Cancer by Sfakianakis Alexandros: 01/05/18

Παρασκευή 5 Ιανουαρίου 2018

Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of signaling pathways and molecular mechanisms of drug resistance

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miR-99a-5p acts as tumor suppressor via targeting to mTOR and enhances RAD001-induced apoptosis in human urinary bladder urothelial carcinoma cells

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The Influences of Chromium Supplementation on Glycemic Control, Markers of Cardio-Metabolic Risk, and Oxidative Stress in Infertile Polycystic ovary Syndrome Women Candidate for In vitro Fertilization: a Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

This study was carried out to investigate the effects of chromium intake on glycemic control, markers of cardio-metabolic risk, and oxidative stress in infertile polycystic ovary syndrome (PCOS) women candidate for in vitro fertilization (IVF). This randomized double-blind, placebo-controlled trial was done among 40 subjects with infertile PCOS candidate for IVF, aged 18–40 years old. Individuals were randomly allocated into two groups to take either 200 μg/day of chromium (n = 20) or placebo (n = 20) for 8 weeks. Biochemical parameters were assessed at baseline and at end-of-trial. Compared with the placebo, taking chromium supplements led to significant reductions in fasting plasma glucose (− 2.3 ± 5.7 vs. + 0.9 ± 3.1 mg/dL, P = 0.03), insulin levels (− 1.4 ± 2.1 vs. + 0.4 ± 1.7 μIU/mL, P = 0.004), homeostatic model of assessment for insulin resistance (− 0.3 ± 0.5 vs. + 0.1 ± 0.4, P = 0.005), and a significant increase in quantitative insulin sensitivity check index (+ 0.004 ± 0.008 vs. − 0.001 ± 0.008, P = 0.03). In addition, chromium supplementation significantly decreased serum triglycerides (− 19.2 ± 33.8 vs. + 8.3 ± 21.7 mg/dL, P = 0.004), VLDL- (− 3.8 ± 6.8 vs. + 1.7 ± 4.3 mg/dL, P = 0.004) and total cholesterol concentrations (− 15.3 ± 26.2 vs. − 0.6 ± 15.9 mg/dL, P = 0.03) compared with the placebo. Additionally, taking chromium supplements was associated with a significant increase in plasma total antioxidant capacity (+ 153.9 ± 46.1 vs. − 7.8 ± 43.9 mmol/L, P < 0.001) and a significant reduction in malondialdehyde values (−0.3 ± 0.3 vs. + 0.1 ± 0.2 μmol/L, P = 0.001) compared with the placebo. Overall, our study supported that chromium administration for 8 weeks to infertile PCOS women candidate for IVF had beneficial impacts on glycemic control, few variables of cardio-metabolic risk, and oxidative stress.

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The Influences of Chromium Supplementation on Glycemic Control, Markers of Cardio-Metabolic Risk, and Oxidative Stress in Infertile Polycystic ovary Syndrome Women Candidate for In vitro Fertilization: a Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

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Pneumocephalus and seizures following combined spinal-epidural for labor

Most cases of pneumocephalus following neuraxial blocks are associated with accidental dural puncture using loss of resistance to air for identification of the epidural space [1]. To our knowledge, there are no published reports in literature following use of saline for loss of resistance. We report the finding of simultaneous pneumocephalus and a cavernoma in a patient who received a combined spinal-epidural analgesia for labor, using loss of resistance to saline (LORS). The patient provided written consent for the authors to publish this report.

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Editorial Board

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Nasotracheal intubation through pharyngeal flap after pharyngeal flap construction

A 24-year-old woman provided her written consent to publish the details of her case. She had undergone multiple surgeries including pharyngeal flap construction for bilateral cleft lip and palate. All previous operations were performed under general anesthesia by oral intubation. In the present procedure, sagittal split ramus osteotomy under general anesthesia with nasotracheal intubation was planned. We obtained the three-dimensional morphological structure of the pharyngeal flap (Fig. 1). The measurements of the cross-section at the narrowest were 5.1×12.8mm for the left orifice and 3.2×13.2mm for the right.

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Clinical experiences of unilateral anterior sub-costal quadratus lumborum block for a nephrectomy

Among several quadratus lumborum (QL) blocks, an anterior sub-costal QL block is a new technique, and there are only a few reports of this new approach in the literature [1,2]. In this case, we reported two cases in which we used the anterior sub-costal QL block for a nephrectomy.

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Clinical effects of prophylactic use of phentolamine in patients undergoing pheochromocytoma surgery

To the Editor,

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Emergency insertion of the LMA protector airway in patients in the lateral position

The LMAR Protector™ Airway (Teleflex Medical Japan, Tokyo, Protector), a new type of second generation airway, has an integrated cuff pressure indicator that allows continuous cuff pressure monitoring at a glance [1,2]. Continuous cuff pressure monitoring contributes to safe management in the perioperative period in all situations. Here, we report two cases in which the Protector was inserted in an emergency situation with the patient in the lateral position.

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Respiratory effect of interscalene brachial plexus block vs combined infraclavicular plexus block with suprascapular nerve block for arthroscopic shoulder surgery

Shoulder surgery typically results in moderate to severe postoperative pain, especially within the first 24h after surgery. The interscalene nerve block (ISB) is one of the most effective analgesic techniques for shoulder surgery. A common adverse effect after ISB remains the occurrence of ipsilateral phrenic nerve block. In the literature [1] diaphragm-sparing nerve blocks alternative to ISB for shoulder surgery, such as supraclavicular block, distal nerve blocks, intraarticular analgesia, has been reported; recently [2] a new combination of suprascapular nerve block (SSB) and infraclavicular block (ICB) seemed to provide surgical anesthesia and satisfactory postoperative analgesia, but, the respiratory effects of this technique are still not well documented.

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Under pressure: Evaluating the role of intraoperative hemodynamics in postoperative acute kidney injury

In this issue of Journal of Clinical Anesthesia, Wu et al. describe their well-designed randomized trial investigating the impact of targeted mean arterial pressure (MAP) ranges on postoperative acute kidney injury (AKI) [1]. Their study is of pressing concern: postoperative AKI remains a source of shared apprehension among anesthesiologists, surgeons, and nephrologists, for which prevention and treatment strategies are a matter of ongoing debate. The healthcare burden of postoperative AKI is well-described: it is common, costly, and life-threatening.

