Treatment of Extramedullary Myeloid Sarcoma With Radiotherapy.

Myeloid sarcoma is a rare pathology with important clinical implications. In this paper, we report the case of a 95-year-old gentleman with an orbital mass, which was later confirmed to be a myeloid sarcoma. We also discuss the role of radiotherapy in regard to this diagnosis in patients.

Duodenal somatostatinoma presenting as obstructive jaundice with the coexistence of a gastrointestinal stromal tumour in neurofibromatosis type 1: a case with review of the literature.

Somatostatinomas are rare neuroendocrine tumours, mostly located in the pancreas or duodenum, with an estimated incidence of 1 in 40 million. Duodenal somatostatinomas (DSs) are usually found in association with neurofibromatosis type 1 (NF1), tuberous sclerosis and Von Hippel-Lindau syndrome. Gastrointestinal stromal tumours (GIST) have also been described in NF1, but the association with somatostatinoma is very uncommon. We report the case of a patient with NF1 who presented with obstructive jaundice due to multiple firm nodules around the ampulla of Vater. A pancreaticoduodenectomy was performed and revealed a 1 cm duodenal/ampullary mass which stained positive for somatostatin, together with a GIST also found on the duodenal wall. Despite its rarity, ampullary somatostatinomas should be considered in the differential diagnosis of biliary tract dilation in patients with NF1.

Diagnosis and Management of an Adenomatoid Uterine Tumor: Ultrasound, Magnetic Resonance Imaging, Surgical Appearance, and Pathology Correlation.

Adenomatoid uterine tumors are rare, and their appearance on medical imaging modalities is not well established. We present a case of an adenomatoid uterine tumor reviewing a unique sonographic presentation, magnetic resonance imaging (MRI), gross surgical appearance of the tumor, and microscopic pathology images. A 29-year-old gravida 0 Caucasian woman presented with dysmenorrhea, menorrhagia, and desire to conceive. Transvaginal ultrasound revealed a 2.7 cm round, well-circumscribed posterior intramural uterine mass. The mass was hyperechoic centrally with a thin hypoechoic rim. Color Doppler imaging revealed a prominent vascular rim around the periphery of the mass as well as central vascularity not typical for a leiomyoma. MRI, with and without intravenous gadolinium, was obtained showing a 2.7 cm posterior fundal mildly enhancing uterine mass suggestive of leiomyoma. The mass had a heterogeneous signal pattern on T2-weighted images, and no fat component was noted within the mass. Repeat transvaginal ultrasound showed interval growth of the mass to 3.5 cm with a lipomatous appearance. Adenomatoid uterine tumors are rare and may be mistaken for uterine leiomyomata. Unique features include sonographic appearance of central hyperechogenicity with a hypoechoic rim and prominent peripheral and central vascularity in conjunction with MRI revealing a heterogeneous signal pattern on T2-weighted images without fat component. Gross surgical appearance reveals a nondiscrete capsule and secretion of mucoid material when the mass is exposed. We present a case of adenomatoid tumor providing sonographic, MRI, surgical, and pathological correlation. The patient subsequently conceived spontaneously and delivered at term by cesarean section. The patient underwent a preoperative evaluation with complete blood count, comprehensive metabolic panel, blood type with antibody screen, and pregnancy test. She underwent laparoscopic excision with robotic assistance for removal of the tumor. Grossly, the uterine mass had a very soft consistency atypical for a uterine leiomyoma making dissection more challenging. During dissection the mass diffusely secreted a mucoid material although the capsule was not disrupted. The lesion was excised intact and was removed from the peritoneal cavity in an endocatch bag without internal morcellation. Microscopic examination revealed an adenomatoid tumor.

The prevalence of viral agents in esophageal adenocarcinoma and Barrett's esophagus: a systematic review.

BACKGROUND AND AIMS: Human papilloma virus (HPV), which may reach the esophagus through orogenital transmission, has been postulated to be associated with esophageal adenocarcinoma (EAC). A systematic review of the literature investigating the prevalence of infectious agents in EAC and Barrett's esophagus (BE) was carried out. METHODS: Using terms for viruses and EAC, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until June 2016 that assessed the prevalence of viral agents in EAC or BE. Random-effects meta-analyses of proportions were carried out to calculate the pooled prevalence and 95% confidence intervals (CIs) of infections in EAC and BE. RESULTS: A total of 30 studies were included. The pooled prevalence of HPV in EAC tumor samples was 13% (n=19 studies, 95% CI: 2-29%) and 26% (n=6 studies, 95% CI: 3-59%) in BE samples. HPV prevalence was higher in EAC tissue than in esophageal tissue from healthy controls (n=5 studies, pooled odds ratio=3.31, 95% CI: 1.15-9.50). The prevalence of Epstein-Barr virus (EBV) in EAC was 6% (n=5, 95% CI: 0-27%). Few studies have assessed other infectious agents. For each of the analyses, considerable between-study variation was observed (I=84-96%); however, sensitivity analyses did not show any major sources of heterogeneity. CONCLUSION: The prevalence of HPV and EBV in EAC is low compared with other viral-associated cancers, but may have been hampered by small sample sizes and detection methods susceptible to fixation processes. Additional research with adequate sample sizes and high-quality detection methods is required.

