Surgical Resection For Pancreatic Cancer Research Articles

Predicting early mortality in resectable pancreatic adenocarcinoma: A cohort study.

414 Background: Overall survival after pancreatic cancer resection remains poor. A subgroup of patients die early (<6 months) and understanding factors associated with early mortality may help identify high-risk patients. The Khorana Score, including baseline hemoglobin, leukocyte and platelet counts, and body mass index [Khorana et al, Blood, 2008], has been shown to be associated with early mortality in solid tumors [Ay et al; Kuderer et al]. We evaluated the role of this score and other prognostic variables in predicting early mortality following resection. Methods: We conducted a cohort study of consecutive patients who underwent surgical resection for pancreatic cancer from January 2006 through June 2013 and were followed at the Cleveland Clinic. Baseline (diagnosis +/- 30 days) parameters were used to define patients as high-risk (Score >=3). Statistically significant univariable associations and a priori prognostic variables were tested in multivariable models; adjusted hazard ratios (HR) are presented. Results: The study population comprised 334 patients. Median age was 67 years; 50% were female; 86% were Caucasian. Pancreatic head was the primary site for 73%; 67% were T3 and 63% were N1 tumors. Median Khorana score was 2; 152 patients (47%) were high-risk. Adjunctive treatment included chemotherapy (70%) and radiation (40%). Post-operative (30-day) mortality was 0.9%. Six-month mortality for the entire cohort was 9.4%, with significantly higher rates for high-risk patients (13.4% vs. 5.6%, p=0.02). In univariable analyses, Khorana score, low hemoglobin, and elevated blood urea nitrogen (BUN) were associated with early mortality; T- and N-stage, as well as margin status (R0/R1), were not. In multivariable analyses (n=326), Khorana score (HR high-risk = 2.31, p=0.039) and elevated BUN (HR = 4.34, p<0.001) were associated with early mortality. Conclusions: Patients at high risk for early mortality after resection of pancreatic adenocarcinoma can be identified using simple baseline patient-related clinical and laboratory parameters rather than tumor characteristics. Future studies could evaluate the benefit of pre-operative interventions targeting patients at high risk for early mortality.

STAT3 as an emerging molecular target in pancreatic cancer

STAT3 as an emerging molecular target in pancreatic cancer Narinder Kumar Sharma,1 Sharmila Shankar,2 Rakesh K Srivastava1 1Department of Pharmacology, Toxicology and Therapeutics, and Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 2Kansas City VA Medical Center, Kansas City, MO, USA Abstract: Pancreatic cancer is the fourth leading cause of cancer related deaths. Although, surgical resection of pancreatic cancer may provide the best chance for cure and long-term survival, due to the late onset of symptoms only 15% to 20% of patients have resectable tumors. Most of the pancreatic tumors have mutations in the K-ras gene, followed by mutations in tumor suppressor genes such as p53 and SMAD4. In addition, there is growing evidence for the potential involvement of signal transducer and activator of transcription 3 (STAT3) in malignant transformation of pancreatic cancer. STAT3 plays critical roles in regulating many physiological functions in normal and malignant tissues, such as inflammation, survival, proliferation, differentiation, and angiogenesis. STAT3 is activated by a wide variety of cytokines, growth factors, and other stimuli. Unlike other members of the STAT family, ablation of STAT3 leads to embryonic lethality and conditional loss of STAT3 protein in adult tissues, leading to a variety of abnormalities, confirming that STAT3 participates in a wide variety of physiological processes. Constitutive activation of STAT3 is implicated in a wide range of human cancers; therefore, STAT3 has been identified as a novel target to treat and prevent cancers. Several STAT3 inhibitors display antitumor effectiveness, and data supporting the use of STAT3 inhibitors are emerging. Different approaches used for the inhibition of activated STAT3 include modulating upstream positive or negative regulators or directly targeting its different domains. These approaches have been used in the inhibition of STAT3 in different cancers, but in this review, we will focus specifically on the inhibition of STAT3 in pancreatic cancer. Keywords: pancreatic cancer, Kras, oncogene, angiogenesis, apoptosis, STAT3

Impact of diabetes mellitus on clinical outcomes in patients undergoing surgical resection for pancreatic cancer: a retrospective, cohort study.

