Outcomes and Profiles of Older Patients Receiving Definitive Radiation Therapy for Muscle-Invasive Bladder Cancer at a Tertiary Medical Center.

PURPOSE: Our purpose was to evaluate the outcomes and profiles of older patients with muscle-invasive bladder cancer (MIBC) treated with definitive radiation therapy (RT) with or without chemotherapy (CHT) at a tertiary medical center. METHODS AND MATERIALS: A retrospective study was conducted for older patients with MIBC who were ≥70 years old and underwent RT with or without CHT between 2000 and 2016. Overall survival (OS) was estimated using the Kaplan-Meier method. Disease-specific survival (DSS), cumulative incidence of progression, patterns of recurrence, and toxicities were examined. Univariate analyses were performed to identify variables associated with OS, DSS, and cumulative incidence of progression, using the Cox proportional hazards model. RESULTS: A total of 84 patients underwent definitive RT with or without CHT. Of these, only 29% were deemed medically fit to undergo radical cystectomy, and the remainder were medically unfit or had surgically unresectable disease. Median age was 81 years. Sixty-one percent, 29%, and 11% had clinical stage II, III, and IV disease, respectively. Eighty-six percent had maximal transurethral resection of bladder tumor before RT. Seventy-three percent received CHT with RT, and 27% had RT alone. Median follow-up was 5.7 years. Median OS was 1.9 years. OS was 42% and 25%, and DSS was 64% and 54% at 3 and 5 years, respectively. On univariate analysis, medical fitness to undergo radical cystectomy, receipt of CHT, lower T stage, and maximal transurethral resection of bladder tumor were associated with better OS; lower T stage was associated with better DSS. The cumulative incidence of progression was 44% and 49% at 3 and 5 years, respectively. Late grade 3 genitourinary and gastrointestinal toxicity were 15% and 4%, respectively. None had grade 4 or 5 toxicity. CONCLUSIONS: Older patients with MIBC referred for RT were often medically unfit or had a surgically unresectable tumor. In these medically compromised patients, definitive RT with or without CHT was well tolerated and yielded encouraging treatment outcomes.

Isolated peripancreatic necrosis (PPN) is associated with better clinical outcomes compared with combined pancreatic and peripancreatic involvement (CPN)- a systematic review and meta-analysis.

BACKGROUND AND AIMS: Peripancreatic necrosis (PPN) is considered as a distinct entity with a better outcome when compared with combined pancreatic and peripancreatic necrosis (CPN), but there is no systematic review to summarize the evidence. Our study aimed to perform a meta-analysis of existing observational studies comparing the outcomes of PPN with CPN. METHODS: Studies in adult patients comparing the outcomes of PPN and CPN from PubMed, Medline, and Scopus databases from inception to November 2018 were systematically searched. The primary outcome was mortality, and secondary outcomes included multi-organ failure, persistent organ failure, infected necrosis, need for interventions including open necrosectomy. Pooled adjusted odds ratios, and 95% confidence intervals (CI) were obtained by the random-effects model. Forrest plots were constructed to show the summary pooled estimate. Heterogeneity was assessed by using I2 measure of inconsistency. RESULTS: A total of 6 studies involving 1851 patients (1295 (70%) with CPN and 556 (30%) with PPN) were included. Patients with CPN had a significantly higher mortality (OR 2.49, 95% CI: 1.61-3.87), risk for multi-organ failure (OR 3.24, 95% CI: 2.38-4.43), persistent organ failure (OR 2.79, 95% CI: 1.53-5.08), and infected necrosis (OR 6.21, 95% CI: 3.85-10.03). They underwent more interventions (OR 5.86, 95% CI: 3.69-9.32), including open necrosectomy (OR 5.04, 95% CI: 3.33-7.63). Heterogeneity was low (I2 = 18.1, p = 0.296), and there was no publication bias. CONCLUSION: Isolated peripancreatic necrosis portends an overall better prognosis when compared to necrosis involves pancreatic parenchyma. Clinicians should recognize this distinction for management decisions.

