Life-threatening intraoperative anaphylaxis as a result of chlorhexidine present in Instillagel

A 70-year-old man with left lower limb critical ischaemia was admitted to our vascular unit for a femoral-popliteal bypass. He had experienced a skin reaction to chlorhexidine 6 months previously during an angioplasty procedure. After intubation, once in the operating theatre, the patient had a urinary catheter inserted using Instillagel. Around 30 min later the patient had a full-blown anaphylactic reaction that required aggressive medical management and the abandoning of surgery. Postoperative allergy testing confirmed that the suspected primary trigger for the anaphylaxis was indeed chlorhexidine, which was present in Instillagel. The patient was also found to have allergies to atracurium and teicoplanin, which had been given on induction. This case report highlights the importance of recognising that Instillagel contains chlorhexidine, and that indeed intraurethral use during routine urinary catheterisation can be a cause of life-threatening anaphylaxis.

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A typical presentation of a hepatocellular carcinoma in a middle-aged patient

Description

A 54-year-old man was admitted to our hospital due to experiencing a sudden, severe pain in the right shoulder after mild exercise. He had been losing weight over the previous month and had noticed a lump near his right shoulder. A chest X-ray showed a lytic lesion in the lateral half of his right collarbone (figure 1A) with a cortical break and the presence of a soft-tissue component. A chest CT scan showed the destruction of the bone and a 10x8x7 cm mass associated with the pathological fracture of the collarbone (figure 1B). The diagnostic workup was completed with an abdominal CT scan, which showed a large hepatic tumour, an alpha-fetoprotein blood test level of 1468 ng/mL (normal range <10 ng/mL) and a fine-needle aspiration cytology, which yielded the final diagnosis of disseminated disease of a hepatocellular carcinoma. Cells showed both TTF-1 and hepatocyte antigen positivity, whereas CK7,...

http://ift.tt/2vZhemW

Effects of Autologous Cytokine-Induced Killer Cells Infusion in Colorectal Cancer Patients: A Prospective Study

Cancer Biotherapy & Radiopharmaceuticals Aug 2017, Vol. 32, No. 6: 221-226.


http://ift.tt/2vkeC0L

In Vivo and In Vitro Effects of ATM/ATR Signaling Pathway on Proliferation, Apoptosis, and Radiosensitivity of Nasopharyngeal Carcinoma Cells

Cancer Biotherapy & Radiopharmaceuticals Aug 2017, Vol. 32, No. 6: 193-203.


http://ift.tt/2v0YfuY

Clinical Effects of CpG-Based Treatment on the Efficacy of Hepatocellular Carcinoma by Skewing Polarization Toward M1 Macrophage from M2

Cancer Biotherapy & Radiopharmaceuticals Aug 2017, Vol. 32, No. 6: 215-219.


http://ift.tt/2vk2vRq

Selected Literature Watch

Cancer Biotherapy & Radiopharmaceuticals Aug 2017, Vol. 32, No. 6: 227-228.


http://ift.tt/2v0Y9U8

A Comprehensive Review on Pharmacotherapeutics of Three Phytochemicals, Curcumin, Quercetin, and Allicin, in the Treatment of Gastric Cancer

Abstract

Objective

Gastric cancer is one of the most common causes of cancer-related death worldwide. Medicinal plants are one of the main sources for discovery of new pharmacological agents especially for treatment of cancers. The aim of the present study is to review pharmacotherapeutic aspects of three mostly studied phytochemicals including curcumin, quercetin, and allicin for management of gastric cancer.

Methods

Scopus, PubMed, Web of Science, and Google Scholar were searched for the effects of curcumin, quercetin, allicin, and their analogs in gastric cancer. Data were collected up to November 2015. The search terms were "curcumin," "quercetin," "allicin," and "gastric cancer" or "cancer."

Results

Curcumin demonstrated anti-angiogenic, anti-proliferative, anti-metastatic, pro-apoptotic, and anti-helicobacter activities. Quercetin inhibited cell growth and induced apoptosis, necrosis, and autophagy as well as anti-Helicobacter activity. Allicin showed apoptotic and anti-Helicobacter properties. All three natural compounds had low bioavailability.

Conclusions

Although preclinical studies demonstrated the activity of curcumin, quercetin, and allicin in gastric cancer, clinical trials are needed to confirm their effectiveness. Applying their possible synergistic action and suitable drug delivery system in clinical studies can be also an attractive approach with the purpose of finding new extremely efficient anti-gastric cancer agents.

Mini-Abstract

Curcumin, quercetin, and allicin seem to be good candidates for management of gastric cancer through their pro-apoptotic, anti-proliferative, and anti-helicobacter activities.

http://ift.tt/2wj9e2u

Activity of anthracycline- and ifosfamide-based chemotherapy in a series of patients affected by advanced myxofibrosarcoma

Abstract

Background

We report on the activity of anthracycline-based and high-dose prolonged-infusion ifosfamide chemotherapy in a retrospective series of patients affected by advanced myxofibrosarcoma treated at Istituto Nazionale Tumori in Milan, Italy, and within the Italian Rare Cancer Network (RTR).

Methods

Advanced myxofibrosarcoma patients treated with anthracycline + ifosfamide and high-dose prolonged-infusion ifosfamide as a single agent from November 2001 to December 2016 were retrospectively reviewed. All pathological diagnosis were centrally reviewed by at least two expert pathologists. Response was evaluated by RECIST, and survival functions were computed.

Results

Among 34 advanced myxofibrosarcoma patients, 13 were treated with front-line anthracycline + ifosfamide chemotherapy (male/female = 6/7, median age 54 years, range 33–72). Overall best response was: 4 partial responses, 3 stable diseases and 6 progressive diseases, with a median progression-free survival of 4 months. Twenty-eight patients received second/further line high-dose prolonged-infusion ifosfamide (male/female = 17/11, median age 55 years, range 27–75 years). We observed 10 partial responses, 4 stable diseases and 14 progressive diseases, with a median progression-free survival of 4 months. Median overall survival was 12 months.

Conclusions

This retrospective analysis suggests that the combination of anthracyclines and ifosfamide is active in myxofibrosarcoma. In patients already treated with a combination of anthracyclines and ifosfamide, high-dose prolonged-infusion ifosfamide showed activity as well.

http://ift.tt/2g0pI97

PI-273, a substrate-competitive, specific small molecule inhibitor of PI4KII{alpha}, inhibits the growth of breast cancer cells

While phosphatidylinositol 4-kinase PI4KIIα has been identified as a potential target for antitumor therapy, the clinical applications of PI4KIIα are limited by a lack of specific inhibitors. Here we report the first small-molecule inhibitor (SMI) of human PI4KIIα. Docking-based and ligand-based virtual screening strategies were first employed to identify promising hits, followed by two rounds of kinase activity inhibition validation. 2-(3-(4-Chlorobenzoyl)thioureido)-4-ethyl-5-methylthiophene-3-carboxamide (PI-273) exhibited the greatest inhibitory effect on PI4KIIα kinase activity (IC50 = 0.47 μM) and suppressed cell proliferation. Surface plasmon resonance (SPR) and thermal shift assays indicated that PI-273 interacted directly with PI4KIIα. Kinetic analysis identified PI-273 as a reversible competitive inhibitor with respect to the substrate phosphatidylinositol (PI), which contrasted with most other PI kinase inhibitors that bind the ATP binding site. PI-273 reduced PI4P content, cell viability, and AKT signaling in wild-type MCF-7 cells but not in PI4KIIα knockout MCF-7 cells, indicating that PI-273 is highly selective for PI4KIIα. Mutant analysis revealed a role of palmitoylation insertion in the selectivity of PI-273 for PI4KIIα. Additionally, PI-273 treatment retarded cell proliferation by blocking cells in G2/M, inducing cell apoptosis and suppressing colony-forming ability. Importantly, PI-273 significantly inhibited MCF-7 cell-induced breast tumor growth without toxicity. PI-273 is the first substrate-competitive, subtype-specific inhibitor of PI4KIIα, the use of which will facilitate evaluations of PI4KIIα as a cancer therapeutic target.

http://ift.tt/2vY1yQN

Monocarboxylate transporter MCT1 promotes tumor metastasis independently of its activity as a lactate transporter

Extracellular acidosis resulting from intense metabolic activities in tumors promotes cancer cell migration, invasion and metastasis. While host cells die at low extracellular pH, cancer cells resist, as they are well equipped with transporters and enzymes to regulate intracellular pH homeostasis. A low extracellular pH further activates proteolytic enzymes that remodel the extracellular matrix to facilitate cell migration and invasion. Monocarboxylate transporter MCT1 is a passive transporter of lactic acid that has attracted interest as a target for small molecule drugs to prevent metastasis. In this study, we present evidence of a function for MCT1 in metastasis beyond its role as a transporter of lactic acid. MCT1 activated transcription factor NF-κB to promote cancer cell migration independently of MCT1 transporter activity. While pharmacological MCT1 inhibition did not modulate MCT1-dependent cancer cell migration, silencing or genetic deletion of MCT1 in vivo inhibited migration, invasion and spontaneous metastasis. Our findings raise the possibility that pharmacological inhibitors of MCT1-mediated lactic acid transport may not effectively prevent metastatic dissemination of cancer cells.

http://ift.tt/2wiuIwo

STRAP promotes stemness of human colorectal cancer via epigenetic regulation of the NOTCH pathway

NOTCH signaling exerts essential roles in normal and malignant intestinal physiology and the homeostasis of cancer stem-like cells (CSC), but the basis for this latter role remains obscure. The signaling scaffold protein STRAP is upregulated in several cancers where it promotes tumorigenicity and metastasis. Here we report a novel oncogenic function for STRAP in maintaining CSC subpopulations in a heterogeneous mixture by antagonizing formation of the chromatin modifier PRC2 and by epigenetically activating NOTCH signals in human colorectal cancer (CRC). Silencing STRAP sensitized CRC cells to chemotherapeutic drugs in vitro and in vivo. STRAP depletion also contributed to a reduced stem-like phenotype of CRC cells, as indicated by reduced expression of the CSC signature and NOTCH signaling regulators in vitro and by diminished tumorigenesis in vivo. Genes encoding some upstream activators of NOTCH were highly enriched for H3K27me3, which form repressive chromatin domains upon STRAP silencing. Mechanistically, STRAP competitively disrupted association of the PRC2 subunits EZH2 and SUZ12, thereby inhibiting PRC2 assembly. Restoring the NOTCH pathway by lentiviral expression of NICD1 or HES1 in STRAP-depleted tumor cells reversed the CSC phenotype. In 90 CRC clinical specimens, a significant positive correlation was documented between the expression of STRAP and HES1. Overall, our findings illuminated a novel STRAP-NOTCH1-HES1 molecular axis as a CSC regulator in CRC, with potential implications to improve treatment of this disease.

http://ift.tt/2vYmA1z

Large Subcapsular Splenic Hematoma with a Large Pancreatic Pseudocyst Was Successfully Treated with Splenic Arterial Embolization and Ultrasound-Guided Percutaneous Drainage of Pancreatic Pseudocyst

