Neoadjuvant Chemotherapy and Radiation Improves Recurrence-free and Overall Survival in Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: The objective of this study is to analyze the outcomes of patients with resectable/borderline resectable PDAC who receive total neoadjuvant therapy vs upfront surgery. METHODS AND ANALYSIS: Patients who were treated at a single institution from 2006 to 2021 were included. The primary outcome was overall survival (OS). Secondary outcomes included disease free survival (DFS), rates of lymph node positivity, and R0 resection. All survival analyses were performed with intention-to-treat. RESULTS: 26 patients received neoadjuvant chemotherapy and radiation (TNT), 28 received neoadjuvant chemotherapy only (NAC), and 168 received upfront surgery. Demographics were comparable across all three groups. Patients who received TNT or NAC had longer OS and DFS compared to the surgery first patients (P < .01). Patients who received TNT had a lymph node positivity rate of 0% at time of surgery compared to 5.3% and 13.3% in the NAC and surgery-first groups, respectively (P < .01). The rate of R0 resection did not differ between groups (P = .17). CONCLUSION: Patients with resectable/borderline resectable PDAC who receive neoadjuvant therapy have longer OS and RFS relative to those who receive upfront surgery.

Can we let our patients sleep in the hospital? A randomized controlled trial of a pragmatic sleep protocol in surgical oncology patients.

BACKGROUND: Postoperative inpatients experience increased stress due to pain and poor restorative sleep than non-surgical inpatients. OBJECTIVES AND METHODS: A total of 101 patients, undergoing major oncologic surgery, were randomized to a postoperative sleep protocol (n = 50) or standard postoperative care (n = 51), between August 2020 and November 2021. The primary endpoint of the study was postoperative sleep time after major oncologic surgery. Sleep time and steps were measured using a Fitbit Charge 4®. RESULTS: There was no statistically significant difference found in postoperative sleep time between the sleep protocol and standard group (median sleep time of 427 min vs. 402 min; p = 0.852, respectively). Major complication rates were similar in both groups (7.4% vs. 8.9%). Multivariate analysis found sex and Charlson Comorbidity Index to be significant factors affecting postoperative sleep time and step count. Postoperative delirium was only observed in the standard group, although this did not reach statistical significance. There were no in hospital mortalities. CONCLUSION: The use of a sleep protocol was found to be safe in our study population. There was no statistical difference in postoperative sleep time or major complications. Institution of a more humane sleep protocol for postoperative inpatients should be considered.

Utility and costs of surveillance imaging for low- and very low-risk gastrointestinal stromal tumors.

BACKGROUND: There is limited evidence on the optimal surveillance approach in patients with low- and very low-risk gastrointestinal stromal tumors, resulting in inconsistent and arbitrary approaches to surveillance in this population. In this study, we reviewed our institutional approach to surveillance in patients with low- and very low-risk gastrointestinal stromal tumors and the costs associated with detecting recurrence. METHODS: We retrospectively reviewed consecutive adult patients treated for low- and very low-risk gastrointestinal stromal tumors at our institution from 2010 to 2019. Data collected included patient and tumor characteristics, surgical management, and postoperative follow-up. Surveillance-related expenses were calculated using estimates of average costs obtained from our institution. A cost analysis was performed to evaluate estimated yearly costs based on the surveillance strategy used. RESULTS: There were 60 patients included. The mean age at diagnosis was 63.9 (±12.5) years. The primary tumor was typically in the stomach (73%; n = 44). Computed tomography scan of the abdomen and pelvis with intravenous contrast was the most common surveillance modality (total = 226 scans). No recurrences were identified. Median follow-up duration was 49.0 (interquartile range = 19.5-61.5) months. The mean number of surveillance images per patient was 4 (±2.6). Surveillance imaging was obtained more frequently than just annually in 83% (n = 50) of patients, with an estimated yearly cost of $2,840.77 (interquartile range = $2,273.62-$3,895.92) and no detection of recurrence. CONCLUSION: In this study population, patients with low- and very low-risk gastrointestinal stromal tumors underwent frequent imaging studies for surveillance with little yield and at substantial cost. Further multi-institutional studies on practice patterns and outcomes of surveillance are warranted to better inform standardized surveillance recommendations.

