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Lung Cancer ; 138: 95-101, 2019 12.
Article in English | MEDLINE | ID: mdl-31678832

ABSTRACT

OBJECTIVE: Lymph node (LN) metastases predict survival in patients with non-small cell lung cancer (NSCLC) treated with curative surgery. Nevertheless, prognostic differences within the same nodal (N) status have been reported. Consequently, the International Association for the Study of Lung Cancer (IASLC) proposed to stratify patients with limited nodal disease (pN1) from low (pN1a) to high (pN1b) nodal tumor burden. This study aimed to validate the IASLC proposal in a large single-center surgical cohort of patients with pN1 NSCLC. MATERIAL AND METHODS: Data from 317 patients with pN1 NSCLC treated between January 2012 and December 2016, were retrospectively analyzed. Associations between distribution of LN metastases and survival were analyzed for different classification models-toward nodal extension (pN1a: one station involved; pN1b: multiple stations involved) and toward location (pN1 in the hilar [LN#10/11] or peripheral zone [LN#12-14]). RESULTS: Tumor-specific survival (TSS) in the entire pN1 cohort was 67.1% at five years. Five-year TSS rates for pN1a and pN1b patients were comparable (67.6% vs. 66.5%, p = 0.623). Significant survival differences from pN1a to pN1b were observed only in patients with adenocarcinoma histology and completed adjuvant chemotherapy (5-year TSS: pN1a, 80.4% vs. pN1b, 49.6%; p = 0.005). TSS for LN metastases in the hilar zone/peripheral zone or in both zones was 68.2% and 59.9%, respectively (p = 0.068). In multivariate analysis, adjuvant chemotherapy, squamous cell histology, and nodal disease limited to one zone nodal disease were identified as independent beneficial prognostic factors (p < 0.05). CONCLUSION: pN1 in only one region (hilar or lobar) was associated with better outcome than metastatic affection of both regions after surgery and adjuvant therapy. A stratification towards single (pN1a) and multiple (pN1b) N1-metastases was found of prognostic relevance only in adenocarcinoma. Prospective multicenter analysis of prognostic subgroups in N1 NSCLC is required to evaluate its clinical impact for consideration in future TNM classification.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Lymph Nodes/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/surgery , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging/methods , Prognosis , Retrospective Studies , Survival Rate , Tumor Burden
3.
Chirurg ; 90(9): 697-703, 2019 Sep.
Article in German | MEDLINE | ID: mdl-31161248

ABSTRACT

BACKGROUND: Interventional bronchoscopy is an indispensable option to manage bronchopleural and tracheopleural fistulas in patients in a poor general condition and at high risk for developing postoperative complications. METHODS: This article is based on a search in the PubMed database for relevant publications and own experiences as surgeons and pneumologists. RESULTS: Various interventional techniques can be used for the treatment of bronchopleural and tracheopleural fistulas. Currently, the insertion of stents or endobronchial valves is the most frequently used treatment. Ideally, the attending anesthesiologist will have experience with high frequency jet ventilation and the attending surgeon will have experience with rigid bronchoscopy, flexible bronchoscopy, and interventional bronchoscopy. DISCUSSION: Due to a lack of standardized treatment recommendations, individual treatment plans must be decided according to the location of the bronchopleural or tracheopleural fistula and taking existing comorbidities into account.


Subject(s)
Bronchial Fistula , Pleural Diseases , Bronchial Fistula/surgery , Bronchoscopy , Humans , Pleural Diseases/surgery , Pneumonectomy , Postoperative Complications , Stents , Treatment Outcome
5.
Eur J Neurol ; 26(6): 919-926, 2019 06.
Article in English | MEDLINE | ID: mdl-30659722