Subcapsular splenic hematoma is a rare complication of pancreatitis. The management for subcapsular splenic hematoma remains controversial. We herein report a case of a large subcapsular splenic hematoma with a large pancreatic pseudocyst, which was successfully treated with splenic arterial embolization and ultrasound- (US-) guided percutaneous drainage of pancreatic pseudocyst, for the first time. A 44-year-old male suffered from recurrent abdominal pain for more than two years. He had previous 3 episodes of pancreatitis. A subcapsular splenic hematoma (16.0 × 16.0 × 7.6 cm) with pancreatic pseudocyst (13.5 × 10.0 × 8.0 cm) was shown on abdominal computed tomography (CT). He underwent splenic arterial embolization to decrease the blood supply of the spleen and then ultrasound-guided percutaneous drainage of the large pancreatic pseudocyst. After 2 weeks, the repeated CT-Abdomen showed the disappearance of pancreatic pseudocyst and multiple areas of infarction on the spleen, while the splenic subcapsular hematoma had also significantly reduced. The patient was discharged after almost a month of his hospital admission with the drainage tube attached, and about 2 weeks later the drainage tube was removed upon CT scan confirmation of decrease in the volume of the subcapsular hematoma. Patient had no abdominal symptoms at the 1.5-year follow-up.

http://ift.tt/2x7bwzv

ITIH4: Effective Serum Marker, Early Warning and Diagnosis, Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor evolved from cirrhosis. It is quite significant to seek accurate, easy markers for early warning and diagnosis of HCC. Through prospective cohort follow-up study and mass spectrometry, we discovered and verified a serum marker valuable for early warning and diagnosis. Follow-up observation was performed on cirrhosis patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was adopted to detect the serums of patients, and the serum polypeptides with a potential value in early HCC warning and diagnosis were screened. Electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-Q-TOF-MS/MS) was exploited to identify these screened polypeptides. Moreover, the serum marker concentration was determined by ELISA to validate the clinical value of the serum marker. Among 109 cirrhosis patients followed up for two years, 29 patients (26.6%) finally progressed into HCC. MALDI-TOF MS shows that the concentration of a 3155.66Da polypeptide was significantly different between the patients that progressed into HCC and those not. Through MS/MS identification, it is confirmed that the polypeptide is inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4). The serum ITIH4 concentrations in two groups were measured with ELISA and compared with Alpha-fetoprotein (AFP). Results show that serum ITIH4 and AFP concentrations were negatively correlated (r=−0.263, p=0.0006), and the ITIH4 concentration had a significant intergroup difference (p=0.000). Receiver operating characteristic (ROC) curve indicates that its predictive value (area under the curve, AUC) is 0.667, superior to AFP. For the patients progressing into HCC, serum samples were separately collected when they were recruited and diagnosed as cirrhosis. Measurement on these samples reveals that ITIH4 was declining during the progression of HCC (p=0.006). By virtue of mass spectrometry, we discovered and identified a biomarker valuable for early HCC warning and diagnosis. This marker overperforms the commonly used AFP, demonstrating a bright prospect.

http://ift.tt/2vTd5SM

ITIH4: Effective Serum Marker, Early Warning and Diagnosis, Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor evolved from cirrhosis. It is quite significant to seek accurate, easy markers for early warning and diagnosis of HCC. Through prospective cohort follow-up study and mass spectrometry, we discovered and verified a serum marker valuable for early warning and diagnosis. Follow-up observation was performed on cirrhosis patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was adopted to detect the serums of patients, and the serum polypeptides with a potential value in early HCC warning and diagnosis were screened. Electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-Q-TOF-MS/MS) was exploited to identify these screened polypeptides. Moreover, the serum marker concentration was determined by ELISA to validate the clinical value of the serum marker. Among 109 cirrhosis patients followed up for two years, 29 patients (26.6%) finally progressed into HCC. MALDI-TOF MS shows that the concentration of a 3155.66Da polypeptide was significantly different between the patients that progressed into HCC and those not. Through MS/MS identification, it is confirmed that the polypeptide is inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4). The serum ITIH4 concentrations in two groups were measured with ELISA and compared with Alpha-fetoprotein (AFP). Results show that serum ITIH4 and AFP concentrations were negatively correlated (r=−0.263, p=0.0006), and the ITIH4 concentration had a significant intergroup difference (p=0.000). Receiver operating characteristic (ROC) curve indicates that its predictive value (area under the curve, AUC) is 0.667, superior to AFP. For the patients progressing into HCC, serum samples were separately collected when they were recruited and diagnosed as cirrhosis. Measurement on these samples reveals that ITIH4 was declining during the progression of HCC (p=0.006). By virtue of mass spectrometry, we discovered and identified a biomarker valuable for early HCC warning and diagnosis. This marker overperforms the commonly used AFP, demonstrating a bright prospect.

http://ift.tt/2vTd5SM

Performance of ovarian cyst fluid fine-needle aspiration cytology

BACKGROUND

Although ovarian fine-needle aspiration (FNA) cytology is not commonly used as a primary modality of diagnosis for patients with ovarian lesions, many ovarian cysts are aspirated intraoperatively and occasionally for diagnostic purposes. Therefore, the ability to interpret these specimens remains critical. Previous studies have suggested a high specificity but low sensitivity as a limitation. The objective of the current study was to further explore the use and performance of ovarian cyst FNA for diagnosing malignancy at the study institution.

METHODS

The electronic database was searched from 1998 through 2016 for ovarian cyst fluid cytology specimens; any concurrent or follow-up surgical pathology; and clinical information including patient age, radiology findings, and procedure type. Test performance was calculated using the surgical pathology diagnosis as the gold standard.

RESULTS

A total of 459 ovarian cyst FNA specimens had the following diagnoses: 416 (90.6%) were diagnosed as benign, 32 (7.0%) as atypical, 4 (0.9%) as suspicious, and 7 (1.5%) as malignant. Overall, 300 specimens (65.4%) had a corresponding surgical pathology specimen. On follow-up, the rate of malignancy (including borderline neoplasms) for benign FNA was 10 of 264 specimens (3.8%), that for atypical FNA was 0 of 24 specimens (0%), that for suspicious FNA was 5 of 5 specimens (100%), and that for malignant FNA was 7 of 7 specimens (100%). Test sensitivity was 54.0% and test specificity was 100%. The positive predictive value was 1.00 and the negative predictive value was 0.97, with a disease (malignancy) prevalence of 7.33%.

CONCLUSIONS

Ovarian cyst fluid cytology is highly specific and moderately sensitive for the detection of ovarian malignancies. A negative FNA is reassuring for patients with a low pretest probability of malignancy. Cancer (Cancer Cytopathol) 2017. © 2017 American Cancer Society.

http://ift.tt/2v0pJAL

Identification of distinct cytomorphologic features in the diagnosis of NIFTP at the time of preoperative FNA: Implications for patient management

BACKGROUND

A major reclassification occurred with the redesignation of noninvasive encapsulated follicular variant of papillary thyroid carcinoma as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its indolent nature. The aim of this study was to determine whether distinct cytomorphologic features could be identified on preoperative fine-needle aspiration (FNA) when NIFTP cases were compared with invasive follicular variant of papillary thyroid carcinoma (FVPTC) subtypes.

METHODS

Thyroid resection cases with the diagnosis of FVPTC from 2012 to 2016 were reclassified as NIFTP, invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC), and invasive FVPTC subtypes. Corresponding FNA specimens were retrieved and retrospectively reviewed. A univariate analysis using Fisher's exact test was performed to determine any differences in the frequencies of various cytomorphologic features among NIFTP, IEFVPTC, and FVPTC cases. A multivariate analysis was performed to identify any independent salient features that would be helpful in differentiating NIFTP from its invasive counterparts.

RESULTS

The study population consisted of 93 cases, including 51 cases of NIFTP, 21 cases of IEFVPTC, and 21 cases of infiltrative FVPTC. Demographics such as age, sex, and tumor size were comparable across the 3 groups. A predominantly microfollicular pattern, an absence of nuclear pseudo-inclusions, and less frequent nuclear elongations and grooves were significantly more likely to be associated with NIFTP versus its invasive counterparts. The absence of nuclear pseudo-inclusions and the presence of a microfollicular pattern were the only independent predictors of a NIFTP diagnosis.

CONCLUSIONS

This study demonstrates that NIFTP cases have distinguishing cytomorphologic characteristics in comparison with invasive FVPTC cases. Therefore, a preoperative cytologic evaluation provides clues that can aid in the distinction between NIFTP and its invasive counterparts. Cancer Cytopathol 2017. © 2017 American Cancer Society.

http://ift.tt/2vj4DIY

A pattern-based risk-stratification scheme for salivary gland cytology: A multi-institutional, interobserver variability study to determine applicability

BACKGROUND

Salivary gland aspiration cytology is useful in the preoperative management of patients but remains challenging, because of the extensive morphologic overlap of some tumors limits the ability to always determine the presence of malignancy. In response to this challenge, there has been increasing drive to develop a risk-based categorization scheme for salivary gland aspirates. Herein, the authors examine the interobserver variability of 1 such pattern and risk-based system.

METHODS

Select smears and cell-block sections of 50 salivary gland aspirates from 2 large academic centers were digitally imaged. These scanned slides were independently and blindly reviewed by 4 cytopathologists, and each aspirate was assigned to 1 of the proposed pattern-based categories if it was considered neoplastic by the observer. Interobserver agreement was scored and aggregated risks of malignancy were calculated for cases with available surgical follow-up.

RESULTS

In total, 42 samples (84%) were considered neoplastic by at least 2 observers and were scored for interobserver agreement: 10 of 42 (23.8%) had uniform agreement, 14 of 42 (33.3%) had majority agreement, and 5 of 42 (11.9%) had divided agreement. Only 9 of 42 samples (21.4%) had minimal agreement, and 4 of 42 (9.5%) had no agreement. Condensation of similar categories was able to improve interobserver agreement and still maintain stratified risk of malignancy.