Diabetes mellitus (DM) has a bidirectional association with pancreatic cancer (PaC); however, its effect on clinical outcomes has not been thoroughly evaluated. We analyzed these data in a large sample of PaC subjects who had undergone surgical resection. Subjects enrolled in the Mayo Clinic Pancreatic Cancer SPORE registry from 2000 to 2010 who had resection with curative intent were identified (n=488). Tumor size, cancer stage, and postoperative median survival were evaluated. Median survivals were compared with Kaplan-Meier curves and Cox proportional hazards regression modeling. A total of 275 (56%) subjects had DM before surgery. DM subjects had larger tumors compared with those without DM (3.6 cm vs. 3.3, P=0.002), even after controlling for covariates including age, body mass index, and tumor grade. Cancer stage at the time of surgery was not affected by DM status (P=0.575). Preoperative DM was not associated with an increased risk of death using a multivariable survival analysis (hazard ratio 1.06, 95% confidence interval 0.81-1.38, P=0.676). The median survival following cancer resection was similar between subjects with and without DM (24 vs. 26 months, P=0.610). In addition, postoperative survival was similar on the basis of the duration of DM (new-onset vs. long-standing) and prior use of antidiabetic treatments in diabetic subjects. PaC subjects with DM have larger tumors than nondiabetic subjects. Despite this observation, preoperative DM does not negatively impact the cancer stage at the time of surgery or postoperative survival. Thus, the effect of DM on tumor size is either overshadowed by early metastatic spread of the cancer or is mitigated by the tumor resection.

A tumour score with multidetector spiral CT for venous infiltration in pancreatic cancer: influence on borderline resectable

A tumour score for venous invasion in patients with pancreatic adenocarcinoma was evaluated by means of computed tomography (CT), in order to improve the assessment of medical treatment and clinical outcome with special attention to borderline resectable disease. Fifty-six consecutive patients who underwent curative surgical resection for pancreatic cancer were analysed. On the basis of CT criteria, tumour involvement of the portal vein (PV) and superior mesenteric vein (SMV) was graded according to an adapted 4-point scale: score 1, definite absence of invasion; score 2, probable absence of invasion; score 3, probable presence of invasion; score 4, definite presence of invasion. Correlations between the venous infiltration scores and the patients' clinical features were also evaluated. After radiological evaluation of PV and SMV grades of infiltration, 21/56 (37%) and 37/56 (66%) patients, respectively, were found to have borderline resectable disease. The 4-point scale achieved a sensitivity of 80%, a specificity of 96% and an accuracy of 93% in the evaluation of the PV, and a sensitivity of 100%, a specificity of 94% and an accuracy of 95% in the evaluation of the SMV. Analysis of the distribution of clinical characteristics by PV and SMV infiltration showed that both scores correlated with the presence of distal metastasis (p=0.016 and p=0.028, respectively), and resection margins status (p=0.015 and p=0.006, respectively). This adapted tumour score is reliable for assessing venous invasion and might improve preoperative staging in patients with borderline resectable pancreatic cancer.

The Promise of Modern Radiotherapy in Resected Pancreatic Adenocarcinoma: A Response to Bekaii-Saab et al.