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Incidence of lower-extremity muscle weakness after quadratus lumborum block

Since the original publication on the quadratus lumborum (QL) block in 2013, various approaches for QL block administration have been reported [1,2]. Lower-extremity muscle weakness after a posterior QL block has been reported as a complication [3]. However, there have been no reports of lower-extremity muscle weakness after a QL block using other approaches. We investigated the incidence of lower-extremity muscle weakness after each type of QL block.

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Lack of generalizability of observational studies' findings for turnover time reduction and growth in surgery based on the State of Iowa, where from one year to the next, most growth was attributable to surgeons performing only a few cases per week

Three observational studies at large teaching hospitals found that reducing turnover times resulted in the surgeons performing more cases. We sought to determine if these findings are generalizable to other hospitals, because, if so, reducing turnover times may be an important mechanism for hospitals to use for growing caseloads.

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Lidocaine post-nasal dripping (LPND): An easy way for awake nasal intubation

Several techniques of topical anesthesia for awake fiberoptic intubation (AFOI) have been described such as "spray as you go" [1,2], nebulization [2], atomization [3,4] transtracheal injection [5]. These require multiple complicated steps [1,2], specialized equipment [2–4], and are invasive [5].

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Severe type B lactic acidosis and insulin-resistant hyperglycemia related to cadaveric kidney transplantation

Lactic acidosis, increased lactate levels >2mmol/L with a high anion gap metabolic acidosis, commonly occurs due to hypoperfusion/hypoxia (type A) but may also arise due to other causes, often overlooked, such as thiamine deficiency (type B) [1]. We report the perioperative occurrence of severe type B lactic acidosis with insulin-resistant hyperglycemia related to cadaveric kidney transplantation and its rapid resolution after intravenous thiamine administration. Written consent was obtained from the patient.

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Use of dexmedetomidine in a cardiac intensive care unit

Delirium, pain and agitation, known as the "triad of Intensive Care Units (ICU)" [1] are very common in critical patients. At least 20% of patients develop delirium during their stay in the ICU, reaching 80% in those receiving mechanical ventilation [2]. There is a need to identify these patients for appropriate treatment and prevention, as this neuronal dysfunction is associated with increased mortality, length of hospitalization, dependency and disability at discharge [3,4].

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Bilateral adductor canal block catheters in patients undergoing simultaneous bilateral knee arthroplasty: A series of 17 patients

Continuous adductor canal blocks (ACB) have been shown to reduce pain with knee flexion, decrease opioid consumption, and enhance ambulation following total knee arthroplasty [1]. Of the patients who undergo bilateral knee arthroplasties, a small subset have the procedures performed during the same operative encounter rather than a staged procedure [2]. These patients present additional perioperative pain and rehabilitation challenges, in addition to a longer length of hospital stay [2,3]. Adequate analgesia is imperative for immediate postoperative rehabilitation; however, there is a paucity of research regarding regional techniques for simultaneous bilateral knee arthroplasty (SBKA).

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Videolaryngoscope versus Macintosh laryngoscope for tracheal intubation in adults with obesity: A systematic review and meta-analysis

Videolaryngoscopy has become more common since the 2000s. Despite several anecdotal reports in the literature, it remains unclear whether videolaryngoscopy is superior to direct Macintosh laryngoscopy for tracheal intubation in adults with obesity. This systematic review and meta-analysis focused on prospective randomised trials comparing videolaryngoscopes with the Macintosh laryngoscope for tracheal intubation in adults with obesity.

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Retroclavicular approach to infraclavicular brachial plexus block for distal radius fracture in a patient with implanted pacemaker

Patients with implanted pacemaker underwent upper limb surgery under regional anesthesia in the literature are rarely. We report a case of successful retroclavicular approach to infraclavicular brachial plexus block (RA-IBPB) in a patient with implanted pacemaker and with requiring open osteosynthesis due to distal radius fracture.

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Anesthetic management for laparoscopic sleeve gastrectomy to a child

Anesthesia for obese children undergoing weight loss surgery poses a challenge for the anesthetists given that this population has high risk of developing psychosocial and medical comorbidities such as pulmonary and cardiovascular disorders, hypertension, dyslipidemia, obstructive sleep apnea and type 2 diabetes mellitus [1–3].

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Ketorolac dose-response for acute pain is well known and the safety rules for adequate prescribing are clear

The study by Duttchen et al. [1] shows almost no difference in analgesic efficacy when comparing 15 and 30mg of IV ketorolac given intraoperatively to provide postoperative pain relief. In the discussion, the authors indicate that another 2017 study performed in an emergency department similarly showed that in patients with acute pain 10, 15 and 30mg are of similar analgesic efficacy [2], suggesting that these data are new.

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Takotsubo cardiomyopathy complicating thoracoabdominal aortic aneurysm repair

We describe the management of a patient with symptomatic spinal cord hypoperfusion after thoracoabdominal aortic aneurysm repair, where the neurological insult and associated emotional stress precipitated Takotsubo cardiomyopathy. Transthoracic Echocardiography showed akinetic mid and apical left ventricular segments, while basal segments were spared. Emergent coronary angiography ruled out acute coronary syndrome. Excess catecholamines have been postulated as a contributing mechanism to the disease, therefore, catecholamines were avoided to prevent further myocardial injury.

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Centile charts for cranial sutures in children younger than 1 year based on ultrasound measurements

Abstract

Background

Cranial US allows for the evaluation of premature closure (synostosis) or abnormal widening of the cranial sutures. An understanding of the normal anatomy is required to help define the presence or absence of abnormality.

Objective

To provide reference for normal ultrasound measurements of cranial sutures during the child's first year.

Materials and methods

We included children ages 0 to 12 months who were referred to the hospital during 2011–2013 for radiographic evaluation of cranial sutures. Cranial US study was focused on evaluating the sagittal, coronal, lambdoid and metopic sutures. We measured the hypoechoic gap between the bones (patent suture). Two readers performed the measurements, blinded to clinical indications and previous reports. Estimates of the 10^th, 25^th, 50^th, 75^th and 90^th percentiles were achieved for ages 1–12 months.

