIST progressive disease (PD), stable disease (SD), and partial response (PR) were 3, 90, and 7 %, respectively. An interface was observed between the tumor and a major mesenteric artery and/or vein in 19 (66 %) and 24 (83 %) patients, respectively; after therapy with FAS, 17 (59 %) and 22 (76 %) had persistent interface with artery and/or vein. Fourteen (48 %) patients underwent pancreatectomy, 7 (50 %) required vascular management, and 9 (64 %) operations were R0. The median overall survival of unresected and resected patients was 41 months (95 % CI, 16–66) and 112 months (95 % CI, 104–120) (P = 0.04). Although patients receiving FAS for locoregionally advanced pNETs are unlikely to progress during systemic therapy, significant “downstaging” appears uncommon.

BACKGROUND Previous studies have suggested that preoperative chemoradiation (CRT) is associated with an improved margin-negative resection rate among patients who undergo pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). However, the optimal preoperative regimen has not been established. METHODS All patients with PDAC who received chemotherapy and/or CRT followed by PD between 1999 and 2014 were retrospectively reviewed. The effects of 2 external-beam radiation regimens-a standard course of 50.4 Gy in 28 fractions and a hypofractionated course of 30 Gy in 10 fractions-were compared. Differences in clinicopathologic characteristics, locoregional recurrence (LR), and overall survival (OS) were assessed. RESULTS Among 472 patients who received preoperative therapy, 224 (47.5%) received 30 Gy, 221 (46.8%) received 50.4 Gy, and 27 (5.7%) received chemotherapy alone. Patients who received 50.4 Gy were more likely to have advanced-stage disease and to have received induction and postoperative chemotherapy, but there was no difference in the R1 margin status, treatment effect, LR, or OS between the 2 radiation groups (all P values > .05). Patients who received preoperative CRT had a lower rate of LR than patients who received preoperative chemotherapy alone (P < .01). In a multivariate Cox proportional hazards analysis, 50.4 Gy was associated with OS and LR similar to those associated with 30 Gy, whereas the absence of preoperative radiation was associated with a higher rate of LR (odds ratio, 2.21; 95% confidence interval, 1.04-4.70) and similar OS. CONCLUSIONS Preoperative hypofractionated CRT was associated with similar local control and OS in comparison with standard CRT in patients undergoing PD for PDAC. The use of chemotherapy alone without CRT was associated with poorer local control but similar survival. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2671-2679. © 2016 American Cancer Society.

Loss of skeletal muscle and inferior muscle quality are associated with poor prognosis in patients undergoing preoperative treatment for pancreatic cancer, so maintaining skeletal muscle health before surgery may help accelerate patients’ functional recovery and improve their quality of life following surgery. While exercise helps maintain or increase skeletal muscle in individuals undergoing cancer treatment, its efficacy during pancreatic cancer treatment is unclear. Accordingly, in this study we compared changes in skeletal muscle quantity (skeletal muscle index [SMI]) and quality (skeletal muscle density [SMD]) during preoperative pancreatic cancer treatment in participants in a home-based exercise program (EP) and a historical cohort of patients who received the usual care (UC) with no formal exercise programming. Recommendations for the EP cohort included both aerobic and resistance exercise. We assessed changes in SMI and SMD using computed tomography scans administered at treatment planning (T0, prior to EP enrollment) and preoperative restaging (T1) for 33 EP and 64 UC patients and compared changes between groups. The UC patients had statistically significant SMI decreases from T0 to T1 (−1.4 ± 3.8 cm2/m2; p = .005), while the EP patients did not (0.2 ± 3.2 cm2/m2; p = .7). The SMI loss was significantly worse for the UC than for the EP patients ( p = .03). Neither group demonstrated statistically significant changes in SMD from T0 to T1, nor did the groups differ in the amount of change in SMD. An adjusted linear regression model demonstrated that EP participation was significantly associated with better SMI maintenance ( p = .02). These results suggest that participation in a home-based EP during preoperative treatment may help improve skeletal muscle health and clinical and quality of life outcomes for pancreatic cancer survivors.

