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1.
Can J Gastroenterol Hepatol ; 2021: 5212953, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34888264

RESUMO

Introduction: Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver malignancies and is currently the fourth most common cause of cancer-related death worldwide. Due to varying underlying etiologies, the prognosis of HCC differs greatly among patients. It is important to develop ways to help stratify patients upon initial diagnosis to provide optimal treatment modalities and follow-up plans. The current study uses Artificial Neural Network (ANN) and Classification Tree Analysis (CTA) to create a gene signature score that can help predict survival in patients with HCC. Methods: The Cancer Genome Atlas (TCGA-LIHC) was analyzed for differentially expressed genes. Clinicopathological data were obtained from cBioPortal. ANN analysis of the 75 most significant genes predicting disease-free survival (DFS) was performed. Next, CTA results were used for creation of the scoring system. Cox regression was performed to identify the prognostic value of the scoring system. Results: 363 patients diagnosed with HCC were analyzed in this study. ANN provided 15 genes with normalized importance >50%. CTA resulted in a set of three genes (NRM, STAG3, and SNHG20). Patients were then divided in to 4 groups based on the CTA tree cutoff values. The Kaplan-Meier analysis showed significantly reduced DFS in groups 1, 2, and 3 (median DFS: 29.7 months, 16.1 months, and 11.7 months, p < 0.01) compared to group 0 (median not reached). Similar results were observed when overall survival (OS) was analyzed. On multivariate Cox regression, higher scores were associated with significantly shorter DFS (1 point: HR 2.57 (1.38-4.80), 2 points: 3.91 (2.11-7.24), and 3 points: 5.09 (2.70-9.58), p < 0.01). Conclusion: Long-term outcomes of patients with HCC can be predicted using a simplified scoring system based on tumor mRNA gene expression levels. This tool could assist clinicians and researchers in identifying patients at increased risks for recurrence to tailor specific treatment and follow-up strategies for individual patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34866343

RESUMO

BACKGROUND: Although the number of minimally invasive liver resection (MILR) has been steadily increasing in many institutions, minimally invasive anatomic liver resection (MIALR) remains a complicated procedure that has not been standardized. We present the results of a survey among expert liver surgeons as a benchmark for standardizing MIALR. METHOD: We administered this survey to 34 expert liver surgeons who routinely perform MIALR. The survey contained questions on personal experience with liver resection, inflow/outflow control methods, and identification techniques of intersegmental/sectional planes (IPs). RESULTS: All 34 participants completed the survey; 24 experts (70%) had more than 11 years of experience with MILR, and over 80% of experts had performed over 100 open resections and MILRs each. Regarding the methods used for laparoscopic or robotic anatomic resection, the Glissonean approach (GA) was a more frequent procedure than the hilar approach (HA). Although hepatic veins were considered essential landmarks, the exposure methods varied. The top three techniques that the experts recommended for identifying IPs were creating a demarcation line, indocyanine green (ICG) negative staining method, and intraoperative ultrasound. CONCLUSION: MIALR remains a challenging procedure; however, a certain degree of consensus exists among expert liver surgeons.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34866349

RESUMO

BACKGROUND: The Brisbane 2000 Terminology for Liver Anatomy and Resections, based on Couinaud's segments, did not address how to identify segmental borders and anatomic territories of less than one segment. Smaller anatomic resections including segmentectomies and subsegmentectomies, have not been well defined. The advent of minimally invasive liver resection has enhanced the possibilities of more precise resection due to a magnified view and reduced bleeding, and minimally invasive anatomic liver resection (MIALR) is becoming popular gradually. Therefore, there is a need for updating the Brisbane 2000 system, including anatomic segmentectomy or less. An online "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was hosted on February 23, 2021. METHODS: The Steering Committee invited 34 international experts from around the world. The Expert Committee (EC) selected 12 questions and 2 future research topics in the terminology session. The EC created 7 tentative definitions and 5 recommendations based on the experts' opinions and the literature review performed by the Research Committee. Two Delphi Rounds finalized those definitions and recommendations. RESULTS: This paper presents 7 definitions and 5 recommendations regarding anatomic segmentectomy or less. In addition, two future research topics are discussed. CONCLUSIONS: The PAM-HBP Surgery Consensus has presented the Tokyo 2020 Terminology for Liver Anatomy and Resections. The terminology has added definitions of liver anatomy and resections that were not defined in the Brisbane 2000 system.

