Locally Advanced Pancreatic Cancer: Beyond the borders

Staging and treatment of locally advanced pancreatic cancer.The staging of locally advanced pancreatic cancer (LAPC) remains essential, especially in the current expansion of local therapies.[20] As proper staging of LAPC allows for better understanding of new treatment protocols, since patients with understaged disease are excluded before diluting true outcomes. Furthermore, there are no definitive answers on which regimens should be used as treatment for LAPC. The role of FOLFIRINOX and radiotherapy in the treatment of LAPC is of interest, as they have shown promising results lately. This thesis is divided in two parts. The first part focuses on the staging of LAPC. The second part focuses on the treatment of patients with LAPC

Studying the Effect of Cutting Conditions in Turning Process on Surface Roughness for Different Materials

Surfaces quality is one of the most specified customer requirements for machine parts. The major indication of surfaces quality on machined parts is surface roughness. The research aim is to study the cutting conditions and their effects on the surface roughness. This research will use regression models and neuro-fuzzy to predict surface roughness over the machining time for variety of cutting conditions in turning. In the experimental part for turning, different types of materials (Aluminum alloy, brass alloy, and low carbon steel) were considered with different cutting speed, and feed rate. A linear regression and neuro-fuzzy model depending on statistical-mathematical method between surface roughness, Ra, and cutting condition will be derived, for the three materials. The effect of cutting parameters on surface roughness is evaluated and the optimum cutting condition for minimizing the surface roughness will be determined. The model will be established between the cutting conditions and surface roughness using regression and neuro-fuzzy model. As the results of this work, the linear regression and neuro-fuzzy model will be used in predicting surface roughness, can be used in manufacturing systems, this modeling helps engineer to reduce the efforts and improve the quality

Potentiation of peptide receptor radionuclide therapy by the PARP inhibitor olaparib

Metastases expressing tumor-specific receptors can be targeted and treated by binding of radiolabeled peptides (peptide receptor radionuclide therapy or PRRT). For example, patients with metastasized somatostatin receptor-positive neuroendocrine tumors (NETs) can be treated with radiolabeled somatostatin analogues, resulting in strongly increased progression-free survival and quality of life. There is nevertheless still room for improvement, as very few patients can be cured at this stage of disease. We aimed to specifically sensitize replicating tumor cells without further damage to healthy tissues. Thereto we investigated the DNA damaging effects of PRRT with the purpose to enhance these effects through modulation of the DNA damage response. Although PRRT induces DNA double strand breaks (DSBs), a larger fraction of the induced lesions are single strand breaks (expected to be similar to those induced by external beam radiotherapy) that require poly-[ADP-ribose]-polymerase 1 (PARP-1) activity for repair. If these breaks cannot be repaired, they will cause replication fork arrest and DSB formation during replication. Therefore, we used the PARP-1 inhibitor Olaparib to increase the number of cytotoxic DSBs. Here we show that this new combination strategy synergistically sensitized somatostatin receptor expressing cells to PRRT. We observed increased cell death and reduced cellular proliferation compared to the PRRT alone. The enhanced cell death was caused by increased numbers of DSBs that are repaired with remarkably slow kinetics, leading to genome instability. Furthermore, we validated the increased DSB induction after PARP inhibitor addition in the clinically relevant model of living human NET slices. We expect that this combined regimen can thus augment current PRRT outcomes

The yield of chest computed tomography in patients with locally advanced pancreatic cancer

Objective: To evaluate the incidence of pulmonary metastases on chest computed tomography (CT) in patients with locally advanced pancreatic cancer (LAPC). Methods: All patients diagnosed with LAPC in a single tertiary center (Erasmus MC) between October 2011 and December 2017 were reviewed. The staging chest CT scan and follow-up chest CT scans were evaluated. Pulmonary nodules were divided into three categories: apparent benign, too small to characterize, and apparent malignant. Results: In 124 consecutive patients diagnosed with LAPC, 119 (96%) patients underwent a staging chest CT scan at the initial presentation. In 88 (74%) patients no pulmonary nodules were found; in 16 (13%) patients an apparent benign pulmonary nodule was found, and in 15 (13%) patients a pulmonary nodule too small to characterize was found. Follow-up chest CT scan(s) were performed in 111 (93%) patients. In one patient with either no pulmonary nodule or an apparent benign pulmonary nodule at initial staging, an apparent malignant pulmonary nodule was found on a follow-up chest CT scan. However, a biopsy of the nodule was inconclusive. Of 15 patients in whom a pulmonary nodule too small to characterize was found at staging, 12 (80%) patients underwent a follow-up CT scan; in 4 (33%) of these patients, an apparent malignant pulmonary nodule was found. Conclusion: In patients with LAPC in whom at diagnosis a chest CT scan revealed either no pulmonary nodules or apparent benign pulmonary nodules, routine follow-up chest CT scans is not recommended. Patients with pulmonary nodules too small to characterize are at risk to develop apparent malignant pulmonary nodules during follow-up