Determining the optimal adjuvant management strategy for patients with resected pancreatic adenocarcinoma remains a controversial topic. In particular, defining the role for radiation continues to generate significant debate. As such, we welcome sustained investigation into whether radiation can improve oncologic outcomes after resection of pancreatic cancer. We therefore appreciate the work done by Bekaii-Saab et al. to review their institution’s experience with adjuvant chemoradiation for localized pancreatic cancer in which they find no benefit on overall survival or local control when comparing patients treated with chemoradiation versus chemotherapy alone. Despite their results, we disagree with the authors’ conclusion that there is ‘‘no benefit from chemoradiation over chemotherapy in the adjuvant treatment of pancreas cancer’’ and that ‘‘based on the available data and outside of a clinical trial, patients should be treated with chemotherapy alone following surgery.’’ Appreciation of the potential that modern radiotherapy may have for resected pancreatic cancer requires a historical understanding of early clinical trials that explored chemoradiation, some of which are referenced by the authors. Early institutional reports demonstrated poor local control after surgical resection of pancreatic cancer, with local failure rates of roughly 50 %. 1 As such, the Gastrointestinal Tumor Study Group (GITSG) undertook a clinical trial comparing 5-fluorouracil (5-FU)-based chemoradiation versus observation in patients undergoing Whipple resection. The chemoradiation arm experienced improved 2-year overall survival (42 vs. 15 %, p = 0.03), leading to widespread adoption of adjuvant chemoradiation in the United States. 2 However, this survival benefit could not be replicated in subsequent trials by the European Organization for Research and Treatment of Cancer (EORTC) and the European Study Group for Pancreatic Cancer (ESPAC), with the latter trial demonstrating the best outcomes in patients treated with chemotherapy alone. 3,4 The

Portal Vein Cannulation During Endoscopic Retrograde Cholangiopancreatography

A 68-year-old woman was admitted to our hospital with obstructive jaundice. Abdominal CT scan demonstrated a mass at the head of the pancreas. The patient was diagnosed as having obstructive jaundice caused by pancreatic cancer. We tried to relieve the bile duct obstruction by ERCP (endoscopic retrograde cholangiopancreatography). After several cannulation attempts, we thought that we had achieved deep cannulation of the bile duct and tried to place a biliary plastic stent. During ERCP, however, we noticed massive air in the portal venous system, indicating possible cannulation of the portal vein. The procedure was terminated immediately and abdominal computed tomography revealed air in the portal venous system. Fortunately, there were no subsequent complications. The air in the portal vein had disappeared, ascertained by CT scan taken 5 days later. The patient underwent surgical resection for pancreatic cancer. Isolated portal vein cannulation per se does not usually result in mortality or serious morbidity. (Korean J Med 2014;86:462-465)

Prognostic factors associated with early mortality after surgical resection for pancreatic adenocarcinoma.

Backgrounds/AimsIdentifying pancreatic cancer patients at high risk of early mortality following surgical resection for pancreatic cancer is important to make optimal treatment decisions in multidisciplinary setting. The purpose of this study was to identify the factors related to early mortality in patients who underwent pancreatic resection for pancreatic adenocarcinoma.MethodsWe reviewed our institution's experience with all consecutive patients who underwent pancreatectomy for pancreatic adenocarcinoma from January 2000 to December 2010. One thousand patients were eligible for our study. Fifty-three patients who did not meet the study criteria were excluded. Based on 12 months after surgery, patients were divided into early mortality group or the remaining group. We performed logistic regression analysis to identify predictors of early mortality.ResultsAmong 947 patients who met our study criteria, 302 (31.9%) early mortality (defined as experiencing death within 12 months after surgery) occurred. Multivariate analysis revealed that patient age and surgery time period were statistically significant predictors of early mortality within six months after surgery. Poorly differentiated tumor and adjuvant chemotherapy were statistically significant predictors of early mortality within 12 months after surgery. Total pancreatectomy and lymphovascular invasion were significant (p<0.05) prognostic factors of early mortality within 6 or 12 months after surgery.ConclusionsWe suggest followings to avoid early mortality after pancreatic resection: patients with multiple risk factors related to early mortality after pancreatectomy should be considered for alternative treatment; patient's general condition and surgical technique improvement are important; and adjuvant therapy should be taken into consideration.

