scholarly journals Esophageal regeneration following surgical implantation of a tissue engineered esophageal implant in a pediatric model

2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Sumati Sundaram ◽  
Todd Jensen ◽  
Tina Roffidal ◽  
Karissa Paquin ◽  
Heather Wanczyk ◽  
...  
Keyword(s):  
Survival Time ◽  
Tissue Regeneration ◽  
Time Course ◽  
Ct Imaging ◽  
Congenital Defects ◽  
Term Survival ◽  
Long Term Survival ◽  
Time Points ◽  
Post Implantation

AbstractDiseases of the esophagus, damage of the esophagus due to injury or congenital defects during fetal esophageal development, i.e., esophageal atresia (EA), typically require surgical intervention to restore esophageal continuity. The development of tissue engineered tubular structures would improve the treatment options for these conditions by providing an alternative that is organ sparing and can be manufactured to fit the exact dimensions of the defect. An autologous tissue engineered Cellspan Esophageal ImplantTM (CEI) was surgically implanted into piglets that underwent surgical resection of the esophagus. Multiple survival time points, post-implantation, were analyzed histologically to understand the tissue architecture and time course of the regeneration process. In addition, we investigated CT imaging as an “in-life” monitoring protocol to assess tissue regeneration. We also utilized a clinically relevant animal management paradigm that was essential for long term survival. Following implantation, CT imaging revealed early tissue deposition and the formation of a contiguous tissue conduit. Endoscopic evaluation at multiple time points revealed complete epithelialization of the lumenal surface by day 90. Histologic evaluation at several necropsy time points, post-implantation, determined the time course of tissue regeneration and demonstrated that the tissue continues to remodel over the course of a 1-year survival time period, resulting in the development of esophageal structural features, including the mucosal epithelium, muscularis mucosae, lamina propria, as well as smooth muscle proliferation/migration initiating the formation of a laminated adventitia. Long term survival (1 year) demonstrated restoration of oral nutrition, normal animal growth and the overall safety of this treatment regimen.

scholarly journals Soluble E-Cadherin is an Independent Pretherapeutic Factor for Long-Term Survival in Gastric Cancer

2003 ◽  
Vol 21 (12) ◽  
pp. 2288-2293 ◽  
Author(s):  
Annie On-On Chan ◽  
Kent-Man Chu ◽  
Shiu-Kum Lam ◽  
Benjamin Chun-Yu Wong ◽  
Ka-Fai Kwok ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Time ◽  
Enzyme Linked Immunosorbent Assay ◽  
Independent Factor ◽  
Term Survival ◽  
Long Term Survival ◽  
The World ◽  
The Mean ◽  
E Cadherin

Purpose: To evaluate whether pretherapeutic serum soluble E-cadherin is an independent factor predicting long-term survival in gastric cancer. Gastric cancer remains the second leading cause of cancer-related deaths in the world, but a satisfactory tumor marker is currently unavailable for gastric cancer. Soluble E-cadherin has recently been found to have prognostic value in gastric cancer. Patients and Methods: One hundred sixteen patients with histologically proven gastric adenocarcinoma were included in the trial. Pretherapeutic serum was collected, and soluble E-cadherin was assayed using a commercially available enzyme-linked immunosorbent assay kit. The patients were followed up prospectively at the outpatient clinic. Results: There were 75 men and 41 women, with a mean (± SD) age of 66 ± 14 years. Forty-eight percent of tumors were located in the gastric antrum. The median survival time was 11 months. The mean pretherapeutic value of soluble E-cadherin was 9,159 ng/mL (range, 6,002 to 10,025 ng/mL), and the mean pretherapeutic level of carcinoembryonic antigen was 11 ng/mL (range, 0.3 to 4,895 ng/mL). On multivariate analysis, soluble E-cadherin is an independent factor predicting long-term survival. Ninety percent of patients with a serum level of E-cadherin greater than 10,000 ng/mL had a survival time of less than 3 years (P = .009). Conclusion: Soluble E-cadherin is a potentially valuable pretherapeutic prognostic factor in patients with gastric cancer.

scholarly journals Renal Replacement Therapy in Patients With Stage IV Cancer Admitted to the Intensive Care Unit With Acute Kidney Injury at a Comprehensive Cancer Center Was Not Associated With Survival

2020 ◽  
Vol 37 (9) ◽  
pp. 707-715
Author(s):  
Ala Abudayyeh ◽  
Juhee Song ◽  
Maen Abdelrahim ◽  
Ibrahim Dahbour ◽  
Valda D. Page ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Kidney Injury ◽  
Stage Iv ◽  
Inpatient Mortality ◽  
Survival Times ◽  
Term Survival ◽  
Long Term Survival ◽  
Time Points ◽  
Stage Iv Cancer

