Management Of Pancreatic Cancer Research Articles

The Impact of Residential Segregation on Pancreatic Cancer Diagnosis, Treatment, and Mortality.

Disparities in pancreatic cancer outcomes between black and white patients are well documented. This study aimed to use a more novel index to examine the impact of racial segregation on the diagnosis, management, and outcomes of pancreatic cancer in black patients compared with white patients. Black and white adults with pancreatic cancer in urban counties were identified using data from the 2018 submission of the Surveillance, Epidemiology and End Results (SEER) Program and the 2010 Census. The racial index of dissimilarity (IoD), a validated proxy of racial segregation, was used to assess the evenness with which whites and blacks are distributed across census tracts in each county. Multivariate Poisson regression was performed, and stepwise models were constructed for each of the outcomes. Overall survival was studied using the Kaplan-Meier method. The study enrolled 60,172 adults with a diagnosis of pancreatic cancer between 2005 and 2015. Overall, the black patients (13.8% of the cohort) lived in more segregated areas (IoD, 0.67 vs 0.61; p < 0.05). They were less likely to undergo surgery for localized disease (relative risk [RR], 0.80; 95% confidence interval [CI], 0.76-0.83) and more frequently had a diagnosis of advanced-stage disease (RR, 1.09; 95% CI, 1.01-1.19) with increasing segregation. They also had shorter survival times (9.8 vs 11.4months; p < 0.05). Disparities in advanced-stage disease at diagnosis, surgery for localized disease, and overall survival are directly related to the degree of residential segregation, a proxy for structural racism. In searching for solutions to this problem, it is important to account for the historical marginalization of black Americans.

Endoscopic retrograde cholangiopancreatography guided interventions in the management of pancreatic cancer.

Pancreatic cancer is the leading cause of cancer-related morbidity and mortality with an overall five-year survival of less than 9% in the United States. At presentation, the majority of patients have painless jaundice, pruritis, and malaise, a triad that develops secondary to obstruction, which often occurs late in the course of the disease process. The technical advancements in radiological imaging and endoscopic interventions have played a crucial role in the diagnosis, staging, and management of patients with pancreatic cancer. Endoscopic retrograde cholangiopancreatography (ERCP)-guided diagnosis (with brush cytology, serial pancreatic juice aspiration cytologic examination technique, or biliary biopsy) and therapeutic interventions such as pancreatobiliary decompression, intraductal and relief of gastric outlet obstruction play a pivotal role in the management of advanced pancreatic cancer and are increasingly used due to improved morbidity and complication rates compared to surgical management. In this review, we highlight various ERCP-guided diagnostic and therapeutic interventions for the management of pancreatic cancer.

Nationwide compliance with a multidisciplinary guideline on pancreatic cancer during 6-year follow-up

BackgroundCompliance with national guidelines on pancreatic cancer management could improve patient outcomes. Early compliance with the Dutch guideline was poor. The aim was to assess compliance with this guideline during six years after publication. Materials and methodsNationwide guideline compliance was investigated for three subsequent time periods (2012–2013 vs. 2014–2015 vs. 2016–2017) in patients with pancreatic cancer using five quality indicators in the Netherlands Cancer Registry: 1) discussion in multidisciplinary team meeting (MDT), 2) maximum 3-week interval from final MDT to start of treatment, 3) preoperative biliary drainage when bilirubin >250 μmol/L, 4) use of adjuvant chemotherapy, and 5) chemotherapy for inoperable disease (non-metastatic and metastatic). ResultsIn total, 14 491 patients were included of whom 2290 (15.8%) underwent resection and 4561 (31.5%) received chemotherapy. Most quality indicators did not change over time: overall, 88.8% of patients treated with curative intent were discussed in a MDT, 42.7% were treated with curative intent within the 3-week interval, 62.7% with a resectable head tumor and bilirubin >250 μmol/L underwent preoperative biliary drainage, 57.2% received chemotherapy after resection, and 36.6% with metastatic disease received chemotherapy. Only use of chemotherapy for non-metastatic, non-resected disease improved over time (23.4% vs. 25.6% vs. 29.7%). ConclusionNationwide compliance to five quality indicators for the guideline on pancreatic cancer management showed little to no improvement during six years after publication. Besides critical review of the current quality indicators, these outcomes may suggest that a nationwide implementation program is required to increase compliance to guideline recommendations.