Neoadjuvant Chemoradiation and Duration of Chemotherapy Before Surgical Resection for Pancreatic Cancer: Does Time Interval Between Radiotherapy and Surgery Matter?

Neoadjuvant chemoradiation and chemotherapy provided for borderline or locally advanced, potentially resectable pancreatic adenocarcinoma improves resectability rates. Response to therapy is also an important prognostic factor. There are no data in the literature regarding optimal time interval or duration of chemotherapy after chemoradiation before surgery, and pathologic response rates. Using our database, we evaluated these relationships and the effect on overall and progression-free survival. We retrospectively analyzed the records of 83 patients who underwent neoadjuvant chemoradiation for locally advanced, potentially resectable, and borderline resectable pancreatic cancers before definitive resection. We divided patients into three groups according to time interval between completion of chemoradiation and resection: group A (0-10 weeks), group B (11-20 weeks), and group C (>20 weeks). After chemoradiation, patients underwent ongoing chemotherapy before resection. Pathologic response was defined as major (>95% fibrosis), partial (50-94% fibrosis), or minor (<50% fibrosis). There were 56 patients in group A, 17 patients in group B, and 10 patients in group C. Patients in groups B and C were significantly more likely to experience a major response than group A (p < 0.013). Patients in group C had significantly increased median progression-free and overall survival (p < 0.05). Multivariable classification and regression tree analysis demonstrated pathologic response to be the only significant factor in overall survival. Patients who underwent a prolonged time interval after neoadjuvant chemoradiation with ongoing chemotherapy were more likely to have an improved pathologic response at time of surgical resection, which was associated with improved median overall survival.

AUGIS trainee prize winner: Antimicrobial prophylaxis prior to pancreatico-duodenectomy

AUGIS trainee prize winner: Antimicrobial prophylaxis prior to pancreatico-duodenectomy

Trends in the Treatment of Resectable Pancreatic Adenocarcinoma

BackgroundMultiple prospective, randomized trials have demonstrated that the addition of adjuvant therapy after surgical resection of pancreatic cancer improves survival compared to surgery alone. However, the optimal type of adjuvant therapy, chemotherapy alone, or chemotherapy combined with chemoradiation therapy remains controversial. Our aim was to examine the treatment trends for surgically resectable (stages I and II) pancreatic cancer in the USA using the National Cancer Database. MethodsThe National Cancer Database (NCDB) is a national oncology outcomes database for over 1,500 Commission on Cancer accredited cancer programs. Patients diagnosed with stage I–II pancreatic adenocarcinoma between 2003 and 2010 were selected from the NCDB Hospital Comparison Benchmark Reports. Attention was paid to the initial treatment regimen, such as surgery alone, surgery plus chemotherapy, or surgery plus chemoradiation. In addition, data on hospital setting (teaching hospitals vs. community hospitals) were collected and analyzed. The Cochran–Armitage test for trend was used to assess changes in treatment over time. ResultsFifty-nine thousand ninety-four patients with stage I–II pancreatic adenocarcinoma were included in the analysis. Between 2003 and 2010, the use of surgery alone as first course treatment of stage II disease decreased significantly at both teaching hospitals and community hospitals among patients who underwent surgery (P < 0.0001 for both cases). In the same period, the use of chemotherapy in addition to surgery as treatment of stage I and II disease increased at least twofold at both hospital settings (P < 0.0001 for all cases). Treatment with surgery plus chemoradiation decreased significantly for both stages in both hospital settings (P < 0.0001 for all cases). Nonsurgical treatment for stage II disease was surprisingly high and significantly increased over time (P < 0.001 for both hospital types), ranging from approximately 30–37 % at teaching hospitals and 39–47 % at community hospitals. ConclusionData from the NCDB from 2003 to 2010 illustrate changes in the adjuvant treatment of pancreatic cancer. The use of chemotherapy alone as adjuvant therapy increased whereas the use of multimodality therapy decreased. In addition, there remains an alarmingly high rate of nonsurgical therapy for stage I and II disease.