OBJECTIVE To characterize opioid discharge prescriptions for pancreatectomy patients. BACKGROUND Wide variation in and over-prescription of opioids after surgery contribute to the United States opioid epidemic through persistent use past the postoperative period. Objective strategies guiding discharge opioid prescriptions for oncologic surgery are lacking, and factors driving prescription amount are not fully delineated. METHODS Characteristics of pancreatectomy patients (March 2016-August 2017) were retrospectively abstracted from a prospective database. Discharge opioids prescriptions were converted to oral morphine equivalents (OME). Regression models identified variables associated with discharge OME. RESULTS In 158 consecutive patients, median discharge OME was 250 mg (range 0-3950). Discharge OME was labeled "low" ( 400 mg) for 38 (24%). Only shorter operative time (odds ratio [OR]-0.14, P = 0.004) and inpatient team (OR-15.39, P < 0.001) were independently associated with low discharge OME. Older age was the only variable associated with high discharge OME. Fifty-seven patients (36%) used zero opioids in the last 24-hours predischarge, yet 52 of 57 (91%) still received discharge opioids. Older age (OR-1.07), grade B/C pancreatic fistula (OR-3.84), and epidural use (OR-3.12) were independently associated with zero last-24-hours OME (all P ≤ 0.040). CONCLUSIONS The wide variation in discharge opioid prescriptions is heavily influenced by provider routine/bias and not by objective criteria such as last-24-hours OME. Quality improvement strategies could include aggressive weaning protocols to increase the proportion of patients with zero/near-zero last-24-hour OME and limiting prescriptions to a conservative multiplier of the last-24-hour OME.

Resection of the superior mesenteric and/or portal vein (SMV-PV) is increasingly performed with pancreatectomy for adenocarcinoma. We sought to analyze the impact of cancer at the transected edge(s) of the vein wall.Patients who underwent pancreatectomy with vein resection between 2003 and 2015 at a single center were evaluated. R1 resection was defined per guidelines from the American Joint Commission on Cancer and the College of American Pathologists. Specimens were also evaluated for the presence (V+) or absence (V-) of cancer cells at the transected edge(s) and depth of vein invasion.Among 127 evaluated patients, 114 (90%) received preoperative therapy. R-status was categorized as margin-negative (R0)/V- (n = 72, 57%), R0/V+ (n = 19, 15%), margin-positive (R1)/V- (n = 24, 19%), and R1/V+ (n = 12, 9%). Patients with V- specimens had similar median durations of recurrence-free survival (RFS) (12 vs 9 months) and overall survival (OS) (30 vs 28 months) as did patients with V+ specimens (P 0.05). In contrast, cancer invasion into the lumen was associated with RFS and OS (P 0.05). Among patients who underwent R0 resection, V-status had no association with OS, RFS, or local control (P 0.05).Cancer invasion into the superior mesenteric and/or portal vein was adversely associated with survival, but cancer at the vein edge(s) was not. Transection of the SMV-PV through macroscopically normal vein may be performed to minimize resected vein length without fear of negatively affecting oncologic outcomes.

Perioperative blood transfusion (PBT) during resection of pancreatic adenocarcinoma (PDAC) has been linked to worse short-term and oncologic outcomes. However, little is known about contemporary rates of transfusion utilization among patients requiring pancreaticoduodenectomy with vein resection (PDVR). The primary aims of this study were to evaluate rates of PBT and to identify modifiable factors associated with PBT during PDVR.Patients with PDAC treated with preoperative therapy and PDVR (2008-15) were analyzed from a prospective, single-institution database.Among 120 total patients, approximately half (52.5%) of all patients received PBT; rates decreased significantly in the most recent years [70.7%, 2008-10 vs. 36.8%, 2014-15 (p = 0.013)]. Lower preoperative hemoglobin, greater intraoperative percent drop in hemoglobin, increased EBL, and advanced age were all associated with PBT (p 0.01). The only factors independently associated with PBT by multivariable analysis were age [OR-1.08 per year (95% CI 1.02-1.14)] and EBL [OR-1.30 per 100 mL, (95% CI 1.13-1.50)].PBT for PDVR for PDAC have decreased, with only 1/3 of contemporary patients requiring PBT. As preoperative therapy and PDVR become more ubiquitous, addressing anemia during preoperative therapy and limiting EBL may reduce blood utilization. Re-evaluation of clinical thresholds for transfusions may further reduce transfusion rates.

The impact of preoperative chemoradiation on postoperative morbidity and mortality of patients with pancreatic adenocarcinoma remains controversial.Consecutive pancreatectomies for adenocarcinoma performed between 2011 and 2015 were prospectively monitored for 90 days by using a previously reported surveillance system to determine the association between preoperative chemoradiation and adverse events, pancreatic fistulae, readmissions, and mortality.Among 209 consecutive patients who underwent pancreatectomy, 159 (76 %) experienced at least one adverse event within 90 postoperative days. Patients who received preoperative chemoradiation (n = 137, 66 %) were more likely to have borderline resectable/locally advanced tumors, to have received induction chemotherapy, and to require vascular resection at pancreatectomy than those who did not receive chemoradiation (all P 0.05). Nonetheless, there were no significant differences in the rates of severe complications, readmission, or mortality between these groups (all P 0.05). Among patients who underwent pancreatoduodenectomy, the rate of pancreatic fistula was similar between those who received chemoradiation and those who did not (P = 0.96). In contrast, those who received chemoradiation prior to distal pancreatectomy had a lower rate of pancreatic fistula (P 0.01).Preoperative chemoradiation is not associated with an increase in 90-day morbidity or mortality, and it may reduce the rate of pancreatic fistula following distal pancreatectomy.