Fishery and population dynamics of Protonibea diacanthus (Lacepede) and Otolithoides biauritus (Cantor) landed by trawlers at Vanakbara, Diu along the west coast of India

The fishery and population characteristics of larger sciaenids Protonibea diacanthus (Lacepede) and Otolithoides biauritus(Cantor) landed by trawlers at Vanakbara, Diu were studied for the period 2003 – 2007. The average annual catch of P. diacanthus was 770.6 t and that of O. biauritus was 1018.6 t, together contributing 12% to the total trawl catch at Vanakbara. Majority of the larger sciaenids were landed during September - December. The von Bertalanffy growth equation was Lt = 145.3 [1 – e - 0.14 (t + 0.0738)] for P. diacanthus and Lt = 160 [1 – e - 0.19 (t + 0.0638)] for O. biauritus. The mortality rates M, F and Z computed for P. diacanthus were 1, 0.30 and 0.61 and for O. biauritus were 7, 0.33 and 0.70. The exploitation ratio (E) was 0.49 for P. diacanthus and 0.47 for O. biauritus. A maximum increase in relative yield by 2.7% for P. diacanthus could be realized by decreasing the present level of fishing by 20%, while for O. biauritus the present fishing effort is at optimum level

Low skeletal muscle mass is associated with increased hospital expenditure in patients undergoing cancer surgery of the alimentary tract

Background: Low skeletal muscle mass is associated with poor postoperative outcomes in cancer patients. Furthermore, it is associated with increased healthcare costs in the United States. We investigated its effect on hospital expenditure in a Western-European healthcare system, with universal access. Methods: Skeletal muscle mass (assessed on CT) and costs were obtained for patients who underwent curative-intent abdominal cancer surgery. Low skeletal muscle mass was defined based on pre-established cut-offs. The relationship between low skeletal muscle mass and hospital costs was assessed using linear regression analysis and Mann-Whitney U-tests. Results: 452 patients were included (median age 65, 61.5% males). Patients underwent surgery for colorectal cancer (38.9%), colorectal liver metastases (27.4%), primary liver tumours (23.2%), and pancreatic/periampullary cancer (10.4%). In total, 45.6% had sarcopenia. Median costs were €2,183 higher in patients with low compared with patients with high skeletal muscle mass (€17,144 versus €14,961; P<0.001). Hospital costs incrementally increased with lower sex-specific skeletal muscle mass quartiles (P = 0.029). After adjustment for confounders, low skeletal muscle mass was associated with a cost increase of €4,061 (P = 0.015). Conclusion: Low skeletal muscle mass was independently associated with increased hospital costs of about €4,000 per patient. Strategies to reduce skeletal muscle wasting could reduce hospital costs in an era of incremental healthcare costs and an increasingly ageing population

Efficacy and feasibility of stereotactic radiotherapy after folfirinox in patients with locally advanced pancreatic cancer (LAPC-1 trial)

Background: We conducted a multicentre phase II trial to investigate feasibility and antitumor activity of sequential FOLFIRINOX and Stereotactic Body Radiotherapy (SBRT) in patients with locally advanced pancreatic cancer (LAPC), (LAPC-1 trial). Methods: Patients with biopsy-proven LAPC treated in four hospitals in the Netherlands between December 2014 and June 2017. Patients received 8 cycles of FOLFIRINOX followed by SBRT (5 fractions/8 Gy) if no tumour progression after the FOLFIRINOX treatment was observed. Primary outcome was 1-year overall survival (OS). Secondary outcomes were median OS, 1-year progression-free survival (PFS), treatment-related toxicity, and resection rate. The study is registered with ClinicalTrials.gov, NCT02292745, and is completed. Findings: Fifty patients were included. Nineteen (38%) patients did not receive all 8 cycles of FOLFIRINOX, due to toxicity (n = 12), disease progression (n = 6), or patients’ preference (n = 1). Thirty-nine (78%) patients received the SBRT treatment. The 1-year OS and PFS were 64% (95% CI: 50%-76%) and 3

Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): Study protocol for a multicentre randomized controlled trial

Background: Pancreatic cancer is the fourth largest cause of cancer death in the United States and Europe with over 100,000 deaths per year in Europe alone. The overall 5-year survival ranges from 2-7 % and has hardly improve

Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad: a community study [corrected].

BACKGROUND: A serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA-TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic. METHODS: We obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA-TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1-29 years of a rural area roughly 13-15 and 2-4 months before and 4-6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods. FINDINGS: Roughly 1·8 million individuals aged 1-29 years received one dose of PsA-TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100,000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100,000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (p<0·0001), and an incidence rate ratio of 0·096 (95% CI 0·046-0·198). Despite enhanced surveillance, no case of serogroup A meningococcal meningitis was reported in the three vaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2-4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4-6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002-0·138; p<0·0001). INTERPRETATION: PSA-TT was highly effective at prevention of serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be established. FUNDING: The Bill & Melinda Gates Foundation, the Wellcome Trust, and Médecins Sans Frontères