Bevacizumab combined with capecitabine and oxaliplatin in patients with advanced adenocarcinoma of the small bowel or ampulla of vater: A single-center, open-label, phase 2 study

BACKGROUND

Capecitabine with oxaliplatin (CAPOX) has previously demonstrated clinical activity in patients with small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Herein, the authors conducted a phase 2 trial to evaluate the benefit of adding bevacizumab to CAPOX.

METHODS

In this phase 2, single-arm, single-center, open-label study, patients aged ≥18 years with untreated, advanced SBA or AAC were recruited. Patients received capecitabine at a dose of 750 mg/m² orally twice daily on days 1 to 14, oxaliplatin at a dose of 130 mg/m² intravenously on day 1, and bevacizumab at a dose of 7.5 mg/kg intravenously on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary objectives included response rate, overall PFS, overall survival, and toxicity.

RESULTS

Between August 2011 and November 2014, a total of 30 patients were enrolled into the study (male/female ratio of 13/17; median age of 63 years [range, 33-78 years]; and 7 patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 0, 20 patients with an ECOG PS of 1, and 3 patients with an ECOG PS of 2). Of the 30 patients, 23 (77%) had SBA (18 of duodenal origin and 5 of jejunal/ileal origin) and 7 patients (23%) had AAC (5 of pancreaticobiliary subtype, 1 of mixed subtype, and 1 of intestinal subtype). The most common grade 3 toxicities observed were fatigue and hypertension (7 patients each [23%]), neutropenia (6 patients [20%]), and diarrhea (3 patients [10%]) (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). The probability of PFS at 6 months was 68% (95% confidence interval [95% CI], 52% to 88%). The response rate was 48.3%, with 1 complete response and 13 partial responses; 10 patients achieved stable disease. At a median follow-up of 25.9 months, the median PFS was 8.7 months (95% CI, 4.9-10.5 months) and the median overall survival was 12.9 months (95% CI, 9.2-19.7 months).

CONCLUSIONS

The results of the current study indicate that CAPOX with bevacizumab is an active and well-tolerated regimen for patients with SBA and AAC. These findings support the need for further investigation into the clinical benefit of targeting angiogenesis in patients with SBA and AAC. Cancer 2016. © 2016 American Cancer Society.

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Delirium in patients with advanced cancer: Screening to cure or caring to prevent?

http://ift.tt/2g8JPBG

The impact of health insurance on cancer care in disadvantaged communities

BACKGROUND

Individuals from disadvantaged communities are among the millions of uninsured Americans gaining insurance under the Affordable Care Act. The extent to which health insurance can mitigate the effects of the social determinants of health on cancer care is unknown.

METHODS

This study linked the Surveillance, Epidemiology, and End Results registries to US Census data to study patients diagnosed with the 4 leading causes of cancer deaths between 2007 and 2011. A county-level social determinant score was developed with 5 measures of wealth, education, and employment. Patients were stratified into quintiles, with the lowest quintile representing the most disadvantaged communities. Logistic regression and Cox proportional hazards models were used to estimate associations and cancer-specific survival.

RESULTS

A total of 364,507 patients aged 18 to 64 years were identified (134,105 with breast cancer, 106,914 with prostate cancer, 62,606 with lung cancer, and 60,882 with colorectal cancer). Overall, patients from the most disadvantaged communities (median household income, $42,885; patients below the poverty level, 22%; patients completing college, 17%) were more likely to present with distant disease (odds ratio, 1.6; P < .001) and were less likely to receive cancer-directed surgery (odds ratio, 0.8; P < .001) than the least disadvantaged communities (median income, $78,249; patients below the poverty level, 9%; patients completing college, 42%). The differences persisted across quintiles regardless of the insurance status. The effect of having insurance on cancer-specific survival was more pronounced in disadvantaged communities (relative benefit at 3 years, 40% vs 31%). However, it did not fully mitigate the effect of social determinants on mortality (hazard ratio, 0.75 vs 0.68; P < .001).

CONCLUSIONS

Cancer patients from disadvantaged communities benefit most from health insurance, and there is a reduction in disparities in outcome. However, the gap produced by social determinants of health cannot be bridged by insurance alone. Cancer 2016. © 2016 American Cancer Society.

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Reply to patients with delirium and advanced solid cancer in the emergency department: A challenge for the emergency practitioner, oncologist, and intensivist; and delirium in patients with advanced cancer: Screening to cure or caring to prevent?

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Renal cancer subtypes: Should we be lumping or splitting for therapeutic decision making?

The treatment of advanced renal cell carcinoma has posed a challenge for decades, in part because of common themes related to intrinsic resistance to cytotoxic chemotherapy and the obscure biology of these cancer types. Forward movement in the treatment of the renal cell carcinomas thus can be approached in 2 ways: by splitting the tumor types along histologic and molecular features, in the hopes of coupling highly precision-focused therapy on a subset of patients who have disease with the most potential for benefit; or by lumping the various biologies and histologies together, to include the rarer renal cell carcinoma types with the more common types. The former strategy satisfies the desire for customized precision in treatment delivery, whereas the latter strategy allows clinicians to offer a wider therapeutic menu in a set of diseases we are continuing to learn about on a physiologic and molecular level. Cancer 2016. © 2016 American Cancer Society.

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Patients with delirium and advanced solid cancer in the emergency department: A challenge for the emergency practitioner, oncologist, and intensivist

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Bevacizumab combined with capecitabine and oxaliplatin in patients with advanced adenocarcinoma of the small bowel or ampulla of vater: A single-center, open-label, phase 2 study

BACKGROUND

Capecitabine with oxaliplatin (CAPOX) has previously demonstrated clinical activity in patients with small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Herein, the authors conducted a phase 2 trial to evaluate the benefit of adding bevacizumab to CAPOX.

METHODS

In this phase 2, single-arm, single-center, open-label study, patients aged ≥18 years with untreated, advanced SBA or AAC were recruited. Patients received capecitabine at a dose of 750 mg/m² orally twice daily on days 1 to 14, oxaliplatin at a dose of 130 mg/m² intravenously on day 1, and bevacizumab at a dose of 7.5 mg/kg intravenously on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary objectives included response rate, overall PFS, overall survival, and toxicity.

RESULTS

Between August 2011 and November 2014, a total of 30 patients were enrolled into the study (male/female ratio of 13/17; median age of 63 years [range, 33-78 years]; and 7 patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 0, 20 patients with an ECOG PS of 1, and 3 patients with an ECOG PS of 2). Of the 30 patients, 23 (77%) had SBA (18 of duodenal origin and 5 of jejunal/ileal origin) and 7 patients (23%) had AAC (5 of pancreaticobiliary subtype, 1 of mixed subtype, and 1 of intestinal subtype). The most common grade 3 toxicities observed were fatigue and hypertension (7 patients each [23%]), neutropenia (6 patients [20%]), and diarrhea (3 patients [10%]) (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). The probability of PFS at 6 months was 68% (95% confidence interval [95% CI], 52% to 88%). The response rate was 48.3%, with 1 complete response and 13 partial responses; 10 patients achieved stable disease. At a median follow-up of 25.9 months, the median PFS was 8.7 months (95% CI, 4.9-10.5 months) and the median overall survival was 12.9 months (95% CI, 9.2-19.7 months).

CONCLUSIONS

The results of the current study indicate that CAPOX with bevacizumab is an active and well-tolerated regimen for patients with SBA and AAC. These findings support the need for further investigation into the clinical benefit of targeting angiogenesis in patients with SBA and AAC. Cancer 2016. © 2016 American Cancer Society.

