Pancreatic cancer is a disease in which the cells of the pancreas become malignant. The pancreas has two main functions; (i) it makes juices that help digest food and (ii) produces hormones (including insulin) that conrol how food is used and stored in the body. The vast majority of pancreatic cancers are associated with the part of the pancreas that makes digestive juices - these are known as "exocrine" pancreatic cancers. Only about 1/20 pancreatic cancers start in the hormone producing part of the pancreas ; these are known as "endocrine" pancreatic cancer or "islet cell cancer". There are several types of exocrine pancreatic cancers (based on how the cells appear under the microsope), most are classed as "ductal adenocarcinomas". Pancreatic cancer is rare before the age of 40 years, incidence increases sharply with increasing age.
A national, nonprofit organization, founded in 1997, dedicated to advancing pancreatic cancer research, and providing information, resources and support to pancreatic cancer patients and their families.
An advocacy organization founded by patients and families in 1999 to focus attention on the need to find the cure for pancreatic cancer. The Web site provides details of events, services and informatiion for patients and health professionals.
Cancer Patients Alliance An initiative of the Cancer Patients Alliance, with input from an expert scientific board. It includes a searchable database of clinical trials, FAQs, news and research information relating to pancreatic cancer.
PubMed Central search for free-access publications about Pancreatic Cancer MeSH term: Pancreatic Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
This list of publications is regularly updated (Source: PubMed).
Gruszewska E, Chrostek L, Cylwik B, et al. Serum sialic acid as a marker of pancreatic cancers. Clin Lab. 2013; 59(7-8):781-8 [PubMed] Related Publications
BACKGROUND: The carbohydrate alterations in sialoglycoproteins and sialoglycolipids cause the high serum concentration of sialic acid in many types of cancers. The aim of this study was to evaluate the diagnostic accuracy of total sialic acid (TSA), lipid-bound sialic acid (LSA), and free sialic acid (FSA) in patients with primary pancreatic cancers. METHODS: TSA and LSA concentrations in the sera of 42 patients were measured by the enzymatic and FSA by the thiobarbituric method. RESULTS: The mean levels of TSA, LSA, and FSA in the sera of patients with pancreatic cancers were significantly higher than in controls. Taking into consideration the size and the location of the tumors, regional lymph node and distant metastases, there were no differences in TSA, FSA, and CA 19-9 levels. However, the location of tumors in the pancreas affects LSA levels. The sialic acids, contrary to CA 19-9, are not useful tools in the differential diagnosis of tumors and non-malignant diseases of the pancreas. LSA has the highest sensitivity, negative predictive value, accuracy, and the ability to discriminate cancer patients from healthy controls. The diagnostic power of LSA is similar to CA 19-9. CONCLUSIONS: We suggest that LSA can be useful in the diagnosis and evaluation of the tumor location in patients with primary pancreatic cancers.
Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013; 369(18):1691-703 [PubMed] Related Publications
BACKGROUND: In a phase 1-2 trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine, substantial clinical activity was noted in patients with advanced pancreatic cancer. We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer. METHODS: We randomly assigned patients with a Karnofsky performance-status score of 70 or more (on a scale from 0 to 100, with higher scores indicating better performance status) to nab-paclitaxel (125 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter) on days 1, 8, and 15 every 4 weeks or gemcitabine monotherapy (1000 mg per square meter) weekly for 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles). Patients received the study treatment until disease progression. The primary end point was overall survival; secondary end points were progression-free survival and overall response rate. RESULTS: A total of 861 patients were randomly assigned to nab-paclitaxel plus gemcitabine (431 patients) or gemcitabine (430). The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). The survival rate was 35% in the nab-paclitaxel-gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years. The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group, as compared with 3.7 months in the gemcitabine group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; P<0.001); the response rate according to independent review was 23% versus 7% in the two groups (P<0.001). The most common adverse events of grade 3 or higher were neutropenia (38% in the nab-paclitaxel-gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile neutropenia occurred in 3% versus 1% of the patients in the two groups. In the nab-paclitaxel-gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days. CONCLUSIONS: In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved overall survival, progression-free survival, and response rate, but rates of peripheral neuropathy and myelosuppression were increased. (Funded by Celgene; ClinicalTrials.gov number, NCT00844649.).
Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013; 310(14):1473-81 [PubMed] Related Publications
IMPORTANCE: The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated. OBJECTIVE: To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival. DESIGN, SETTING, AND PATIENTS: CONKO-001 (Charité Onkologie 001), a multicenter, open-label, phase 3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012. INTERVENTIONS: After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone. MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. Patients lost to follow-up were censored on the date of their last follow-up. RESULTS: A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI, 83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95% CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95% CI, 0.61-0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%-11.8%). CONCLUSIONS AND RELEVANCE: Among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN34802808.
Gardner TB, Glass LM, Smith KD, et al. Pancreatic cyst prevalence and the risk of mucin-producing adenocarcinoma in US adults. Am J Gastroenterol. 2013; 108(10):1546-50 [PubMed] Related Publications
OBJECTIVES: The presence of a pancreatic cyst often prompts concern, although the rate of malignant transformation to mucin-producing adenocarcinoma is not known. We aimed to determine the prevalence rate of mucin-producing adenocarcinoma in US adults with pancreatic cysts. METHODS: This retrospective, population-based cross-sectional study calculated the annual number of mucin-producing adenocarcinomas using the Surveillance Epidemiology and End Results (SEER 18) database and the 2010 US census. The overall prevalence rate of cysts in the population was found using data from large cross-sectional imaging studies of incidental cyst prevalence. Prevalence rates were then calculated by dividing the annual number of mucin-producing adenocarcinomas by the cyst prevalence rate. RESULTS: Between 2005 and 2009, 1,137 mucin-producing adenocarcinomas were estimated to be found annually in a US adult population of 137,154,960. The total number of pancreas cysts, given a cyst prevalence rate of 2.5%, was 3,428,874. Therefore, the prevalence rate of mucin-producing adenocarcinoma arising in patients with pancreatic cysts was 33.2 per 100,000 (95% confidence interval (CI): 21.9-44.5). The prevalence rate was 32.8 per 100,000 (95% CI: 21.6-44.0) in women and 33.5 per 100,000 (95% CI: 22.2-44.8) in men. As expected, the rate of malignant transformation increased linearly with advancing age (highest 38.6 per 100,000 in 80- to 84-year-old men). CONCLUSIONS: Malignant transformation of pancreatic cysts into mucin-producing adenocarcinoma in US adults is a very rare event. Current clinical guidelines and resource allocation for pancreatic cyst disease should be reconsidered given these findings.