CONCLUSIONS

The proposed pattern-based risk-stratification scheme, which could be implemented with the forthcoming Milan System, has good overall interobserver agreement and successfully stratifies the risk of malignancy. Some simplification is possible to make the system easier to use and improve interobserver agreement while maintaining stratification of risk. Cancer Cytopathol 2017. © 2017 American Cancer Society.

http://ift.tt/2v0laXc

Association of IL-27 rs153109 and rs17855750 Polymorphisms with Risk and Response to Therapy in Acute Lymphoblastic Leukemia

Abstract

Interleukin (IL)-27 is a cytokine with important anti-cancer activity. This study has evaluated the effects of IL-27 rs153109 and rs17855750 single nucleotide polymorphisms (SNPs) on risk of acute lymphoblastic leukemia (ALL) development, as well as their impact on prognosis and patient survival. A total of 200 patients and 210 healthy subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. We observed a higher frequency of rs153109 AG and rs17855750 TG genotypes and allele G in patients compared to controls (p < 0.001). Combined G variant genotypes (AG + GG and TG + GG) also conferred significantly greater risk of ALL. There was a significant correlation between the genotypes of both SNPs with event-free survival (EFS). Patients with GG genotypes of both SNPs and those of rs153109 AG and rs17855750 TG had a shorter EFS than patients with rs153109 AA and rs17855750 TT genotypes (p ≤ 0.035). Combined G variant genotypes for both SNPs showed poorer response to therapy in all patients (p < 0.027) as well as B-ALL (rs153109, p < 0.001) and T-ALL (rs153109, p = 0.048) patients. In multivariate analysis, rs153109 combined G variant genotype was associated with shorter EFS (relative risk = 9.7, p = 0.026). Among those who relapsed, 87.1% had the rs153109 AG genotype and 77.4% had the rs17855750 TG genotype (p < 0.01). Patients had higher IL-27 serum levels compared to controls, but this did not differ between genotypes. In conclusion, the association of IL-27 rs153109 and rs17855750 polymorphisms with risk of ALL development and their impact on EFS suggested an important role for this cytokine in biology and response to ALL therapy.

http://ift.tt/2g1s485

MicroRNA-34a/EGFR axis plays pivotal roles in lung tumorigenesis

MicroRNA-34a/EGFR axis plays pivotal roles in lung tumorigenesis

Oncogenesis 6, e372 (August 2017). doi:10.1038/oncsis.2017.50

Authors: Y-L Li, X-M Liu, C-Y Zhang, J-B Zhou, Y Shao, C Liang, H-M Wang, Z-Y Hua, S-D Lu & Z-L Ma

http://ift.tt/2wrMCgH

Association of IL-27 rs153109 and rs17855750 Polymorphisms with Risk and Response to Therapy in Acute Lymphoblastic Leukemia

Abstract

Interleukin (IL)-27 is a cytokine with important anti-cancer activity. This study has evaluated the effects of IL-27 rs153109 and rs17855750 single nucleotide polymorphisms (SNPs) on risk of acute lymphoblastic leukemia (ALL) development, as well as their impact on prognosis and patient survival. A total of 200 patients and 210 healthy subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. We observed a higher frequency of rs153109 AG and rs17855750 TG genotypes and allele G in patients compared to controls (p < 0.001). Combined G variant genotypes (AG + GG and TG + GG) also conferred significantly greater risk of ALL. There was a significant correlation between the genotypes of both SNPs with event-free survival (EFS). Patients with GG genotypes of both SNPs and those of rs153109 AG and rs17855750 TG had a shorter EFS than patients with rs153109 AA and rs17855750 TT genotypes (p ≤ 0.035). Combined G variant genotypes for both SNPs showed poorer response to therapy in all patients (p < 0.027) as well as B-ALL (rs153109, p < 0.001) and T-ALL (rs153109, p = 0.048) patients. In multivariate analysis, rs153109 combined G variant genotype was associated with shorter EFS (relative risk = 9.7, p = 0.026). Among those who relapsed, 87.1% had the rs153109 AG genotype and 77.4% had the rs17855750 TG genotype (p < 0.01). Patients had higher IL-27 serum levels compared to controls, but this did not differ between genotypes. In conclusion, the association of IL-27 rs153109 and rs17855750 polymorphisms with risk of ALL development and their impact on EFS suggested an important role for this cytokine in biology and response to ALL therapy.

http://ift.tt/2g1s485

Concurrent assessment of calpain and caspase3 activities in brains of mice with acetaminophen-induced acute hepatic encephalopathy

Abstract

To develop pharmacological therapy for acute hepatic encephalopathy (AHE), understanding the molecular basis for cell injury is essential. Excitotoxic neural cell injury mediated by calpain as a post- receptor mechanism has been proposed as a player in neuronal injury in AHE. Concurrent assessment of Calpain and Caspase3 activities in the brain of AHE mice in acetaminophen- induced mourine model was performed. After induction of AHE by acetaminophen in mice, the model was confirmed by histopathological, biochemical and behavioural studies. The brains were removed, western blot analysis was done and the relative activity of calpain and caspase was estimated and compared to control group calpain but not caspase 3 activity was significantly increased in the AHE group compared to the control brains. Experimentally, this finding is the first to report. Increased calpain activity in liver has been previously reported. To translate both finding it can be suggested that calpain inhibition can be an investigational intervention in saving lives in AHE. To confirm the results, besides more advanced toxicodynamic studies on acetaminophen, the results should be confirmed in other models of AHE in future.

http://ift.tt/2ild3yl

Incidence and survival trends for medulloblastomas in the United States from 2001 to 2013

Abstract

Population-based data examining recent epidemiological trends in medulloblastoma, the most common pediatric brain malignancy, are limited. Therefore, we sought to examine recent population-level trends in medulloblastoma incidence and survival. Central Brain Tumor Registry of the United States (CBTRUS) data were analyzed from 2001 to 2013. Age-adjusted incidence rates (IR) and annual percent changes (APCs) with 95% confidence intervals (CI) were calculated by age, sex, and race. Relative survival rates were calculated by age, sex, and race using Surveillance, Epidemiology and End-Results (SEER) registries; subsets of CBTRUS data. Kaplan–Meier and Cox proportional hazards models were used to examine survival differences. Medulloblastoma incidence remained relatively stable from 2001 to 2013, with minor fluctuations from 2001 to 2009 (APC = 2.2, 95% CI 0.8, 3.5) and 2009–2013 (APC = −4.1, 95% CI −7.5, −0.6). Incidence was highest in patients aged 1–4 years at diagnosis, but patients aged 10–14 years showed increased incidence from 2000 to 2013 (APC = 3.2, 95% CI 0.6, 5.8). Males displayed higher IR relative to females (males: 0.16 vs. females: 0.12), except in patients <1 year-old. Compared to Whites, Blacks displayed a non-significant increase in incidence (APC = 1.7, 95% CI −0.4, 4.0) and in mortality risk (hazard ratio for survival = 0.74; p = 0.09). The current study reports no overall change in medulloblastoma incidence from 2001 to 2013. Male and female patients <1 year-old had equal medulloblastoma incidence rates and poor 5-year relative survival compared to other ages. Non-significant trends in the data suggest disparities in medulloblastoma incidence and survival by race. Thus, analysis of tumor-specific trends by demographic variables can uncover clinically informative trends in cancer burden.

http://ift.tt/2vT2veO

Highlights from the 2017 St. Gallen Breast Cancer Consensus

http://ift.tt/2vSPdPv

NCI Program Supports Small Businesses to Advance Cancer Research Innovation – A Q&A with Michael Weingarten

NCI's Small Business Innovation Research Program recently issued contract solicitations to spur the development of new cancer-related therapies and technologies, including seven opportunities specific to the Cancer Moonshot.

http://ift.tt/2uZjzRi

Glucotoxicity promotes aberrant activation and mislocalization of Ras-related C3 botulinum toxin substrate 1 [Rac1] and metabolic dysfunction in pancreatic islet β-cells: reversal of such metabolic defects by metformin

Abstract

Emerging evidence suggests that long-term exposure of insulin-secreting pancreatic β-cells to hyperglycemic (HG; glucotoxic) conditions promotes oxidative stress, which, in turn, leads to stress kinase activation, mitochondrial dysfunction, loss of nuclear structure and integrity and cell apoptosis. Original observations from our laboratory have proposed that Rac1 plays a key regulatory role in the generation of oxidative stress and downstream signaling events culminating in the onset of dysfunction of pancreatic β-cells under the duress of metabolic stress. However, precise molecular and cellular mechanisms underlying the metabolic roles of hyperactive Rac1 remain less understood. Using pharmacological and molecular biological approaches, we now report mistargetting of biologically-active Rac1 [GTP-bound conformation] to the nuclear compartment in clonal INS-1 cells, normal rat islets and human islets under HG conditions. Our findings also suggest that such a signaling step is independent of post-translational prenylation of Rac1. Evidence is also presented to highlight novel roles for sustained activation of Rac1 in HG-induced expression of Cluster of Differentiation 36 [CD36], a fatty acid transporter protein, which is implicated in cell apoptosis. Finally, our findings suggest that metformin, a biguanide anti-diabetic drug, at a clinically relevant concentration, prevents β-cell defects [Rac1 activation, nuclear association, CD36 expression, stress kinase and caspase-3 activation, and loss in metabolic viability] under the duress of glucotoxicity. Potential implications of these findings in the context of novel and direct regulation of islet β-cell function by metformin are discussed.

http://ift.tt/2xlsn0B

Impact of postoperative radiotherapy and HER2/new overexpression in salivary duct carcinoma

Abstract

Aim

Retrospective Investigation of the prognostic relevance of clinicopathologic parameters in patients with salivary duct carcinoma (SDC).

Methods

An experienced pathologist reviewed 67 patients with de novo SDC or SDC ex pleomorphic adenoma. Paraffin-embedded tumor samples were examined by immunohistochemistry for expression of HER2/neu, androgen (AR), progesterone (PR), estrogen (ER), epidermal growth factor (EGFR) and programmed death ligand 1 (PD-L1-R) receptor. In 45 patients who had cM0 and follow-up data available, survival rates were calculated (Kaplan–Meier method) and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox-regression analysis).

Results

Overexpression of HER2/neu, AR, ER, PR, EGFR, PD-L1-R was found in 25.4%, 84%, 0%, 0%, 17.9%, 16.4% of patients. Overall (OS), disease-free (DFS), distant-metastases-free survival (DMFS) and locoregional control (LRC) were 92.3/72.4/56.9%, 78.2/58.1/58.1%, 85.4/65.2/65.2% and 89.7/81.9/81.9% after 1/3/5 years (medial follow-up 26 months). In univariate analysis a positive resection margin (p = 0.008) and no postoperative radiotherapy (p = 0.001) predict an increased locoregional recurrence rate. In multivariate analysis only postoperative radiotherapy is statistically significant (p = 0.004). Presence of lymph node metastases, a lymph node density >4 and HER2/neu overexpression predict decreased DFS and DMFS. In multivariate HER2/neu overexpression was the only significant predictor for reduced DFS (p = 0.04) and DMFS (p = 0.02).

Conclusion

Postoperative radiotherapy is the only significant predictor for LRC. HER2/neu receptor expression is an independent prognostic factor for decreased DFS and DMFS in patients with SDC. In addition to radio(chemo)therapy, intensified first-line treatment regimens should also be evaluated in the future.

http://ift.tt/2vSoxyf

Homogeneous pancreatic cancer spheroids mimic growth pattern of circulating tumor cell clusters and macrometastases: displaying heterogeneity and crater-like structure on inner layer

Abstract

Purpose

Pancreatic cancer 3D in vitro models including multicellular tumor spheroid (MCTS), single cell-derived tumor spheroid (SCTS), tissue-derived tumor spheroid, and organotypic models provided powerful platforms to mimic in vivo tumor. Recent work supports that circulating tumor cell (CTC) clusters are more efficient in metastasis seeding than single CTCs. The purpose of this study is to establish 3D culture models which can mimic single CTC, monoclonal CTC clusters, and the expansion of macrometastases.

Methods

Seven pancreatic ductal adenocarcinoma cell lines were used to establish MCTS and SCTS using hanging drop and ultra-low attachment plates. Spheroid immunofluorescence staining, spheroid formation assay, immunoblotting, and literature review were performed to investigate molecular biomarkers and the morphological characteristics of pancreatic tumor spheroids.