Reviews on Current Liquid Biopsy for Detection and Management of Pancreatic Cancers

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Pancreatic cancer presents dismal clinical outcomes in patients, and the incidence of pancreatic cancer has continuously increased to likely become the second most common cause of cancer-related deaths by as early as 2030. One of main reasons for the high mortality rate of pancreatic cancer is the lack of tools for early-stage detection. Current practice in detecting and monitoring therapeutic response in pancreatic cancer relies on imaging analysis and invasive endoscopic examination. Liquid biopsy-based analysis of genetic alterations in biofluids has become a fundamental component in the diagnosis and management of cancers. There is an urgent need for scientific and technological advancement to detect pancreatic cancer early and to develop effective therapies. The development of a highly sensitive and specific liquid biopsy tool will require extensive understanding on the characteristics of circulating tumor DNA in biofluids. Here, we have reviewed the current status of liquid biopsy in detecting and monitoring pancreatic cancers and our understanding of circulating tumor DNA that should be considered for the development of a liquid biopsy tool, which will greatly aid in the diagnosis and healthcare of people at risk.

First-line chemotherapy in very elderly patients with metastatic pancreatic cancer: Gemcitabine monotherapy vs combination chemotherapy.

BACKGROUNDCombination chemotherapy (gemcitabine plus nab-paclitaxel and FOLFIRINOX) is widely used as the standard first-line treatment for pancreatic cancer. Considering the severe toxicities of combination chemotherapy, gemcitabine monotherapy (G mono) could be used as a first-line treatment in very elderly patients or those with a low Eastern Cooperative Oncology Group status. However, reports on the efficacy of G mono in patients older than 75 years are limited.AIMTo evaluate the efficacy of G mono and combination chemotherapy by comparing their clinical outcomes in very elderly patients with pancreatic cancer.METHODSWe retrospectively analyzed 104 older patients with pancreatic cancer who underwent chemotherapy with G mono (n = 45) or combination therapy (n = 59) as a first-line treatment between 2011 and 2019. All patients were histologically diagnosed with ductal adenocarcinoma. Primary outcomes were progression-free survival and overall survival. We also analyzed subgroups according to age [65-74 years (elderly) and ≥ 75 years (very elderly)]. Propensity score matching was performed to compare the outcomes between the two chemotherapy groups.RESULTSThe baseline characteristics were significantly different between the two chemotherapy groups, especially regarding age, ratio of multiple metastases, tumor burden, and Eastern Cooperative Oncology Group performance status. After propensity score matching, the baseline characteristics were not significantly different between the chemotherapy groups in elderly and very elderly patients. In the elderly patients, the median progression-free survival (62 d vs 206 d, P = 0.000) and overall survival (102 d vs 302 d, P = 0.000) were longer in the combination chemotherapy group. However, in the very elderly patients, the median progression-free survival (147 d and 174 d, respectively, P = 0.796) and overall survival (227 d and 211 d, respectively, P = 0.739) were comparable between the G mono and combination chemotherapy groups. Adverse events occurred more frequently in the combination chemotherapy group than in the G mono group, especially thromboembolism (G mono vs nab-paclitaxel vs FOLFIRINOX; 8.9% vs 5.9% vs 28%, P = 0.041), neutropenia (40.0% vs 76.5% vs 84.0%, P = 0.000), and neuropathy (0% vs 61.8% vs 28.0%, P = 0.006).CONCLUSIONIn elderly patients, combination therapy is more effective than G mono. However, G mono is superior for the management of metastatic pancreatic cancer in very elderly patients.

