Chance Of Long-term Survival Research Articles

Social Innovation for Sustainability and Social Inclusion

Companies are realising now that business is not only about selling products to rich consumers but also to serve the underserved bottom-of-the-pyramid (BOP) markets. Serving these customers calls for innovative methods. This had led to reinventing business models to expand the nature of their businesses from mere commercial motives to social ones as well; the understanding that businesses succeed if they go beyond their mandate of making profits. The future rests on three paradigm shifts taking place in BOP approaches: innovation, transformation of companies into social enterprises and technological advancements that bring products closer to BOP consumers. That is to say, companies today re-invent their business models and their very approach of doing business. Such companies stand a greater chance of success and long-term survival. This article describes the concepts of social business, social entrepreneurship and social innovation. We illustrate the concepts with mini case studies or examples of several companies that have achieved innovation in products, business models or processes to serve BOP markets. We describe efforts that solve problems of consumers who are disadvantaged because of distance, education or purchasing power. If this ‘social innovation’ betters the life of consumers, it could result in sustainability and inclusive development. The world is slowly realising that the existing business models that place importance on relentless pursuit of profits are causing immense damage to our society and environment. The objectives of business must change. Milton Friedman’s famous saying, ‘the sole purpose of a business is to generate profits for its shareholders’ is no longer accepted today as businesses find that they must cater to social objectives as well. This article describes that this can well be achieved, as illustrated by several companies who achieve both—financial profits and social good. Drawing from examples of successful initiatives, new business models are being created that provide affordable products and services for disadvantaged consumers. We have taken elements from the business models of these companies to figure out what the future looks like. These companies, we find, found solutions through an action-oriented mindset to solve long-standing problems. Firms that embrace experimentation and rapid prototyping stand to win huge new markets and profits. They invest in distribution and training of local resources, develop innovative products and processes, involve stakeholders and above all, build a social purpose in their objectives. Social innovation and social entrepreneurship shift the focus of governments and companies towards neglected or BOP consumers who are otherwise unapproachable. Examples of social innovation show that it touches the lives of millions of people, empowers them and leads to sustainability. Investments in social innovation that are both sustainable and socially inclusive are the need of the hour.

Renal Hypoxic Reperfusion Injury-on-Chip Model for Studying Combinational Vitamin Therapy.

Renal ischemic-reperfusion injury decreases the chances of long-term kidney graft survival and may lead to the loss of a transplanted kidney. During organ excision, the cycle of warm ischemia from the donor and cold ischemia is due to storage in a cold medium after revascularization following organ transplantation. The reperfusion of the kidney graft activates several pathways that generate reactive oxygen species, forming a hypoxic-reperfusion injury. Animal models are generally used to model and investigate renal hypoxic-reperfusion injury. However, these models face ethical concerns and present a lack of robustness and intraspecies genetic variations, among other limitations. We introduce a microfluidics-based renal hypoxic-reperfusion (RHR) injury-on-chip model to overcome current limitations. Primary human renal proximal tubular epithelial cells and primary human endothelial cells were cultured on the apical and basal sides of a porous membrane. Hypoxic and normoxic cell culture media were used to create the RHR injury-on-chip model. The disease model was validated by estimating various specific hypoxic biomarkers of RHR. Furthermore, retinol, ascorbic acid, and combinational doses were tested to devise a therapeutic solution for RHR. We found that combinational vitamin therapy can decrease the chances of RHR injury. The proposed RHR injury-on-chip model can serve as an alternative to animal testing for injury investigation and the identification of new therapies.

The Role of AKT in Soft Tissue Sarcoma: Review and Insights.

Soft tissue sarcomas (STS) are a biologically diverse group of mesenchymal tumors that predominantly exhibit a poor prognosis. Surgical resection is considered the mainstay of treatment and provides the only chance for long-term survival. However, some patients present with locally advanced, unresectable disease, and for those who are able to undergo resection, tumor recurrence occurs in over half of patients. In addition, the efficacy of conventional systemic therapies remains dismal. The serine/threonine kinase AKT pathway is one of the most frequently aberrantly activated signaling pathways that has been verified in many types of human cancer. Dysregulation of the AKT cascade is known to result in tumorigenesis and aggressive clinical behavior for many tumor types, including STS. EGFRs, with its downstream effectors, PI3K and protein kinase B (AKT)/mTOR, have been investigated for decades as promising targets for the treatment of STS, but significant challenges remain and the prognosis of patients with advanced STS has not improved in over two decades. In this review, we will first describe the AKT pathway and its role in STS tumor biology and then discuss the current challenges in targeting the AKT pathway to treat patients with advanced sarcoma.