Results

Of 129 children whose families consented to cranial US, 11 were excluded because of craniosynostosis and 3 for suboptimal quality of cranial US images. In 115 patients measurements of normal cranial sutures were obtained (75 boys [65%], ages 0.26–11.27 months). For each suture, the suture size decreased significantly with age (P<0.001). Only the metopic suture was noted to close completely toward the end of the first year of age. There were no statistically significant differences in age-related suture size by gender.

Conclusion

The current patient series represents a reference of percentiles of normal ultrasound measurements of cranial sutures during the first year of age.

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Centile charts for cranial sutures in children younger than 1 year based on ultrasound measurements

Abstract

Background

Objective

To provide reference for normal ultrasound measurements of cranial sutures during the child's first year.

Materials and methods

Results

Conclusion

The current patient series represents a reference of percentiles of normal ultrasound measurements of cranial sutures during the first year of age.

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Tanshinone IIA induces cell death via Beclin-1-dependent autophagy in oral squamous cell carcinoma SCC-9 cell line

Abstract

Tanshinone IIA (TAN) is one of the major functional compounds of Salvia miltiorrhiza Bunge and possesses the ability to suppress the growth of multiple cancer cell types via its apoptosis- and autophagy-inducing functions. In this study, the effect of TAN therapy on the survival of oral squamous cell carcinoma (OSCC) was evaluated, and the underlying mechanism involved in the treatment was investigated. Human oral squamous cell carcinoma cell SCC-9 was used for in vitro assays and induction in an OSCC xenograft mouse model. The tumor cells were subjected to TAN administration at different concentrations. Then the apoptosis and autophagy processes in SCC-9 cells were evaluated and the activities of Beclin-1/Atg7/Atg12-Atg5 and PI3K/Akt/mTOR pathways were determined. In addition, by knocking down the expression of Beclin-1 in SCC-9 cells, the study also assessed the role of the indicator in the anti-OSCC effect of TAN. Results of in vitro assays were further validated with an OSCC xenograft mouse model. Administration of TAN-induced cell apoptosis and upregulated the expression of cleaved-caspase-3. Simultaneously, the autophagy process in SCC-9 cells was initiated by TAN, which was signaled by the formation of autophagosomes and increase in the ratio of LC3 II/LC3I. The above processes were associated with the activation of Beclin-1/Atg7/Atg12-Atg5 signaling and inhibition of PI3K/Akt/mTOR signaling. Our results also inferred a partially Beclin-1-dependent mechanism of action of TAN in OSCC cells: knockdown of the Beclin-1 blocked the effect of TAN on SCC-9 cells both in vivo and in vitro. Our study provided a preliminary explanation of the mechanism involved in TAN effect: the agent exerted its autophagy-inducing effect against OSCC in a multipronged manner, by both inducing the Beclin-1/Atg7/Atg12-Atg5 pathway and suppressing the PI3K/Akt/mTOR pathway.

Suppressing effect of Tanshinone IIA (TAN) on the survival of oral squamous cell carcinoma (OSCC), which was dependent on the Beclin-1-induced autophagic process.

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Tanshinone IIA induces cell death via Beclin-1-dependent autophagy in oral squamous cell carcinoma SCC-9 cell line

Abstract

Suppressing effect of Tanshinone IIA (TAN) on the survival of oral squamous cell carcinoma (OSCC), which was dependent on the Beclin-1-induced autophagic process.

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Patient-Reported Outcomes in Psychological Treatment for an Adolescent Oncology Patient: A Case Report

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.

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Patient-Reported Outcomes in Psychological Treatment for an Adolescent Oncology Patient: A Case Report

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.

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Preoperative to postoperative change in neutrophil-to-lymphocyte ratio predict survival in colorectal cancer patients

Future Oncology, Ahead of Print.

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Issue Information - Ed Board

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Preoperative to postoperative change in neutrophil-to-lymphocyte ratio predict survival in colorectal cancer patients

Future Oncology, Ahead of Print.

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Issue Information - Ed Board

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Breast carcinoma with 21-gene recurrence score lower than 18: rate of locoregional recurrence in a large series with clinical follow-up

Abstract

Background

The 21-gene recurrence score (RS) assay determines the benefit of adding chemotherapy to endocrine therapy for patients with early stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. The RS risk groups predict the likelihood of distant recurrence and have recently been associated with an increased risk of locoregional recurrence (LRR). This study analyzed clinicopathologic features of patients with low RS and LRR.

Methods

In our institutional database, we identified 1396 consecutive female patients with lymph node negative, ER+/HER2- invasive breast carcinoma and low RS (<18) results, treated at our center from 2008 to 2013. We collected data on clinicopathologic features, treatment and outcome.

Results

The median patient age was 57 years (range 22–90). The median tumor size was 1.2 cm (range 0.3–5.8). Overall, 66.6% (930/1396) women were treated with breast conserving surgery (BCS) and radiation therapy, 3.4% (48/1396) with BCS alone, 29.7% (414/1396) with total mastectomy, and 0.3% (4/1396) with total mastectomy and radiation therapy. Most patients (84.8%; 1184/1396) received endocrine therapy alone, 12.1% (169/1396) were treated with chemotherapy plus endocrine therapy, and only 3.1% (43/1396) received no systemic therapy. At a median follow-up of 52 months, 0.9% (13/1396) of patients developed LRR. Sites of LRR included the ipsilateral breast (n = 8), chest wall (n = 3), axillary node (n = 1), and internal mammary node (n = 1). All patients with LRR had negative resection margins at the initial surgery. The rate of LRR in patients treated with adjuvant endocrine therapy alone was 0.7% (8/1184). All eight patients received standard local treatment. Three patients had lymphovascular invasion but no other significant risk factors for LRR were identified.