van Vliet EI, Krenning EP, Teunissen JJ, et al. Comparison of response evaluation in patients with gastroenteropancreatic and thoracic neuroendocrine tumors after treatment with [177Lu-DOTA0,Tyr3]octreotate. J Nucl Med. 2013; 54(10):1689-96 [PubMed] Related Publications
UNLABELLED: Response Evaluation Criteria In Solid Tumors (RECIST) (unidimensional), Southwest Oncology Group (SWOG) solid tumor response criteria (bidimensional), and their modified variants are commonly used in the tumor response assessment after treatment of gastroenteropancreatic and thoracic neuroendocrine tumors (NETs). In the current study, RECIST, SWOG criteria, modified RECIST (mRECIST), and modified SWOG (mSWOG) criteria were compared in patients with NETs treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). METHODS: Two-hundred sixty-eight Dutch patients with NETs who had been treated with (177)Lu-octreotate between January 2000 and April 2007 were studied. CT or MR imaging scans were analyzed using RECIST, SWOG criteria, mRECIST, and mSWOG criteria (including the tumor response class minor response [decrease of 13%-30% for mRECIST and 25%-50% for mSWOG]). The outcomes were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: Eleven patients had an unknown tumor response and were excluded. The rates of objective response (OR) (complete response + partial response [+minor response for mRECIST/mSWOG]), stable disease, and progressive disease (PD) were 28%, 49%, and 24%, respectively, according to RECIST; 25%, 49%, and 26%, respectively, according to SWOG; 44%, 33%, and 24%, respectively, according to mRECIST; and 45%, 29%, and 26%, respectively, according to mSWOG. In patients who had OR, stable disease, or PD, the median PFS was 26-30, 27-34, and 8 mo, respectively, with any of the 4 response criteria. In patients who had OR, stable disease, or PD, the median OS was 55-57, 56-74, and 11-12 mo, respectively, with any of the 4 response criteria. Subanalyses for patients who had progression before treatment start were comparable. CONCLUSION: Patients with PD as treatment outcome had significantly shorter PFS and OS than patients with an OR or stable disease with all 4 scoring systems. PFS and OS were comparable for patients with tumor regression and stable disease. The addition of the response class minor response did not improve the correlation with PFS and OS. The 4 scoring systems gave comparable results in terms of PFS and OS per categorized outcome.
Kim KW, Krajewski KM, Nishino M, et al. Update on the management of gastroenteropancreatic neuroendocrine tumors with emphasis on the role of imaging. AJR Am J Roentgenol. 2013; 201(4):811-24 [PubMed] Related Publications
OBJECTIVE: The purposes of this article are to review the current management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) based on the 2012 National Comprehensive Cancer Network guidelines and to describe the role of imaging in a multidisciplinary approach. CONCLUSION: The management of GEP-NETs has become complex, requiring a multidisciplinary approach. The World Health Organization classification of GEP-NETs has been revised; the U.S. Food and Drug Administration has approved molecular targeted agents (sunitinib, everolimus) for the treatment of pancreatic NETs; and the National Comprehensive Cancer Network clinical practice guidelines have been updated.
Raman SP, Kawamoto S, Law JK, et al. Institutional experience with solid pseudopapillary neoplasms: focus on computed tomography, magnetic resonance imaging, conventional ultrasound, endoscopic ultrasound, and predictors of aggressive histology. J Comput Assist Tomogr. 2013 Sep-Oct; 37(5):824-33 [PubMed] Related Publications
OBJECTIVE: Solid pseudopapillary neoplasms (SPNs) are low-grade malignancies with an excellent prognosis, albeit with the potential for metastatic disease. This study details our institution's experience with the diagnosis and treatment of SPN, including clinical presentation, multimodality imaging findings, and potential predictors of aggressive tumor behavior. MATERIALS AND METHODS: The institutional pathology database was searched through for all cases of SPN since 1988, yielding 51 patients. The electronic medical record was searched for clinical and demographic information regarding these patients, including age, sex, presenting symptoms, type of surgery, postoperative length of stay, tumor markers, and postsurgical follow-up. All available imaging data were reviewed, including those of 30 patients who underwent multidetector computed tomography, those of 9 patients who underwent magnetic resonance imaging (MRI), those of 3 patients who underwent conventional ultrasound, and those of 11 patients who underwent endoscopic ultrasound. RESULTS: A total of 84% of patients were females, with a mean age of only 33 years. Prognosis was excellent, with a mean follow-up of 3 years without recurrence. Only 1 of the 51 patients developed metastatic disease to the liver 8 years after the surgery. On computed tomography, lesions tended to be large (5.3 cm), well circumscribed (29/30), round/oval (20/30), and encapsulated (23/30). The lesions often demonstrated calcification (14/30) and typically resulted in no biliary or pancreatic ductal dilatation. The lesions ranged from completely cystic to completely solid. On MRI, the lesions often demonstrated a T2 hypointense or enhancing capsule (6/9) and demonstrated internal blood products (5/9). The lesions tended to be devoid of vascularity on conventional ultrasound. Ten patients were found to have "aggressive" histology at presentation (T3 tumor, nodal involvement, perineural invasion, or vascular invasion). No demographic, clinical, or multidetector computed tomographic imaging features were found to correlate with aggressive histology. CONCLUSIONS: Certain imaging features (eg, well-circumscribed mass with calcification, peripheral capsule, internal blood products, and lack of biliary/pancreatic ductal obstruction) on computed tomography and MRI are highly suggestive of the diagnosis of SPN, particularly when visualized in young female patients. However, it is not possible to predict aggressive histology on the basis of imaging findings, clinical presentation, or patient demographic features.
