A personalized approach to pancreatic ductal adenocarcinoma and its application in surgical practice

2021 ◽  
Author(s):  
Dimitrios Schizas ◽  
Alkmini Koumpoura ◽  
Meropi Galari ◽  
Panagiota Economopoulou ◽  
Michail Vailas ◽  
...  
Keyword(s):  
Survival Rates ◽  
Delayed Diagnosis ◽  
Ductal Adenocarcinoma ◽  
Genetic Profile ◽  
Therapeutic Approaches ◽  
Effective Selection ◽  
The Usa ◽  
Pancreatic Duct Adenocarcinoma ◽  
Personalized Approach ◽  
Related Mortality

Pancreatic duct adenocarcinoma is an aggressive tumor which constitutes the fourth leading cause of cancer-related mortality in the USA. Despite the fact that surgery is an integral part of treatment, 5-year survival rates remain unfavorable, partly because of the complex genetic background, delayed diagnosis and also the absence of effective therapeutic approaches. To optimize surgery’s results in recent years, the use of patients’ genetic profile has been implemented through classification into subtypes; subtypes based on mutations which could efficiently lead oncologists to the path of targeted novel neoadjuvant regimens. This approach aims to achieve the most effective selection of patients undergoing surgery, to increase the number of potentially resectable tumors and also control micro-metastases, aiming to extend overall survival.

scholarly journals Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1627 ◽  
Author(s):  
Anita Thyagarajan ◽  
Mamdouh Salman A. Alshehri ◽  
Kelly L.R. Miller ◽  
Catherine M. Sherwin ◽  
Jeffrey B. Travers ◽  
...  
Keyword(s):  
Survival Rates ◽  
Suppressor Cells ◽  
Cell Types ◽  
Therapeutic Agents ◽  
Ductal Adenocarcinoma ◽  
Cancer Therapies ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Resistance ◽  
Cellular Mechanisms ◽  
Immunosuppressive Cell

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating human malignancy with poor prognosis and low survival rates. Several cellular mechanisms have been linked with pancreatic carcinogenesis and also implicated in inducing tumor resistance to known therapeutic regimens. Of various factors, immune evasion mechanisms play critical roles in tumor progression and impeding the efficacy of cancer therapies including PDAC. Among immunosuppressive cell types, myeloid-derived suppressor cells (MDSCs) have been extensively studied and demonstrated to not only support PDAC development but also hamper the anti-tumor immune responses elicited by therapeutic agents. Notably, recent efforts have been directed in devising novel approaches to target MDSCs to limit their effects. Multiple strategies including immune-based approaches have been explored either alone or in combination with therapeutic agents to target MDSCs in preclinical and clinical settings of PDAC. The current review highlights the roles and mechanisms of MDSCs as well as the implications of this immunomodulatory cell type as a potential target to improve the efficacy of therapeutic regimens for PDAC.

scholarly journals Sinonasal mucosal melanoma: treatment strategies and survival rates for a rare disease entity

2021 ◽  
Author(s):  
Alexandros Andrianakis ◽  
Peter Kiss ◽  
Markus Pomberger ◽  
Axel Wolf ◽  
Dietmar Thurnher ◽  
...  
Keyword(s):  
Rare Disease ◽  
Survival Data ◽  
Survival Rates ◽  
Delayed Diagnosis ◽  
Distant Metastases ◽  
Primary Treatment ◽  
Mucosal Melanoma ◽  
Disease Entity ◽  
Improve Outcome ◽  
Initial Symptoms

Summary Background Sinonasal mucosal melanoma (SNMM) is a rare disease entity comprising 0.4–1.3% of all melanomas. Surgery with free margins has been the primary treatment over decades. Neither the addition of radiotherapy nor chemotherapy could significantly improve outcome rates of this devastating malignancy. This study presents our clinical experience with SNMM over a 19-year period and summarizes the current body of literature on SNMM. Methods This retrospective analysis included 12 patients with SNMM treated from 2001 to 2019 at an academic center. Additionally, a literature review of the last 29 years on treatment and survival data of SNMM was conducted. Results Main initial symptoms were epistaxis and nasal obstruction. Of the patients 9 underwent endoscopic surgery, 6 received adjuvant therapy. 3 patients who did not undergo surgery, received chemoradiotherapy, radiotherapy alone, and chemotherapy alone, respectively. At the time of diagnosis 2 patients had distant metastases and 4 patients developed distant metastases during the course of the disease. Mean overall survival (OS) was 30.6 months, 3‑year and 5‑year OS were 25%, and 18.2%, respectively. Conclusion Unspecific symptoms and hidden anatomic locations lead to delayed diagnosis and increased rates of metastatic dissemination. Distant metastasis is the main treatment failure in SNMM. Surgery with free margins remains the primary treatment for SNMM. Adjuvant radiotherapy might improve local control in individual cases but efficient systemic therapy is needed to improve outcome rates. To evaluate and define more effective targeted treatment options and improve outcome rates, homogeneous data and prospective multicentric analysis are needed.