4.
Life Sci ; : 120214, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34890591

RESUMO

AIMS: Although separate blockage of either IL33/ST2 or PD-L/PD-1 axes has been shown to be beneficial in many tumors, co-blockage of IL33/ST2 and PD-L/PD-1 hasn't been studied yet. MAIN METHODS: 4T1 breast cancer and CT26 colon cancer were inducted in BALB/C wild type (WT) and BALB/C ST2 knockout mice, after which mice underwent anti PD-1 and anti IL-33 treatment. KEY FINDINGS: Co-blockage of IL33/ST2 and PD-L/PD-1 delayed tumor appearance and slowed tumor growth. Enhanced NK cell cytotoxicity against 4T1 tumor cells in ST2 knockout anti-PD-1 treated mice was associated with overexpression of miRNA-150 and miRNA-155, upregulation of NFκB and STAT3, increased expression of activation markers and decreased expression of immunosuppressive markers in splenic and primary tumor derived NK cells. NK cells from ST2 knockout anti-PD-1 treated mice tend to proliferate more and are less prone to apoptosis. Accumulation of immunosuppressive myeloid derived suppressor cells and regulatory T cells was significantly impaired in spleen and primary tumor of ST2 knockout anti-PD-1 treated mice. SIGNIFICANCE: Co-blockage of IL3/ST2 and PD-L/PD-1 axes impedes tumor progression more efficiently than single blockage of either axes, thus offering potential new approach to immunotherapy of tumors.

5.
Front Immunol ; 12: 785222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899751

RESUMO

While neutrophil extracellular traps (NETs) are important for directly promoting cancer growth, little is known about their impact on immune cells within the tumor microenvironment (TME). We hypothesize that NETs can directly interact with infiltrating T cells to promote an immunosuppressive TME. Herein, to induce a NET-rich TME, we performed liver Ischemia/Reperfusion (I/R) in an established cancer metastasis model or directly injected NETs in subcutaneous tumors. In this NET-rich TME, the majority of CD4+ and CD8+ tumor infiltrating lymphocytes expressed multiple inhibitory receptors, in addition these cells showed a functional and metabolic exhausted phenotype. Targeting of NETs in vivo by treating mice with DNAse lead to decreased tumor growth, decreased NET formation and higher levels of functioning T cells. In vitro, NETs contained the immunosuppressive ligand PD-L1 responsible for T cell exhaustion and dysfunction; an effect abrogated by using PD-L1 KO NETs or culturing NETs with PD-1 KO T cells. Furthermore, we found elevated levels of sPDL-1 and MPO-DNA, a NET marker, in the serum of patients undergoing surgery for colorectal liver metastases resection. Neutrophils isolated from patients after surgery were primed to form NETs and induced exhaustion and dysfunction of human CD4+ and CD8+ T cells. We next targeted PD-L1 in vivo by injecting a blocking antibody during liver I/R. A single dose of anti-PD-L1 during surgery lead to diminished tumors at 3 weeks and functional T cells in the TME. Our data thus reveal that NETs have the capability of suppressing T cell responses through metabolic and functional exhaustion and thereby promote tumor growth. Furthermore, targeting of PD-L1 containing NETs at time of surgery with DNAse or anti-PD-L1 lead to diminished tumor growth, which represents a novel and viable strategy for sustaining immune competence within the TME.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34806126