Lymphangiosarcoma

Lymphangiosarcoma is a rare and aggressive malignancy. It is always associated with chronic lymphedema. This disease was described in 1948 by F.W. Stewart and N. Treves in 6 patients undergoing mastectomy. The incidence of lymphangiosarcoma is varied from 0.07 to 0.45 %. Average time of developing lymphangiosarcoma after mastectomy is 10.3 years. The etiology of this malignant tumor remains uncertain. Histologically LAS arises from epithelial cells of lymphatic vessels in the area of chronic lymphedema. There is no standard treatment of lymphangiosarcoma. Radiation therapy and chemotherapy do not significantly improve the survival rate. At the moment, wide local excision and amputation offer the best chance for long-term survival. Unfortunately, the prognosis remains poor.The study objective – is to draw attention to lymphangiosarcoma and to show the importance of its prevention.

The Liver Pre-Metastatic Niche in Pancreatic Cancer: A Potential Opportunity for Intervention.

Simple SummaryPatients with pancreatic cancer have a very poor chance of long-term survival. This is usually due to advanced disease at the time of diagnosis, which commonly includes occult or clinically obvious liver metastases. Emerging evidence suggests that organs that develop metastases exhibit microscopic changes that favor metastatic growth, collectively known as “pre-metastatic niches”. Such pre-metastatic niches result from various signals originating from the primary pancreatic tumor that reprogram immune and other cells in the liver and other organs, thus enabling the growth of cancer cells once they spread. In this review, we summarize the latest discoveries regarding the liver pre-metastatic niche in pancreatic cancer. We are optimistic that intensified future research will help to reveal powerful diagnostic markers and targetable therapeutic pathways, which will ultimately benefit patients.Cancer-related mortality is primarily a consequence of metastatic dissemination and associated complications. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and tends to metastasize early, especially in the liver. Emerging evidence suggests that organs that develop metastases exhibit microscopic changes that favor metastatic growth, collectively known as “pre-metastatic niches”. By definition, a pre-metastatic niche is chronologically established before overt metastatic outgrowth, and its generation involves the release of tumor-derived secreted factors that modulate cells intrinsic to the recipient organ, as well as recruitment of additional cells from tertiary sites, such as bone marrow—all orchestrated by the primary tumor. The pre-metastatic niche is characterized by tumor-promoting inflammation with tumor-supportive and immune-suppressive features, remodeling of the extracellular matrix, angiogenic modulation and metabolic alterations that support growth of disseminated tumor cells. In this paper, we review the current state of knowledge of the hepatic pre-metastatic niche in PDAC and attempt to create a framework to guide future diagnostic and therapeutic studies.

Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma: Where Do We Go?

The incidence of pancreatic ductal adenocarcinoma (PDAC) has been on the rise in recent years; however, its clinical diagnosis and treatment remain challenging. Although surgical resection remains the only chance for long-term patient survival, the likelihood of initial resectability is no higher than 20%. Neoadjuvant therapy (NAT) in PDAC aims to transform the proportion of inoperable PDACs into operable cases and reduce the likelihood of recurrence to improve overall survival. Ongoing phase 3 clinical trial aims to validate the role of NAT in PDAC therapy, including prolongation of survival, increased R0 resection, and a higher proportion of negative lymph nodes. Controversies surrounding the role of NAT in PDAC treatment include applicability to different stages of PDAC, chemotherapy regimens, radiation, duration of treatment, and assessment of effect. This review aims to summarize the current progress and controversies of NAT in PDAC.