Establishment and preliminary outcomes of a palliative care research network.

OBJECTIVE: The difficulties in conducting palliative care research have been widely acknowledged. In order to generate the evidence needed to underpin palliative care provision, collaborative research is considered essential. Prior to formalizing the development of a research network for the state of Victoria, Australia, a preliminary study was undertaken to ascertain interest and recommendations for the design of such a collaboration. METHOD: Three data-collection strategies were used: a cross-sectional questionnaire, interviews, and workshops. The questionnaire was completed by multidisciplinary palliative care specialists from across the state (n = 61); interviews were conducted with senior clinicians and academics (n = 21) followed by two stakeholder workshops (n = 29). The questionnaire was constructed specifically for this study, measuring involvement of and perceptions of palliative care research. RESULTS: Both the interview and the questionnaire data demonstrated strong support for a palliative care research network and aided in establishing a research agenda. The stakeholder workshops assisted with strategies for the formation of the Palliative Care Research Network Victoria (PCRNV) and guided the development of the mission and strategic plan. SIGNIFICANCE OF RESULTS: The research and efforts to date to establish the PCRNV are encouraging and provide optimism for the evolution of palliative care research in Australia. The international implications are highlighted.

Maxillary sinus inflammatory myofibroblastic tumors: a review and case report.

An inflammatory myofibroblastic tumor (IMT) is an immunohistochemically diverse entity demonstrating neoplastic and nonneoplastic qualities. Although IMTs can arise in any area of the body, lesions arising in certain sites, namely, the nasal cavity, paranasal sinuses, and pterygopalatine fossa, demonstrate a heightened neoplastic and invasive potential. Despite case specific complete tumor regression and disease remission in response to pharmacotherapeutics, a subset of IMTs remain resistant to all forms of therapy. We present such a case, a 34-year-old female patient, with a highly resistant, maxillary sinus IMT. Her refractory, ALK-1 negative IMT has not responded well to novel therapies reported in current literature. This case suggests the role of zonal expressivity within a single lesion as a probable mechanism for its highly resistant nature and should promote determination of each IMT's cytogenetic profile to provide more effective targeted therapy. Paper includes a literature review of all maxillary sinus IMTs from 1985 to 2014 along with their immunohistochemical staining, treatments, and outcomes.

Effects of the probiotic Lactobacillus animalis in murine Mycobacterium avium subspecies paratuberculosis infection.

BACKGROUND: MAP is a suspected zoonotic pathogen and the causative agent of Johne's Disease in cattle and other ruminant animals. With over $1 billion dollars in loss to the dairy industry due to Johne's Disease, efforts to eliminate or reduce MAP from cattle are of importance. The purpose of this study was to determine if daily intake of probiotics could eliminate or reduce Johne's Disease associated symptoms and pathogenesis by MAP. Post infection, animals are often asymptomatic carriers with limited shedding of the pathogen, proving early detection to be difficult. Disease and symptoms often appear 3-4 years after infection with antibiotic treatment proving ineffective. Symptoms include chronic gastrointestinal inflammation leading to severe weight-loss from poor feed and water intake cause a wasting disease. These symptoms are similar to those found in individuals with Crohn's Disease (CD); MAP has been implicated by not proven to be the causative agent of CD. Probiotics administered to livestock animals, including dairy and beef cattle have demonstrated improvements in cattle performance and health. Our objectives included determining the benefits of Lactobacillus animalis (strain name: NP-51) in MAP infected BALB/c mice by evaluating systemic and gastrointestinal response by the host and gut microbiota. Male and female animals were fed 1×106 CFU/g probiotics in sterile, powdered mouse chow daily and infected with 1 × 107 CFU/ml MAP and compared to controls. Animals were evaluated for 180 days to assess acute and chronic stages of disease, with sample collection from animals every 45 days. MAP concentrations from liver and intestinal tissues were examined using real time-PCR methods and the expression of key inflammatory markers were measured during MAP infection (interferon-gamma [IFN-Υ], Interleukin-1α, IL-12, IL-10, IL-6, and Tumor necrosis factor alpha [TNF-α]). RESULTS: Our results demonstrate administration of probiotics reduces production of IFN-Υ and IL-6 while increasing TNF-α and IL-17 in chronic disease; healthful immune responses that reduce chronic inflammation associated to MAP infection. CONCLUSIONS: We observed that the immune system's response in the presence of probiotics to MAP contributes towards host health by influencing the activity of the immune system and gut microbial populations.