Conclusions

Our study of node negative, ER+/HER2- breast cancer patients with low RS observed extremely low rates of LRR: 0.9% (13/1396) in the whole cohort and 0.7% (8/1184) in patients treated with endocrine therapy alone. As the largest series to date, we report detailed clinicopathologic data and clinical outcomes of this cohort and provide a comprehensive characterization of patients who developed LRR.

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A systematic review of clinic and community intervention to increase fecal testing for colorectal cancer in rural and low-income populations in the United States – How, what and when?

Abstract

Background

Interventions to improve fecal testing for colorectal cancer (CRC) exist, but are not yet routine practice. We conducted this systematic review to determine how implementation strategies and contextual factors influenced the uptake of interventions to increase Fecal Immunochemical Tests (FIT) and Fecal Occult Blood Testing (FOBT) for CRC in rural and low-income populations in the United States.

Methods

We searched Medline and the Cochrane Library from January 1998 through July 2016, and Scopus and clinicaltrials.gov through March 2015, for original articles of interventions to increase fecal testing for CRC. Two reviewers independently screened abstracts, reviewed full-text articles, extracted data and performed quality assessments. A qualitative synthesis described the relationship between changes in fecal testing rates for CRC, intervention components, implementation strategies, and contextual factors. A technical expert panel of primary care professionals, health system leaders, and academicians guided this work.

Results

Of 4218 citations initially identified, 27 unique studies reported in 29 publications met inclusion criteria. Studies were conducted in primary care (n = 20, 74.1%), community (n = 5, 18.5%), or both (n = 2, 7.4%) settings. All studies (n = 27, 100.0%) described multicomponent interventions. In clinic based studies, components that occurred most frequently among the highly effective/effective study arms were provision of kits by direct mail, use of a pre-addressed stamped envelope, client reminders, and provider ordered in-clinic distribution. Interventions were delivered by clinic staff/community members (n = 10, 37.0%), research staff (n = 6, 22.2%), both (n = 10, 37.0%), or it was unclear (n = 1, 3.7%). Over half of the studies lacked information on training or monitoring intervention fidelity (n = 15, 55.6%).

Conclusions

Studies to improve FIT/FOBT in rural and low-income populations utilized multicomponent interventions. The provision of kits through the mail, use of pre-addressed stamped envelopes, client reminders and in-clinic distribution appeared most frequently in the highly effective/effective clinic-based study arms. Few studies described contextual factors or implementation strategies. More robust application of guidelines to support reporting on methods to select, adapt and implement interventions can help end users determine not just which interventions work to improve CRC screening, but which interventions would work best in their setting given specific patient populations, clinical settings, and community characteristics.

Trial registration

In accordance with PRISMA guidelines, our systematic review protocol was registered with PROSPERO, the international prospective register of systematic reviews, on April 16, 2015 (registration number CRD42015019557).

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Doxorubicin resistance in breast cancer cells is mediated by extracellular matrix proteins

Abstract

Background

Cancer cell resistance to therapeutics can result from acquired or de novo-mediated factors. Here, we have utilised advanced breast cancer cell culture models to elucidate de novo doxorubicin resistance mechanisms.

Methods

The response of breast cancer cell lines (MCF-7 and MDA-MB-231) to doxorubicin was examined in an in vitro three-dimensional (3D) cell culture model. Cells were cultured with Matrigel™ enabling cellular arrangements into a 3D architecture in conjunction with cell-to-extracellular matrix (ECM) contact.

Results

Breast cancer cells cultured in a 3D ECM-based model demonstrated altered sensitivity to doxorubicin, when compared to those grown in corresponding two-dimensional (2D) monolayer culture conditions. Investigations into the factors triggering the observed doxorubicin resistance revealed that cell-to-ECM interactions played a pivotal role. This finding correlated with the up-regulation of pro-survival proteins in 3D ECM-containing cell culture conditions following exposure to doxorubicin. Inhibition of integrin signalling in combination with doxorubicin significantly reduced breast cancer cell viability. Furthermore, breast cancer cells grown in a 3D ECM-based model demonstrated a significantly reduced proliferation rate in comparison to cells cultured in 2D conditions.

Collectively, these novel findings reveal resistance mechanisms which may contribute to reduced doxorubicin sensitivity.

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An Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer [Research Watch]

Stress-activated ADRB2 signaling promotes tumor innervation and PDAC development.

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Determination of mTORC1 Complex Structures Reveals Regulatory Mechanisms [Research Watch]

RHEB promotes allosteric activation of mTOR whereas PRAS40 blocks substrate recruitment sites.

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Glutaminolysis Drives Lung Cancer Metastasis via the PLAG1-GDH1 Axis [Research Watch]

PLAG1-mediated GDH1 upregulation promotes LKB1-deficient lung cancer anoikis resistance.

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Myeloproliferative Neoplasms May Be Sensitive to Dual BET/JAK Inhibition [Research Watch]

In myeloproliferative neoplasms (MPN) chromatin changes promote NF-B signaling to drive inflammation.

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Expressions and clinical significance of HER4 and CD44 in sinonasal mucosal malignant melanoma

Sinonasal mucosal malignant melanoma (SNMMM) is a rare disease. The aim of this study was to investigate the expressions of HER4 and CD44 in human SNMMM tissues and their relationship with the clinicopathological features and prognosis of patients. In total, 64 paraffin-embedded samples of SNMMM treated in our hospital from 29 December 1999 to 24 June 2011 were collected. HER4 and CD44 were detected in the tissues of SNMMM by immunohistochemistry. The differences in the HER4 and CD44 expressions in the tissues were evaluated and matched with clinicopathological parameters and the survival rate, respectively. The positive rates of the HER4 and CD44 expressions were 70.3 and 65.6%, respectively; the positive expression of HER4 was correlated with a positive expression of CD44 (P0.05). The expressions of HER4 and CD44 were not significantly correlated with sex, age, pigment, tumor site, etc. (P>0.05). Our results further emphasize a correlation between HER4 and CD44 expressions in SNMMM tissues and point out that a positive HER4 expression might be an important factor in valuing the prognosis of patients with SNMMM. *Wenjia Zhu and Shimin Li contributed equally to the writing of this article. Correspondence to Shuyi Wang, MD, Department of Pathology, Eye and ENT Hospital, Fudan University, #83 Fenyang Road, Xuhui District, Shanghai 200031, China Tel: +86 138 168 80539; fax: +86 021 643 77134;e-mail: wangshuyi@eent.shmu.edu.cn Received August 7, 2017 Accepted December 14, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Comparative outcomes and toxicities for ruthenium-106 versus palladium-103 in the treatment of choroidal melanoma