Abstract 916: Dec2, a circadian rhythm gene is necessary for disseminated tumor cell survival in a novel murine model of pancreatic cancer dormancy

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a proclivity for early metastasis. Resection remains the only chance for long term survival though most patients die from metastatic recurrence. While most patients recur within the first two years, many develop recurrence much later indicating they harbor dormant disseminated tumor cells (dDTCs). Currently there are no murine models which recapitulate this disease pattern and as a result pancreatic cancer dormancy is poorly understood. We sought to better understand PDAC dormancy using a novel murine model of human pancreatic cancer from which we investigate the genetic and molecular contributions to dormancy. A model of resected PDAC was developed using murine PDAC cells expressing luciferase/mCherry orthotopically implanted into FVB hosts. Primary tumors are resected after 4 weeks and mice followed for recurrence. dDTCs’ are harvested from the livers of mice without evidence of recurrence by fluorescence activated cell sorting (FACS) and subjected to transcriptomic profiling using single cell RNA sequencing. Dec2’s contribution to dormancy was evaluated by overexpression and knockout using CRISPR. Overall survival in the mouse model mirrored 41,552 stage I, II PDAC patients from the National Cancer Database with similar frequency and location of recurrence. One third of mice exhibited latent recurrence with median survival of 568 days before succumbing to recurrence. These mice were used to study dDTCs. Transcriptomic profiling of FACS sorted dDTCs revealed a distinct transcriptome from primary tumors and early recurrences, indicating cell plasticity. dDTCs exhibited decreased proliferation markers and upregulated genes involved in immune modulation, cell stemness, linoleic acid (LA) metabolism, and Dec2. dDTCs were resistant to chemotherapy. An in vitro model of dormancy was constructed in which LA treatment inhibited cell proliferation and increased Dec2. Dec2 overexpression resulted in cell quiescence, and knockout increased apoptosis with LA exposure. Dec2-KO cells implanted in the murine model dramatically improved survival compared to Dec-WT cells (Dec2-WT median survival 30 days, Dec2-KO median survival was not reached, p=0.013). Livers of mice in the resection model where Dec2-KO cells were used had decreased dDTC burden with fewer mice showing detectable luciferase gDNA (p<0.01) indicating that loss of Dec2 reduced survival of dDTC’s. This is the first murine model of pancreatic cancer dormancy that recapitulates outcomes of resected PDAC patients. These studies reveal pancreatic cancer dormancy is characterized by a distinct, plastic cellular state characterized by chemotherapy resistance. Dec2 appears required for dormancy, its absence leads to disseminated tumor cell apoptosis. This suggests Dec2 may be a therapeutic target in pancreatic cancer dormancy. Citation Format: Anthony S. Casabianca, Chris Harris, Crissy Dudgeon, Darren R. Carpizo. Dec2, a circadian rhythm gene is necessary for disseminated tumor cell survival in a novel murine model of pancreatic cancer dormancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 916.

Short- and long-term outcomes following robotic and open resection for intrahepatic cholangiocarcinoma: A national cohort study

BackgroundCurative-intent liver resection with porta hepatis lymphadenectomy provides the best chance for long-term survival for patients with intrahepatic cholangiocarcinoma (ICC). While the robotic approach has been increasingly utilized, its impact on perioperative and long-term outcomes of patients with ICC are largely unknown. MethodsPatients with stages I-III ICC who underwent surgical resection between 2004 and 2017 were identified from the National Cancer Database. Descriptive statistics and multivariate models were constructed to examine the association between surgical approach and surgical and oncological outcomes. ResultsA total of 1876 patients with ICC who underwent open (n = 1804, 96.2%) and robotic-assisted (n = 72, 3.8%) resection were identified. Following surgery, patients who underwent a robotic-assisted resection had a shorter length of hospital stay yet there was no difference in 30-day readmission or 90-day mortality. Older age, disease stage, and higher comorbidity were associated with worse OS. Patients undergoing robotic-assisted surgery had no difference in long-term risk of death compared with patients who underwent an open procedure. ConclusionThis national cohort study demonstrated that the robotic approach for patients undergoing resection for ICC resulted in a shorter hospitalization while not compromising oncological outcomes such as negative margins, postoperative mortality, and long-term survival.

