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1.
Background: Microscopic residual tumor often occurs after thermal ablation for medium-large hepatocellular carcinoma (HCC), leading to early aggressive recurrence or late relapse during follow-up. The mechanism how microscopic residual HCC cells survive sublethal heat stress and develop rapid outgrowth remains poorly understood.

Methods: HCC cells were exposed to sublethal heat treatment and co-cultured with conditioned media from activated HSCs (HSC-CM). Changes of cell proliferation, parameters of cell autophagy and activation of signaling pathways in heat-treated residual HCC cells were analyzed. An HCC orthotopic model was subjected to partial thermal ablation and antitumor effects of a combined treatment regimen were studied.

Results: HCC cells survived sublethal heat stress via activation of autophagy. HSC-CM enhanced autophagic survival within 24?h and then promoted proliferation of heat-treated residual HCC cells through HGF/c-Met signaling. Inhibition of autophagy or c-Met increased apoptosis of heat-treated residual HCC cells and reversed the protective effect of HSC-CM. HGF modulated biological status in autophagic survival or proliferation of heat-treated residual HCC through HGF/c-Met/ERK signaling and downstream components of ATG5/Beclin1 or cyclinD1. In an animal model, inhibiting autophagy in combination with c-Met inhibitor significantly thwarted tumor progression of residual HCC after incomplete thermal ablation via the suppressed autophagy, the decreased proliferation and the increased apoptosis.

Conclusions: Activated HSCs promote progression of residual HCC cells after sublethal heat treatment from autophagic survival to proliferation via HGF/c-Met signaling. A combined treatment regimen of inhibiting autophagy and c-Met signaling could be used to suppress tumor progression of residual HCC after incomplete thermal ablation.  相似文献   


2.
Purpose: This study aimed to assess the safety and technical feasibility of percutaneous ablation therapy for lymph node (LN) metastases of hepatocellular carcinoma (HCC).

Material and Methods: A total of 31 consecutive HCC patients with LN metastases who were treated with ablation were included in this retrospective study. Percutaneous ablation was performed under local anesthesia and computed tomography–guidance. The primary endpoint was technique success; secondary endpoints were overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS). Survival curves were constructed using Kaplan-Meier method.

Results: The median diameter of metastatic LNs was 30?mm (range, 10–77?mm). The 1-, 3-, and 5-year OS rates were 74.6%, 50.3%, and 50.3%, respectively. The 1-, 3-, and 5-year PFS rates were 24.7%, 0%, and not available for calculation (NA), respectively. The 1-, 3-, and 5-year LPFS rates were 78.7%, 69.9%, and 69.9%, respectively. The technique success and technical effectiveness rates were 100% and 64.5%, respectively. The technical effectiveness rates were 65.4% (17/26) and 60% (3/5) in abdominal LN metastases and distant LN metastases, respectively. Only one patient (1/31, 3.2%) had major complications (massive pleural effusion and severe pneumonia) related to ablation. Minor complications related to ablation included mild abdominal pain (10/31, 32.3%) and self-limiting hematoma (2/31, 6.5%). No ablation-related death occurred.

Conclusion: Percutaneous ablation appears to be a safe and feasible method for treatment of metastatic LNs in patients with HCC.  相似文献   


3.
Background: Microwave ablation (MWA) has several advantages over radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). We aimed to compare the efficacy and safety of MWA with those of RFA for HCC from the perspectives of percutaneous and laparoscopic approaches.

Methods: PubMed/MEDLINE, Embase, the Cochrane library, and China Biology Medicine databases were searched. Studies comparing the efficacy and safety of MWA with those of RFA in patients with HCC were considered eligible. Complete ablation (CA), local recurrence (LR), disease-free survival (DFS), overall survival (OS), and the major complication rate were compared between MWA and RFA.

Results: Four randomized controlled trials and 10 cohort studies were included. For percutaneous ablation, no significant difference was found between MWA and RFA regarding CA, LR, DFS, OS, and the major complication rate. A subgroup analysis of tumors measuring ≥3?cm revealed no difference in CA and LR for percutaneous ablation. For laparoscopic ablation, a significantly lower LR rate and a non-significant trend toward a higher major complication rate were observed for the MWA group (odds ratio [OR] 2.16, 95% confidence interval [CI] 1.16–4.02, p?=?.01 for LR; OR 0.21, 95% CI 0.04–1.03, p?=?.05 for major complication rate). CA, DFS, and OS were similar between the two groups.