A Comparison of Ultrasound and Fluoroscopy-guided Celiac Plexus Neurolysis in Patients with Pancreatic Cancer

Background &amp; Aims: Celiac plexus neurolysis is an elegant way of reducing pain in patients with pancreatic cancer. The aim of this work was to compare the effectiveness of ultrasound versus fluoroscopy-guided celiac plexus neurolysis in pancreatic cancer management. Methods: This study included 60 patients presenting with pancreatic cancer pain; who were subjected to one session of celiac plexus neurolysis and were divided equally into two groups: - Group (1): included 30 patients (12 femalesamp;18 males); who were exposed to ultrasound (US)- guided celiac plexus neurolysis and group (2): included 30 patients (10 females &amp; 20 males) who were exposed to fluoroscopy-guided celiac plexus neurolysis. Abdominal pain was assisted by visual analogue score (VAS). Results: Regarding VAS, our results revealed that all patients showed improvement after celiac plexus neurolysis either through ultrasound technique or via percutaneous fluoroscopy technique. Furthermore, the ultrasound group recorded more significant pain relief with improved VAS than the fluoroscopy group immediately and on long-term follow-up with mean ± SD as follows: - Immediately (9.2 ± 0.8) to (2.5 ± 0.7) vs. (9.1 ± 0.7) to (3.5 ± 0.82, respectively); After 1 week (1.1 ± 0.8 vs. 3.6 ± 1.7, respectively), after 1 month ( 1 ± 0.9 vs. 3.7 ± 1.9), after three months (1.7 ± 1.01 vs. 5.9 ± 1.7, respectively) and after 6 months (2.3 ± 0.6 vs. 7.5 ± 1.6, respectively). Conclusion: The study revealed that ultrasound-guided celiac plexus neurolysis is more durable, tolerable, effective and safe compared to fluoroscopy-guided neurolysis of patient suffering from pancreatic cancer pain.

Repurposing Pimavanserin, an Anti-Parkinson Drug for Pancreatic Cancer Therapy

Despite major advances in cancer treatment, pancreatic cancer is still incurable and the treatment outcomes are limited. The aggressive and therapy-resistant nature of pancreatic cancer warrants the need for novel treatment options for pancreatic cancer management. Drug repurposing is emerging as an effectual strategy in the treatment of various diseases, including cancer. In the present study, we evaluated the anticancer effects of pimavanserin tartrate (PVT), an antipsychotic drug used for the treatment of Parkinson disease psychosis. PVT significantly suppressed the proliferation and induced apoptosis in various pancreatic cancer cells and gemcitabine-resistant cells with minimal effects on normal pancreatic epithelial cells and lung fibroblasts. Growth-suppressive and apoptotic effects of PVT were mediated by the inhibition of the Akt/Gli1 signaling axis. The oral administration of PVT suppressed subcutaneous and orthotopic pancreatic tumor xenografts by 51%–77%. The chronic administration of PVT did not demonstrate any general signs of toxicity or change in behavioral activity of mice. Our results indicate that pancreatic tumor growth suppression by PVT was orchestrated by the inhibition of Akt/Gli1 signaling. Since PVT is already available in the clinic with an established safety profile, our results will accelerate its clinical development for the treatment of patients with pancreatic cancer.