Introduction: In patients with advanced cancer, prolongation of life with treatment often incurs substantial emotional and financial expense. Among hospitalized patients with cancer since acute kidney injury (AKI) is known to be associated with much higher odds for hospital mortality, we investigated whether renal replacement therapy (RRT) use in the intensive care unit (ICU) was a significant independent predictor of worse outcomes. Methods: We retrospectively reviewed patients admitted in 2005 to 2014 who were diagnosed with stage IV solid tumors, had AKI, and a nephrology consult. The main outcomes were survival times from the landmark time points, inpatient mortality, and longer term survival after hospital discharge. Logistic regression and Cox proportional regression were used to compare inpatient mortality and longer term survival between RRT and non-RRT groups. Propensity score-matched landmark survival analyses were performed with 2 landmark time points chosen at day 2 and at day 7 from ICU admission. Results: Of the 465 patients with stage IV cancer admitted to the ICU with AKI, 176 needed RRT. In the multivariate logistic regression model after adjusting for baseline serum albumin and baseline maximum Sequential Organ Failure Assessment (SOFA), the patients who received RRT were not significantly different from non-RRT patients in inpatient mortality (odds ratio: 1.004 [95% confidence interval: 0.598-1.684], P = .9892). In total, 189 patients were evaluated for the impact of RRT on long-term survival and concluded that RRT was not significantly associated with long-term survival after discharge for patients who discharged alive. Landmark analyses at day 2 and day 7 confirmed the same findings. Conclusions: Our study found that receiving RRT in the ICU was not significantly associated with inpatient mortality, survival times from the landmark time points, and long-term survival after discharge for patients with stage IV cancer with AKI.

A randomized phase III trial of secondary cytoreductive surgery in later recurrent ovarian cancer: SOC1/SGOG-OV2.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6001-6001 ◽  
Author(s):  
Rongyu Zang ◽  
Jianqing Zhu ◽  
Tingyan Shi ◽  
Jihong Liu ◽  
Dongsheng Tu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Time ◽  
Cytoreductive Surgery ◽  
Interim Analysis ◽  
Phase Iii ◽  
Term Survival ◽  
Long Term Survival ◽  
Secondary Cytoreductive Surgery ◽  
Line Therapy

6001 Background: In China, secondary cytoreductive surgery (SCR) has been standard of care in some high volume cancer centers for ovarian cancer (OC) and most pts prefer surgery over the past two decades. Although GOG213 showed no OS benefit, the debate on selected pts and the conflict with certain local clinical care is still open. Methods: Pts with 1st relapsed OC after 6m+ platinum-free interval (PFI) were eligible if predicted to be a potential R0 by iMODEL score combined with PET-CT image and were randomized to SCR followed by chemotherapy (surgery arm) vs 2nd line chemotherapy alone (no surgery arm). Co-primary endpoint is PFS and OS. The 2nd endpoint is accumulated treatment-free survival (TFSa), which was defined as the overall survival time minus the time of surgery and chemotherapy after randomization. We report analysis of PFS and interim analysis of TFSa. Results: 357 pts were randomized 2012-2019. 6.3% of 175 pts were operated in no surgery arm and cross-over rate was 36.9% in 2nd+ relapsed pts of no surgery arm. 97% and 96% of pts received a platinum-containing 2nd line therapy. Complete resection (R0) rate was 76.7% in overall and 61.1% in pts with iMODEL> 4.7. 60 d mortality rates were 0 % in both surgery and no surgery arm. Postoperative 30 d complication rate with ≥ grade 3 was 5.2%. The median follow-up was 36.0 m. Median PFS was 17.4 m and 11.9 m in surgery and no surgery arm, respectively (HR 0.58, 95% CI 0.45-0.74, p < 0.001). Median time to start of first subsequent therapy (TFST) was 18.1 m vs 13.6 m in favor of the surgery arm (HR 0.59, 95%CI 0.46-0.76). 1.1% and 10.1% of pts underwent Bevacizumab and PARPi maintenance in the 2nd line therapy. The OS and TFSa was immatured. The median TFSa was unreached and 39.5 m in R0 subgroup and no surgery arm, respectively (HR0.59, 95%CI 0.38-0.91). TFSa in surgery arm showed a better long-term survival than that in no surgery group (restricted mean survival time from 60 to 72m: 6.2m vs 4.2m). Conclusions: SCR in selected pts resulted in a dramatically significant extension of PFS. The interim analysis of TFSa indicate that SCR might contribute to long-term survival.

