Τρίτη 12 Ιουνίου 2018

Clinical significance of extrathyroidal extension according to primary tumor size in papillary thyroid carcinoma

Publication date: Available online 12 June 2018
Source:European Journal of Surgical Oncology
Author(s): Lihua Liu, Chan Oh, Jae Hyung Heo, Hee Sung Park, Kyungmin Lee, Jae Won Chang, Seung-Nam Jung, Bon Seok Koo
BackgroundExtrathyroidal extension (ETE) is a risk factor for poor papillary thyroid carcinoma (PTC) outcomes. However, the clinical significance of ETE according to primary tumor size has not been well-established. The purpose of this study was to compare differences in clinical outcomes, according to the presence and extent of ETE, between different primary tumor size groups.MethodsIn total, 381 patients with PTC underwent total thyroidectomy with or without lymph node (LN) dissection from 2004 to 2010. We divided the patients into two groups according to primary tumor size: ≤ 1 cm or > 1 cm. Each group was further divided into subgroups according to the presence of ETE (ETE vs. no ETE) and degree of ETE (microscopic ETE vs. macroscopic ETE). The clinicopathological features and rate of recurrence during follow-up were compared among groups.ResultsAmong the PTC patients with primary tumors >1 cm, patients with ETE had a higher recurrence rate than those without ETE, and only macroscopic ETE affected recurrence in patients with PTC > 1cm (P < 0.05). However, there was no significant difference in recurrence rates between those without ETE and those with microscopic ETE (P=0.100). When the primary tumor size was less than 1 cm, there were no difference in recurrence rates between the groups with or without ETE, or between the groups with microscopic and macroscopic ETE (P >0.05).ConclusionsOur data suggests that the presence and degree of ETE may be associated with PTC outcome based on primary tumor size.



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Improved Targeting and Tumor Retention of a Newly Synthesized Antineoplaston A10 Derivative by Intratumoral Administration: Molecular Docking, Technetium 99m Radiolabeling, and In Vivo Biodistribution Studies

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


https://ift.tt/2JQPLNA

Cancers, Vol. 10, Pages 197: Antiviral Drugs for EBV

Cancers, Vol. 10, Pages 197: Antiviral Drugs for EBV

Cancers doi: 10.3390/cancers10060197

Authors: Joseph S. Pagano Christopher B. Whitehurst Graciela Andrei

Epstein&ndash;Barr virus (EBV) infects up to 95% of the adult human population, with primary infection typically occurring during childhood and usually asymptomatic. However, EBV can cause infectious mononucleosis in approximately 35&ndash;50% cases when infection occurs during adolescence and early adulthood. Epstein&ndash;Barr virus is also associated with several B-cell malignancies including Burkitt lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disease. A number of antiviral drugs have proven to be effective inhibitors of EBV replication, yet have resulted in limited success clinically, and none of them has been approved for treatment of EBV infections.



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Histological study of the thin membranous structure made of dense connective tissue around the esophagus in the upper mediastinum

Abstract

Background

The structure of the fascia in upper mediastinum has already been reported from gross anatomical viewpoints by Sarrazin. But it is necessary to understand meticulous anatomy for thoracoscopic or mediastinoscopic surgery. So herein, we investigate histologically the thin membranous structure made of dense connective tissues.

Methods

Semi-sequential transverse sections of the mediastinum were obtained from three cadavers. Hematoxylin and eosin staining, Elastica van Gieson staining, and Masson trichrome staining were performed to identify the presence and location of the thin membranous structure made of dense connective tissues.

Results

The "visceral sheath" and "vascular sheath," as previously described by Sarrazin, were observed histologically. These two thin membranous structures do not surround the esophagus and trachea cylindrically. In addition, the "visceral sheath" on the right side of the upper mediastinum was unclear in comparison to the left side. The "visceral sheath" (on the left side) gradually became unclear, and seemed to almost disappear; the esophagus was found to be very close to the thoracic duct on the caudal side of the bifurcation of the trachea. Although the left recurrent nerve was located inside the "visceral sheath" in all cadavers, the left recurrent nerve lymph nodes were located inside the "visceral sheath" in cadaver 1 and between the "visceral sheath" and "vascular sheath" in cadaver 3.

Conclusion

The "visceral sheath" around the esophagus in the upper mediastinum was histologically demonstrated; however, the findings were not constant.



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Incidence and clinical parameters associated with eribulin mesylate-induced peripheral neuropathy

Publication date: Available online 12 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Bin Zhao, Hong Zhao, Jiaxin Zhao
Eribulin mesylate is a microtubule-targeting agent that has been approved for the treatment of breast cancer and liposarcoma. Due to its novel mechanism of action, eribulin therapy induces a distinct profile of adverse events, including peripheral neuropathy. However, the incidence and risk of eribulin-related neurotoxicities are unclear. Here, we conducted a systematic search of PubMed and Embase from their inception to October 2017. Eligible studies included trials in which eribulin was intravenously administered at a standard dose of 1.4 mg/m2 over 2-5 minutes on days 1 and 8 on a 21-day cycle. The events of all-grade and high-grade peripheral neuropathy were collected to calculate the overall incidence and relative risk (RR). A total of thirty-two studies containing 6,129 subjects were included in this analysis. The incidences of all-grade and high-grade eribulin monotherapy-related peripheral neuropathy were 28% (95% confidence interval [CI], 24%-32%) and 4% (95% CI, 3%-5%), respectively. Subgroup analysis further revealed that a higher incidence of neurotoxicities was observed in patients with breast cancer and those with longer treatment duration. Moreover, eribulin-treated subjects had a significantly increased risk of all-grade (RR, 2.00; 95% CI, 1.70-2.35; p = 0.008) and high-grade (RR, 3.68; 95% CI, 2.30-5.89; p<0.001) neurotoxicities. Our results suggested that patients treated with eribulin had an increased risk of developing peripheral neuropathy.

Graphical abstract

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Radiation therapy in renal cell carcinoma

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Publication date: Available online 12 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Francesca De Felice, Vincenzo Tombolini




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Antiangiogenic therapy: markers of response, “normalization” and resistance

Publication date: Available online 12 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Karima El Alaoui-Lasmaili, Béatrice Faivre
Currently in cancer treatment, one premise is to use antiangiogenic therapies in association with chemotherapy or radiotherapy to augment their efficacy by benefiting from the vascular "normalization" induced by antiangiogenic therapy. This concept defines the time during which the tumor blood vessels adopt normal-like morphology and functionality, i.e. the blood vessels become more mature, the perfusion augments and hypoxia decreases. To date, there is such a diversity of treatment protocols where the type of antiangiogenic to adopt, its dose and duration of administration are different, that knowing when and how to treat is problematic. In this review, we analyzed thoroughly preclinical and clinical studies that use antiangiogenic treatments to benefit from the "normalization" and showed that the effects depend on the type of antiangiogenic administrated (anti-VEGF, anti-VEGFR, Multi-Kinase Inhibitor) and on the duration of treatment. Finally, biomarkers of "normalization" and resistance that could be used in the clinic are presented.