Results

Single cells experienced different growth patterns to form SCTS, like signet ring-like cells, blastula-like structures, and solid core spheroids. However, golf ball-like hollow spheroids could also be detected, especially when DanG and Capan-1 cells were cultivated with fibroblast-conditioned medium (p < 0.05). The size of golf ball-like hollow spheroids hardly grew after getting matured. Only DanG and Capan-1 could establish SCTS- and MCTS-derived hollow spheroids using hanging drop plates and ultra-low attachment plates. Other PDA cell lines could also establish tumor spheroid with hanging drop plates by adding methylated cellulose. Tumor spheroids derived from pancreatic cancer cell line DanG possessed asymmetrically distributed proliferation center, immune-checkpoint properties. ß-catenin, Ki-67, and F-actin were active surrounding the crater-like structure distributing on the inner layer of viable rim cover of the spheroids, which was relevant to well-differentiated tumor cells.

Conclusions

It is possible to establish 3D CTC cluster models from homogenous PDA cell lines using hanging drop and ultra-low attachment plates. PDA cell line displays its own intrinsic properties or heterogeneity. The mechanism of formation of the crater-like structure as well as golf ball-like structure needs further exploration.

http://ift.tt/2xkWRzX

ROS-modulated therapeutic approaches in cancer treatment

Abstract

Purpose

Reactive oxygen species (ROS) are produced in cancer cells as a result of increased metabolic rate, dysfunction of mitochondria, elevated cell signaling, expression of oncogenes and increased peroxisome activities. Certain level of ROS is required by cancer cells, above or below which lead to cytotoxicity in cancer cells. This biochemical aspect can be exploited to develop novel therapeutic agents to preferentially and selectively target cancer cells.

Methods

We searched various electronic databases including PubMed, Web of Science, and Google Scholar for peer-reviewed english-language articles. Selected articles ranging from research papers, clinical studies, and review articles on the ROS production in living systems, its role in cancer development and cancer treatment, and the role of microbiota in ROS-dependent cancer therapy were analyzed.

Results

This review highlights oxidative stress in tumors, underlying mechanisms of different relationships of ROS and cancer cells, different ROS-mediated therapeutic strategies and the emerging role of microbiota in cancer therapy.

Conclusion

Cancer cells exhibit increased ROS stress and disturbed redox homeostasis which lead to ROS adaptations. ROS-dependent anticancer therapies including ROS scavenging anticancer therapy and ROS boosting anticancer therapy have shown promising results in vitro as well as in vivo. In addition, response to cancer therapy is modulated by the human microbiota which plays a critical role in systemic body functions.

http://ift.tt/2wqHWrw

Heterogeneous oncologic outcomes according to surgical pathology in high-risk prostate cancer: implications for better risk stratification and preoperative prediction of oncologic outcomes

Abstract

Purpose

To evaluate the better risk stratification based on surgical pathology, and to predict oncologic outcomes after radical prostatectomy (RP) with a better scoring system in high-risk prostate cancer (PCa) patients.

Methods

We evaluated high-risk PCa patients (PSA >20 ng/ml, ≥cT3a, or Gleason score 8–10) who underwent RP between 2007 and 2013 at our institute. We classified patients into three groups according to their pathologic outcomes: favorable (pT2, Gleason score ≤7, and node negative), intermediate (specimen-confined disease (pT2-3a, node negative PCa with negative surgical margins) but not in the favorable group), and unfavorable (the remaining patients). We developed a risk stratification scoring system to predict prognostic outcomes after RP and validated our scoring system to estimate its predictive accuracy.

Results

Among a total of 356 patients, 95 (26.7%), 115 (32.3%), and 146 (41%) were in the favorable, intermediate, and unfavorable prognostic groups, respectively. The 5-year biochemical recurrence-free survival rates of the patients in each group were 87.8, 64.6, and 41.4%, respectively. We developed a scoring system based on preoperative PSA, clinical stage, percentage of tumor positive core, and percentage of cores with a Gleason score 8–10. This demonstrated internally and externally validated concordance indices of 0.733 and 0.772, respectively.

Conclusions

Using our scoring system, we can predict which patients with high-risk PCa would benefit more from RP. Thus, this system can be used in patient counseling to determine an optimal treatment strategy for high-risk PCa.

http://ift.tt/2xkVv8f

Quality Indicators for Sentinel Lymph Node Biopsy in Breast Cancer: Applicability and Clinical Relevance in a Non-screened Population

Abstract

Quality Indicators for Sentinel Lymph Node Biopsy in Breast Cancer: Applicability and Clinical Relevance in a Non-screened Population: sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as standard of care for management of early breast cancer. This study assessed our SLNB program against 11 published quality indicators (QIs). All breast cancer patients who underwent SLNB in our centre from June 2013–Dec 2015 were included. Clinical, pathological and follow-up data were extracted from the institutional REDCap data system. Analysis was done with SPSS 23. Following validation, 234 patients had SLNB, always performed along with primary surgery. Identification rate was 95.3% and > 1 SLN was identified in 72% of patients. SLNB positivity was 33%, of these, 100% underwent ALND. Overall 91% of QI eligible patients underwent SLNB. No ineligible patients (T4) underwent SLNB. For the patients who had radio colloid, injection criteria were met for 100%. Pathological evaluation and reporting criteria were met for 100% of patients. There were no axillary recurrences in a median follow-up of 2 years. 7.6% patients had SLN negative on frozen section but positive on final histology. 7.2% of patients with clinical negative nodes had pN2 disease in final histopathology report after surgery. Sixty percent of patients who had completion ALND had only positive SLN. This study supports the applicability of published QI of SLNB in a non-screened cohort of early breast cancer patients. Although QI were useful, modification based on patient characteristics and resource availability may be needed. These indicators can be used as audit tools to improve the overall accuracy of the procedure.

http://ift.tt/2wqCHrF

Issue Information

http://ift.tt/2ikrK4N

Arterial thoracic outlet syndrome secondary to hypertrophy of the anterior scalene muscle

Abstract

Thoracic outlet syndrome (TOS) was first introduced in literature by Peet et al. in 1956. Since then is has been studied extensively and subcategorized into at least four closely related syndrome. Neurogenic TOS due to the compression of brachial plexus, arterial TOS in cases of compression of the subclavian artery, venous TOS in cases of compression of the subclavian vein, and non-specific type of TOS. Neurogenic TOS is by far the most common consisting of 95% of the cases, followed by venous and lastly arterial. Arterial TOS comprises ~1% of all TOS cases, they are caused largely by presence of cervical rib and/or anomalies of first rib. Here we describe arterial TOS caused by hypertrophy of the anterior scalene muscle in a 65-year-old male. Patient underwent successful open surgical repair with Dacron interposition graft. Postoperative course was unremarkable. Patient was discharged home on POD 2.

http://ift.tt/2wwQTie

Does omphalocele major undergo spontaneous closure?

Abstract

The early surgical management of omphalocele major in Africa predisposes neonates to surgical complications which are often worsened by the presence of associated anomalies. Conservative management using available escharotics results in early skin cover by secondary wound healing. This delays the need for fascial closure and avoids neonatal surgical risks thus improving survival. We present a case of omphalocele major that underwent spontaneous closure during conservative management with honey dressing without surgical intervention.

http://ift.tt/2wx6vlJ

Aggressive angiomyxoma of the perineum: a rare presentation in a male with 4 years follow up

Abstract

Angiomyxoma are rare myxoid cells tumours that occur predominantly in women in the fourth decade. They are classified as the less aggressive superficial and the deeper aggressive variety commonly called aggressive angimyxomas. We report a rare perineal aggressive angiomyxoma in a 79-year-old male presenting with a painless perineo-scrotal mass. Radiological investigations confirmed a lobulated well-defined mass separate from the testicles and histology following wide local excision confirmed aggressive angiomyxoma. He remains recurrence free at 4 years of surveillance which is the among longest reported follow-up for perineal angiomyxoma.

http://ift.tt/2wx6uOH

Impact of postoperative radiotherapy and HER2/new overexpression in salivary duct carcinoma

Abstract

Aim

Retrospective Investigation of the prognostic relevance of clinicopathologic parameters in patients with salivary duct carcinoma (SDC).

Methods

An experienced pathologist reviewed 67 patients with de novo SDC or SDC ex pleomorphic adenoma. Paraffin-embedded tumor samples were examined by immunohistochemistry for expression of HER2/neu, androgen (AR), progesterone (PR), estrogen (ER), epidermal growth factor (EGFR) and programmed death ligand 1 (PD-L1-R) receptor. In 45 patients who had cM0 and follow-up data available, survival rates were calculated (Kaplan–Meier method) and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox-regression analysis).

Results

Overexpression of HER2/neu, AR, ER, PR, EGFR, PD-L1-R was found in 25.4%, 84%, 0%, 0%, 17.9%, 16.4% of patients. Overall (OS), disease-free (DFS), distant-metastases-free survival (DMFS) and locoregional control (LRC) were 92.3/72.4/56.9%, 78.2/58.1/58.1%, 85.4/65.2/65.2% and 89.7/81.9/81.9% after 1/3/5 years (medial follow-up 26 months). In univariate analysis a positive resection margin (p = 0.008) and no postoperative radiotherapy (p = 0.001) predict an increased locoregional recurrence rate. In multivariate analysis only postoperative radiotherapy is statistically significant (p = 0.004). Presence of lymph node metastases, a lymph node density >4 and HER2/neu overexpression predict decreased DFS and DMFS. In multivariate HER2/neu overexpression was the only significant predictor for reduced DFS (p = 0.04) and DMFS (p = 0.02).

Conclusion

Postoperative radiotherapy is the only significant predictor for LRC. HER2/neu receptor expression is an independent prognostic factor for decreased DFS and DMFS in patients with SDC. In addition to radio(chemo)therapy, intensified first-line treatment regimens should also be evaluated in the future.

http://ift.tt/2vSoxyf

Prediction of new brain metastases after radiosurgery: validation and analysis of performance of a multi-institutional nomogram

Abstract

Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients' DBF risk within the validation dataset (c-index = 0.631) and Heller's explained relative risk (HERR) = 0.173 (SE = 0.048). Absolute number of metastases was evaluated for its ability to predict DBF in the derivation and validation datasets, and was inferior to the nomogram. A nomogram high-risk threshold yielding a 2.1-fold increased need for early WBRT was identified. Nomogram values also correlated to number of brain metastases at time of failure (r = 0.38, p < 0.0001). We present a multi-institutionally validated prognostic model and nomogram to predict risk of DBF and guide risk-stratification of patients who are appropriate candidates for radiosurgery versus upfront WBRT.

http://ift.tt/2vXfR80

Sentinel lymph node mapping in endometrial cancer: comparison of fluorescence dye with traditional radiocolloid and blue

Abstract

Sentinel lymph node (SLN) mapping in endometrial cancer (EMCA) is rapidly gaining acceptance in the clinical community. As compared to a full lymphadenectomy in every patient, to a selective lymphadenectomy after frozen section of uterus in selected patients with intrauterine risk factors or to a strategy in which a lymphadenectomy is always omitted, SLN mapping seems to be a reasonable and oncologically safe middle ground. Various protocols can be used when applying an SLN mapping. In this manuscript we review the characteristics, toxicity and clinical impact of technetium-99m radiocolloid (Tc-99m), of the blue dyes (methylene blue, isosulfan blue and patent blue) and of indocyanine green (ICG). ICG has an excellent toxicity profile, has higher overall and bilateral detection rates as compared to blue dyes and higher bilateral detection rates as compared to a combination of Tc-99m and blue dye. The detrimental effect of BMI on the detection rates is attenuated when ICG is used as a tracer. The ease of use of the ICG SLN mapping is perceived by the patients as a better quality of care delivered. Whenever possible, ICG should be favored over the other tracers for SLN mapping in EMCA patients.

http://ift.tt/2wgETl3

Lenalidomide in combination with bendamustine and prednisolone in relapsed/refractory multiple myeloma: results of a phase 2 clinical trial (OSHO-#077)

Abstract

Introduction

While lenalidomide monotherapy is established for relapsed and/or refractory multiple myeloma (MM) treatment, combination therapies including lenalidomide are still under investigation in a number of phase 2/3 studies. In the current study, a treatment regime of lenalidomide (Revlimid^®), bendamustine and prednisolone (RBP) was tested in patients with relapsed/refractory MM.