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Delirium in patients with advanced cancer: Screening to cure or caring to prevent?

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The impact of health insurance on cancer care in disadvantaged communities

BACKGROUND

Individuals from disadvantaged communities are among the millions of uninsured Americans gaining insurance under the Affordable Care Act. The extent to which health insurance can mitigate the effects of the social determinants of health on cancer care is unknown.

METHODS

This study linked the Surveillance, Epidemiology, and End Results registries to US Census data to study patients diagnosed with the 4 leading causes of cancer deaths between 2007 and 2011. A county-level social determinant score was developed with 5 measures of wealth, education, and employment. Patients were stratified into quintiles, with the lowest quintile representing the most disadvantaged communities. Logistic regression and Cox proportional hazards models were used to estimate associations and cancer-specific survival.

RESULTS

A total of 364,507 patients aged 18 to 64 years were identified (134,105 with breast cancer, 106,914 with prostate cancer, 62,606 with lung cancer, and 60,882 with colorectal cancer). Overall, patients from the most disadvantaged communities (median household income, $42,885; patients below the poverty level, 22%; patients completing college, 17%) were more likely to present with distant disease (odds ratio, 1.6; P < .001) and were less likely to receive cancer-directed surgery (odds ratio, 0.8; P < .001) than the least disadvantaged communities (median income, $78,249; patients below the poverty level, 9%; patients completing college, 42%). The differences persisted across quintiles regardless of the insurance status. The effect of having insurance on cancer-specific survival was more pronounced in disadvantaged communities (relative benefit at 3 years, 40% vs 31%). However, it did not fully mitigate the effect of social determinants on mortality (hazard ratio, 0.75 vs 0.68; P < .001).

CONCLUSIONS

Cancer patients from disadvantaged communities benefit most from health insurance, and there is a reduction in disparities in outcome. However, the gap produced by social determinants of health cannot be bridged by insurance alone. Cancer 2016. © 2016 American Cancer Society.

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Molecular Profiling of Thymoma and Thymic Carcinoma: Genetic Differences and Potential Novel Therapeutic Targets

Abstract

Thymoma and thymic carcinoma are thymic epithelial tumors (TETs). We performed a molecular profiling to investigate the pathogenesis of TETs and identify novel targets for therapy. We analyzed 37 thymomas (18 type A, 19 type B3) and 35 thymic carcinomas. The sequencing of 50 genes detected nonsynonymous mutations in 16 carcinomas affecting ALK, ATM, CDKN2A, ERBB4, FGFR3, KIT, NRAS and TP53. Only two B3 thymomas had a mutation in noncoding regions of the SMARCB1 and STK11 gene respectively. Three type A thymomas harbored a nonsynonymous HRAS mutation. Fluorescence in situ hybridization detected in 38 % of carcinomas a CDKN2A, in 32 % a TP53 and in 8 % an ATM gene deletion, whereas only one B3 thymoma exhibited a CDKNA deletion, and none of the type A thymomas showed a gene loss. Sequencing of the total miRNA pool of 5 type A thymomas and 5 thymic carcinomas identified the C19MC miRNA cluster as highly expressed in type A thymomas, but completely silenced in thymic carcinomas. Furthermore, the miRNA cluster C14MC was downregulated in thymic carcinomas. Among non-clustered miRNAs, the upregulation of miR-21, miR-9-3 and miR-375 and the downregulation of miR-34b, miR-34c, miR-130a and miR-195 in thymic carcinomas were most significant. The expression of ALK, HER2, HER3, MET, phospho-mTOR, p16^INK4A, PDGFRA, PDGFRB, PD-L1, PTEN and ROS1 was investigated by immunohistochemistry. PDGFRA was increased in thymic carcinomas and PD-L1 in B3 thymomas and thymic carcinomas. In summary, our results reveal genetic differences between thymomas and thymic carcinomas and suggest potential novel targets for therapy.

http://ift.tt/2faajhp

Effect of Follicle Stimulating Hormone Receptor Gene Polymorphisms in Cervical Cancer Risk

Abstract

For the first time in the word, we investigated the association between five FSHR polymorphisms with the risk of cervical cancer among Tunisians. Study subjects comprised 112 Cervical Cancer (CC) patients and 164 control women. Genotyping of FSHR rs6166, rs1007541, rs11692782, rs2055571 and rs1394205 variants was done by realtime PCR, with defined clusters. The allelic distributions of the tested FSHR SNPs were comparable between CC patients and control women. In contrast, the heterozygous genotype of rs1007541 was associated with 1.8-fold increased risk of CC. Stratification according to FIGO staging revealed that the minor allele of rs1007541 was more frequent among advanced tumor stage patients, with 11-fold increased risk of CC [P < 0.0001; OR (95 % CI) = 11.32 (7.46–17.18)]. However, no significant allelic association was revealed in the rest of analyzed FSHR SNPs. Haploview analysis showed high Linkage disequilibrium (LD) between rs2055571 and rs1394205. Haplotype analysis revealed a lack of association between cases and controls. However, analysis of CC patient subgroups demonstrated enrichment of GGTAG haplotype in early tumor stage [P = 0.025; OR (95 % CI) = 0.07 (0.01–0.70)]. The FSHR variants and haplotypes may be a genetic markers for CC susceptibility and evolution among Tunisian women.

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Prognostic Value of microRNA-9 in Various Cancers: a Meta-analysis

Abstract

Recently, there are more and more evidences from studies have revealed the association between microRNA-9 (miR-9) expression and outcome in multiple cancers, but inconsistent results have also been reported. It is necessary to rationalize a meta analysis of all available data to clarify the prognostic role of miR-9. Eligible studies were selected through multiple search strategies and the quality was assessed by MOOSE. Data was extracted from studies according to the key statistics index. All analyses were performed using STATA software. Twenty studies were selected in the meta-analysis to evaluate the prognostic role of miR-9 in multiple tumors. MiR-9 expression level was an independent prognostic biomarker for OS in tumor patients using multivariate and univariate analyses. High expression levels of miR-9 was demonstrated to associated with poor overall survival (OS) (HR = 2.23, 95 % CI: 1.56–3.17, P < 0.05) and recurrence free survival/progress free survival (RFS/PFS) (HR = 2.08, 95 % CI: 1.33–3.27, P < 0.05). Subgroup analysis showed that residence region (China and Japan), sample size, cancer type (solid or leukemia), follow-up months and analysis method (qPCR) did not alter the predictive value of miR-9 on OS in various cancers. Furthermore, no significant associations were detected for miR-9 expression and lymph node metastasis or distant metastasis. The present results suggest that promoted miR-9 expression is associated with poor OS in patients with general cancers.

http://ift.tt/2faar0k

Molecular Profiling of Thymoma and Thymic Carcinoma: Genetic Differences and Potential Novel Therapeutic Targets