Functional role of 18F-FDG PET/CT imaging in pancreatic ductal adenocarcinoma patients with diabetes

pancreatic resection have decreased over the past decades, pancreatic cancer still has a dismal prognosis. We hypothesized that survival of resected pancreas head cancer have improved recently. Methods: A total of 401 patients underwent surgical resection for pancreatic adenocarcinoma of head. Patients who underwent in 1995– 2005 (Period 1) were compared with patients in 2006–2011 (Period 2). Results: Overall 5-year survival rate of entire 401 patients was 21.4%. The 5-year survival rate of 241 patients in Period 2 was increased from 15.6% to 26.0 % compared with that of 160 patients in Period 1(Median survival 14.0 months Vs 21.0 months, p1⁄40.001 by log-rank test). Between two periods, there was no significant difference in age, sex, T stage, tumor size, R status and a level of CA 19-9. Whereas N1 disease, poorly differentiation and adjuvant therapy were significantly higher rate in Period 2 compared with those of Period 1. In Period 2, 66.7% of patients were treated by adjuvant therapy compared with 53.% of patients in Period 1(p1⁄40.016). And by multivariate analysis, adjuvant therapy as well as tumor size(more than 2.5 cm), tumor differentiation, and R status were revealed as independent prognostic factors. On subgroup analysis, patients with tumor size (more than 2.5 cm), N1 disease, or well to moderately differentiation had a survival improvement by adjuvant therapy. Conclusions: The survival of pancreatic adenocarcinoma of head following surgical resection has substantially improved in the 2000s. Adjuvant therapy increases overall survival in patients who underwent surgical resection for pancreatic cancer and recently more frequent use of adjuvant therapy accounts for survival improvement in part. So, adjuvant therapy should be considered unless patients have a poor performance status, especially with N1 disease, large tumor or well to moderately differentiation.

T cells dominate the immune infiltrate in human pancreatic cancer. (P2195)

Abstract The absence of an effective immune response to pancreatic cancer is thought to contribute to the poor prognosis of this devastating disease. Recent studies using murine models of pancreatic cancer suggest that regulatory cells within the tumor microenvironment prevent effector CD8 T cells from entering and eliminating tumors. In order to gain a detailed understanding of the immune response to the human disease, we performed flow cytometry to study fresh tumor and blood from patients undergoing surgical resection for pancreatic cancer. Within the dense immune tumor infiltrate, a majority of the cells expressed CD3 (68.2 +/- 13.5%). The distribution of CD4 and CD8 T cells was, on average, comparable to the blood. However, we found significantly elevated levels of inflammatory IL-17 producing CD4 Th17 cells regulatory and CD25+FoxP3+ T cells within the tumor. Although there was a higher percentage of Tregs among the CD4 T cells in the tumor than in the blood, we found that the CD4 and CD8 T cells within the tumor were as capable of producing the inflammatory cytokines IFN-gamma (CD8: tumor 73.2% +/- 17.2%, blood 60 +/- 26%; CD4: tumor 33.3% +/- 12.3%, blood 24.2% +/- 13.9%) and IL-17 (CD4: tumor 4.3% +/- 4.2%, blood 1.35% +/- 1.3%) as their counterparts in the blood. In order to determine the relationship between the T cells and cancer cells, we performed CD3 immunohistochemistry and determined that infiltrating CD3+ cells are typically in close proximity to cancer cells.

Abstract 726: Fluorophore-conjugated antibodies improve surgical resection of pancreatic cancer leading to prolonged disease-free survival and overall survival in orthotopic mouse models.