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Novel Trifluoromethylated Enobosarm Analogues with Potent Anti-androgenic Activity in vitro and Tissue Selectivity in vivo.

Prostate cancer often develops anti-androgen resistance, possibly via androgen receptor (AR) mutations which change antagonists to agonists. Novel therapies with increased anticancer activity, whilst overcoming current drug resistance are urgently needed. Enobosarm has anabolic effects on muscle and bone whilst having no effect on the prostate. Here we describe the activity of novel chemically modified enobosarm analogues. The rational addition of bis-trifluoromethyl groups into ring B of enobosarm, profoundly modified their activity, pharmacokinetic and tissue distribution profiles. These chemical structural modifications resulted in an improved AR binding affinity - by increasing the molecular occupational volume near helix 12 of AR. In vitro, the analogues SK33 and SK51 showed very potent antiandrogenic activity, monitored using LNCaP/AR-Luciferase cells where growth, PSA and luciferase activity were used as AR activity measurements. These compounds were 10-fold more potent than bicalutamide and 100-fold more potent than enobosarm within the LNCaP model. These compounds were also active in LNCaP/BicR cells with acquired bicalutamide resistance. In vivo, using the AR-Luc reporter mice, these drugs showed potent AR inhibitory activity in the prostate and other AR-expressing tissues e.g. testes, seminal vesicles and brain. These compounds do not inhibit AR activity in the skeletal muscle, and spleen - thus indicating a selective tissue inhibitory profile. These compounds were also active in vivo in the Pb-PTen deletion model. SK33 and SK51 have significantly different and enhanced activity profiles compared to enobosarm, and are ideal candidates for further development for prostate cancer therapy with potentially fewer side effects.



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Allogeneic hematopoietic cell transplantation in patients with GATA2 deficiency—a case report and comprehensive review of the literature

Abstract

Recently, an immunodeficiency syndrome caused by guanine-adenine-thymine-adenine 2 (GATA2) deficiency has been described. The syndrome is characterized by (i) typical onset in early adulthood, (ii) profound peripheral blood cytopenias of monocytes, B lymphocytes, and NK cells, (iii) distinct susceptibility to disseminated non-tuberculous mycobacterial (NTM) and other opportunistic infections (particularly human papillomavirus), and (iv) a high risk of developing hematologic malignancies (myelodysplastic syndromes (MDS); acute myeloid leukemias (AML)). Considerable clinical heterogeneity exists among patients with GATA2 deficiency, but once infectious symptoms occur or MDS/AML arises, survival declines significantly. Allogeneic hematopoietic cell transplantation (HCT) currently provides the only curative treatment option for both MDS/AML and dysfunctional immunity with life-threatening opportunistic infections. Strategies regarding timing of allogeneic HCT, antimicrobial prophylaxis and treatment, intensity of the preparative regimen, and optimal donor and graft source have not been clearly defined due to the rarity of the disease. Here, we provide a comprehensive analysis of the available literature and published case reports on the use of allogeneic HCT in patients with GATA2 deficiency. In addition, a case of a young woman with GATA2 deficiency, who developed an immune reconstitution inflammatory syndrome in her mycobacterial skin lesions post allogeneic HCT is presented and illustrates distinct problems encountered in this disease context.



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Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

Purpose: The oral BCL-2 inhibitor venetoclax is an effective therapy for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including disease with high-risk genomic features such as chromosome 17p deletion (del[17p]) or progressive disease following B-cell receptor pathway inhibitors. Experimental Design: We conducted a comprehensive analysis of the safety of 400mg daily venetoclax monotherapy in 350 patients with CLL using an integrated dataset from three phase-I/II studies. Results: Median age was 66 years and 60% had del(17p). Patients had received a median of three prior therapies (range: 0-15); 42% previously received ibrutinib or idelalisib. Median duration of exposure to venetoclax was 16 months (0-56). In the pooled analysis, the most common adverse events (AEs) of any grade were diarrhea (41%), neutropenia (40%), nausea (39%), anemia (31%), fatigue (28%), and upper respiratory tract infection (25%). The most common grade 3/4 AEs were neutropenia (37%), anemia (17%), and thrombocytopenia (14%). With the current 5-week ramp-up dosing, the incidence of laboratory TLS was 1.4% (2/166), none had clinical sequelae, and all of these patients were able to ramp-up to a daily dose of 400mg. Grade 3/4 neutropenia was manageable with growth-factor support and dose adjustments; the incidence of serious infections in these patients was 15%. Ten percent of patients discontinued venetoclax due to AEs and 8% died while on study, with the majority of deaths in the setting of disease progression. Conclusions: Venetoclax as a long-term continuous therapy is generally well-tolerated in patients with R/R CLL when initiated with the current treatment algorithm.



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Safety and Efficacy of Anlotinib, a Multikinase Angiogenesis Inhibitor, in Patients With Refractory Metastatic Soft Tissue Sarcoma

Purpose: The prognosis for patients with refractory soft-tissue sarcoma (STS) is dismal. Anlotinib has previously shown antitumor activity on STS in preclinical and phase I studies. Experimental Design: Patients 18 years and older, progressing after anthracycline-based chemotherapy, naïve from angiogenesis inhibitors, with at least one measurable lesion according to RECIST 1.1, were enrolled. The main subtypes eligible were: undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), alveolar soft part sarcoma (ASPS) and clear cell sarcoma (CCS). Participants were treated with anlotinib. The primary endpoint was progression-free rate at 12 weeks (PFR 12 weeks). Results: 166 patients were included in the final analysis. Overall, the PFR 12 weeks was 68% and objective response rate was 13% (95% CI 7.6%-18%). The median progression free survival (PFS) and overall survival (OS) were 5.6 and 12 months respectively. The PFR 12 weeks, median PFS and OS were: 58%, 4.1 and 11 months for UPS (n=19); 63%, 5.6 and 13 months for LPS (n=13); 75%, 11 and 15 months for LMS (n=26); 75%, 7.7 and 12 months for SS (n=47); 81%, 5.6 and 12 months for FS (n=18); 77%, 21 and not reached for ASPS (n=13); 54%, 11 and 16 months for CCS (n=7); 44%, 2.8 and 8.8 months for other sarcoma (n=23), respectively. The most common clinically significant grade 3 or higher adverse events were hypertension (4.8%), triglyceride elevation (3.6%) and pneumothorax (2.4%). No treatment-related death occurred. Conclusions: Anlotinib showed antitumor activity in several STS entities. The toxicity was manageable.