Conclusions: Percutaneous (P)-MWA had similar therapeutic effects compared with P-RFA for HCC. Patients undergoing laparoscopic MWA had a lower LR rate; however, their major complication rate appeared to be higher. The superiority of MWA over RFA remains unclear and needs to be confirmed by high-quality evidence.  相似文献   


4.
Purpose/Objectives: Young adult cancer patients undergo stress at a time when their primary source of psychosocial support may be changing. Our goal was to provide insight into the expectations young adult patients and their family caregivers for types of psychosocial support.

Research Approach: Semi-structured interviews.

Participants: Fifteen patients, 9 caregivers recruited from an AYA clinic.

Methodological Approach: Thematic content analysis using the constant comparison method.

Findings: Two themes were identified. First, families described coordinating support around strengths to determine who would take on caregiving roles/tasks. Second, families described the importance of patient-caregiver relationship status/history in determining trust and expectations.

Interpretation: Family strengths and existing relationships can impact caregiving roles and expectations for families of young adult cancer patients.

Implications for Psychosocial Providers: Cancer clinics may need to involve members of the psychosocial provider team to better understand the family dynamics of their patients and how these relate to support.  相似文献   


5.
Objectives: Prostate cancer (PCa) stigma and its relationship to quality of life (QoL) is a relatively new finding. As the experiences of couples facing PCa are shared, the study examined the relationship between of PCa stigma, QoL, and relationship satisfaction of PCa survivors and their spouses.

Design: A correlational design with dyadic data was used.

Sample: Participants (N?=?80 dyads) were PCa survivors and their spouses sampled from an oncology center and PCa support groups.

Methods: Structural equation modeling was used to assess how stigma related to the QoL and relationship satisfaction of participants.

Findings: Stigma had a negative association with QoL, but not relationship satisfaction. There were no significant demographic differences in regards to stigma.

Conclusion: Overall, stigma has a relationship with the experience of couples, but not with every aspect of their experience.

Implications for psychosocial providers: Implications for clinicians in regards to addressing PCa stigma with clients and areas for future research are discussed.  相似文献   


6.
Purpose/Objectives: The study examined whether the bond with a companion dog is associated with well-being among people with cancer, and described the perceived benefits, challenges, and needs accompanying the relationship with the dog.

Design: The design was cross-sectional.

Sample: Participants were 140 people recently diagnosed with cancer with at least one dog in their household.

Methods: The online survey included measures of the human–pet bond, depressive symptoms, positive affect, and health-related quality of life, as well as open-ended questions about the experience of having a dog since being diagnosed with cancer.

Findings: Although the bond with a companion dog was not directly linked with well-being, the association between the human–pet bond and depressive symptoms depended in part on treatment status.

Conclusions: Companion dogs may play an important role in the lives of people recently diagnosed with cancer.

Implications for psychosocial providers: Health care providers can help to support the bond with a companion dog.  相似文献   


7.
Purpose: Mouse double-stranded DNA-dependent protein kinase (DNA-PK) activity is heat sensitive. Recovery of heat-inactivated DNA repair activity is a problem after combination therapy with radiation and heat. We investigated the mechanism of recovery of heat-inactivated DNA-PK activity.

Methods: Hybrid cells containing a fragment of human chromosome 8 in scid cells (RD13B2) were used. DNA-PK activity was measured by an in vitro assay. Immunoprecipitation of the nuclear extract was performed with an anti-Ku80 antibody. Proteins co-precipitated with Ku80 were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and detected by Western blotting using anti-heat shock protein (HSP)72 and anti-heat shock cognate protein (HSC)73 antibodies. HSC73 was overexpressed with the pcDNA3.1 vector. Short hairpin (sh)RNA was used to downregulate HSC73 and HSP72.