Abstract We established orthotopic mouse models of human pancreatic cancer with fragments of BxPC-3-RFP tumor. Two weeks after implantation, mice were randomized to FGS or bright-field surgery (BS). FGS was performed 24 hrs after tail vein injection of anti-CEA-Alexa 488. Completeness of resection was assessed from pre- and postoperative images obtained with the OV-100 Small Animal Imaging System. Whole body images of mice were obtained postoperatively to assess for recurrence and mice were followed until premorbid to measure survival. We achieved a complete resection of pancreatic cancers in 92% of mice in the FGS group as compared to 58% in the BS group (p=0.002). Preoperative tumor burden was not significantly different between groups (p=0.424). However, FGS afforded a significantly smaller mean postoperative tumor burden compared to BS: 0.0004 ± SE 0.0003 mm2 vs. 0.0841 ± SE 0.027 mm2, p=0.004. On average, mice in the FGS experienced a greater reduction in tumor burden: 99.99% vs 97.72%, p=0.01. FGS reduced recurrence rates from 95% to 50% (p=0.002) and lengthened mean disease-free survival from 7 weeks to 30.5 weeks (p&amp;lt;0.001). The FGS group experienced longer overall survival compared to the BS group: 16.5 weeks vs. 37 weeks (p=0.001). Cure rate was improved with FGS from 5% to 50% (p=0.003). Furthermore, FGS more than doubled the one-year postoperative survival rate from 3 mice in the BLS group to 8 mice in the FGS group (p=0.005). This novel approach has potential to improve outcomes in the surgical treatment of pancreatic cancer. Survival and recurrence according to surgical mode. Surgical Mode Disease-Free Survival Overall Survival Recurrence Rate Bright-Field Surgery 7 weeks 16.5 weeks 95% Fluorescence-Guided Surgery 30.5 weeks 37 weeks 50% Citation Format: Cristina A. Metildi, Sharmeela Kaushal, Mark A. Talamini, George A. Luiken, Robert M. Hoffman, Michael Bouvet. Fluorophore-conjugated antibodies improve surgical resection of pancreatic cancer leading to prolonged disease-free survival and overall survival in orthotopic mouse models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 726. doi:10.1158/1538-7445.AM2013-726

RE: CA 19-9 in Potentially Resectable Pancreatic Cancer: Perspective to Adjust Surgical and Preoperative Therapy