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Inhibition of HER2 Enriches for Jagged1-dependent Breast Cancer Stem Cells: Role for Membrane Jagged1

Purpose: Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer is driven by cells possessing stem-like properties of self-renewal and differentiation, referred to as Cancer Stem Cells (CSCs). CSCs are implicated in radiotherapy, chemotherapy resistance, and tumor recurrence. Notch promotes breast CSCs survival and self-renewal, and overexpression of Notch1 and the Notch ligand Jagged1 predict poor outcome. Resistance to anti-HER2 therapy in HER2+ breast cancer requires Notch1, and that combination of trastuzumab and a Gamma Secretase Inhibitor (GSI) prevents tumor relapse in xenograft models. Experimental Design: The current study investigates mechanisms by which HER2 tyrosine kinase activity regulates Notch-dependent CSC survival and tumor initiation. Results: Lapatinib-mediated HER2 inhibition shifts the population of HER2+ breast cancer cells from low membrane Jagged1 expressing to higher levels, independent of sensitivity to anti-HER2 treatment within the bulk cell population. This increase in membrane Jagged1 is associated with higher Notch receptor expression, activation, and enrichment of CSCs in vitro and in vivo. Importantly, lapatinib treatment results in growth arrest and cell death of Jagged1 low-expressing cells while the Jagged1 high-expressing cells continue to cycle. High membrane Jagged1 protein expression predicts poor overall cumulative survival in women with HER2+ breast cancer. Conclusions: These results indicate that higher membrane Jagged1 expression may be used to either predict response to anti-HER2 therapy or for detection of Notch sensitive CSCs post therapy. Sequential blockade of HER2 followed by Jagged1 or Notch could be more effective than simultaneous blockade to prevent drug resistance and tumor progression.



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A Rapidly Fatal Case of Low-Dose Methotrexate Toxicity

An 82-year-old female presented with multiple oral ulcers and malena for 1 week. Her laboratory tests revealed pancytopenia and acute renal failure. She had history of rheumatoid arthritis for which she was taking 7.5 mg methotrexate weekly and stage 4 chronic kidney disease from diabetic nephropathy. During the hospital stay, she developed pneumonia and septic shock requiring norepinephrine and vasopressin. She underwent continuous venovenous hemodiafiltration. Leucovorin, filgrastim, and multiple packed red blood cell and platelet transfusions were given. She remained hypotensive and pancytopenic despite all interventions. She died on day 6 of hospital stay from acute hypoxic respiratory failure due to septic shock.

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Midlife weight gain is a risk factor for obesity-related cancer

Midlife weight gain is a risk factor for obesity-related cancer

Midlife weight gain is a risk factor for obesity-related cancer, Published online: 13 June 2018; doi:10.1038/s41416-018-0106-x

Midlife weight gain is a risk factor for obesity-related cancer

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Midlife weight gain is a risk factor for obesity-related cancer



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Hematologic variables associated with brain failure in patients with small-cell lung cancer

We sought factors associated with the development of brain metastases after treatment of small cell lung cancer (SCLC) in patients without brain involvement at diagnosis.

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Response to Alongi et al.

We thank Dr. Alongi and colleagues for their interest in and comments on our article on acute rectal toxicity following EBRT for prostate cancer with either weekly portal imaging or daily CBCT (The RIC-study) [1].

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Artificial intelligence in radiation oncology: A specialty-wide disruptive transformation?

Artificial intelligence (AI) is emerging as a technology with the power to transform established industries, and with applications from automated manufacturing to advertising and facial recognition to fully autonomous transportation. Advances in each of these domains have led some to call AI the "fourth" industrial revolution [1]. In healthcare, AI is emerging as both a productive and disruptive force across many disciplines. This is perhaps most evident in Diagnostic Radiology and Pathology, specialties largely built around the processing and complex interpretation of medical images, where the role of AI is increasingly seen as both a boon and a threat.

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Idelalisib in a patient with refractory Waldenström’s macroglobulinemia complicated by anuric renal failure: a case report

Waldenström's macroglobulinemia is a rare B-cell lymphoma. The gold standard treatment for Waldenström's macroglobulinemia is an anti-CD20 antibody (rituximab) in combination with alkylating agents and dexamet...

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The PPARγ agonist rosiglitazone sensitizes the BH3 mimetic (−)‐gossypol to induce apoptosis in cancer cells with high level of Bcl‐2

Molecular Carcinogenesis, EarlyView.


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The homeodomain transcription factor MEIS1 triggers chemokine expression and is involved in CD8+ T‐lymphocyte infiltration in early stage ovarian cancer

Molecular Carcinogenesis, EarlyView.


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Reply to: Synoptic operative reports for quality improvement in pediatric cancer care

Pediatric Blood &Cancer, EarlyView.


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Low‐dose azacitidine maintenance therapy after allogeneic stem cell transplantation for high‐risk pediatric acute myeloid leukemia

Pediatric Blood &Cancer, EarlyView.


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Using the MEDiPORT humanoid robot to reduce procedural pain and distress in children with cancer: A pilot randomized controlled trial

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2HKbhOL

Dramatic bone remodeling following larotrectinib administration for bone metastasis in a patient with TRK fusion congenital mesoblastic nephroma

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2JPkOJB

Clinical utility of endocrine markers predicting myocardial siderosis in transfusion dependent thalassemia major

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2HJ8cym

Two cancer‐predisposing variants in one family: Incidental finding of a fumarate hydrogenase (FH) germline variant in a family with Li–Fraumeni syndrome

Pediatric Blood &Cancer, EarlyView.


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Unfavorable presentation but comparable outcome: Presentation and outcome of children with nodular lymphocyte predominant Hodgkin lymphoma from India

Pediatric Blood &Cancer, EarlyView.


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A case of inherited type 1 and type 2A von Willebrand disease confirmed by diagnostic exome sequencing

Pediatric Blood &Cancer, EarlyView.


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Aprepitant for the prevention of chemotherapy‐induced nausea and vomiting in paediatric subjects: An analysis by age group

Pediatric Blood &Cancer, EarlyView.


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Treatment of pediatric plasma cell myeloma type post‐transplant lymphoproliferative disorder with modern risk‐directed therapy

Pediatric Blood &Cancer, EarlyView.


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Outcome of children and adolescents with Down syndrome treated on Dana‐Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium protocols 00–001 and 05‐001

Pediatric Blood &Cancer, EarlyView.


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Long‐term psychological and educational outcomes for survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study

Cancer, EarlyView.


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Examining urban and rural differences in perceived timeliness of care among cancer patients: A SEER‐CAHPS study

Cancer, EarlyView.


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Reply to The persistent uncertainty of when to recommend allogeneic stem cell transplantation in follicular lymphoma

Cancer, EarlyView.


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The persistent uncertainty of when to recommend allogeneic stem cell transplantation in follicular lymphoma

Cancer, EarlyView.


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High cyclin A expression, but not Ki67, is associated with early recurrence in desmoid tumors

Journal of Surgical Oncology, EarlyView.


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Reply to: “Association between neutrophil‐lymphocyte ratio and prognosis after potentially curative resection for gastric cancer”

Journal of Surgical Oncology, EarlyView.


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Association between neutrophil‐lymphocyte ratio and prognosis after potentially curative resection for gastric cancer

Journal of Surgical Oncology, EarlyView.