Venous tumor thrombi have been reported in as many as 33 % of patients with pancreatic neuroendocrine tumors (pNETs). Surgical thrombectomy is often used to manage tumor thrombi that develop in association with cancers of the liver or kidney. We have likewise used thrombectomy to extract portal venous tumor thrombi in selected cases of pNET. We describe all cases of portal venous thrombectomy that were performed at our institution between 2007 and 2014 and illustrate the thrombectomy techniques we used in detail. In addition, we report the results of a PubMed search for English-language articles that were published between 1990 and 2014 and that described surgical therapy for portal venous thrombus developing in association with pNETs. Among 245 patients with pNET that underwent pancreatectomy at our institution, 26 (11 %) patients required surgical management of tumor involvement of the portal vein or its tributaries concomitant with pancreatectomy, including 9 (3.8 %) patients who underwent portal venous tumor thrombectomy. Eight cases describing surgical management of tumor thrombus including two additional cases of portal venous tumor thrombectomy were identified in the medical literature. Among patients with pNET who underwent thrombectomy at our institution, all nine had non-functioning tumors and eight (89 %) had tumors of the body and/or tail of the pancreas. Six (67 %) were treated with systemic therapy prior to pancreatectomy. Seven (78 %) patients are alive at a median follow-up of 33 months (range 3 to 97). Venous tumor thrombectomy may be used to safely and effectively extract thrombi from the portal venous system in selected patients with advanced pNET concomitant with pancreatectomy.

We previously demonstrated that a major pathologic response to preoperative therapy, defined histopathologically by the presence of less than 5% viable cancer cells in the surgical specimen, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma. However, to our knowledge, the patients most likely to experience a significant response to therapy are undefined.To identify clinical factors associated with major pathologic response in a large cohort of patients who underwent preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma.Retrospective review of a prospectively maintained database at University of Texas MD Anderson Cancer Center. The study included 583 patients with histopathologically confirmed pancreatic ductal adenocarcinoma who received preoperative therapy prior to pancreatectomy between 1990 and 2015.Preoperative therapy consisted of systemic chemotherapy alone (n = 38; 6.5%), chemoradiation alone (n = 261; 44.8%), or both (n = 284; 48.7%) prior to pancreatoduodenectomy (n = 514; 88.2%), distal pancreatectomy (n = 62; 10.6%), or total pancreatectomy (n = 7; 1.2%).Clinical variables associated with a major pathologic response (pathologic complete response or5% residual cancer cells) were evaluated using logistic regression.Among all patients, the mean (SD) age was 63.7 (9.2) years, and 53.0% were men. A major pathologic response was seen in 77 patients (13.2%) including 23 (3.9%) who had a complete pathologic response. The median overall survival duration was significantly longer for patients who had a major response than for those who did not (73.4 months vs 32.2 months, P .001). On multivariate logistic regression, only age younger than 50 years, baseline serum cancer antigen 19-9 level less than 200 U/mL, and gemcitabine as a radiosensitizer were associated with a major response. The number of these positive factors was associated with the likelihood of a major response in a stepwise fashion (0, 7.5%; 1, 12.7%; 2, 16.9%; 3, 35.7%; P = .009).Although a major pathologic response occurs infrequently following preoperative therapy for pancreatic ductal adenocarcinoma, it is associated with a significantly improved prognosis. Of the patient- and treatment-related factors we analyzed, only young age, low baseline cancer antigen 19-9, and gemcitabine as a radiosensitizer were associated with a major pathologic response. Given its association with long-term survival, better predictors of response and more effective preoperative regimens should be aggressively sought.

Patients with borderline resectable pancreatic adenocarcinoma have primary tumors within the pancreas that involve the mesenteric vasculature to a limited degree. Their tumors are nonetheless at high-risk for a microscopically positive surgical resection margin and/or early treatment failure when pancreatectomy is performed de novo. The optimal treatment strategy for these patients has not been established; however, relatively favorable outcomes can be achieved with systemic chemotherapy and radiation therapy (RT) prior to intended resection. In this article, we discuss the modalities used to stage localized pancreatic cancer, the concept of borderline resectable pancreatic cancer (BRPC), the rationale for the use of preoperative therapy, and review recent publications, placing special emphasis on the necessity of appropriate patient selection and coordinating multimodality management to maximize outcomes.