RESUMO

PURPOSE: The aim of this study was to examine the link between psychological, behavioral, and social factors and survival in patients diagnosed with gastrointestinal cancer. METHODS: A cohort of gastrointestinal cancer patients were administered a battery of questionnaires that assessed trauma, depression, social support, sleep, diet, exercise, quality of life, tobacco and alcohol use, pain, and fatigue. Analyses included Pearson's correlations, analyses of variance, Kaplan Meier survival, and Cox regression analyses. RESULTS: Of the 568 patients, the majority were male (57.9%) and Caucasian (91.9%), with a mean age of 61 (S.D. = 10.7). The level of perceived social support was comparable to patients with other medical conditions. Sociodemographic predictors of social support included the number of years of education (r = 0.109, p = 0.05), marital status (F(6,387) = 5.465, p ≤ 0.001), and whether the patients' income met the family's basic needs (F(1,377) = 25.531, p < 0.001). Univariate analyses revealed that older age (p < 0.001), male gender (p = 0.007), being black (p = 0.005), diagnosis of hepatocellular carcinoma (p = 0.046), higher body mass index (p = 0.022), larger tumor size (p = 0.032), initial treatment including chemotherapy rather than surgery (p < 0.001), and lower level of perceived social support (p = 0.037) were associated with poorer survival. Using multivariate Cox regression and adjusting for all factors found to be significant in univariate survival analyses, older age (p = 0.024) and lower perceived social support (HR = 0.441, 95% CI = 0.233, 0.833; p = 0.012) were the factors that remained significantly associated with poorer survival. CONCLUSION: There are several biological and psychosocial factors that predict cancer mortality. Social support appears to be a robust factor affecting mortality in gastrointestinal cancer patients.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34779150

RESUMO

BACKGROUND: The concept of minimally invasive anatomic liver resection (MIALR) is gaining popularity. However, specific technical skills need to be acquired to safely perform MIALR. The "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was developed as a special program during the 32nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). METHODS: Thirty-four international experts gathered online for the consensus. A Research Committee performed a comprehensive literature review, classifying studies according to the Scottish Intercollegiate Guidelines Network method. Based on the literature review and experts' opinions, tentative recommendations were drafted and circulated among experts using online Delphi Rounds. Finally, formulated recommendations were presented online in the Expert Consensus Meeting of the JSHBPS on February 23rd, 2021. The final recommendations were validated and finalized by the 2nd Delphi Round in May 2021. RESULTS: Seven clinical questions were selected, and 22 recommendations were formulated. All recommendations reached more than 85% consensus among experts at the final Delphi Round. CONCLUSIONS: The Expert Consensus Meeting for safely performing MIALR has presented a set of clinical guidelines based on available literature and experts' opinions. We expect these guidelines to have a favorable effect on the safe implementation and development of MIALR.

10.
Cancers (Basel) ; 13(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202373

RESUMO

Less morbidity is considered among the advantages of laparoscopic liver resection (LLR) for HCC patients. However, our previous international, multi-institutional, propensity score-based study of emerging laparoscopic repeat liver resection (LRLR) failed to prove this advantage. We hypothesize that these results may be since the study included complex LRLR cases performed during the procedure's developing stage. To examine it, subgroup analysis based on propensity score were performed, defining the proximity of the tumors to major vessels as the indicator of complex cases. Among 1582 LRLR cases from 42 international high-volume liver surgery centers, 620 cases without the proximity to major vessels (more than 1 cm far from both first-second branches of Glissonian pedicles and major hepatic veins) were selected for this subgroup analysis. A propensity score matching (PSM) analysis was performed based on their patient characteristics, preoperative liver function, tumor characteristics and surgical procedures. One hundred and fifteen of each patient groups of LRLR and open repeat liver resection (ORLR) were earned, and the outcomes were compared. Backgrounds were well-balanced between LRLR and ORLR groups after matching. With comparable operation time and long-term outcome, less blood loss (283.3±823.0 vs. 603.5±664.9 mL, p = 0.001) and less morbidity (8.7 vs. 18.3 %, p = 0.034) were shown in LRLR group than ORLR. Even in its worldwide developing stage, LRLR for HCC patients could be beneficial in blood loss and morbidity for the patients with less complexity in surgery.