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Obesity is associated with larger soft‐tissue sarcomas, more surgical complications, and more complex wound closures (obesity leads to larger soft‐tissue sarcomas)

Journal of Surgical Oncology, EarlyView.


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The effect of a simultaneous versus a staged resection of metastatic colorectal cancer on time to adjuvant chemotherapy

Journal of Surgical Oncology, EarlyView.


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Electrochemotherapy pre‐treatment in primary squamous vulvar cancer. Our preliminary experience

Journal of Surgical Oncology, EarlyView.


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Desmoplastic small round cell tumor: A nationwide study of a rare sarcoma

Journal of Surgical Oncology, EarlyView.


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The association of renal cell carcinoma with gastrointestinal stromal tumors

Journal of Surgical Oncology, EarlyView.


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Prognostic impact of postoperative complication after pancreatoduodenectomy for pancreatic adenocarcinoma stratified by the resectability status

Journal of Surgical Oncology, EarlyView.


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The efficacy of combination of induction chemotherapy and irreversible electroporation ablation for patients with locally advanced pancreatic adenocarcinoma

Journal of Surgical Oncology, EarlyView.


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Reconstruction with constrained scapular prosthesis after total scapulectomy for scapular malignant tumor

Journal of Surgical Oncology, EarlyView.


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Reply to “Intraoperative distal compression in supermicrosurgical lymphaticovenous anastomosis for lymphedema”

Journal of Surgical Oncology, EarlyView.


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The effect of age on anastomotic leakage in colorectal cancer surgery: A population‐based study

Journal of Surgical Oncology, EarlyView.


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Association between Ki‐67 expression and clinical outcomes among patients with clinically node‐negative, thick primary melanoma who underwent nodal staging

Journal of Surgical Oncology, EarlyView.


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Prognostic power of lymph node station ratio for resected esophageal squamous cell carcinoma patients deserves additional investigation

Journal of Surgical Oncology, EarlyView.


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Checkpoint blockade in esophagogastric cancer

Journal of Surgical Oncology, EarlyView.


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Association of low‐activity ALDH2 and alcohol consumption with risk of esophageal cancer in Chinese adults: A population‐based cohort study

International Journal of Cancer, EarlyView.


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A prospective evaluation of plasma polyphenol levels and colon cancer risk

International Journal of Cancer, EarlyView.


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The effects of Self‐Book© art therapy on cancer‐related distress in female cancer patients during active treatment: A randomized controlled trial

Psycho-Oncology, EarlyView.


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Observers' response to facial disfigurement from head and neck cancer

Psycho-Oncology, EarlyView.


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Using generalized estimating equations and extensions in randomized trials with missing longitudinal patient reported outcome data

Psycho-Oncology, EarlyView.


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Factors associated with self‐reported history of depression diagnosis among cancer survivors aged 18 years and over in the United States

Psycho-Oncology, EarlyView.


https://ift.tt/2JKGS81

Increase in incidental detection of thyroid cancer in Osaka, Japan

Cancer Science, EarlyView.


https://ift.tt/2JvqCZf

Chronic liver injury promotes hepatocarcinoma cell seeding and growth, associated with infiltration by macrophages

Cancer Science, EarlyView.


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HSPC159 promotes proliferation and metastasis by inducing epithelial‐mesenchymal transition and activating the PI3K/Akt pathway in breast cancer

Cancer Science, EarlyView.


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Stromal barriers to nanomedicine penetration in the pancreatic tumor microenvironment

Cancer Science, EarlyView.


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Lymph flow guided irradiation of regional lymph nodes in patients with cervical cancer: Preliminary analysis of scintigraphic data

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Publication date: Available online 12 June 2018
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Sergey Nikolaevich Novikov, Pavel Ivanovich Krzhivitskii, Sergey Vasilevich Kanaev, Igor Viktorovitch Berlev, Margarita Viktorovna Kargopolova, Zaur Ibragimov, Mikhail Bisyarin, Valentina Vladimirovna Saveleva
PurposeTo evaluate patterns of lymph flow from primary lesions in patients with cervical cancer and to determine how useful for radiotherapy planning this information can be.Materials and methodsSPECT–CT visualization of sentinel (SLN) lymph nodes (LNs) was performed in 36 primary patients with IB-IIB cervical cancer. The acquisition started 120–240min after 4 peritumoral injections of 99mTc-radiocolloids (150–300MBq in 0.4–1ml). We determined localization of LN with uptake of radiocolloids, type of lymph flow (mono-, bi-lateral) and lymph flow patterns (supraureteral paracervical, infraureteral paracervical and directly to para-aortic LNs).ResultsSLNs were visualized in 31 of 36 women. Bilateral lymph-flow was detected in 22 (71%), monolateral – in the other 9 (29%) cases. The distribution of SLNs was as follows: external iliac – 64.5%, internal iliac – 54.8%, obturator – 32.2%, common iliac – 35.5% and pre-sacral 3.2%. Para-aortic LNs were visualized in 5 (16.1%) patients. The supraureteral paracervical pattern of lymph flow was identified in 22, infraureteral paracervical – in 4 and their combination – in the other 5 women.ConclusionVisualization of an individual pattern of lymph flow from primary cervical cancer can be considered as a promising tool for optimization of the volume of irradiated regional LNs.



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Correction to: Comprehensive Registry of Esophageal Cancer in Japan, 2011

In the original publication of the article, the below name of institutions were not included in the table of Institution-registered cases in 2011.



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OncoArray Links Dozens of DNA Variants to Risk for Common Cancers

Researchers with the NCI-supported GAME-ON initiative and OncoArray Network are publishing studies identifying dozens of new genetic variants associated with the risk for developing some of the most common cancers.



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Association between pathologic factors and ERG expression in prostate cancer: finding pivotal networking

Abstract

Purpose

To evaluate associations between pathologic factors and erythroblast transformation-specific (ETS)-related gene (ERG) expression in prostate cancer patients. Using next-generation sequencing, we identified target genes and regulatory networks.

Methods

ERG expression in 60 radical prostatectomies was compared with pathological findings by association rule mining with the Apriori algorithm. Whole-exome and RNA sequencing were performed on three formalin-fixed, paraffin-embedded ERG-positive and negative prostate cancer samples. A network diagram identifying dominant altered genes was constructed using Cytoscape open-source bioinformatics platform and GeneMania plugin.

Results

Pathologic conditions positive for perineural invasion, apical margins, and Gleason score 3 + 4 = 7 were significantly more likely to be ERG-positive than other pathologic conditions (p = 0.0008), suggesting an association between ERG positivity, perineural invasion, apical margins, and Gleason score 3 + 4 = 7 (Firth's logistic regression: OR 42.565, 95% CI 1.670–1084.847, p = 0.0232). Results of whole-exome and RNA sequencing identified 97 somatic mutations containing common mutated genes. Regulatory network analysis identified NOTCH1, MEF2C, STAT3, LCK, CACNA2D3, PCSK7, MEF2A, PDZD2, TAB1, and ASGR1 as pivotal genes. NOTCH1 appears to function as a hub, because it had the highest node degree and betweenness. NOTCH1 staining was found 8 of 60 specimens (13%), with a significant association between ERG and NOTCH1 positivity (p = 0.001).

