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Background: The 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)., Methods: Consecutive 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., Results: The 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)., Conclusions: Despite 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.

Background: The impact of preoperative chemoradiation on postoperative morbidity and mortality of patients with pancreatic adenocarcinoma remains controversial., Methods: 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., Results: 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)., Conclusion: 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.

Background: Venous resection may be required to achieve complete resection of pancreatic cancers. We assessed the ability of radiographic criteria to predict the need for superior mesenteric-portal vein (SMV-PV) resection and the presence of histologic vein invasion., Methods: All patients who underwent pancreaticoduodenectomy from 2004 to 2011 at the authors' institution were identified. Preoperative pancreatic protocol CT images were re-reviewed to characterize the extent of tumor-vein circumferential interface (TVI) as demonstrating no interface, ≤ 180° of vessel circumference, >180° of vessel circumference, or occlusion. Findings were correlated with the need for venous resection, histologic venous invasion, and survival., Results: A total of 254 patients underwent pancreaticoduodenectomy and met inclusion criteria; 98 (39.6 %) required SMV-PV resection. In our cohort, 76.4 % of patients received neoadjuvant chemoradiation. The TVI classification system predicted with fair accuracy both the need for SMV-PV resection at the time of surgery and histologic invasion of the vein. In particular, 89.5 % of patients with TVI > 180° or occlusion required SMV-PV resection. Of those, 82.4 % had documented histologic SMV-PV invasion. TVI ≤ 180° was associated with favorable overall survival compared to a greater circumferential interface., Conclusions: A tomographic classification of the tumor-SMV-PV interface can predict the need for venous resection, pathologic venous involvement, and survival. To assist in treatment planning, a standardized assessment of this anatomic relationship should be routinely performed.

Barriers to multimodality therapy (MMT) completion among patients with resectable pancreatic adenocarcinoma include early cancer progression and postoperative major complications (PMC). We sought to evaluate the influence of these factors on MMT completion rates of patients treated with neoadjuvant therapy (NT) and surgery-first (SF) approaches. We evaluated all operable patients treated for clinically resectable pancreatic head adenocarcinoma at our institution from 2002 to 2007. Rates of MMT completion, 90-day PMC, and overall survival (OS) were evaluated. Ninety-five of 115 (83 %) NT and 29/50 (58 %) SF patients completed MMT. Patients who completed MMT lived longer than those who did not (36 vs. 11 months, p < 0.001). The most common reason that NT (11 %) and SF (26 %) patients failed to complete MMT was early disease progression. The rates of PMC among NT and SF patients were similar. Among SF patients, 69 % with no PMC completed MMT versus 29 % after PMC (p = 0.040). PMC were associated with decreased OS in SF patients but not in NT patients. The impact of early cancer progression and PMC upon completion of MMT is reduced by delivery of nonoperative therapies prior to pancreaticoduodenectomy. NT sequencing is a practical treatment strategy, particularly for patients at high biological or perioperative risk.

Background: For ampullary carcinoma (AC), the lymph node ratio (LNR) has been associated with overall survival. However, the use of the LNR to predict distant recurrence risk remains unknown. The purpose of this study was to determine if the LNR is associated with distant recurrence risk., Methods: One hundred forty three patients with AC who underwent pancreaticoduodenectomy between 1989 and 2011 were identified from a single-institution prospective database. Data on clinicopathologic factors and recurrence were analyzed., Results: At a median follow-up of 43 months (62 months for survivors), 55 patients (38 %) had developed recurrent disease, with a median time to recurrence of 13 months. Patients with a LNR ≥ 0.15 were more likely to have T3/4 tumors, advanced stage lymphovascular (LVI), or perineural invasion (PNI) and develop recurrent disease. Univariate analysis demonstrated that T-stage, lymph node status, AJCC stage, LVI, PNI, and LNR were significantly associated with decreased time to distant recurrence (TTDR). In multivariate stepwise regression, only LNR and LVI were significantly associated with decreased TTDR., Conclusions: A high positive LNR is associated with distant recurrence after surgical resection of AC. Given the high risk of disease recurrence, consideration for adjuvant therapy is warranted in patients with a LNR ≥ 0.15.

Objectives: To determine the influence of neoadjuvant chemoradiation and standardized dissection of the superior mesenteric artery upon the oncologic outcome of patients with localized pancreatic adenocarcinoma., Methods: One hundred ninety-four patients with pancreatic adenocarcinoma who underwent pancreaticoduodenectomy between 2004 and 2008 were evaluated. The retroperitoneal dissection was performed directly along the superior mesenteric artery in all cases. A standard histopathologic protocol that measured the "superior mesenteric artery (SMA) margin distance" between cancer cells and the superior mesenteric artery was employed., Results: Seventy-six percent of patients received neoadjuvant chemoradiation. The SMA margin was positive in 4% of patients but an additional 22% of patients with a negative margin had a SMA margin distance of ≤1 mm. Preoperative CT images overestimated the SMA margin distance in 73% of cases. Patients who received chemoradiation had longer SMA margin distances than those who did not. Patients who received chemoradiation and had a SMA margin of >1 mm had the lowest recurrence rates. Administration of neoadjuvant chemoradiation and lower estimated blood loss were independently associated with longer progression-free survival on multivariate analysis., Conclusions: Preoperative chemoradiation and meticulous dissection of the superior mesenteric artery maximize the distance between cancer cells and the SMA margin and may influence locoregional control.

Major vascular resection performed at the time of pancreaticoduodenectomy (PD) for adenocarcinoma remains controversial. We analyzed all patients who underwent vascular resection (VR) at the time of PD for any histology at a single institution between 1990 and 2002. Preoperative imaging criteria for PD included the absence of tumor extension to the celiac axis or superior mesenteric artery (SMA). Tangential or segmental resection of the superior mesenteric or portal veins was performed when the tumor could not be separated from the vein. As a separate analysis, all patients who underwent PD with VR for pancreatic adenocarcinoma were compared to all patients who underwent standard PD for pancreatic adenocarcinoma. A total of 141 patients underwent VR with PD. Superior mesenteric-portal vein resections included tangential resection with vein patch (n=36), segmental resection with primary anastomosis (n=35), and segmental resection with autologous interposition graft (n=55). Hepatic arterial resections were performed in 10 patients, and resections of the anterior surface of the inferior vena cava were performed in 5 patients. PD was performed for pancreatic adenocarcinoma in 291 patients; standard PD was performed in 181 and VR in 110. Median survival was 23.4 months in the group that required VR and 26.5 months in the group that underwent standard PD (P=0.177). A Cox proportional hazards model was constructed to analyze the effects of potential prognostic factors (VR, tumor size, T stage, N status, margin status) on survival. The need for VR had no impact on survival duration. In conclusion, properly selected patients with adenocarcinoma of the pancreatic head who require VR have a median survival of approximately 2 years, which does not differ from those who undergo standard PD and is superior to historical patients believed to have locally advanced disease treated nonoperatively.