ABSTRACT
Patients with metastatic breast cancer have high and continually increasing rates of brain metastases. During the course of the disease, brain metastases can occur in up to 30% of these patients. In most cases, brain metastases are diagnosed after significant disease progression. The blood-tumor barrier increases the difficulty of treating brain metastasis by preventing accumulation of chemotherapy within metastases at therapeutically effective concentrations. Traditional therapies, such as surgical resection, radiotherapy, and chemotherapy, have poor efficacy, as reflected by a low median survival rate of 5-8% after post-diagnosis. Low-intensity focused ultrasound (LiFUS) is a new treatment for enhancing drug accumulation within the brain and brain malignancies. In this study, we elucidate the effect of clinical LiFUS combined with chemotherapy on tumor survival and progression in a preclinical model of triple-negative breast cancer metastasis to the brain. LiFUS significantly increased the tumor accumulation of 14C-AIB and Texas Red compared to controls (p< 0.01). LiFUS-mediated opening of the BTB is size-dependent, which is consistent with our previous studies. Mice receiving LiFUS with combinatorial Doxil and paclitaxel showed a significant increase in median survival (60 days) compared to other groups. LiFUS plus combinatorial chemotherapy of paclitaxel and Doxil also showed the slowest progression of tumor burden compared to chemotherapy alone or individual chemotherapy and LiFUS combinations. This study shows that combining LiFUS with timed combinatorial chemotherapeutic treatment is a potential strategy for improving drug delivery to brain metastases.
ABSTRACT
Major cancer deaths can be ascribed to distant metastasis to which the assembly of pericellular fibronectin (periFN) on suspended tumor cells (STCs) in the bloodstream that facilitate endothelial attachment can lead. Even though mangosteen pericarps (MP) extracts and the major component α-mangostin (α-MG) exhibit potent cancer chemopreventive properties, whether they can prophylactically and therapeutically be used as dietary nutraceuticals to prevent distant metastasis by suppressing periFN assembly on STCs within the circulation remains obscure. Immunofluorescence staining, MTT assays, flow cytometric assays, immunoblotting, and experimental metastasis mouse models were used to detect the effects of MP extracts or α-MG on periFN on STCs, tumor cell proliferation and apoptosis, the AKT activity, and tumor lung metastasis. The periFN assembly on STCs was significantly diminished upon treatments of STCs with either α-MG or MP extracts in a dose-dependent manner without inhibiting cell proliferation and viability due to increased AKT activity. Pretreatment of STCs with α-MG appeared to suppress tumor lung metastasis and prolong mouse survival rates. Oral gavage with MP extracts could therapeutically, but not prophylactically, prevent lung metastasis of STCs. We concluded that MP extracts or the major component α-MG may therapeutically serve as a potent anti-metastatic nutraceutical.
ABSTRACT
BACKGROUND: With the development of laparoscopic techniques and the broad clinical application of various anastomotic types, anal-preserving low anterior rectal resection and ultra-low anterior rectal resection have been popularized. Some patients with rectal cancer have retained their anus and improved their quality of life. Nevertheless, the incidence of postoperative anastomotic stenosis remains high, and anastomotic occlusion is even rarer. CASE PRESENTATION: We report a case of anastomotic occlusion in a patient with rectal cancer, which occurred after undergoing laparoscopic low anterior rectal resection + prophylactic terminal ileal fistulation at our department. Under endoscopy, we used a small guidewire to break through the occluded anastomosis, thereby finding the lacuna. After endoscopic balloon dilation, digital anal dilatation, and continuous dilator-assisted dilation, the desired efficacy was achieved, ultimately recovering ileal stoma. Postoperative follow-up condition was generally acceptable, without symptoms like abdominal pain, bloating, or difficulty in defecation. CONCLUSION: Numerous factors cause postoperative anastomotic stenosis in patients with rectal cancer. Complete occlusion of anastomosis occurs relatively rare in clinical practice, and is challenging to treat. This case was our first attempt to remove the anastomotic occlusion successfully, which avoided re-operation or pain from the permanent fistula.