I am really not a pessimist, but several concepts continue to surround the surgical management of pancreatic adenocarcinoma: (1) despite improvements in radiologic technology, a significant fraction of patients are still found to have unresectable disease in the operating room, (2) despite improvements in perioperative care and team-based patient management, a significant fraction of patients develop complications of surgical resection that may lead to immediate death, delayed death, or dramatically decreased quality of life, (3) the vast majority of patients will die from recurrent disease despite a a curativea resection, and (4) improvements in adjuvant therapy have lagged behind the treatment of other solid organ malignancies and offer only small improvements in median survival. If I were a pessimist, I would never operate on these patients, but instead I continue to hold out hope that each patient may be that uncommon 5or 10-year survivor following surgical resection of pancreatic cancer. Nearly a decade has passed since the association of carbohydrate antigen (CA) 19-9 with some aspect of the biology of pancreatic cancer was first reported. Since that time, various roles of CA 19-9 in the management of patients with pancreatic adenocarcinoma have been described including the differentiation of benign from malignant pancreatic disease, prediction of resectable disease, identification of patients for selective staging laparoscopy, the identification of patients at risk for early recurrence and death following potentially curative resection, and for use in the surveillance for disease recurrence. Yet for each of these aspects, the specific role of CA 19-9 is only part of clinical assessment and decision making in these patients. Before beginning the discussion, it is critical to understand what CA 19-9 is and how it can be used as a a tumor marker.a CA 19-9 was first identified following the screening patient sera by hybridoma-derived monoclonal antibodies. One such antibody, 1116 NS 19-9 developed by Koprowski et al., 3 was shown to react with a sialylated lacto-N-fucopentaose II, which was present in high levels in sera of patients with colon, gastric, and pancreatic cancer. Based on the screening of a variety of tumors by immunohistochemical methods as well as sera from patients with a variety of gastrointestinal and gynecologic cancers, CA 19-9 was felt to be specific for malignancy and termed a a tumor markera . In screening sera from more than 1,000 blood donors, CA 19-9 was found to be undetectable ino~8o%, and waso\37 U/ml in all but six samples, hence the threshold value of 37 U/ml for a normala . Yet 4o% of a parallel study population of patients with benign disease (such as inflammatory bowel disease, pancreatitis, or gastrointestinal polyps) had CA 19-9 levelso [37 U/ml. Thus, CA 19-9 is not a perfect tumor marker in terms of sensitivity (79o% for pancreatic adenocarcinoma, 50o% for gastric carcinoma, and 46o% for advanced colorectal carcinoma) and specificity (98.5o%). However, it is pretty good when compared with other tumor markers such as CEA, alphafetoprotein or CA 125. There are three important limitations of CA 19-9 that must be recognized as they are critical to the implementation in patients with suspected pancreatic cancer. The first is that CA 19-9 is a sialylated Lewis (a) antigen, which is normally expressed on the surface of erythrocytes. Up to 10o% of the white population will not express any detectable level of CA 19-9 because of absence of fucosyltransferase, one of the enzymes involved in the biosynthesis. Therefore, in up to 10o% of patients with pancreatic adenocarcinoma, CA 19-9 will be undetectable and therefore of no utility in any aspect of clinical decision making. The second aspect relates to the lack of perfect specificity in which patients with benign disease can have Society of Surgical Oncology 2013

Impact of diabetes mellitus on clinical outcomes in patients undergoing surgical resection for pancreatic cancer

Impact of diabetes mellitus on clinical outcomes in patients undergoing surgical resection for pancreatic cancer

Fluorophore-conjugated antibodies improve surgical resection of pancreatic cancer leading to prolonged disease-free survival and overall survival in orthotopic mouse models

Fluorophore-conjugated antibodies improve surgical resection of pancreatic cancer leading to prolonged disease-free survival and overall survival in orthotopic mouse models

Imaging-guided curative surgical resection of pancreatic cancer in a xenograft mouse model

Pancreatic cancer is the fourth leading cause of cancer related deaths in North America. The poor survival statistics are due to the fact that there are no reliable tests for early diagnosis and no effective therapies once metastasis has occurred. Surgical resection is the only curative treatment for pancreatic cancer; however, only less than 15% of the patients are eligible for surgery at diagnosis. New therapies are urgently needed for this malignant disease. And combinational therapy including surgery, chemotherapy and molecular targeted therapy may further improve the efficacy of individual therapies. However, a reliable mouse model which mimics the human disease and can be used for testing the surgical treatment and surgery-based combinational therapy is not available. In this study, we have established a mouse model for curative surgical resection of pancreatic cancer. Human pancreatic cancer cells were used to create orthotopic xenografts in nude mice, distal pancreatectomy was performed using imaging-guided technology to remove the pancreatic tumors, and sham surgery was performed in the control group. All mice survived the operation and no complication was observed. Surgical resection at early stage improved the survival rate and quality of life of the mice compared with the sham surgery and surgical resection at the late stage. If combined with other therapies such as chemotherapy and molecular targeted therapy, it could further improve the outcome of pancreatic cancer. This mouse model is a useful tool to study the surgical therapy and the tumor recurrence of pancreatic cancer, and could potentially impact the therapeutic choices for this deadly disease.