Abstract

Thymoma and thymic carcinoma are thymic epithelial tumors (TETs). We performed a molecular profiling to investigate the pathogenesis of TETs and identify novel targets for therapy. We analyzed 37 thymomas (18 type A, 19 type B3) and 35 thymic carcinomas. The sequencing of 50 genes detected nonsynonymous mutations in 16 carcinomas affecting ALK, ATM, CDKN2A, ERBB4, FGFR3, KIT, NRAS and TP53. Only two B3 thymomas had a mutation in noncoding regions of the SMARCB1 and STK11 gene respectively. Three type A thymomas harbored a nonsynonymous HRAS mutation. Fluorescence in situ hybridization detected in 38 % of carcinomas a CDKN2A, in 32 % a TP53 and in 8 % an ATM gene deletion, whereas only one B3 thymoma exhibited a CDKNA deletion, and none of the type A thymomas showed a gene loss. Sequencing of the total miRNA pool of 5 type A thymomas and 5 thymic carcinomas identified the C19MC miRNA cluster as highly expressed in type A thymomas, but completely silenced in thymic carcinomas. Furthermore, the miRNA cluster C14MC was downregulated in thymic carcinomas. Among non-clustered miRNAs, the upregulation of miR-21, miR-9-3 and miR-375 and the downregulation of miR-34b, miR-34c, miR-130a and miR-195 in thymic carcinomas were most significant. The expression of ALK, HER2, HER3, MET, phospho-mTOR, p16^INK4A, PDGFRA, PDGFRB, PD-L1, PTEN and ROS1 was investigated by immunohistochemistry. PDGFRA was increased in thymic carcinomas and PD-L1 in B3 thymomas and thymic carcinomas. In summary, our results reveal genetic differences between thymomas and thymic carcinomas and suggest potential novel targets for therapy.

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Effect of Follicle Stimulating Hormone Receptor Gene Polymorphisms in Cervical Cancer Risk

Abstract

For the first time in the word, we investigated the association between five FSHR polymorphisms with the risk of cervical cancer among Tunisians. Study subjects comprised 112 Cervical Cancer (CC) patients and 164 control women. Genotyping of FSHR rs6166, rs1007541, rs11692782, rs2055571 and rs1394205 variants was done by realtime PCR, with defined clusters. The allelic distributions of the tested FSHR SNPs were comparable between CC patients and control women. In contrast, the heterozygous genotype of rs1007541 was associated with 1.8-fold increased risk of CC. Stratification according to FIGO staging revealed that the minor allele of rs1007541 was more frequent among advanced tumor stage patients, with 11-fold increased risk of CC [P < 0.0001; OR (95 % CI) = 11.32 (7.46–17.18)]. However, no significant allelic association was revealed in the rest of analyzed FSHR SNPs. Haploview analysis showed high Linkage disequilibrium (LD) between rs2055571 and rs1394205. Haplotype analysis revealed a lack of association between cases and controls. However, analysis of CC patient subgroups demonstrated enrichment of GGTAG haplotype in early tumor stage [P = 0.025; OR (95 % CI) = 0.07 (0.01–0.70)]. The FSHR variants and haplotypes may be a genetic markers for CC susceptibility and evolution among Tunisian women.

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Prognostic Value of microRNA-9 in Various Cancers: a Meta-analysis

Abstract

Recently, there are more and more evidences from studies have revealed the association between microRNA-9 (miR-9) expression and outcome in multiple cancers, but inconsistent results have also been reported. It is necessary to rationalize a meta analysis of all available data to clarify the prognostic role of miR-9. Eligible studies were selected through multiple search strategies and the quality was assessed by MOOSE. Data was extracted from studies according to the key statistics index. All analyses were performed using STATA software. Twenty studies were selected in the meta-analysis to evaluate the prognostic role of miR-9 in multiple tumors. MiR-9 expression level was an independent prognostic biomarker for OS in tumor patients using multivariate and univariate analyses. High expression levels of miR-9 was demonstrated to associated with poor overall survival (OS) (HR = 2.23, 95 % CI: 1.56–3.17, P < 0.05) and recurrence free survival/progress free survival (RFS/PFS) (HR = 2.08, 95 % CI: 1.33–3.27, P < 0.05). Subgroup analysis showed that residence region (China and Japan), sample size, cancer type (solid or leukemia), follow-up months and analysis method (qPCR) did not alter the predictive value of miR-9 on OS in various cancers. Furthermore, no significant associations were detected for miR-9 expression and lymph node metastasis or distant metastasis. The present results suggest that promoted miR-9 expression is associated with poor OS in patients with general cancers.

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The role of deubiquitinases in breast cancer

Abstract

Although growing numbers of oncoproteins and pro-metastatic proteins have been extensively characterized, many of these tumor-promoting proteins are not good drug targets, which represent a major barrier to curing breast cancer and other cancers. There is a need, therefore, for alternative therapeutic approaches to destroying cancer-promoting proteins. The human genome encodes approximately 100 deubiquitinating enzymes (DUBs, also called deubiquitinases), which are amenable to pharmacologic inhibition by small molecules. By removing monoubiquitin or polyubiquitin chains from the target protein, DUBs can modulate the degradation, localization, activity, trafficking, and recycling of the substrate, thereby contributing substantially to the regulation of cancer proteins and pathways. Targeting certain DUBs may lead to destabilization or functional inactivation of some key oncoproteins or pro-metastatic proteins, including non-druggable ones, which will provide therapeutic benefits to cancer patients. In breast cancer, growing numbers of DUBs are found to be aberrantly expressed. Depending on their substrates, specific DUBs can either promote or suppress mammary tumors. In this article, we review the role and mechanisms of action of DUBs in breast cancer and discuss the potential of targeting DUBs for cancer treatment.

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The role of deubiquitinases in breast cancer

Abstract

Although growing numbers of oncoproteins and pro-metastatic proteins have been extensively characterized, many of these tumor-promoting proteins are not good drug targets, which represent a major barrier to curing breast cancer and other cancers. There is a need, therefore, for alternative therapeutic approaches to destroying cancer-promoting proteins. The human genome encodes approximately 100 deubiquitinating enzymes (DUBs, also called deubiquitinases), which are amenable to pharmacologic inhibition by small molecules. By removing monoubiquitin or polyubiquitin chains from the target protein, DUBs can modulate the degradation, localization, activity, trafficking, and recycling of the substrate, thereby contributing substantially to the regulation of cancer proteins and pathways. Targeting certain DUBs may lead to destabilization or functional inactivation of some key oncoproteins or pro-metastatic proteins, including non-druggable ones, which will provide therapeutic benefits to cancer patients. In breast cancer, growing numbers of DUBs are found to be aberrantly expressed. Depending on their substrates, specific DUBs can either promote or suppress mammary tumors. In this article, we review the role and mechanisms of action of DUBs in breast cancer and discuss the potential of targeting DUBs for cancer treatment.

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Ganglioneuroma of the pancreas in a 4-year-old girl

Ganglioneuroma (GN) is the uncommon, benign representative of the peripheral neuroblastic tumours (PNTs), which arise from primitive sympathetic ganglion cells. PNTs comprise one of the most common groups of neoplastic diseases in infants and children, but its occurrence in the pancreas is rare. We report a 4-year-old girl with GN of the pancreas requiring pancreaticoduodenectomy as a definitive therapy and with a great outcome, and we review the published literature.

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Hereditary angioedema (HAE): a cause for recurrent abdominal pain

A 44-year-old Hispanic woman presented to the emergency room with a 2-day history of sudden onset of severe cramping left lower quadrant abdominal pain associated with ~20 episodes diarrhoea. Abdominal CT scan exhibited bowel wall oedema and acute extensive colitis. On the basis of the preliminary diagnosis of acute abdomen, the patient was admitted under the surgical team and treated for acute colitis. Since her family history was significant for hereditary angioedema (HAE), complement studies were performed which revealed low complement C4 levels and abnormally low values of C1q esterase inhibitor. Thus, the diagnosis of HAE type I was established. This case report summarises that the symptoms of HAE are often non-specific, hence making the underlying cause difficult to diagnose.