ABSTRACT

BACKGROUND AND PURPOSE: Post-ischaemic immune cell invasion into the brain is well characterized in animal stroke models and contributes to neuronal damage. Therefore, it represents a promising therapeutic target. Cerebrospinal fluid (CSF) is easily accessible and may reflect cellular events within the parenchyma. However, comprehensive studies on CSF immune cells in patients with stroke are lacking. METHODS: In a retrospective cohort study, we performed extensive immune-cell profiling in CSF and peripheral blood of patients with acute ischaemic stroke and healthy controls. In patients with stroke, infarct size was quantified on follow-up imaging. RESULTS: Overall, 90 patients with ischaemic stroke and 22 controls were included in our study. After stroke, the total protein was increased (537.3 vs. 353.2 mg/L, P = 0.008) and the mean total white cell count was slightly but non-significantly elevated (1.76 vs. 0.50 cells/µL, P = 0.059). Proportions of CSF lymphocytes, monocytes and granulocytes and their respective subsets did not differ between patients with stroke and controls. In addition, there were no associations between proportions of major leukocyte subsets in CSF and the time from symptom onset to CSF sampling, infarct size or infarct localization. CONCLUSIONS: Ischaemic stroke induces only a very slight increase of CSF immune cells without changes in the composition of immune cell subsets, thus indicating that parenchymal inflammation is not sufficiently reflected in the CSF. Our findings suggest that CSF is not a major invasion route for immune cells and that CSF cell analyses are not suitable as biomarkers to guide future immune therapies for stroke.


Subject(s)
Brain Ischemia/cerebrospinal fluid , Immunophenotyping , Leukocytes/immunology , Lymphocytes/immunology , Monocytes/immunology , Stroke/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , Female , Humans , Leukocyte Count , Male , Middle Aged , Retrospective Studies
6.
World J Urol ; 37(10): 2147-2153, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30671638

ABSTRACT

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. RESULTS: Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. CONCLUSION: Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.


Subject(s)
Laser Therapy , Prostatectomy/methods , Prostatic Neoplasms/surgery , Delphi Technique , Humans , Laser Therapy/standards , Male , Practice Guidelines as Topic , Prostatectomy/standards
7.
HLA ; 2018 Jun 10.
Article in English | MEDLINE | ID: mdl-29888557

ABSTRACT

The impact of de novo donor-specific anti-HLA antibodies (DSA) on outcomes in lung transplantation is still a matter of debate. We hypothesize that differentiating DSA by persistent and transient appearance may offer an additional risk assessment. The clinical relevance of HLA-antibodies was investigated prospectively in 72 recipients with a median follow-up period of 21 months. The presence of HLA-antibodies was analysed by single antigen bead assay prior to and after (3 weeks, 3, 6, 12 and 18 months) transplantation. In 23 patients (32%) de novo DSA were detected. In 10 of these patients (44%) DSA persisted throughout the follow-up period whereas 13 of these patients (56%) had transient DSA. There was a trend towards lower one-year-survival in DSA positive compared to DSA negative patients (83% versus 94%; p=0.199). Remarkably, patients with persistent DSA had significantly reduced survival (one-year survival 60%) compared with both patients without DSA and those with transient DSA (p=0.005). Persistent DSA represented an independent prognostic factor for reduced overall survival in multivariate analysis (HR 8.3, 95% CI 1.8-37.0; p=0.006). Persistence of DSA during the first year after transplantation seems to be more harmful for lung allograft function than transiently detected DSA at an early stage. This article is protected by copyright. All rights reserved.

8.
Prostate Cancer Prostatic Dis ; 20(4): 401-406, 2017 12.
Article in English | MEDLINE | ID: mdl-28462943

ABSTRACT

BACKGROUND: Given the central role of the media in disseminating information to the public, we analyzed news coverage of the recent publication from ProtecT to assess views on treatment, the level of detail presented and degree of bias. METHODS: We applied a predefined search strategy to identify all news articles reporting on ProtecT within 30 days of its publication. Articles were independently assessed by two urologists and two lay persons using five-point Likert scales. Descriptive statistics and analysis of variance were used. RESULTS: Of 33 unique articles identified, 20 (61%) conveyed negative views on definitive treatment for localized prostate cancer (PCa), while 29 (88%) expressed favorable views of active surveillance/monitoring (AM). Nevertheless, fewer than half of the articles described what AM entails (n=15; 46%) or the rate of treatment in the AM arm (n=12; 36%). Moreover, while 32 (97%) articles highlighted the absence of a difference in cancer-specific mortality at 10 years, only 17 (52%) mentioned the need for longer follow-up. A total of 17 (52%) articles had a notable degree of perceived bias (⩾4/5 on Likert scale), with shorter articles (P=0.02), articles covering few content areas (P=0.03) and articles that did not detail what AM entails (P=0.003) containing significantly increased bias. CONCLUSIONS: The majority of news articles regarding ProtecT presented an adverse view of definitive treatment for localized PCa relative to AM, but failed to highlight key nuances of the trial. Healthcare professionals and the lay public should be cautious in acquiring medical news through the general media. Additionally, the urologic community must continue to improve the quality of disseminated information, for example, through proactively engaging with the media, through social media and/or through participation in continuing education lecture series, so as to guide the knowledge translation process, especially upon publication of such potentially influential studies.