Conclusions

Evaluating the association between ERG expression and pathologic factors, and identifying the regulatory network and pivotal hub may help to understand the clinical significance of ERG-positive prostate cancer.



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Mcl-1 phosphorylation without degradation mediates sensitivity to HDAC inhibitors by liberating BH3-only proteins

Mcl-1, a pro-survival Bcl-2 family protein, is frequently overexpressed in cancer cells and plays a critical role in therapeutic resistance. It is well known that anti-cancer agents induce phosphorylation of Mcl-1, which promotes its binding to E3 ubiquitin ligases and subsequent proteasomal degradation and apoptosis. However, other functions of Mcl-1 phosphorylation in cancer cell death have not been well characterized. In this study, we show in colon cancer cells that histone deacetylase inhibitors (HDACi) induce GSK3β-dependent Mcl-1 phosphorylation, but not degradation or downregulation. The in vitro and in vivo anticancer effects of HDACi were dependent on Mcl-1 phosphorylation and were blocked by genetic knock-in (KI) of a Mcl-1 phosphorylation site mutant. Phosphorylation-dead Mcl-1 maintained cell survival by binding and sequestering BH3-only Bcl-2 family proteins PUMA, Bim, and Noxa, which were upregulated and necessary for apoptosis induction by HDACi. Resistance to HDACi mediated by phosphorylation-dead Mcl-1 was reversed by small-molecule Mcl-1 inhibitors that liberated BH3-only proteins. These results demonstrate a critical role of Mcl-1 phosphorylation in mediating HDACi sensitivity through a novel and degradation-independent mechanism. These results provide new mechanistic insights on how Mcl-1 maintains cancer cell survival and suggest that Mcl-1-targeting agents are broadly useful for overcoming therapeutic resistance in cancer cells.

https://ift.tt/2sRpHIv

Integrative genome-wide analysis of long noncoding RNAs in diverse immune cell types of melanoma patients

Genome-wide identification and characterization of long non-coding RNAs (lncRNAs) in individual immune cell lineages helps us better understand the driving mechanisms behind melanoma and advance personalized patient treatment. To elucidate the transcriptional landscape in diverse immune cell types of peripheral blood cells (PBC) in stage IV melanoma, we used whole transcriptome RNA sequencing to profile lncRNAs in CD4+, CD8+, and CD14+ PBC from 132 patient samples. Our integrative computational approach identified 27,625 expressed lncRNAs, 2,744 of which were novel. Both T cells (i.e., CD4+ and CD8+ PBC) and monocytes (i.e., CD14+ PBC) exhibited differential transcriptional expression profiles between melanoma patients and healthy subjects. Cis- and trans-level co-expression analysis suggested that lncRNAs are potentially involved in many important immune-related pathways and the programmed cell death receptor 1 (PD-1) checkpoint pathways. We also identified 9 gene co-expression modules significantly associated with melanoma status, all of which were significantly enriched for three mRNA translation processes. Age and melanoma traits closely correlated with each other, implying that melanoma contains age-associated immune changes. Our computational prediction analysis suggests that many cis- and trans-regulatory lncRNAs could interact with multiple transcriptional and post-transcriptional regulatory elements in CD4+, CD8+, and CD14+ PBC, respectively. These results provide novel insights into the regulatory mechanisms involving lncRNAs in individual immune cell types in melanoma and can help expedite cell type-specific immunotherapy treatments for such diseases.

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Type I Chiari Malformation Presenting in an Adult

Description 

Type I Chiari malformations (CMs) is an acquired or congenital disorder characterised by the presence of the cerebellar tonsils at 5 mm or below of the spinal canal, which can result in abnormal cerebrospinal fluid flow and produce headaches, syrinx or hydrocephalus. CMs are still considered an uncommon disease with a prevalence in the USA of less than 1%.1 2 We present a 44-year-old man with no medical history who presented to the emergency department complaining of nausea, vomiting, vertigo and a 2-day history of headaches exacerbated with Valsalva manoeuvres. He was initially admitted with a working diagnosis of ischaemic stroke and underwent a CT scan of the brain, which was unremarkable. Further work-up with brain MRI disclosed incidental cerebellar herniation 6.5 mm below the foramen magnum (figure 1) and no abnormalities in spinal canal MRIs. The patient was treated symptomatically with oral...



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Marantic endocarditis: incidental infarcts leading to diagnosis of pancreatic cancer

Non-bacterial thrombotic endocarditis (NBTE) is a well-described phenomenon associated with malignancies due to hypercoaguable state. In the setting of pancreatic cancer, NBTE is more commonly diagnosed postmortem. We describe a case of a man who was diagnosed with pancreatic carcinoma after incidental finding of NBTE. Imaging incidentally revealed multiple strokes, bilateral renal and splenic infarcts, while subsequent workup for cardioembolic source demonstrated a 1.1x0.7 cm mitral valve vegetation. As multiple blood cultures were sterile and patient lacked clinical signs of infection, an underlying malignancy was suspected. CT abdomen demonstrated a dilated pancreatic duct, MRI showed a 2.8x2.2 cm pancreatic head mass. Endoscopic biopsy of the mass revealed pancreatic adenocarcinoma. Other than NBTE, there were no other clinical or laboratory findings to clearly suggest pancreatic cancer. Thus, incidental discovery of this mitral valve vegetation led to the diagnosis of pancreatic malignancy.



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Herpes zoster with cutaneous dissemination: a rare presentation of an uncommon pathology in children

Herpes zoster, caused by varicella zoster virus (VZV) reactivation, affects mainly the adult population, although it can occur in children. This happens when primary infection (varicella) has occurred at a very young age or in immunocompromised patients. Complications are rare in healthy individuals. They include VZV cutaneous dissemination, which affects 2%–10% of immunocompromised patients.

We present a previously healthy child, with history of varicella during her first month of life, which presented at age 8 with a severe case of herpes zoster, complicated with cutaneous dissemination. Immunity study was unremarkable. Causes, management and follow-up are discussed.



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Central nervous system blast crisis of chronic myeloid leukaemia misdiagnosed as tubercular meningitis

Chronic Myeloid Leukaemia (CML) presenting with isolated Central Nervous System (CNS) blast crisis is an uncommon entity. A 22-year-old man, diagnosed with chronic phase CML in 2011 and was in haematological and cytogenetic remission until July 2016, had acute onset headache and vomiting with meningeal signs and was admitted elsewhere, investigated by brain imaging and cerebrospinal fluid (CSF) analysis and suspected to have tubercular meningitis, for which steroids and antitubercular medications were started. The patient's sensorium further deteriorated, and Ventriculoperitoneal shunt surgery was done for hydrocephalus by a neurosurgeon. After 2 months of the illness, he was admitted to our hospital with a persistent headache, vomiting and altered sensorium. CSF for cytospin confirmed myeloid blasts. He was still in haematological remission. So, a diagnosis of isolated CNS blast crisis was made. The patient was started on triple intrathecal chemotherapy and cranial radiotherapy. He had improvement with treatment and is still in remission.



