A case of ectopic liver tissue adherent to the gallbladder

Abstract

We report a case of a 30-year-old lady who presented to the emergency department with a 1 day history of severe epigastric pain which radiated to the back. Focused history, physical exam findings, haematological and radiological investigations, including ultrasound scanning of the abdomen, supported the diagnosis of acute gallstone pancreatitis. She was managed conservatively and underwent elective laparoscopic cholecystectomy at a later date. Intraoperatively, there was noted to be a small nodule loosely adherent to the gallbladder serosa. Histology from this nodule revealed it to be a portion of anatomically normal liver parenchyma also referred to as ectopic liver tissue (ELT). ELT is a rare developmental abnormality in which normally functioning liver tissue develops at an extra-hepatic site. ELT is known to have an increased risk of neoplastic transformation and so we believe it to be of clinical importance.

https://ift.tt/2K1Ag26

Acute-right-ventricular-failure post-cardiotomy: RVAD as a bridge to a successful recovery

Abstract

This is the case of a 57-year-old woman who underwent coronary-artery-bypass-grafting following a diagnosis of NSTEMI with triple-coronary-vessel-disease. During separation from cardiopulmonary-bypass she developed acute severe-right-ventricular-failure refractory to inotropic support and intra-aortic-balloon-pump-counterpulsation. Therefore VA-ECMO was established in order to separate the patient from cardiopulmonary-bypass. VA-ECMO was then transitioned to RVAD support which allowed complete recovery of RV-function and subsequent explantation. The patient was eventually discharged home.

https://ift.tt/2JRXbRh

Disseminated Mycobacterium abscessus infection with spondylodiscitis of thoracic spine

Abstract

A case is presented of an immunosuppressed 51-year-old man with spondylodiscitis of the thoracic vertebrae from Mycobacterium abscessus infection, in context of disseminated multi-systemic infection with pulmonary and gastrointestinal involvement. Multiple challenges in the diagnosis and management of this confounding case are outlined. The patient underwent aggressive surgical debridement via T8–T10 vertebrectomy plus reconstruction, and right hemicolectomy to obtain source control. This was followed by prolonged combination antibiotic therapy. At time of manuscript patient is 10 months post-surgery and 18 months from initial presentation, with excellent surgical outcome and control of the infection. The unique microbiological and clinical characteristics of M. abscessus are briefly outlined. A synopsis of the relevant literature is given highlighting the relative paucity of evidence to aid management of this unpredictable infection. Current best practice guideline recommends combination of medical therapy and aggressive surgical debridement for infections caused by M. abscessus.

https://ift.tt/2M6g7IR

Evaluation Breast Cancer Information on The Internet in Arabic

Abstract

Nowadays, medical information regarding various diseases and disorders is available online. The Internet has become the first choice for the patient when it comes to gathering detailed information about a disease or problem. Therefore, in view of this frequent occurrence, the information that is provided online needs to be accurate; providing comprehensive facts, transparency, and quality. A study was carried out to determine the accuracy of information related to breast cancer on various websites. Websites which share information online about breast cancer, in the Arabic language, were selected. The quality of the websites was to be evaluated; however, there is no standard method for evaluating the quality of health websites. Hence, a rating form was developed for this study, to determine the completeness and transparency of a specific number of websites using three popular search engines. A 16-item questionnaire was prepared and validated to determine the quality of individual websites in addition to using the DISCERN instrument for assessing consumer health information. Most of the websites (approximately 47%) were deemed to be commercial in nature. Thirty-three percent were developed by non-profit organizations. They disseminated information concerning the risk factors (93%), screening, mammography (93%), surgical treatment (93%), chemotherapy (89%), radiotherapy (93%), and complementary medicine (0%) surrounding the treatment of breast cancer. About 67% of the websites were estimated to give completely correct information. Incidentally, only five websites had a healthcare professional or expert as the author, while nine of them had no author. Although numerous breast cancer-related websites exist, most do a poor job in providing Arabic-speaking women with comprehensive information about breast cancer surgery. Providing easily-accessible, high-quality online information has the potential to significantly improve patients' experiences.

https://ift.tt/2JPxgK0

Fifty Years of Rhabdomyosarcoma studies on both sides of the Pond and Lessons Learned

Publication date: Available online 19 June 2018
Source:Cancer Treatment Reviews
Author(s): Carola A.S. Arndt, Gianni Bisogno, Ewa Koscielniak
We review and summarize the highlights of almost five decades of cooperative group trials in rhabdomyosarcoma on both sides of the Atlantic, concentrating on chemotherapy regimens, what has been learned, and where remaining challenges are. The most important achievements have been to decrease or omit the dose of alkylator therapy for many patients , to clarify after much controversy that doxorubicin does not improve the outcome of patients even in the highest risk groups, and to show that high dose chemotherapy and stem cell rescue do not improve the outcome of the highest risk patients. In North America, vincristine/actinomycin/cyclophosphamide (VAC) remains an important part of therapy, whereas in Europe the alkylating agent of choice is ifosfamide. The highest risk patients, namely those with the poorest prognostic score, have had no improvement in outcome since the first cooperative group trial in 1972 and remain the greatest challenge. Philosophical differences between European and North American strategies still revolve somewhat around the total burden of therapy received, that is should certain groups of patients be spared aggressive local control in order to reduce late effects, recognizing that it is not possible to identify priori the children that can be cured with this approach exposing the whole population to a higher risk of relapse. Collaboration and joining resources may help answer some difficult questions.



https://ift.tt/2M84oJV

Analgesic effect of long-acting somatostatin receptor agonist pasireotide in a patient with acromegaly and intractable headaches

A 22-year-old woman presented with worsening vision loss and headaches. A diagnosis of acromegaly was confirmed after detection of an invasive pituitary macroadenoma and biochemical testing. Despite two attempts of surgical debulking of the tumour and administration of long-acting octreotide and cabergoline, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were uncontrolled. The patient experienced persistent headaches despite surgery, gamma knife radiation and ventriculoperitoneal shunt placement; she was then enrolled in the ACCESS trial (ClinicalTrials.gov identifier, NCT01995734). Pasireotide (Signifor; Signifor LAR) was initiated, which led to reduced GH and IGF-1 levels and resolution of her intractable headaches. This highlights the use of monthly pasireotide in resolving headaches and improved biochemical control in a patient with acromegaly. We postulate that the headaches improved due to an analgesic and/or anti-inflammatory effect mediated by somatostatin receptors targeted by pasireotide. This may represent an additional benefit of pasireotide and requires further investigation.

https://ift.tt/2tnCzp9

Cogans syndrome with pyoderma gangrenosum: management of two uncommon disorders with aggressive presentation in a patient

Pyoderma gangrenosum (PG) coexisting with Cogan's syndrome (CS) is uncommon, although cutaneous manifestations are known to develop in CS. A middle-aged white female patient had chronic relapsing PG requiring ciclosporin and prednisolone. Despite receiving optimal doses of ciclosporin and prednisolone, she developed acute vestibulo-auditory symptoms as a result of CS. Ciclosporin was switched to methotrexate and prednisolone was increased. However, she continued to develop acute scleritis, requiring methylprednisolone pulses, and still had further flares of PG. Her methotrexate was held off when she developed severe pneumonia and she then received a trial of intravenous immunoglobulins (IVIG) for her recurrent leg ulcers. Unfortunately, she failed to respond to IVIG. Her ulcers eventually responded to six doses of monthly intravenous cyclophosphamide induction. Although CS is not an antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, we used pulse cyclophosphamide, based on the experience of cyclophosphamide efficacy in severe ANCA-associated vasculitis (AAV). Following induction, both diseases currently remain under control with azathioprine as maintenance treatment.

https://ift.tt/2MINnH0

Case of severe acute lupus myocarditis and multiple-organ failure

We report a case of severe lupus myocarditis with rapid, acute deterioration to cardiogenic shock and multiorgan failure, highlighting the importance of early identification and treatment of acute presentations in patients with systemic lupus erythematosus. A 31-year-old woman with previously diagnosed subacute cutaneous lupus erythematosus initially presented with abdominal pain and frank per-rectal bleeding. She deteriorated rapidly with type 1 respiratory failure and acute kidney injury requiring dialysis secondary to acute cardiac failure with a prolonged intensive care unit admission, over a month. A significantly elevated troponin, global hypokinesia on echocardiogram and normal coronary artery angiogram and cardiac MRI lead to the diagnosis of acute lupus myocarditis as the cause for the cardiogenic shock. She was treated with high-dose corticosteroids and eventually made a full recovery, with cardiac function returning to normal.

https://ift.tt/2tnCt0L

Reactive hypoglycaemia: a rarely considered 'stroke mimic in non-diabetic individuals

Hypoglycaemia is a well-documented 'stroke mimic'. The literature documents numerous case reports of patients presenting with focal neurological deficits subsequently attributed to hypoglycaemia. The significant majority of these cases are found in patients with pre-existing diabetes. We present case histories of two patients with no history of diabetes presenting to secondary care with reactive hypoglycaemia causing transient symptoms that were responsible for referral as a possible transient ischaemic attack. Although uncommon, metabolic disturbances such as hypoglycaemia should be considered in all patients presenting as a suspected stroke, even if they are not known to have diabetes.

https://ift.tt/2t8Isr4

Enhancement of PTSD treatment through social support in Idobata-Nagaya community housing after Fukushimas triple disaster

Cognitive–behavioural therapy is a first-line treatment for post-traumatic stress disorder (PTSD), but it is difficult to implement in disaster settings. We report the case of an 80-year-old Japanese woman, who was diagnosed with PTSD after the 2011 triple disaster (earthquake, tsunami and nuclear plant accident) in Fukushima. Her recovery was greatly enhanced by the social support she received while living in Idobata-Nagaya community housing, established by Soma city in Fukushima, where residents could naturally discuss their traumatic experiences. Habituation to traumatic memories and processing of cognitive aspects of the psychological trauma, which are therapeutic mechanisms of trauma-focused psychotherapies, spontaneously occurred in this setting. The details of this case support the effectiveness of Idobata Nagaya as a provider of psychological first aid, an evidence-informed approach to assist children, adolescents, adults and families in the aftermath of a disaster.

https://ift.tt/2ypvYjJ

Bilateral chorea/ballismus: detection and management of a rare complication of non-ketotic hyperglycaemia

Non-ketotic hyperglycaemia (NKH) is the most common metabolic cause of hemichorea-hemiballismus (HC-HB) and an often-reversible condition. A 68-year-old man presented to the emergency department with a severe hyperglycaemic episode and altered mental status. He was treated appropriately and discharged home after his blood glucose levels were normal with an improvement of mental status. Four weeks after the discharge, he returned with flailing movements of bilateral upper and lower limbs. MRI of the brain revealed hyperintensities of the bilateral putamen on T1-weighted imaging. The patient's symptoms improved with a combination of amantadine, clonazepam and tetrabenazine. Several hypotheses involving gemistocytes, calcification and petechial haemorrhage were proposed in support of imaging abnormalities in the striatum. Dopamine-depleting agents and neuroleptics are used in the treatment of chorea. It is recommended to try a dose of tetrabenazine in patients with NKH-induced HC-HB if no improvement is appreciated with initial treatment of glycaemic control.

https://ift.tt/2MHgECa

Intravenous immunoglobulin therapy for dengue capillary leak syndrome in a renal allograft recipient