For the treatment of choroidal melanoma, palladium-103 (103Pd) and ruthenium-106 (106Ru) plaque brachytherapy shows reduced toxicity compared with the historical standard iodine-125. No report has directly compared the clinical outcomes between 103Pd and 106Ru, and the reasons for the selection of one over the other remain purely theoretical. Patients with choroidal melanoma with apical tumor height up to 5 mm were included. Patients from Emory University were treated with 103Pd between 1993 and 2012. Patients from Cleveland Clinic were treated with 106Ru between 2005 and 2010. Medical records were retrospectively reviewed. We compared post-treatment visual acuity (VA), toxicity, and oncologic outcomes. 103Pd patients (n=124) and 106Ru patients (n=42) had a median follow-up of 4.2 and 5.0 years, respectively. Radiation retinopathy-free survival was similar for both radioisotopes, but 106Ru had lower grades of retinopathy (P=0.006). 103Pd was associated with worse VA preservation (≥20/40) by year 3 (odds ratio: 3.8; 95% confidence interval: 1.01–14.31, P=0.048). 103Pd was associated with higher distant metastases-free survival (DMFS) in multivariate analysis (hazard ratio: 0.10; 95% confidence interval: 0.02–0.38; P

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Local Anesthetic Systemic Toxicity: A Review of Recent Case Reports and Registries

This review summarizes presenting features, management, and outcomes of local anesthetic systemic toxicity (LAST) from published cases and those submitted to online registries capturing use of intravenous lipid emulsion (ILE) therapy. The results of single-center and multicenter registries and epidemiologic studies complement this information. Between March 2014 and November 2016, 47 separate cases of LAST were described in 35 peer-reviewed articles. Local anesthetic systemic toxicity events occurred as a result of penile blocks (23%), local infiltration (17%), and upper/lower extremity, torso, and neuraxial blockade. Twenty-two patients (47%) were treated with ILE, and 2 patients (4.3%) died. During the same time period, 11 cases submitted to lipidrescue.org were treated with ILE and survived. The incidence of LAST reported in registries is 0.03% or 0.27 (95% confidence interval, 0.21–0.35) per 1000 peripheral nerve blocks (denominator of 251,325). Seizure (53% and 61% from case reports and registries, respectively) was the most common presenting feature. Accepted for publication October 9, 2017. Address correspondence to: Marina Gitman, MD, Department of Anesthesiology, College of Medicine, University of Illinois, 1740 W Taylor St, Suite 3200 W, Chicago, IL 60612 (e-mail: gitman@uic.edu). The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Relevance of 3d culture systems to study osteosarcoma environment

The efficacy of pre-operative preparation with intravenous iron and/or erythropoietin in anaemic patients undergoing orthopaedic surgery: An observational study

BACKGROUND Pre-operative anaemia and transfusion are common among patients undergoing elective orthopaedic surgery. Application of 'patient blood management' might be the most effective way to reduce both anaemia and transfusion. Pre-operative administration of iron and/or erythropoietin (EPO) is one of the cornerstones of the first pillar of patient blood management, but in a daily clinical setting, efficacy and long-term safety of this measure have not been analysed thoroughly to date. OBJECTIVE To investigate the influence of pre-operative preparation (PREP) of patients with iron and/or EPO on peri-operative transfusion needs and long-term survival. DESIGN AND METHODS This was a single-centre, retrospective study. After approval of our local ethics committee, data of 5518 patients who received total hip or total knee replacement between 2008 and 2014 were included. Patients receiving iron and/or EPO were included in the PREP group, whereas patients without iron and/or EPO were included in the no preparation group. From the full data set, a bias-reduced subset of 662 patients was obtained by means of propensity score-matching to compare peri-operative red blood cell utilisation and long-term survival of patients between groups. RESULTS Patients in the PREP group needed a lower number of units of red blood cells than patients in the no preparation group (0.2 ± 0.8 vs. 0.5 ± 1.3, P

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Effect of pressure-controlled inverse ratio ventilation on dead space during robot-assisted laparoscopic radical prostatectomy: A randomised crossover study of three different ventilator modes

BACKGROUND Pressure-controlled inverse inspiratory to expiratory ratio ventilation (PC-IRV) is thought to be beneficial for reducing the dead space volume. OBJECTIVE To investigate the effects of PC-IRV on the components of dead space during robot-assisted laparoscopic radical prostatectomy (RLRP). DESIGN A randomised crossover study of three different ventilator modes. SETTING A single university hospital from September 2014 to April 2015. PATIENTS Twenty consecutive study participants undergoing RLRP. INTERVENTIONS Patients were ventilated sequentially with three different modes in random order for 30 min: volume control ventilation (VCV; inspiratory to expiratory ratio 0.5), pressure control ventilation (PCV; inspiratory to expiratory ratio 0.5) and PC-IRV. Inverse inspiratory to expiratory ratio was adjusted individually by observing the expiratory flow-time wave to prevent the risk of dynamic pulmonary hyperinflation. MAIN OUTCOME MEASURES The primary outcome included physiological dead space (VDphys), airway dead space (VDaw), alveolar dead space (VDalv) and shunt dead space (VDshunt). VDphys was calculated by Enghoff's method. We also analysed respiratory dead space (VDresp) and VDaw using a novel analytical method. Then, VDalv and VDshunt were calculated by VDalv = VDresp − VDaw and VDshunt = VDphys − VDresp, respectively. RESULTS The VDphys/expired tidal volume (VTE) ratio in PC-IRV (29.2 ± 4.7%) was significantly reduced compared with that in VCV (43 ± 8.5%) and in PCV (35.9 ± 3.9%). The VDshunt/VTE in PC-IRV was significantly smaller than that in VCV and PCV. VDaw/VTE in PC-IRV was also significantly smaller than that in VCV but not that in PCV. There was no significant change in VDalv/VTE. CONCLUSION PC-IRV with the inspiratory to expiratory ratio individually adjusted by the expiratory flow-time wave decreased VDphys/VTE in patients undergoing RLRP. TRIAL REGISTRATION University Hospital Medical Information Network in Japan 000014004. Correspondence to Go Hirabayashi, MD, Department of Anaesthesiology, Mizonokuchi Hospital, Teikyo University School of Medicine, 3–8–3 Mizonokuchi, Takatsu-ku, Kawasaki, Kanagawa 213–8507, Japan Tel: +81 44 844 3333; fax: +81 44 844 3390; e-mail: hirabayashi1967@gmail.com Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