Methods

In the previously completed phase 1 study RBP with a dose of 75 mg/m² bendamustine days 1–2, prednisolone 100 mg days 1–4 and 25 mg lenalidomide days 1–21 was well tolerated.

Results

Between July 2011 and September 2013, 25 patients were included in this analysis. The median number of previous treatments was 1 (range 1–2). Twenty-two patients (88%) responded after at least two cycles of RBP (one sCR, five nCR, eight VGPR and eight PR). The median time to first haematological response was 28 days, and median time to best response was 56 days. Due to increased haematological toxicity a dose reduction in most patients required in subsequent cycles of therapy. The median progression-free and overall survival was 22 and 38 months, respectively.

Summary

In conclusion RBP is a highly effective therapy for patients with relapsed/refractory MM. In contrast to our phase 1 study, dose reduction was necessary in many patients because of haematological toxicity.

http://ift.tt/2vXeZjG

Systemic Inflammation Response Index (SIRI), cancer stem cells and survival of localised gastric adenocarcinoma after curative resection

Abstract

Purpose

Systemic Inflammation Response Index (SIRI), based on peripheral neutrophil, monocyte, and lymphocyte counts, was recently developed and used as a marker to predict the survival of patients with malignant tumours. Cancer stem cells (CSCs) can contribute to gastric cancer progression and recurrence. It is not clear whether SIRI is associated with CSCs during gastric cancer development.

Methods

The SIRI was developed in a training cohort of 455 gastric cancer patients undergoing curative resection between 2007 and 2009, and validated in a validation cohort of 327 patients from 2010 to 2011. CD44 + CSCs were measured on tumour sections by immunohistochemical analysis.

Results

An optimal cut-off point for the SIRI of 0.82 divided the gastric cancer patients into a low SIRI group (SIRI < 0.82) and a high SIRI group (SIRI ≥ 0.82) in the training cohort. Compared with patients who had a SIRI < 0.82, patients who had a SIRI ≥ 0.82 had a shorter disease-free survival (DFS) (HR 2.529; 95% CI 1.922–3.326; p < 0.001) and shorter disease-special survival (DSS) (HR 2.692; 95% CI 2.022–3.585; p < 0.001) in the training cohort, comparable DFS and DSS findings were observed in the validation cohort, even for patients in pathological TNM stage of I subgroup. A SIRI ≥ 0.82 was significantly associated with older age, larger tumour, higher pathological TNM stage, lymphovascular invasion, and perineural invasion. Additionally, patients in the low SIRI group were prone to DFS and DSS benefits from postoperative adjuvant chemotherapy. Univariate and multivariate analyses revealed that SIRI was an independent predictor for DFS and DSS. Furthermore, gastric cancer patients with CD44 + CSCs scores had higher SIRI level (mean 1.198 vs. 0.835; p < 0.001). In patients with CD44 + CSCs, those with SIRI ≥ 0.82 had higher recurrence rates and shorter survival time than patients with SIRI < 0. 82.

Conclusions

SIRI was a useful prognostic indicator of poor outcomes in patients with gastric cancer and is a promising tool for gastric cancer treatment strategy decisions. The dismal outcomes in patients with high SIRI might be related to CSCs.

http://ift.tt/2whoxsG

Septic abortion presenting as a right lower trapezius abscess secondary to Bacteroides fragilis bacteraemia

A 43-year-old Japanese woman was evaluated in the outpatient department for right shoulder pain and fever, which began 5 days earlier. MRI of the right shoulder revealed a high-intensity area deep in the right trapezius muscle. Aspiration revealed purulent fluid, and Gram staining of the fluid showed Gram-negative bacilli. The patient was also found to be profoundly anaemic and to have a positive urine pregnancy test. On admission, we initiated intravenous ampicillin–sulbactam and aztreonam. She underwent dilatation and curettage for septic abortion and surgical drainage of the right shoulder abscess. Bacteroides fragilis was isolated from the blood, uterine aspiration and abscess samples. On hospital day 4, a whole-body CT scan revealed no other abscesses, and ampicillin–sulbactam was continued for 28 days. The patient was discharged on hospital day 29. Gram staining is an important tool for evaluating infectious aetiologies.

http://ift.tt/2vicbMk

Herpes simplex transmission to chest and face through autoinoculation in an infant

A 4-month-old female infant presented with a vesicular lesion on her left hand present since 1 day. A few days prior to presentation, she had a similar lesion on the lower lip. Two days after presentation, she returned with new lesions on her thorax and upper eyelid. PCR of the vesicle was positive for herpes simplex virus type 1. The transmission to her chest and face probably resulted from autoinoculation, caused by rubbing of the hand on other parts of the body. Transmission of herpes simplex through skin-to-skin contact is a common route of infection in people engaging in contact sports. Antiviral therapy was started because of the extensiveness and expansion of lesions and risk of developing herpetic keratitis. The patient completely recovered. This case shows that in an otherwise healthy infant, multiple herpetic skin lesions were not due to disseminated infection, but through autoinoculation.

http://ift.tt/2uYFmZu

Novel use of rituximab in macrophage activation syndrome secondary to systemic lupus erythematosus

Macrophage activation syndrome (MAS) is a rare disease characterised by aberrant immune hyperactivation of T lymphocytes and macrophages driven by cytokine dysfunction. The HLH-2004 protocol is commonly used for the treatment of MAS, but significant toxicities are associated. We describe a case of MAS secondary to systemic lupus erythematosus in a young female that responded well to rituximab in lieu of etoposide. She continues to be in remission 1 year following the completion of rituximab infusion and is maintained on hydroxychloroquine. This case highlights the need for further research on the use of rituximab and other available biologics in the setting of MAS in order to help guide further alternative treatment decisions.

http://ift.tt/2vhtMEg

Parosteal lipoma mimicking a breast tumor

Description

Parosteal lipoma is a rare benign tumour that is composed mainly of mature adipose tissue, and is contiguous to the periosteum of the underlying bone.1 Most parosteal lipomas are asymptomatic, but some may present motor and/or sensory deficits.2

A woman was seen in our office complaining a left breast tumour. The woman first noticed the tumour several years ago and underwent breast cancer screening annually but was never required for further evaluation. The tumour was slowly growing, and was associated with pain when lying in a prone position. On physical examination, a soft tumour measuring 9 cm could be felt in the lower-inner quadrant of the left breast, and was firmly fixed to the chest wall. Mammogram showed a well-circumscribed, smooth, lipomatous mass containing a coral-like calcification (figure 1). Breast ultrasonogram showed a large lipomatous nodule near the caudal end of the...

http://ift.tt/2vhGra9

Ponticulus posticus of atlas vertebrae: an incidental finding in Malaysian orthodontic patients

Description

Ponticulus posticus is a normal anatomical variant of atlas vertebrae (C1) and resides in the posterior arch of atlas in relation to vertebral artery. It is an incidental finding visualised from lateral cephalograms taken for routine orthodontic treatment purpose. Ponticulus posticus in Latin means 'little posterior bridge'. Other synonyms for ponticulus are arcuate foramen, kimerle anomaly, retroarticular foramen and retocondylar foramen.1 An overall incidence of ponticulus posticus has been reported to be 16.7%. Literature reveals a higher incidence in females compared with males and this anomaly was age independent.2

This additional bone formation is formed by the calcification of posterior-atlanto occipital membrane. Radiographically, three variations are seen in this normal variant according to Miki et al: a complete form, partial form and calcified form of ponticulus posticus.1 The complete form is where the bony ring is fully formed, thus, resembling a foramen....

http://ift.tt/2vh9nz5

Near-toe amputation from prolonged compression stocking use

Description

A 73-year-old man was referred to the acute medical team by his general practitioner with a suspected diabetic footinfection. He had a background of type 2 diabetes mellitus, chronic venous insufficiency and ulcers, peripheral vascular disease and deep venous thromboses (DVT).

The patient revealed that he had not removed his compression stockings for 4 months. He had chronic venous changes bilaterally, a swollen, erythematous right leg and foul-smelling discharge from his right foot with a deep wound at the base of his fourth toe due to compression by the distal edge of the stocking, with partial amputation of this digit (figure 1).

Figure 1

Photograph of patient's right foot showing near amputation of fourth toe.

X-ray of his foot (figure 2) showed bone destruction of the right fourth toe in keeping with osteomyelitis. Venous Doppler scans showed acute and chronic...

http://ift.tt/2uYaKHL

Renal insufficiency in patients with multiple myeloma

Summary

Renal insufficiency in patients with multiple myeloma represents a major challenge for the treating physician. In patients with etiologically unclear renal failure it is important to consider multiple myeloma as a possible cause of such renal failure. The diagnosis and treatment of these patients is interdisciplinary, in cooperation with hemato-oncologists, radiologists, nephrologists and intensive care specialists. The main goal of all treatment methods is the rapid reduction of pathological free light chains in the serum, resulting in an improvement of renal function. Equally important is the avoidance of nephrotoxic drugs and iodinated contrast agents in patients with renal insufficiency and multiple myeloma. A few new drugs have been used in the systemic treatment of patients with multiple myeloma (MM) and renal failure with much success, especially the beneficial use of pomalidomide is interesting and other drugs will follow soon.

http://ift.tt/2ikgmWQ

At-home cancer screening: a solution for China and other developing countries with a large population and limited number of healthcare practitioners

Five-year survival rate for patients with all cancers combined, in China, is only 30.9%, which is much lower than those in developed countries. The three main reasons for the low cancer curative rates in China...

http://ift.tt/2ijQLxc

MicroRNA-34a/EGFR axis plays pivotal roles in lung tumorigenesis

http://ift.tt/2vhhHid

Ectopic cerebellar tissue in the occipital bone: a case report

Ectopic cerebellar tissue located distantly from the normal cerebellum is very rare, and its pathophysiology remains to be elucidated.

http://ift.tt/2vRNqdb

Klippel–Trenaunay–Weber syndrome with atypical presentation of hypersplenism and nephrotic syndrome: a case report

Klippel–Trenaunay–Weber syndrome is a rare syndrome; unfortunately, very few studies of the connection between hypersplenism, nephrotic syndrome, and Klippel–Trenaunay–Weber syndrome have been published.

http://ift.tt/2x5yarT

A Rare Case of Cavitary Lesion of the Lung Caused by Mycoplasma pneumoniae in an Immunocompetent Patient