Subject(s)
Information Dissemination , Prostatic Neoplasms/mortality , Social Media , Clinical Trials as Topic , Disease-Free Survival , Humans , Male , Prostatic Neoplasms/therapy
9.
Prostate Cancer Prostatic Dis ; 20(3): 294-299, 2017 09.
Article in English | MEDLINE | ID: mdl-28349978

ABSTRACT

BACKGROUND: Whole-gland extirpation or irradiation is considered the gold standard for curative oncological treatment for localized prostate cancer, but is often associated with sexual and urinary impairment that adversely affects quality of life. This has led to increased interest in developing therapies with effective cancer control but less morbidity. We aimed to provide details of physician consensus on patient selection for prostate focal therapy (FT) in the era of contemporary prostate cancer management. METHODS: We undertook a four-stage Delphi consensus project among a panel of 47 international experts in prostate FT. Data on three main domains (role of biopsy/imaging, disease and patient factors) were collected in three iterative rounds of online questionnaires and feedback. Consensus was defined as agreement in ⩾80% of physicians. Finally, an in-person meeting was attended by a core group of 16 experts to review the data and formulate the consensus statement. RESULTS: Consensus was obtained in 16 of 18 subdomains. Multiparametric magnetic resonance imaging (mpMRI) is a standard imaging tool for patient selection for FT. In the presence of an mpMRI-suspicious lesion, histological confirmation is necessary prior to FT. In addition, systematic biopsy remains necessary to assess mpMRI-negative areas. However, adequate criteria for systematic biopsy remains indeterminate. FT can be recommended in D'Amico low-/intermediate-risk cancer including Gleason 4+3. Gleason 3+4 cancer, where localized, discrete and of favorable size represents the ideal case for FT. Tumor foci <1.5 ml on mpMRI or <20% of the prostate are suitable for FT, or up to 3 ml or 25% if localized to one hemi-gland. Gleason 3+3 at one core 1mm is acceptable in the untreated area. Preservation of sexual function is an important goal, but lack of erectile function should not exclude a patient from FT. CONCLUSIONS: This consensus provides a contemporary insight into expert opinion of patient selection for FT of clinically localized prostate cancer.


Subject(s)
Patient Selection , Prostatic Neoplasms/radiotherapy , Humans , Male , Prostatic Neoplasms/diagnostic imaging
10.
Br J Pharmacol ; 174(12): 1514-1532, 2017 06.
Article in English | MEDLINE | ID: mdl-26920226

ABSTRACT

Forkhead box, class O (FOXO) transcription factors are major regulators of diverse cellular processes, including fuel metabolism, oxidative stress response and redox signalling, cell cycle progression and apoptosis. Their activities are controlled by multiple posttranslational modifications and nuclear-cytoplasmic shuttling. Recently, post-transcriptional regulation of FOXO synthesis has emerged as a new regulatory level of their functions. Accumulating evidence suggests that this post-transcriptional mode of regulation of FOXO activity operates in response to stressful stimuli, including oxidative stress. Here, we give a brief overview on post-transcriptional regulation of FOXO synthesis by microRNAs (miRNAs) and by RNA-binding regulatory proteins, human antigen R (HuR) and quaking (QKI). Aberrant post-transcriptional regulation of FOXOs is frequently connected with various disease states. We therefore discuss characteristic examples of FOXO regulation at the post-transcriptional level under various physiological and pathophysiological conditions, including oxidative stress and cancer. The picture emerging from this summary points to a diversity of interactions between miRNAs/miRNA-induced silencing complexes and RNA-binding regulatory proteins. Better insight into these complexities of post-transcriptional regulatory interactions will add to our understanding of the mechanisms of pathological processes and the role of FOXO proteins. LINKED ARTICLES: This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.