Apixaban for Extended Thromboprophylaxis After Oncologic Resection: Outcomes and Cost Analysis.

BACKGROUND: Patients undergoing oncologic resection are at risk of developing venous thromboembolism (VTE), and this can lead to increased morbidity and hospital costs. Low-molecular weight heparin (LMWH) is recommended as extended thromboprophylaxis (ETP) in high-risk patients and has been shown to reduce rates of VTE. METHODS: This is a retrospective review of consecutive patients undergoing resection for oncologic indications at a single institution from May 2016 to May 2019. This study evaluated the use of apixaban as ETP at discharge. The primary outcomes were deep vein thrombosis (DVT), pulmonary embolism (PE), or mesenteric/portal venous thromboembolism at 30, 60, and 90 days postoperatively. RESULTS: A total of 600 patients were included; 449 patients received no ETP, and 151 patients received apixaban. PE occurred in 1.1, 1.6, and 2.3% of patients without ETP and 0, 0, and .7% of patients in the apixaban group (at 30, 60, and 90 days; P = .338, P = .201, and P = .306, respectively). DVT occurred in 1.8, 2.1, and 2.8% of patients without ETP and 0, 0, and 1.4% in the apixaban group (P = .211, P = .121, and P = .535, respectively). The total cost, including ETP and readmission for VTE, per patient was US $5.51 more in the apixaban group. CONCLUSION: Apixaban therapy for ETP did not produce a statistically significant reduction in VTE events in our patients. Future studies should include more patients in a prospective multicenter trial.

Surgeon Burnout and Usage of Personal Communication Devices: Examining the Technology "Empowerment/Enslavement Paradox".

INTRODUCTION: Access to patients' electronic medical records (EMRs) on personal communication devices (PCDs) is beneficial but can negatively impact surgeons. In a recent op-ed, Cohen et al. explored this technology "empowerment/enslavement paradox" and its potential effect on surgeon burnout. We examined if there is a relationship between accessing EMRs on PCDs and surgeon burnout. METHODS: This was a cohort study with retrospective and prospective arms. Trainees and attendings with a background in general surgery completed the Maslach Burnout Index for Medical Personnel, a validated survey scored on three areas of burnout (emotional exhaustion, depersonalization, and low personal accomplishment). Data on login frequency to EMRs on PCDs over the previous 6 mo were obtained. Pearson correlation coefficients were calculated to determine if burnout and login frequency were associated. RESULTS: There were 52 participants included. Residents were 61.5% (n = 32) of participants. The mean login frequency over 6 mo was 431.0 ± 323.9. The mean scores (out of 6) for emotional exhaustion, depersonalization, and personal accomplishment were 2.3 ± 1.1, 1.9 ± 1.2, and 4.9 ± 0.8, respectively. There was no correlation between burnout and logins. Residents had higher median depersonalization scores (2.3 versus 1.2, P = 0.03) and total logins (417.5 versus 210.0, P < 0.001) than attendings. Participants who overestimated logins had higher median emotional exhaustion and depersonalization scores than those who underestimated (2.6 versus 1.4, P = 0.03, and 2.4 versus 0.8, P = 0.003, respectively). CONCLUSIONS: Using EMRs on PCDs is common, but frequency of logins did not correlate with burnout scores in this study. However, perception of increased workload may contribute to experiencing burnout.

Timing and necessity of staging imaging in clinical stage II cutaneous melanoma: Cost-effectiveness and clinical decision analysis.