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Pericardiectomy as a diagnostic and therapeutic procedure

A 70-year-old man presented with recent onset, predominantly right-sided heart failure. Echocardiogram demonstrated features of hypertensive heart disease and was suggestive of, but non-diagnostic for, constrictive pericarditis (CP). CT demonstrated mild pericardial thickening. Right heart catheterisation showed elevation and equalisation of diastolic pressures in all cardiac chambers with early rapid filling, minimal ventricular interdependence, and no dissociation of intrathoracic and intracardiac pressures. While several features pointed towards CP, the minimal ventricular interdependence and no dissociation of intrathoracic and intracardiac pressures suggested other pathology. Diagnostic pericardiectomy was performed, after which the central venous pressure decreased from 22 to 12 mm Hg. Pathology revealed pericardial fibrosis. The patient experienced sustained resolution of his heart failure. A potential explanation for lack of CP criteria was the presence of hypertensive heart disease. CP needs to be considered when approaching patients with heart failure as diagnostic evaluation can be multifaceted and treatment curative.

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Medial rectus muscle cysticercosis: an assessment using ultrasonography and CT

Description

A 9-year-old boy presented with the history of progressive pain, watering and abduction limitation for 1-week duration. Medical history revealed two episodes of recurrent congestion on the nasal side and watering 2 and 4 week's prior. On examination visual acuity was 20/200 improving to 20/40 with refraction and 20/20 in right and left eye, respectively; extraocular motility was severely restricted in abduction and elevation with minimal restriction in depression and adduction (figure 1). Fundus examination showed localised choroidal mount on the nasal retina without any intraocular cyst. Ultrasonography of the orbit revealed a large cyst in the medial rectus muscle with peripheral high amplitude spike echo (figure 2A). Subsequent CT imaging of the head and neck showed a well-defined large cyst in medial rectus indenting the globe with a peripheral high amplitude dot, without any intracranial foci (figure 2B). Both the ultrasonography...

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Multimodality imaging in Bertolottis syndrome: an important cause of low back pain in young adults

Description

A 30-year-old woman presented to the orthopaedics outpatient department with low back pain (LBP) for 4 weeks, not relieved on medications. She had no known comorbidities. On examination, there was movement restriction of the lower spine and focal right posterior lumbar tenderness. Blood routines showed raised acute inflammatory markers. Imaging work-up included a routine frontal radiograph of the lumbar spine which showed a lumbosacral transition vertebra with enlarged right transverse process (figure 1). Sacroilliac joints appeared normal. Plain MRI of the lumbar spine was performed which revealed lumbosacral transitional vertebra (LSTV) with enlarged transverse process articulating with the sacral ala bilaterally forming diarthroidal joint (Castellvi type IIb) and the subchondral bone of this joint showed T2 short inversion recovery hyperintense signals and hypointense signals on T1-weighted images, which was suggestive of marrow oedema. The intervening cartilage was also hyperintense. There were no signal abnormalities on...

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Issue Information - Ed Board

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Issue Information - Ed Board

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Primary hyperoxaluria: spectrum of clinical and imaging findings

Abstract

Primary hyperoxaluria is a rare autosomal recessive inborn error of metabolism with three known subtypes. In primary hyperoxaluria type 1, the most common of the subtypes, a deficiency in the hepatic enzymes responsible for the metabolism of glycoxylate to glycine, leads to excessive levels of glyoxylate, which is converted to oxalate. The resultant elevation in serum and urinary oxalate that characterizes primary hyperoxaluria leads to calcium oxalate crystal deposition in multiple organ systems (oxalosis). We review the genetics, pathogenesis, variable clinical presentation and course of this disease as well as its treatment. Emphasis is placed on the characteristic imaging findings before and after definitive treatment with combined liver and renal transplantation.

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Primary hyperoxaluria: spectrum of clinical and imaging findings

Abstract

Primary hyperoxaluria is a rare autosomal recessive inborn error of metabolism with three known subtypes. In primary hyperoxaluria type 1, the most common of the subtypes, a deficiency in the hepatic enzymes responsible for the metabolism of glycoxylate to glycine, leads to excessive levels of glyoxylate, which is converted to oxalate. The resultant elevation in serum and urinary oxalate that characterizes primary hyperoxaluria leads to calcium oxalate crystal deposition in multiple organ systems (oxalosis). We review the genetics, pathogenesis, variable clinical presentation and course of this disease as well as its treatment. Emphasis is placed on the characteristic imaging findings before and after definitive treatment with combined liver and renal transplantation.

http://ift.tt/2eXFajy

Clinical outcomes of fungating breast cancer treated with palliative radiotherapy

Abstract

Purpose

Locally advanced, fungating breast cancer is a distressing condition that is frequently seen worldwide. Radiation is particularly useful in reducing the associated symptoms such as discharge, bleeding and pain. However, there is surprisingly limited data regarding the efficacy of radiation in controlling symptoms in patients with this condition.

Methods and materials

Records of 35 patients with fungating breast cancer were retrospectively reviewed. Study end points included tumor and symptom response (including response rates, duration of response), median survival, and treatment toxicity, which was scored using the Common Toxicity Criteria v3.0. To investigate for a dose-response relationship, patients were divided into two subgroups using the median biological effective dose (BED) of radiation. Patients in the higher BED subgroup (40 Gy₁₀ or greater) were compared to those in the lower BED group (less than 40 Gy₁₀) using the Fisher's exact test.

Results

Median age was 59 years (range 40–91 years). Thirty-two patients (91 %) had tumor size larger than 5 cm and nine patients (26 %) had known distant metastatic disease at the time of treatment. Dose-fractionation regimen ranged from 20 Gy in 5 fractions to 65 Gy in 26 fractions. Median survival was 11.7 months. Actuarial 12-month survival was 58 %. There was no difference between the high-dose and the low-dose groups, and higher radiation dose was not found to be associated with a longer duration of palliation or survival. No patients experienced grade 3 or 4 toxicity.

Conclusion

Radiotherapy is effective palliative treatment for patients with fungating breast cancer. High response rates of up to 90 % can be expected, with a median local progression-free survival of 10 months. With the advent of dose escalation techniques such as intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), it is now technically possible to deliver high radiation doses to patients with low toxicity and risk to the adjacent normal organs. Nevertheless, whether higher doses or longer courses of radiotherapy confer better local control is a potential subject for further study.

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Clinical outcomes of fungating breast cancer treated with palliative radiotherapy

Abstract

Purpose

Locally advanced, fungating breast cancer is a distressing condition that is frequently seen worldwide. Radiation is particularly useful in reducing the associated symptoms such as discharge, bleeding and pain. However, there is surprisingly limited data regarding the efficacy of radiation in controlling symptoms in patients with this condition.

Methods and materials

Records of 35 patients with fungating breast cancer were retrospectively reviewed. Study end points included tumor and symptom response (including response rates, duration of response), median survival, and treatment toxicity, which was scored using the Common Toxicity Criteria v3.0. To investigate for a dose-response relationship, patients were divided into two subgroups using the median biological effective dose (BED) of radiation. Patients in the higher BED subgroup (40 Gy₁₀ or greater) were compared to those in the lower BED group (less than 40 Gy₁₀) using the Fisher's exact test.