Yamamura S, Oda S, Utsunomiya D, et al. Dynamic computed tomography of locally advanced pancreatic cancer: effect of low tube voltage and a hybrid iterative reconstruction algorithm on image quality. J Comput Assist Tomogr. 2013 Sep-Oct; 37(5):790-6 [PubMed] Related Publications
OBJECTIVE: The objective of this study was to evaluate the effect of a low-tube-voltage technique and hybrid iterative reconstruction (HIR) on image quality at dynamic computed tomography (CT) of the pancreas. METHODS: The study included 18 consecutive patients (10 women, 8 men; mean age, 68.5 ± 9.5 years) with locally advanced pancreatic cancer who received chemotherapy and had stable disease during the 100- and 120-kV CT studies. The 120-kV images were reconstructed using filtered back projection, and the 100-kV images were postprocessed using filtered back projection and HIR. Scans obtained during 3 pancreatic phases were subjected to quantitative and qualitative analysis. RESULTS: The mean effective dose was significantly lower under the 100- than the 120-kV protocols (29.2 ± 3.6 vs 52.1 ± 5.1 mSv; P < 0.01). The mean contrast-to-noise ratio of the pancreatic cancer and the visual scores were significantly higher under 100 kV with HIR than those under the other 2 protocols (P < 0.01). CONCLUSIONS: Use of low tube voltage and HIR can provide significantly improved image quality at pancreatic dynamic CT.
Sahora K, Mino-Kenudson M, Brugge W, et al. Branch duct intraductal papillary mucinous neoplasms: does cyst size change the tip of the scale? A critical analysis of the revised international consensus guidelines in a large single-institutional series. Ann Surg. 2013; 258(3):466-75 [PubMed] Related Publications
OBJECTIVE: The aim of this study was to critically analyze the safety of the revised guidelines, with focus on cyst size and worrisome features in the management of BD-IPMN. BACKGROUND: The Sendai guidelines for management of branch duct (BD) intraductal papillary mucinous neoplasm (IPMN) espouse safety of observation of asymptomatic cysts smaller than 3 cm without nodules (Sendai negative). Revised international consensus guidelines published in 2012 suggest a still more conservative approach, even for lesions of 3 cm or larger. By contrast, 2 recent studies have challenged the safety of both guidelines, describing invasive carcinoma or carcinoma in situ in 67% of BD-IPMN smaller than 3 cm and in 25% of "Sendai-negative" BD-IPMN. METHODS AND RESULTS: Review of a prospective database identified 563 patients with BD-IPMN. A total of 240 patients underwent surgical resection (152 at the time of diagnosis and 88 after being initially followed); the remaining 323 have been managed by observation with median follow-up of 60 months. No patient developed unresectable BD-IPMN carcinoma during follow-up. Invasive cancer arising in BD-IPMN was found in 23 patients of the entire cohort (4%), and an additional 21 patients (3.7%) had or developed concurrent pancreatic ductal adenocarcinoma. According to the revised guidelines, 76% of resected BD-IPMN with carcinoma in situ and 95% of resected BD-IPMN with invasive cancer had high-risk stigmata or worrisome features. The risk of high-grade dysplasia in nonworrisome lesions smaller than 3 cm was 6.5%, but when the threshold was raised to greater than 3 cm, it was 8.8%, and 1 case of invasive carcinoma was found. CONCLUSIONS: Expectant management of BD-IPMN following the old guidelines is safe, whereas caution is advised for larger lesions, even in the absence of worrisome features.
Owens P, Henry-Tillman R, Badgwell B Predictors of stage and the application of curative-intent surgery in pancreatic cancer: a population-based analysis from the Arkansas Cancer Registry. J Ark Med Soc. 2013; 110(2):43-5 [PubMed] Related Publications
BACKGROUND: The purpose of this study was to describe the characteristics of pancreatic cancer subjects within the state of Arkansas. METHODS: Pancreatic cancer patients diagnosed from 5/1997 to 12/2007 were identified from the Arkansas Cancer Registry. Analysis was performed to identify variables associated with advanced-stage and curative-intent surgery. RESULTS: For 3,227 subjects, only grade was associated with advanced stage pancreatic cancer. Age > 80, pancreatic cancer site not specified, and grade were associated with curative-intent surgery. CONCLUSIONS: Studies utilizing the Arkansas Cancer Registry are feasible and can identify variables associated with stage and treatment.
Hammer ST, Owens SR Pancreatoblastoma: a rare, adult pancreatic tumor with many faces. Arch Pathol Lab Med. 2013; 137(9):1224-6 [PubMed] Related Publications
Pancreatoblastomas are malignant epithelial neoplasms of the pancreas that are heterogeneous and have variable cellular differentiation, complicating the diagnosis. We report a case of pancreatoblastoma occurring in an adult patient, presenting as a pancreatic head mass with liver metastasis and jaundice. The initial liver biopsy diagnosis was metastatic neuroendocrine carcinoma based on morphology and synaptophysin positivity. At pancreatic resection, the diagnostic features of pancreatoblastoma were recognized. We review the radiologic and pathologic differential diagnosis, histologic heterogeneity, clinical presentation, and associated genetic syndromes for this unusual tumor that can mimic other types of pancreatic neoplasia.
Stolzenberg-Solomon RZ, Schairer C, Moore S, et al. Lifetime adiposity and risk of pancreatic cancer in the NIH-AARP Diet and Health Study cohort. Am J Clin Nutr. 2013; 98(4):1057-65 [PubMed] Article available free on PMC after 01/10/2014 Related Publications
BACKGROUND: The association of excess body weight across a lifetime with pancreatic cancer has not been examined extensively. OBJECTIVE: We determined the association for body mass index (BMI) at different ages and adiposity duration and gain with incident pancreatic adenocarcinoma in the NIH-AARP Diet and Health Study cohort. DESIGN: Participants aged 50-71 y completed questionnaires at baseline (1995-1996) and 6 months later that queried height and weight history. We calculated HRs and 95% CIs by using Cox proportional hazards models adjusted for age, smoking, sex, and intakes of energy and total fat. Results: Over an average follow-up of 10.5 y, 1206 and 2122 pancreatic cancer cases were identified in the subcohort who completed the second questionnaire (n = 273,975) and the baseline cohort (n = 501,698), respectively. Compared with normal weight, overweight or obesity at ages 18, 35, 50, or >50 y (baseline BMI) was significantly associated with pancreatic cancer, with HRs ranging from 1.15 to 1.53. A longer duration of BMI (in kg/m(2)) >25.0 was significantly associated with pancreatic cancer (overall HR per 10-y increment of duration: 1.06; 95% CI: 1.02, 1.09), with individuals who reported diabetes having the greatest risk (HR per 10-y increment of duration: 1.18; 95% CI: 1.05, 1.32; P-interaction = 0.01) and rates. A substantial gain in adiposity (>10 kg/m(2)) after age 50 y was significantly associated with increased pancreatic cancer risk. The etiologic fraction of pancreatic cancer explained by adiposity at any age was 14% overall and 21% in never smokers. CONCLUSION: Overweight and obesity at any age are associated with increased pancreatic cancer.