A 45-year-old man presented 4 months after ABOi renal transplantation with febrile illness and bicytopenia necessitating cessation of mycophenolate mofetil. Dengue non-structural protein 1 antigen (NS1 Ag) test was positive. Lowest total leucocyte count was 3.1x10⁹/L and platelet count was 14x10⁹/L. As fever subsided, patient became tachypneic with abdominal distention and hypotension. Ultrasonographic evaluation revealed ascites, gall bladder wall oedema and bilateral pleural effusion consistent with dengue capillary leak syndrome. He developed massive ascites with abrupt weight gain of 4 kg within 24 hours and worsening renal dysfunction. Patient was deteriorating rapidly in spite of adequate supportive care and we gave a trial of intravenous immunoglobulin (0.5 g/kg/day) for 5 days. Patient improved from day 2, and by day 3, he became haemodynamically stable and recovered completely. Patient was stable at discharge and is on regular follow-up.

https://ift.tt/2ysvTMg

Active bleeding from intercostal artery pseudoaneurysm after a percutaneous tube thoracostomy drainage procedure: diagnosis with CT angiography and treatment with transarterial coil embolisation

Description

Intercostal artery (ICA) pseudoaneurysm related to tube thoracostomy drainage procedure is not commonly encountered.1 But when haemothoraces develops due to pseudoaneurysms, they could be timely detected by CT with CT angiography (CTA) and treated via transarterial embolisation with mini coils.2 3 We report the case of a 9-year-old female child with medullobalstoma involving her brain and spine who was admitted for scheduled chemotherapy. She developed progressive dyspnoea (with oxygen saturation80%) and a right pleural effusion was noted. Subsequently, a right-sided thoracentesis with pigtail catheter insertion was performed. After thoracentesis, her respiratory pattern improved with decreased fluid drained from the pigtail catheter and thus the pigtail was removed. However, her shortness of breath with decreased breath sounds over the right lung fields recurred the next day. Repeat thoracentesis revealed bloody fluid. CT with CTA showed right haemothorax with active bleeding from the...

https://ift.tt/2MHgElE

A quick scoping review of efficacy, safety, economic, and health-related quality-of-life outcomes of short- and long-acting erythropoiesis-stimulating agents in the treatment of chemotherapy-induced anemia and chronic kidney disease anemia

Publication date: Available online 19 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Luiz H. Arantes, Jeffrey Crawford, Pere Gascon, Mark Latymer, Vincent Launay-Vacher, Catherine Rolland, Florian Scotte, Jay Wish
Erythropoiesis-stimulating agents (ESAs) are man-made forms of erythropoietin used in the treatment of anemia. This quick-scoping review of systematic literature reviews (SLRs) was conducted to define the clinical, economic, and health-related quality of life (HRQoL) outcomes for short-acting and long-acting ESAs in patients with chronic kidney disease–induced anemia (CKD-IA) and patients with chemotherapy-induced anemia (CIA). Embase, Medline, and the Cochrane Database of Systematic Reviews were searched from their establishment until October 2017. SLRs related to the use of short-acting and long-acting ESAs in the treatment of CIA and CKD-IA were included. Forty-eight studies met the inclusion criteria. The evidence suggests little difference in efficacy, HRQoL, and safety outcomes among ESA types. Cost-effectiveness and market price are likely to become determining factors driving the choice of agent. Comparative studies and costing models accounting for the utilization of biosimilars are needed to establish which ESAs are more cost-effective.



https://ift.tt/2yqjokc

Ablative stereotactic radiotherapy for oligometastatic colorectal cancer: Systematic review

Publication date: Available online 19 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): J. Kobiela, P. Spychalski, G. Marvaso, D. Ciardo, V. Dell'Acqua, F. Kraja, A. Błażyńska-Spychalska, A.J. Łachiński, A. Surgo, R. Glynne-Jones, B.A. Jereczek-Fossa
BackgroundSBRT is a novel modality in treatment for oligometastatic colorectal cancer. We aimed to perform a systematic review of results of SBRT in maintaining LC (local control) for CRC liver and lung oligometastases.Materials and methodsThe review was performed according to PRISMA and PICO guidelines. Database search using keywords: stereotactic, colon, colorectal, cancer, sbrt, sabr returned 457 results. 15 were included in the study. Only cohorts with CRC histology and reported LC were included.ResultsFor liver LC rates ranged from 50% to 100% after 1 year and 32% to 91% after 2 years. BED range 40.5-262.5 Gy (Grays). For lung LC rates ranged from 62% to 92% after 1 one year and from 53% to 92% after 2 years. BED range 51.3-262.5 Gy.ConclusionsSBRT of oligometastatic CRC offers high LC with low morbidity and toxicity. It requires more observational studies and randomized trials but available data on clinical efficacy is promising, however not yet matured.



https://ift.tt/2tboJXG

Pharmacokinetics variability: Why nanoparticles are not just magic-bullets in oncology

Publication date: Available online 19 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Anne Rodallec, Sebastien Benzekri, Bruno Lacarelle, Joseph Ciccolini, Raphaelle Fanciullino
Developing nanoparticles to improve the specificity of anticancer agents towards tumor tissue and to better control drug delivery is a rising strategy in oncology. An increasing number of forms (e.g., conjugated nanoparticles, liposomes, immunoliposomes…) are now available on the shelves and numerous other scaffolds (e.g., dendrimeres, nanospheres, squalenes …) are currently at various stages of development. However, as of today most nanoparticles made available remain lipidic carriers. Pharmacokinetic variability is a major, yet largely underestimated issue with liposomal nanoparticles. A wide variety of causes (e.g., tumor type and disease staging, comorbidities, patient's immune system) can explain this variability, which can in return negatively impact pharmacodynamic endpoints such as poor efficacy or severe toxicities. This review aims to cover the main causes for erratic pharmacokinetics observed with most nanoparticles, especially liposomes used in oncology. Should the main causes of such variability be identified, specific studies in non-clinical or clinical development stages could be undertaken using dedicated models (i.e., mechanistic or semi-mechanistic mathematical models such as PBPK approaches) to better describe nanoparticles pharmacokinetics and decipher PK/PD relationships. In addition, identifying relevant biomarkers or parameters likely to impact nanoparticles pharmacokinetics would allow for either the modification of their characteristics to reduce the influence of the expected variability during development phases or the development of biomarker-based adaptive dosing strategies to maintain an optimal efficacy/toxicity balance. Broadly, we call for the development of comprehensive distribution studies and state-of-the-art modeling support to better understand and anticipate nanoparticle pharmacokinetics in oncology.



https://ift.tt/2LZT5mI

DDX3 activates CBC-eIF3-mediated translation of uORF-containing oncogenic mRNAs to promote metastasis in HNSCC

Mutated or dysregulated DDX3 participates in the progression and metastasis of cancer via its multiple roles in regulating gene expression and cellular signaling. Here we show that the high expression levels of DDX3 in head and neck squamous cell carcinoma (HNSCC) correlate with lymph node metastasis and poor prognosis and demonstrate that DDX3 is essential for the proliferation, invasion, and metastasis of oral squamous cell carcinoma (OSCC) cells. Microarray analyses revealed that DDX3 is required for the expression of a set of pro-metastatic genes including ATF4-modulated genes in an aggressive OSCC cell line. DDX3 activated translation of ATF4 and a set of its downstream targets, all of which contain upstream open reading frames (uORF). DDX3 promoted translation of these targets, likely by skipping the inhibitory uORF. DDX3 specifically enhanced the association of the cap-binding complex (CBC) with uORF-containing mRNAs and facilitated recruitment of the eukaryotic initiation factor 3 (eIF3). CBC and certain eIF3 subunits contributed to the expression of metastatic related gene expression. Taken together, our results indicate a role for the novel DDX3-CBC-eIF3 translational complex in promoting metastasis.

https://ift.tt/2ylVTZw

Computational characterization of suppressive immune microenvironments in glioblastoma

The immunosuppressive microenvironment in glioblastoma (GBM) prevents an efficient antitumoral immune response and enables tumor formation and growth. Although an understanding of the nature of immunosuppression is still largely lacking, it is important for successful cancer treatment through immune system modulation. To gain insight into immunosuppression in GBM, we performed a computational analysis to model relative immune cell content and type of immune response in each GBM tumor sample from The Cancer Genome Atlas RNA-seq dataset. We uncovered high variability in immune system-related responses and in the composition of the microenvironment across the cohort, suggesting immunological diversity. Immune cell compositions were associated with typical alterations such as IDH mutation or inactivating NF1 mutation/deletion. Furthermore, our analysis identified three GBM subgroups presenting different adaptive immune responses: Negative, Humoral, and Cellular-
like. These subgroups were linked to transcriptional GBM subtypes and typical genetic alterations. All G-CIMP and IDH-mutated samples were in the Negative group, which was also enriched by cases with focal amplification of CDK4 and MARCH9. IDH1-mutated samples showed lower expression and higher DNA methylation of MHC-I -type HLA genes. Overall, our analysis reveals heterogeneity in the immune microenvironment of GBM and identifies new markers for immunosuppression. Characterization of diverse immune responses will facilitate patient stratification and improve personalized immunotherapy in the future.

https://ift.tt/2lntmcO

Inactivation of citron kinase inhibits medulloblastoma progression by inducing apoptosis and cell senescence.

Medulloblastoma (MB) is the most common malignant brain tumor in children. Current treatment for MB consists of surgery followed by irradiation of the whole neuraxis and high-dose multi-agent chemotherapy, a partially effective strategy associated with highly invalidating side effects. Therefore, identification and validation of novel target molecules capable of contrasting MB growth without disturbing brain development is needed. Citron kinase protein (CITK), encoded by primary microcephaly gene MCPH17, is required for normal proliferation and survival of neural progenitors. Constitutive loss of CITK leads to cytokinesis failure, chromosome instability, and apoptosis in the developing brain, but has limited effects on other tissues. On this basis, we hypothesized that CITK could be an effective target for MB treatment. In MB cell lines DAOY and ONS-76, CITK knockdown increased both cytokinesis failure and DNA damage, impairing proliferation and inducing cell senescence and apoptosis via TP53 or TP73. Similar effects were obtained in the NeuroD-SmoA1 transgenic mouse model, in which CITK deletion increased apoptotic cells and senescence markers such as P21CIP1, P27KIP1, and P16INK4A. Most importantly, CITK deletion decreased tumor growth and increased overall survival in these mice, with no apparent side effects. These results suggest that CITK can be a useful molecular target for MB treatment.

https://ift.tt/2ywtOiu

Transcription factor YY1 promotes cell proliferation by directly activating the pentose phosphate pathway

Tumor cells alter their metablosim to meet their demand for macromolecules, support a high rate of proliferation as well as cope with oxidative stress. The transcription factor yin yang 1 (YY1) is upregulated in various types of tumors and is crucial for tumor cell proliferation and metastasis. However, its role in tumor cell metabolic reprogramming is poorly understood. Here we show that YY1 alters tumor cell metabolism by activating glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway. By stimulating the pentose phosphate pathway, YY1 enhanced production of nucleotides and DNA synthesis, decreased intracellular reactive oxygen species levels, and promoted antioxidant defense by supplying increased reducing power in the form of NADPH. Importantly, YY1-mediated regulation of the pentose phosphate pathway in tumor cells occurred not through p53, but rather through direct activation of G6PD transcription by YY1. Regulation of pentose phosphate pathway activity through G6PD was strongly related to YY1-induced proliferation of tumor cells and tumorigenesis. Together, our results describe a novel role for YY1 in regulating G6PD in a p53-independent manner, which links its function in tumorigenesis to metabolic reprogramming in tumor cells.