Subject(s)
Forkhead Transcription Factors/metabolism , MicroRNAs/metabolism , Protein Processing, Post-Translational , RNA-Binding Proteins/metabolism , Receptors, Antigen/metabolism , Animals , Humans
11.
Prostate Cancer Prostatic Dis ; 20(1): 1-6, 2017 03.
Article in English | MEDLINE | ID: mdl-27801900

ABSTRACT

BACKGROUND: Utilization of active surveillance (AS) for prostate cancer is increasing. Optimal selection criteria for this approach are undefined and questions remain on how best to expand inclusion beyond typical men with very low- or low-risk disease. We sought to review the current experience with AS for men with intermediate-risk featuresMethods:PubMed was queried for all relevant original publications describing outcomes for men with prostate cancer managed with AS. Outcomes for patients with intermediate-risk features as defined by the primary investigators were studied when available and compared with similar risk men undergoing immediate treatment. RESULTS: Cancer-specific survival for men managed initially with AS is similar to results published with immediate radical intervention. A total of five published AS series describe some outcomes for men with intermediate-risk features. Definitions of intermediate risk vary between studies. Men with Gleason 7 disease experience higher rates of clinical progression and are more likely to undergo treatment over time. Intermediate-risk men with Gleason 6 disease have similar outcomes to low-risk men. Men with Gleason 7 disease appear at higher risk for metastatic disease. Novel technologies including imaging and biomarkers may assist with patient selection and disease surveillance. CONCLUSIONS: The contemporary experiences of AS for men with intermediate-risk features suggest that although these men are at higher risk for eventual prostate-directed treatment, some are not significantly compromising chances for longer-term cure. Men with more than minimal Gleason pattern 4, however, must be carefully selected and surveyed for early signs of progression and may be at increased risk of metastases. Incorporating information from advanced imaging and biomarker technology will likely individualize future treatment decisions while improving overall surveillance strategies.


Subject(s)
Prostatic Neoplasms/epidemiology , Biomarkers, Tumor , Genetic Predisposition to Disease , Germ-Line Mutation , Humans , Male , Multimodal Imaging/methods , Neoplasm Grading , Outcome Assessment, Health Care , Polymorphism, Single Nucleotide , Population Surveillance , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/etiology , Prostatic Neoplasms/therapy , Risk Assessment , Risk Factors
12.
Prostate Cancer Prostatic Dis ; 19(3): 305-10, 2016 09.
Article in English | MEDLINE | ID: mdl-27349497

ABSTRACT

BACKGROUND: Although much research has examined the relationship between lifestyle and prostate cancer (PCa) risk, few studies focus on the relationship between lifestyle and PCa progression. The present study examines this relationship among men initially diagnosed with low- to intermediate-risk PCa and managed with active surveillance (AS). METHODS: Men enrolled in two separate AS programs were recruited for this study. Data regarding clinical, demographic and lifestyle characteristics were collected. Results were then compared between men whose disease remained low- to intermediate-risk and men whose disease progressed. RESULTS: Demographic, clinical and physical characteristics were similar between comparative groups and cohorts, with the exception that age at the time of diagnosis and questionnaire was increased among men whose disease progressed. Lifestyle scores among men who remained low- to intermediate-risk were higher than those whose risk progressed; however, scores were only significant in one cohort on univariable analysis. On multivariable analysis, the only predictor of progression was age at diagnosis. Physical activity was consistently higher in both low risk groups, although this difference was insignificant. Consistent differences in other lifestyle variables were not observed. CONCLUSIONS: Age remains an important predictor of PCa progression. Improving lifestyle characteristics among men initially managed with AS might help to reduce the risk of progression. Given the limitations of this study, more rigorous investigation is required to confirm whether lifestyle characteristics influence the progression of low- to intermediate-risk PCa.