Learn and Adapt, or Perish: The Case of the F35 Lightning II

We assess to what extent a (co)evolutionary macro level approach enhances our understanding of learning in governance processes. We ask the question: in what ways do actors learn to improve their chances of long-term survival in complex governance processes? We deploy a model of collective decision making moulded upon fitness landscapes to analyze a longitudinal case study of collective (political and administrative) decision making, namely the process of developing and acquiring the F35 Lightning II fighter jet. The study demonstrates that actors learn how to ensure survival over time but create a failing megaproject in the process.

SURG-05. Survival and functional outcomes in pediatric thalamic and thalamopeduncular low grade gliomas

BACKGROUND: Childhood thalamopeduncular gliomas arise at the interface of thalamus and cerebral peduncle. The optimal treatment is total resection but not at the cost of neurological function. We present long-term clinical and oncological outcomes of maximal safe resection. METHODS: Retrospective review of prospectively collected data: demography, symptomatology, imaging, extent of resection, surgical complications, histology, functional and oncological outcome. RESULTS: During 16-year period (2005-20) 21 patients were treated at our institution. These were 13 girls and 8 boys (mean age 7.6 years). Presentation included progressive hemiparesis in 9 patients, raised intracranial pressure in 9 patients and cerebellar symptomatology in 3 patients. The tumor was confined to the thalamus in 6 cases. Extent of resection was judged on postoperative imaging as total (6), near-total (6) and less extensive (9). Surgical complications included progression of baseline neurological status in 6 patients, 5 of these gradually improved to preoperative status. All tumors were classified as low-grade gliomas. Disease progression was observed in 9 patients (median progression free survival 7.3 years). At last follow-up (median 6.1 years) all patients were alive; median Lansky score of 90. Seven patients were without evidence of disease, 6 had stable disease, 7 stable following progression and 1 had progressive disease managed expectantly. CONCLUSION: Pediatric patients with low grade thalamopeduncular gliomas have excellent long-term functional and oncological outcomes even when gross total resection is not achievable. Surgery should aim at total resection; however neurological function should not be endangered due to excellent chance for long-term survival.

The Latest on Lung Ablation.

Lung cancer is the second most common cancer in both men and women. Despite smoking cessation efforts and advances in lung cancer detection and treatment, long-term survival remains low. For early-stage primary lung carcinoma, surgical resection offers the best chance of long-term survival; however, only about one-third of patients are surgical candidates. For nonsurgical candidates, minimally invasive percutaneous thermal ablation therapies have become recognized as safe and effective treatment alternatives, including radiofrequency ablation, microwave ablation, and cryoablation. Lung ablation is also an acceptable treatment for limited oligometastatic and oligorecurrent diseases. This article discusses the technologies and techniques available for tumor ablation of thoracic malignancies, as well as new treatments on the horizon.

P-197 Impact of local treatments on survival of patients with liver metastases from colorectal cancer (CRC) in real-life setting

Liver is the most common site of metastases from CRC. Up to 70% of CRC patients develop liver metastases in their course of disease. Surgical resection is the only treatment that offers a chance of long-term survival, however, only a minority of patients is suitable for upfront surgery. Local therapies (including hybrid therapy approach) can be used to attain hepatic disease control in unresectable patients and possibly affect overall prognosis.

Outcomes and Allograft Survival of Patients Who Underwent a Second Kidney Transplant and Were Followed Up for 10 Years

Kidney transplantation is the treatment of choice for end-stage kidney disease, and a second transplantation becomes an opportunity for a better chance for long-term survival and quality of life. This study aimed to evaluate the outcomes and graft survival of patients transplanted a second time in comparison with single kidney transplant patients. This retrospective observational study was conducted using a cohort of kidney transplant patients from 2008 to 2018. Fifty patients who underwent first transplant were randomly selected as group 1 (G1), and 31 patients who received a second kidney transplant as group 2 (G2). Outcomes, graft, and patient survival were assessed. G2 patients had higher proportions of rejection episodes and graft loss than G1. Fifteen (48.39%) patients from G2 maintained functioning grafts during follow-up, while 16 (51.61%) lost their grafts. The 10-year graft survival rate for patients with first transplant was 76.66%; it was 46.09% for retransplanted patients (P=0.005). There was no statistically significant difference in patient survival between G1 and G2. Allograft survival rates of the first and second transplant with living donors had no statistically significant difference, but for deceased donors, poor graft survival was observed for the second allograft.