Results

Median age was 59 years (range 40–91 years). Thirty-two patients (91 %) had tumor size larger than 5 cm and nine patients (26 %) had known distant metastatic disease at the time of treatment. Dose-fractionation regimen ranged from 20 Gy in 5 fractions to 65 Gy in 26 fractions. Median survival was 11.7 months. Actuarial 12-month survival was 58 %. There was no difference between the high-dose and the low-dose groups, and higher radiation dose was not found to be associated with a longer duration of palliation or survival. No patients experienced grade 3 or 4 toxicity.

Conclusion

Radiotherapy is effective palliative treatment for patients with fungating breast cancer. High response rates of up to 90 % can be expected, with a median local progression-free survival of 10 months. With the advent of dose escalation techniques such as intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), it is now technically possible to deliver high radiation doses to patients with low toxicity and risk to the adjacent normal organs. Nevertheless, whether higher doses or longer courses of radiotherapy confer better local control is a potential subject for further study.

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2016 publication schedule

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Engineering wonders

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2016 publication schedule

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Engineering wonders

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Issue Information

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Signalling pathways in UHRF1-dependent regulation of tumor suppressor genes in cancer

Abstract

Epigenetic silencing of tumor suppressor genes (TSGs) through DNA methylation and histone changes is a main hallmark of cancer. Ubiquitin-like with PHD and RING Finger domains 1 (UHRF1) is a potent oncogene overexpressed in various solid and haematological tumors and its high expression levels are associated with decreased expression of several TSGs including p16 ^INK4A , BRCA1, PPARG and KiSS1. Using its several functional domains, UHRF1 creates a strong coordinated dialogue between DNA methylation and histone post-translation modification changes causing the epigenetic silencing of TSGs which allows cancer cells to escape apoptosis. To ensure the silencing of TSGs during cell division, UHRF1 recruits several enzymes including histone deacetylase 1 (HDAC1), DNA methyltransferase 1 (DNMT1) and histone lysine methyltransferases G9a and Suv39H1 to the right place at the right moment. Several in vitro and in vivo works have reported the direct implication of the epigenetic player UHRF1 in tumorigenesis through the repression of TSGs expression and suggested UHRF1 as a promising target for cancer treatment. This review describes the molecular mechanisms underlying UHRF1 regulation in cancer and discusses its importance as a therapeutic target to induce the reactivation of TSGs and subsequent apoptosis.

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Signalling pathways in UHRF1-dependent regulation of tumor suppressor genes in cancer

Abstract

Epigenetic silencing of tumor suppressor genes (TSGs) through DNA methylation and histone changes is a main hallmark of cancer. Ubiquitin-like with PHD and RING Finger domains 1 (UHRF1) is a potent oncogene overexpressed in various solid and haematological tumors and its high expression levels are associated with decreased expression of several TSGs including p16 ^INK4A , BRCA1, PPARG and KiSS1. Using its several functional domains, UHRF1 creates a strong coordinated dialogue between DNA methylation and histone post-translation modification changes causing the epigenetic silencing of TSGs which allows cancer cells to escape apoptosis. To ensure the silencing of TSGs during cell division, UHRF1 recruits several enzymes including histone deacetylase 1 (HDAC1), DNA methyltransferase 1 (DNMT1) and histone lysine methyltransferases G9a and Suv39H1 to the right place at the right moment. Several in vitro and in vivo works have reported the direct implication of the epigenetic player UHRF1 in tumorigenesis through the repression of TSGs expression and suggested UHRF1 as a promising target for cancer treatment. This review describes the molecular mechanisms underlying UHRF1 regulation in cancer and discusses its importance as a therapeutic target to induce the reactivation of TSGs and subsequent apoptosis.

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Notch3 inhibits epithelial–mesenchymal transition by activating Kibra-mediated Hippo/YAP signaling in breast cancer epithelial cells

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Notch3 inhibits epithelial–mesenchymal transition by activating Kibra-mediated Hippo/YAP signaling in breast cancer epithelial cells

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ZFP36L2 promotes cancer cell aggressiveness and is regulated by antitumor microRNA-375 in pancreatic ductal adenocarcinoma

Abstract

Due to its aggressive nature, pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and hard-to-treat malignancies. Recently developed targeted molecular strategies have contributed to remarkable improvements in the treatment of several cancers. However, such therapies have not been applied to PDAC. Therefore, new treatment options are needed for PDAC based on current genomic approaches. Expression of microRNA-375 (miR-375) was significantly reduced in miRNA expression signatures of several types of cancers, including PDAC. The aim of this study was to investigate the functional roles of miR-375 in PDAC cells and to identify miR-375-regulated molecular networks involved in PDAC aggressiveness. The expression levels of miR-375 were markedly downregulated in PDAC clinical specimens and cell lines (PANC-1 and SW1990). Ectopic expression of miR-375 significantly suppressed cancer cell proliferation, migration and invasion. Our in silico and gene expression analyses and luciferase reporter assay showed that zinc finger protein 36 ring finger protein-like 2 (ZFP36L2) was a direct target of miR-375 in PDAC cells. Silencing ZFP36L2 inhibited cancer cell aggressiveness in PDAC cell lines, and overexpression of ZFP36L2 was confirmed in PDAC clinical specimens. Interestingly, Kaplan–Meier survival curves showed that high expression of ZFP36L2 predicted shorter survival in patients with PDAC. Moreover, we investigated the downstream molecular networks of the miR-375/ZFP36L2 axis in PDAC cells. Elucidation of tumor-suppressive miR-375-mediated PDAC molecular networks may provide new insights into the potential mechanisms of PDAC pathogenesis.

This article is protected by copyright. All rights reserved.

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ZFP36L2 promotes cancer cell aggressiveness and is regulated by antitumor microRNA-375 in pancreatic ductal adenocarcinoma

Abstract

Due to its aggressive nature, pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and hard-to-treat malignancies. Recently developed targeted molecular strategies have contributed to remarkable improvements in the treatment of several cancers. However, such therapies have not been applied to PDAC. Therefore, new treatment options are needed for PDAC based on current genomic approaches. Expression of microRNA-375 (miR-375) was significantly reduced in miRNA expression signatures of several types of cancers, including PDAC. The aim of this study was to investigate the functional roles of miR-375 in PDAC cells and to identify miR-375-regulated molecular networks involved in PDAC aggressiveness. The expression levels of miR-375 were markedly downregulated in PDAC clinical specimens and cell lines (PANC-1 and SW1990). Ectopic expression of miR-375 significantly suppressed cancer cell proliferation, migration and invasion. Our in silico and gene expression analyses and luciferase reporter assay showed that zinc finger protein 36 ring finger protein-like 2 (ZFP36L2) was a direct target of miR-375 in PDAC cells. Silencing ZFP36L2 inhibited cancer cell aggressiveness in PDAC cell lines, and overexpression of ZFP36L2 was confirmed in PDAC clinical specimens. Interestingly, Kaplan–Meier survival curves showed that high expression of ZFP36L2 predicted shorter survival in patients with PDAC. Moreover, we investigated the downstream molecular networks of the miR-375/ZFP36L2 axis in PDAC cells. Elucidation of tumor-suppressive miR-375-mediated PDAC molecular networks may provide new insights into the potential mechanisms of PDAC pathogenesis.

This article is protected by copyright. All rights reserved.