https://ift.tt/2ljysGY

Attenuated TRAF3 fosters alternative activation of NF-{kappa}B and reduced expression of anti-viral interferon, TP53, and RB to promote HPV-positive head and neck cancers

Human papilloma viruses (HPV) are linked to an epidemic increase in oropharyngeal head and neck squamous cell carcinomas (HNSCC), which display viral inactivation of tumor suppressors TP53 and RB1 and rapid regional spread. However, the role of genomic alterations in enabling modulation of pathways that promote the aggressive phenotype of these cancers is unclear. Recently, a subset of HPV+ HNSCC has been shown to harbor novel genetic defects or decreased expression of TNF-receptor-associated-factor-3 (TRAF3). TRAF3 has been implicated as a negative regulator of alternative NF-κB pathway activation, and activator of anti-viral type-I interferon (IFN) response to other DNA viruses. How TRAF3 alterations affect pathogenesis of HPV+ HNSCC has not been extensively investigated. Here, we report that TRAF3-deficient HPV+ tumors and cell lines exhibit increased expression of alternative NF-κB pathway components and transcription factors NF-κB2/RELB. Overexpression of TRAF3 in HPV+ cell lines with decreased endogenous TRAF3 inhibited NF-κB2/RELB expression, nuclear localization, and NF-κB reporter activity, while increasing the expression of IFNA1 mRNA and protein and sensitizing cells to its growth inhibition. Overexpression of TRAF3 also enhanced TP53 and RB tumor suppressor proteins and decreased HPV E6 oncoprotein in HPV+ cells. Correspondingly, TRAF3 inhibited cell growth, colony formation, migration, and resistance to TNF-α and cisplatin-induced cell death. Conversely, TRAF3 knockout enhanced colony formation and proliferation of an HPV+ HNSCC line expressing higher TRAF3 levels. Together, these findings support a functional role of TRAF3 as a tumor suppressor modulating established cancer hallmarks in HPV+ HNSCC.

https://ift.tt/2yrWclM

Epithelial-mesenchymal transition in human prostate cancer demonstrates enhanced immune evasion marked by IDO1 expression

Cancer invasion and metastasis are driven by epithelial-to-mesenchymal transition (EMT), yet the exact mechanisms that account for EMT in clinical prostate cancer are not fully understood. Expression of N-cadherin is considered a hallmark of EMT in clinical prostate cancer. In this study, we determined the molecular mechanisms associated with N-cadherin expression in prostate cancer patients. We performed laser capture micro-dissection of matched N-cadherin-positive and -negative prostate cancer areas from patient samples (n=8) followed by RNA sequencing. N-cadherin expression was significantly associated with an immune regulatory signature including profound upregulation of indoleamine 2,3-dioxygenase (IDO1) (log2 fold change=5.1; p=2.98E-04). Fluorescent immune stainings of patient samples confirmed expression of IDO1 protein and also its metabolite kynurenine in primarily N-cadherin-positive areas. N-cadherin-positive areas also exhibited a local decrease of intraepithelial cytotoxic (CD8+) T cells and an increase of immune suppressive regulatory T cells (CD4+/FoxP3+). In conclusion, EMT in clinical prostate cancer is accompanied by upregulated expression of IDO1 and an increased number of regulatory T cells. These data indicate that EMT, which is an important step in tumor progression, can be protected from effective immune control in prostate cancer patients.

https://ift.tt/2li5xDg

Recurrent RARB Translocations in Acute Promyelocytic Leukemia lacking RARA Translocation

Translocations of retinoic acid receptor-α (RARA), typically PML-RARA, are a genetic hallmark of acute promyelocytic leukemia (APL). However, because a small fraction of APL lack translocations of RARA, we focused here on APL cases without RARA translocation to elucidate the molecular etiology of RARA-negative APL. We performed whole-genome sequencing, PCR, and FISH for five APL cases without RARA translocations. Four of five RARA-negative APL cases had translocations involving retinoic acid receptor-β (RARB) translocations, and TBL1XR1-RARB was identified as an in-frame fusion in three cases; one case had an RARB rearrangement detected by FISH, although the partner gene could not be identified. When transduced in cell lines, TBL1XR1-RARB homodimerized and diminished transcriptional activity for the retinoic acid receptor pathway in a dominant negative manner. TBL1XR1-RARB enhanced the replating capacity of mouse bone marrow cells and inhibited myeloid maturation of human cord blood cells as PML-RARA did. However, the response of APL with RARB translocation to retinoids was attenuated compared to that of PML-RARA, an observation in line with the clinical resistance of RARB-positive APL to ATRA. Our results demonstrate that the majority of RARA-negative APL have RARB translocations, thereby forming a novel, distinct subgroup of APL. TBL1XR1-RARB as an oncogenic protein exerts effects similar to those of PML-RARA, underpinning the importance of retinoic acid pathway alterations in the pathogenesis of APL.

https://ift.tt/2tjy3YJ

Influence of smoking, body mass index and other factors on the preventive effect of nonsteroidal anti-inflammatory drugs on colorectal cancer risk

Nonsteroidal anti-inflammatory drugs (NSAIDs) use has consistently been associated with lower risk of colorectal cancer (CRC); however, studies showed inconsistent results on which cohort of individuals may benefit most. We performed multivariable logistic regression analysis to systematically test for the interaction between regular use of NSAIDs and other lifestyle and dietary factors on CRC risk among 11,894 cases and 15,999 controls. Fixed-effects meta-analyses were used for stratified analyses across studies for each risk factor and to summarize the estimates from interactions. Regular use of any NSAID, aspirin, or non-aspirin NSAIDs was significantly associated with a lower risk of CRC within almost all subgroups. However, smoking status and BMI were found to modify the NSAID-CRC association. Aspirin use was associated with a 29% lower CRC risk among never-smokers (OR = 0.71; 95% CI: 0.64, 0.79), compared to 19% and 17% lower CRC risk among smokers of pack-years below median (OR = 0.81; 95% CI: 0.71, 0.92) and above median (OR = 0.83; 95% CI: 0.74, 0.94), respectively (p-interaction = 0.048). The association between any NSAID use and CRC risk was also attenuated with increasing BMI (p-interaction = 0.075). Collectively, these results suggest that obese individuals and heavy smokers are unlikely to benefit as much as other groups from the prophylactic effect of aspirin against CRC.

https://ift.tt/2lhDqnA

Neoadjuvant-intensive androgen deprivation therapy selects for prostate tumor foci with diverse subclonal oncogenic alterations

Primary prostate cancer (PCa) can have extensive microheterogeneity, but its contribution to the later emergence of metastatic castration-resistant PCa (mCRPC) remains unclear. In this study, we microdissected residual PCa foci in radical prostatectomies from 18 men treated with neoadjuvant intensive androgen deprivation therapy (leuprolide, abiraterone acetate, and prednisone) and analyzed them for resistance mechanisms. Transcriptome profiling showed reduced but persistent androgen receptor (AR) activity in residual tumors with no increase in neuroendocrine differentiation. Proliferation correlated negatively with AR activity but positively with decreased RB1 expression, and whole exome sequencing (WES) further showed enrichment for RB1 genomic loss. In 15 cases where 2 or 3 tumor foci were microdissected, WES confirmed a common clonal origin but identified multiple oncogenic alterations unique to each focus. These findings show that subclones with oncogenic alterations found in mCRPC are present in primary PCa and are selected for by neoadjuvant-intense androgen deprivation therapy. In particular, this study indicates that subclonal RB1 loss may be more common than previously appreciated in intermediate- to high-risk primary PCa and may be an early event, independent of neuroendocrine differentiation, in the development of mCRPC. Comprehensive molecular analyses of primary PCa may detect aggressive subclones and possibly inform adjuvant strategies to prevent recurrence.

https://ift.tt/2tjxTk5

Tumor-Educated Platelets as a Noninvasive Biomarker Source for Cancer Detection and Progression Monitoring

Liquid biopsies represent a potential revolution in cancer diagnostics as a noninvasive method for detecting and monitoring diseases, complementary to or even replacing current tissue biopsy approaches. Several blood-based biosources and biomolecules, such as cell-free DNA and RNA, proteins, circulating tumor cells, and extracellular vesicles, have been explored for molecular test development. We recently discovered the potential of tumor-educated blood platelets (TEP) as a noninvasive biomarker trove for RNA biomarker panels. TEPs are involved in the progression and spread of several solid tumors, and spliced TEP RNA surrogate signatures can provide specific information on the presence, location, and molecular characteristics of cancers. So far, TEP samples from patients with different tumor types, including lung, brain, and breast cancers, have been tested, and it has been shown that TEPs from patients with cancer are distinct from those with inflammatory and other noncancerous diseases. It remains to be investigated how platelets are "educated," which mechanisms cause intraplatelet RNA splicing, and whether the relative contribution of specific platelet subpopulations changes in patients with cancer. Ultimately, TEP RNA may complement currently used biosources and biomolecules employed for liquid biopsy diagnosis, potentially enhancing the detection of cancer in an early stage and facilitating noninvasive disease monitoring. Cancer Res; 78(13); 1–6. ©2018 AACR.

https://ift.tt/2lntl8K

The importance of indocyanine green near‐infrared fluorescence angiography in perfusion assessment in vascularized omentum lymphatic transplant

Journal of Surgical Oncology, EarlyView.


https://ift.tt/2li5h7g

Laparoscopic proximal gastrectomy for gastric neoplasms

Journal of Surgical Oncology, EarlyView.


https://ift.tt/2ysLXxs

Integrating Radiosensitivity and Immune Gene Signatures for Predicting Benefit of Radiotherapy in Breast Cancer

Purpose: Breast cancer is a heterogeneous disease and not all patients respond equally to adjuvant radiotherapy. Predictive biomarkers are needed to select patients who will benefit from the treatment and spare others the toxicity and burden of radiation. Experimental Design: We first trained and tested an intrinsic radiosensitivity gene signature to predict local recurrence after radiotherapy in three cohorts of 948 patients. Next, we developed an antigen processing and presentation-based immune signature by maximizing the treatment interaction effect in 129 patients. To test their predictive value, we matched patients treated with or without radiotherapy in an independent validation cohort for clinicopathologic factors including age, ER status, HER2 status, stage, hormone-therapy, chemotherapy, and surgery. Disease specific survival (DSS) was the primary endpoint. Results: Our validation cohort consisted of 1,439 patients. After matching and stratification by the radiosensitivity signature, patients who received radiotherapy had better DSS than patients who did not in the radiation-sensitive group (hazard ratio [HR]=0.68, P=0.059, n=322), while a reverse trend was observed in the radiation-resistant group (HR=1.53, P=0.059, n=202). Similarly, patients treated with radiotherapy had significantly better DSS in the immuneeffective group (HR=0.46, P=0.0076, n=180), with no difference in DSS in the immunedefective group (HR=1.27, P=0.16, n=348). Both signatures were predictive of radiotherapy benefit (P_interaction=0.007 and 0.005). Integration of radiosensitivity and immune signatures further stratified patients into three groups with differential outcomes for those treated with or without radiotherapy (P_interaction=0.003). Conclusions: The proposed signatures have the potential to select patients who are most likely to benefit from radiotherapy.

https://ift.tt/2tmIkn0

Cancer-Associated Fibroblasts Affect Intratumoral CD8+and FoxP3+ T Cells via Interleukin 6 in the Tumor Microenvironment