Collins BT, Murad FM, Wang JF, Bernadt CT Rapid on-site evaluation for endoscopic ultrasound-guided fine-needle biopsy of the pancreas decreases the incidence of repeat biopsy procedures. Cancer Cytopathol. 2013; 121(9):518-24 [PubMed] Related Publications
BACKGROUND: Rapid on-site evaluation (ROSE) for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsy of the pancreas provides immediate feedback regarding cellular adequacy to aid in obtaining a definitive diagnosis and has the potential to avoid repeat procedures. The objective of the current study was to measure the impact of ROSE service on the incidence of repeat EUS FNA biopsy procedures. METHODS: Over a consecutive 3-year period, the pathology database at Washington University Medical Center was searched for patients with both an initial and subsequent EUS FNA biopsy demonstrating a solid lesion of the pancreas. These were divided temporally between the time before and after the introduction of ROSE service. Reports were reviewed and results were recorded. RESULTS: A total of 379 patients underwent ROSE service and 377 patients did not. The percentage of repeat non-ROSE EUS FNA cases was 5.8% and the percentage of repeat ROSE EUS FNA cases was 2.9%. The use of the ROSE service was found to decrease the number of repeat procedures by approximately 50% (P = .024). For those patients who underwent a repeat EUS-FNA procedure, the ROSE service provided a higher rate of definitive diagnosis among patients undergoing repeat procedures (67%) versus the non-ROSE cohort (27%). CONCLUSIONS: The use of ROSE for EUS-FNA biopsy of the pancreas was found to result in fewer patients undergoing repeat procedures. Patients who required a repeat procedure with the use of ROSE had a higher percentage of definitive diagnostic categorization on the repeat biopsy. Initial use of ROSE for EUS-FNA of solid pancreatic lesions was found to decrease the number of patients who required a repeat procedure.
Pham H, Ekaterina Rodriguez C, Donald GW, et al. miR-143 decreases COX-2 mRNA stability and expression in pancreatic cancer cells. Biochem Biophys Res Commun. 2013; 439(1):6-11 [PubMed] Article available free on PMC after 13/09/2014 Related Publications
Small non-coding RNAs, microRNAs (miRNA), inhibit the translation or accelerate the degradation of message RNA (mRNA) by targeting the 3'-untranslated region (3'-UTR) in regulating growth and survival through gene suppression. Deregulated miRNA expression contributes to disease progression in several cancers types, including pancreatic cancers (PaCa). PaCa tissues and cells exhibit decreased miRNA, elevated cyclooxygenase (COX)-2 and increased prostaglandin E2 (PGE2) resulting in increased cancer growth and metastases. Human PaCa cell lines were used to demonstrate that restoration of miRNA-143 (miR-143) regulates COX-2 and inhibits cell proliferation. miR-143 were detected at fold levels of 0.41 ± 0.06 in AsPC-1, 0.20 ± 0.05 in Capan-2 and 0.10 ± 0.02 in MIA PaCa-2. miR-143 was not detected in BxPC-3, HPAF-II and Panc-1 which correlated with elevated mitogen-activated kinase (MAPK) and MAPK kinase (MEK) activation. Treatment with 10 μM of MEK inhibitor U0126 or PD98059 increased miR-143, respectively, by 187 ± 18 and 152 ± 26-fold in BxPC-3 and 182 ± 7 and 136 ± 9-fold in HPAF-II. miR-143 transfection diminished COX-2 mRNA stability at 60 min by 2.6 ± 0.3-fold in BxPC-3 and 2.5 ± 0.2-fold in HPAF-II. COX-2 expression and cellular proliferation in BxPC-3 and HPAF-II inversely correlated with increasing miR-143. PGE2 levels decreased by 39.3 ± 5.0% in BxPC-3 and 48.0 ± 3.0% in HPAF-II transfected with miR-143. Restoration of miR-143 in PaCa cells suppressed of COX-2, PGE2, cellular proliferation and MEK/MAPK activation, implicating this pathway in regulating miR-143 expression.
Atema JJ, Eshuis WJ, Busch OR, et al. Association of preoperative symptoms of gastric outlet obstruction with delayed gastric emptying after pancreatoduodenectomy. Surgery. 2013; 154(3):583-8 [PubMed] Related Publications
BACKGROUND: Delayed gastric emptying (DGE) is among the most common complications after pancreatoduodenectomy (PD) and might demand postoperative nutritional support. The aim of this study was to investigate the association between preoperative symptoms of gastric outlet obstruction and DGE after PD in an attempt to identify patients in whom placement of a feeding tube at time of operation might be beneficial. METHODS: We analyzed a consecutive series of 401 patients undergoing PD from a prospective database. Preoperative symptoms of nausea, vomiting, loss of appetite, weight loss, postprandial complaints, and dysphagia were retrospectively determined. Primary outcome was clinically relevant DGE according to the International Study Group of Pancreatic Surgery classification and the necessity of postoperative insertion of a nasojejunal feeding tube. RESULTS: The incidence of clinically relevant DGE was 33.2% (133/401 patients). A nasojejunal feeding tube was inserted in 119 patients (29.7%). Patients having ≥2 symptoms of gastric outlet obstruction except weight loss (50 patients; 12.5%), were at a greater risk of developing both DGE (21.1% vs 8.2%; P < .001) and the need for insertion of a feeding tube (21.8% vs 8.5%; P < .001). In multivariable logistic regression analysis, the presence of ≥2 symptoms of gastric outlet obstruction other than weight loss remained a significant predictor of DGE (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7-5.8) and the need for insertion of a nasojejunal feeding tube (OR, 3.1; 95% CI, 1.7-5.7). CONCLUSION: The preoperative presence of ≥2 symptoms of gastric outlet obstruction is a significant predictor of postoperative DGE after PD. By applying this risk factor, patients in whom placement of a feeding tube during surgery should be considered can be identified.