Results: The activity of heat-inactivated DNA-PK recovered to about 50% of control during an additional incubation at 37?°C after heat treatment at 44?°C for 15?min in the presence of cycloheximide (which inhibits de novo protein synthesis). Maximal recovery was observed within 3?h of incubation at 37?°C after heat treatment. Constitutively expressed HSC73, which folds newly synthesized proteins, reached maximal levels 3?h after heat treatment using a co-immunoprecipitation assay with the Ku80 protein. Inhibiting HSC73, but not HSP72, expression with shRNA decreased the recovery of DNA-PK activity after heat treatment.

Conclusions: These results suggest that de novo protein synthesis is unnecessary for recovery of some heat-inactivated DNA-PK. Rather, it might be reactivated by the molecular chaperone activity of HSC73, but not HSP72.  相似文献   


8.
Purpose: To retrospectively evaluate the accuracy of a novel software platform for assessing completeness of percutaneous thermal ablations.

Materials & methods: Ninety hepatocellular carcinomas (HCCs) in 50 patients receiving percutaneous ultrasound-guided microwave ablation (MWA) that resulted in apparent technical success at 24-h post-ablation computed tomography (CT) and with ≥1-year imaging follow-up were randomly selected from a 320 HCC ablation database (2010–2016). Using a novel volumetric registration software, pre-ablation CT volumes of the HCCs without and with the addition of a 5?mm safety margin, and corresponding post-ablation necrosis volumes were segmented, co-registered and overlapped. These were compared to visual side-by-side inspection of axial images.

Results: At 1-year follow-up, CT showed absence of local tumor progression (LTP) in 69/90 (76.7%) cases and LTP in 21/90 (23.3%). For HCCs classified by the software as “incomplete tumor treatments”, LTP developed in 13/17 (76.5%) and all 13 (100%) of these LTPs occurred exactly where residual non-ablated tumor was identified by retrospective software analysis. HCCs classified as “complete ablation with <100% 5?mm ablative margins” had LTP in 8/49 (16.3%), while none of 24 HCCs with “complete ablation including 100% 5?mm ablative margins” had LTP. Differences in LTP between both partially ablated HCCs vs completely ablated HCCs, and ablated HCCs with <100% vs with 100% 5?mm margins were statistically significant (p?<?.0001 and p?=?.036, respectively). Thus, 13/21 (61.9%) incomplete tumor treatments could have been detected immediately, were the software available at the time of ablation.

Conclusions: A novel software platform for volumetric assessment of ablation completeness may increase the detection of incompletely ablated tumors, thereby holding the potential to avoid subsequent recurrences.  相似文献   


9.
Introduction: Currently, basic understanding of heterogeneity and complexity of tumors is depicted at molecular, cellular, genetic, epigenetic and metabolic adaptations levels.

Areas covered: There are appreciable numbers of views to pinpoint signaling axis that support metabolic adaptations of cancer cells in response to environmental pressures including nutritional factors and drug treatments. Specifically, nutritional deprivation and autophagy in certain types of cancer are linked to the abilities of cancer cells to use arginine in an auxotrophic or prototrophic manner.

Expert opinion: Hence, this paper highlights the current scope of arginine- and autophagy-centered metabolic adaptations across tumor types and possible avenues to bring tumors towards cytotoxic or cytostatic death.  相似文献   


10.
Objective: The aim of this study was to introduce a management strategy for nerve damage occurring during radiofrequency ablation (RFA).

Methods: From January 2016 to October 2017, 17 patients who experienced the symptoms of nerve damage during RFA were enrolled in this study. If damage to nerves was suspected during RFA, ablation was stopped immediately, and a cold solution of 5% dextrose was injected directly into the space where the nerves were located until symptoms improved. Patients were followed up after the procedure until symptoms had resolved. The clinical data of patients who received a cold dextrose solution injection for nerve damage were compared with those who did not receive such an injection.

Results: Of 17 patients who experienced nerve damage, 12 received an injection of cold dextrose solution shortly after the emergence of symptoms. While resolution of symptoms was seen in all 17 patients, the mean time to recovery was significantly faster in the 12 patients who received treatment with an injection of cold dextrose solution than in those patients who did not receive such a treatment (p value = .041).