Purpose: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a central role in tumor progression. We investigated whether CAFs can regulate tumor-infiltrating lymphocytes (TILs) and their role in tumor immunosuppression. Experimental Design: 140 cases of esophageal cancer were analyzed for CAFs and CD8⁺or forkhead box protein 3 (FoxP3⁺) TILs by immunohistochemistry. We analyzed cytokines using murine or human fibroblasts and cancer cells. Murine-derived fibroblasts and cancer cells were also inoculated into BALB/c or BALB/c-nu/numice, and the tumors treated with recombinant interleukin 6 (IL-6) or anti-IL-6 antibody. Results: CD8⁺TILs and CAFs were negatively correlated in intra-tumoral tissues (P< 0.001), while FoxP3⁺TILs were positively correlated (P< 0.001) in esophageal cancers. Co-cultured Colon26 cancer cells and fibroblasts resulted in accelerated tumor growth in BALB/c mice, along with decreased CD8⁺and increased FoxP3⁺TILs, compared with cancer cells alone. In vitro, IL-6 was highly secreted in both murine and human cancer cell/fibroblast co-cultures. IL-6 significantly increased Colon26 tumor growth in immune-competent BALB/c (P< 0.001) with fewer CD8⁺TILs than untreated tumors (P< 0.001), whereas no difference in BALB/c-nu/numice. In contrast, FoxP3⁺TILs increased in IL-6-treated tumors (P< 0.001). IL-6 antibody blockade of tumors co-cultured with fibroblasts resulted not only in regression of tumor growth but also in the accumulation of CD8⁺TILs in intra-tumoral tissues. Conclusions:CAFs regulate immunosuppressive TIL populations in the TME via IL-6. IL-6 blockade, or targeting CAFs, may improve pre-existing tumor immunity and enhance the efficacy of conventional immunotherapies.

https://ift.tt/2MCAH4x

Chemotherapy sensitizes therapy-resistant cells to mild hyperthermia by suppressing heat shock protein 27 expression in triple negative breast cancer

Purpose: Triple-negative breast cancer (TNBC) is a clinically aggressive disease with poor prognosis. Conventional chemotherapeutics are generally able to shrink the tumor mass, but often fail to completely eradicate cancer stem-like cells (CSCs) that are responsible for high risk of relapse and frequent metastases. In this study, we examined thermal sensibility of CSCs, developed an approach that enabled concurrent elimination of both the bulk of cancer cells and CSCs, and investigated the underlying mechanism. Experimental Design: We designed a platform consisting of gold nanoparticle-coated porous silicon microparticle (AuPSM) that was also loaded with docetaxel micelles (mDTX) to enable concurrent killing of the bulk of cancer cells by released mDTX and CSCs by mild hyperthermia upon stimulation of AuPSM with near infrared. In addition, we examined the role of heat shock proteins in sensitizing CSC killing. Finally, we applied mDTX-loaded AuPSM to treat mice with SUM159 and 4T1 orthotopic tumors, and evaluated tumor growth and tumor metastasis. Results: MDA-MB-231 and SUM159 TNBC cells treated with mDTX-loaded AuPSM and mild hyperthermia displayed significantly reduced efficiencies in mammosphere formation than those treated with mDTX alone or mild hyperthermia alone. Combination treatment also completely inhibited SUM159 orthotopic tumor growth and 4T1 tumor metastasis. Mechanistically, DTX treatment suppressed expression of heat shock protein 27 in cancer cells including the CSCs, rendering cells sensitive to mild hyperthermia. Conclusions:Our results indicate that chemotherapy sensitizes CSC to mild hyperthermia. We have developed an effective therapeutic approach to eliminate therapy-resistant cells in TNBC.

https://ift.tt/2tm3t0I

Prognostic value of methylator phenotype in stage III colon cancer treated with oxaliplatin-based adjuvant chemotherapy

Purpose: There are conflicting results concerning the prognostic value of the CpG island methylator phenotype (CIMP) in non-metastatic colon cancer (CC) patients. We studied this phenotype in stage III CC characterized for mismatch repair (MMR), RAS and BRAF status and treated with adjuvant FOLFOX-based regimen. Experimental Design: Tumor samples of 1907 patients enrolled in the PETACC-8 adjuvant phase 3 trial were analyzed. The method used was methylation-specific PCR where CIMP+ status was defined by methylation of at least three of the five following genes: IGF2, CACNA1G, NEUROG1, SOCS1, and RUNX3. Association between CIMP status and overall survival (OS), disease-free survival (DFS), and survival after recurrence (SAR), was assessed by Cox model adjusted for prognostic factors and treatment arm (FOLFOX4 ± cetuximab). Results: CIMP status was successfully determined in 1867 patients (97.9%): 275 (14.7%) tumors were CIMP+. Compared to CIMP- patients, CIMP+ patients were more frequently older (p=0.002), females (p=0.04), with right-sided (p<0.0001), grade 3-4 (p<0.0001), pN2 (p=0.001), dMMR (p<0.0001), BRAF mutated (p<0.0001), and RAS wild-type (p<0.0001) tumors. In multivariate analysis, CIMP+ status was associated with shorter OS (HR: 1.46; 95%CI 1.02 - 1.94; p=0.04) and SAR (HR: 1.76; 95%CI 1.20 - 2.56; p<0.0004); but not DFS (HR: 1.15 95%CI 0.86 - 1.54; p=0.34). A non-significant trend of detrimental effect of cetuximab was observed in patients with CIMP+ tumors for OS, DFS, and SAR. Conclusions: In a large cohort of well-defined stage III CC patients, CIMP+ phenotype is associated with a shorter OS and SAR but not to DFS.

https://ift.tt/2MG1HAq

Expression patterns of programmed death ligand 1 correlate with different microenvironments and patient prognosis in hepatocellular carcinoma

Expression patterns of programmed death ligand 1 correlate with different microenvironments and patient prognosis in hepatocellular carcinoma

Expression patterns of programmed death ligand 1 correlate with different microenvironments and patient prognosis in hepatocellular carcinoma, Published online: 20 June 2018; doi:10.1038/s41416-018-0144-4

Expression patterns of programmed death ligand 1 correlate with different microenvironments and patient prognosis in hepatocellular carcinoma

https://ift.tt/2I6ctfx

Increased sensitivity to apoptosis upon endoplasmic reticulum stress-induced activation of the unfolded protein response in chemotherapy-resistant malignant pleural mesothelioma

Increased sensitivity to apoptosis upon endoplasmic reticulum stress-induced activation of the unfolded protein response in chemotherapy-resistant malignant pleural mesothelioma

Increased sensitivity to apoptosis upon endoplasmic reticulum stress-induced activation of the unfolded protein response in chemotherapy-resistant malignant pleural mesothelioma, Published online: 20 June 2018; doi:10.1038/s41416-018-0145-3

Increased sensitivity to apoptosis upon endoplasmic reticulum stress-induced activation of the unfolded protein response in chemotherapy-resistant malignant pleural mesothelioma

https://ift.tt/2tbfff2

Important ESTRO dates

https://ift.tt/2li0Xoy

Contents

https://ift.tt/2tnIHO3

Editorial Board

https://ift.tt/2lis9Do

Monitoring pulmonary health in Swiss childhood cancer survivors

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2M2AbM6

Pneumococcal vaccination coverage among children with sickle cell anemia, sickle cell trait, and normal hemoglobin

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2JQyeWH

Comparison of fixed versus traditional weight‐based dosing of rasburicase in a pediatric population

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2M6yehA

Vaccine immunotherapy with ARNAX induces tumor‐specific memory T cells and durable anti‐tumor immunity in mouse models

Cancer Science, EarlyView.


https://ift.tt/2MDYH7i

Evaluation of two prognostic indices for adult T‐cell leukemia/lymphoma in the subtropical endemic area, Okinawa, Japan

Cancer Science, EarlyView.


https://ift.tt/2JXsnux

Synergy between peroxisome proliferator‐activated receptor γ agonist and radiotherapy in cancer

Cancer Science, EarlyView.


https://ift.tt/2JQyyon

IDH‐mutated astrocytomas with 19q‐loss constitute a subgroup that confers better prognosis

Cancer Science, EarlyView.


https://ift.tt/2K01eaa

Therapies based on targeting Epstein‐Barr virus lytic replication for EBV‐associated malignancies

Cancer Science, EarlyView.


https://ift.tt/2JQxWz5

Long non‐coding RNA FOXD2‐AS1 contributes to colorectal cancer proliferation through its interaction with microRNA‐185‐5p

Cancer Science, EarlyView.


https://ift.tt/2M3SArT

Blockade of ONECUT2 expression in ovarian cancer inhibited tumor cell proliferation, migration, invasion and angiogenesis

Cancer Science, EarlyView.


https://ift.tt/2MELifp

Issue Information

Cancer Cytopathology, Volume 126, Issue 6, Page 365-370, June 2018.


https://ift.tt/2I3dlBJ

Stronger medical links for umbilical cord blood

Cancer Cytopathology, Volume 126, Issue 6, Page 371-372, June 2018.


https://ift.tt/2t8FTVK

Combination therapy of ipilimumab and nivolumab induced thyroid storm in a patient with Hashimoto’s disease and diabetes mellitus: a case report

Recently, immune checkpoint inhibitors have widely been used for the management of advanced melanoma. However, high-grade immune-related adverse events can occur, particularly with combination immunotherapy. W...

https://ift.tt/2JRecen

Is immune checkpoint inhibition part of standard therapy for stage III non‐small cell lung cancer?

Cancer, EarlyView.


https://ift.tt/2M3qLQw

Older women with a family history of breast cancer face increased risk of the disease

Cancer, Volume 124, Issue 13, Page 2673-2673, July 1, 2018.


https://ift.tt/2tbnBDa

Issue Information

Cancer, Volume 124, Issue 13, Page 2661-2670, July 1, 2018.


https://ift.tt/2M09yY4

Scientists probe link between stress and cancer

Cancer, Volume 124, Issue 13, Page 2671-2672, July 1, 2018.


https://ift.tt/2JP0icS

Multicenter, randomized, double‐blind phase 2 trial of FOLFIRI with regorafenib or placebo as second‐line therapy for metastatic colorectal cancer

Cancer, EarlyView.


https://ift.tt/2I5UuG3

Quality of life as a prognostic indicator of survival: A pooled analysis of individual patient data from Canadian Cancer Trials Group clinical trials

Cancer, EarlyView.


https://ift.tt/2JS7HIv

Variation in prostate cancer treatment and spending among Medicare shared savings program accountable care organizations

Cancer, EarlyView.


https://ift.tt/2M7WS1J

Life stress as a risk factor for sustained anxiety and cortisol dysregulation during the first year of survivorship in ovarian cancer

Cancer, EarlyView.


https://ift.tt/2JP031s

Erratum: Dudley B, Karloski E, Monzon FA, et al. Germline mutation prevalence in individuals with pancreatic cancer and a history of previous malignancy. Cancer. 2018;124:1691‐1700.