Mycoplasma pneumoniae is an atypical bacterium that most commonly causes upper respiratory tract infections, but it can also cause pneumonia, referred to as "walking pneumonia." Although cavitary lesions are present in a wide variety of infectious and noninfectious processes, those attributable to M. pneumoniae are extremely uncommon; thus, to date, epidemiological studies are lacking. Here, we present a rare case of a 20-year-old male, referred to us from a psychiatric facility for evaluation of a cough, who was found to have a cavitary lesion in the right upper lobe. An extensive workup for cavitary lesion was negative, but his mycoplasma IgM level was high. A computed tomography (CT) of the chest confirmed the presence of a cavitary lesion. After treatment with levofloxacin antibiotics, a follow-up CT showed complete resolution of the lesion. Our case is a rare presentation of mycoplasma pneumonia as a cavitary lesion in a patient without any known risk factors predisposing to mycoplasma infection. Early recognition and treatment with an appropriate antibiotic may lead to complete resolution of the cavitary lesion.

http://ift.tt/2fYoGL2

Risk of Serous Endometrial Carcinoma in Women With Pathogenic BRCA1/2 Variant After Risk-Reducing Salpingo-Oophorectomy

Abstract

It has recently been shown that the risk of a rare subtype of endometrial carcinoma (serous type) in women carrying a germline BRCA1/2 pathogenic variant is increased. We assessed the incidence of serous endometrial carcinoma in an independent prospective cohort study of 369 BRCA1/2 women (1779 woman-years of follow-up) who underwent risk-reducing salpingo-oophorectomy by laparoscopy. This occurrence in two BRCA1 carriers led us to estimate that BRCA1/2 carriers present a higher risk than the control population (standardized incidence ratio = 32.2, 95% confidence interval = 11.5 to 116.4, P < .001, two-sided chi-square test, 1 degree of freedom). In addition, in both tumors, the wild-type BRCA1 allele was lost, indicating the inactivation of the BRCA1 gene and arguing for a link with endometrial carcinogenesis. Prophylactic hysterectomy could be discussed with informed women through a shared decision-making process although the estimated 3% life-long risk is moderate. Additional studies are required to establish future prophylactic surgery guidelines.

http://ift.tt/2v6QS12

Percutaneous management of complex acquired aortic coarctation in an adult with tetralogy of Fallot and pulmonary atresia

Michael D Seckeler, Emily Lawson, Brent J Barber, Scott E Klewer

Annals of Pediatric Cardiology 2017 10(3):295-297

We present the case of a female adult with complex cyanotic congenital heart disease who had long-standing thoracic aortic obstruction due to scarring from earlier surgical procedures. She was symptomatic but felt to be too high risk for surgical intervention. With careful planning, she was able to undergo successful stenting of her aorta with subsequent clinical improvement. This case highlights some of the complexities of caring for adults with congenital heart disease and the importance of a thorough understanding of their anatomy and physiology and prior interventions before undertaking interventions.

http://ift.tt/2wh8VW6

Change of guard: Introducing the new editor of the Annals of Pediatric Cardiology, Dr. KS Iyer

Raman Krishna Kumar

Annals of Pediatric Cardiology 2017 10(3):223-223



http://ift.tt/2wgNoNb

Quantification of ventricular unloading by 3D echocardiography in single ventricle of left ventricular morphology following superior cavo-pulmonary anastomosis and Fontan completion – a feasibility study

Deepa Sasikumar, Bijulal Sasidharan, Baiju S Dharan, Arun Gopalakrishnan, Kavasseri M Krishnamoorthy, Sivasubramanian Sivasankaran

Annals of Pediatric Cardiology 2017 10(3):224-229

Background: Three-dimensional echocardiography. (3DE) is comparable to cardiac magnetic resonance imaging for estimating ventricular volume in congenital heart diseases. However, there are limited data on estimation of ventricular volumes by 3DE in univentricular heart and change in ventricular volumes after surgical creation of cavopulmonary connection. We sought to quantify the unloading of the single ventricle of left ventricular. (LV) morphology by 3DE after superior cavopulmonary anastomosis. (SCPA) or Fontan operation over a period of 3 months and thereby derive a preliminary 3DE data set on this patient subset. Patients and Methods: Eighteen patients with functional single ventricle of LV morphology, who underwent SCPA or completion of Fontan circulation, were included in the study. Volume of the ventricle was estimated by 3DE before surgery and after surgery. (in the early postoperative phase and 3 months after surgery), and indexed end-diastolic volume. (EDV), end.systolic volume. (ESV), and ejection fraction. (EF) were derived. Results: Twelve patients underwent SCPA and six patients underwent staged completion of Fontan circulation. Before surgery, EDV was similar in both groups. There was a significant fall in EDV immediately after SCPA (from 48.3 ± 14.9 ml/m2 to 39.5 ± 12.3 ml/m2). However, EDV increased at 3 months' follow-up to 41.3 ± 10.5 ml/m2. There was no significant fall in EDV immediately after Fontan operation (47.2 ± 10.1 ml/m2−46.6 ± 14.2 ml/m2), but EDV continued to fall at 3 months of follow-up (44.7 ± 10. ml/m2). There was no significant change in ESV in either group, but EF fell significantly after SCPA. Conclusions: We provide preliminary information on 3DE volume data of single ventricle of LV morphology and the pattern of unloading after SCPA and Fontan operation. Immediate significant volume unloading occurred after SCPA which tended to catch-up after 3 months, whereas continued fall in ventricular volume with time was noted after Fontan.

http://ift.tt/2vWX7FX

Hypoplastic left heart syndrome with coronary-cameral fistulas: Echocardiographic demonstration of coronary artery steal and successful interventional treatment

Arshid Mir, Mary Niu, Merick Yamada, Ed Overholt

Annals of Pediatric Cardiology 2017 10(3):306-309

We report a case of a patient with hypoplastic left heart syndrome with significant coronary-cameral fistulas and exertional symptoms from coronary steal. Symptoms resolved following successful coil occlusion of his left ventricle.

http://ift.tt/2wgIRu3

Speckle tracking evaluation of right ventricular functions in children with sickle cell disease

Osama Abd Rab Elrasol Tolba, Mohamed Ramadan El-Shanshory, Mohamed Abd Elaziz El-Gamasy, Walid Ahmed El-Shehaby

Annals of Pediatric Cardiology 2017 10(3):230-233

Background: Cardiac dysfunction is a risk factor for death in patients with sickle cell disease (SCD). Aim of the Work: Aim of the work is to evaluate the right ventricular systolic and diastolic functions by tissue Doppler and speckling tracking imaging in children with SCD. Subjects and Methods: Thirty children with SCD and thirty controls were subjected to clinical, laboratory evaluations, and echocardiographic study using GE Vivid 7 (GE Medical System, Horten, Norway with a 3.5-MHz multifrequency transducer) including; Two-dimensional and tissue Doppler echocardiographic study (lateral tricuspid valve annulus peak E' velocity, lateral tricuspid valve annulus peak A' velocity, E'/A' ratio, isovolumetric relaxation time, lateral tricuspid valve annulus S' and septal S' waves and peak longitudinal systolic strain [PLSS] and time to PLSS) were done in six right ventricular segments. Results: There was a significant decrease in right ventricular systolic and diastolic function in patients group when compared to controls. Conclusions: Children with SCD have impaired right ventricular systolic and diastolic functions when compared to healthy children with early evaluation of the systolic dysfunction by speckle tracking imaging technique.

http://ift.tt/2whc5sK

Flecainide toxicity in a preterm neonate with permanent junctional reciprocating tachycardia

Balaganesh Karmegaraj, Danish Menon, Mukund A Prabhu, Balu Vaidyanathan

Annals of Pediatric Cardiology 2017 10(3):288-292

We report a case of flecainide toxicity in a premature neonate with permanent junctional reciprocating tachycardia which was managed successfully by reversal of the sodium blockade with intravenous sodium bicarbonate and supportive care. This report highlights the importance of strict supervision and monitoring while administering antiarrhythmic drugs in neonates and prompt institution of appropriate remedial action for treatment when toxicity is suspected.

http://ift.tt/2wgIT59

Intraocular pressure in children after congenital heart surgery: A single-center study

Sunali Goyal, Paul H Phillips, Lamonda A Corder, Michael J Robertson, Xiomara Garcia, Michael L Schmitz, Punkaj Gupta

Annals of Pediatric Cardiology 2017 10(3):234-239

Background: The impact of varied cardiac physiologies on intraocular pressure (IOP) among children undergoing heart operations is unknown. Aim: The aim of this study was to determine the IOP among children with varying cardiovascular physiologies and varying hemodynamics after their heart operation. Setting and Design: This was a prospective, observational study. Materials and Methods: Patients ≤18 years undergoing congenital heart surgery were included in this study. IOP measurement was performed by Icare® tonometer between 3 and 14 days after heart operation. Statistical Analysis: Summary statistics were estimated for all demographic, anthropometric, and clinical data. Results: A total of 116 eyes from 58 children were included. The mean and standard deviation age was 28.4 (45.8) months. Single-ventricle anatomy was present in 26 patients (45%). Despite similar heart rate and blood pressure, the mean IOP among the patients with single-ventricle anatomy was significantly elevated as compared to patients with two-ventricle anatomy (18 mm Hg vs. 12 mm Hg, P < 0.001). There was no difference in IOP measurements based on the complexity of operation performed. We noted that patients undergoing surgical palliation with central shunt (21 mm Hg), Fontan operation (19 mm Hg), bidirectional Glenn operation (19 mm Hg), Norwood operation (19 mm Hg), or definitive repairs such as tetralogy of Fallot repair (17 mm Hg), and atrioventricular canal repair (19 mm Hg) were associated with the highest IOPs in the study cohort. Conclusions: This study demonstrates that IOPs vary with varying cardiovascular physiology after pediatric cardiac surgery.

http://ift.tt/2vWnyvn

Anomalous origin of the left brachiocephalic artery in the right aortic arch: Is there a method to the madness?