Conclusions: In the event of thermal damage to adjacent nerve structures during RFA, the direct injection of a cold dextrose solution is a simple and effective treatment that can result in rapid symptom resolution.  相似文献   


11.
Background: High intensity focused ultrasound (HIFU) ablation is a promising treatment for benign thyroid nodules but because bleeding complications can occur following any intervention to the thyroid gland, the safety and efficacy of HIFU ablation were evaluated in patients who continued taking an anti-coagulation or anti-platelet agent during treatment.

Methods: From 2015 to 2017, 303 patients who underwent a single-session ablation for a benign thyroid nodule were analyzed. The primary study endpoint was thyroid bleeding, intra-lesional or peri-thyroidal hematoma or neck bruising diagnosed within 4?days of the treatment. Other endpoints included treatment-related complications, extent of nodule shrinkage and symptom score. Nodule volume was estimated by ultrasound. Extent of nodule shrinkage (by volume reduction ratio) (VRR)=?[Baseline volume – volume at 6-month]/[Baseline volume]?×?100. Obstructive symptom score (by 0– 10 visual analog scale, VAS) was evaluated after treatment.

Results: Twelve patients continued taking an anti-coagulation or anti-platelet agent while the other 291 patients did not during treatment. No patients in either group suffered active thyroid bleeding, intralesional/pericapsular hematoma or subcutaneous neck bruising in the first 4?days of treatment. Complication rate and the 6-month VRR were comparable between the two groups (0.0% vs. 1.7%, p?=?1.000 and 55.96% vs. 61.29%, respectively, p?=?.073).

Conclusions: HIFU ablation is a feasible treatment in patients who continue to take an anti-coagulation or anti-platelet agent during treatment and might be preferable in patients who continuously require an anti-coagulation or anti-platelet agent for one reason or another during treatment.  相似文献   


12.
13.
Background: Radiofrequency ablation is a minimally-invasive treatment method that aims to destroy undesired tissue by exposing it to alternating current in the 100?kHz–800?kHz frequency range and heating it until it is destroyed via coagulative necrosis. Ablation treatment is gaining momentum especially in cancer research, where the undesired tissue is a malignant tumor. While ablating the tumor with an electrode or catheter is an easy task, real-time monitoring the ablation process is a must in order to maintain the reliability of the treatment. Common methods for this monitoring task have proven to be accurate, however, they are all time-consuming or require expensive equipment, which makes the clinical ablation process more cumbersome and expensive due to the time-dependent nature of the clinical procedure.

Methods: A machine learning (ML) approach is presented that aims to reduce the monitoring time while keeping the accuracy of the conventional methods. Two different hardware setups are used to perform the ablation and collect impedance data at the same time and different ML algorithms are tested to predict the ablation depth in 3 dimensions, based on the collected data.

Results: Both the random forest and adaptive boosting (adaboost) models had over 98% R2 on the data collected with the embedded system-based hardware instrumentation setup, outperforming Neural Network-based models.

Conclusions: It is shown that an optimal pair of hardware setup and ML algorithm (Adaboost) is able to control the ablation by estimating the lesion depth within a test average of 0.3mm while keeping the estimation time within 10ms on a ×86–64 workstation.  相似文献   


14.
Introduction: Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality in the world. The majority of the patients present at an advanced or incurable stage where neither locoregional treatment nor combination treatment of locoregional treatment and systemic therapies is feasible. For decades sorafenib was the only treatment option available for advanced HCC. However, with the advent of new and more effective therapies recently, the overall prognosis of advanced HCC has improved significantly.

Areas covered: This review summarises the current systemic treatment options available and future prospects in the management of advanced HCC where patients are not suitable for locoregional treatment.

Expert opinion: New effective targeted therapeutics have dramatically changed the treatment landscape for advanced HCC. The incorporation of sequential therapy including sorafenib or lenvatinib as first-line treatment and immunotherapy, regorafenib or cabozantinib as second-line treatment have significantly improved outcomes for patients with advanced HCC. Further development of novel combinations of these new agents and predictive/prognostic biomarkers are being explored. Efforts should also be made to tailor treatment to individual patients based on etiology, clinical and molecular factors.  相似文献   


15.
Background: Secondary hyperparathyroidism (SHPT) is a frequently encountered problem in patients with end-stage renal disease (ESRD). Some patients with severe SHPT could not be managed by medical treatment and are ineligible for surgical resection.