BACKGROUND: Preoperative imaging in clinical stage II melanoma is not indicated per National Comprehensive Cancer Network (NCCN) guidelines but remains common in clinical practice. METHODS: Patients presenting with cutaneous clinical stage II melanoma from 2007 to 2019 were retrospectively reviewed. A clinical decision analysis with cost data was designed to understand ideal practice patterns in managing stage II melanoma, with pre-versus selective post-operative imaging as the initial decision node. RESULTS: There were 277 subjects included, and 143 underwent preoperative imaging (49.5%). This changed management (i.e. no surgery) in one patient (0.4%). Overall, 16 patients had additional findings on imaging (5.8%). Upfront surgery with selective postoperative imaging was a more cost-effective strategy than routine performance of preoperative imaging, with savings of $1677 per patient. CONCLUSION: Preoperative imaging is a low yield, costly approach for patients with clinical stage II melanoma with minimal impact on the decision to proceed with surgical management.

Kirsten rat sarcoma (KRAS) oncogene mutation predicts magnitude of response and outcomes in hepatic arterial infusion pump therapy of unresectable colorectal liver metastases.

Background: The Kirsten rat sarcoma (KRAS) mutation predicts negative outcomes following resection of colorectal liver metastases (CRLM) and adjuvant hepatic arterial infusion (HAI) pump chemotherapy. Less is known on the effects of KRAS mutation on tumor response in patients with unresectable CRLM undergoing HAI chemotherapy with floxuridine. Methods: This is a retrospective cohort study investigating the effects of KRAS mutation on tumor response in patients with unresectable CRLM treated with HAI chemotherapy. Primary endpoint was objective response rate (ORR), secondary endpoints included overall tumor response and conversion to resectability. Results: Twenty-five patients with unresectable liver metastases from colorectal cancer were treated with HAI chemotherapy between 2017-2019. Median number of liver lesions was 12 (range, 1-59) and almost all (n=24) had prior chemotherapy before starting HAI therapy. Median number of cycles administered via HAI pump was 6 (range, 3-12). Overall decrease in liver tumor burden was 63.5% (median; range, -257-100%) with an ORR of 20/25 (80%) and 10 (40%) patients converting to resectable status. Eleven (44%) patients had KRAS positive tumors. When compared to wild-type, KRAS positive tumors had less overall percent decrease (58% vs. 70%; P=0.04) and ORR (7/11 vs. 13/13; P=0.03). Fewer patients with KRAS positive tumors converted to resectable status during HAI therapy (2/11 vs. 8/13; P=0.05). At a median follow-up of 14.6 months (range, 4.0-36.6 months), overall survival is 45% among KRAS-positive and 77% for wild type patients. Conclusions: KRAS mutational status in patients with unresectable liver metastases from colorectal cancer predicts worse response to HAI chemotherapy compared to wild type.

Recurrence and survival after curative-intent treatment for colorectal liver metastases: Implications for adjuvant liver-directed regional chemotherapy.

BACKGROUND: This study investigates tumor recurrence patterns and their effect on postrecurrence survival following curative-intent treatment of colorectal liver metastases (CRLM) to identify those who stand to benefit the most from adjuvant liver-directed therapy. METHODS: This is a retrospective analysis of all patients that underwent liver resection and/or ablation for CRLM between 2007 and 2019. Postrecurrence survival was compared between recurrence locations. Risk factors for liver recurrence were sought. RESULTS: The study included 227 patients. Majority were treated with resection (71.0%) while combination resection/ablation (18.9%) and ablation alone (11.0%), were less common. At a median follow-up of 3.0 years, recurrence was observed in 151 (66.5%) patients. Of those, liver, lung, and peritoneal recurrence were most common at 66.9%, 49.6%, and 9.2%, respectively. Median postrecurrence survival after liver, lung, and multisite recurrence was 39.6-, 68.4-, and 33.6 months, respectively. High tumor grade (p < 0.014), perineural invasion (p = 0.002), and N0 node status (p = 0.017) of primary tumor correlated with liver recurrence on multivariate analysis. CONCLUSIONS: Tumor grade, perineural invasion, and N0 node status of the primary tumor are associated with increased risk of liver recurrence after CRLM resection and represent a target population that may benefit the most from adjuvant liver-directed regional chemotherapy.