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Bilateral Mydriasis Secondary to Propofol Administration in a Patient With Hypertensive Cerebellar Hemorrhage

No abstract available

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Complexity, Variation, and the Ever-moving Cheese

imageNo abstract available

https://ift.tt/2l2XFVV

Journal Club

No abstract available

https://ift.tt/2t0p3aQ

A Narrative Review of Adherence to Subarachnoid Hemorrhage Guidelines

imageOver the past 2 decades, a large number of guidelines for aneurysmal subarachnoid hemorrhage (aSAH) management have been proposed. The primary aim of these "evidence-based" guidelines is to improve the care of aSAH patients by summarizing and making current knowledge readily available to clinicians. However, an investigation into aSAH guidelines, their changes along time and their successful translation into clinical practice is still lacking. We performed a literature search of historical events and subarachnoid hemorrhage guidelines using the Entrez PubMed NIH, Embase, and Cochrane databases for articles published up to November of 2016. Data were summarized for guidelines on aSAH management and cross-sectional studies of their application. A total of 11 guidelines and 10 cross-sectional studies on aSAH management were analyzed. The use of nimodipine for the treatment of SAH is the only recommendation that remained consistent across guidelines over time (r=0.82; P

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Spurious Hypoxemia During Craniotomy

imageNo abstract available

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General Anesthesia and Young Brain: What is New?

Considering that growing population of very young children is exposed to general anesthesia every year, it is of utmost importance to understand how and whether such practice may affect the development and growth of their very immature and vulnerable brains. Compelling evidence from animal studies suggests that an early exposure to general anesthesia is detrimental to normal brain development leading to structural and functional impairments of neurons and glia, and long-lasting impairments in normal emotional and cognitive development. Although the evidence from animal studies is overwhelming and confirmed across species examined from rodents to non–human primates, the evidence from human studies is inconsistent and not conclusive at present. In this review we focus on new developments in animal studies of anesthesia-induced developmental neurotoxicity and summarize recent clinical studies while focusing on outcome measures and exposure variables in terms of their utility for assessing cognitive and behavioral development in children.

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Epidural Blood Patch in Children Under Anesthesia: Is There an Indication for Neuromonitoring?

imageNo abstract available

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Endovascular Treatment of Acute Ischemic Stroke Under General Anesthesia: Predictors of Good Outcome

imageBackground: The choice of anesthetic technique, general anesthesia (GA) versus Monitored Anesthesia Care, may impact the outcome of patients undergoing endovascular treatment of acute ischemic stroke (AIS). The aim of this study was to identify the factors associated with good discharge outcome in patients receiving GA for AIS. Materials and Methods: Electronic medical records of patients above 18 years old who underwent endovascular treatment of AIS under GA at a Comprehensive Stroke Center from 2010 to 2014 were reviewed. Good outcome was defined as discharge modified Rankin Score 0 to 2 and poor outcome as modified Rankin Score 3 to 6; logistic regression analysis was performed to examine the association between the clinical characteristics and the outcome. Results: In total, 88 patients (56 males), aged 63±15 years with median National Institute of Health Stroke Scale (NIHSS) score 16 (range, 4 to 38) were included. Nineteen (22%) patients had good outcome and 78 (88%) had systolic blood pressure below the guideline recommended 140 mm Hg under GA. After adjusting for age and NIHSS score, the independent predictors of good discharge outcomes were higher maximum end-tidal carbon dioxide (odds ratio [OR], 1.14; confidence interval [CI], 1.02-1.28; P=0.02) and extubation after endovascular treatment (OR, 26.31; CI, 4.80-144.12; P

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Cerebral Sinus Thrombosis in Parturient

imageNo abstract available

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Scheduled Intravenous Acetaminophen Improves Patient Satisfaction With Postcraniotomy Pain Management: A Prospective, Randomized, Placebo-controlled, Double-blind Study

imageBackground: Postcraniotomy pain can be difficult to manage with opioids due to opioid-related side effects, including drowsiness, nausea/vomiting, confusion, and pupillary changes, potentially masking the signs of postoperative neurological deterioration. Intravenous (IV) acetaminophen, a nonopioid analgesic, has been reported to have opioid-sparing effects after abdominal and orthopedic surgeries. This study investigates whether IV acetaminophen has similar effects after craniotomy. Materials and Methods: In this prospective, randomized, placebo-controlled, double-blind clinical trial, 100 adult patients scheduled to undergo supratentorial craniotomy for excision of a brain mass were randomized to receive either IV acetaminophen or placebo preincision and then every 6 hours for a total of 24 hours after surgery. Total 24-hour opioid consumption, pain scores, satisfaction with overall pain management, time to meet postanesthesia care unit discharge criteria, and incidence of opioid-related side effects were compared. Results: There was no difference in the 24-hour postoperative opioid consumption in morphine equivalents between the IV acetaminophen group (median, 11 mg; n=45) and the placebo group (median, 10.1 mg; n=41). No statistically significant difference of visual analog scale pain score was observed between 2 treatment groups. Patient satisfaction with overall postoperative pain management was significantly higher in the IV acetaminophen group than the placebo group on a 1 to 10 scale (8.1±0.4 vs. 6.9±0.4; P=0.03). There was no significant difference in secondary outcomes, including the incidence of opioid-related side effects. Conclusions: IV acetaminophen, as adjunctive therapy for craniotomy procedures, did not show an opioid-sparing effect in patients for the 24 hours after craniotomy; however, it was associated with improved patient satisfaction regarding overall pain control.

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JNA Editorial – July 2018

No abstract available

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Ventilation With High or Low Tidal Volume With PEEP Does Not Influence Lung Function After Spinal Surgery in Prone Position: A Randomized Controlled Trial

imageBackground: Spinal surgery in the prone position is accompanied by increased intrathoracic pressure and decreased respiratory compliance. This study investigated whether intraoperative lung protective mechanical ventilation improved lung function evaluated with pulmonary function tests in patients at risk of postoperative pulmonary complications (PPCs) after major spinal surgery in the prone position. Methods: Seventy-eight patients at potential risk of PPCs were randomly assigned to the protective group (tidal volume; 6 mL/kg predicted body weight, 6 cm H2O positive end-expiratory pressure with recruitment maneuvers) or the conventional group (10 mL/kg predicted body weight, no positive end-expiratory pressure). The primary efficacy variables were assessed by pulmonary function tests, performed before surgery, and 3 and 5 days afterward. Results: Postoperative forced vital capacity (2.17±0.1 L vs. 1.91±0.1 L, P=0.213) and forced expiratory volume in 1 second (1.73±0.08 L vs. 1.59±0.08 L, P=0.603) at postoperative day (POD) 3 in the protective and conventional groups, respectively, were similar. Trends of a postoperative decrease in forced vital capacity (P=0.586) and forced expiratory volume in 1 second (P=0.855) were similar between the groups. Perioperative blood-gas analysis variables were comparable between the groups. Patients in the protective and conventional groups showed similar rates of clinically significant PPCs (8% vs. 10%, P>0.999). Conclusions: In patients at potential risk of developing PPCs undergoing major spinal surgery, we did not find evidence indicating any difference between the lung protective and conventional ventilation in postoperative pulmonary function and oxygenation.