What factors affect long-term survival after responding to gefitinib in advanced non-small cell lung cancer? Real-world evidence.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18007-e18007
Author(s):  
Yoshiko Takeuchi ◽  
Fumio Imamura ◽  
Satoshi Morita ◽  
Masahide Mori ◽  
Kiyoshi Komuta ◽  
...  
Keyword(s):  
Survival Time ◽  
Treatment Regimen ◽  
Medical Records ◽  
Egfr Mutation ◽  
Performance Status ◽  
Primary Objective ◽  
Term Survival ◽  
Long Term Survival ◽  
Gefitinib Treatment

e18007 Background: After gefitinib was approved in July 2002, we experience long-term surviving patients in the actual clinical setting. However, it is not clear how the factors or treatment strategy are contributing to the long-term surviving patients.We evaluated the effects of clinical backgrounds and treatment histories on overall survival (OS). Methods: We extracted information on advanced NSCLC patients with the following inclusion criteria from the medical records: 1) Patients who were diagnosed by October 2010 and treated with gefitinib after July 2002: 2) Performance status (PS) 0 – 2, 3) PR, CR, or long SD (6 months or more) by gefitinib treatment : 4) Patients who had not received curative surgical operation or curative radiation therapy. Primary objective is to evaluate survival time of the patients who responded to gefitinib and clarify the relationship between clinical factors and survival time. We also conducted “Dynamic Treatment Regimen Analysis (DTRA)” to explore key treatment regimen and sequence of regimens contributing to long-term survival. Results: The medical records of total of 275 patients were extracted. 44% (122/275) were EGFR mutation examined and 93% (114/122) has shown the EGFR mutation positive. The mean age was 65 years, 72% (198/275) were women, 66% (182/275) were non-smokers, and 90% (247/275) had adenocarcinoma histology. 20% (54/275) and 21% (58/275) underwent re-administration and beyond PD administration of gefitinib respectively. Median survival time (MST) was 615 day (95% C.I; 519-691). 10% patients survived for more than 5 years. The multivariate Cox analysis demonstrated that sex (p=0.0108) and gefitinib re-administration (p=0.0012) were significant independent factors for long-term OS. Grade 3/4 interstitial lung disease, skin, diarrhea, and liver dysfunction were observed in 1.5%, 4.4%, 1.1%, and 13.1% of the patients, respectively. Conclusions: This study suggests that sex and gefitinib re-administration, may have significant affects on OS in long survivors after responding gefitinib treatment.

Long-term survival of femoral neck fracture patients age over ninety: Arthroplasty compare with conservative treatment

2020 ◽  
Author(s):  
Yang Liu ◽  
Chong-wei Zhang ◽  
Xiao-dan Zhao
Keyword(s):  
Treatment Group ◽  
Conservative Treatment ◽  
Femoral Neck ◽  
Femoral Neck Fracture ◽  
Term Survival ◽  
Long Term Survival ◽  
Time Points ◽  
Neck Fracture ◽  
The Difference

Abstract Background The aging of the China population is expected to lead to increasing of nonagenarian and centenarian.The mortality rates of nonagenarian hip fracture patients would return to an equivalent mortality risk to the normal population at five years after injury. It is imperative to evaluate the 5-year mortality for this small but very challenging subgroup patients in order to optimize patient management. The main purpose of the current retrospective study was to compare the five-year survival between arthroplasty treatment and conservative treatment of femoral neck fracture patients age over 90 years during the same 16 -year period.Methods From January 1998 to December 2014, all consecutive nonagenarian and centenarian patients with femoral neck fracture admitted to our hospital were included for evaluation. The primary outcome was defined as thirty-day mortality, 1-year, 3-year, and 5-year mortality after injury. Survival status analysis was performed by the Kaplan–Meier method for mortality. Using the log-rank test, the stratified analyses were performed to compare the difference of overall cumulative mortality and three-time points (1-year, 3-year, and 5-year) mortality after injury were performed to compare the difference of survival distributions.Results Over the 16-year study period, the arthroplasty group and the conservative treatment group included 33 and 53 patients, respectively. The long-term survival probability of the arthroplasty group is significantly higher than the conservative treatment group( p=0.002277). The survival time of the arthroplasty group is significantly higher than the conservative treatment group(Median(P75-P25)=53(59) versus Median(P75-P25)=22(52), p=0.001). The difference of five time points (1-year, 2-year, 3-year, 4-year, and 5-year) mortality between the conservative group and arthroplasty group is significant except for 30-day mortality.The stratified analyses of overall cumulative mortality and three-time points (1-year, 3-year, and 5-year) mortality after injury demonstrated that the arthroplasty group is significant higher than the conservative treatment group.Conclusions Our study demonstrate that, compared with conservative treatment, arthroplasty surgery is more likely to improve the long-term survival of femoral neck fracture patients over 90s. What can be expected is that nearly half of patients will survive more than five years after surgery.