Tumor and serum levels of per- and polyfluoroalkyl (PFAS) in hepatobiliary and gastrointestinal malignancy.

BACKGROUND: There has been significant controversy over the carcinogenic potential of per- and polyfluoroalkyl substances (PFAS). STUDY DESIGN: A total of 37 serum and tumor samples from patients with hepatobiliary and gastrointestinal malignancy were tested for 24 analytes of PFAS. RESULTS: At least one PFAS analyte was found in 97% (36/37) of the serum samples and 41% (15/37) of the tumor samples. The serum Perfluorooctanesulfonic acid (PFOS) levels were significantly higher than the national levels (6.77 ng/mL vs. 5.20 ng/mL; p = 0.038). Patients with PFOS in tumor samples had significantly higher levels in serum when compared to tumor samples without PFOS (9.4 ng/mL vs 5.5 ng/mL; p = 0.015). CONCLUSIONS: Patients were found to have significantly higher levels of PFOS when compared to the reported national levels. Additionally, the patients with higher serum levels of PFOS also had tumor positive samples.

Recurrence patterns and postrecurrence survival after curative intent resection for pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma has a high rate of recurrence after resection. We aimed to investigate patterns of recurrence of pancreatic ductal adenocarcinoma to identify opportunities for targeted intervention toward improving survival. METHODS: This was a retrospective analysis of consecutive patients that underwent curative-intent resection for pancreatic ductal adenocarcinoma between 2007 and 2015. Recurrence and survival were analyzed based on site of recurrence. Multiple clinicopathologic factors were calculated for likelihood of site-specific recurrence. RESULTS: The study included 221 patients with median follow-up of 83 months. Median overall and recurrence-free survival was 19 and 13 months, respectively. Recurrence was observed in 71.9% patients. Local recurrence occurred in 16.4%, distant recurrence in 67.3%, and combined in 15.9%. The most common site of distant recurrence was the liver (49.7%) followed by lung (31.8%) and peritoneum (16.6%). Median time to liver recurrence was shortest (5 months, 95% confidence interval 1.7-8.3) and post recurrence survival was poor (4 months, 95% confidence interval 1.9-6.1). Patients with poorly differentiated tumors on pathology were 4.8 times more likely to recur in the liver (odds ratio 4.83, 95% confidence interval 1.7-13.9). CONCLUSION: Liver metastasis after resection of pancreatic ductal adenocarcinoma occurs most frequently, earliest after surgery, and is rapidly fatal. Liver-directed therapies represent a target for future study.

Preoperative tranexamic acid does not reduce transfusion rates in major oncologic surgery: Results of a randomized, double-blind, and placebo-controlled trial.

BACKGROUND AND OBJECTIVES: Allogeneic blood transfusions are associated with worse postoperative outcomes in oncologic surgery. The aim of this study was to introduce a preoperative intervention to reduce transfusion rates in this population. METHODS: Adult patients undergoing major oncologic surgery in five categories with similar transfusion rates were recruited. Enrollees received a single preoperative intravenous dose of placebo or tranexamic acid (1000 mg). The primary outcome measure was perioperative transfusion rate. Secondary outcome measures included: estimated blood loss, thromboembolic events, morbidity, hospital length of stay, and readmission rate. RESULTS: Seventy-six patients were enrolled, 39 in the tranexamic acid group and 37 in the placebo group, respectively. Demographics and surgery type were equivalent between groups. The transfusion rates were 8 out of 39 (20.5%) in the tranexamic acid group and 5 out of 37 (13.5%) in the placebo group, respectively (P = .418). Median estimated blood loss was 400 mL (interquartile range [IQR] = 150-600) in the tranexamic acid group compared with 300 mL (IQR = 150-800) in the placebo group (P = .983). There was one pulmonary embolism in each arm and no deep venous thrombosis (P > .999). CONCLUSION: Preoperative administration of tranexamic acid at a 1000 mg intravenous dose does not decrease transfusion rates or estimated blood loss in patients undergoing major oncologic surgery.

