Laura Prakash

Preoperative Therapy and Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: a 25-Year Single-Institution Experience

BackgroundThe purpose of this study was to evaluate a single-institution experience with delivery of preoperative therapy to patients with pancreatic ductal adenocarcinoma (PDAC) prior to pancreatoduodenectomy (PD).MethodsConsecutive patients (622) with PDAC who underwent PD following chemotherapy and/or chemoradiation between 1990 and 2014 were retrospectively reviewed. Preoperative treatment regimens, clinicopathologic characteristics, operative details, and long-term outcomes in four successive time periods (1990–1999, 2000–2004, 2005–2009, 2010–2014) were evaluated and compared. ResultsThe average number of patients per year who underwent PD following preoperative therapy as well as the proportion of operations performed for borderline resectable and locally advanced (BR/LA) tumors increased over time. The use of induction systemic chemotherapy, as well as postoperative adjuvant chemotherapy, also increased over time. Throughout the study period, the mean EBL decreased while R0 margin rates and vascular resection rates increased overall. Despite the increase in BR/LA resections, locoregional recurrence (LR) rates remained similar over time, and overall survival (OS) improved significantly (median 24.1, 28.1, 37.3, 43.4 months, respectively, p < 0.0001).ConclusionsDespite increases in case complexity, relatively low rates of LR have been maintained while significant improvements in OS have been observed. Further improvements in patient outcomes will likely require disruptive advances in systemic therapy.

Superior mesenteric artery margin of posttherapy pancreaticoduodenectomy and prognosis in patients with pancreatic ductal adenocarcinoma

Negative-margin resection is crucial to favorable prognosis in patients with pancreatic ductal adenocarcinoma. However, the definition of a negative superior mesenteric artery margin (SMAM) varies. The College of American Pathologists defines positive SMAM as the presence of tumor cells at the margin, whereas the European protocol is based on a 1 mm clearance. In this study, we examined the prognostic significance of the SMAM distance in 411 consecutive pancreatic ductal adenocarcinoma patients who completed neoadjuvant therapy and pancreaticoduodenectomy. Per College of American Pathologists criteria, 32 (7.8%) had positive margins, and 379 (92.2%) had negative margins. Among margin-negative group, SMAM was ⩽1, 1.0 to 5.0, and >5.0 mm in 66, 145, and 168 patients, respectively. There was no difference in either disease-free survival (DFS) or overall survival (OS) between the positive-margin group and SMAM⩽1 mm (P>0.05). However, patients with SMAM 1.0 to 5.0 mm had better OS than those with positive margins or SMAM⩽1 mm (P=0.02). Patients with SMAM>5.0 mm had better DFS and OS than those with SMAM 1.0 to 5.0 mm and those with positive margins or SMAM⩽1 mm (P<0.01). By multivariate analysis, the SMAM distance, tumor differentiation, lymph node metastasis, and histopathologic tumor response grade were independent prognostic factors for both DFS and OS. SMAM distance correlated with lower ypT and AJCC stages, smaller tumor size, better histopathologic tumor response grade, fewer lymph node metastases, and recurrences (P<0.05). Thus our results strongly support use of SMAM>1 mm for R0 resection in posttherapy pancreaticoduodenectomy specimens.

Impact of hypofractionated and standard fractionated chemoradiation before pancreatoduodenectomy for pancreatic ductal adenocarcinoma.

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.

Association of Clinical Factors With a Major Pathologic Response Following Preoperative Therapy for Pancreatic Ductal Adenocarcinoma

Importance 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. Objective 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. Design, Setting, and Participants 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. Exposures 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%). Main Outcomes and Measures Clinical variables associated with a major pathologic response (pathologic complete response or <5% residual cancer cells) were evaluated using logistic regression. Results 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). Conclusions and Relevance 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.

Selective Perioperative Administration of Pasireotide is More Cost-Effective Than Routine Administration for Pancreatic Fistula Prophylaxis

BackgroundIn 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.Study DesignConsecutive 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.ResultsAmong 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 < 0.001) on the basis of diagnosis, pancreatic duct diameter, and body mass index. Patients who underwent DP were allocated to three groups with a grade B/C POPF risk of 14, 26, or 44% (P = 0.05) on the basis of pancreatic duct diameter alone. Although the routine administration of pasireotide to all 315 patients would have theoretically saved

Angiogenin/Ribonuclease 5 Is an EGFR Ligand and a Serum Biomarker for Erlotinib Sensitivity in Pancreatic Cancer.

30,892 over standard care, restriction of pasireotide to only patients at high risk for POPF would have led to a cost savings of

Multimodality management of borderline resectable pancreatic adenocarcinoma

831,916.ConclusionPreoperative clinical characteristics can be used to characterize patients’ risk for POPF following pancreatectomy. Selective administration of pasireotide only to patients at high risk for grade B/C POPF may maximize the cost-efficacy of prophylactic pasireotide.

Vein resection during pancreaticoduodenectomy for pancreatic adenocarcinoma: Patency rates and outcomes associated with thrombosis

Pancreatic ribonuclease (RNase) is a secreted enzyme critical for host defense. We discover an intrinsic RNase function, serving as a ligand for epidermal growth factor receptor (EGFR), a member of receptor tyrosine kinase (RTK), in pancreatic ductal adenocarcinoma (PDAC). The closely related bovine RNase A and human RNase 5 (angiogenin [ANG]) can trigger oncogenic transformation independently of their catalytic activities via direct association with EGFR. Notably, high plasma ANG level in PDAC patients is positively associated with response to EGFR inhibitor erlotinib treatment. These results identify a role of ANG as a serum biomarker that may be used to stratify patients for EGFR-targeted therapies, and offer insights into the ligand-receptor relationship between RNase and RTK families.

The role of preoperative therapy prior to pancreatoduodenectomy for distal cholangiocarcinoma.

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.

After Pancreatectomy, the “90 Days from Surgery” Definition Is Superior to the “30 Days from Discharge” Definition for Capture of Clinically Relevant Readmissions

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).