17 research outputs found
Primary splenic lymphoma presenting with ascites
An 84 year-old gentleman presented with abdominal distension, anorexia and occasional epigastric pain over a four-week period. Blood parameters revealed a hypochromic microcytic anaemia. Both CT and US scan identified ascites and a mass in the left upper quadrant. An ascitic tap was performed identifying bloody ascites and the presence of reactive mesothelial cells on cytology. A subsequent laparotomy and splenectomy was performed. Histology of the resected spleen revealed a Grade 2 follicular lymphoma (Figure 2). The patient had an uneventful postoperative recovery and was well at 6 months follow up. The spleen is an organ with an important immunological function. Primary splenic involvement occurs in less than 1% of non-hodgkin’s lymphoma. Symptoms of primary splenic lymphoma (PSL) include pyrexia, weight-loss, night sweats, generalised weakness and left upper quadrant pain secondary to spleno - megaly. Ascites is a rare presenting feature of PSL. This report illustrates a case of primary splenic lymphoma which poses diagnostic challenges for the pathologist and clinician and ultimately requires definitive splenectomy to confirm a diagnosis
Modern management of pyogenic hepatic abscess: a case series and review of the literature
<p>Abstract</p> <p>Background</p> <p>Pyogenic hepatic abscesses are relatively rare, though untreated are uniformly fatal. A recent paradigm shift in the management of liver abscesses, facilitated by advances in diagnostic and interventional radiology, has decreased mortality rates. The aim of this study was to review our experience in managing pyogenic liver abscess, review the literature in this field, and propose guidelines to aid in the current management of this complex disease.</p> <p>Methods</p> <p>Demographic and clinical details of all patients admitted to a single institution with liver abscess over a 5 year period were reviewed. Clinical presentation, aetiology, diagnostic work-up, treatment, morbidity and mortality data were collated.</p> <p>Results</p> <p>Over a 5 year period 11 patients presented to a single institution with pyogenic hepatic abscess (55% males, mean age 60.3 years). Common clinical features at presentation were non-specific constitutional symptoms and signs. Aetiology was predominantly gallstones (45%) or diverticular disease (27%). In addition to empiric antimicrobial therapy, all patients underwent radiologically guided percutaneous drainage of the liver abscess at diagnosis and only 2 patients required surgical intervention, including one 16-year old female who underwent hemi-hepatectomy for a complex and rare Actinomycotic abscess. There were no mortalities after minimum follow-up of one year.</p> <p>Conclusions</p> <p>Pyogenic liver abscesses are uncommon, and mortality has decreased over the last two decades. Antimicrobial therapy and radiological intervention form the mainstay of modern treatment. Surgical intervention should be considered for patients with large, complex, septated or multiple abscesses, underlying disease or in whom percutaneous drainage has failed.</p
Different mechanisms for resistance to trastuzumab versus lapatinib in HER2- positive breast cancers -- role of estrogen receptor and HER2 reactivation
Introduction: The human epidermal growth factor receptor 2 (HER2)-targeted therapies trastuzumab (T) and lapatinib (L) show high efficacy in patients with HER2-positive breast cancer, but resistance is prevalent. Here we investigate resistance mechanisms to each drug alone, or to their combination using a large panel of HER2-positive cell lines made resistant to these drugs.
Methods: Response to L + T treatment was characterized in a panel of 13 HER2-positive cell lines to identify lines that were de novo resistant. Acquired resistant lines were then established by long-term exposure to increasing drug concentrations. Levels and activity of HER2 and estrogen receptor (ER) pathways were determined by qRT-PCR, immunohistochemistry, and immunoblotting assays. Cell growth, proliferation, and apoptosis in parental cells and resistant derivatives were assessed in response to inhibition of HER or ER pathways, either pharmacologically (L, T, L + T, or fulvestrant) or by using siRNAs. Efficacy of combined endocrine and anti-HER2 therapies was studied in vivo using UACC-812 xenografts.