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Safety of Sodium Bicarbonate for Control of ICP (Letter)

No abstract available

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Feasibility of Protective Ventilation During Elective Supratentorial Neurosurgery: A Randomized, Crossover, Clinical Trial

imageBackground: Traditional ventilation approaches, providing high tidal volumes (Vt), produce excessive alveolar distention and lung injury. Protective ventilation, employing lower Vt and positive end-expiratory pressure (PEEP), is an attractive alternative also for neuroanesthesia, when prolonged mechanical ventilation is needed. Nevertheless, protective ventilation during intracranial surgery may exert dangerous effects on intracranial pressure (ICP). We tested the feasibility of a protective ventilation strategy in neurosurgery. Materials and Methods: Our monocentric, double-blind, 1:1 randomized, 2×2 crossover study aimed at studying the effect size and variability of ICP in patients undergoing elective supratentorial brain tumor removal and alternatively ventilated with Vt 9 mL/kg—PEEP 0 mm Hg and Vt 7 mL/kg—PEEP 5 mm Hg. Respiratory rate was adjusted to maintain comparable end-tidal carbon dioxide between ventilation modes. ICP was measured through a subdural catheter inserted before dural opening. Results: Forty patients were enrolled; 8 (15%) were excluded after enrollment. ICP did not differ between traditional and protective ventilation (11.28±5.37, 11 [7 to 14.5] vs. 11.90±5.86, 11 [8 to 15] mm Hg; P=0.541). End-tidal carbon dioxide (28.91±2.28, 29 [28 to 30] vs. 28.00±2.17, 28 [27 to 29] mm Hg; P

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Epidural Injection of Platelet Rich Plasma for Postlumbar Puncture Headaches

imageNo abstract available

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Trends and Outcomes of Early Versus Late Percutaneous Endoscopic Gastrostomy Placement in Patients With Traumatic Brain Injury: Nationwide Population-based Study

imageBackground: Oral intake for traumatic brain injury (TBI) patients is often not an option because of facial trauma, swallowing dysfunctions, altered consciousness, etc. These patients often require percutaneous endoscopic gastrostomy (PEG) placement for nutrition support. To date, there is lack of studies examining the relationship between the timing of PEG placement and patient outcome in the TBI group. Methods: We conducted a population-based study in a retrospective cohort of TBI patients undergoing PEG, using the national inpatient sample for years 2011 to 2013. Results: A total of 96,625 patients were identified for TBI and 3343 of those patients received PEG. TBI patients who undergo an early or late PEG placement had a higher rate of in-hospital mortality, when compared with patients with a standard timing of PEG placement. Late PEG was preferably placed in patients with higher Charlson index and trauma-related comorbidities, and these patients had a higher incidence of complications, that is, sepsis, urinary tract infection, acute respiratory distress syndrome/pneumonia, and deep vein thrombosis/pulmonary embolism. When stratified by mortality-risk groups, early PEG was associated with higher rates of in-hospital mortality while standard PEG was associated with best mortality outcomes in low–mortality-risk group and moderate–mortality-risk group. Conclusions: The results of this study suggest that if a PEG placement is indicated for a TBI patient, a standard (7 to 14 d) timing may be associated with better patient outcomes. However, secondary to limitations associated with the use of administrative databases, further prospective studies are needed to establish clear guidelines regarding the optimal timing of placing PEG in TBI patients.

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A Pediatric Case With Takotsubo Cardiomyopathy and Neurogenic Pulmonary Edema Due to an Epidural Hemorrhage

imageNo abstract available

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Intraoperative Neurological Monitoring With Evoked Potentials During Carotid Endarterectomy Versus Cooperative Patients Under General Anesthesia Technique: A Retrospective Study

imageIntroduction: The best technique to evaluate contralateral carotid flow during carotid endarterectomy (CEA) is still debated; an accurate detection of efficient contralateral blood flow can avoid unnecessary shunt placement and its complications. The aim of this retrospective observational study was to evaluate and compare the safety and efficacy of general anesthesia with motor-evoked potential and somatosensory-evoked potentials (mSSEP and tcMEP) versus cooperative patients under general anesthesia (CPGA) technique for CEA. Primary outcome was the rate of technical failure. The procedural time and shunt incidence between the 2 neuromonitoring strategies were also analyzed. Patients and Methods: A total of 331 patients who consecutively underwent CEA were included (100 patients in the CPGA group and 231 in the mSSEP+tcMEP group). The anesthesia technique was customized according to the cerebral monitoring needs. Comparison between groups was performed along with risk analysis. Results: Electrophysiological monitoring seems to be a safe and effective strategy of neuromonitoring during CEA. Compared with the CPGA technique, it ensures fewer technical failures, reduces surgical and anesthesiological time and, moreover, it may reduce shunt risk/incidence. The incidence of shunt between the CPGA group and mSSEP+tcMEP was statistically different (CPGA 12%, mSSEP+tcMEP 5.2%; P=0.02), and the relative risk reduction in the mSSEP+tcMEP group, compared with the CPGA group, was 0.57. Conclusions: mSSEP and tcMEP neuromonitoring was associated with less technical failure and procedural time than asleep-awake-asleep strategy. The evoked potential neuromonitoring may be an alternative technique to awake clinical assessment during CEA.

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Life-threatening Tachyarrhythmia Following Intra-Arterial Milrinone for Cerebral Vasospasm

imageNo abstract available

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Effect of Albumin in Combination With Mannitol on Whole-blood Coagulation In Vitro Assessed by Thromboelastometry

imageBackground: Albumin and mannitol may interfere with hemostasis, but their coinfluence is unclear. We aimed to determine the effects of albumin alone and in combination with mannitol or Ringer acetate (RAC) on hemostasis in crossover in vitro study. Materials and Methods: From citrated fresh whole blood withdrawn from 10 volunteers, we prepared 2.5, 5, 10, 15, and 20 vol% dilutions of 4% albumin (Alb group). Each sample was thereafter diluted by 15% mannitol (Alb/Man group) or RAC (Alb/RAC group) at a ratio of 9:1. Using thromboelastometry, FibTEM (fibrinogen ROTEM) and ExTEM (extrinsic ROTEM) tests were performed. Results: A 20 vol%, but not 2.5 to 15 vol% dilution of albumin caused a prolonged clot formation time, α-angle decrease, and maximum clot firmness (MCF) weakening compared with undiluted sample (P

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Sclerotic Bone Metastasis in Pulmonary Adenocarcinoma

Pulmonary adenocarcinoma is one of the major types of lung cancers in which metastasis is very common and it accounts approximately to one-third of all primary pulmonary cancers. Although a minority of patients with lung cancer are asymptomatic, which gets usually detected in routine chest radiography, most of the patients present with some symptoms. Lung cancer metastasis may occur virtually in every organ system. Patients with non-small-cell lung cancer commonly have extrathoracic metastases to the adrenal glands, liver, brain, bones, and lymph nodes at presentation. Approximately one-third of patients with lung cancer will present with symptoms related to extrathoracic spread. Metastasis to the bone is not uncommon in lung cancer; however, osteoblastic bone metastasis is very rare. Here we present a 30-year-old female diagnosed to have pulmonary adenocarcinoma with multiple sclerotic bony lesions in the vertebra.