Boone BA, Steve J, Krasinskas AM, et al. Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer. J Surg Oncol. 2013; 108(4):236-41 [PubMed] Article available free on PMC after 01/09/2014 Related Publications
BACKGROUND: Trials examining FOLFIRINOX in metastatic pancreatic cancer demonstrate higher response rates compared to gemcitabine-based regimens. There is currently limited experience with neoadjuvant FOLFIRINOX in pancreatic cancer. METHODS: Retrospective review of outcomes of patients with borderline resectable or locally unresectable pancreatic cancer who were recommended to undergo neoadjuvant treatment with FOLFIRINOX. RESULTS: FOLFIRINOX was recommended for 25 patients with pancreatic cancer, 13 (52%) unresectable and 12 (48%) borderline resectable. Four patients (16%) refused treatment or were lost to follow-up. Twenty-one patients (84%) were treated with a median of 4.7 cycles. Six patients (29%) required dose reductions secondary to toxicity. Two patients (9%) were unable to tolerate treatment and three patients (14%) had disease progression on treatment. Seven patients (33%) underwent surgical resection following treatment with FOLFIRINOX alone, 2 (10%) of which were initially unresectable. Two patients underwent resection following FOLFIRINOX + stereotactic body radiation therapy (SBRT). The R0 resection rate for patients treated with FOLFIRINOX ± SBRT was 33% (55% borderline resectable, 10% unresectable). A total of five patients (24%) demonstrated a significant pathologic response. CONCLUSIONS: FOLFIRINOX is a biologically active regimen in borderline resectable and locally unresectable pancreatic cancer with encouraging R0 resection and pathologic response rates.
Arem H, Reedy J, Sampson J, et al. The Healthy Eating Index 2005 and risk for pancreatic cancer in the NIH-AARP study. J Natl Cancer Inst. 2013; 105(17):1298-305 [PubMed] Article available free on PMC after 04/09/2014 Related Publications
BACKGROUND: Dietary pattern analyses characterizing combinations of food intakes offer conceptual and statistical advantages over food- and nutrient-based analyses of disease risk. However, few studies have examined dietary patterns and pancreatic cancer risk and none focused on the 2005 Dietary Guidelines for Americans. We used the Healthy Eating Index 2005 (HEI-2005) to estimate the association between meeting those dietary guidelines and pancreatic cancer risk. METHODS: We calculated the HEI-2005 score for 537 218 men and women in the National Institutes of Health-American Association of Retired Persons Diet and Health Study using responses to food frequency questionnaires returned in 1995 and 1996. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of pancreatic cancer according to HEI-2005 quintiles and explored effect modification by known risk factors. P interaction values were calculated using the Wald test. All statistical tests were two-sided. RESULTS: We identified 2383 incident, exocrine pancreatic cancer cases (median = 10.5 years follow-up). Comparing participants who met the most dietary guidelines (Q5) with those who met the fewest guidelines (Q1), we observed a reduced risk of pancreatic cancer (HR = 0.85, 95% CI = 0.74 to 0.97). Among men there was an interaction by body mass index (P interaction = .03), with a hazard ratio of 0.72 (95% CI = 0.59 to 0.88) comparing Q5 vs Q1 in overweight/obese men (body mass index ≥ 25 kg/m(2)) but no association among normal weight men. CONCLUSIONS: Our findings support the hypothesis that consuming a high-quality diet, as scored by the HEI-2005, may reduce the risk of pancreatic cancer.
Kim PT, Wei AC, Atenafu EG, et al. Planned versus unplanned portal vein resections during pancreaticoduodenectomy for adenocarcinoma. Br J Surg. 2013; 100(10):1349-56 [PubMed] Related Publications
BACKGROUND: The management of portal vein (PV) involvement by pancreatic adenocarcinoma during pancreaticoduodenectomy (PD) is controversial. The aim of this study was to compare the outcomes of unplanned and planned PV resections as part of PD. METHODS: An analysis of PD over 11 years was performed. Patients who had undergone PV resection (PV-PD) were identified, and categorized into those who had undergone planned or unplanned resection. Postoperative and oncological outcomes were compared. RESULTS: Of 249 patients who underwent PD for pancreatic adenocarcinoma, 66 (26·5 per cent) had PV-PD, including 27 (41 per cent) planned and 39 (59 per cent) unplanned PV resections. Twenty-five of 27 planned PV resections were circumferential PV-PD, whereas 25 of 39 unplanned PV resections were partial PV-PD. Planned PV resections were performed in slightly younger patients (mean(s.d.) 60(9) versus 65(10) years; P = 0·031), and associated with longer operating times (mean(s.d.) 602(131) versus 458(83) min; P < 0·001) and more major complications (26 versus 5 per cent; P = 0·026). Planned PV resections were associated with a lower rate of positive margins (4 versus 44 per cent; P < 0·001) despite being carried out for larger tumours (mean(s.d.) 3·9(1·4) versus 2·9(1·0) cm; P = 0·002). There was no difference in survival between the two groups (P = 0·998). On multivariable analysis, margin status was a significant predictor of survival. CONCLUSION: Although planned PV resections for pancreatic adenocarcinoma were associated with higher rates of postoperative morbidity than unplanned resections, R0 resection rates were better.
Mohelnikova-Duchonova B, Brynychova V, Hlavac V, et al. The association between the expression of solute carrier transporters and the prognosis of pancreatic cancer. Cancer Chemother Pharmacol. 2013; 72(3):669-82 [PubMed] Related Publications
OBJECTIVES: The aim of this study was to investigate the prognostic significance of fourteen anticancer drug-relevant solute carrier transporters (SLCs) in pancreatic cancer in the context of clinical-pathological characteristics and the KRAS mutation status of tumors. METHODS: Tumors and non-neoplastic pancreatic tissues were obtained from 32 histologically verified patients with pancreatic ductal adenocarcinoma. The transcript profile of SLCs was assessed using quantitative real-time PCR. KRAS mutations in exon 2 were assessed by high-resolution melting analysis and confirmed by sequencing. RESULTS: SLC22A3 and SLC22A18 were upregulated and SLC22A1, SLC22A2, SLC22A11, SLC28A1, SLC28A3 and SLC29A1 were downregulated when compared with non-neoplastic pancreatic tissues. Moreover, significantly lower levels of SLC22A1, SLC22A11 and SLC29A1 were found in tumors with angioinvasion. There was also a significantly higher transcript level of SLC28A1 in tumors with regional lymph nodes affected by metastasis. The study found that a high expression of SLC28A1 was significantly associated with poor overall survival in unselected patients. In contrast, a high expression of SLC22A3 or SLC29A3 was significantly associated with longer overall survival in patients treated with nucleoside analogs. Protein expression of SLC22A1, SLC22A3 and SLC29A3 in tumor tissues of patients with pancreatic carcinoma was observed by immunoblotting for the first time. Finally, SLC levels were not found to be associated with KRAS mutation status in exon 2. CONCLUSIONS: This study identified a number of associations of transcript levels of SLCs with prognosis of pancreatic cancer patients.