Is there a role for Ytrrium-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma?

BACKGROUND: Selective internal radiation therapy (SIRT) with Ytrrium-90 (Y-90) has been used to treat hepatic malignancies with success. This study focuses on the efficacy and safety of Y-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma (ICC). METHODS: A single-institution retrospective case review was performed for patients with unresectable and metastatic ICC treated with Y-90 between 2006 and 2016. RESULTS: Seventeen patients with ICC underwent 21 Y-90 treatments. Four patients had undergone prior liver resection, and six patients had extrahepatic disease at the time of treatment. Five year overall survival was 26.8%, with a median survival of 33.6 months. One patient underwent margin negative liver resection after a single treatment. Complications were appreciated in two cases. Ninety-day mortality was 0%. CONCLUSION: Treatment of ICC using Y-90 is a safe and promising procedure. Further research is needed to clarify its role in the treatment of unresectable and metastatic ICC.

Non-neoplastic epithelial cysts of the pancreas: a rare, benign entity.

OBJECTIVES: With the increased use of cross-sectional radiologic imaging in recent years, cystic lesions of the pancreas are being diagnosed with greater frequency. While pseuodocysts have historically accounted for the majority of benign pancreatic cysts, there are a number of rare, benign cystic lesions of the pancreas that can mimic neoplastic cysts. The objective of this study was to review a single institution's experience with these benign cystic lesions of the pancreas. METHODS: We conducted a retrospective analysis of all patients who underwent surgical resection for pancreatic disease from 2005 to 2012 at our institution. Out of a total of 947 pancreatic resections, we identified those cases performed for cystic disease, and focused upon the clinicopathologic data of patients with non-neoplastic pancreatic cysts. RESULTS: Of the 947 pancreatic resections, 256 (27%) were performed for cystic disease. Sixteen cases (6.3%) out of the total of 256 pancreatic operations performed for cystic disease were found to have non-neoplastic cystic lesions of the pancreas. Preoperative imaging revealed primary lesions in all patients, eight of which were found incidentally. Of these lesions, 14 were suspected preoperatively to be mucinous neoplasms and two to harbor pancreatic adenocarcinoma. However, postoperative pathology revealed eight patients with ductal retention cysts, three squamoid cysts, one mucinous non-neoplastic cyst, one congenital ciliated foregut cyst, one lymphoepithelial cyst, and two endometrial cysts. Two patients had complications postoperatively, one pancreatic fistula and one SMV thrombosis. Both complications resolved with conservative management. CONCLUSIONS: Non-neoplastic epithelial pancreatic cysts are rare, benign lesions. In our institutional experience, these lesions are often indistinguishable from cystic neoplasms of the pancreas preoperatively. As such, many of these lesions are resected unknowingly. It is important for the clinician to be well informed of the nature of these lesions, in the hopes to avoid unnecessary resection whenever possible.