scholarly journals Impact of SARS-COV-2 Pandemic on Kidney Cancer Management

Kidney Cancer ◽  
2021 ◽  
pp. 1-14
Author(s):  
Melissa Bersanelli ◽  
Camillo Porta
Keyword(s):  
Survival Rates ◽  
Delayed Diagnosis ◽  
Case Series ◽  
Cost Benefit ◽  
Original Data ◽  
Immune Checkpoint Blockade ◽  
Retrospective Case ◽  
Renal Masses ◽  
Term Survival ◽  
Cancer Management

Background: The SARS-CoV-2 pandemic still has a huge impact on the management of many chronic diseases such as cancer. Few data are presently available reagarding how the management of renal cell carcinoma (RCC) has changed due to this unprecedented situation. Objective: To discuss the challenges and issues of the diagnosis and treatment of RCC in the COVID-19 era, and to provide recommendations based on the collected literature and our personal experience. Methods: Systematic review of the available Literature regarding the management of RCC during the SARS-CoV-2 pandemic. Results: Our review showed a prevalence of narrative publications, raising the issue of the real relevance of the evidence retrieved. Indeed, the only original data about RCC and COVID-19 found were a small retrospective case series and two surveys, providing either patients’ or physicians’ viewpoints. Conclusions: The expected delayed diagnosis of RCC could lead to an increase of advanced/metastatic cases; thus, proper therapeutic choices for patients with small renal masses should be carefully evaluated case by case, in order to avoid negative effects on long-term survival rates. The controversial interaction between immune checkpoint blockade and COVID-19 pathogenesis is more hypothetical than evidence-based, and thus immunotherapy should not be denied, whenever appropriate. To avoid treatments which won’t have an impact on patients’ survival, a honest and accurate evaluation of the cost/benefit ratio of each treatment option should be always performed. Finally, SARS-CoV-2 swab positivity should not prevent the continuation of ongoing active treatments in asymptomatic cases, or or after symptoms’ resolution.

scholarly journals Organoid technology for personalized pancreatic cancer therapy

2021 ◽  
Author(s):  
Axel Bengtsson ◽  
Roland Andersson ◽  
Jonas Rahm ◽  
Karthik Ganganna ◽  
Bodil Andersson ◽  
...  
Keyword(s):  
Drug Screening ◽  
Response Prediction ◽  
Metabolic Imaging ◽  
Ductal Adenocarcinoma ◽  
3D Bioprinting ◽  
Preclinical Models ◽  
Liquid Handling ◽  
Technical Solutions ◽  
Pancreatic Cancer Therapy ◽  
Related Mortality

Abstract Background Pancreatic ductal adenocarcinoma has the lowest survival rate among all major cancers and is the third leading cause of cancer-related mortality. The stagnant survival statistics and dismal response rates to current therapeutics highlight the need for more efficient preclinical models. Patient-derived organoids (PDOs) offer new possibilities as powerful preclinical models able to account for interpatient variability. Organoid development can be divided into four different key phases: establishment, propagation, drug screening and response prediction. Establishment entails tailored tissue extraction and growth protocols, propagation requires consistent multiplication and passaging, while drug screening and response prediction will benefit from shorter and more precise assays, and clear decision-making tools. Conclusions This review attempts to outline the most important challenges that remain in exploiting organoid platforms for drug discovery and clinical applications. Some of these challenges may be overcome by novel methods that are under investigation, such as 3D bioprinting systems, microfluidic systems, optical metabolic imaging and liquid handling robotics. We also propose an optimized organoid workflow inspired by all technical solutions we have presented.

scholarly journals Toward Resolving the Challenges of Sepsis Diagnosis

2004 ◽  
Vol 50 (8) ◽  
pp. 1301-1314 ◽  
Author(s):  
Shawn D Carrigan ◽  
George Scott ◽  
Maryam Tabrizian
Keyword(s):  
Medical Diagnosis ◽  
Delayed Diagnosis ◽  
High Sensitivity ◽  
The United States ◽  
Immune Monitoring ◽  
Diagnostic Methods ◽  
Magic Bullet ◽  
Sepsis Diagnosis ◽  
The Past ◽  
Related Mortality

Abstract Sepsis in the United States has an estimated annual healthcare cost of $16.7 billion and leads to 120 000 deaths. Insufficient development in both medical diagnosis and treatment of sepsis has led to continued growth in reported cases of sepsis over the past two decades with little improvement in mortality statistics. Efforts over the last decade to improve diagnosis have unsuccessfully sought to identify a “magic bullet” proteic biomarker that provides high sensitivity and specificity for infectious inflammation. More recently, genetic methods have made tracking regulation of the genes responsible for these biomarkers possible, giving current research new direction in the search to understand how host immune response combats infection. Despite the breadth of research, inadequate treatment as a result of delayed diagnosis continues to affect approximately one fourth of septic patients. In this report we review past and present diagnostic methods for sepsis and their respective limitations, and discuss the requirements for more timely diagnosis as the next step in curtailing sepsis-related mortality. We also present a proposal toward revision of the current diagnostic paradigm to include real-time immune monitoring.