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Receptor Conversion in Distant Breast Cancer Metastases: A Systematic Review and Meta-analysis

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Abstract

Background

In metastatic breast cancer, hormone and/or human epidermal growth factor receptor 2 (HER2)–targeted therapy decision-making is still largely based on tissue characteristics of the primary tumor. However, a change of estrogen receptor alpha (ERα), progesterone receptor (PR), and HER2 status in distant metastases has frequently been reported. The actual incidence of this phenomenon has been debated.

Methods

We performed a meta-analysis including 39 studies assessing receptor conversion from primary breast tumors to paired distant breast cancer metastases. We noted the direction of change (positive to negative or vice versa) and performed subgroup analyses for different thresholds for positivity, the type of test used to assess HER2 receptor status, and metastasis location–specific differences (two-sided tests).

Results

Overall, the incidence of receptor conversion varied largely between studies. For ERα, PR, and HER2, we found that random effects pooled positive to negative conversion percentages of 22.5% (95% confidence interval [CI] = 16.4% to 30.0%), 49.4% (95% CI = 40.5% to 58.2%), and 21.3% (95% CI = 14.3% to 30.5%), respectively. Negative to positive conversion percentages were 21.5% (95% CI = 18.1% to 25.5%), 15.9% (95% CI = 11.3% to 22.0%), and 9.5% (95% CI = 7.4% to 12.1%). Furthermore, ERα discordance was statistically significantly higher in the central nervous system and bone compared with liver metastases (20.8%, 95% CI = 15.0% to 28.0%, and 29.3%, 95% CI = 13.0% to 53.5%, vs 14.3%, 95% CI = 11.3% to 18.1, P = .008 and P < .001, respectively), and PR discordance was higher in bone (42.7%, 95% CI = 35.1% to 50.6%, P < .001) and liver metastases (47.0%, 95% CI = 41.0% to 53.0%, P < .001) compared with central nervous system metastases (23.3%, 95% CI = 16.0% to 32.6%).

Conclusions

Receptor conversion for ERα, PR, and HER2 occurs frequently in the course of disease progression in breast cancer. Large prospective studies assessing the impact of receptor conversion on treatment efficacy and survival are needed. Meanwhile, reassessing receptor status in metastases is strongly encouraged.

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Epithelial ovarian cancer mortality among Hispanic women: Sub-ethnic disparities and survival trend across time: An analysis of SEER 1992–2013

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Chen Chen, Talar W. Markossian, Abigail Silva, Yelena N. Tarasenko
BackgroundOver the past half century the proportion of Hispanics in the US population has been steadily increasing, and groups of Hispanic origin have diversified. Despite notable racial and ethnic disparities in ovarian cancer (OC) mortality, population-based studies on OC among Hispanic females are lacking.ObjectivesTo examine sub-ethnic disparities in OC mortality and survival trends using the Surveillance, Epidemiology, and End Results Program (SEER) 18 data on Hispanic women diagnosed with epithelial OC during 1992–2013.MethodsThe disparities in OC 5 year survival and mortality were examined using log-rank tests and Cox proportional hazards models, adjusted for sociodemographic and pathological characteristics, time of diagnosis, receipt of resection surgery and county socioeconomic status. Trends in 5-year survival rates were examined using joinpoint regression models.ResultsThe 5-year survival was lowest in Puerto Ricans (median survival: 33 months; survival rate: 31.07%) and was highest in the "Other" Hispanic subgroup (median survival: 59 months; survival rate: 49.14%) (log-rank test: P < 0.001). The OC-specific death hazards in Mexicans (HRadj: 0.82, 95%CI: 0.67–1.00, P = 0.048), South or Central Americans (HRadj: 0.77, 95%CI: 0.62–0.96, P = 0.005) and Other Hispanics (HRadj: 0.76, 95%CI: 0.63–0.92, P = 0.038) were significantly lower than for Puerto Ricans. Mortality rates of Cubans and Puerto Ricans were not significantly different. During 1992–2008, there were non-significant increasing trends in the 5-year all-cause and OC-specific survival rates: from 43.37% to 48.94% (APC = 0.41, P = 0.40) and from 48.72% to 53.46% (APC = 0.29, P = 0.50), respectively.ConclusionsOC mortality in Hispanic patients varied by sub-ethnicity. This heterogeneity should be considered in future cancer data collection, reports and research.

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Epithelial ovarian cancer mortality among Hispanic women: Sub-ethnic disparities and survival trend across time: An analysis of SEER 1992–2013

Editorial Board

Publication date: January 2018
Source:Cancer Genetics, Volume 220

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Oncogene addiction and radiation oncology: effect of radiotherapy with photons and carbon ions in ALK-EML4 translocated NSCLC

Patients with Echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) positive lung cancer are sensitive to ALK-kinase inhibitors. TAE684 is a potent second generation ALK inhi...

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Oncogene addiction and radiation oncology: effect of radiotherapy with photons and carbon ions in ALK-EML4 translocated NSCLC

Varicocele due to renal arteriovenous malformation mimicking a renal tumor: a case report

Renal arteriovenous malformation is an aberrant vascular connection between the renal artery and vein. Acquired renal arteriovenous malformation (arteriovenous fistulae) accounts for approximately 70% of renal...

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Isocitrate dehydrogenase 1 mutation subtypes at site 132 and their translational potential in glioma

CNS Oncology, Ahead of Print.