Subject(s)
Life Style , Prostatic Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , Cohort Studies , Disease Progression , Feeding Behavior , Humans , Male , Middle Aged , Neoplasm Grading , Odds Ratio , Population Surveillance , Prognosis , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Risk Factors , Surveys and Questionnaires , Time Factors
13.
Nervenarzt ; 87(6): 645-59, 2016 Jun.
Article in German | MEDLINE | ID: mdl-26927677

ABSTRACT

With the approval of various substances for the immunotherapy of multiple sclerosis (MS), treatment possibilities have improved significantly over the last few years. Indeed, the choice of individually tailored preparations and treatment monitoring for the treating doctor is becoming increasingly more complex. This is particularly applicable for monitoring for a treatment-induced compromise of the immune system. The following article by members of the German Multiple Sclerosis Skills Network (KKNMS) and the task force "Provision Structures and Therapeutics" summarizes the practical recommendations for approved immunotherapy for mild to moderate and for (highly) active courses of MS. The focus is on elucidating the substance-specific relevance of particular laboratory parameters with regard to the mechanism of action and the side effects profile. To enable appropriate action to be taken in clinical practice, any blood work changes that can be expected, in addition to any undesirable laboratory findings and their causes and relevance, should be elucidated.


Subject(s)
Immunotherapy/adverse effects , Immunotherapy/methods , Monitoring, Immunologic/methods , Multiple Sclerosis/immunology , Multiple Sclerosis/therapy , Humans , Immunocompetence/drug effects , Immunocompetence/immunology , Multiple Sclerosis/classification
14.
Zentralbl Chir ; 140 Suppl 1: S36-42, 2015 Oct.
Article in German | MEDLINE | ID: mdl-26351762

ABSTRACT

BACKGROUND: Tuberculosis is still one of the most common infectious diseases along with HIV and malaria and therefore represents a serious problem in the health sector. Due to immigrants and refugees, the disease is also present in Europe. The global increase of multidrug resistant tuberculosis leads to a highly significant and current importance of sufficient therapeutic measures. In recent years, this fact has led to a reevaluation of surgical therapy in the context of an interdisciplinary and multimodal treatment of multidrug resistant tuberculosis. In addition, despite an effective treatment of drug sensitive tuberculosis with antibiotics, there are still indications for surgery in the treatment of tuberculosis. Beside massive hemoptysis as an emergency indication for surgical intervention, secondary complications of tuberculosis such as aspergilloma, chronic hemoptysis, pneumothorax, bronchopleural fistula and destroyed lung remain indications for surgery. CONCLUSION: The indication for surgery should always be made in a multimodal therapeutic approach by an interdisciplinary team, taking patient age and functional analysis into account. Effective antibiotic therapy should be performed before and after surgery in order to achieve a sustained treatment success.


Subject(s)
Tuberculosis, Multidrug-Resistant/surgery , Tuberculosis, Pulmonary/surgery , Adult , Antibiotics, Antitubercular/therapeutic use , Child , Combined Modality Therapy , Cooperative Behavior , Cross-Sectional Studies , Emigrants and Immigrants , Humans , Interdisciplinary Communication , Pulmonary Aspergillosis/diagnosis , Pulmonary Aspergillosis/epidemiology , Pulmonary Aspergillosis/surgery , Pulmonary Aspergillosis/transmission , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/transmission , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/transmission
15.
Nervenarzt ; 86(10): 1236-47, 2015 Oct.
Article in German | MEDLINE | ID: mdl-26269289

ABSTRACT

In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.


Subject(s)
Allergy and Immunology/standards , Immunosuppressive Agents/administration & dosage , Immunotherapy/standards , Multiple Sclerosis/drug therapy , Neurology/standards , Practice Guidelines as Topic , Dose-Response Relationship, Drug , Drug Administration Schedule , Germany , Humans , Immunosuppressive Agents/standards , Multiple Sclerosis/immunology
16.
Prostate Cancer Prostatic Dis ; 18(4): 303-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26215782

ABSTRACT

Prostate cancer is the second most frequently diagnosed cancer in the world. Localized disease can be effectively treated with radiation therapy or radical prostatectomy. However, advanced prostate cancer is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced prostate cancer. One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence. Metformin, a common oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti-neoplastic effects. Specifically, metformin targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer. Metformin acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial ATP production. This forces tumor cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. Metformin could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional cancer therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in tumor propagation and therapeutic resistance and the role of metformin as a potential prostate CSC sensitizer to current anticancer therapies.