Cancer, EarlyView.


https://ift.tt/2M09h7u

Symptoms of posttraumatic stress disorder among hospitalized patients with cancer

Cancer, EarlyView.


https://ift.tt/2JQNWkB

Quality of life in patients with proton‐treated pediatric medulloblastoma: Results of a prospective assessment with 5‐year follow‐up

Cancer, EarlyView.


https://ift.tt/2I5U5n1

Beyond classic risk adjustment: Socioeconomic status and hospital performance in urologic oncology surgery

Cancer, EarlyView.


https://ift.tt/2JOZPaC

Iron overload in patients with myelodysplastic syndromes: An updated overview

Cancer, EarlyView.


https://ift.tt/2I5U0jd

The classification of pediatric and young adult renal cell carcinomas registered on the Children's Oncology Group (COG) protocol AREN03B2 after focused genetic testing

Cancer, EarlyView.


https://ift.tt/2tauVPw

Expression patterns of programmed death ligand 1 correlate with different microenvironments and patient prognosis in hepatocellular carcinoma

https://ift.tt/2tn2Pjt

Increased sensitivity to apoptosis upon endoplasmic reticulum stress-induced activation of the unfolded protein response in chemotherapy-resistant malignant pleural mesothelioma

https://ift.tt/2MFOY0A

Course and predictors of supportive care needs among Mexican breast cancer patients: A longitudinal study

Psycho-Oncology, EarlyView.


https://ift.tt/2K4ESHR

“Spirituality” hardly facilitates our understanding of existential distress—But “everyday life” might

Psycho-Oncology, EarlyView.


https://ift.tt/2I4QmWL

Re‐validation and screening capacity of the 6‐item version of the Cancer Worry Scale

Psycho-Oncology, EarlyView.


https://ift.tt/2K6ucZe

Predicting nonadherence to adjuvant endocrine therapy in women with early stage breast cancer

Psycho-Oncology, EarlyView.


https://ift.tt/2I4cS20

A forbidden topic at the end of life: “What about you after I'm gone?”

Psycho-Oncology, EarlyView.


https://ift.tt/2K6WiUi

Associations between the smoking‐relatedness of a cancer type, cessation attitudes and beliefs, and future abstinence among recent quitters

Psycho-Oncology, EarlyView.


https://ift.tt/2I4cKzy

Facing death alone or together? Investigating the interdependence of death anxiety, dysfunctional attitudes, and quality of life in patient‐caregiver dyads confronting lung cancer

Psycho-Oncology, EarlyView.


https://ift.tt/2K6W7bA

Determinants for local tumour control probability after radiotherapy of anal cancer

Anal squamous cell carcinoma is primarily treated with radiotherapy (RT), but the optimal RT dose for anal tumours of different sizes is not known. The purpose of this study was to identify determinants for local tumour control probability (LTCP).

https://ift.tt/2K4A4SP

Estimating the need for palliative radiotherapy for non-small cell lung cancer: A criterion-based benchmarking approach

Estimates of appropriate treatment rates are required for monitoring and improving access to cancer care. Optimal utilization rates for palliative radiotherapy (PRT) for patients with non-small cell lung cancer (NSCLC) remain undefined. We aim to estimate the appropriate PRT rate for the general NSCLC population.

https://ift.tt/2K0AOW5

Inverse planning and inverse implanting for breast interstitial brachytherapy. Introducing a new anatomy specific breast interstitial template (ASBIT)

An innovative template, based on thoracic cage surface reconstructions for breast interstitial brachytherapy was developed. Hybrid-inverse-planning-optimisation-based implantations and brachytherapy plans, using three custom anthropomorphic breast phantoms, were utilised for its validation. A user independent, inverse planning and inverse implanting technique is proposed.

https://ift.tt/2K9Toy2

Cardiac mortality in limited-stage small cell lung cancer

Life expectancy of patients with limited-stage small cell lung cancer (LS-SCLC) continues to rise; thus, characterization of long-term toxicities is essential. Although there are emerging data linking cardiac irradiation doses with survival for non-small cell lung cancer, there are currently minimal data on cardiac-specific mortality (CSM) in LS-SCLC. The goal of this investigation was to evaluate CSM between left- and right-sided cases.

https://ift.tt/2I2ZMlN

Simultaneous PET/MRI in assessing the response to chemo/radiotherapy in head and neck carcinoma: initial experience

Abstract

The purpose of the study was to assess by simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) the response to chemotherapy (CHT) and/or radiotherapy (RT) in patients with head and neck squamous cell carcinoma (HNSCC). Five patients with HNSCC underwent simultaneous PET/MRI examination before and after CHT and/or RT. Standard uptake volume (SUV), apparent diffusion coefficient (ADC), Ktrans, Kep, Ve, and iAUC pre- and post-treatment values were extracted and compared. The response to treatment was assessed according to RECIST criteria and classified as complete response (CR), partial response (PR), stable disease (SD), and progression disease (PD). In patient 1, PR was observed with increased ADC, Ktrans, and Ve values and reduction of SUV, iAUC, and Kep values; during clinical and instrumental follow-up, the patient experienced disease progression. Patient 2, classified as PR, showed increased ADC values and reduction of SUV and all perfusion parameters; follow-up demonstrated disease stability. Patient 3, considered as SD, showed increase of ADC and all perfusion values with a mild decrease of SUV; PD was observed during clinical and instrumental follow-up. Patients 4 and 5 showed a CR with no detectable tumor lesions at post-treatment PET/MRI examination, confirmed by 1-year follow-up. Multiparametric evaluation with simultaneous PET/MRI could be a useful tool to assess and predict the response to CHT and/or RT in patients with HNSCC.

https://ift.tt/2yrAheo

Urethra-sparing stereotactic body radiotherapy for prostate cancer: how much can the rectal wall dose be reduced with or without an endorectal balloon?

This is a dosimetric comparative study intended to establish appropriate low-to-intermediate dose-constraints for the rectal wall (Rwall) in the context of a randomized phase-II trial on urethra-sparing stereotac...

https://ift.tt/2thTZU4

Acquired factor XII deficiency following transanal excision of rectal lesion by transanal minimally invasive surgery (TAMIS): a case report and literature review

Abstract

Background

Local excision (LE) is currently one of the most effective methods used in cases of large benign polyps, not suitable for endoscopic treatment, or early-stage neoplasms. LE is also alternative to anterior rectal resection in selected patients suffering from major comorbidities and limits for major abdominal procedure. Furthermore, LE results in less pain, reduced impact on bowel function, shorter duration of hospital stay, and lower rates of morbidity, mortality and stoma creation. In particular, early data on transanal minimally invasive surgery (TAMIS) are promising, but they come from single centre case series related to small groups of patients and more data are needed to draw a final conclusion on the safety of this novel approach for transanal resection.

Case presentation

A 62-year-old woman, following a positive faecal occult blood test and with unremarkable medical history, was admitted to hospital for excision of a large flat neoplastic lesion. Endoscopic biopsy demonstrated a tubular adenoma with high-grade dysplasia and was decided to proceed with surgical excision by TAMIS. After surgery, short-term outcomes revealed prolonged activated partial thromboplastin time, undetectable factor XII activity, fever, and partial dehiscence of rectal wall defect suture. Cross-mixing studies of patient plasma show no correction in either the immediate or incubated activated partial thromboplastin time, indicating the presence of an acquired factor XII inhibitor. Activated partial thromboplastin time and factor XII improved in the following weeks without any specific therapy in addition to antibiotic therapy.

Conclusion

This is the first report in which acquired inhibitor of coagulation factor XII is associated with a specific surgical procedure. This case has shown how trans-anal excision of rectal lesions, even when performed by minimally invasive means such as in case of TAMIS, is not free of complications. We consider the acute infection, resulting from early dehiscence of the suture, the trigger in an abnormal immune response, and inhibitor development.

https://ift.tt/2yr9f6U

Tumor-Suppressive Function of miR-30d-5p in Prostate Cancer Cell Proliferation and Migration by Targeting NT5E

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 5, Page 203-211, June 2018.


https://ift.tt/2tk9gUk

The Effect of Computed Tomography-Guided 125I Radioactive Particle Implantation in Treating Cancer and Its Pain

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 5, Page 176-181, June 2018.


https://ift.tt/2MCP5Kg

On Reviewing

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 5, Page 167-168, June 2018.


https://ift.tt/2tiVwt9

Exploration of a F(ab′)2 Fragment as the Targeting Agent of α-Radiation Therapy: A Comparison of the Therapeutic Benefit of Intraperitoneal and Intravenous Administered Radioimmunotherapy

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 5, Page 182-193, June 2018.


https://ift.tt/2t7byHk

Effects of hsa_circRBM23 on Hepatocellular Carcinoma Cell Viability and Migration as Produced by Regulating miR-138 Expression

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 5, Page 194-202, June 2018.


https://ift.tt/2ymmt4X

Identification of hub genes with prognostic values in gastric cancer by bioinformatics analysis

Abstract

Background

Gastric cancer (GC) is a prevalent malignant cancer of digestive system. To identify key genes in GC, mRNA microarray GSE27342, GSE29272, and GSE33335 were downloaded from GEO database.

Methods

Differentially expressed genes (DEGs) were obtained using GEO2R. DAVID database was used to analyze function and pathways enrichment of DEGs. Protein-protein interaction (PPI) network was established by STRING and visualized by Cytoscape software. Then, the influence of hub genes on overall survival (OS) was performed by the Kaplan-Meier plotter online tool. Module analysis of the PPI network was performed using MCODE. Additionally, potential stem loop miRNAs of hub genes were predicted by miRecords and screened by TCGA dataset. Transcription factors (TFs) of hub genes were detected by NetworkAnalyst.

Results

In total, 67 DEGs were identified; upregulated DEGs were mainly enriched in biological process (BP) related to angiogenesis and extracellular matrix organization and the downregulated DEGs were mainly enriched in BP related to ion transport and response to bacterium. KEGG pathways analysis showed that the upregulated DEGs were enriched in ECM-receptor interaction and the downregulated DEGs were enriched in gastric acid secretion. A PPI network of DEGs was constructed, consisting of 43 nodes and 87 edges. Twelve genes were considered as hub genes owing to high degrees in the network. Hsa-miR-29c, hsa-miR-30c, hsa-miR-335, hsa-miR-33b, and hsa-miR-101 might play a crucial role in hub genes regulation. In addition, the transcription factors-hub genes pairs were displayed with 182 edges and 102 nodes. The high expression of 7 out of 12 hub genes was associated with worse OS, including COL4A1, VCAN, THBS2, TIMP1, COL1A2, SERPINH1, and COL6A3.

Conclusions

The miRNA and TFs regulation network of hub genes in GC may promote understanding of the molecular mechanisms underlying the development of gastric cancer and provide potential targets for GC diagnosis and treatment.

https://ift.tt/2M3XAgp

Prognosis of elderly gastric cancer patients after surgery: a nomogram to predict survival

Abstract

This study aimed to identify clinicopathological factors associated with the outcome of elderly patients with gastric cancer (GC), and to construct a nomogram for individual risk prediction. Tumor characteristics of 143 patients aged ≥ 80 years underwent surgery for GC were collected and analyzed by uni- and multivariate analyses. A prognostic nomogram was constructed using the factors which resulted to be significantly associated with overall survival. Discrimination of nomogram was tested by Kaplan–Meier (KM) curves and boxplots. With a median follow up of 18.37 months, overall 1-year survival rate was 51% and it was 60 and 40% for older and younger than 83 years, respectively (P = 0.003). Univariate analysis indicated that age (P = 0.008), pre-operatory performance status (P < 0.001), depth of invasion (P = 0.007), lymph nodes involvement (P < 0.001), and residual tumor (P < 0.001) were significant prognostic factors. Based on these variables, a nomogram to predict 3, 6, 12, and 24 months survival probability after GC surgery was developed. KM and boxplots according to the range of nomogram total points highlighted the appropriateness of distinguish the patients' survival in all the subgroups. Moreover, this nomogram exhibited superior prognostic discrimination between intermediate stages (II–III) than AJCC-TNM classification. This study showed that after good surgical selection, the prognosis of elderly GC patients may be influenced by several clinicopathological factors. Therefore, a predictive nomogram to distinguish more accurately fit patients may allow physicians to individualize treatments and to detect those patients who may benefit from an intensive multidisciplinary approach.

https://ift.tt/2MCnLvq

A rare case of perivascular epithelioid cell tumor (PEComa) of the greater omentum

Abstract

Background

A tumor composed exclusively or predominantly of human melanin black 45 (HMB45)-positive epithelioid cells is called a perivascular epithelioid cell tumor (PEComa). We report a very rare case of a PEComa of the greater omentum.