A 10-year experience of leiomyosarcoma of the inferior vena cava.

Leiomyosarcoma of the inferior vena cava (IVC) is rare. The study reviewed patients with IVC leiomyosarcoma in our hospital in the past ten years. Twenty patients diagnosed with IVC leiomyosarcoma between October 2010 and October 2020 were enrolled. Their clinical manifestations, treatments, and follow-up results were analyzed. The sarcoma was located in the lower IVC segment in six patients, with 13 in the middle and one in the upper IVC segment. Eighteen patients underwent R0 resection. After resection, 16 patients (80%) had primary repair of the IVC, while four patients underwent ligation. During a mean follow-up of 37.7months, seven patients died due to tumor metastasis, four patients were alive with the tumor recurrence and other nine patients were alive without recurrence. The management of the IVC after tumor resection depended on the tumor location and size. R0 resection provided a chance for long term survival.

Hair safe study: Effects of scalp cooling on hair preservation and hair regrowth in breast cancer patients receiving chemotherapy - A prospective interventional study

Hair safe study: Effects of scalp cooling on hair preservation and hair regrowth in breast cancer patients receiving chemotherapy - A prospective interventional study

A phase 2 trial of deep-inspiration breath hold in radiotherapy of gastric lymphomas.

Radiotherapy (RT) is an important part in the treatment of gastric lymphomas and the prognosis after radiotherapy is very good with a good chance of long-term survival, so prevention of long-term adverse effects is important. In patients with gastric lymphomas cardiac late effects are of most concern. The aim of this study was to assess if the dose to the heart could be reduced with deep inspiration breath-hold (DIBH) without compromising the dose to the target or increasing the risk of other late effects. Fifteen patients with gastric lymphoma were included. RT plans were made using DIBH and Free breathing (FB)scans. Clinical target volume (CTV) was the stomach plus 1cm margin. The heart and surrounding organs at risk (OAR) were contoured. Two sets of plan comparisons were made, one with 1cm CTV to planning target volume (PTV) margin in both DIBH and FB and one set with an additional 5mm CTV to PTV margin in cranio-caudal direction with FB. Datasets were analysed with Wilcoxon signed rank test for non-parametric paired data. All patients tolerated the procedures and were treated with volumetric arc therapy technique in DIBH. Target coverage was kept equal between FB and DIBH, while a statistically significant reduction of the estimated does to the heart was seen with DIBH. Median mean heart dose was reduced from 7.1Gy (5.7-12) to a median of 3.2Gy (1.2-7.0) and heart V20 from a median of 54 (17-106) cm3 to 15. (0.0-78) cm3. The estimated mean doses to the liver, duodenum, pancreas and spinal cord were at the same level. This clinical trial of RT with DIBH for gastric lymphomas showed that the heart dose could be reduced without compromising PTV coverage. The doses to abdominal OARs were similar with FB and DIBH.

Risk Factors of Low Birth Weight in Pakistan

Introduction: Birth weight is a reliable and sensitive indicator of a new-born’s chances of long-term survival, growth, and physical and psychosocial development. There is little research in Pakistan that documents valuable data such as detailed maternal consumption data and psychological factors and links them to low birth weight. The aim was to estimate the LBW proportion and to assess the factors influencing birth weight. Methods: This cross-sectional study was held in the community medicine department in collaboration with Obstetrics and Gynecology department of Jinnah hospital, Lahore and Darul Sehat Hospital, Karachi for the duration of four months from February 2021 to July 2021. A total of 130 patients were selected in consecutive samples, and then a questionnaire was given to them. Results: Among 130 women, the LBW frequency was 16.9%, and the mean birth weight was 2.7 ± 0.6 kg. We also found a significant relationship between birth weight and per capita income, maternal weight gain during pregnancy, number of prenatal visits, maternal education, tobacco use and nutritional stress, and egg consumption. Multivariate analysis showed a significant relationship between maternal weight gain and birth weight during pregnancy, tobacco use, and stress. Conclusion: More people were found to have access to basic prenatal care measures such as nutrition, free iron supplements, and regular prenatal checks, indicating a positive effect on birth weight in the study population. While several factors have been shown to be related to each other, the focus should be on psychological and nutritional factors. Keywords: Low birth weight, Related factors, Dietetics, Psychological.