Green tea polyphenols and 1-α-OH-vitamin D3 attenuate chronic inflammation-induced myocardial fibrosis in female rats.

Studies have suggested that 1-α-OH-vitamin D3 and green tea polyphenols (GTPs) are promising dietary supplements for mitigating chronic inflammation-induced fibrosis of vessels because of their anti-inflammatory properties. This study evaluated (1) the impact of 1-α-OH-vitamin D3 on myocardial fibrosis in female rats with chronic inflammation and (2) if 1-α-OH-vitamin D3 and GTPs have an additive or synergistic effect to attenuate myocardial fibrosis in these female rats. A 3-month study of a 2 (no 1-α-OH-vitamin D3 vs. 0.05 µg/kg 1-α-OH-vitamin D3, five times per week) ×2 (no GTPs vs. 0.5% GTPs in drinking water) factorial design in lipopolysaccharide (LPS)-administered female rats was performed. Additionally, a group receiving placebo administration was used to compare with a group receiving LPS administration only to evaluate the effect of LPS. Masson's Trichrome staining evaluated myocardial fibrosis in coronary vessels and surrounding myocardium. Spleen cyclooxygenase-2 mRNA expression was determined by real-time polymerase chain reaction. Total lipid profiles were also determined. Whole blood was used for differential cell counts. Data were analyzed by two-way analysis of variance followed by mean separation procedures. At 3 months LPS administration induced myocardial fibrosis in vessels and surrounding myocardium, spleen cyclooxygenase-2 mRNA expression, and elevated leukocyte counts, whereas both 1-α-OH-vitamin D3 administration and GTPs supplementation significantly attenuated these pro-inflammatory events. The inhibitory effects of 1-α-OH-vitamin D3 and GTPs seem to be an individual effect, instead of an additive or synergistic effect. 1-α-OH-vitamin D3 and GTPs lowered red blood cell counts, hematocrit, and hemoglobin. Neither 1-α-OH-vitamin D3 nor GTPs affected lipid profiles. In summary, both 1-α-OH-vitamin D3 administration and GTPs supplementation mitigate myocardial fibrosis through suppression of a chronic inflammation innate immune response.

Green tea polyphenols avert chronic inflammation-induced myocardial fibrosis of female rats.

OBJECTIVE: Green tea proposes anti-inflammatory properties which may attenuate chronic inflammation-induced fibrosis of vessels. This study evaluated whether green tea polyphenols (GTP) can avert fibrosis or vascular disruption along with mechanisms in rats with chronic inflammation. TREATMENTS: Forty 3-month-old female rats were assigned to a 2 (placebo vs. lipopolysaccharide, administration) × 2 (no GTP vs. 0.5% GTP in drinking water) factorial design for 12 weeks. METHODS: Masson's trichrome staining evaluated myocardial fibrosis in coronary vessels and surrounding myocardium. Whole blood specimens were counted for differentials. Spleen tumor necrosis factor-α (TNF-α) mRNA expression was determined by real-time RT-PCR. Data were analyzed by two-way analysis of variance (ANOVA) followed by mean separation procedures. RESULTS: After 12 weeks, lipopolysaccharide administration induced myocardial fibrosis in vessels and surrounding myocardium, spleen TNF-α mRNA expression, and leukocytes, while GTP supplementation in drinking water significantly averted such observation. CONCLUSIONS: GTP attenuates myocardial fibrosis through a suppression of chronic inflammation and innate immune responses.

High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila.

High-fat-diet (HFD)-induced obesity is a major contributor to diabetes and cardiovascular disease, but the underlying genetic mechanisms are poorly understood. Here, we use Drosophila to test the hypothesis that HFD-induced obesity and associated cardiac complications have early evolutionary origins involving nutrient-sensing signal transduction pathways. We find that HFD-fed flies exhibit increased triglyceride (TG) fat and alterations in insulin/glucose homeostasis, similar to mammalian responses. A HFD also causes cardiac lipid accumulation, reduced cardiac contractility, conduction blocks, and severe structural pathologies, reminiscent of diabetic cardiomyopathies. Remarkably, these metabolic and cardiotoxic phenotypes elicited by HFD are blocked by inhibiting insulin-TOR signaling. Moreover, reducing insulin-TOR activity (by expressing TSC1-2, 4EBP or FOXO), or increasing lipase expression-only within the myocardium-suffices to efficiently alleviate cardiac fat accumulation and dysfunction induced by HFD. We conclude that deregulation of insulin-TOR signaling due to a HFD is responsible for mediating the detrimental effects on metabolism and heart function.