Results: ER or its downstream products increased in four out of the five ER+/HER2+ lines, and was evident in one of the two intrinsically resistant lines. In UACC-812 and BT474 parental and resistant derivatives, HER2 inhibition by T reactivated HER network activity to promote resistance. T-resistant lines remained sensitive to HER2 inhibition by either L or HER2 siRNA. With more complete HER2 blockade, resistance to L-containing regimens required the activation of a redundant survival pathway, ER, which was up-regulated and promoted survival via various Bcl2 family members. These L-and L + T-resistant lines were responsive to fulvestrant and to ER siRNA. However, after prolonged treatment with L, but not L + T, BT474 cells switched from depending on ER as a survival pathway, to relying again on the HER network (increased HER2, HER3, and receptor ligands) to overcome L's effects. The combination of endocrine and L + T HER2-targeted therapies achieved complete tumor regression and prevented development of resistance in UACC-812 xenografts.
Conclusions: Combined L + T treatment provides a more complete and stable inhibition of the HER network. With sustained HER2 inhibition, ER functions as a key escape/survival pathway in ER-positive/HER2-positive cells. Complete blockade of the HER network, together with ER inhibition, may provide optimal therapy in selected patients
The race for Ebola drugs: pharmaceuticals, security and global health governance
The international Ebola response mirrors two broader trends in global health governance: (1) the framing of infectious disease outbreaks as a security threat; and (2) a tendency to respond by providing medicines and vaccines. This article identifies three mechanisms that interlink these trends. First, securitisation encourages technological policy responses. Second, it creates an exceptional political space in which pharmaceutical development can be freed from constraints. Third, it creates an institutional architecture that facilitates pharmaceutical policy responses. The ways in which the securitisation of health reinforces pharmaceutical policy strategies must, the article concludes, be included in ongoing efforts to evaluate them normatively and politically
Modern management of pyogenic hepatic abscess: a case series and review of the literature
Background
Pyogenic hepatic abscesses are relatively rare, though untreated are uniformly fatal. A recent paradigm shift in the management of liver abscesses, facilitated by advances in diagnostic and interventional radiology, has decreased mortality rates. The aim of this study was to review our experience in managing pyogenic liver abscess, review the literature in this field, and propose guidelines to aid in the current management of this complex disease.
Methods
Demographic and clinical details of all patients admitted to a single institution with liver abscess over a 5 year period were reviewed. Clinical presentation, aetiology, diagnostic work-up, treatment, morbidity and mortality data were collated.
Results
Over a 5 year period 11 patients presented to a single institution with pyogenic hepatic abscess (55% males, mean age 60.3 years). Common clinical features at presentation were non-specific constitutional symptoms and signs. Aetiology was predominantly gallstones (45%) or diverticular disease (27%). In addition to empiric antimicrobial therapy, all patients underwent radiologically guided percutaneous drainage of the liver abscess at diagnosis and only 2 patients required surgical intervention, including one 16-year old female who underwent hemi-hepatectomy for a complex and rare Actinomycotic abscess. There were no mortalities after minimum follow-up of one year.
Conclusions
Pyogenic liver abscesses are uncommon, and mortality has decreased over the last two decades. Antimicrobial therapy and radiological intervention form the mainstay of modern treatment. Surgical intervention should be considered for patients with large, complex, septated or multiple abscesses, underlying disease or in whom percutaneous drainage has failed.peer-reviewe
Modern management of pyogenic hepatic abscess: a case series and review of the literature
Background
Pyogenic hepatic abscesses are relatively rare, though untreated are uniformly fatal. A recent paradigm shift in the management of liver abscesses, facilitated by advances in diagnostic and interventional radiology, has decreased mortality rates. The aim of this study was to review our experience in managing pyogenic liver abscess, review the literature in this field, and propose guidelines to aid in the current management of this complex disease.
Methods
Demographic and clinical details of all patients admitted to a single institution with liver abscess over a 5 year period were reviewed. Clinical presentation, aetiology, diagnostic work-up, treatment, morbidity and mortality data were collated.