Xue Y, Abou Tayoun AN, Abo KM, et al. MicroRNAs as diagnostic markers for pancreatic ductal adenocarcinoma and its precursor, pancreatic intraepithelial neoplasm. Cancer Genet. 2013; 206(6):217-21 [PubMed] Related Publications
Since the discovery of small non-coding RNAs, the analysis of microRNA (miRNA) expression patterns in human cancer have provided new insights into cancer biology. Evidence suggests that deregulated miRNA expression is associated with pancreatic cancer development. In this study, we analyzed the expression of several miRNAs in different types of pancreatic disease to determine if miRNA expression could aid in the diagnosis of pancreatic ductal adenocarcinoma (PDAC) and its precursor, pancreatic intraepithelial neoplasm (PanIN). Pancreatic resection specimens were selected, which included PDAC (n = 16), benign pancreatic parenchyma from corresponding carcinoma cases (n = 16), chronic pancreatitis (n = 4), normal pancreatic parenchyma (n = 5), and PanIN (n = 5). The expression levels of five miRNA (miR-148a, miR-217, miR-21, miR-196a, and miR-10b) were assessed by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) assays. Our data demonstrate that compared to the normal pancreatic parenchyma, miR-148a and miR-217 expression levels were down-regulated in PanIN, particularly in PanIN II-III and PDAC, whereas the level of miR-196 was significantly up-regulated in PDAC and its precursor, PanIN II-III. In addition, we observed that miR-21 was significantly overexpressed in PDAC, and miR-10b was highly expressed in PanIN II-III. Our study demonstrates that certain miRNAs, especially miR-148a, miR-217, and miR-196a, are significantly deregulated in PDAC, including in the early stage of PDAC. These markers can potentially be used as diagnostic markers to distinguish PDAC and its precursor from benign lesions.
Bosetti C, Turati F, Dal Pont A, et al. The role of Mediterranean diet on the risk of pancreatic cancer. Br J Cancer. 2013; 109(5):1360-6 [PubMed] Article available free on PMC after 03/09/2014 Related Publications
BACKGROUND: The Mediterranean diet has been shown to have a beneficial role on various neoplasms, but data are scanty on pancreatic cancer. METHODS: We analysed data from two case-control studies conducted in Italy between 1983 and 2008, including 362 and 326 pancreatic cancer cases and 1552 and 652 hospital-controls, respectively. A Mediterranean Diet Score (MDS) summarising major characteristics of the Mediterranean diet was used in the two studies separately and overall. Two further scores of adherence to the Mediterranean diet were applied in the second study only, the Mediterranean Dietary Pattern Adherence Index (MDP) and the Mediterranean Adequacy Index (MAI). RESULTS: Odds ratios (ORs) for increasing levels of the scores (i.e., increasing adherence) were estimated using multiple logistic regression models. Odds ratio for a MDS score ≥6 compared with <3 was 0.57 (95% confidence interval (CI) 0.34-0.95) in the first study, 0.51 (95% CI 0.29-0.92) in the second study, and 0.48 (95% CI 0.35-0.67) overall. A trend of decreasing risk was observed also for the MDP and MAI the ORs for the highest vs the lowest quintile being 0.44 (95% CI 0.27-0.73) for MDP and 0.68 (95% CI 0.42-1.11) for the MAI. The results were consistent across strata of age, sex, education, body mass index, alcohol drinking, tobacco smoking, and diabetes. CONCLUSION: Our study provides evidence that a priori-defined scores measuring adherence to the Mediterranean diet are favourably associated with pancreatic cancer risk.
Jacobs MJ, Kamyab A Total laparoscopic pancreaticoduodenectomy. JSLS. 2013 Apr-Jun; 17(2):188-93 [PubMed] Article available free on PMC after 03/09/2014 Related Publications
INTRODUCTION: Total laparoscopic pancreaticoduodenectomy (TLPD) remains one of the most advanced laparoscopic procedures. Owing to the evolution in laparoscopic technology and instrumentation within the past decade, laparoscopic pancreaticoduodenectomy is beginning to gain wider acceptance. METHODS: Data were collected for all patients who underwent a TLPD at our institution. Preoperative evaluation consisted of computed tomography scan with pancreatic protocol and selective use of magnetic resonance imaging and/or endoscopic ultrasonography. The TLPD was done with 6 ports on 3 patients and 5 ports in 2 patients and included a celiac, periportal, peripancreatic, and periduodenal lymphadenectomy. Pancreatic stents were used in all 5 cases, and intestinal continuity was re-established by intracorporeal anastomoses. RESULTS: Five patients underwent a TLPD for suspicion of a periampullary tumor. There were 3 women and 2 men with a mean age of 60 years and a mean body mass index of 32.8. Intraoperatively, the mean operative time was 9 hours 48 minutes, with a mean blood loss of 136 mL. Postoperatively, there were no complications and a mean length of stay of 6.6 days. There was no lymph node involvement in 4 out of 5 specimens. The pathological results included intraductal papillary mucinous neoplasm in 2 patients, pancreatic adenocarcinoma in 1 patient (R0 resection), benign 4-cm periampullary adenoma in 1 patient, and a somatostatin neuroendocrine carcinoma in 1 patient (R0, N1). CONCLUSION: TLPD is a viable alternative to the standard Whipple procedure. Our early experience suggests decreased length of stay, quicker recovery, and improved quality of life. Complication rates appear to be improved or equivalent.