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Progression-Free Survival at 24 Months (PFS24) and Subsequent Outcome For Patients With Diffuse Large B-Cell Lymphoma (DLBCL) Enrolled On Randomized Clinical Trials

Abstract
Background
Patients with diffuse large B-cell lymphoma treated with first-line anthracycline based immunochemotherapy and remaining in remission at two years have excellent outcomes. This study assessed overall survival (OS) stratified by progression-free survival at 24 months (PFS24) using individual patient data from patients with DLBCL enrolled in multi-center, international randomized clinical trials as part of the SEAL collaboration.
Patients and Methods
PFS24 was defined as being alive and progression-free 24 months after study entry. OS from PFS24 was defined as time from identified PFS24 status until death due to any cause. OS was compared to each patient's age-, sex-, and country-matched general population using expected survival and standardized mortality ratios (SMRs).
Results
5853 patients enrolled in trials in the SEAL database received rituximab as part of induction therapy and were included in this analysis. The median age was 62 years (range 18-92), and 56% were greater than 60 years of age. At a median follow-up of 4.4 years, 1337 patients (23%) had disease progression, 1489 (25%) had died, and 5101 had sufficient follow-up to evaluate PFS24. 1423 evaluable patients failed to achieve PFS24 with a median OS of 7.2 months (95% CI 6.8-8.1) after progression; 5-year OS after progression was 19% and SMR was 32.1 (95% CI: 30.0-34.4). 3678 patients achieved PFS24; SMR after achieving PFS24 was 1.22 (95% CI: 1.09-1.37). The observed OS versus expected OS at 3, 5, and 7 years after achieving PFS24 was 93.1% vs. 94.4%, 87.6% vs. 89.5%, and 80.0% vs. 83.7%, respectively.
Conclusion
Patients treated with rituximab containing anthracycline-based immunochemotherapy on clinical trials who are alive without progression at 24 months from the onset of initial therapy have excellent outcomes with survival that is marginally lower but clinically indistinguishable from the age-, sex-, and country-matched background population for seven years after achieving PFS24.

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Improving Clinical Proficiency Using a 3-Dimensionally Printed and Patient-Specific Thoracic Spine Model as a Haptic Task Trainer

Background and Objectives Advanced haptic simulators for neuraxial training are expensive, have a finite life, and are not patient specific. We sought to demonstrate the feasibility of developing a custom-made, low-cost, 3-dimensionally printed thoracic spine simulator model from patient computed tomographic scan data. This study assessed the model's practicality, efficiency as a teaching tool, and the transfer of skill set into patient care. Methods A high-fidelity, patient-specific thoracic spine model was used for the study. Thirteen residents underwent a 1-hour 30-minute training session prior to performing thoracic epidural analgesia (TEA) on patients. We observed another group of 14 residents who were exposed to the traditional method of training during their regional anesthesia rotation for thoracic epidural placement. The TEA was placed for patients under the supervision of attending anesthesiologists, who were blinded to the composition of the study and control groups. As a primary outcome, data were collected on successful TEAs, which was defined as a TEA that provided full relief of sensation across the entire surgical area as assessed by both a pinprick and temperature test. Secondary outcomes included whether any assistance from the attending physician was required and failed epidurals. Results A total of 27 residents completed the study (14 in the traditional training, 13 in the study group). We found that the residents who underwent training with the simulator had a significantly higher success rate (11 vs 4 successful epidural attempts, P = 0.002) as compared with the traditional training group. The control group also required significantly more assistance from the supervising anesthesiologist compared with the study group (5 vs 1 attempt requiring guidance). The number needed to treat (NNT) for the traditional training group was 1.58 patients over the study period with a 95% confidence interval of 1.55 to 1.61. Conclusions By using patient-specific, 3-dimensionally printed, thoracic spine models, we demonstrated a significant improvement in clinical proficiency as compared with traditional teaching models. Accepted for publication January 31, 2018. Address correspondence to: Robina Matyal, MD, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215 (e-mail: rmatyal1@bidmc.harvard.edu). Research support was provided by the Foundation for Anesthesia Education and Research Grant. The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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The 8th edition American Joint Committee on gastric cancer pathological staging classification performs well in a population with high proportion of locally advanced disease

Publication date: Available online 11 June 2018
Source:European Journal of Surgical Oncology
Author(s): Shu-Fang Huang, Ti-Hsuan Chien, Wen-Liang Fang, Frank Wang, Chun-Yi Tsai, Jun-Te Hsu, Chun-Nan Yeh, Tse-Ching Chen, Ren-Chin Wu, Cheng-Tang Chiu, Ta-Sen Yeh
BackgroundThe 8th edition of AJCC gastric cancer pathological staging system (AJCC8) derived from the IGCA database needs an external validated in cohorts with higher proportion of advanced disease.Patients and methodsA total of 5,386 gastric cancer patients treated at Chang Gung Memorial Hospital (CGMH) and Veteran General Hospital in Taipei (TVGH) were enrolled. Clinicopathological data of the IGCA series and the CGMH/TVGH cohort were compared. Cumulative survival curves of the CGMH/TVGH cohort as stratified by the AJCC7 and the AJCC8 were compared. Lymph node ratio (LNR) was analyzed in patients with N3b disease.ResultsPatients in the CGMH/TVGH cohort were older and had more advanced tumor stage (stage III, 49% versus 26%, p<0.001) than those in the IGCA cohort. The median survival of stages IIIA, IIIB, and IIIC as defined by the AJCC 8 were 49, 27 and 15 months, respectively, with narrower 95% confidence intervals, in comparison with 62, 30 and 18 months, respectively, as defined by the AJCC7. The AJCC8 exhibited better homogeneity within stages and discriminatory ability between stages, compared to the AJCC7. Six hundred and four patients with N3b disease were stratified by LNR into three subgroups, and their median survival were 31, 17, and 11 months, respectively (p<0.001). LNR further appeared as a powerful outcome predictor of N3b disease (HR, 3.1).ConclusionThe AJCC8 performs well in patients with high proportion of advanced gastric cancer. We recommend that LNR is a supplementary prognostic indicator for N3b disease.



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