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Isocitrate dehydrogenase 1 mutation subtypes at site 132 and their translational potential in glioma

Methods

We determined the prevalence and rate of accumulation in the dentate nucleus and globus pallidus on unenhanced T1-weighted MRI from VHL and TSC patients. We compared the signal intensities of these regions to the signal intensity of the pons. We evaluated the impact of number of MRIs, kidney function and liver function on Gadolinium accumulation.

Results

Twenty eight VHL patients and 24 TSC patients were included. The prevalence of accumulation in the dentate nucleus and globus pallidus increased linearly according to number of Gadolinium enhanced MRIs and was higher in the VHL group (100%). A significant linear correlation between number of MRIs and increased signal intensity was observed in the VHL group.

Conclusions

Gadolinium accumulation occurs in almost all patients undergoing contrast MRI screening after >5 MRIs. We advocate a screening protocol for patients with hereditary tumor syndromes that minimizes the Gadolinium dose. This can be accomplished by using a single administration to simultaneously screen for brain, spine and/or abdominal lesions, using an MRI protocol focused on either VHL- or TSC-specific lesions. Higher prevalence and rate of accumulation in VHL patients may be explained by the typical vascular leakage accompanying central nervous system hemangioblastomas.

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Drug Combination Improves Outlook for Some Patients with Chronic Lymphocytic Leukemia

Interim results from an ongoing clinical trial show that patients with relapsed or refractory chronic lymphocytic leukemia treated with rituximab plus venetoclax have longer progression-free survival compared with patients treated with chemotherapy.

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Central nervous system gadolinium accumulation in patients undergoing periodical contrast MRI screening for hereditary tumor syndromes

Abstract

Background

Methods

Results

Conclusions

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Notch3 inhibition in PaSCs can inhibit the activation, proliferation and migration of PaSCs and reduce the PaSC-induced pro-tumorigenic effect. Therefore, Notch3 silencing in PaSCs is a potential novel therapeutic option for patients with PDAC.

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MiR-199a/b-3p inhibits gastric cancer cell proliferation via down-regulating PAK4/MEK/ERK signaling pathway

High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer

Abstract

Background

Breast cancer anti-estrogen resistance 1 (BCAR1/p130cas) is a hub for diverse oncogenic signaling cascades and promotes tumor development and progression.

Methods

Results

Conclusion

The results of our study identify BCAR1 as a prognostic biomarker with potential clinical value for risk stratification of ERG-negative prostate cancer.

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Regulation of pancreatic stellate cell activation by Notch3

Abstract

Background

Methods

Results

Conclusions

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Phase II trial of ipilimumab in melanoma patients with preexisting humoural immune response to NY-ESO-1

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): G.M. Haag, I. Zoernig, J.C. Hassel, N. Halama, J. Dick, N. Lang, L. Podola, J. Funk, C. Ziegelmeier, S. Juenger, M. Bucur, L. Umansky, C.S. Falk, A. Freitag, I. Karapanagiotou-Schenkel, P. Beckhove, A. Enk, D. Jaeger
BackgroundImmune checkpoint therapy has dramatically changed treatment options in patients with metastatic melanoma. However, a relevant part of patients still does not respond to treatment. Data regarding the prognostic or predictive significance of preexisting immune responses against tumour antigens are conflicting. Retrospective data suggested a higher clinical benefit of ipilimumab in melanoma patients with preexisting NY-ESO-1–specific immunity.Patients and methodsTwenty-five patients with previously untreated or treated metastatic melanoma and preexisting humoural immune response against NY-ESO-1 received ipilimumab at a dose of 10 mg/kg in week 1, 4, 7, 10 followed by 3-month maintenance treatment for a maximum of 48 weeks. Primary endpoint was the disease control rate (irCR, irPR or irSD) according to immune-related response criteria (irRC). Secondary endpoints included the disease control rate according to RECIST criteria, progression-free survival and overall survival (OS). Humoural and cellular immune responses against NY-ESO-1 were analysed from blood samples.ResultsDisease control rate according to irRC was 52%, irPR was observed in 36% of patients. Progression-free survival according to irRC was 7.8 months, according to RECIST criteria it was 2.9 months. Median OS was 22.7 months; the corresponding 1-year survival rate was 66.8%. Treatment-related grade 3 AEs occurred in 36% with no grade 4–5 AEs. No clear association was found between the presence of NY-ESO-1–specific cellular or humoural immune responses and clinical activity.ConclusionIpilimumab demonstrated clinically relevant activity within this biomarker-defined population. NY-ESO-1 positivity, as a surrogate for a preexisting immune response against tumour antigens, might help identifying patients with a superior outcome from immune checkpoint blockade.Clinical trial information: NCT01216696

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Identification of the pericardiacophrenic vein on CT

Abstract

Background

To evaluate the depictability of pericardiacophrenic veins (PCPV) as landmarks for the location of the phrenic nerves on multi-detector-row computed tomography (MDCT), and to investigate the usefulness of depicting the PCPV to aid differential diagnosis of anterior mediastinal lesions.

Methods

Fifty-six patients with anterior mediastinal lesions (Fifty lesions originated from the thymus, six were of non-thymic origin) were evaluated. Contrast-enhanced CT scans of the chest were performed in all cases before diagnosis, and 22 of these scans were performed with electrocardiographic (ECG) gating. Two chest radiologists assessed the depictability of the PCPV and the positional relationship between the center of each anterior mediastinal lesion and the ipsilateral PCPV.

Results

The use of ECG gating increased the PCPV depiction rate in the lower left part of the mediastinum. The depiction rate of the left PCPV was significantly higher than that of the right PCPV. All 50 tumors of thymic origin and 3 of the 6 tumors of non-thymic origin were located on the medial side of the ipsilateral PCPV. The 3 lesions located on the lateral side of the ipsilateral PCPV were of non-thymic origin (p = 0.0007).

Conclusion

The use of ECG gating during MDCT may improve the depictability of the PCPV in the lower left section of the anterior mediastinum. Solitary anterior mediastinal lesions located on the lateral side of the ipsilateral PCPV are likely to be of non-thymic origin.