A systematic review of instruments related to family caregivers of palliative care patients.

Support for family caregivers is a core function of palliative care. However, there is a lack of consistency in the way needs are assessed, few longitudinal studies to examine the impact of caregiving, and a dearth of evidence-based interventions. In order to help redress this situation, identification of suitable instruments to examine the caregiving experience and the effectiveness of interventions is required. A systematic literature review was undertaken incorporating representatives of the European Association for Palliative Care's International Palliative Care Family Caregiver Research Collaboration and Family Carer Taskforce. The aim of the review was to identify articles that described the use of instruments administered to family caregivers of palliative care patients (pre and post-bereavement). Fourteen of the 62 instruments targeted satisfaction with service delivery and less than half were developed specifically for the palliative care context. In approximately 25% of articles psychometric data were not reported. Where psychometric results were reported, validity data were reported in less than half (42%) of these cases. While a considerable variety of instruments have been administered to family caregivers, the validity of some of these requires further consideration. We recommend that others be judicious before developing new instruments for this population.

Surgical team behaviors and patient outcomes.

BACKGROUND: Little evidence exists that links teamwork to patient outcomes. We conducted this study to determine if patients of teams with good teamwork had better outcomes than those with poor teamwork. METHODS: Observers used a standardized instrument to assess team behaviors. Retrospective chart review was performed to measure 30-day outcomes. Multiple logistic regressions were calculated to assess the independence of the association between teamwork with patient outcome after adjusting for American Society of Anesthesiologists (ASA) score. RESULTS: In univariate analyses, patients had increased odds of complications or death when the following behaviors were exhibited less frequently: information sharing during intraoperative phases, briefing during handoff phases, and information sharing during handoff phases. Composite measures of teamwork across all operative phases were significantly associated with complication or death after adjusting for ASA score (odds ratio 4.82; 95% confidence interval, 1.30-17.87). CONCLUSION: When teams exhibited infrequent team behaviors, patients were more likely to experience death or major complication.

Lung metastasis 21 years after initial diagnosis of osteosarcoma: a case report.

INTRODUCTION: To the best of our knowledge, this case report describes the longest disease-free interval between primary diagnosis and metastatic recurrence of an osteosarcoma. CASE PRESENTATION: A 35-year-old Caucasian American man presented with asymptomatic lung metastases 21 years after being diagnosed and treated for lower extremity osteosarcoma. He underwent curative lung resection, but 2 years thereafter developed metastatic disease in the scapula and tibia and, after resection and chemotherapy, is in remission 1 year later. CONCLUSION: This case highlights the importance of long follow-up periods and continued surveillance of osteosarcoma patients after initial curative treatment.

Implementation of a high-alert medication program.

INTRODUCTION: Greater than 500,000 doses of high-alert medications are administered throughout the Kaiser Permanente Northern California (KPNC) Program on an annual basis. High-alert medications (HAM) carry a higher risk of harm than other medications and errors in the administration of HAM can have catastrophic clinical outcomes. The purpose of this project is to ensure safe medication practices and to eliminate medication errors that cause harm to our patients.The Program: KPNC leadership, physicians, nurses, pharmacists, quality leaders, and labor unions worked with regional and local medication safety committees to: 1) standardize high-alert medication-handling practices; 2) enhance education programs related to medication practices, embedding these into annual core competencies of all staff who handle high-alert medications; 3) develop monitoring functions at both the regional and local levels to ensure sustainability and ongoing systems improvements. Begun in December 2005, this program covers the delivery of high-alert medications across the continuum of care and affects all patients receiving HAM. MEASURES: The initial phase of the monitoring process was put in place to measure compliance with implementation. Over the first few months of the program the 90% minimal threshold was surpassed with regional overall compliance of 95%. Following this initial process, the Regional Medication Safety Committee developed monitoring tools. Department managers carry out these concurrent observational audits at the medical centers with oversight by the Assistant Administrators for Quality and Service. These audits are designed to measure whether or not all medications on the HAM list are handled specifically to policy requirements, eg, independent double-checks, HAM stickers, etc. Audit specifications are provided for each audit tool. Medical Center audit results from the third quarter of 2006 through the third quarter of 2007 have shown a regional aggregate of 97.7% compliance. As the high percentages of compliance have held constant over time, more actionable metrics are being put in place for 2008.To determine whether or not the program is reducing HAM errors, data from the regional Quality and Risk database (MIDAS) related to all high-alert medication errors was reviewed. Two interventions were of note: in July of 2005, there was a renewed effort to educate leaders, managers, physicians, and staff on responsible reporting in a "just culture" and the introduction of the new Responsible Reporting Form. An increase in reporting was noted at this time. In December 2005, the HAM program was introduced. There is a statistically significant drop in errors reported for 23 consecutive months following this program. These findings were similar for all phases of the delivery process. A powerful indicator of improvement is the average days between major injury and death. As of November 30, 2007, it has been 232 days since the last significant negative event was reported due to a HAM. CONCLUSION: This program has been implemented in all of the KPNC Medical Centers and is in the process of being implemented in all KP regions. This spread has been endorsed by the Medical Directors Quality Committee and by the KP Boards of Directors. The Interregional Medication Safety Committee is overseeing the spread process. A toolkit containing all of the required tools plus additional materials and information has been developed and made available throughout KP. The program is the recipient of the 2007 Lawrence Patient Safety Award.