Case presentation

MRI conducted to examine the orthopedic disease of the patients, a 49-year-old Japanese woman, also identified a tumor in her pelvis. A CT scan revealed a tumor mass on the right side of the pelvic floor and clear nutrient vessels originating from the splenic and celiac arteries. An omental primary tumor or accessory spleen was thus suspected, and tumor resection was performed. The tumor was a light brown solid tumor with a smooth margin, measuring 5.2 × 3.8 × 3.5 cm. Histopathologically, the tumor was composed mainly of spindle and epithelioid cells, and large and small blood vessel formation was observed. In the immunohistochemical staining, tumor cells were positive for human melanin black 45 (HMB-45) and Melan-A and partially positive for alpha-smooth muscle actin. The final diagnosis was PEComa of the greater omentum.

Conclusions

Although omental PEComa is very rare, it should be considered as a differential disease of an omental primary tumor.

https://ift.tt/2I3pk1Z

Uniform intratumoral distribution of radioactivity produced using two different radioagents, 64 Cu-cyclam-RAFT-c(-RGDfK-) 4 and 64 Cu-ATSM, improves therapeutic efficacy in a small animal tumor model

Abstract

Background

The present study proposed a new concept for targeted radionuclide therapy (TRT) to improve the intratumoral distribution of radioactivity using two different radiopharmaceuticals. We examined the efficacy of a combination of a tetrameric cyclic Arg-Gly-Asp (cRGD) peptide-based radiopharmaceutical, ⁶⁴Cu-cyclam-RAFT-c(-RGDfK-)₄ (⁶⁴Cu-RaftRGD, an α_Vβ₃ integrin [α_Vβ₃] tracer), and ⁶⁴Cu-diacetyl-bis (N⁴-methylthiosemicarbazone) (⁶⁴Cu-ATSM, a supposed tracer for hypoxic metabolism) in a small animal tumor model.

Results

Mice with subcutaneous α_Vβ₃-positive U87MG glioblastoma xenografts were used. The intratumoral distribution of a near-infrared dye, Cy5.5-labeled RAFT-c(-RGDfK-)₄ (Cy5.5-RaftRGD), ⁶⁴Cu-RaftRGD, and ⁶⁴Cu-ATSM was visualized by fluorescence imaging and autoradiography of the co-injected Cy5.5-RaftRGD with ⁶⁴Cu-RaftRGD or ⁶⁴Cu-ATSM at 3 h postinjection. Mice were treated with a single intravenous dose of the vehicle solution (control), 18.5 or 37 MBq of ⁶⁴Cu-RaftRGD or ⁶⁴Cu-ATSM, or a combination (18.5 MBq of each agent). The tumor volume, tumor cell proliferation, body weight, survival, and tumor and organ uptake of radiopharmaceuticals were assessed. It was shown that Cy5.5-RaftRGD colocalized with ⁶⁴Cu-RaftRGD and could be used as a surrogate for the radioactive agent. The intratumoral distribution of Cy5.5-RaftRGD and ⁶⁴Cu-ATSM was discordant and nearly complementary, indicating a more uniform distribution of radioactivity achievable with the combined use of ⁶⁴Cu-RaftRGD and ⁶⁴Cu-ATSM. Neither ⁶⁴Cu-RaftRGD nor ⁶⁴Cu-ATSM showed significant effects on tumor growth at 18.5 MBq. The combination of both (18.5 MBq each) showed sustained inhibitory effects against tumor growth and tumor cell proliferation and prolonged the survival of the mice, compared to that by either single agent at 37 MBq. Interestingly, the uptake of the combination by the tumor was higher than that of ⁶⁴Cu-RaftRGD alone, but lower than that of ⁶⁴Cu-ATSM alone. The kidneys showed the highest uptake of ⁶⁴Cu-RaftRGD, whereas the liver exhibited the highest uptake of ⁶⁴Cu-ATSM. No obvious adverse effects were observed in all treated mice.

Conclusions

The combination of ⁶⁴Cu-RaftRGD and ⁶⁴Cu-ATSM achieved an improved antitumor effect owing to the more uniform intratumoral distribution of radioactivity. Thus, combining different radiopharmaceuticals to improve the intratumoral distribution would be a promising concept for more effective and safer TRT.

https://ift.tt/2M4KlMq

C11 Methionine PET (MET-PET) Imaging of Glioblastoma for Detecting Post-operative Residual Disease and Response to Chemoradiation Therapy

Publication date: Available online 18 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Yingbing Wang, Otto Rapalino, Pedram Heidari, Jay Loeffler, Helen A. Shih, Kevin Oh, Umar Mahmood
Purpose/ObjectivesResponse criteria of glioblastoma after chemoradiation do not account for metabolic changes that occur after treatment. The purpose of this study is to evaluate the utility of positron emission tomography imaging with C11 Methionine (MET-PET) for detecting changes that occur after chemoradiation therapy and the value of molecular biomarkers for predicting magnitude of metabolic response.Materials and MethodsNewly diagnosed glioblastoma patients undergoing standard chemoradiation treatment were enrolled in this prospective imaging study with MET-PET scan performed within 3 days following surgical resection and again at 4 weeks after completion of chemoradiation. Near contemporaneous contrast enhanced MRI (ceMRI) was performed within 2 weeks of each MET-PET. MET-PET imaging was analyzed for SUVmax, SUVmean, and SUVvolume on a multimodality workstation (Syngovia 24B, Siemens).ResultsA total of 18 subjects underwent baseline post-operative MET-PET imaging, of which 14 subjects underwent post-chemoradiation MET-PET imaging. Among subjects who showed residual MET-avid disease on immediate post-operative MET-PET scans and also underwent post-chemo radiation MET-PET imaging (n=10), mean ΔSUVmax was -40% (range -100%-0%), mean ΔSUVmean was -35% (range -100%-0%), and mean ΔSUV volume was -64% (range -100%-0%). Δtumor/brain reference was -40% (range -100%-0%) using SUVmax and -35% (range -100%-0%) using SUVmean. In contrast, none of the T2 weighted images on ceMRI showed reduction in abnormal T2/FLAIR signal by greater than 25% by visual assessment. ΔSUVmax, ΔSUVmean, and ΔSUVvolume correlated with MGMT methylation status (p=0.01), but not with EGFR, or c-MET amplification status. All patients were IDH-1 wildtype.ConclusionsMET-PET scanning shows significant decrease in metabolic signal at 1 month post-chemoradiation compared to the immediate post-operative period, even when T2/FLAIR changed little. MGMT promoter methylation status further predicts differential metabolic responses. MET-PET may be a useful tool for delineation of radiation targets and assessment of response.

Teaser

C11 Methionine PET may be a useful tool for delineation of radiation targets and assessment of response in glioblastoma. C11 Methionine PET scanning can show a significant decrease in extent of MET-avid glioblastoma at 1 month after completion of chemoradiation compared to the immediate post-operative period, even when T2/FLAIR changes little. MGMT promoter methylation status further predicts differential metabolic responses.


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Quantitative Imaging for Radiation Oncology

Publication date: Available online 18 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Uulke A. van der Heide, Daniela Thorwarth




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Long-Term Impact of Regional Nodal Irradiation in Patients with Node-Positive Breast Cancer Treated with Neoadjuvant Systemic Therapy

Publication date: Available online 19 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Shane R. Stecklein, Minjeong Park, Diane D. Liu, Janeiro J. Valle Goffin, Abigail S. Caudle, Elizabeth A. Mittendorf, Carlos H. Barcenas, Sarah Mougalian, Wendy A. Woodward, Vicente Valero, Aysegul A. Sahin, Wei T. Yang, Simona F. Shaitelman
BackgroundThe impact of regional nodal irradiation (RNI) on locoregional recurrence (LRR) and any disease recurrence (DR) in women with node-positive breast cancer who receive neoadjuvant systemic therapy (NAT) is unknown.MethodsThe impact of RNI on LRR and DR was estimated with the cumulative incidence method in 1289 women with stage II-III breast cancer with cytologically confirmed axillary metastases who received NAT, 1989-2007. Multicovariate Cox regression analysis was performed to examine the effect of RNI after accounting for other predictive and prognostic variables.ResultsThe median follow-up after definitive surgery was 10.2 years. Axillary pCR was observed in 368 of 1289 patients (28.5%). On univariate analysis, axillary pCR reduced 10-year LRR risk from 9.7% to 4.8% (P=.006) and DR risk from 43.0% to 17.0% (P<.001). RNI was administered to 1080 of 1289 patients (83.8%). On univariate analysis, RNI did not affect 10-year LRR risk (no RNI, 9.4%; RNI, 8.1%; P=.62) or DR risk (no RNI, 31.3%; RNI, 36.5%; P=.16). On multicovariate analysis, RNI significantly reduced the risk of LRR (hazard ratio [HR], 0.497; 95% CI, 0.279-0.884; P=.02) and DR (HR, 0.731; 95% CI, 0.541-0.988; P=.04), and showed a particularly strong reduction in risk of DR in patients with HER2+ disease who received trastuzumab (HR, 0.237; 95% CI, 0.109-0.517; P=.0003). A nomogram to predict 10-year LRR risk with and without RNI has been generated to assist clinicians in individualizing treatment decisions based on patient and disease characteristics and response to NAT.ConclusionsAdjuvant RNI reduces risk of LRR and DR in breast cancer patients with axillary metastases who receive NAT across subtypes and particularly decreases the risk of DR in HER2+ breast cancer treated with trastuzumab. Enrollment on the NSABP B-51/RTOG 1304 protocol is encouraged to help determine whether RNI can be omitted in patients with axillary pCR to NAT.



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Tumor shrinkage during chemoradiation in locally advanced cervical cancer patients: prognostic significance, and impact for image-guided adaptive brachytherapy

Publication date: Available online 18 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Antoine Schernberg, Sophie Bockel, Pierre Annede, Ingrid Fumagalli, Alexandre Escande, Fabien Mignot, Manon Kissel, Philippe Morice, Enrica Bentivegna, Sebastien Gouy, Eric Deutsch, Christine Haie-Meder, Cyrus Chargari
ObjectiveTo study the prognostic value of gross tumor volume (GTV) shrinkage and its dosimetric implication in a large cohort of cervical cancer patients receiving definitive chemoradiotherapy plus image—guided adaptive brachytherapy (IGABT).Materials and MethodsClinical records of consecutive patients treated in our Institution between February 2004 and November 2015 by concurrent chemoradiotherapy (45Gy in 25 fractions +/- lymph node boosts) followed by a magnetic resonance imaging (MRI)-guided adaptive pulse-dose rate brachytherapy were included. The prognostic value of GTV and its evolution after chemoradiotherapy were examined first on initial staging MRI and then at time of brachytherapy. All measures and measurement cutoff were selected using time-dependent Area Under the Curve for 3-year progression-free survival (PFS).ResultsGTV evolution between diagnosis and the time of brachytherapy was assessed in 247 patients. After chemoradiotherapy, complete response was observed in 75 patients (28%). Optimal cutoffs were GTV=55cc at diagnosis, GTV=7.5cc at brachytherapy, and GTV reduction ≥90%. All patients with volume above or reduction below these cutoffs had significant reduced overall survival (OS), PFS, local control (LC) and distant metastasis control (DMC) (p<0.001). Patients with anemia at diagnosis had a lower tumor volume response rate (p<0.001). In multivariate analysis, incorporating the FIGO stage, N+ stage, anemia, and dosimetric parameters for IGABT, GTV optimal volume reduction after chemoradiotherapy was independently associated with improved OS, PFS, LC, and DMC (p<0.001).ConclusionThese results could provide a rationale for dose de-escalation studies in brachytherapy for patients displaying optimal GTV volumetric reduction after chemoradiotherapy, and may reinforce the need for dose escalation in poor responding patients.