11.
Front Immunol ; 12: 705465, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262574

RESUMO

Liver allograft recipients are more likely to develop transplantation tolerance than those that receive other types of organ graft. Experimental studies suggest that immune cells and other non-parenchymal cells in the unique liver microenvironment play critical roles in promoting liver tolerogenicity. Of these, liver interstitial dendritic cells (DCs) are heterogeneous, innate immune cells that appear to play pivotal roles in the instigation, integration and regulation of inflammatory responses after liver transplantation. Interstitial liver DCs (recruited in situ or derived from circulating precursors) have been implicated in regulation of both ischemia/reperfusion injury (IRI) and anti-donor immunity. Thus, livers transplanted from mice constitutively lacking DCs into syngeneic, wild-type recipients, display increased tissue injury, indicating a protective role of liver-resident donor DCs against transplant IRI. Also, donor DC depletion before transplant prevents mouse spontaneous liver allograft tolerance across major histocompatibility complex (MHC) barriers. On the other hand, mouse liver graft-infiltrating host DCs that acquire donor MHC antigen via "cross-dressing", regulate anti-donor T cell reactivity in association with exhaustion of graft-infiltrating T cells and promote allograft tolerance. In an early phase clinical trial, infusion of donor-derived regulatory DCs (DCreg) before living donor liver transplantation can induce alterations in host T cell populations that may be conducive to attenuation of anti-donor immune reactivity. We discuss the role of DCs in regulation of warm and liver transplant IRI and the induction of liver allograft tolerance. We also address design of cell therapies using DCreg to reduce the immunosuppressive drug burden and promote clinical liver allograft tolerance.

12.
Am J Surg ; 222(4): 731-738, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33840443

RESUMO

BACKGROUND: We compared the outcomes of laparoscopic hepatectomy (LH) vs. open hepatectomy (OH) for intrahepatic cholangiocarcinoma (iCCA). METHODS: A systematic review of the MEDLINE, EMBASE, Scopus, and Cochrane Library databases was performed using PRISMA guidelines (end-of-search date: 08-June-2020). Individual patient data on overall survival (OS) and recurrence-free survival (RFS) were extracted. Random-effects meta-analyses, and one- and two-stage survival analyses were conducted. RESULTS: Eight retrospective cohort studies comparing LH (n = 544) vs. OH (n = 2256) were identified. LH demonstrated lower overall complication (Risk ratio [RR] = 0.64, 95% confidence interval [CI]: 0.46-0.90; p = 0.01), surgical lymphadenectomy (RR = 0.74, 95% CI: 0.58-0.93; p = 0.01) and margin-positive resection (RR = 0.78, 95% CI: 0.62-0.99; p = 0.04) rates, and higher recurrence-free rate (RR = 1.24, 95% CI: 1.01-1.51; p = 0.04) vs. OH. In Cox regression, no difference was observed regarding OS (Hazard Ratio [HR] = 1.11, 95% CI: 0.65-1.91; p = 0.70) and RFS (HR = 1.19, 95% CI: 0.74-1.90; p = 0.47). CONCLUSION: The use of LH should be considered when feasible in well-selected iCCA patients by hepatobiliary surgeons with experience in minimally-invasive surgery.


Assuntos
Colangiocarcinoma/mortalidade , Colangiocarcinoma/cirurgia , Hepatectomia/métodos , Humanos , Laparoscopia , Tempo de Internação , Duração da Cirurgia , Complicações Pós-Operatórias , Análise de Sobrevida
13.
Transl Oncol ; 14(6): 101059, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33735820

RESUMO

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Lenvatinib oral chemotherapy is approved as a first-line treatment of patients with unresectable HCC. The efficacy and therapeutic duration of lenvatinib are limited by drug resistance, and the mechanism is unclear. IRF2 is a constitutive transcription factor associated with the development of various cancers by regulating cancer cell growth, apoptosis, and drug resistance. However, the potential role of IRF2 in lenvatinib resistance in HCC has not been explored. In this study, we found that IRF2 promoted proliferation, inhibited apoptosis, and increased lenvatinib resistance of HCC cells by regulating ß-catenin expression. Silencing IRF2 downregulated the expression of ß-catenin, while overexpressing IRF2 upregulated ß-catenin. Moreover, the expression of ß-catenin and IRF2 was positively correlated in HCC tissues. Inhibiting ß-catenin with XAV-939 effectively abrogated ß-catenin expression caused by lenvatinib treatment. These findings identify an important function of IRF2 in HCC and demonstrate a mechanism of lenvatinib resistance of HCC cells. Targeting IRF2 may be a potential strategy to improve the therapeutic effect of lenvatinib on HCC.