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Survival outcomes following repeat surgery for recurrent glioblastoma: a single-center retrospective analysis

Abstract

The aim of the present study is to evaluate the impact of extent of resection at initial and repeat craniotomy on overall survival of patients with recurrent glioblastoma. The authors retrospectively reviewed the records of all adults patients who underwent repeat resection of recurrent glioblastoma following radiation and chemotherapy at an academic tertiary-care institution between 2011 and 2015. We evaluated the survival outcomes with regard to extent of resection considering both the initial and repeat resections. The role of possible prognostic factors that may affect survival after repeat resection, including age, preoperative performance status, tumor location and adjuvant treatment, was evaluated using Cox regression analyses. Forty-eight patients were included in this study. The overall median survival of 14 patients who had subtotal resection at recurrence after initial subtotal resection did not statistically differ from seven patients who had gross-total resection at recurrence after initial subtotal resection (18 months vs. 22 months, p = 0.583). The overall median survival of 13 patients who had gross-total resection at recurrence after initial gross-total resection was significantly increased compared with survival of 13 patients who had subtotal resection at recurrence after initial gross-total resection (47 months vs. 14 months, p = 0.009). A Cox proportional hazards model was created demonstrating that preoperative performance status at recurrence (HR 0.418, p = 0.035) and the extent of repeat resection (HR 0.513, p = 0.043) were independent predictors of survival. Gross-total resection at repeat craniotomy is associated with longer overall survival and should be performed whenever possible in patients with recurrent glioblastoma and in good performance status.

http://ift.tt/2fyuh5W

Use of diffusion-weighted MRI to modify radiosurgery planning in brain metastases may reduce local recurrence

Abstract

Stereotactic radiosurgery (SRS) is an effective and well tolerated treatment for selected brain metastases; however, local recurrence still occurs. We investigated the use of diffusion weighted MRI (DWI) as an adjunct for SRS treatment planning in brain metastases. Seventeen consecutive patients undergoing complete surgical resection of a solitary brain metastasis underwent image analysis retrospectively. SRS treatment plans were generated based on standard 3D post-contrast T1-weighted sequences at 1.5T and then separately using apparent diffusion coefficient (ADC) maps in a blinded fashion. Control scans immediately post operation confirmed complete tumour resection. Treatment plans were compared to one another and with volume of local recurrence at progression quantitatively and qualitatively by calculating the conformity index (CI), the overlapping volume as a proportion of the total combined volume, where 1 = identical plans and 0 = no conformation whatsoever. Gross tumour volumes (GTVs) using ADC and post-contrast T1-weighted sequences were quantitatively the same (related samples Wilcoxon signed rank test = −0.45, p = 0.653) but showed differing conformations (CI 0.53, p < 0.001). The diffusion treatment volume (DTV) obtained by combining the two target volumes was significantly greater than the treatment volume based on post contrast T1-weighted MRI alone, both quantitatively (median 13.65 vs. 9.52 cm³, related samples Wilcoxon signed rank test p < 0.001) and qualitatively (CI 0.74, p = 0.001). This DTV covered a greater volume of subsequent tumour recurrence than the standard plan (median 3.53 cm³ vs. 3.84 cm³, p = 0.002). ADC maps may be a useful tool in addition to the standard post-contrast T1-weighted sequence used for SRS planning.

http://ift.tt/2fR0Tek

Acknowledgement of reviewers 2015

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Impact of concurrent chemotherapy with radiation therapy for elderly patients with newly diagnosed glioblastoma: a review of the National Cancer Data Base

Abstract

To investigate the utilization and overall survival (OS) impact of concurrent chemotherapy in combination with radiation therapy (RT) for elderly glioblastoma (GBM) patients. Elderly patients (age >70) with supratentorial and nonmetastatic GBM who received RT of 20–75 Gy with concurrent single-agent chemotherapy (ChemoRT) or without (RT alone) during 2004–2012 were identified from the National Cancer Data Base (NCDB). The Cochran-Armitage test was used for trend analysis. Hazard ratios (HR) and 95% confidence intervals (CIs) were determined using Cox proportional hazards. Propensity score analysis was performed to reduce selection bias in treatment allocation. A total of 5252 patients were identified (RT alone: n = 1389; ChemoRT: n = 3863). There was increasing utilization of chemotherapy during this period (45–80%, P < .001). A similar trend was also observed for the subset of age >80 (25–68%, P < .001). ChemoRT was associated with significantly better OS than RT alone (HR 0.79, 95% CI 0.70–0.89, P < .001) on multivariate analysis, and similar OS benefit was demonstrated with 1202 pairs of propensity-matched patients (HR 0.79, 95% CI 0.73–0.86, P < .001). For the matched pair, the median OS was 5.8 months with ChemoRT and 5.0 months with RT alone; the 2-year OS rate was 9% with ChemoRT and 4% with RT alone (P < .001). Concurrent chemotherapy has been administered with RT for the majority of elderly GBM patients. Addition of chemotherapy to RT for elderly GBM patients is associated with significantly improve OS in routine clinical practice.

http://ift.tt/2fQWRCC

Survival outcomes following repeat surgery for recurrent glioblastoma: a single-center retrospective analysis

Abstract

The aim of the present study is to evaluate the impact of extent of resection at initial and repeat craniotomy on overall survival of patients with recurrent glioblastoma. The authors retrospectively reviewed the records of all adults patients who underwent repeat resection of recurrent glioblastoma following radiation and chemotherapy at an academic tertiary-care institution between 2011 and 2015. We evaluated the survival outcomes with regard to extent of resection considering both the initial and repeat resections. The role of possible prognostic factors that may affect survival after repeat resection, including age, preoperative performance status, tumor location and adjuvant treatment, was evaluated using Cox regression analyses. Forty-eight patients were included in this study. The overall median survival of 14 patients who had subtotal resection at recurrence after initial subtotal resection did not statistically differ from seven patients who had gross-total resection at recurrence after initial subtotal resection (18 months vs. 22 months, p = 0.583). The overall median survival of 13 patients who had gross-total resection at recurrence after initial gross-total resection was significantly increased compared with survival of 13 patients who had subtotal resection at recurrence after initial gross-total resection (47 months vs. 14 months, p = 0.009). A Cox proportional hazards model was created demonstrating that preoperative performance status at recurrence (HR 0.418, p = 0.035) and the extent of repeat resection (HR 0.513, p = 0.043) were independent predictors of survival. Gross-total resection at repeat craniotomy is associated with longer overall survival and should be performed whenever possible in patients with recurrent glioblastoma and in good performance status.

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Use of diffusion-weighted MRI to modify radiosurgery planning in brain metastases may reduce local recurrence

Abstract

Stereotactic radiosurgery (SRS) is an effective and well tolerated treatment for selected brain metastases; however, local recurrence still occurs. We investigated the use of diffusion weighted MRI (DWI) as an adjunct for SRS treatment planning in brain metastases. Seventeen consecutive patients undergoing complete surgical resection of a solitary brain metastasis underwent image analysis retrospectively. SRS treatment plans were generated based on standard 3D post-contrast T1-weighted sequences at 1.5T and then separately using apparent diffusion coefficient (ADC) maps in a blinded fashion. Control scans immediately post operation confirmed complete tumour resection. Treatment plans were compared to one another and with volume of local recurrence at progression quantitatively and qualitatively by calculating the conformity index (CI), the overlapping volume as a proportion of the total combined volume, where 1 = identical plans and 0 = no conformation whatsoever. Gross tumour volumes (GTVs) using ADC and post-contrast T1-weighted sequences were quantitatively the same (related samples Wilcoxon signed rank test = −0.45, p = 0.653) but showed differing conformations (CI 0.53, p < 0.001). The diffusion treatment volume (DTV) obtained by combining the two target volumes was significantly greater than the treatment volume based on post contrast T1-weighted MRI alone, both quantitatively (median 13.65 vs. 9.52 cm³, related samples Wilcoxon signed rank test p < 0.001) and qualitatively (CI 0.74, p = 0.001). This DTV covered a greater volume of subsequent tumour recurrence than the standard plan (median 3.53 cm³ vs. 3.84 cm³, p = 0.002). ADC maps may be a useful tool in addition to the standard post-contrast T1-weighted sequence used for SRS planning.