Ma JX, Sun YL, Wang YQ, et al. Triptolide induces apoptosis and inhibits the growth and angiogenesis of human pancreatic cancer cells by downregulating COX-2 and VEGF. Oncol Res. 2013; 20(8):359-68 [PubMed] Related Publications
Triptolide (TPL) inhibits the growth and proliferation of a wide range of human cancer cells, but the underlying mechanism is largely unknown. Here, we report that TPL induces apoptosis and inhibits proliferation of PANC-1 pancreatic cancer cells by downregulating cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). Cell viability and apoptosis were measured by MTT assay and flow cytometry. Real-time PCR and Western blot were used to examine the expression of COX-2 and VEGF. The Matrigel angiogenesis and Transwell migration were employed to assess tube formation and cell migration. Pancreatic cancer mouse xenografts were established to investigate the in vivo antitumor effects of TPL. TUNEL staining and immunohistochemistry were used to detect the apoptosis rate and protein expression in tumor tissues. TPL inhibited the proliferation of pancreatic cancer cells in a time and concentration-dependent manner and decreased the expression of COX-2 and VEGF in vitro. Furthermore, medium from TPL-treated PANC-1 cells inhibited the proliferation, migration, and tube formation of HUVECs. TPL significantly reduced the growth of pancreatic cancer mouse xenografts, accompanied by an induction of apoptosis, inhibition of angiogenesis, and reduction of COX-2 and VEGF. Our data indicate that suppressing the expression of COX-2 and VEGF may be one of the molecular mechanisms by which TPL induces apoptosis and inhibits the growth and angiogenesis of human pancreatic cancer cells.
Le DT, Lutz E, Uram JN, et al. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother. 2013; 36(7):382-9 [PubMed] Article available free on PMC after 01/09/2014 Related Publications
Preclinical reports support the concept of synergy between cancer vaccines and immune checkpoint blockade in nonimmunogenic tumors. In particular, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibodies have been successfully combined with GM-CSF cell-based vaccines (GVAX). Ipilimumab (anti-CTLA-4) has been tested as a single agent in patients with pancreatic ductal adenocarcinoma (PDA) resulting in a delayed response at a dose of 3 mg/kg. Our study evaluated ipilimumab 10 mg/kg (arm 1) and ipilimumab 10 mg/kg + GVAX (arm 2). A total of 30 patients with previously treated advanced PDA were randomized (1:1). Induction doses were administered every 3 weeks for a total of 4 doses followed by maintenance dosing every 12 weeks. Two patients in arm 1 showed evidence of stable disease (7 and 22 wk) but none demonstrated CA19-9 biochemical responses. In contrast, 3 patients in arm 2 had evidence of prolonged disease stabilization (31, 71, and 81 wk) and 7 patients experienced CA19-9 declines. In 2 of these patients, disease stabilization occurred after an initial period of progression. The median overall survival (OS) (3.6 vs. 5.7 mo, hazards ratio: 0.51, P = 0.072) and 1 year OS (7 vs. 27%) favored arm 2. Similar to prior ipilimumab studies, 20% of patients in each arm had grade 3/4 immune-related adverse events. Among patients with OS > 4.3 months, there was an increase in the peak mesothelin-specific T cells (P = 0.014) and enhancement of the T-cell repertoire (P = 0.031). In conclusion, checkpoint blockade in combination with GVAX has the potential for clinical benefit and should be evaluated in a larger study.
Han S, Kim K, Thakkar N, et al. Role of hypoxia inducible factor-1α in the regulation of the cancer-specific variant of organic anion transporting polypeptide 1B3 (OATP1B3), in colon and pancreatic cancer. Biochem Pharmacol. 2013; 86(6):816-23 [PubMed] Related Publications
Organic anion transporting polypeptide 1B3 (OATP1B3) was initially considered to be a liver-specific transporter, mediating the uptake of a variety of endogenous and xenobiotic substances. Over the past decade, several investigations reported that OATP1B3 is also expressed across multiple types of cancers. Only recently, our laboratory and others demonstrated the identity of cancer-specific OATP1B3 variants (csOATP1B3) arising from the use of an alternative transcription initiation site, different from the wildtype (WT) OATP1B3 expressed in the normal liver. However, the mechanisms regulating the expression of csOATP1B3 remained unknown. In our current study, we investigated the role of hypoxia and the involvement of hypoxia inducible factor-1α (HIF-1α) in regulating the transcription of csOATP1B3. Our RT-PCR and immunoblotting results indicated that csOATP1B3, but not WT OATP1B3, can be induced in response to ambient or chemical hypoxia (upon exposure to 1% O₂ or cobalt chloride). Reporter assays with deletion and mutated constructs of the csOATP1B3 promoter revealed a functional hypoxia response element (HRE) located in the proximal upstream region. Constructs harboring the HRE displayed the upregulated reporter gene expression in response to hypoxia, but not when mutated. Electrophoretic mobility shift assays using a biotin-labeled csOATP1B3 promoter HRE probe indicated the binding of HIF-1α, which was blocked by an excess of unlabeled csOATP1B3 probe. Furthermore, siRNA-based knockdown of HIF-1α caused a substantial decrease in the expression level of csOATP1B3. Taken together, these findings demonstrate that the transcription of csOATP1B3 is actively engaged during hypoxia, through a commonly utilized pathway involving HIF-1α.
Singh N, Das P, Datta Gupta S, et al. Prognostic significance of extracellular matrix degrading enzymes-cathepsin L and matrix metalloproteases-2 [MMP-2] in human pancreatic cancer. Cancer Invest. 2013; 31(7):461-71 [PubMed] Related Publications
In the present study, we assessed the expression of extracellular matrix (ECM) degrading proteases-cathepsin L and matrix metalloprotease-2 (MMP-2) in pancreatic cancer tissue and correlated their levels with clinicopathological parameters and survival. Both the proteases were expressed in the majority of the tumor tissues examined. Staining intensity of cathepsin L was significantly higher in the tumor stroma compared to tumor epithelium while MMP-2 staining showed no such difference. Both proteases showed correlation with some of the clinicopathological parameters but only cathepsin L expression in tumor epithelium predicted a poor prognosis for the disease.