Tumor recurrence is independent of pancreatic fistula in patients after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: Recurrence of pancreatic adenocarcinoma after pancreaticoduodenectomy (PD) can be increased in patients with pancreatic fistula (PF). The purpose of our study was to determine if a relationship exists between PF and tumor recurrence (both peritoneal and local) in patients after PD for pancreatic ductal adenocarcinoma. STUDY DESIGN: A single-institution, retrospective analysis of 221 patients who underwent PD from January 2001 to December 2009 was conducted. Electronic charts and medical records were queried for tumor characteristics, recurrence, and complications. Presence and grading of PF was determined using the criteria of the International Study Group on Pancreatic Fistula. Data were analyzed using chi-square and Kaplan-Meier survival statistics. RESULTS: There were 114 male and 107 female patients. Mean age was 66 years (range 35 to 91 years). The vast majority (84%) of patients had stage II disease; 143 (65%) had positive lymph nodes (median 2 positive nodes; range 1 to 17 positive nodes). Pancreatic fistula developed in 23 patients (grade A, n = 9; grade B, n = 13; grade C, n = 1; 10.2%). Peritoneal recurrence was noted in 20 patients (9%). Of the 23 patients with PF, peritoneal recurrence developed in 3 (13%). Of the 198 patients without PF, peritoneal recurrence developed in 17 (10%). Local recurrence occurred in 47 patients (21%), 5 (2%) in patients with PF and 42 (21%) in those without PF (p = NS). In Kaplan-Meier survival analysis, there was no significant difference in recurrence-free survival (p = 0.4) and overall survival (p = 0.3) for those with PF vs those without PF. CONCLUSIONS: Patients with PF after PD were not found to have a significant increase in local or peritoneal recurrence. Therefore, in this analysis, postoperative PF does not appear to serve as an adverse prognostic marker.

Is resection equivalent to transplantation for early cirrhotic patients with hepatocellular carcinoma? A meta-analysis.

BACKGROUND: Whether liver resection or liver transplantation is optimal therapy for patients with hepatocellular carcinoma (HCC) remains undefined. A meta-analysis was conducted to answer this question. STUDY DESIGN: This study performed a systematic review of the published literature between January 2000 and April 2012. RESULTS: Nine retrospective studies, totaling 2,279 patients (989 resected and 1,290 transplanted), met the selection criteria. Older patients with larger tumors and less severe cirrhosis were identified in the resection group. At 1 year, resection demonstrated significantly higher overall [odds ratio (OR) = 1.54; 95 % confidence interval (CI), 1.19-1.98; p = 0.001], but equivalent disease-free survival (OR = 0.93; 95 % CI, 0.53-1.63; p = 0.80). At 5 years, there was no difference in overall survival (OR = 0.86; 95 % CI, 0.61-1.21; p = 0.38), but a higher disease-free survival in transplanted patients was observed (OR = 0.39; 95 % CI, 0.24-0.63; p < 0.001). When limiting our analysis to studies conducted in an intent-to-treat fashion, there was no difference in 5 year overall survival (OR = 1.18; 95 % CI, 0.92-1.51; p = 0.19), but a significantly higher disease-free survival (OR = 0.76; 95 % CI, 0.57-1.00; p = 0.05) in transplanted patients. At 10 years, transplantation had higher overall and disease-free survival rates. CONCLUSION: Liver transplantation in patients with HCC results in increased late disease-free and overall survival when compared with liver resection. Nonetheless, the benefit of liver transplantation is offset by higher short-term mortality, donor organ availability, and long transplant wait times associated with more patient deaths. Understanding these differences in survival is helpful in guiding treatment. However, a properly controlled prospective trial is needed to define how best to treat HCC patients who are candidates for either therapy.

Management of infected caval filter with simultaneous aortic pseudoaneurysm and retroperitoneal perforation: a case report and literature review.

Inferior vena cava (IVC) filters have been reported to have complication rates up to 35%. Penetration of surrounding retroperitoneal structures is an uncommon, but potentially serious, complication, with several reports in the literature. We present a unique case of a 34-year-old intravenous drug user with infected IVC filter struts penetrating multiple structures simultaneously. Definitive operative management was necessary for removal of filter struts from the aorta, the second part of the duodenum and the iliopsoas muscle. Drainage and debridement of an associated iliopsoas abscess was performed, followed by aortic and caval reconstruction.

Surgical Apgar score predicts perioperative morbidity in patients undergoing pancreaticoduodenectomy at a high-volume center.