Long-Term Embolic Outcomes After Detection of Left Ventricular Thrombus by Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Imaging: A Matched Cohort Study.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is more sensitive than echocardiography for the detection of intracardiac thrombus because of its unique ability to identify thrombus based on tissue characteristics related to avascularity. The long-term prognostic significance of left ventricular (LV) thrombus detected by LGE CMR is unknown. METHODS: We performed a matched cohort study of consecutive adult patients with LV thrombus detected by LGE CMR who were matched on the date of CMR, age, and LV ejection fraction to up to 3 patients without LV thrombus. We investigated the long-term incidence of a composite of embolic events: stroke, transient ischemic attack, or extracranial systemic arterial embolism. We also compared outcomes among patients with LV thrombus detected by LGE CMR stratified by whether the LV thrombus was also detected by echocardiography or not. RESULTS: Of 157 LV thrombus patients, 155 were matched to 400 non-LV thrombus patients. During a median follow-up of 3.3 years, the cumulative incidence of embolism was significantly higher in LV thrombus patients compared with the matched non-LV thrombus patients (P<0.001), with annualized rates of 3.7% and 0.8% for LV thrombus and matched non-LV thrombus patients, respectively. LV thrombus was the only independent predictor of the composite embolic end point (hazard ratio, 3.99 [95% CI, 1.54-10.35]; P=0.004). The cumulative incidence of embolism was not different in patients with LV thrombus that was also detected by echocardiography versus patients with LV thrombus not detected by echocardiography (P=0.25). CONCLUSIONS: Despite contemporary antithrombotic treatment, LV thrombus detected by LGE CMR is associated with a 4-fold higher long-term incidence of embolism compared with matched non-LV thrombus patients. LV thrombus detected by LGE CMR but not by echocardiography is associated with a similar risk of embolism as that detected by both LGE CMR and echocardiography.

Proton Therapy for Stage IIA-B Seminoma: A New Standard of Care for Treating Retroperitoneal Nodes.

Currently there has been no published report describing the use of proton beam therapy for stage II testicular seminoma. A 31-year-old man presenting with a right testicular mass and a 2.7-cm aortocaval lymph node received a diagnosis of stage IIB testicular seminoma. He was treated with scanning proton beam therapy, as a means of improving the therapeutic ratio of radiation therapy over conventionally used x-ray radiation therapy. The patient achieved a complete response and remained free of relapse at 15 months post proton beam therapy. The advantageous dose deposition characteristics of proton beam, allowing much lower radiation doses to normal tissues, should be exploited when radiation therapy is applied for stage II testicular seminoma or for an isolated retroperitoneal lymph node relapse of stage I disease initially managed with surveillance.

Increased expression of ADAMTS13 mRNA correlates with ischemic cerebrovascular disease in systemic lupus erythematosus patients.

OBJECTIVE: We investigated ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif, member 13) messenger RNA levels as a biomarker of disease features in systemic lupus erythematosus. METHODS: We measured and compared messenger RNA (mRNA) levels of ADAMTS13 in peripheral blood cells in patients with systemic lupus erythematosus and healthy control subjects by whole-genome microarray. We retrospectively analyzed the correlations of ADAMTS13 mRNA expression with clinical features, laboratory parameters, therapeutic features, and disease activity (according to the Systemic Lupus Erythematosus Disease Activity Index). We also examined the association of three single nucleotide polymorphisms (rs4962145, rs2285467, and rs685523) of the ADAMTS13 gene with patient characteristics. RESULTS: In 309 patients, the median ADAMTS13 mRNA expression levels were significantly higher in blood cells of systemic lupus erythematosus patients than in 23 healthy controls (p = .03). Notably, ADAMTS13 mRNA expression levels were significantly higher in systemic lupus erythematosus patients with a history of stroke (p = .02) or transient ischemic attack (p = .02). Among the three single nucleotide polymorphisms analyzed, rs2285467 was significantly associated with stroke (p = .03) and anticardiolipin antibodies (p = .04). CONCLUSIONS: Increased expression of ADAMTS13 mRNA in blood cells is associated with the presence of ischemic cerebrovascular disease in systemic lupus erythematosus patients and suggests a potential role for ADAMTS13 in the pathogenesis of ischemic cerebrovascular disease in these patients.