Subject(s)
Laparoscopy , Rectal Neoplasms , Anastomosis, Surgical/adverse effects , Anastomotic Leak/surgery , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Humans , Laparoscopy/adverse effects , Laparoscopy/methods , Postoperative Complications/epidemiology , Quality of Life , Rectal Neoplasms/complications , Rectal Neoplasms/surgery , Retrospective StudiesABSTRACT
PURPOSE: This paper aims to explore the reasons for and the subsequent longer-term impact of the closure of the Barlinnie Special Unit (BSU). DESIGN/METHODOLOGY/APPROACH: The paper is both descriptive, providing an overview of the work of the BSU, and conceptual in that it argues that the limits of "prisoner rehabilitation" are observed in the closure of the BSU, which sounds a warning for other penal therapeutic communities and what it means to operate effectively. FINDINGS: The BSU which assisted long-term, difficult and violent prisoners moderate their prison behaviour and then to live non-offending lives, lost the confidence of government ministers and officials, as well as senior prison managers and, seemingly, the public, so closed after being in operation for 21 years. The impact of this has been that the Scottish Prison Service has not introduced, or attempted to introduce, a similar regime for managing and treating violent and disruptive prisoners. PRACTICAL IMPLICATIONS: There are important lessons to be learned from the BSU experience for all who manage and work in specialist, prison therapeutic units or within prison therapeutic regimes. This includes balancing the therapeutic elements of the regime, which may involve engaging in practices which are outside the norm for custodial establishments, with those establishments' security and operational requirements, so as to not to create a disconnect between addressing offending behaviour and maintaining expected standards of wider prison conduct. ORIGINALITY/VALUE: While there have been previous evaluations of the BSU, the longer-term impact has neither been previously considered and nor has the unit's closure been considered from a penal philosophical perspective.
Subject(s)
Prisoners , Prisons , Humans , Therapeutic CommunityABSTRACT
The aim of the present study was to calculate the cost-effectiveness of on-demand and prophylactic treatments of severe haemophilia A for Bulgarian patients. The point of view is that of all patients suffering from severe haemophilia A. An epidemiological model was created, which includes data regarding the number of patients divided into age groups up to 74 years. In the model, the transition age from prophylactic to on-demand treatment was gradually increased to up to 40 years. Costs of blood clotting factor, hospitalization, major surgery and indirect costs were considered; incremental cost-effectiveness ratio was calculated. The results showed that despite the increase in the costs for factor VIII with 20 million BGN, the saving obtained from other health services and indirect expenses reduce the overall expenses with 5.3 million BGN. If there is a gradual increase in the age when patients are transferred from a prophylactic to an on-demand regimen, the costs for factor VIII would increase from 10.4 million to 19.7 million BGN, but due to a decrease in indirect costs as well as other health service costs, the total costs would decrease. The sensitivity analysis showed that the costs for clotting factor VIII are what influences the cost-effectiveness in both regimes. This indicates that decreases in the factor VIII cost will increase the overall efficiency in both regimes. In conclusion, the application of the prophylactic regime for patients up to 40 years of age will provide better treatment, increase the quality of life and decrease the incremental costs.
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OBJECTIVE:To discuss the curative effects,adverse drug reactions(ADRs)and cost—effectiveness of 3 kinds of nitroimidazole drugs for treatment of trichomonal vaginitis.METHODS:111 cases of trichomonal vaginitis were randomly divided into 3 groups,administered with metronidazol(group A),tinidazole (group B),and ornidazol(group C)respectively,the curative effects and ADRs were observed and cost-effectiveness analysis was made in all groups.RESULTS:The costs in 3 groups were 0.74 yuan,33.6 yuan and 41.2 yuan respectively.The cure rates were 59.4%,81.6%and 97.2%,respectively.The cost-effectiveness ratios were 0.01,0.41,and 0.42 respectively.The increment cost -effectiveness ratios in group B and C were 1.48 and 1.07,as compared with group A.The occurrences of ADRs were 62.2%,18.4%,and11.1%respectively.CONCLUSION:Among 3 regimes,regime C is the preferred one.
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OBJECTIVE:To evaluate the cost-effectiveness of 3 therapeutic regimes in the treatment of functional dyspepsia. METHODS:125 cases were randomly divided into 3 groups,group A was treated with domperidone,group B was treated with domperidone plus doxepin hydrochloride,and group C was treated with domperidone plus famotidine,the curative effects of the 3 group were observed after oral administration and the cost-effectiveness analysis was conducted as well. RESULTS:The costs for group A,B and C were 792.56 yuan,800.12 yuan and 803.76 yuan,respectively;The effective rates were 51.17%,82.50%and 71.43%,respectively;The cost-effectiveness ratio were 15.49,9.70 and 11.25,respectively;The incremental cost-effectiveness ratios of group B and C vs. group A were 0.24 and 0.55,respectively. CONCLUSION:Regime B was superior among the other two therapeutic regimes.