Examination of tracheal allografts after long-term survival in dogs

2020 ◽  
Vol 59 (1) ◽  
pp. 155-161
Author(s):  
Tao Lu ◽  
Yiwei Huang ◽  
Yulei Qiao ◽  
Yongxing Zhang ◽  
Yu Liu
Keyword(s):  
Extracellular Matrix ◽  
Term Survival ◽  
Airway Patency ◽  
Long Term Survival ◽  
Time Points ◽  
The Status ◽  
Collagen Ii ◽  
Safranin O ◽  
And Cartilage

Abstract OBJECTIVES Little is known on the outcome of tracheal allografts after long-term survival. This study aimed to explore the changes in structure and composition by evaluating the status of the mucosa and cartilage of allografts with long-term survival in dogs. METHODS Eight tracheal allografts that survived for ˃9 months were enrolled in our study. Epithelium, revascularization, monocyte infiltration and fibrosis were evaluated histologically. The fluorescent dye 4′-6-diamidino-2-phenylindole was used to evaluate the presence of chondrocyte nuclei. Glycosaminoglycan was detected using safranin-O staining and collagen II was evaluated using immunohistochemistry. RESULTS The 8 animals survived from 277 to 783 days. Bronchoscopy demonstrated that 6 allografts showed no stenosis; 2 cases developed slight stenosis, but could maintain airway patency. Histological examination showed that the epithelium covered the surface of the allografts. In comparison to fresh tracheal controls, allografts demonstrated mild monocyte infiltration, evident revascularization and mild fibrosis in the mucosa or submucosa (all P &lt; 0.05). There were a few viable chondrocytes scattered in the cartilage after long-term survival. Moreover, glycosaminoglycan and collagen II were significantly decreased in the allografts compared with fresh trachea (all P &lt; 0.05). CONCLUSIONS For tracheal allografts with long-term survival after transplantation, only a few viable chondrocytes were retained, and the extracellular matrix of the cartilage demonstrated degeneration. Despite this, the airway could maintain patency. Notably, the significance of monocyte infiltration in the mucosa or submucosa at different time points warrants further study.

scholarly journals Transient immunosuppressive treatment leads to long-term retention of allogeneic myoblasts in hybrid myofibers.

1994 ◽  
Vol 127 (6) ◽  
pp. 1923-1932 ◽  
Author(s):  
G K Pavlath ◽  
T A Rando ◽  
H M Blau
Keyword(s):  
Time Course ◽  
Immunosuppressive Treatment ◽  
Immunological Response ◽  
Genetically Engineered ◽  
Term Survival ◽  
Long Term Survival ◽  
Term Retention ◽  
Long Term Retention ◽  
Myoblast Transplantation

Normal and genetically engineered skeletal muscle cells (myoblasts) show promise as drug delivery vehicles and as therapeutic agents for treating muscle degeneration in muscular dystrophies. A limitation is the immune response of the host to the transplanted cells. Allogeneic myoblasts are rapidly rejected unless immunosuppressants are administered. However, continuous immunosuppression is associated with significant toxic side effects. Here we test whether immunosuppressive treatment, administered only transiently after allogeneic myoblast transplantation, allows the long-term survival of the transplanted cells in mice. Two immunosuppressive treatments with different modes of action were used: (a) cyclosporine A (CSA); and (b) monoclonal antibodies to intracellular adhesion molecule-1 and leukocyte function-associated molecule-1. The use of myoblasts genetically engineered to express beta-galactosidase allowed quantitation of the survival of allogeneic myoblasts at different times after cessation of the immunosuppressive treatments. Without host immunosuppression, allogeneic myoblasts were rejected from all host strains tested, although the relative time course differed as expected for low and high responder strains. The allogeneic myoblasts initially fused with host myofibers, but these hybrid cells were later destroyed by the massive immunological response of the host. However, transient immunosuppressive treatment prevented the hybrid myofiber destruction and led to their long-term retention. Even four months after the cessation of treatment, the hybrid myofibers persisted and no inflammatory infiltrate was present in the tissue. Such long-term survival indicates that transient immunosuppression may greatly increase the utility of myoblast transplantation as a therapeutic approach to the treatment of muscle and nonmuscle disease.

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