14.
Br J Cancer ; 125(1): 101-111, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33772151

RESUMO

BACKGROUND: CHK1 is considered an oncogene with overexpression in numerous cancers. However, CHK1 signalling regulation in hepatocellular carcinoma (HCC) remains unclear. METHODS: CHEK1 mRNA, protein, pri-miR-195 and miR-195 expression in HCC tissue was determined by qPCR, WB and IF staining assay. Survival analyses in HCC with high- and low-CHEK1 mRNA expression was performed using TCGA database. Relative luciferase activity was investigated in HCC cells transfected with p-CHEK1 3'UTR. Apoptosis was detected by TUNEL assay. NK and CD8+ T cells were analysed by flow cytometry. RESULTS: CHK1 is increased in human HCC tumours compared with non-cancerous liver. High CHK1 predicts worse prognosis. IFN-γ suppresses CHK1 via IRF-1 in HCC cells. The molecular mechanism of IRF-1 suppressing CHK1 is post-transcriptional by promoting miR-195 binding to CHEK1 mRNA 3'UTR, which exerts a translational blockade. Upregulated IRF-1 inhibits CHK1, which induces apoptosis of HCC cells. Likewise, CHK1 inhibition augments cellular apoptosis in HCC tumours. This effect may be a result of increased tumour NK cell infiltration. However, IRF-1 expression or CHK1 inhibition also upregulates PD-L1 expression via increased STAT3 phosphorylation. CONCLUSIONS: IRF-1 induces miR-195 to suppress CHK1 protein expression. Both increased IRF-1 and decreased CHK1 upregulate cellular apoptosis and PD-L1 expression in HCC.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33787072

RESUMO

BACKGROUND: The main aim of this survey was to analyze how liver surgeons perform liver resections and to define their conception of anatomic procedures within the incorporation of minimally invasive liver surgery (MILS). METHODS: The survey was distributed among liver surgeons. It mainly focused on personal experience on open and MILS, methods and landmarks, and experience on anatomic resections and Glissonean approach. RESULTS: A total of 445 valid answers from 54 countries was obtained. Surgeons performing MILS mainly have below 10 years of experience (81.8% of responders) and one third has never done complex MILS. New techniques, including indocyanine green demarcation are marginally used (<25%). More than 60% of surgeons do not make a full exposure of hepatic veins during MILS, mainly due to the risk of injury or not considering it to be of utility. Although 88% of responders agreed with the concept of anatomic resection as the "resection along the border/watersheds of each order division identified by the portal vein flow", only 55% of surgeons have ever performed MILS Glissonean approaches. CONCLUSIONS: Liver anatomy is not a static concept. Anatomic resections need training and precision. Standardization of complex anatomic resections by a minimally invasive approach should be encouraged.

16.
Cancer Lett ; 506: 95-106, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33689775

RESUMO

Interferon regulatory factor 1 (IRF-1) is a tumor suppressor gene in cancer biology with anti-proliferative and pro-apoptotic effect on cancer cells, however mechanisms of IRF-1 regulating tumor microenvironment (TME) in hepatocellular carcinoma (HCC) remain only partially characterized. Here, we investigated that IRF-1 regulates C-X-C motif chemokine 10 (CXCL10) and chemokine receptor 3 (CXCR3) to activate anti-tumor immunity in HCC. We found that IRF-1 mRNA expression was positively correlated with CXCL10 and CXCR3 through qRT-PCR assay in HCC tumors and in analysis of the TCGA database. IRF-1 response elements were identified in the CXCL10 promoter region, and ChIP-qPCR confirmed IRF-1 binding to promote CXCL10 transcription. IRF-2 is a competitive antagonist for IRF-1 mediated transcriptional effects, and overexpression of IRF-2 decreased basal and IFN-γ induced CXCL10 expression. Although IRF-1 upregulated CXCR3 expression in HCC cells, it inhibited proliferation and exerted pro-apoptotic effects, which overcome proliferation partly mediated by activating the CXCL10/CXCR3 autocrine axis. In vitro and in vivo studies showed that IRF-1 increased CD8+ T cells, NK and NKT cells migration, and activated IFN-γ secretion in NK and NKT cells to induce tumor apoptosis through the CXCL10/CXCR3 paracrine axis. Conversely, this effect was markedly abrogated in HCC tumor bearing mice deficient in CXCR3. Therefore, the IRF-1/CXCL10/CXCR3 axis contributes to the anti-tumor microenvironment in HCC.