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Identification of the pericardiacophrenic vein on CT

Abstract

Background

Methods

Results

Conclusion

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Relevance of 3d culture systems to study osteosarcoma environment

Abstract

Osteosarcoma (OS) is the most common primary malignant tumor of bone, which preferentially develops lung metastasis. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for patients with metastatic or recurrent OS remains dramatically poor. Novel therapies are therefore required to slow progression and eradicate the disease. Furthermore, to better understand the cellular and molecular mechanisms responsible for OS onset and progression, the development of novel predictive culture systems resembling the native three-dimensional (3D) tumor microenvironment are mandatory. 'Tumor engineering' approaches radically changed the previous scenario, through the development of advanced and alternative 3D cell culture in vitro models able to tightly mimic the in vivo tumor microenvironment.

In this review, we will summarize the state of the art in this novel area, illustrating the different methods and techniques employed to realize 3D OS cell culture models and we report the achieved results, which highlight the efficacy of these models in reproducing the tumor milieu. Although data need to be further validated, the scientific studies reviewed here are certainly promising and give new insights into the clinical practice.

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Relevance of 3d culture systems to study osteosarcoma environment

Abstract

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Treatment of a complex orthopaedic infection due to extensively drug-resistant Pseudomonas aeruginosa

According to the Centers for Disease Control and Prevention (CDC), approximately 51 000 healthcare-associated infections caused by Pseudomonas aeruginosa occur annually in the USA, more than 6000 of which (13%) are caused by multidrug resistant (MDR) strains. Ceftolozane/tazobactam (TOL/TAZ) (Zerbaxa) was approved by the US Food and Drug Administration (FDA) in December 2014 for the treatment of complicated intra-abdominal and urinary tract infections. At this time, clinical data on the role of TOL/TAZ treatment outside of FDA-approved indications is limited. Herein, we present a case of extensively drug-resistant (XDR) P. aeruginosa osteomyelitis of the upper extremity, which was successfully treated with TOL/TAZ for 8 weeks with optimal clinical and laboratory responses. Monotherapy with TOL/TAZ appears effective for treatment of complicated bone and joint infections with XDR P. aeruginosa in combination with comprehensive surgical management, particularly when few antibiotic options exist.

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Axillary artery aneurysm combined with brachial plexus palsy due to Takayasu arteritis

We report the case of a young female patient who presented with a right axillary artery aneurysm with neurological symptoms due to Takayasuarteritis (TA). Decompression of the aneurysm and arterial repair with an interposition vein bypass resulted in a full recovery. The case emphasises that peripheral aneurysms can occur due to TA and that there may be neurological complications.

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Uterocutaneous fistula following B-Lynch suture for primary postpartum haemorrhage

A 30-year-old woman, who had undergone emergency lower segment caesarean section (LSCS) for failed induction 2 months back, presented with a fistulous opening along with discharge from her previous incision scar. She had developed a massive primary postpartum haemorrhage at the time of LSCS 2 months back, which was managed with B-Lynch suture and vessel ligation. Fistulogram revealed a connection between the uterus and the skin. The diagnosis was confirmed by a contrast-enhanced CT scan. Patient was subjected to laparotomy. She was found to have an extensive necrosis of the anterior uterine wall. Total abdominal hysterectomy was done to avoid the risk of sepsis and haemorrhage. Postoperative period was uneventful. Histopathological examination confirmed the necrosis of the uterine wall. This case describes an extremely rare occurrence of uterocutaneous fistula as a result of uterine infarction following the application of B-Lynch suture for primary postpartum haemorrhage.

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Efficacy and safety of maintenance electroconvulsive therapy for sustaining resolution of severe aggression in a major neurocognitive disorder

We report a novel electroconvulsive therapy (ECT) regimen for sustaining the resolution of behavioural and psychological symptoms of dementia (BPSD) using alternating acute and maintenance ECT (M-ECT) trials. A 64-year-old man presenting with major neurocognitive disorder was admitted for acute behavioural disturbances and physical aggression. With few treatment options, the impact on patients' quality of life often supersedes cognitive symptoms and is a predictor of long-term institutionalisation. Recent studies indicate that ECT may be an effective and safe way to address BPSD. Clinicians have little information about when and how to stop a successful course of acute ECT or the long-term advantages of M-ECT with subsequent intermittent acute ECT. This case emphasises the benefit of M-ECT and describes potential challenges associated with abrupt discontinuation. This case is the first to detail tapering ECT for treatment of aggression in dementia by interchanging acute and M-ECT courses in response to symptom burden.

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Varicella zoster meningitis: an atypical case of zoster reactivation in immunocompetent young adult

Varicella virus is a neurotropic virus that can reactivate later in life to cause zoster or shingles. Typically, it affects elderly, immunocompromised population. We report an unusual case of an immunocompetent young adult presenting with occipital headache and zoster rash, without preherpetic and postherpetic neuralgia, who was diagnosed with varicella meningitis on Polymerase chain reaction (PCR). He was treated with intravenous acyclovir and later discharged on famciclovir. Diagnosis of varicella meningitis is difficult in the absence of typical features of zoster rash and requires high index of suspicion. Rapid diagnostic tests including varicella PCR and antithecal antibody testing can help in the confirmation of varicella zoster meningitis.

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Postsurgical pyoderma gangrenosum after an autologous stem cell transplantation for multiple myeloma

We report a man who underwent autologous stem cell transplantation (ASCT) for multiple myeloma. Two months after ASCT, he presented with necrotising cholecystitis due to gallbladder stones and was submitted to laparoscopic cholecystectomy. About a week later, he developed progressive skin ulcers at sites where trochanters had been inserted. Progressive enlargement and necrotic aspect of these ulcers took place despite debridement and large spectrum antibiotics. New ulcers developed at the site of enoxaparin injection at the right arm (pathergy phenomenon). A skin biopsy and clinical evaluation favoured the diagnosis of pyoderma gangrenosum (PG). He was treated with daily methylprednisolone and dapsone with improvement of the lesions. This is the first case in the literature of PG after ASCT. Despite the risk factors, the onset of an autoinflammatory disease right after the transplant is intriguing since PG is extremely rare in immunocompromised patients.

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