Subject(s)
Antineoplastic Agents/therapeutic use , Metformin/therapeutic use , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Antineoplastic Agents/pharmacology , Biomarkers , Drug Resistance, Neoplasm , Humans , Male , Metformin/pharmacology , Mitochondria/drug effects , Mitochondria/metabolism , Oxidative Phosphorylation/drug effects , Phenotype , Prostate/cytology , Prostate/metabolism , Prostate/pathology , Prostatic Neoplasms/pathology , Treatment Outcome
17.
Br J Cancer ; 112(6): 977-82, 2015 Mar 17.
Article in English | MEDLINE | ID: mdl-25688739

ABSTRACT

BACKGROUND: Men undergoing treatment of clinically localised prostate cancer may experience a number of treatment-related complications, which affect their quality of life. METHODS: On the basis of population-based retrospective cohort of men undergoing surgery, with or without subsequent radiotherapy, or radiotherapy alone for prostate cancer in Ontario, Canada, we measured the incidence of treatment-related complications using administrative and billing data. RESULTS: Of 36 984 patients, 15 870 (42.9%) underwent surgery alone, 4519 (12.2%) underwent surgery followed by radiotherapy, and 16 595 (44.9%) underwent radiotherapy alone. For all end points except urologic procedures, the 5-year cumulative incidence rates were lowest in the surgery only group and highest in the radiotherapy only group. Intermediary rates were seen in the surgery followed by radiotherapy group, except for urologic procedures where rates were the highest in this group. Although age and comorbidity were important predictors, radiotherapy as the primary treatment modality was associated with higher rates for all complications (adjusted hazard ratios 1.6-4.7, P=0.002 to <0.0001). CONCLUSIONS: In patients treated for prostate cancer, radiation after surgery increases the rate of complications compared with surgery alone, though these rates remain lower than patients treated with radiation alone. This information may inform patient and physician decision making in the treatment of prostate cancer.


Subject(s)
Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Aged , Cohort Studies , Humans , Kaplan-Meier Estimate , Male , Ontario , Postoperative Complications/etiology , Quality of Life , Radiotherapy/adverse effects , Retrospective Studies , Treatment Outcome
18.
Ann Oncol ; 26(2): 368-74, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25425475

ABSTRACT

BACKGROUND: In a phase III trial in patients with castration-resistant prostate cancer (CRPC) and bone metastases, denosumab was superior to zoledronic acid in reducing skeletal-related events (SREs; radiation to bone, pathologic fracture, surgery to bone, or spinal cord compression). This study reassessed the efficacy of denosumab using symptomatic skeletal events (SSEs) as a prespecified exploratory end point. PATIENTS AND METHODS: Patients with CRPC, no previous bisphosphonate exposure, and radiographic evidence of bone metastasis were randomized to subcutaneous denosumab 120 mg plus i.v. placebo every 4 weeks (Q4W), or i.v. zoledronic acid 4 mg plus subcutaneous placebo Q4W during the blinded treatment phase. SSEs were defined as radiation to bone, symptomatic pathologic fracture, surgery to bone, or symptomatic spinal cord compression. The relationship between SSE or SRE and time to moderate/severe pain was assessed using the Brief Pain Inventory Short Form. RESULTS: Treatment with denosumab significantly reduced the risk of developing first SSE [HR, 0.78; 95% confidence interval (CI) 0.66-0.93; P = 0.005] and first and subsequent SSEs (rate ratio, 0.78; 95% CI 0.65-0.92; P = 0.004) compared with zoledronic acid. The treatment differences in the number of patients with SSEs or SREs were similar (n = 48 and n = 45, respectively). Among patients with no/mild pain at baseline, both SSEs and SREs were associated with moderate/severe pain development (P < 0.0001). Fewer patients had skeletal complications, particularly fractures, when defined as SSE versus SRE. CONCLUSION: In patients with CRPC and bone metastases, denosumab reduced the risk of skeletal complications versus zoledronic acid regardless of whether the end point was defined as SSE or SRE.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Neoplasms/secondary , Denosumab/therapeutic use , Prostatic Neoplasms, Castration-Resistant/pathology , Aged , Bone Neoplasms/complications , Double-Blind Method , Humans , Male , Middle Aged
19.
Prostate Cancer Prostatic Dis ; 17(4): 320-4, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25179591