Assuntos
Carcinoma Hepatocelular/imunologia , Quimiocina CXCL10/fisiologia , Fator Regulador 1 de Interferon/fisiologia , Neoplasias Hepáticas/imunologia , Receptores CXCR3/fisiologia , Animais , Apoptose , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Quimiocina CXCL10/genética , Feminino , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas , Linfócitos T/imunologia
17.
Eur J Health Econ ; 22(4): 585-604, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33740153

RESUMO

BACKGROUND: Following the publication of reports from landmark international consensuses (Louisville 2008 and Morioka 2014), minimally invasive hepatectomy became widely accepted as a legitimate alternative to open surgery. We aimed to compare the operative, hospitalization, and total economic costs of open (OLR) vs. laparoscopic (LLR) vs. robotic liver resection (RLR). METHODS: We performed a systematic literature review (end-of-search date: July 3, 2020) according to the PRISMA statement. Random-effects meta-analyses were conducted. Quality assessment was performed with the Cochrane Risk of Bias tool for randomized controlled trials, and the Newcastle-Ottawa Scale for non-randomized studies. RESULTS: Thirty-eight studies reporting on 3847 patients (1783 OLR; 1674 LLR; 390 RLR) were included. The operative costs of LLR were significantly higher than those of OLR, while subgroup analysis also showed higher operative costs in the LLR group for major hepatectomy, but no statistically significant difference for minor hepatectomy. Hospitalization costs were significantly lower in the LLR group, with subgroup analyses indicating lower costs for LLR in both major and minor hepatectomy series. No statistically significant difference was observed regarding total costs between LLR and OLR both overall and on subgroup analyses in either major or minor hepatectomy series. Meta-analyses showed higher operative, hospitalization, and total costs for RLR vs. LLR, but no statistically significant difference regarding total costs for RLR vs. OLR. CONCLUSION: LLR's higher operative costs are offset by lower hospitalization costs compared to OLR leading to no statistically significant difference in total costs, while RLR appears to be a more expensive alternative approach.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Custos e Análise de Custo , Hepatectomia , Humanos , Tempo de Internação , Estudos Retrospectivos , Resultado do Tratamento
18.
Contemp Clin Trials ; 105: 106295, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33556589

RESUMO

BACKGROUND: The NIH consensus statement on cancer-related symptoms concluded the most common and debilitating were depression, pain and fatigue [1-6]. Although the comorbidity of these symptoms is well known and may have similar underlying biological mechanisms no intervention has been developed to reduce these symptoms concurrently. The novel web-based stepped collaborative care intervention delivered by telemedicine is the first to be tested in people diagnosed with cancer. METHODS: We plan to test a web-based stepped collaborative care intervention with 450 cancer patients and 200 caregivers in the context of a randomized controlled trial. The primary endpoint is quality of life with other primary outcomes including patient-reported depression, pain, fatigue. Secondary outcomes include patient serum levels of pro-inflammatory cytokines and disease progression. We also will assess informal caregiver stress, depression, and metabolic abnormalities to determine if improvements in patients' symptoms also relate to improvement in caregiver outcomes. RESULTS: The trial is ongoing and a total of 382 patients have been randomized. Preliminary analyses of the screening tools used for study entry suggest that Center for Epidemiological Studies-Depression (CESD) scale has good sensitivity and specificity (0.81 and 0.813) whereas the scale used to assess pain (0.47 and 0.91) and fatigue (0.11 and 0.91) had poor sensitivity but excellent specificity. Using the AUROC, the best cut point for the CES-D was 19, for pain was 4.5; and for fatigue was 2.5. Outcomes not originally proposed included health care utilization and healthcare charges. The first 100 patients who have been followed a year post-treatment, and who were less than 75 years and randomized to the web-based stepped collaborative care intervention, had lower rates of complications after surgery [χ2 = 5.45, p = 0.02]. For patients who survived 6 months or less and were randomized to the web-based stepped collaborative care intervention, had lower rates of 90-day readmissions when compared to patients randomized to the screening and referral arm [χ2 = 4.0, p = 0.046]. Patients randomized to the collaborative care intervention arm had lower overall health care activity-based costs of $16,758 per patient per year when compared to the screening and referral arm. DISCUSSION: This novel web-based stepped stepped collaborative care intervention, delivered via telemedicine, is expected to provide a new strategy to improve the quality of life in those diagnosed with cancer and their caregivers. TRIAL REGISTRATION: ClinicalTrials.govNCT02939755.