Purpose: Our objective was to evaluate the efficacy, safety of microwave ablation (MWA) on these patients.

Materials and Methods: Between 1 April 2015 and 28 February 2017, 35 patients (M/F 19/16, age 49.8?±?12.9?years) were enrolled. All patients were treated with MWA. Levels of intact parathyroid hormone (iPTH) and of serum calcium and phosphorus were compared pre- and post-ablation. Repeated-measures ANOVA was used to compare treatment outcomes pre- and post-ablation.

Results: Complete ablation was achieved in all 63 glands in the 35 patients with SHPT. The mean follow-up time was 15.9?±?2.2?months. The maximum gland diameter was 6–31?mm (mean, 14.9?±?5.5?mm). The trends of the changes in iPTH and calcium levels showed a curve: the level of iPTH and calcium at 6?months post-ablation were lower than those pre-ablation (both p?<?.0001); after then iPTH remained relatively stable and the end of follow up, with no rebound (p?<?.0001), while instead of calcium at the end of follow up was not significantly lower than pre-ablation (p?=?.462). The trend in the change in phosphate levels showed a straight line; the level of phosphate at 6?months post-ablation and at the end of follow up both were significantly lower than pre-MWA (p?<?.001). There was no major complication.

Conclusions: In this series, MWA was used successfully to treat SHPT patients who are ineligible for surgical resection.  相似文献   


16.
Objective: To evaluate the long-term clinical effect of high-intensity focussed ultrasound (HIFU) as a non-invasive modality for ablation of abdominal wall endometriosis (AWE) foci.

Methods: All women who were diagnosed with cutaneous endometriosis and underwent HIFU ablation and 4-year follow-up were included. Patient symptoms, imaging performed, HIFU ablation, recurrence, lesion location, size and number were collected and analyzed.

Results: A total of 51 women with 57 painful abdominal wall masses with a median volume of 4.00?cm3 and a mean age of 30.5±2.12 years were treated with HIFU. The main symptoms were a palpable painful abdominal mass (93%), protrusion of the skin (28.1%, 16) or lack of protrusion of the skin (71.9%, 41). Ultrasound was initially performed in 100% (51) of women, whereas 6% (3) required MRI examinations to distinguish the features and range of the masses. Ablation was performed with a median 300?s of sonication time, 40?min treatment time, 150?W of power and 41800?J of total energy to treat lesions that were a median volume of 3.83?cm3. No severe complications occurred, except in one patient with a first-degree skin burn, during the 48-month follow-up period. The pooled recurrence of cutaneous endometriosis occurred in 3.9% (2) of women.

Conclusion: The diagnosis of AWE should be confirmed with imaging of the lesion number, location, size and features before HIFU ablation. HIFU should be the first choice for the treatment of AWE as it is a non-invasive method, with high efficiency and safety and rapid postoperative recovery.  相似文献   


17.
Purpose: Examine the relationship between mental health comorbidities and health services outcomes in non-elderly adults with head and neck cancer (HNC).

Design: Retrospective, cross-sectional.

Sample: Non-elderly adults with a primary diagnosis of HNC in U.S. Department of Defense (TRICARE) administrative claims data for fiscal years (FY) 2007–2014.

Methods: Linear regression and generalized linear models were used to examine predictors of reimbursed cost and healthcare utilization, respectively.

Findings: On average, there were 2944 HNC patients each year, the majority age 55–64, male, military retirees or family members of retirees, cared for in civilian facilities, and residing in the U.S. southern region. Between FY2007 and FY2014, there were slight increases in prevalence rates for diagnosed depression (12.4%–13.1%), anxiety (8.2%–11.9%), adjustment disorders (3.7%–5.8%), and drug use disorders (10.3%–19.4%), and a slight decrease in alcohol use disorders (12.3%–11.4%). In the cost regression model, depression and anxiety were the seventh and eighth strongest predictors (p?<?.001), behind hospice use, treatment modalities, chronic physical conditions, and tobacco use. In the utilization regression models, depression, adjustment disorder, and anxiety ranked seventh, ninth, and eleventh as the strongest predictors for the number of ambulatory visits; anxiety, depression and substance use disorder ranked fifth, sixth, and eighth in the model examining predictors of the number of annual hospitalizations; and anxiety and depression ranked fifth and sixth in the model examining predictors of the annual number of bed days.