Mani Ram Krishna, Ganesh Kumar Gnanappa, Rachel Fitzpatrick, Julian Ayer, David Winlaw

Annals of Pediatric Cardiology 2017 10(3):301-303

The anomalous origin of the left brachiocephalic artery in a right sided aortic arch is a rare vascular ring which might lead to esophageal compression. The exact embryological origin of this anomaly is still widely debated. We present an infant who presented with esophageal compression symptoms and review the various hypotheses about the embryological origin of this anomaly.

http://ift.tt/2whc3B8

Initial experience with the 3.3 Fr Mongoose® pigtail catheter for aortic angiography during patent ductus arteriosus closure in small patients

Zachary Hena, Nicole J Sutton, Gregory J Gates, Benjamin H Taragin, Robert H Pass

Annals of Pediatric Cardiology 2017 10(3):240-244

Background: Smaller femoral arterial sheaths may be associated with fewer vascular complications. The 3.3 Fr Mongoose® Pediavascular pigtail catheter is a catheter that allows higher flow rates, potentially resulting in improved angiographic quality. We reviewed our experience with this small catheter during patent ductus arteriosus (PDA) closure. Materials and Methods: Review of patients ≤20 kg in whom the Mongoose® catheter was used during PDA closure from 12/13 to 4/15. Angiographic efficacy and procedural details were compared to ten 4 Fr catheter cases. Comparisons were performed using Mann–Whitney U-test; P < 0.05 was statistically significant. Results: Twelve (9 female) patients were catheterized with a 3.3 Fr Mongoose®. Median weight 10.5 kg (range 6.4–18.2), height 81 cm (range 37–111), and body surface area (BSA) 0.47 m2 (range 0.33–0.75) were similar to ten patients (3 females) in the 4 Fr control group (P = NS); median weight 9.9 kg (range 6–16.8), height 80 cm (range 64–102), and BSA 0.46 m2 (range 0.31–0.74). Angiographic quality was subjectively adequate with both with no difference in the median pixel density between the two techniques (3.3 Fr: 76.7 [range 33.5–90] and 4 Fr: [70; 38–102]; P = NS). Contrast used was similar between the groups (3.3 Fr: median 4.2 ml/kg and 4 Fr: 4.9 ml/kg; P = NS). Median radiation dose was similar in the two groups (3.3 Fr: 28.1 mGy [range 17.2–38] and 4 Fr: 38 mGy [range 20.4–58.5]; P = NS). All ducts were closed at latest follow-up ( P = NS). No complications were encountered. Conclusions: The 3.3 Fr Mongoose® allowed similar angiography to the 4 Fr pigtail catheter, allowing safe and effective transcatheter PDA closure in small children.

http://ift.tt/2wgL3Sn

Staphylococcal endocarditis after chicken pox in a child with structurally normal heart

Dheeraj Deo Bhatt, Nihit Kharkwal, Dinesh Kumar Yadav

Annals of Pediatric Cardiology 2017 10(3):312-313



http://ift.tt/2wgq0iF

Does heart-type fatty acid-binding protein predict clinical outcomes after pediatric cardiac surgery?

Egmond S Evers, Varsha Walavalkar, Suresh Pujar, Latha Balasubramanian, Frits W Prinzen, Tammo Delhaas, Ward Y Vanagt, Shreesha Maiya

Annals of Pediatric Cardiology 2017 10(3):245-247

Introduction: The early identification of vulnerable pediatric cardiac surgery patients can help clinicians provide them with timely support. Heart-type fatty acid-binding protein. (H-FABP) is an early biomarker of myocardial injury in acute myocardial infarction in adults. In this study, we evaluated the correlations between postoperative H-FABP, creatine kinase-myocardial band (CK-MB), troponin-I, total bypass time, and clinical outcomes. Methods: In 32 pediatric patients that underwent ventricular septal defect. closure we measured H-FABP, troponin-I and CK-MB preoperatively and 1, 3, and 6 h after aortic declamping. Spearman's Rho correlations were calculated between laboratory and clinical parameters including inotropic support duration, aortic cross-clamp time, total bypass time, ventilation.weaning.time, and total Intensive Care Unit stay. Results: H-FABP, CK-MB, troponin-I, and total bypass time have a similarly weak to moderate correlation with clinical outcome measures. Conclusions: The predictive value of H-FABP for clinical outcome is not stronger than that of CK-MB, Troponin-I, or bypass times.

http://ift.tt/2vWCl9l

Chronic antepartum maternal hyperoxygenation in a case of severe fetal Ebstein's anomaly with circular shunt physiology

Alisa Arunamata, David M Axelrod, Katherine Bianco, Sowmya Balasubramanian, Amy Quirin, Theresa A Tacy

Annals of Pediatric Cardiology 2017 10(3):284-287

Perinatal mortality remains high among fetuses diagnosed with Ebstein's anomaly of the tricuspid valve. The subgroup of patients with pulmonary valve regurgitation is at particularly high risk. In the setting of pulmonary valve regurgitation, early constriction of the ductus arteriosus may be a novel perinatal management strategy to reduce systemic steal resulting from circular shunt physiology. We report the use of chronic antepartum maternal oxygen therapy for constriction of the fetal ductus arteriosus and modulation of fetal pulmonary vascular resistance in a late presentation of Ebstein's anomaly with severe tricuspid valve regurgitation, reversal of flow in the ductus arteriosus, and continuous pulmonary valve regurgitation.

http://ift.tt/2vWRAyY

Brugada syndrome in children - Stepping into unchartered territory

Shashank P Behere, Steven N Weindling

Annals of Pediatric Cardiology 2017 10(3):248-258

Brugada syndrome (BrS) is an autosomal dominant inherited channelopathy. It is associated with a typical pattern of ST-segment elevation in the precordial leads V1–V3 and potentially lethal ventricular arrhythmias in otherwise healthy patients. It is frequently seen in young Asian males, in whom it has previously been described as sudden unexplained nocturnal death syndrome. Although it typically presents in young adults, it is also known to present in children and infants, especially in the presence of fever. Our understanding of the genetic pathogenesis and management of BrS has grown substantially considering that it has only been 24 years since its first description as a unique clinical entity. However, there remains much to be learned, especially in the pediatric population. This review aims to discuss the epidemiology, genetics, and pathogenesis of BrS. We will also discuss established standards and new innovations in the diagnosis, prognostication, risk stratification, and management of BrS. Literature search was run on the National Center for Biotechnology Information's website, using the Medical Subject Headings (MeSH) database with the search term "Brugada Syndrome" (MeSH), and was run on the PubMed database using the age filter (birth–18 years), yielding 334 results. The abstracts of all these articles were studied, and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles were further explored and read in full.

http://ift.tt/2wgThtU

Congenital left atrial appendage aneurysm: Atypical presentation

Mehdi Bamous, Mahdi Aithoussa, Ayoub Abetti, Abdelatif Boulahya

Annals of Pediatric Cardiology 2017 10(3):293-294

Congenital left atrial appendage aneurysm is a rare condition caused by dysplasia of the atrial muscles. We report a case of a 14-year-old boy, with a 5-month history of cough and in sinus rhythm. Transthoracic echocardiography and computerized tomographic angiography confirmed the aneurysm of the left atrial appendage which was resected through median sternotomy on cardiopulmonary bypass. This case is presented not only for its rarity but also for its atypical clinical presentation.

http://ift.tt/2vWPoaH

Human herpesvirus 6-induced inflammatory cardiomyopathy in immunocompetent children

Surabhi Reddy, Eva Eliassen, Gerhard R Krueger, Bibhuti B Das

Annals of Pediatric Cardiology 2017 10(3):259-268

Over the last decade, human herpesvirus 6 (HHV-6) has been implicated in the etiology of pediatric myocarditis and subsequent dilated cardiomyopathy (DCM). This review provides an overview of recent literature investigating the pathophysiological relevance of HHV-6 in inflammatory cardiomyopathy. We examined 11 cases of previously published pediatric myocarditis and/or DCM associated with HHV-6 and also our experience of detection of virus particles in vascular endothelium of HHV-6 positive endomyocardial biopsy tissue by electron microscopy. The exact role of the presence of HHV-6 and its load remains controversial as the virus is also found in the heart of healthy controls. Therefore, the question remains open whether and how cardiac HHV-6 may be of pathogenetic importance. Quantitative polymerase chain reaction or mRNA testing allows differentiation between low-level latent virus found in asymptomatic myocardium and active HHV-6 infection. Although only a small number of pediatric cases have been reported in literature, HHV-6 should be considered as a causative agent of inflammatory cardiomyopathy, especially in children under three who might be experiencing a primary infection. Future studies are needed to establish a threshold for determining active infection in biopsy samples and the role of coinfections other cardiotropic viruses.

http://ift.tt/2vWFUMT

Consideration of pyloric stenosis as a cause of feeding dysfunction in children with cyanotic heart disease

Nayan T Srivastava, John J Parent, Marcus S Schamberger

Annals of Pediatric Cardiology 2017 10(3):298-300

Feeding difficulty has been reported at a higher incidence in infants with cyanotic heart disease and single ventricle physiology necessitating specialized feeding strategies. However, structural causes of feed intolerance in this subset of patients should not be ignored. This case series highlights three recent cases of pyloric stenosis in infants with left-sided obstructive lesions at our institution. In all three cases, the initial presumed diagnosis was feeding intolerance related to heart disease, and there was significant clinical improvement following identification and correction of pyloric stenosis.

http://ift.tt/2vWPXl1

Clarifying the anatomy and physiology of totally anomalous systemic venous connection

Saurabh Kumar Gupta, Rajnish Juneja, Robert H Anderson, Gurpreet S Gulati, Velayoudam Devagorou

Annals of Pediatric Cardiology 2017 10(3):269-277

The description of totally anomalous systemic venous connection is limited to case reports. In this review, we seek to clarify anatomic, physiologic, and hemodynamic aspects of this extremely rare anomaly. We also present findings of two patients in whom connection of all the systemic veins was anomalous. In the first patient, with usual atrial arrangement, all systemic veins, including the coronary sinus, were connected anomalously to the morphologically left atrium. Limited left-to-right shunt across an atrial septal defect provided the only source of blood flow to the lungs. The diagnosis was established by saline contrast echocardiography and cardiac catheterization. Extreme hypoplasia of the right ventricle precluded corrective surgery, so we performed a bidirectional Glenn operation, along with atrial septectomy. The second patient had isomerism of the left atrial appendages, which creates problems in the definition in anatomic terms since the connection of the systemic veins can never be normal anatomically when both atriums possess a morphologically left appendage. Our patient, nonetheless, had all the systemic and pulmonary veins, connected to the left-sided atrial chamber which then connected to the left ventricle, thus producing hemodynamics of totally anomalous systemic venous connection. We propose an algorithm for evaluation of this hemodynamic combination and discuss management options. We also intend to clarify the potential differences between connection and drainage, with particular attention to the arrangement of atrial appendages. Even though the hemodynamics may be comparable, in anatomic terms, both systemic and pulmonary venoatrial connection will always be anomalous with isomeric atrial appendages.

http://ift.tt/2wg303w

Central perforation of atretic pulmonary valve using coronary microcatheter

Saurabh Kumar Gupta, Rajnish Juneja, Anita Saxena

Annals of Pediatric Cardiology 2017 10(3):304-305

Percutaneous perforation of pulmonary valve, using 0.014" guidewires meant for coronary artery chronic total occlusion (CTO), is increasingly being performed for select cases of pulmonary atresia with intact ventricular septum (PA-IVS). Despite growing experience, procedural failures and complications are not uncommon. Even in infants treated successfully, the orifice created in the atretic pulmonary valve is eccentric. In this report, we present usefulness of coronary microcatheter in alignment of perforating coronary guidewire to the center of atretic pulmonary valve resulting in central perforation.

http://ift.tt/2vWCjyf

Anomalous origin of right pulmonary artery from innominate artery: Repair using pulmonary artery pedicled flap plasty

Roy Varghese, Jai Ganesh, Jeeva Nandam, Sujathaa Ravikumar, Sivakumar Kothandam

Annals of Pediatric Cardiology 2017 10(3):278-280

Origin of the right pulmonary artery from innominate artery is an exceedingly rare anomaly. We report two cases with this anomaly that underwent surgical repair. The surgical technique described achieves tissue-to-tissue anastomosis using a pedicled flap from the main pulmonary artery.

http://ift.tt/2vWPUFR

Ductal aneurysm with postsubclavian coarctation of aorta in an adult

Dibya Ranjan Behera, Krishna Kumar Mohanan Nair, Bijulal Sasidharan

Annals of Pediatric Cardiology 2017 10(3):310-311

We describe a case of ductal aneurysm in an adult patient with post subclavian coarctation of aorta, which is a very rare association.