Breeding for improved blanchability in peanut: phenotyping, genotype × environment interaction and selection

2018 ◽  
Vol 69 (12) ◽  
pp. 1237 ◽  
Author(s):  
G. C. Wright ◽  
M. G. Borgognone ◽  
D. J. O Connor ◽  
R. C. N. Rachaputi ◽  
R. J. Henry ◽  
...  
Keyword(s):  
Low Cost ◽  
Peanut Butter ◽  
Environment Interaction ◽  
Breeding Lines ◽  
Seed Supply ◽  
Genotype Environment Interaction ◽  
Effective Selection ◽  
The Usa ◽  
Speed Up ◽  
Very High

Breeding for improved blanchability—the propensity of the testa (skin) to be removed from the kernel following rapid heat treatment—is a priority for improvement in the Australian Peanut Breeding Program (APBP). Easy removal of the testa by blanching is required for processing of peanuts into peanut butter and various other confectionary products. Thus, blanchability is an economically important trait in any newly released cultivar in Australia. A better understanding of the range of genetic variation, nature of inheritance and genotype×environment (G×E) interactions, and the development of a low-cost method to phenotype in early generations, could speed up breeding for this trait. Studies were conducted to develop a low-cost, rapid method utilising minimal amounts of seed to phenotype in early generations, along with an assessment of G×E interactions over a range of years and environments to derive optimal selection protocols. Use of a smaller kernel sample size than standard (50 vs 200g) was effective for accurately assessing blanchability in breeding lines and could allow selection in early generations (e.g. in seed produced from a single F2 plant where seed supply is adequate). G×E interaction for blanchability was shown to be very low. Genotypic variance explained 62–100% of the total variance for blanchability, assessed in two diverse germplasm pools including 107 accessions in the USA mini-core over three environments and multiple APBP breeding lines grown over nine different years–environments. Genotypic correlations between all environments were very high (~0.60–0.96), with heritability for the blanchability trait estimated to be very high (0.74–0.97) across the 13 trials. The results clearly demonstrate that effective selection for improved blanchability can be conducted in early generations and in a limited number of contrasting environments to ensure consistency of results.

Survival of fish passing downstream at a small hydropower facility

2018 ◽  
Vol 69 (12) ◽  
pp. 1870 ◽  
Author(s):  
Stephen V. Amaral ◽  
Benjamin S. Coleman ◽  
Jenna L. Rackovan ◽  
Kelly Withers ◽  
Benjamin Mater
Keyword(s):  
Mississippi River ◽  
River Flow ◽  
Survival Rates ◽  
Fish Populations ◽  
Negative Effects ◽  
Small Hydropower ◽  
The Usa ◽  
Pass Through ◽  
Hydro Project ◽  
Total Project

Hydropower dams can negatively affect upstream and downstream migratory fish populations in many ways, such as blocking access to upstream habitats and causing injuries or mortality during downstream passage. For downstream passage at projects in the USA, federal regulators and agencies responsible for oversight of hydropower facilities typically require assessment studies and mitigation to address negative effects, with a primary goal of minimising fish impingement and turbine entrainment and mortality. So as to assess the effects of downstream passage of fish populations at a unique, small hydro project on the Mississippi River, impingement and entrainment rates, Oberymeyer gate passage, spillway gate passage, turbine survival, and total downstream passage survival were estimated. It was determined that 85% of fish passing downstream at the project would be small enough to pass through the bar spacing of the trash racks and 15% would be physically excluded. When 55% of river flow enters the turbine intake channel, the total project survival rates were estimated to be 77.3% with an Obermeyer gate bypass rate of 10 and 96.6% with a gate bypass rate of 90%. Therefore, any effects on local fish populations resulting from the operation of the project are expected to be negligible and inconsequential on the basis of expected survival rates for the range and probability of river flows occurring at the project.