Vitamin D insufficiency is common in patients with nonmetastatic prostate cancer.

Because an inverse relationship between serum 25-hydroxyvitamin D (25[OH]D) levels and the risk of prostate cancer has been suggested, it was hypothesized that vitamin D insufficiency would be common in patients with prostate cancer. To test the hypothesis, an exploratory study was conducted to examine serum 25(OH)D levels in a cohort of patients with nonmetastatic prostate cancer. The study aim was to assess the prevalence of vitamin D insufficiency in these patients. Vitamin D insufficiency was defined as serum 25(OH)D less than 75 nmol/L. Serum 25(OH)D levels measured prospectively at baseline and, then, yearly during a 5-year follow-up were analyzed. Various parameters were examined to assess their possible association with vitamin D insufficiency at baseline, using both a univariate analysis and a logistic regression model. Analyses including descriptive statistics for all variables were carried out with SAS version 9.1 (SAS Institute, Cary, NC). A total of 106 patients were available for analysis. The median age was 66.3 years. At baseline, mean and median vitamin D level was 72.4 and 70.0 nmol/L, respectively. Sixty-four patients (60.4%) met the definition of vitamin D insufficiency with serum 25(OH)D less than 75 nmol/L. Forty (37.7%), 20 (18.9%), and 2 patients (1.9%) had serum 25(OH)D less than 62.5, less than 50, and less than 25 nmol/L, respectively. On a logistic regression model, season was the only significant variable associated with vitamin D insufficiency. Of a total 477 serum 25(OH)D measurements from the baseline and yearly follow-ups, 187 (39.2%) met the definition of vitamin D insufficiency. In conclusion, vitamin D insufficiency was prevalent among patients with nonmetastatic prostate cancer.

Can radiotherapy be a viable salvage treatment option for the relapsed seminoma confined to the infra-diaphragm region recurring after primary chemotherapy for bulky stage II seminoma?

There has been a paucity of research describing a potential role of radiotherapy as salvage treatment for recurrent seminoma following primary chemotherapy for bulky stage IIC seminoma. We report a case of a bulky stage IIC seminoma relapsed in the pelvis after primary chemotherapy and surgery for post-chemotherapy residual mass, which was subsequently salvaged with radiotherapy. The patient has remained free of relapse at 3.7 years post-salvage radiotherapy. This case demonstrates that radiotherapy can be a salvage therapeutic option for recurrent seminoma following primary chemotherapy for bulky stage IIC seminoma, provided that the recurrent tumour is confined to a limited area of the infradiaphragmatic region. There is a need for further study to examine the potential role of radiotherapy as a salvage therapeutic tool for post-chemotherapy recurrent seminoma.

Neurotensin receptor type 1 regulates ethanol intoxication and consumption in mice.

Neurotensin receptor type 1 (NTS1) is known to mediate a variety of biological functions of neurotensin (NT) in the central nervous system. In this study, we found that NTS1 null mice displayed decreased sensitivity to the ataxic effect of ethanol on the rotarod and increased ethanol consumption when given a free choice between ethanol and tap water containing bottles. Interestingly, the administration of NT69L, a brain-permeable NT analog, increased ethanol sensitivity in wild-type littermates but had no such effect in NTS1 null mice, suggesting that NTS1 contributes to NT-mediated ethanol intoxication. Furthermore, the daily treatment of NT69L, for 4 consecutive days, significantly reduced alcohol preference and consumption in wild-type littermates but had no such effects in NTS1 null mice in a two-bottle drinking experiment. Our study provides evidence for possible pharmacological roles of NT69L in which it increases sensitivity to the ataxic effect, and decreases voluntary consumption, of ethanol. Our study also demonstrates NTS1-mediated behavioral effects of NT69L. Therefore, our findings will be useful for understanding some aspects of alcoholism as well as to develop novel pharmacological therapeutic options for humans.