Chao Y, Wu CY, Wang JP, et al. A randomized controlled trial of gemcitabine plus cisplatin versus gemcitabine alone in the treatment of metastatic pancreatic cancer. Cancer Chemother Pharmacol. 2013; 72(3):637-42 [PubMed] Related Publications
PURPOSE: To compare the efficacy and toxicity of single-agent gemcitabine with gemcitabine plus cisplatin (G + C) in patients with metastatic pancreatic cancer METHODS: Forty-six patients with metastatic pancreatic cancer were randomized to receive gemcitabine alone (n = 25; 1,000 mg m(-2)) or G + C (n = 21; 1,000 mg m(-2) gemcitabine and 25 mg m(-2) cisplatin). Treatments were administered once a week for 3 weeks and repeated every 4 weeks. RESULTS: Patient characteristics were comparable between the gemcitabine alone and G + C groups. The gemcitabine dose intensity was similar between the gemcitabine alone and G + C groups (684 ± 32 vs. 617 ± 31 mg m(-2) week(-1)). The cisplatin dose intensity was 15.1 ± 0.9 mg m(-2) week(-1) × 9.9 ± 1.8 weeks. Partial response rates were 8 % (2/25) for gemcitabine alone and 4.8 % (1/21) for G + C (p = 1). The median survival and median time to progression were 7.7 and 4.6 months for gemcitabine alone and 7.9 and 3.6 months for G + C, respectively (p = 0.752 and p = 0.857, respectively). Clinical benefit was 36 % for gemcitabine alone and 29 % for G + C (p = 0.592). Quality-adjusted life months were 5.6 ± 0.3 for the gemcitabine alone group and 3.8 ± 0.2 for the G + C group (p < 0.001). The frequency of grade 3/4 neutropenia (8 vs. 19 %) and anemia (8 vs. 10 %) and the number of hospitalization days per month of survival (4.7 ± 1.3 vs. 6.3 ± 1.6 days; p = 0.431) were not significantly different between patients who received gemcitabine alone and those who received G + C. However, patients in the G + C group had a higher rate of thrombocytopenia than did patients in the gemcitabine alone group (62 vs. 24 %; p = 0.009). CONCLUSIONS: Gemcitabine alone and G + C had comparable and modest response rates in metastatic pancreatic cancer, but gemcitabine alone produced less toxicities than did G + C.
Eng OS, Goswami J, Moore D, et al. Intraoperative fluid administration is associated with perioperative outcomes in pancreaticoduodenectomy: a single center retrospective analysis. J Surg Oncol. 2013; 108(4):242-7 [PubMed] Related Publications
BACKGROUND: Recent studies on perioperative fluid administration in patients undergoing major abdominal surgery have suggested that increased fluid loads are associated with worse perioperative outcomes. However, results of retrospective analyses of the relationship between intraoperative fluid (IOF) administration and perioperative outcomes in patients undergoing pancreaticoduodenectomy (PD) are conflicted. We sought to investigate this relationship in patients undergoing PD at our academic center. METHODS: A retrospective analysis of 124 patients undergoing PD from 2007 to 2012 was performed. IOF administration rate (ml/kg/hr) was correlated with perioperative outcomes. Outcomes were also stratified by preoperative serum albumin level. RESULTS: Regression analyses were performed comparing independent perioperative variables, including IOF rate, to four outcomes variables: length of stay, severity of complications, number of complications per patient, and 30-day mortality. Both univariate and multivariate regression analyses showed IOF rate correlated with one or more perioperative outcomes. Patients with an albumin ≤ 3.0 g/dl who received more than the median IOF rate experienced more severe complications, while patients with an albumin >3.0 g/dl did not. CONCLUSION: Increased IOF administration is associated with worse perioperative outcomes in patients undergoing PD. Patients with low preoperative serum albumin levels (≤ 3.0 g/dl) may be a group particularly sensitive to volume overload.
Alvarez R, Musteanu M, Garcia-Garcia E, et al. Stromal disrupting effects of nab-paclitaxel in pancreatic cancer. Br J Cancer. 2013; 109(4):926-33 [PubMed] Article available free on PMC after 20/08/2014 Related Publications
BACKGROUND: Nab-paclitaxel and gemcitabine have demonstrated a survival benefit over gemcitabine alone in advanced pancreatic cancer (PDA). This study aimed to investigate the clinical, biological, and imaging effects of the regimen in patients with operable PDA. METHODS: Patients with operable PDA received two cycles of nab-paclitaxel and gemcitabine before surgical resection. FDG-PET and CA19.9 tumour marker levels were used to measure clinical activity. Effects on tumour stroma were determined by endoscopic ultrasound (EUS) elastography. The collagen content and architecture as well as density of cancer-associated fibroblasts (CAFs) were determined in the resected surgical specimen and compared with a group of untreated and treated with conventional chemoradiation therapy controls. A co-clinical study in a mouse model of PDA was conducted to differentiate between the effects of nab-paclitaxel and gemcitabine. RESULTS: A total of 16 patients were enrolled. Treatment resulted in significant antitumour effects with 50% of patients achieving a >75% decrease in circulating CA19.9 tumour marker and a response by FDG-PET. There was also a significant decrement in tumour stiffness as measured by EUS elastography. Seven of 12 patients who completed treatment and were operated had major pathological regressions. Analysis of residual tumours showed a marked disorganised collagen with a very low density of CAF, which was not observed in the untreated or conventionally treated control groups. The preclinical co-clinical study showed that these effects were specific of nab-paclitaxel and not gemcitabine. CONCLUSION: These data suggest that nab-paclitaxel and gemcitabine decreases CAF content inducing a marked alteration in cancer stroma that results in tumour softening. This regimen should be studied in patients with operable PDA.
Wang J, Zhang W, Sun L, et al. Dietary energy density is positively associated with risk of pancreatic cancer in urban Shanghai Chinese. J Nutr. 2013; 143(10):1626-9 [PubMed] Article available free on PMC after 01/10/2014 Related Publications
Regular consumption of energy-dense foods predisposes to obesity and type 2 diabetes, both of which are suggested risk factors for pancreatic cancer. The aim of this study was to investigate whether energy density of foods is an independent risk factor for pancreatic cancer. In this population-based case-control study in urban Shanghai, 908 patients with pancreatic cancer and 1067 normal controls, aged 35-79 y, were recruited. The energy density for overall diet was calculated from food-frequency questionnaire data. Energy density (adjusted for age, sex, and total energy intake) was significantly higher in cases (6.08 ± 0.04 kJ/g) than in controls (5.91 ± 0.04 kJ/g) (P = 0.003). Energy density was positively associated with pancreatic cancer risk (OR: 1.16 per unit increase; 95% CI: 1.07, 1.27; P < 0.001). In adjusted analysis, the risk of pancreatic cancer was 72% greater (OR: 1.72; 95% CI: 1.25, 2.35; P = 0.001) in the highest quintile of energy density compared with the lowest quintile. In this case-control study, dietary energy density is positively associated with risk of pancreatic cancer. This association should be further investigated in prospective studies.