ABSTRACT

BACKGROUND: Bicalutamide is a widely used, relatively non-toxic anti-androgen, particularly when used in combination with androgen deprivation. In men on combined androgen blockade (CAB), the typical dose is 50 mg per day. For men receiving monotherapy with bicalutamide anti-androgen, the dose is 150 mg per day. The objective was to determine the PSA response rate to increasing bicalutamide to 150 mg per day in men who develop castrate-resistant prostate cancer (CRPC) on CAB with goserelin acetate and bicalutamide 50 mg per day. METHODS: A national, multicentre, phase 2, open-label study in men on CAB with a rising PSA>2.0. The primary end point of the trial was PSA response at 12 months, defined as a decline by 50% or more compared with baseline value. Partial response was defined as a PSA decline of 10-49%. Secondary end points were duration of PSA response, change in slope of serum PSA, change in ratio of free PSA: total PSA at 3 months, 6 months and 12 months as compared with baseline; duration of the bicalutamide withdrawal response after discontinuation; the rate of cardiovascular events; and toxicity. The study was initially planned to accrue 100 patients, but was closed early due to diminishing accrual. RESULTS: Sixty-four patients were accrued; 61 patients received trial treatment and constituted the intention-to-treat (ITT) cohort. 70% were M0. Among 59 evaluable ITT patients, 13 (22%) patients had a >50% PSA decline, 5 (8%) had a decline between 10 and 50%, 4 (7%) had stabilization and 37 (63%) had PSA progression. The median duration was 3.7 months (95% confidence interval of 0.92-6.21 months). CONCLUSION: In patients with early biochemical failure on CAB with bicalutamide 50 mg, an increase in dose to 150 mg of bicalutamide resulted in a PSA response of ⩾ 50% in 22% of patients. Toxicity was mild. Bicalutamide dose intensification may benefit a subset of patients with CRPC. We believe this relatively inexpensive approach warrants further evaluation.


Subject(s)
Androgen Antagonists/administration & dosage , Anilides/administration & dosage , Drug Resistance, Neoplasm/drug effects , Nitriles/administration & dosage , Prostatic Neoplasms/drug therapy , Tosyl Compounds/administration & dosage , Aged , Aged, 80 and over , Androgen Antagonists/adverse effects , Anilides/adverse effects , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Canada , Dose-Response Relationship, Drug , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Nitriles/adverse effects , Prostate-Specific Antigen/blood , Prostatic Neoplasms/mortality , Tosyl Compounds/adverse effects
20.
HNO ; 62(1): 41-3, 2014 Jan.
Article in German | MEDLINE | ID: mdl-23515593

ABSTRACT

A 16-year-old patient presented with recurrent cervical swelling to the right side of the neck on coughing and sneezing. Although present since childhood, the symptoms had progressed over the preceding year. Immediately prior to this period a bilateral tonsillectomy had been performed for recurrent tonsillitis. Magnetic resonance imaging revealed a complete lateral cervical fistula extending between the thyroid and submandibular glands on the right side of the neck. Successful surgical resection accomplished complete removal of the fistula.


Subject(s)
Edema/etiology , Fistula/etiology , Submandibular Gland Diseases/etiology , Thyroid Diseases/etiology , Tonsillectomy/adverse effects , Adolescent , Edema/pathology , Edema/prevention & control , Female , Fistula/diagnosis , Fistula/surgery , Humans , Neck/surgery , Reoperation , Submandibular Gland Diseases/diagnosis , Submandibular Gland Diseases/surgery , Thyroid Diseases/diagnosis , Thyroid Diseases/surgery , Treatment Outcome
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