The US brewing industry, strategic windows and survival

2014 ◽  
Vol 20 (4) ◽  
pp. 434-458 ◽  
Author(s):  
Lynn A. Walter ◽  
Linda F. Edelman ◽  
Keneth J. Hatten
Keyword(s):  
Dynamic Capabilities ◽  
Survival Rates ◽  
Second Phase ◽  
Brewing Industry ◽  
Content Type ◽  
Operational Capabilities ◽  
Select Group ◽  
The Us ◽  
The Usa

Purpose – This paper aims to investigate how dynamic capabilities enabled survival in a select group of brewers, during one of the lengthiest and most severe industry consolidations in history. In doing so, we advance Abell’s (1978) theory of strategic windows through integration with the resource-based view of the firm. Design/methodology/approach – Using a mixed method approach, we first apply case study methods to develop hypotheses around the timing and level of operational capability required for survival. In the second phase, we test these hypothesized estimations on the USA Brewing population. Findings – Indicate that brewers which had advanced distribution and manufacturing operational capabilities before the strategic window of opportunity closed had higher survival rates. Practical implications – This study reinforces the importance of making timely strategic investments in capabilities. Originality/value – The integration of strategic window and capability theories advances our understanding of the roles that capabilities and time play in determining firm survival.

scholarly journals Factors affecting overall survival in ductal adenocarcinoma of the pancreatic head. Experience of one center

2021 ◽  
Vol 11 (1) ◽  
pp. 20-28
Author(s):  
D.  M. Kuchin ◽  
Ya.  I. Kolesnik ◽  
H.  G. Torgomyan ◽  
V.  E. Zagainov
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Vascular Invasion ◽  
Survival Rates ◽  
Pancreatic Head ◽  
Ductal Adenocarcinoma ◽  
Factors Affecting ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Major Factors

Purpose. To identify major factors affecting the overall survival (OS). To select the cohort of patients with the best prognosis.Materials and methods. A retrospective analysis included data of 268 patients, 128 men and 140 women, with median age of 59±10,53 (30 to 83) years. For multivariate analysis of survival, patients were selected who underwent pancreaticoduodenectomy (PD) for ductal adenocarcinoma of the pancreatic head.Results. Our study demonstrated that histologically verified vascular invasion (detected only in 30 % of patients who underwent PD with resection of the major vessels) statistically significantly affected the OS. The increased CA19-9 level over 500 U / L (detected in 32,3 % of cases) is the factor that significantly worsens the OS. Patients with high grade adenocarcinoma have significantly better survival rates compared with patients who have moderately or poorly differentiated adenocarcinoma (p = 0.014; median 26 months, 95 % CI 4.4–47.6 versus median 17 months, 95 % CI 15–19, an median: 13 months, 95 % CI 5–21, respectively). Also, the use of adjuvant chemotherapy has a positive effect on long-term outcomes (p = 0.0001; median 26 months, 95 % CI 21.7–30.3 versus median 13 months, 95 % CI 11.3–14.7).Conclusion. A well-differentiated tumor and the use of adjuvant chemotherapy significantly increase the OS of patients. Poorly differentiated tumor, CA19-9 level over 500 U / mL and the histologically confirmed vascular invasion significantly worsen the prognosis of these patients.

Survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma

2020 ◽  
Vol 21 (4) ◽  
pp. 127-130
Author(s):  
V. U. Rayn ◽  
◽  
A. A. Chernov ◽  
S. O. Zabotkin ◽  
◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Soft Tissues ◽  
Abdominal Cavity ◽  
Survival Rates ◽  
Pancreatic Head ◽  
Ductal Adenocarcinoma ◽  
En Bloc ◽  
Free Survival ◽  
Pancreatic Head Cancer

Aim. To access overall and event-free survival rates in patients after surgical treatment of localized and locally spread pancreatic head cancer. Materials and methods. A single center observational trial was conducted at a low-volume pancreatic surgery center in Khanty-Mansiysk. Data were collected retrospectively from 2007 to 2019. Patients with resectable tumors were included into the study whose final histology showed pancreatic ductal adenocarcinoma and en-bloc resection. According to the technical facilities and actual clinical protocols all patients received surgical treatment only and were then monitored. Data on progression patterns and survival rates were collected and calculated using Kaplan-Meier survival analysis. Results. Median overall survival (OS) after R0 pancreaticoduodenectomy was 16,8 months (IQR 10,9-23,5). Median progression-free survival was 10,6 mo. (IQR 8,0-20,7). OS in jaundiced patients was 4,9 mo. shorter than in patients without jaundice at the diagnosis (р = 0,011). Patients with serum bilirubin level < 100 μmol/l lived on average 7.2 months longer (p = 0.014). Most frequent sites of primary progression were liver and peritoneum, lungs, bones, lymph nodes of the abdominal cavity / retroperitoneal space, less often metastases were found in the skin and soft tissues. In 21.4% of cases metastases were found in several organs simultaneously with most frequent combination of liver and peritoneum, liver and lungs, lungs and bones. The median survival after progression was 7.1 ± 4.8 months Conclusion. Pancreatic duct adenocarcinoma has a high potential for progression and has therefore poor prognosis. To improve long-term outcomes, it is advisable to apply additional therapeutic options perioperatively.

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