Serum CA19-9 is a Significant Predictor among Preoperative Parameters for Early Recurrence after Resection of Pancreatic Adenocarcinoma

ObjectiveTo evaluate the preoperative factors predictive of postoperative early recurrence in patients with resected pancreatic cancer focusing on the serum CA19-9 value. MethodsOne hundred fifty-four patients undergoing surgical resection for pancreatic cancer were enrolled in this study. Univariate and multivariate analyses were performed to determine the predictors of early recurrence which was defined as relapse within 6 months after surgery. ResultsOn ROC curve analysis, the cutoff value of CA19-9 was determined to be 100 U/ml. Of 73 patients with CA19-9 value ≥ 100 U/ml, 39 (53 %) had early recurrence. In contrast, only 9 of 81 patients (11 %) with CA19-9 value < 100 U/ml developed a recurrence at an early period (p < 0.001). Multivariate analysis revealed that CA19-9 value ≥ 100 U/ml (odds ratio, 11.2) were significant predictors of early recurrence. The overall 3- and 5-year survival rates and median survival times were 47.3 %, 40.1 %, and 31 months in patients with CA19-9 value < 100 U/ml and 21.2 %, 9.4 %, and 16 months in patients with CA19-9 value ≥ 100 U/ml (p < 0.001). ConclusionsA preoperative CA19-9 value ≥ 100 U/ml was a significant predictor of early recurrence and a poor prognosis after resection for pancreatic adenocarcinoma.

Comparison of Outcomes and the Use of Multimodality Therapy in Young and Elderly People Undergoing Surgical Resection of Pancreatic Cancer

To compare outcomes and the use of multimodality therapy in young and elderly people with pancreatic cancer undergoing surgical resection. Retrospective, single-institution study. National Cancer Institute/National Comprehensive Cancer Network cancer center. Two hundred three individuals who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma at Duke University Medical Center comprised the study population. Participants were divided into three groups based on age (<65, n=97; 65-74, n=74; ≥75, N=32). Perioperative outcomes, the use of multimodality therapy, and overall survival of the different age groups were compared. Similar rates of perioperative mortality and morbidity were observed in all age groups, but elderly adults were more likely to be discharged to a rehabilitation or skilled nursing facility. A similar proportion of participants received neoadjuvant therapy, but a smaller proportion of elderly participants received adjuvant therapy. Overall survival was similar between the age groups. Predictors of poorer overall survival included coronary artery disease, positive resection margin, and less-differentiated tumor histology. Treatment with neoadjuvant and adjuvant therapy were predictors of better overall survival. Carefully selected elderly individuals experience similar perioperative outcomes and overall survival to those of younger individuals after resection of pancreatic cancer. There appears to be a significant disparity in the use of adjuvant therapy between young and elderly individuals.

MicroRNA Expression as a Predictive Marker for Gemcitabine Response after Surgical Resection of Pancreatic Cancer

BackgroundTo improve the prognosis of patients after resection of pancreatic cancer, the most appropriate and efficient treatment should be provided to specific subsets of patients. Our aim was to identify promising microRNAs as markers to predict responses to gemcitabine in patients with resected pancreatic cancer.MethodsTwo gemcitabine-resistant pancreatic cancer cell lines were established, and global microRNA expression analyses was performed by quantitative reverse transcription–polymerase chain reaction (qRT-PCR). Eleven miRNAs were selected as putative predictive markers and analyzed by means of macrodissected formalin-fixed, paraffin-embedded samples obtained from 90 patients with or without gemcitabine treatment after resection of pancreatic cancer.ResultsWe identified 24 microRNAs whose expression was altered in gemcitabine-resistant cells. qRT-PCR analyses showed that patients with high miR-142-5p and miR-204 expression had significantly longer survival times than those with low miR-142-5p (P = 0.0077) and miR-204 (P = 0.0054) expression in the gemcitabine-treated group. This was not seen in the nontreated group. Multivariate analyses showed that miR-142-5p expression was an independent prognostic marker only in patients treated with gemcitabine (P = 0.034).ConclusionsmiR-142-5p is a promising predictive marker for gemcitabine response in patients with resected pancreatic cancer.