Minimally invasive surgery for pancreatic cancer

Pancreatic cancer is the most lethal malignancy of the digestive organs. Although pancreatic resection is essential to radically cure this refractory disease, the multi-organ resection involved, as well as sequelae such as glucose tolerance insufficiency and severe complications impose a heavy burden on these patients. Since the late twentieth century, minimally invasive surgery has become more popular for the surgical management of digestive disease and pancreatic cancer. Minimally invasive pancreatic resection (MIPR), including pancreaticoduodenectomy and distal pancreatectomy, is now a treatment option for pancreatic cancer. Some evidence suggests that MIPR for pancreatic cancer provides comparable oncological outcomes to open surgery, with some advantages in perioperative outcomes. However, as this evidence is retrospective, prospective investigations, including randomized controlled trials, are necessary. Because neoadjuvant therapy for resectable or borderline-resectable pancreatic cancer and conversion surgery for initially unresectable pancreatic cancer has become more common, the feasibility of MIPR after neoadjuvant therapy or as conversion surgery requires further assessment. It is expected that progress in surgical techniques and devices, as well as the standardization of surgical procedures and widespread educational programs will improve the outcomes of MIPR.

Pancreaticoduodenectomy: Outcomes of a complex surgical procedure from a developing country

BackgroundPancreaticoduodenectomy (PD) plays an integral part in the management of pancreatic, periampullary and duodenal cancers, along with a few other pathologies of this region. Despite advances in surgery PD continues to have significant morbidity and noteworthy mortality. The aim of this study is to provide an in-depth report on the patient characteristics, indications and the outcomes of PD) in a tertiary cancer hospital in Pakistan. Materials and methodsThe study population included patients who underwent PD between January 1, 2014 and march 31, 2019, at Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC) in Pakistan. The data was retrospectively analyzed from the Hospital Information System (HIS), which is a prospectively maintained patient electronic database of SKMCH&RC. Patient characteristics, procedural details and post-operative outcomes according to internationally accepted definitions were reported. ResultsA total of 161 patients underwent PD at our hospital in the study period at a median age of 53 years, ranging from 19 to 78 years. 62% of the patients were males while 37% were females. Jaundice was the most common presenting symptom (64.6%), followed by abdominal pain (26.7%). PD with pancreaticogastrostomy was performed in 110 patients (68.3%), while pancreaticojejunostomy was performed in the rest of the cohort. Surgical site infection (SSI) was observed in 64 patients (40%). The incidence of Pancreatic Fistula grade C based on the International Study Group on Pancreatic Fistula (ISGPF) definition was 7.45% (n = 12). The 30 days mortality rate was 3.1%. Median survival of the cohort was 21 ±1.13 months and disease-free survival was 16±2.62 months. ConclusionPD can be performed with acceptable morbidity and mortality in a resource constrained country, as long as it is undertaken in a high-volume center. This is in keeping with data published from other well-reputed international centers.

Neoadjuvant chemotherapy is associated with improved survival in patients with left-sided pancreatic adenocarcinoma.

Neoadjuvant chemotherapy is used infrequently in the management of distal pancreatic cancers. We investigated outcomes associated with neoadjuvant chemotherapy or up-front surgery in patients undergoing distal pancreatectomy. The National Cancer Database (2004-2016) was queried for patients with pancreas cancer who underwent distal pancreatectomy. Demographics, clinical characteristics, postoperative outcomes, pathologic outcomes, and overall survival were analyzed by univariate and multivariate analysis. Six thousand five-hundred and twenty-three patients were included, including 5,643 who underwent up-front distal pancreatectomy and 880 who received neoadjuvant therapy. Factors associated with receipt of neoadjuvant chemotherapy included care at academic/research programs, higher education level, higher clinical T stage, higher clinical N stage, and elevated carbohydrate antigen 19-9 level. Patients who received neoadjuvant therapy had fewer positive lymph nodes, higher margin-negative resection rate, lower 30-day readmission rate, and lower 90-day mortality rate. Patients who received neoadjuvant therapy had longer median overall survival (28.8 vs 22.0 months; P < .001). On multivariate analysis, neoadjuvant therapy remained independently associated with improved survival (hazards ratio, 0.72; 95% confidence inteval, 0.63-0.82; P < .001). Neoadjuvant therapy in patients with left-sided pancreatic cancers is associated with improved pathologic outcomes as well as longer overall survival. Neoadjuvant therapy should be considered in all patients with PDAC regardless of tumor location.

Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease.

This review highlights current treatments, limitations, and pitfalls in the management of pancreatic cancer and discusses current research in novel targets and drug development to overcome these clinical challenges. We begin with a review of the clinical landscape of pancreatic cancer, including genetic and environmental risk factors, as well as limitations in disease diagnosis and prevention. We next discuss current treatment paradigms for pancreatic cancer and the shortcomings of targeted therapy in this disease. Targeting major driver mutations in pancreatic cancer, such as dysregulation in the KRAS and TGFβ signaling pathways, have failed to improve survival outcomes compared with nontargeted chemotherapy; thus, we describe new advances in therapy such as Ras-binding pocket inhibitors. We then review next-generation approaches in nanomedicine and drug delivery, focusing on preclinical advancements in novel optical probes, antibodies, small-molecule agents, and nucleic acids to improve surgical outcomes in resectable disease, augment current therapies, expand druggable targets, and minimize morbidity. We conclude by summarizing progress in current research, identifying areas for future exploration in drug development and nanotechnology, and discussing future prospects for management of this disease.

GC–MS Analysis of Ethanol Leaves Extract of Solanum Americana

GC-MS analysis was carried out in order to investigate the phytoconstituents present in the ethanolic extract of Solanum americana leaves. The structural formula of the phytochemicals of S. americana leaves were determined by analysing of the spectra of GC-MS using the reference standard of National Institute of Standard and Technology (NIST). GC-MS analysis of S. americana leaves showed the presence of eighteen bioactive compounds. The compounds are 4-(5-(2-Naphthoxy)pentylthio)-5-chloro-uracil, propanamide, 2-(dimethylamino)-N-[2-methyl-1-[[3,3a,12,13,14,15,16,16a-octahydro-8-methoxy-13,16-dioxo-14, 4-Amino-1-methyl-5-nitropyrazole, 1,2-Benzenediol, o-octanoyl-o'-(thiophen-2-acetyl), 7H-1,4-Dioxino[2,3-c]xanthen-7-one, 2,3-dihydro-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-5-methoxy, benzoic acid, p-(cyclohexyloxy)-, 3-(2-methylpiperidino)propyl ester, quinoline, 6,6'-[2,6-naphthalenediyldi-2,1-ethenediyl]bis[1-ethyl-1,2,3,4-tetrahydro, 2,5,8,9,11-Pentaacetoxy-2,3-dihydrospiro(4H)benzofuro[2,3-g]-1-benzopyran-4,2'(5'H)-furan]-5'-one, 4-(d-Xylosyloxy)-6,7-dimethoxy-9-[3,4-(methylenedioxy)phenyl]naphtho[2,3-c]furan-1(3H)-one, benzenamine, N,N-didodecyl-4-nitro, 1-Hydroxy-3-(hydroxymethyl)anthraquinone, O,O'-bis(trimethylsilyl), d-Glucopyranoside, 1,4a,5,7a-tetrahydro-7-(methoxymethyl)cyclopenta[c]pyran-1,5-diyl[bis-, 2,2',3,3',4,4',6,6', 5,12-Naphthacenedione, 6,8,10,11-tetrakis(acetyloxy)-8-[(acetyloxy)acetyl]-7,8,9,10-tetrahydro-1-methoxy, salicylic acid, monoanhydride with 1-butaneboronic acid, cyclic ester, tetrabenzo[e,i,o,s][1,4,7,11,14,18]dithiatetraazacycloeicosine, 11,12,13,14,26,27-hexahydro, 6-Chloro-2-(3,5-diphenyl-pyrazol-2-yl)-benzothiazole, (23S,24S,25S)-26,26-dichloro-23-ethyl-6_-methoxy-3_,5:24,26-dicyclocholestane, 9H-Carbazole-9-carboxaldehyde, 1-hydroxy-3-methyl-2-(3-methyl-2-butenyl) and 2,4-cyclopentadiene-1,2,3,4-tetracarboxylic acid, 5-(4-bromo-2-quinolinyl)-, tetramethyl ester. It was concluded that the phytocompounds support the use of S. americana leaves for the management of pancreatic cancer, prostate cancer, asthma, allergic rhinitis, and osteoarthritis