http://ift.tt/2vWNtD0

Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression

Abstract

Interleukin 6 (IL-6) was abundant in the tumor microenvironment and played potential roles in tumor progression. In our study, the expression of IL-6 in tumor tissues from 36 gastric cancer (GC) patients was significantly higher than in non-tumor tissues. Moreover, the number of CD163⁺CD206⁺ M2 macrophages that infiltrated in tumor tissues was significantly greater than those infiltrated in non-tumor tissues. The frequencies of M2 macrophages were positively correlated with the IL-6 expression in GC tumors. We also found that IL-6 could induce normal macrophages to differentiate into M2 macrophages with higher IL-10 and TGF-β expression, and lower IL-12 expression, via activating STAT3 phosphorylation. Accordingly, knocking down STAT3 using small interfering RNA decreased the expression of M2 macrophages-related cytokines (IL-10 and TGF-β). Furthermore, supernatants from IL-6-induced M2 macrophages promote GC cell proliferation and migration. Moreover, IL-6 production and CD163⁺CD206⁺ M2 macrophage infiltration in tumors were associated with disease progression and reduced GC patient survival. In conclusion, our data indicate that IL-6 induces M2 macrophage differentiation (IL-10^highTGF-β^highIL-12 _p35^low) by activating STAT3 phosphorylation, and the IL-6-induced M2 macrophages exert a pro-tumor function by promoting GC cell proliferation and migration.

http://ift.tt/2vRIpl5

Chest reconstruction using a custom-designed polyethylene 3D implant after resection of the sternal manubrium

http://ift.tt/2fXBd1n

CT-guided 125I interstitial brachytherapy for pelvic recurrent cervical carcinoma after radiotherapy

http://ift.tt/2ikAfNo

Clinicopathologic characteristics, therapy and outcomes of patients with primary ureteral small cell carcinoma: a case series and systematic review of the literature

http://ift.tt/2fYH0nj

Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression

Abstract

Interleukin 6 (IL-6) was abundant in the tumor microenvironment and played potential roles in tumor progression. In our study, the expression of IL-6 in tumor tissues from 36 gastric cancer (GC) patients was significantly higher than in non-tumor tissues. Moreover, the number of CD163⁺CD206⁺ M2 macrophages that infiltrated in tumor tissues was significantly greater than those infiltrated in non-tumor tissues. The frequencies of M2 macrophages were positively correlated with the IL-6 expression in GC tumors. We also found that IL-6 could induce normal macrophages to differentiate into M2 macrophages with higher IL-10 and TGF-β expression, and lower IL-12 expression, via activating STAT3 phosphorylation. Accordingly, knocking down STAT3 using small interfering RNA decreased the expression of M2 macrophages-related cytokines (IL-10 and TGF-β). Furthermore, supernatants from IL-6-induced M2 macrophages promote GC cell proliferation and migration. Moreover, IL-6 production and CD163⁺CD206⁺ M2 macrophage infiltration in tumors were associated with disease progression and reduced GC patient survival. In conclusion, our data indicate that IL-6 induces M2 macrophage differentiation (IL-10^highTGF-β^highIL-12 _p35^low) by activating STAT3 phosphorylation, and the IL-6-induced M2 macrophages exert a pro-tumor function by promoting GC cell proliferation and migration.

http://ift.tt/2vRIpl5

Treatment of childhood astrocytomas with irinotecan and cisplatin

Abstract

Background

Previously we described the outcome of children with spinal cord astrocytoma treated with irinotecan and cisplatin (I/C). We here report the review of the initial institutional experience using this combination for children with low-grade glioma (LGG).

Procedure

I/C chemotherapy consisted of weekly cisplatin (30 mg/m²) and irinotecan (50–65 mg/m²) for a total maximum of 16 doses, administered in an outpatient basis.

Results

Between November 2002 and December 2009, 46 children (median age 6.3 years; range 0.3–17.7) with glioma were treated. We here report the cohort of 31 patients with LGG. Patients received a median of 16 cycles of I/C (range 8–16). The overall objective response [complete response (CR) + partial response (PR)] and disease control (CR + PR + stable disease) rates to I/C treatment were 6.5% [95% confidence interval (CI), 0.8–21.4%] and 93.5% (95% CI 78.6–99.2%), respectively. Disease control persisted for a median of 65 months. Toxicity was predominantly myelosuppression only seen in heavily pretreated patients. Survival analysis shows 5-year event-free survival (EFS) of 54% and 5-year overall survival (OS) of 80%.

Conclusion

I/C chemotherapy produced disease control and clinical improvement in a majority of children with low-grade glioma, with manageable toxicity.

http://ift.tt/2wwpRr4

Rocuronium bromide: clinical application of single-dose pharmacokinetic models to continuous infusion

http://ift.tt/2vW3IjT

Pharmacokinetic and pharmacodynamics of intravenous dexmedetomidine in morbidly obese patients undergoing laparoscopic surgery

Abstract

Background

This study was designed to investigate the pharmacokinetics and pharmacodynamics of dexmedetomidine in morbidly obese patients undergoing laparoscopic surgery.

Methods

Morbidly obese (body mass index ≥40 kg/m²) and normal weight patients scheduled for elective laparoscopic surgery were included (n = 8, each group). After baseline hemodynamic measurement, dexmedetomidine 1 μg/kg was administered over 10 min. General anesthesia was induced with propofol 1.5 mg/kg and fentanyl 4 μg/kg 20 min after completion of dexmedetomidine infusion; the lungs were mechanically ventilated after tracheal intubation. The pharmacokinetics of dexmedetomidine was analyzed by a noncompartment model. Hemodynamic data and peripheral oxygen saturation (SpO₂) were measured up to 30 min after starting dexmedetomidine infusion. Sedation level was measured with the Observer's Assessment of Alertness/Sedation (OAA/S) scale.

Results

Peak plasma concentration, area under the curve to infinity, elimination half-life, and apparent volume of distribution were significantly larger in morbidly obese than in normal weight patients (3.75 ± 0.56 vs. 2.54 ± 0.32 µg/l, P < 0.001; 2174 ± 335 vs. 1594 ± 251 ng h/l, P < 0.001; 225 ± 55 vs. 158 ± 53 min, P = 0.02; 310 ± 63 vs. 164 ± 41 l, P < 0.001, respectively). Although clearance was also higher in obese patients than in normal body weight patients (58.6 ± 10.7 vs. 44.9 ± 9.0 l/h, P = 0.02), it was lower in obese patients than in normal body weight patients after normalization to total body weight (0.47 ± 0.07 vs. 0.64 ± 0.09 l/h/kg, P < 0.001). There were no differences in systolic or diastolic blood pressure or heart rate between the two groups within the 30 min. Sedation level was deeper and SpO₂ was lower in morbidly obese than in normal weight patients. More patients in the morbidly obese patient group experienced deeper sedation after the start of the dexmedetomidine infusion (P < 0.05).

Conclusion

The pharmacokinetics and pharmacodynamics of dexmedetomidine are significantly different in morbidly obese patients compared with normal weight patients. Level of sedation was significantly deeper, and oxygen saturation was significantly lower, in morbidly obese than in normal weight patients, probably resulting from higher plasma concentration after infusion of 1.0 µg/kg.

Clinical trial number, registry URL

ClinicalTrials.gov (NCT01864187), http://ift.tt/2vWvn43.

http://ift.tt/2wgpEIX

Treatment of childhood astrocytomas with irinotecan and cisplatin

Abstract

Background

Previously we described the outcome of children with spinal cord astrocytoma treated with irinotecan and cisplatin (I/C). We here report the review of the initial institutional experience using this combination for children with low-grade glioma (LGG).

Procedure

I/C chemotherapy consisted of weekly cisplatin (30 mg/m²) and irinotecan (50–65 mg/m²) for a total maximum of 16 doses, administered in an outpatient basis.

Results

Between November 2002 and December 2009, 46 children (median age 6.3 years; range 0.3–17.7) with glioma were treated. We here report the cohort of 31 patients with LGG. Patients received a median of 16 cycles of I/C (range 8–16). The overall objective response [complete response (CR) + partial response (PR)] and disease control (CR + PR + stable disease) rates to I/C treatment were 6.5% [95% confidence interval (CI), 0.8–21.4%] and 93.5% (95% CI 78.6–99.2%), respectively. Disease control persisted for a median of 65 months. Toxicity was predominantly myelosuppression only seen in heavily pretreated patients. Survival analysis shows 5-year event-free survival (EFS) of 54% and 5-year overall survival (OS) of 80%.

Conclusion

I/C chemotherapy produced disease control and clinical improvement in a majority of children with low-grade glioma, with manageable toxicity.

http://ift.tt/2wwpRr4

Tracking MET de-addiction in lung cancer: a road towards the oncogenic target.

Publication date: Available online 20 August 2017
Source:Cancer Treatment Reviews
Author(s): S. Pilotto, L. Carbognin, N. Karachaliou, P.C. Ma, R. Rosell, G. Tortora, E. Bria
The discovery of druggable oncogenic drivers (i.e. EGFR and ALK), along with the introduction of comprehensive tumor genotyping techniques into the daily clinical practice define non-small-cell lung cancer (NSCLC) as a group of heterogeneous diseases, requiring a context-personalized clinico-therapeutical approach. Among the most investigated biomarkers, the MET proto-oncogene has been extensively demonstrated to play a crucial role throughout the lung oncogenesis, unbalancing the proliferation/apoptosis signaling and influencing the epithelial-mesenchymal transition and the invasive phenotype. Nevertheless, although different mechanisms eliciting the aberrant MET-associated oncogenic stimulus have been detected in lung cancer (such as gene amplification, increased gene copy number, mutations and MET/HGF overexpression), to date no clinically impactful results have been achieved with anti-MET tyrosine kinase inhibitors and monoclonal antibodies in the context of an unselected or MET enriched population. Recently, MET exon 14 splicing abnormalities have been identified as a potential oncogenic target in lung cancer, able to drive the activity of MET inhibitors in molecularly selected patients.In this paper, the major advancement and drawbacks of MET history in lung cancer are reviewed, underlying the renewed scientific euphoria related to the recent identification of MET exon 14 splicing variants as an actionable oncogenic target.



http://ift.tt/2vRxrw5

Right-left or midgut-hindgut?

http://ift.tt/2fXtLmL

Optimizing tumor immune response through combination of radiation and immunotherapy

Abstract

Radiation therapy and immunotherapy are two highly evolving modalities for the treatment of solid tumors. Immunotherapeutic drugs can either stimulate the immune system via immunogenic pathways or target co-inhibitory checkpoints. An augmented tumor cell recognition by host immune cells can be achieved post-irradiation, as irradiated tissues can release chemical signals which are sensed by the immune system resulting in its activation. Different strategies combining both treatment modalities were tested in order to achieve a better therapeutic response and longer tumor control. Both regimens act synergistically to one another with complimentary mechanisms. In this review, we explore the scientific basis behind such a combination, starting initially with a brief historical overview behind utilizing radiation and immunotherapies for solid tumors, followed by the different types of these two modalities, and the biological concept behind their synergistic effect. We also shed light on the common side effects and toxicities associated with radiation and immunotherapy. Finally, we discuss previous clinical trials tackling this multimodality combination and highlight future ongoing research.

http://ift.tt/2x4rQRB