Completion of FLOT Therapy, Regardless of Tumor Regression, Significantly Improves Overall Survival in Patients with Esophageal Adenocarcinoma.

Simple SummaryMultimodal therapy concepts, including surgery and systemic therapy, are the mainstay in the treatment of esophageal adenocarcinoma. Despite the technical advances in the surgical field and the widespread use of chemoradiation therapy, the prognosis and overall survival for esophageal cancer remains poor. Therapy with a continuous infusion of 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT protocol) has been shown to improve the overall survival for patients with esophageal adenocarcinoma. However, uncertainty exists as to whether patients with poor tumor responses should complete the chemotherapy following surgery. The aim of our study was to analyze the effect of neoadjuvant and adjuvant FLOT therapy on the outcomes of patients following an esophagectomy for adenocarcinoma, with the focus on the tumor regression grading and the completion of the systemic therapy. We showed that the completion of the systemic therapy, regardless of the tumor regression grading, improved the outcomes of patients with esophageal adenocarcinoma. Subgroup analyses further showed that complications from chemotherapy reduced the overall survival, while surgical complications did not.Esophageal cancer is the eighth most common cancer worldwide, with poor prognosis and high mortality. The combination of surgery and systemic therapy provide the best chances for long-term survival. The purpose of this study was to analyze the impact of the FLOT protocol on the overall survival of patients following surgery for esophageal adenocarcinoma, with a focus on the patients who did not benefit in terms of pathological remission from the neoadjuvant therapy. A retrospective analysis of all the patients who underwent esophagectomies from 2012 to 2017 for locally advanced adenocarcinomas of the esophagus at a tertiary medical center was performed. The results show that the completion of systemic therapy, regardless of the tumor regression grading, had a significant positive impact on the overall survival. The patients with complete regression and complete systemic therapy showed the best outcomes. Anastomotic insufficiency did not negatively impact the long-term survival, while complications of the systemic therapy led to significantly reduced overall survival. We conclude that adjuvant systemic therapy should, when possible, always be completed, regardless of the tumor regression, following an esophagectomy.

DEPEND study protocol: early detection of patients with pancreatic cancer – a pilot study to evaluate the utility of faecal elastase-1 and 13C-mixed triglyceride breath test as screening tools in high-risk individuals

IntroductionPancreatic cancer (PC) is the fifth leading cause of cancer-related death in the UK. The incidence of PC is increasing, with little or no improvement in overall survival and the...

Risk of recurrence and long-term mortality following radical cystectomy for bladder cancer

Purpose To investigate the risk of recurrence and long-term mortality after radical cystectomy (RC) for bladder cancer (BC) at a high-volume tertiary referral center in Denmark over 19 years. Materials and methods Patients undergoing RC between the 1st of January 2000 to 31st of December 2018 were included. Patient data were manually retrieved from electronic patient files. Follow-up ended 18th of May 2020. Cumulative incidences were used to assess risk of recurrence and mortality using competing risk modelling. Cause-specific Cox regression models were used for multivariable analysis. Results A total of 1267 patients underwent RC of which 1042 were eligible for analysis. Overall mortality was 40% and 56% after 5 and 10 years, respectively. The cumulative incidence of recurrence and BC specific mortality was high within the first 2 years. Only 3.2% of the patients with recurrence were alive at the end of follow-up. The cumulative incidence of BC mortality after 5 years was 6.7% (95% CI 3.6–9.9) and 10% (95% CI 6.8–14) for patients with ≤ pT1bN0 and pT2N0, respectively. For patients with lymph node positive disease the cumulative incidence of BC mortality after 5 years was 65% (95% CI 58–71). Conclusions We found a significant risk of recurrence and disease-specific mortality following RC for BC, especially within the first 2 years following surgery. Our data seem comparable to other large cohorts. The chance of long-term survival following recurrence is low and there is a continuous need to improve adjuvant or salvage strategies following RC.