Factors Associated with Treatment and Survival of Early Stage Pancreatic Cancer in the Era of Modern Chemotherapy: An Analysis of the National Cancer Database.

Background: Underutilization of operative management of early stage pancreatic cancer is associated with sociodemographic variables, including age, race, facility type, insurance, and education. It is currently unclear how these variables are associated with survival in patients who undergo surgery.Methods: Patients with clinical stage I pancreatic adenocarcinoma were identified within the National Cancer Database (2010–2016). Utilization of surgery and nonoperative management was determined. Nonclinical factors associated with nonoperative management were identified by multivariable analysis. The association between nonclinical factors and survival was assessed in patients who received operative management.Results: A total of 17,833 patients with clinical stage I pancreatic cancer were identified, and 41.2% underwent operative intervention. Approximately 46% of nonoperatively managed patients lacked a contraindication. Operatively managed patients had longer overall survival (OS) than those who were nonoperatively managed or untreated (25.1 months vs. 11.1 months vs. 5.1 months, p < 0.0001). Factors associated with nonoperative management included age, black/Hispanic race, nonacademic facilities, nonprivate health insurance, lower education level, and lower income. In operatively managed patients, nonclinical factors associated with lower OS included Medicaid (hazard ratio [HR] 1.27) and treatment at nonacademic facilities (HR 1.20–1.22). Patients on Medicaid received less adjuvant therapy and had higher 30- and 90-day mortality rates. Patients treated at nonacademic facilities received less neoadjuvant therapy, had worse pathologic outcomes, and had higher 30- and 90-day mortality rates.Conclusions: Surgical management is underutilized in clinical stage I pancreatic cancer. Primary insurance payor and facility type appear to be associated with OS in patients who undergo operative management.

Implementation of a standardized approach to borderline resectable pancreatic cancer in a multisite community oncology program

BackgroundTreatment paradigms for borderline resectable pancreatic cancer are evolving with increasing use of neoadjuvant chemotherapy and neoadjuvant chemoradiation. Variations in the definition of borderline resectable pancreatic cancer and neoadjuvant approaches have made standardizing care for borderline resectable pancreatic cancer difficult. We report an effort to standardize management of borderline resectable pancreatic cancer throughout Sanford Health, a large community oncology network. MethodsStarting in October 2013, cases of pancreatic adenocarcinoma without known metastatic disease were categorized as borderline resectable pancreatic cancer if they met ≥1 of the following criteria: (1) abutment of superior mesenteric, common hepatic, or celiac arteries with <180° involvement, (2) venous involvement deemed potentially suitable for reconstruction, and/or (3) biopsy-proven lymph node involvement. Patients with borderline resectable pancreatic cancer were treated with neoadjuvant chemotherapy followed by reimaging and surgery if venous involvement had improved; if disease remained borderline resectable, patients underwent neoadjuvant chemoradiation and surgical exploration as long as reimaging did not reveal evidence of progressive disease. ResultsForty-three patients from October 2013 to April 2017 were diagnosed with borderline resectable pancreatic cancer. Twelve of 42 (29%) patients proceeded to surgical exploration directly after neoadjuvant chemotherapy; 23 (55%) received neoadjuvant chemoradiation. Overall, 28/43 (65%) underwent exploration with 19 (44%) able to undergo resection. Of those, 14/19 (74%) attained R0 resection and 11/19 (58%) were pathologic N0. No pretreatment or treatment variables were associated with resection rates; resection was the only variable associated with survival. ConclusionThis report demonstrates the feasibility of implementing a standardized approach to borderline resectable pancreatic cancer across multiple sites over a wide geographic area. Adherence to protocol therapies was good and surgical outcomes are similar to many reported series.