Assuntos
Intervenção Baseada em Internet , Neoplasias , Telemedicina , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/terapia , Fadiga/epidemiologia , Fadiga/terapia , Humanos , Neoplasias/terapia , Qualidade de Vida
19.
HPB (Oxford) ; 23(6): 927-936, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33189566

RESUMO

BACKGROUND: We assessed if the risk of post-liver transplant mortality within 24 h could be stratified at the time of listing using the liver transplant risk score (LTRS). Secondary aims were to assess if the LTRS could stratify the risk of 30-day, 1-year mortality, and survival beyond the first year. METHODS: MELD, BMI, age, diabetes, and the need for dialysis were the five variables used to calculate the LTRS during patients' evaluation for liver transplantation. Mortality rates at 24 h, 30 days, and 1-year were compared among groups of patients with different LTRS. Patients with ABO-incompatibility, redo, multivisceral, partial graft and malignancies except for hepatocellular carcinoma were excluded. Data of 48,616 adult liver transplant recipients were extracted from the Scientific Registry of Transplant Recipients between 2002 and 2017. RESULTS: 24-h mortality was 0.9%, 1.0%, 1.1%, 1.7%, 2.3%, 2.0% and 3.5% for patients with LTRS of 0,1,2,3,4, 5 and ≥ 6, respectively (P < 0.001). 30-day mortality was 3.5%, 4.2%, 4.9%, 6.2%, 7.6%, 7.2% and 10.1% respectively (P < 0.001). 1-year mortality was 8.6%, 10.8%, 12.9%, 13.9%, 18.5%, 20.3% and 28.6% respectively (P < 0.001). 10-year survival was 61%, 56%, 57%, 54%, 47%, and 31% for patients with 0, 1, 2, 3, 4, 5 and ≥ 6 points respectively (P < 0.001). CONCLUSION: Perioperative mortality and long-term survival of patients undergoing LT can be accurately estimated at the time of listing by the LTRS.

20.
Hepatology ; 73(6): 2494-2509, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32924145

RESUMO

BACKGROUND AND AIMS: Liver ischemia/reperfusion injury (IRI) induces local and systemic inflammation in which neutrophil extracellular traps (NETs) are major drivers. IRI markedly augments metastatic growth, which is consistent with the notion that the liver IRI can serve as a premetastatic niche. Exercise training (ExT) confers a sustainable protection, reducing IRI in some animal models, and has been associated with improved survival in patients with cancer; however, the impact of ExT on liver IRI or development of hepatic metastases is unknown. APPROACH AND RESULTS: Mice were randomized into exercise (ExT) and sedentary groups before liver IRI and tumor injection. Computerized dynamic network analysis of 20 inflammatory mediators was used to dissect the sequence of mediator interactions after ischemia/reperfusion (I/R) that induce injury. ExT mice showed a significant decrease in hepatic IRI and tissue necrosis. This coincided with disassembly of complex networks among inflammatory mediators seen in sedentary mice. Neutrophil infiltration and NET formation were decreased in the ExT group, which suppressed the expression of liver endothelial cell adhesion molecules. Concurrently, ExT mice revealed a distinct population of infiltrating macrophages expressing M2 phenotypic genes. In a metastatic model, fewer metastases were present 3 weeks after I/R in the ExT mice, a finding that correlated with a marked increase in tumor-suppressing T cells within the tumor microenvironment. CONCLUSIONS: ExT preconditioning mitigates the inflammatory response to liver IRI, protecting the liver from injury and metastases. In light of these findings, potential may exist for the reduction of liver premetastatic niches induced by liver IRI through the use of ExT as a nonpharmacologic therapy before curative surgical approaches.

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