Teaser

The prognostic value of GTV and its evolution after chemoradiotherapy, assessed in 247 patients were examined first on initial staging MRI and then at time of brachytherapy. In multivariate analysis, GTV optimal volume reduction was independently associated with improved overall survival and local control (p<0.001). Patients with optimal GTV reduction had no significant benefit from dose escalation D90 CTVHR ≥80Gy (p>0.3) while patients without optimal GTV reduction may have (p<0.05).


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Patient reported outcomes in NRG Oncology RTOG 0938, evaluating two ultrahypofractionated regimens for prostate cancer

Publication date: Available online 18 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Himanshu R. Lukka, Stephanie L. Pugh, Deborah W. Bruner, Jean-Paul Bahary, Colleen A.F. Lawton, Jason A. Efstathiou, Rajat J. Kudchadker, Lee E. Ponsky, Samantha A. Seaward, Ian S. Dayes, Darindra D. Gopaul, Jeff M. Michalski, Guila Delouya, Irving D. Kaplan, Eric M. Horwitz, Mack Roach, Wayne H. Pinover, David C. Beyer, John O. Amanie, Howard M. Sandler, Lisa A. Kachnic
BackgroundThere is considerable interest in very short (ultrahypofractionated) radiotherapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience and resource allocation benefits.ObjectiveTo demonstrate that detectable changes in health related quality of life measured by the bowel and urinary domains of the Expanded Prostate Cancer Index Composite (EPIC-50) were not substantially worse than baseline.Design, Setting, and ParticipantsXXXX is a non-blinded randomized phase II study of NCCN low risk prostate cancer where each arm is compared to a historical control.Intervention(s)Patients were randomized to five fractions (7.25Gy in two weeks), or twelve fractions (4.3Gy in 2.5 weeks).Outcome Measurements and Statistical AnalysisThe co-primary endpoints were the proportion of patients with a change in EPIC bowel score at one year (baseline to one-year) >five points and in EPIC urinary score >two points tested with a one-sample binomial test.Resultsand Limitations: 127 patients were enrolled to five fractions (121 analyzed) and 128 to twelve fractions (125 analyzed). Median follow-up for all patients at the time of analysis was 3.8 years. The one year frequency for >five point change in bowel score for five and twelve fractions were 29.8%(p<0.001) and 28.4%(p<0.001) respectively. The one year frequency for >two point change in urinary score for five and twelve fractions were 45.7%(p<0.001) and 42.2%(p<0.001) respectively. For five and twelve fractions 32.9% of patients had a drop in 1 year EPIC sexual score ≥ 11 points (p=0.34) while 30.9% of patients had a drop in 1 year EPIC sexual score ≥11 points (p=0.20) in the twelve fraction arm respectively. DFS at two years is 93.3% (95% CI: 88.8, 97.8) and 88.3% (95% CI: 82.5, 94.0) in the five and twelve fraction arms, respectively. There was no late grade 4 or 5 treatment-related urinary or bowel toxicity.ConclusionsThis study confirms that based on changes in bowel and urinary domains and toxicity (acute and late) the five and twelve fractions regimens are well tolerated. These ultrahypofractionated approaches need to be compared to current standard radiotherapy regimens

Teaser

The urinary and rectal quality of life outcomes reported by prostate cancer patients undergoing 5 & 12 prostate radiotherapy treatments are comparable to current standard 38-44 radiotherapy treatments. These shorter radiotherapy treatments need to be compared to the current standard radiotherapy treatments in a larger study.


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Acute single appendicitis in a female with a duplicated appendix

Abstract

Appendiceal duplication is a rare congenital anomaly with an estimated incidence ranging from 0.004 to 0.009%. Preoperative diagnosis of a duplicated appendix is often difficult and is usually done intraoperatively. Histopathological examination of the surgical specimen is mandatory to confirm the presence of two appendices. In this case we report a female patient with acute inflammation in one of her two appendices. Surgeons should always bear in mind this rare anomaly to avoid serious ethical and legal consequences.

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Sodium polystyrene sulfonate crystals in the gastric wall of a patient with upper gastrointestinal bleeding and gastric perforation: an incidental finding or a pathogenic factor?

Abstract

Sodium polystyrene sulfonate, or Kayexalate, is an ion-exchange resin used to treat hyperkalemia. It is sometimes used with sorbitol, an osmotic laxative that prevents constipation. Small and large bowel necrosis and perforation due to Kayexalate were previously reported. However, no previous cases of gastric perforation were described. We present a case of gastric perforation in a 48-year-old patient, with chronic kidney disease (CKD), lung transplant under chronic corticosteroids, and two previous Nissen fundoplications. He presented with sudden epigastralgia, hematemesis and hemodynamic instability. Esophagogastroduodenoscopy was not able to localize the site of bleeding. Surgical exploration revealed perforation of the lesser curvature of the stomach. Antrectomy with a Billroth II reconstruction was performed. Pathological examination revealed no abnormalities except fibrinoleukocytic debris with Kayexalate crystals in the gastric wall. Kayexalate is believed to be a trigger for the gastric injury in a patient with tissues impaired by corticosteroids, CKD and immunosuppressors.

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Association of Interindividual Variation in Plasma Oxytocin With Postcesarean Incisional Pain

Oxytocin has known antinociceptive effects and is upregulated perinatally. This pilot study investigated the association of plasma oxytocin and postcesarean incisional pain. Plasma samples from 18 patients undergoing elective cesarean delivery were drawn at 1 hour preoperatively and 1 and 24 hours postoperatively and analyzed by using enzyme-linked immunosorbent assay. Pain was assessed at 1 day, 8 weeks, 3 months, and 6 months postoperatively. Incisional pain at 24 hours was inversely correlated with 1- and 24-hour oxytocin levels, with higher plasma oxytocin associated with lower pain (ρ, −0.52 and −0.66; P

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Parasympathetic Tone Activity Evaluation to Discriminate Ketorolac and Ketorolac/Tramadol Analgesia Level in Swine

BACKGROUND: Evaluation of nociceptive–antinociceptive balance during general anesthesia is still challenging and routinely based on clinical criteria. Analgesic drug delivered may be optimized with parasympathetic tone activity (PTA) monitor. This study compares ketorolac and ketorolac/tramadol balance analgesia using a PTA monitor. METHODS: Pain intensity response was assessed using a 0–100 numerical state scale (PTA) after nociceptive stimuli in pigs under stable sevoflurane anesthesia. Bispectral index, heart rate, noninvasive blood pressure, and respiratory parameters were also measured. Animals were divided into 3 groups: without analgesia, ketorolac, and ketorolac/tramadol. Mean values or mean areas under the curve (AUC) in selected time periods were compared over time and between groups through a mixed-model repeated measures analysis of variance and nonparametric Kruskal-Wallis tests, followed by Bonferroni or Dunn's multiple comparisons. RESULTS: It was observed a significant decrease in the PTA AUC mean value after application of the stimulus in animals treated without analgesia and only with ketorolac. The PTA AUC mean value in the control group was significantly lower than the corresponding mean in ketorolac group. The ketorolac/tramadol group showed the highest PTA AUC mean values, significantly different from those obtained for the other 2 groups, with no significant differences detected over time. Bispectral index means showed no statistically significant differences either over time periods or between different treatment groups. Heart rate showed only a statistically significant increase in AUC mean between without analgesia and ketorolac/tramadol group, in the time period after the stimulus application. Noninvasive blood pressure means showed no statistically significant differences over time and between treatment groups. CONCLUSIONS: This study shows that a low dose combination of ketorolac and tramadol is sufficient to block the pain responses induced with a needle holder in pigs 20 minutes after its administration. The PTA monitor was able to clearly recognize the analgesic level between treatments and may be used to optimize analgesic drug delivered. Accepted for publication May 10, 2018. Funding: This work is supported by European Investment Funds by FEDER/COMPETE/POCI–Operacional Competitiveness and Internacionalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT–Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013. The authors declare no conflicts of interest. 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. Reprints will not be available from the authors. Address correspondence to Carlos J. Leitão, DVM, Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal. Address e-mail to carlos.leitão.35@gmail.com. © 2018 International Anesthesia Research Society

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Comparison of Broadband and Discrete Wavelength Near-Infrared Spectroscopy Algorithms for the Detection of Cytochrome aa3 Reduction

BACKGROUND: Cytochrome aa3, the terminal component of the electron transport chain, absorbs near-infrared radiation (NIR) differentially depending on its oxidation state (Cytox), which can in theory be measured using near-infrared spectroscopy (NIRS) by relating light absorption at specific wavelengths to chromophore concentrations. Some NIRS algorithms use discrete wavelengths, while others analyze a band of NIR (broadband NIRS). The purpose of this study was to test the ability of discrete wavelength and broadband algorithms to measure changes in Cytox (primary outcome), and to determine whether or not a discreet wavelength NIRS algorithm could perform similarly to a broadband NIRS algorithm for the measurement of Cytox in a staged hypoxia–cyanide model (hypoxia and cyanide have oppositional effects on tissue saturation, but both cause cytochrome reduction). METHODS: Twenty Sprague-Dawley rats were anesthetized with isoflurane, intubated, and instrumented. Blood pressure, end-tidal carbon dioxide, and arterial oxygen saturation were measured. A halogen light source transmitted NIR transcranially. NIR from the light source and the skull was transmitted to 2 cooled charge-coupled device spectrometers. Rats were subjected to anoxia (fraction of inspired oxygen, 0.0) until arterial oxygen saturation decreased to 70%. After recovery, 5 mg/kg sodium cyanide was injected intravenously. The cycle was repeated until cardiac arrest occurred. Relative concentrations of hemoglobin and cytochrome aa3 were calculated using discreet wavelength and broadband NIRS algorithms. RESULTS: Hypoxia led to an increase in calculated deoxyhemoglobin (0.20 arbitrary units [AUs]; 95% confidence interval [CI], 0.17–0.22; P

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Development of a Rescue Echocardiography Protocol for Noncardiac Surgery Patients

Intraoperative transesophageal echocardiography (TEE) is a helpful diagnostic tool when hemodynamic compromise is encountered during noncardiac surgery. At our institution, a Rescue Echo Protocol was created to provide a structured means for requesting and performing a rescue TEE. We analyzed our institutional utilization of this service and found that it was used throughout the spectrum of patients' American Society of Anesthesiologists classifications and surgical services. We demonstrated that 72.9% of rescue examinations resulted in a change in management, supporting the use of TEE as a diagnostic tool during hemodynamic compromise. Accepted for publication April 12, 2018. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Genevieve E. Staudt, MD, Department of Pediatric Anesthesiology, Vanderbilt University Medical Center, Suite 3116, Nashville, TN 37232. Address e-mail to genevieve.e.staudt@vanderbilt.edu. © 2018 International Anesthesia Research Society