Immuno-Surgical Management of Pancreatic Cancer with Analysis of Cancer Exosomes.

Exosomes (EXs), a type of extracellular vesicles secreted from various cells and especially cancer cells, mesenchymal cells, macrophages and other cells in the tumor microenvironment (TME), are involved in biologically malignant behaviors of cancers. Recent studies have revealed that EXs contain microRNAs on their inside and express proteins and glycolipids on their outsides, every component of which plays a role in the transmission of genetic and/or epigenetic information in cell-to-cell communications. It is also known that miRNAs are involved in the signal transduction. Thus, EXs may be useful for monitoring the TME of tumor tissues and the invasion and metastasis, processes that are associated with patient survival. Because several solid tumors secrete immune checkpoint proteins, including programmed cell death-ligand 1, the EX-mediated mechanisms are suggested to be potent targets for monitoring patients. Therefore, a companion therapeutic approach against cancer metastasis to distant organs is proposed when surgical removal of the primary tumor is performed. However, EXs and immune checkpoint mechanisms in pancreatic cancer are not fully understood, we provide an update on the recent advances in this field and evidence that EXs will be useful for maximizing patient benefit in precision medicine.

P-285 Therapeutic management of exocrine pancreatic cancer in elderly patients

P-285 Therapeutic management of exocrine pancreatic cancer in elderly patients

P-338 Advanced pancreatic adenocarcinoma in daily clinical practice: A single-center experience

Pancreatic adenocarcinoma (AC) is a systemic disease with early metastatic spread and poor survival rate. Palliative chemotherapy (CT) is the treatment of choice for advanced stages. Also, palliative surgical and endoscopic techniques are meant to improve quality of life and make the patient more comfortable. Moreover, the majority of pancreatic cancer patients present with pain at the time of diagnosis. Pain management can be challenging in light of the aggressive nature of this cancer. The aim of this study was to evaluate the oncological approach to advanced pancreatic ductal AC in daily clinical practice. We conducted a retrospective analysis of all patients diagnosed with pancreatic AC treated at our Medical Oncology Department between 2008 and 2016, then we analyzed the cohort of patients with metastatic disease. We evaluated gender, clinical history, performance status (ECOG), tumour location, tumour stage, biliary stent, albumin rate, white blood cell rate, liver function, and treatment approach. Univariate analysis for OS was estimated using the Kaplan-Meier method with statistical significance (p < 0.05) of differences evaluated by log-rank test. Cox regression model was carried out for multivariate analysis. All statistical analysis was performed using SPSS version 25.0. 114 patients were identified; 43% female and 57% male; median age at diagnosis was 63.3 years (range 41-111). All patients had AC histopathological type. We evaluated 78 patients (68,4%) with metastatic disease. They had a baseline ECOG performance status at cycle 1 of first-line CT of 1, 2, 3, 4 in 40%, 40%, 16%, 4% patients. The primary tumor was located in the head of the pancreas in 59,6% patients. T3 and T4 stages were found in 64,9% of patients. Liver/peritoneum/lymph node/lung/multiorgan metastases were present in 17/10/09/19/23 patients. Time to diagnosis was less than three months in 50.9% of patients. 21 patients had been treated for pain at baseline, and 22 had undergone biliary drainage prior to the initial CT. 60,3% of patients received CT. 58% of patients received first-line CT. The most used first-line CT regimen was gemcitabine (46,2%). Second-line CT was performed in 13 patients (16,7%), and 4 patients received third-line CT. The most used CT regimen in the 2nd and 3rd lines was capecitabine. The median overall survival (mOS) was 3,9 months (95% CI, 0.2-7.1) from diagnosis. mOS from diagnosis was 2.4 months (95% CI, 0.2-11.6) for patients who received 1 line only, 8.3 months (95% CI, 0.5-16.5) for patients who received 2 lines and 16.3 months (95% CI, 4.1-35.2) for those who received 3 lines. Univariate and multivariate analysis showed that ECOG PS (p = 0.002) was associated with poor prognosis. This retrospective analysis highlighted the prescribing profile of systemic CT at Algerian Tlemcen Hospital. We demonstrated poor overall survival of metastatic pancreatic cancer. Survival was poorest in those receiving a single line of CT. Patients should receive multiple sequences of chemotherapy whenever possible. We are aware of the limitations of a retrospective study. Further studies like these are needed to evaluate the management of advanced pancreatic cancer in real-world clinical practice.