Results
Over a 5 year period 11 patients presented to a single institution with pyogenic hepatic abscess (55% males, mean age 60.3 years). Common clinical features at presentation were non-specific constitutional symptoms and signs. Aetiology was predominantly gallstones (45%) or diverticular disease (27%). In addition to empiric antimicrobial therapy, all patients underwent radiologically guided percutaneous drainage of the liver abscess at diagnosis and only 2 patients required surgical intervention, including one 16-year old female who underwent hemi-hepatectomy for a complex and rare Actinomycotic abscess. There were no mortalities after minimum follow-up of one year.
Conclusions
Pyogenic liver abscesses are uncommon, and mortality has decreased over the last two decades. Antimicrobial therapy and radiological intervention form the mainstay of modern treatment. Surgical intervention should be considered for patients with large, complex, septated or multiple abscesses, underlying disease or in whom percutaneous drainage has failed
A review of expression profiling of circulating micrornas in men with prostate cancer
MicroRNAs (miRNAs) are small non-coding RNAs that are involved in gene regulation and expression. These molecules have been implicated in the pathogenesis of several malignancies.
MiRNAs have the potential to be both a tissue-and blood-based biomarker for cancer diagnosis, classification, prognosis and response to treatment.
The levels of dysregulated miRNAs in the circulation of individuals make miRNAs an ideal biomarker for the detection of prostate cancer.
The present study provides a comprehensive review of the expression profiling of miRNAs in the circulation of men with prostate cancer.
Further research is necessary to identify if circulating miRNAs have the potential to be a biomarker for prostate cancer in clinical practice
A review of expression profiling of circulating micrornas in men with prostate cancer
MicroRNAs (miRNAs) are small non-coding RNAs that are involved in gene regulation and expression. These molecules have been implicated in the pathogenesis of several malignancies.
MiRNAs have the potential to be both a tissue-and blood-based biomarker for cancer diagnosis, classification, prognosis and response to treatment.
The levels of dysregulated miRNAs in the circulation of individuals make miRNAs an ideal biomarker for the detection of prostate cancer.
The present study provides a comprehensive review of the expression profiling of miRNAs in the circulation of men with prostate cancer.
Further research is necessary to identify if circulating miRNAs have the potential to be a biomarker for prostate cancer in clinical practice
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The paradox of MRI for breast cancer screening: high-risk and dense breasts-available evidence and current practice.
In the mid-1990s, the identification of BRCA1/2 genes for breast cancer susceptibility led to testing breast MRI accuracy in screening women at increased risk. From 2000 onwards, ten intraindividual comparative studies showed the marked superiority of MRI: the sensitivity ranged 25-58% for mammography, 33-52% for ultrasound, 48-67% for mammography plus ultrasound, and 71-100% for MRI; specificity 93-100%, 91-98%, 89-98%, and 81-98%, respectively. Based on the available evidence, in 2006-2007, the UK National Institute for Clinical Excellence and the American Cancer Society recommended MRI screening of high-risk women, followed by other international guidelines. Despite evidence-based medicine ideally requiring randomised controlled trials (RCTs) for policy changes regarding screening procedures, breast MRI for high-risk screening was adopted in many countries worldwide. In 2019, the results of the "DENSE" RCT were published in favour of breast MRI screening of women with extremely dense breasts compared to mammography alone, showing a reduction of more than 80% of the interval cancer rate in women who attended MRI screening. Even though international recommendations in favour of this practice were issued, substantial obstacles still prevent health systems from adopting breast MRI for screening women with extremely dense breasts. A paradox is evident: we adopted a screening procedure without evidence from RCTs, and now that we have this level-1 evidence for the same procedure, we fail to do so. This critical review tries to explain the differences between the two cases, as examples of the complex pathways of translating radiological research into everyday practice.Critical relevance statement The high-level evidence in favour of breast MRI screening of women with extremely dense breasts is failing to persuade policy makers to translate this into clinical practice.Key points• Breast MRI screening of high-risk women was adopted on basis of the evidence provided by test accuracy comparative studies showing an MRI performance greatly superior to that of mammography.• Breast MRI screening of women with extremely dense breasts has not been adopted although the evidence of a large reduction in interval cancer rate from a RCT.• We illustrate the differences between the two cases, as an example of the complex ways of translation of radiological research in clinical practice according to the EBM theory