Conclusions: We found strong evidence that mental health comorbidities impact cost and utilization among HNC patients, independent of other factors.

Implications for Psychosocial Providers or Policy: Addressing mental health comorbidities among HNC patients may reduce cost and improve resource efficiency.  相似文献   


18.
Objective: This hermeneutic phenomenological study was conducted with the aim to determine the emotions and coping methods of Turkish parents whose children were diagnosed with cancer.

Methods: Data were collected through in-person, in-depth interviews with 12 parents (8 mothers, 4 fathers). The semi-structured interview form was developed based on Elisabeth Kübler-Ross's model of the five stages of grief (denial, anger, bargaining, depression and acceptance) with the addition of questions on coping methods.

Data interpretation proceeded through three phases: superficial reading, structural analysis and comprehensive understanding.

Results: All the parents made statements indicating their devastation while expressing their feelings at the moment they learned of the diagnosis. After overcoming the first shock, most thought it was a false diagnosis, and some thought it was a test from God. The parents were angry mostly with the doctors, themselves, their spouses and God. All the parents participating in the study stated that they had regrets about the past. Most engaged in more emotion-oriented and fewer problem-focused coping efforts. However, some parents used negative coping methods.

Conclusion: These parents need help from healthcare professionals to come to terms with their grief.  相似文献   


19.
Introduction: In 2005, sorafenib was the first targeted therapy approved for advanced renal cell carcinoma (RCC), transforming treatment. In hepatocellular carcinoma (HCC), for more than a decade, sorafenib remained the only approved systemic therapy to have demonstrated a survival benefit in first-line unresectable HCC. In 2013, sorafenib was the first targeted agent approved for patients with differentiated thyroid cancer (DTC) refractory to radioactive iodine treatment.

Areas covered: This review discusses the development, advances, and challenges associated with sorafenib use in RCC, HCC, and DTC over the past decade. A search was performed on PubMed and key congresses as required, with no time limits.

Expert commentary: Sorafenib has had a lasting impact on the therapeutic landscape of RCC, HCC, and DTC, and remains an important treatment option despite a rapidly evolving treatment landscape. Extensive clinical and real-world experience has been invaluable in improving patient management and maximizing benefit from treatment. Ongoing clinical trials continue to evaluate sorafenib in different settings, and in combination with other therapies in HCC and DTC. We have no doubt that sorafenib will continue to be an important treatment option in the coming years.  相似文献   


20.
Purpose: To (a) describe the decision-making experience and psychosocial outcome of sibling hematopoietic stem cell (HSC) donors, and (b) to determine the feasibility of completing a prospective and longitudinal assessment of HSC sibling donors at a single institution.

Design: A mixed-methods approach was utilized.

Sample and methods: 12 potential siblings HSC donors aged 10–21?years completed various psychological measures and participated in semi-structured interviews at three time points in the donation experience: pre-donation, within 1?week after the harvest procedure, and six months post-donation. Caregivers also completed parent-proxy measures.

Findings: Qualitative analysis indicated donors want to make their own decision about donation but may not be given the option or may feel that there is no choice given their limited awareness of alternative options. Donors felt well prepared for the donation procedure but demonstrated a poor understanding of possible recipient outcomes. A minority of donors endorsed emotional distress prior to and after donation; however, this was not linked to recipient health. Forty percent of donors felt that they had inadequate support following their donation. Small sample size restricted quantitative data analysis.

Conclusions and implications: Utilizing a donor advocate offers opportunity to work with donors to encourage decision-making tied to ideals rather obligation, increase education about possible recipient outcomes, and offer support at key times, such as when a recipient dies. Future research should include prospective multi-site studies.  相似文献   


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