The PPARγ Agonist Rosiglitazone Enhances the Radiosensitivity of Human Pancreatic Cancer Cells.

PurposeAs radiation therapy is widely used for the management of pancreatic cancer, identifying novel targets to improve the radiosensitivity of cancer cells is beneficial. Rosiglitazone, a specific peroxisome proliferator-activated receptor γ (PPARγ) agonist, has an inhibitory effect on various types of cancer cells. The purpose of this paper is to investigate the effect of rosiglitazone on the radiosensitivity of pancreatic cancer cells and the potential mechanism.Materials and MethodsPPARγ expression in pancreatic cancer and adjacent tissues was evaluated using immunohistochemistry analysis. The viability, migration and invasion ability of PANC1 and PaTu8988 cells were detected using MTT assay, scratch-wound assay and transwell invasion assay. The effect of rosiglitazone on radiosensitivity of the cells was determined using the clonogenic assay. PANC1 cells were inoculated into BALB/c mice to establish tumors. Microarray was used to investigate changes of genes involved.ResultsHigher PPARγ expression was demonstrated in pancreatic cancer tissues compared with para-carcinoma tissues. Rosiglitazone inhibited the cell viability and enhanced the radiation-induced anti-migration and anti-invasion effect. Rosiglitazone potentiated the radiosensitivity of pancreatic cancer cells and PANC1 xenografts. Microarray analysis revealed that rosiglitazone plus radiation altered the expression of multiple genes and affected multiple pathways.ConclusionRosiglitazone enhances the radiosensitivity of human pancreatic cancer cells in vitro and in vivo via complex mechanisms.

Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage.

Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.

The Evolutionary Origins of Recurrent Pancreatic Cancer.

Surgery is the only curative option for stage I/II pancreatic cancer; nonetheless, most patients will experience a recurrence after surgery and die of their disease. To identify novel opportunities for management of recurrent pancreatic cancer, we performed whole-exome or targeted sequencing of 10 resected primary cancers and matched intrapancreatic recurrences or distant metastases. We identified that recurrent disease after adjuvant or first-line platinum therapy corresponds to an increased mutational burden. Recurrent disease is enriched for genetic alterations predicted to activate MAPK/ERK and PI3K-AKT signaling and develops from a monophyletic or polyphyletic origin. Treatment-induced genetic bottlenecks lead to a modified genetic landscape and subclonal heterogeneity for driver gene alterations in part due to intermetastatic seeding. In 1 patient what was believed to be recurrent disease was an independent (second) primary tumor. These findings suggest routine post-treatment sampling may have value in the management of recurrent pancreatic cancer. SIGNIFICANCE: The biological features or clinical vulnerabilities of recurrent pancreatic cancer after pancreaticoduodenectomy are unknown. Using whole-exome sequencing we find that recurrent disease has a distinct genomic landscape, intermetastatic genetic heterogeneity, diverse clonal origins, and higher mutational burden than found for treatment-naïve disease.See related commentary by Bednar and Pasca di Magliano, p. 762.This article is highlighted in the In This Issue feature, p. 747.