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Acknowledgement of reviewers 2015

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Impact of concurrent chemotherapy with radiation therapy for elderly patients with newly diagnosed glioblastoma: a review of the National Cancer Data Base

Abstract

To investigate the utilization and overall survival (OS) impact of concurrent chemotherapy in combination with radiation therapy (RT) for elderly glioblastoma (GBM) patients. Elderly patients (age >70) with supratentorial and nonmetastatic GBM who received RT of 20–75 Gy with concurrent single-agent chemotherapy (ChemoRT) or without (RT alone) during 2004–2012 were identified from the National Cancer Data Base (NCDB). The Cochran-Armitage test was used for trend analysis. Hazard ratios (HR) and 95% confidence intervals (CIs) were determined using Cox proportional hazards. Propensity score analysis was performed to reduce selection bias in treatment allocation. A total of 5252 patients were identified (RT alone: n = 1389; ChemoRT: n = 3863). There was increasing utilization of chemotherapy during this period (45–80%, P < .001). A similar trend was also observed for the subset of age >80 (25–68%, P < .001). ChemoRT was associated with significantly better OS than RT alone (HR 0.79, 95% CI 0.70–0.89, P < .001) on multivariate analysis, and similar OS benefit was demonstrated with 1202 pairs of propensity-matched patients (HR 0.79, 95% CI 0.73–0.86, P < .001). For the matched pair, the median OS was 5.8 months with ChemoRT and 5.0 months with RT alone; the 2-year OS rate was 9% with ChemoRT and 4% with RT alone (P < .001). Concurrent chemotherapy has been administered with RT for the majority of elderly GBM patients. Addition of chemotherapy to RT for elderly GBM patients is associated with significantly improve OS in routine clinical practice.

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The Buried Bumper Syndrome: External Bumper Extraction after Radial Mini Incisions and Replacement through an Adjacent Tract

Although considered as a safe method to provide long-term nutritional support, percutaneous endoscopic gastrostomy (PEG) may be complicated by a buried bumper syndrome (BBS), a life-threatening condition. Removal of the PEG tube with its buried bumper and reinsertion of a new PEG tube is often necessary. Since its description in 1988, less than 50 cases of BBS managed by external extraction of the buried bumper have been reported. We report a case of buried bumper that was removed by external traction without the need for endoscopic or laparoscopic treatment but with the need of two radial millimeter skin incisions after abdominal CT study and finally immediate PEG replacement but through an adjacent site.

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Hemorrhagic Lacrimation and Epistaxis in Acute Hemorrhagic Edema of Infancy

Acute hemorrhagic edema of infancy is an uncommon benign cutaneous vasculitis. Despite its worrisome presentation, it carries good prognosis with rarely reported systemic involvement. Management of these cases has been an area of debate with majority of physicians adopting conservative modalities. We report a case that presented with classic triad of rash, low grade fever, and peripheral edema along with two rarely reported manifestations in literature: hemorrhagic lacrimation and epistaxis.

http://ift.tt/2fP8sOQ

Cooperation of MLL/AF10(OM-LZ) with PTPN11 activating mutation induced monocytic leukemia with a shorter latency in a mouse bone marrow transplantation model

Abstract

PTPN11 mutation, a RAS signaling pathway mutation, is associated with MLL translocations in acute leukemia. A girl with MLL/AF10 AML was found to carry PTPN11^G503A. To study the impact of PTPN11 ^G503A cooperating with MLL/AF10 on leukemogenesis, we established a retroviral transduction/transplantation mouse model. Compared with the MLL/AF10(OM-LZ) leukemia cells harboring PTPN11 ^wt, the cells harboring PTPN11^G503A were hypersensitive to GM-CSF and IL3, and more resistant to death upon treatment with daunorubicin but sensitive to cytarabine. The cells harboring PTPN11^G503A autonomously differentiated into macrophages (1.8%) in the medium containing IL3. Further studies showed that the cells had an elevated (∼2.9-fold) Csf1 transcription level and secreted more (∼4.5-fold) M-CSF to the medium which can stimulate monocyte/macrophage differentiation of BM cells. Mice transplanted with the cells harboring PTPN11^G503A had a higher concentration of M-CSF in plasma. When mixed with the MLL/AF10(OM-LZ) leukemia cells harboring PTPN11 ^wt, the cells harboring PTPN11^G503A had an increased competitive engraftment and clonal expansion in the BM and spleen of recipient mice, although no competitive growth advantage was observed in the in vitro co-culturing assays. The mice transplanted with the MLL/AF10(OM-LZ) cells harboring PTPN11 ^wt developed myelomonocytic leukemia, while those transplanted with the cells harboring PTPN11^G503A induced monocytic leukemia in a shorter latency. Our results demonstrated that addition of PTPN11^G503A to MLL/AF10 affected cell proliferation, chemo-resistance, differentiation, in vivo BM recruitment/clonal expansion and accelerated disease progression. This article is protected by copyright. All rights reserved.

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Cooperation of MLL/AF10(OM-LZ) with PTPN11 activating mutation induced monocytic leukemia with a shorter latency in a mouse bone marrow transplantation model

Abstract

PTPN11 mutation, a RAS signaling pathway mutation, is associated with MLL translocations in acute leukemia. A girl with MLL/AF10 AML was found to carry PTPN11^G503A. To study the impact of PTPN11 ^G503A cooperating with MLL/AF10 on leukemogenesis, we established a retroviral transduction/transplantation mouse model. Compared with the MLL/AF10(OM-LZ) leukemia cells harboring PTPN11 ^wt, the cells harboring PTPN11^G503A were hypersensitive to GM-CSF and IL3, and more resistant to death upon treatment with daunorubicin but sensitive to cytarabine. The cells harboring PTPN11^G503A autonomously differentiated into macrophages (1.8%) in the medium containing IL3. Further studies showed that the cells had an elevated (∼2.9-fold) Csf1 transcription level and secreted more (∼4.5-fold) M-CSF to the medium which can stimulate monocyte/macrophage differentiation of BM cells. Mice transplanted with the cells harboring PTPN11^G503A had a higher concentration of M-CSF in plasma. When mixed with the MLL/AF10(OM-LZ) leukemia cells harboring PTPN11 ^wt, the cells harboring PTPN11^G503A had an increased competitive engraftment and clonal expansion in the BM and spleen of recipient mice, although no competitive growth advantage was observed in the in vitro co-culturing assays. The mice transplanted with the MLL/AF10(OM-LZ) cells harboring PTPN11 ^wt developed myelomonocytic leukemia, while those transplanted with the cells harboring PTPN11^G503A induced monocytic leukemia in a shorter latency. Our results demonstrated that addition of PTPN11^G503A to MLL/AF10 affected cell proliferation, chemo-resistance, differentiation, in vivo BM recruitment/clonal expansion and accelerated disease progression. This article is protected by copyright. All rights reserved.