OBJECTIVES: Pancreaticoduodenectomy (PD) remains a procedure that carries considerable morbidity. Numerous studies have evaluated factors to predict patients at risk. The aim of this study was to determine whether the surgical Apgar score (SAS) predicts perioperative morbidity and mortality. METHODS: We examined 553 patients undergoing successful PD between January 2000 and December 2010. Postoperative complications were graded using the Clavien scale, and the SAS (range, 0-10) was determined. The Cochran-Armitage test for trend was used to determine the association between grouped SAS scores (0-2, 3-4, 5-6, 7-8, and 9-10) and each of the outcomes. RESULTS: The average patient age was 64 years, and there was an even distribution of males and females. There were 11 perioperative deaths (2%), 186 grade 2 or higher complications (34%), and 86 major complications (grades 3-5, 16%). Additionally, 61 patients developed pancreatic fistulae (11%). Statistical analysis determined that SAS was a significant predictor of grade 2 or higher complications (p < 0.0001), major morbidity (p = 0.01), and pancreatic fistula (p = 0.04) but not mortality (p = 0.20). CONCLUSIONS: We demonstrate that the SAS is a significant predictor of perioperative morbidity for patients undergoing PD. This score should be used to identify patients at higher risk in order to prioritize use of postoperative critical care beds and hospital resources.

Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials.

BACKGROUND: Neoadjuvant treatment has proven beneficial for many gastrointestinal (GI) malignancies, but no phase III trials have been completed examining this approach in pancreatic cancer. This meta-analysis examines the best available phase II trials using neoadjuvant treatment for resectable and borderline/unresectable pancreatic adenocarcinoma. METHODS: Phase II trials were identified using a MEDLINE search, and the Cochrane Central Register of Controlled Trials from 1960 to July 2010. Patients were divided into 2 groups: Patients with initially resectable tumors (group A), and patients with borderline/unresectable tumors (group B). Primary outcome measures were rate of resection and survival. Pooled proportions and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. RESULTS: A total of 14 phase II clinical trials including 536 patients were analyzed. After treatment, resectability was 65.8% (95% CI, 55.4-75.6%) compared with 31.6% in group B (95% CI, 14.0-52.5%). A partial response was observed in patients with borderline/unresectable tumors; 31.8 (95% CI, 24.2-39.8%) in group B and 9.5% (95% CI, 2.9-19.4%) in group A (P = .003). Progressive disease was seen in 17.0% (95% CI, 11.9-22.7) of patients in group A versus 21.8% (95% CI, 10.1-36.5%) in group B (P = .006). Median survival in resected patients was 23 months for group A and 22 months for group B. CONCLUSION: Neoadjuvant treatment seems to have some activity in patients with borderline/unresectable pancreatic adenocarcinoma. Nearly one third of tumors initially deemed marginal for operative intervention were able to be ultimately resected after treatment. Until more effective targeted chemotherapeutics are developed, the only group of patients with pancreatic cancer that may benefit from neoadjuvant treatment are those with locally advanced disease.

Anti-angiogenic agents in pancreatic cancer: a review.

Pancreatic cancer is the fourth leading cause of cancer related death in the United States, with a 5-year survival of less than five percent. Since the majority of patients have locally advanced or metastatic disease at the time of diagnosis, there has been little progress made to extend survival. For over ten years, chemotherapy with gemcitabine has been standard treatment for those patients with advanced pancreatic cancer, prolonging survival by only 5-6 months. To improve upon this modest benefit, several investigations have explored other strategies aimed at curbing pancreatic cancer growth. Because pancreatic cancer has been found to have a profoundly hypoxic environment with high vascular in-growth, several agents have been developed to target the angiogenesis process. Major emphasis has been placed on anti- vascular endothelial growth factor (VEGF) models and the epidermal growth factor receptor (EGFR) signaling pathway. Over the past several years, a number of phase II and phase III trials have combined gemcitabine with these novel treatments, with the hope of prolonging survival in patients with pancreatic cancer. This review will discuss these therapies and their potential application in a clinical setting.