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Anesthesiology: Clinical Case Reviews

No abstract available

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A Randomized Trial of Continuous Noninvasive Blood Pressure Monitoring During Noncardiac Surgery

BACKGROUND: Intraoperative hypotension is associated with postoperative mortality. Early detection of hypotension by continuous hemodynamic monitoring might prompt timely therapy, thereby reducing intraoperative hypotension. We tested the hypothesis that continuous noninvasive blood pressure monitoring reduces intraoperative hypotension. METHODS: Patients ≥45 years old with American Society of Anesthesiologists physical status III or IV having moderate-to-high-risk noncardiac surgery with general anesthesia were included. All participating patients had continuous noninvasive hemodynamic monitoring using a finger cuff (ClearSight, Edwards Lifesciences, Irvine, CA) and a standard oscillometric cuff. In half the patients, randomly assigned, clinicians were blinded to the continuous values, whereas the others (unblinded) had access to continuous blood pressure readings. Continuous pressures in both groups were used for analysis. Time-weighted average for mean arterial pressure

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LncRNA MALAT1 promotes migration and invasion of non-small-cell lung cancer by targeting miR-206 and activating Akt/mTOR signaling

Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) functions as a crucial regulator of metastasis in lung cancer. The aim of this study is to unravel the underlying mechanisms of lncRNA MALAT1 in non-small-cell lung cancer (NSCLC). A cohort of 36 NSCLC tumor tissues and adjacent normal tissues was collected postoperatively from patients with NSCLC. qRT-PCR was performed to detect the expression of MALAT1 in both NSCLC tissues and cell lines. Cell migration and invasion were monitored by wound healing assay and transwell invasion assay. Western blot was used to detect the expression levels of epithelial–mesenchymal transition proteins and Akt/mTOR key components after treatment. Dual luciferase reporter assay coupled with qRT-PCR was used to verify the direct interaction between MALAT1 and miR-206. MALAT1 was significantly up-regulated in both NSCLC tissues and cell lines. High expression of MALAT1 correlated positively with tumor size and lymphatic metastasis in NSCLC, whereas no correlation was found between MALAT1 expression and sex, age, clinical stage, and histological grade. We also showed that MALAT1 promoted epithelial–mesenchymal transition, cell migration, and invasion by activating Akt/mTOR signaling in A549 and H1299 cells. miR-206 was a direct downstream target of MALAT1 in NSCLC. MALAT1 promoted cell migration and invasion by sponging miR-206 in NSCLC cells. In addition, miR-206 inhibited MALAT1-mediated activation of Akt/mTOR signaling in A549 and H1299 cells. lncRNA MALAT1 promotes migration and invasion of NSCLC by targeting miR-206 and activating Akt/mTOR signaling. Correspondence to Yi Tang, MM, 1st Department of Thoracic Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan Province, People's Republic of China Tel: +86 731 8865 1900; e-mail: yitang7895@163.com Received October 31, 2017 Accepted April 27, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A case of complete response to nivolumab after long-term progression-free survival with tyrosine kinase inhibitor

Nivolumab is an effective and tolerable treatment for metastatic renal cell carcinoma, showing longer median overall survival than everolimus and achieving a good percentage of objective response, stable disease, and prolonged responses. However, very few cases have been reported in the literature of a complete response to nivolumab in the metastatic pretreated setting. Here, we report a case of complete response to nivolumab in II line following sunitinib in a metastatic clear cell renal cell carcinoma with favorable risk according to the IMDC criteria. This is also an interesting case on the use of immunotherapy following a long period of antiangiogenetic therapy, underlining the importance of the sequence of treatment to achieve the best possible outcome in terms of prolonged overall survival, progression-free survival, and objective response. *Veronica Mollica and Vincenzo Di Nunno contributed equally to the writing of this article. Correspondence to Francesco Massari, MD, Division of Oncology, S. Orsola-Malpighi Hospital, Via Albertoni n. 15, Bologna 40138, Italy Tel: +39 051 214 2575; fax: +39 051 636 2764; e-mail: francesco.massari@aosp.bo.it Received April 1, 2018 Accepted May 29, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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LncRNA MALAT1 promotes epithelial-to-mesenchymal transition of esophageal cancer through Ezh2-Notch1 signaling pathway

To investigate effect of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on epithelial-to-mesenchymal transition (EMT) of esophageal cancer (EC) and role of enhancer of zeste homolog 2 (Ezh2)-Notch1 signaling pathway in the process. The expression of MALAT1 was determined in four EC cell lines by real-time PCR. TE-1 and EC109 cells were transfected with sh-MALAT1 to inhibit expression of MALAT1 or transfected with pcDNA3.1-Ezh2 to overexpress Ezh2. Invasion and migration assays were conducted to analyze cell metastasis, and expressions of Ezh2-Notch1 signaling-related proteins as well as EMT related proteins were determined using both real-time PCR and western blot. MALAT1 was significantly up-regulated in all EC cell lines compared with the normal cells. Silencing MALAT1 using shRNA could significantly inhibit cell viability (reduced almost 30% of cell viability compared with the control), invasion (reduced almost 30% of cell migration compared with the control), and migration (reduced almost 50% of cell migration compared with the control) of both TE-1 and EC109 cells (P

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MiR-29a inhibited intestinal epithelial cells autophagy partly by decreasing ATG9A in ulcerative colitis

Ulcerative colitis (UC), with high morbidity has become one of the fastest-growing severe illnesses in the world. Although MiR-29a is highly expressed in the tissues of UC patients, the mechanism of miR-29a involved in the specific pathogenesis of UC is not known. In this study, a GFP-light chain 3 (LC3) immunofluorescence assay was used to observe the formation of the autophagic spot; qRT-PCR and western blotting analyses were carried out to detect the expression of autophagy-related proteins, including BECN1, Autophagy-related gene (ATG)5, ATG16L, and transcription factor EB. The dual-fluorescence reporter assay was used to analyze the direct effect of miR-29a on ATG9A; experimental dextran sulfate sodium-induced colitis in mice was used to establish the UC model. Our studies showed that the overexpression of miR-29a not only suppressed the production of GFP-LC3 autophagy spots but also inhibited the level of LC3II/LC3I and upregulated the expression of P62 in HT29 and HCT116 cells. Moreover, the results showed that miR-29a directly targeted the 3′UTR region of ATG9A mRNA to suppress the activation of HT29 and HCT116 cells' autophagy. Also, overexpression of ATG9A rescued rapamycin-induced autophagy that was inhibited by overexpression of miR-29a. In addition, miR-29a also affected the expression of autophagy-related proteins (BECN1, ATG5, ATG16L1, and transcription factor EB). Notably, miR-29a was upregulated, whereas ATG9A was downregulated in the experimental dextran sulfate sodium-induced colitis in mice. In effect, this study showed that miR-29a inhibits rapamycin-induced intestinal epithelial cells' autophagy partly by decreasing ATG9A in UC. These findings may provide new insights that may help control the inflammation in UC. Correspondence to Miao Ouyang, MD, Gastroenterology Department, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, People's Republic of China Tel: +86 073 189 753 999; fax: +86 13 907 482 825; e-mail: ouyangmiao1115@163.com Received November 17, 2017 Accepted March 28, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Emergence times and airway reactions during general anaesthesia with remifentanil and a laryngeal mask airway: A multicentre randomised controlled trial

BACKGROUND Avoidance of airway complications and rapid emergence from anaesthesia are indispensable for the use of a laryngeal mask airway (LMA). Evidence from adequately powered randomised studies with a low risk of bias for the optimal anaesthetic in this context is limited. OBJECTIVE We tested the hypothesis that when using remifentanil-based intra-operative analgesia, desflurane would be the most suitable anaesthetic: with noninferiority in the occurrence of upper airway complications and superiority in emergence times compared with sevoflurane or propofol. DESIGN A prospective, randomised, multicentre, partially double-blinded, three-arm, parallel-group study. SETTING Two university and two regional German hospitals, from February to October 2015. PATIENTS A total of 352 patients (age 18 to 75 years, ASA physical status I to III, BMI less than 35 kg m−2 and fluent in German) were enrolled in this study. All surgery was elective with a duration of 0.5 to 2 h, and general anaesthesia with a LMA was feasible. INTERVENTION The patients were randomised to receive desflurane, sevoflurane or propofol anaesthesia. MAIN OUTCOME MEASURES This study was powered for the primary outcome 'time to state date of birth' and the secondary outcome 'intra-operative cough'. Time to emergence from anaesthesia and the incidence of upper airway complications were assessed on the day of surgery. RESULTS The primary outcome was analysed for 343 patients: desflurane (n=114), sevoflurane (n=111) and propofol (n=118). The desflurane group had the fastest emergence. The mean (± SD) times to state the date of birth following desflurane, sevoflurane and propofol were 8.1 ± 3.6, 10.1 ± 4.0 and 9.8 ± 5.1 min, respectively (P 

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The LAS VEGAS risk score for prediction of postoperative pulmonary complications: An observational study

BACKGROUND Currently used pre-operative prediction scores for postoperative pulmonary complications (PPCs) use patient data and expected surgery characteristics exclusively. However, intra-operative events are also associated with the development of PPCs. OBJECTIVE We aimed to develop a new prediction score for PPCs that uses both pre-operative and intra-operative data. DESIGN This is a secondary analysis of the LAS VEGAS study, a large international, multicentre, prospective study. SETTINGS A total of 146 hospitals across 29 countries. PATIENTS Adult patients requiring intra-operative ventilation during general anaesthesia for surgery. INTERVENTIONS The cohort was randomly divided into a development subsample to construct a predictive model, and a subsample for validation. MAIN OUTCOME MEASURES Prediction performance of developed models for PPCs. RESULTS Of the 6063 patients analysed, 10.9% developed at least one PPC. Regression modelling identified 13 independent risk factors for PPCs: six patient characteristics [higher age, higher American Society of Anesthesiology (ASA) physical score, pre-operative anaemia, pre-operative lower SpO2 and a history of active cancer or obstructive sleep apnoea], two procedure-related features (urgent or emergency surgery and surgery lasting ≥ 1 h), and five intra-operative events [use of an airway other than a supraglottic device, the use of intravenous anaesthetic agents along with volatile agents (balanced anaesthesia), intra-operative desaturation, higher levels of positive end-expiratory pressures > 3 cmH2O and use of vasopressors]. The area under the receiver operating characteristic curve of the LAS VEGAS risk score for prediction of PPCs was 0.78 [95% confidence interval (95% CI), 0.76 to 0.80] for the development subsample and 0.72 (95% CI, 0.69 to 0.76) for the validation subsample. CONCLUSION The LAS VEGAS risk score including 13 peri-operative characteristics has a moderate discriminative ability for prediction of PPCs. External validation is needed before use in clinical practice. TRIAL REGISTRATION The study was registered at Clinicaltrials.gov, number NCT01601223. Correspondence to Ary Serpa Neto, MD, MSc, PhD, Department of Critical Care, Hospital Israelita Albert Einstein, 621 Albert Einstein Avenue, São Paulo, 03178-200 Brazil. Tel: +55 112 1511521; e-mail: aryserpa@terra.com.br 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 (https://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

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