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Sinonasal glomangiopericytoma treated with preoperative embolisation and endoscopic sinus surgery

Elizabeth Psoma, Petros D Karkos, Stamatia Dova, Michail Gavriilidis, Konstantinos Markou, Constantinos Kouskouras, Afroditi Haritanti and Stefanos Finitsis

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Sinonasal glomangiopericytoma treated with preoperative embolisation and endoscopic sinus surgery

Elizabeth Psoma, Petros D Karkos, Stamatia Dova, Michail Gavriilidis, Konstantinos Markou, Constantinos Kouskouras, Afroditi Haritanti and Stefanos Finitsis

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Rare Paravertebral and Skull Base Metastases in Prostate Cancer

Prostate cancer is the most commonly diagnosed visceral cancer in the United States. A majority of cases exhibit an insidious course and nonaggressive tumor behavior. Prostate cancer can manifest as lesions which remain localized, regionally invading or metastasize to lymph nodes, bones, and lungs. Here, we report a unique case of metastatic prostate cancer to the right upper mediastinum, presenting as a paravertebral mass within 2 years of initial tissue diagnosis. Paravertebral spread has not been described for prostate cancer, and herein, we discuss the clinical presentation, diagnostic workup, and possible therapeutic options available in light of the literature.
Case Rep Oncol 2016;9:738–746

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Splenic Angiosarcoma: A Diagnostic Splenectomy Finding

Splenic tumors are not frequent. Blood vessel neoplasms are a rare category of tumors and have an extremely low incidence in the spleen. This case report aims to describe a 57-year-old woman in whom a routine imaging examination had shown splenic cysts. During her follow-up, the cysts became larger and increased in number. A diagnostic splenectomy was performed and its analysis showed a rare splenic angiosarcoma.
Case Rep Oncol 2016;9:733–737

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Combined Acute Haemolytic and Secondary Angle Closure Glaucoma following Spontaneous Intraocular Haemorrhages in a Patient on Warfarin

Background: To report the first described case of combined haemolytic and acute angle closure glaucoma secondary to spontaneous intraocular haemorrhages in a patient on excessive anticoagulation. To the best of our knowledge, this is the first case reported in the literature presenting with raised intraocular pressure due to both mechanisms. Case Description: A 90-year-old woman presented with acute pain and reduction in vision in the left eye. Her intraocular pressure (IOP) was 55 mm Hg. There were red tinted blood cells in the anterior chamber giving it a reddish hue. The patient was known to have advanced wet macular degeneration. She was taking oral warfarin for atrial fibrillation. Her international normalised ratio (INR) was 7.7. B-scan ultrasound of posterior segment showed vitreous and suprachoroidal haemorrhages. An ultrabiomicroscopic examination confirmed open angles. A diagnosis of haemolytic glaucoma secondary to intraocular haemorrhages was made. The IOP was controlled medically. Warfarin was withdrawn and oral vitamin K therapy was initiated leading to a rapid INR reduction. Three days later, her anterior chamber became progressively shallower causing a secondary acute angle closure which was managed medically. After 2 months, the left IOP was well-controlled without any medications and the eye was not inflamed. Her vision in that eye remained perception of light. Conclusion: Patients with suprachoroidal haemorrhages should be closely monitored as they might subsequently develop acute angle closure despite an initially open angle and well-controlled INR and IOP. Excessive anticoagulation needs to be prevented to minimise the risk of sight-threatening complications.
Case Rep Ophthalmol 2016;7:233–238

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Diagnostic accuracy of p16INK4a immunohistochemistry in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis

ABSTRACT

The accurate diagnosis of human papillomavirus (HPV) causality in oropharyngeal squamous cell carcinomas (OPSCC) is likely to influence therapeutic decisions in affected patients in the near future. We conducted a systematic review and meta-analysis to determine the diagnostic accuracy of p16^INK4a immunohistochemistry (IHC) to identify HPV-induced OPSCC. We identified all studies that performed p16^INK4a IHC (index test) and HPV E6/E7 mRNA detection using an amplification-based method (gold standard to indicate a transforming relevance of HPV) in OPSCC. Testing with one or more comparator tests (HPV DNA PCR, HPV DNA in-situ hybridization (ISH) and p16^INK4a IHC/HPV DNA PCR combined testing) was an optional criterion for inclusion. Among 1,636 retrieved studies 24 fulfilled the inclusion criteria. The pooled sensitivity of p16^INK4a IHC, HPV DNA PCR, HPV DNA ISH and p16^INK4a IHC/HPV DNA PCR combined testing was 94% (95%-confidence interval (CI) 91-97%), 98% (94-100%), 85% (76-92%) and 93% (87-97%), respectively. The pooled specificity was 83% (78-88%), 84% (74-92%), 88% (78-96%) and 96% (89-100%), respectively. p16^INK4a IHC/HPV DNA PCR combined testing was as sensitive as either p16^INK4a IHC or HPV DNA PCR alone but significantly more specific than either separate test. In conclusion, p16^INK4a IHC is very sensitive but moderately specific to diagnose HPV-transformed OPSCC when used as a single test. Combined p16^INK4a IHC and HPV DNA PCR testing significantly enhances specificity while maintaining high sensitivity. This diagnostic test combination thus represents an attractive testing strategy for the reliable diagnosis of HPV-induced OPSCC in the clinical setting and may constitute an inclusion criterion for future therapeutic trials. This article is protected by copyright. All rights reserved.

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Diagnostic accuracy of p16INK4a immunohistochemistry in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis

ABSTRACT

The accurate diagnosis of human papillomavirus (HPV) causality in oropharyngeal squamous cell carcinomas (OPSCC) is likely to influence therapeutic decisions in affected patients in the near future. We conducted a systematic review and meta-analysis to determine the diagnostic accuracy of p16^INK4a immunohistochemistry (IHC) to identify HPV-induced OPSCC. We identified all studies that performed p16^INK4a IHC (index test) and HPV E6/E7 mRNA detection using an amplification-based method (gold standard to indicate a transforming relevance of HPV) in OPSCC. Testing with one or more comparator tests (HPV DNA PCR, HPV DNA in-situ hybridization (ISH) and p16^INK4a IHC/HPV DNA PCR combined testing) was an optional criterion for inclusion. Among 1,636 retrieved studies 24 fulfilled the inclusion criteria. The pooled sensitivity of p16^INK4a IHC, HPV DNA PCR, HPV DNA ISH and p16^INK4a IHC/HPV DNA PCR combined testing was 94% (95%-confidence interval (CI) 91-97%), 98% (94-100%), 85% (76-92%) and 93% (87-97%), respectively. The pooled specificity was 83% (78-88%), 84% (74-92%), 88% (78-96%) and 96% (89-100%), respectively. p16^INK4a IHC/HPV DNA PCR combined testing was as sensitive as either p16^INK4a IHC or HPV DNA PCR alone but significantly more specific than either separate test. In conclusion, p16^INK4a IHC is very sensitive but moderately specific to diagnose HPV-transformed OPSCC when used as a single test. Combined p16^INK4a IHC and HPV DNA PCR testing significantly enhances specificity while maintaining high sensitivity. This diagnostic test combination thus represents an attractive testing strategy for the reliable diagnosis of HPV-induced OPSCC in the clinical setting and may constitute an inclusion criterion for future therapeutic trials. This article is protected by copyright. All rights reserved.

http://ift.tt/2eSks1p