Activated FOXO-mediated insulin resistance is blocked by reduction of TOR activity.

Reducing insulin/IGF signaling allows for organismal survival during periods of inhospitable conditions by regulating the diapause state, whereby the organism stockpiles lipids, reduces fertility, increases stress resistance, and has an increased lifespan. The Target of Rapamycin (TOR) responds to changes in growth factors, amino acids, oxygen tension, and energy status; however, it is unclear how TOR contributes to physiological homeostasis and disease conditions. Here, we show that reducing the function of Drosophila TOR results in decreased lipid stores and glucose levels. Importantly, this reduction of dTOR activity blocks the insulin resistance and metabolic syndrome phenotypes associated with increased activity of the insulin responsive transcription factor, dFOXO. Reduction in dTOR function also protects against age-dependent decline in heart function and increases longevity. Thus, the regulation of dTOR activity may be an ancient "systems biological" means of regulating metabolism and senescence, that has important evolutionary, physiological, and clinical implications.

Characterization of exposure to low levels of viable Penicillium chrysogenum conidia and allergic sensitization induced by a protease allergen extract from viable P. Chrysogenum conidia in mice.

BACKGROUND: Previous evidence by our laboratory has shown that mice inoculated with viable Penicillium Chrysogenum conidia or spores at levels comparable to those found in contaminated buildings induced spore antigen-specific allergic responses. We proposed that mice exposed to low levels of viable P. Chrysogenum conidia would not develop allergic symptoms. We also hypothesized that the symptoms induced by high numbers of conidia were the result of sensitization to allergens released by the conidia. METHODS: C57BL/6 and BALB/c mice were exposed to 1 x 10(2) viable P. Chrysogenum conidia by intranasal instillation weekly for a period of 11 weeks. C57BL/6 mice were also sensitized to a viable P. Chrysogenum conidia protease extract by intraperitoneal injections for a period of 6 weeks followed by intranasal challenge with protease extract, viable, or nonviable P. Chrysogenum conidia for 2 weeks. RESULTS: C57BL/6 mice inoculated with low numbers of conidia developed no significant lung inflammation or increased serum immunoglobulins. Mice sensitized to the protease extract and challenged with both protease extract and viable conidia produced significant increases in serum IgE and IgG1. Mice sensitized to and challenged with the protease extract developed significant eosinophilia and mucus hyperproduction as determined by bronchoalveolar lavage and histopathological examination of lung tissue. CONCLUSIONS: Mice did not develop allergic symptoms in response to challenge with low levels of P. Chrysogenum conidia. Protease allergens from viable conidia induced specific allergic responses in mice, indicating the importance of P. Chrysogenum conidia in allergic sensitization to the organism.

Ceruminous gland adenoid cystic carcinoma with contralateral metastasis to the brain.

We present the case of a 38-year-old man with an adenoid cystic carcinoma originating from the ceruminous glands of the external ear canal. The patient subsequently presented with a contralateral brain mass that was also diagnosed as adenoid cystic carcinoma. To our knowledge, contralateral metastasis to the brain of a patient with an adenoid cystic carcinoma of the ceruminous glands has not been reported previously. This rare neoplasm should be considered in the differential diagnosis of poorly differentiated carcinomas metastatic to the central nervous system in patients with occult malignant neoplasms.