Angiogenesis, Invasion, and Metastasis Characteristics of Hepatocellular Carcinoma

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A germline missense mutation in exon 3 of the MSH2 gene in a Lynch syndrome family: correlation with phenotype and localization assay

Abstract

Lynch syndrome is caused by germline mutations in any of the MisMatch Repair (MMR) genes. About 37% of MSH2 variants are missense variants causing single amino-acid substitutions. Whether missense variants affect the normal function of MMR proteins is crucial both to provide affected families a more accurate risk assessment and to offer predictive testing to family members. Here we report one family, fulfilling both Amsterdam I and II criteria and Bethesda guidelines, referred to our center for genetic counselling. The proband and some of her relatives have been investigated for microsatellite instability (MSI), immunohistochemical MMR protein staining, direct sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA). Also Subcellular Localization Assay and Splice site predictions analyses were used. A germline missense variant of uncertain significance (exon 3, p.Val161Asp) was found in MSH2 gene in proband and in some relatives. The variant was associated with lack of expression of MSH2 protein (DMMR) and MSI-High status in tumour tissues. The localization assay of the MSH2 protein showed an abnormal subcellular localization pattern of the corresponding protein. Finally, splice-site prediction analysis ruled out a potential role of new splice sites as the cause behind the lack of expression of MSH2 protein and we suppose a potential correlation with other forms of post-transcriptional regulation (circular RNAs). The variant here reported shows a high correlation with phenotype and is located in an evolutionary conserved domain. The localization assay also suggest a potential pathogenic role, thus supporting further research on this matter.

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Cancer survivorship and opioid prescribing rates: A population-based matched cohort study among individuals with and without a history of cancer

BACKGROUND

Little is known about opioid prescribing among individuals who have survived cancer. Our aim is to examine a predominantly socio-economically disadvantaged population for differences in opioid prescribing rates among cancer survivors compared with matched controls without a prior diagnosis of cancer.

METHODS

This was a retrospective population-wide matched cohort study. Starting in 2010, individuals residing in Ontario, Canada, who were 18 to 64 years of age and at least 5 years past their cancer diagnosis were matched to controls without a prior cancer diagnosis based on sex and calendar year of birth. Follow-up was terminated at any indication of cancer recurrence, second malignancy, or new cancer diagnosis. To examine the association between survivorship and the rate of opioid prescriptions, an Andersen-Gill recurrent event regression model was implemented, adjusting for numerous individual-level characteristics and also accounting for the matched design.

RESULTS

The rate of opioid prescribing was 1.22 times higher among survivors than among their corresponding matched controls (adjusted relative rate, 1.22; 95% CI, 1.11-1.34). Individuals from lower income quintiles who were younger, were from rural neighborhoods, and had more comorbidities had significantly higher prescribing rates. Sex was not associated with prescribing rates. This increased rate of opioid prescribing was also seen among survivors who were 10 or more years past their cancer diagnosis (compared with their controls).

CONCLUSION

This study demonstrates substantially higher opioid prescribing rates among cancer survivors, even long after attaining survivorship. This raises concerns about the diagnosis and management of chronic pain problems among survivors stemming from their cancer diagnosis or treatment. Cancer 2017. © 2017 American Cancer Society.

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Germline BRCA mutations in Asian patients with pancreatic adenocarcinoma: a prospective study evaluating risk category for genetic testing

Summary

Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy. Analyses for germline BRCA mutations were performed if patients had one or more first-degree or second-degree relatives with breast or ovarian cancers or had a personal medical history of these diseases. DNA was extracted from whole blood, and all coding exons and their flanking intron regions of BRCA1 and BRCA2 were sequenced. Results A total of 175 patients were screened for personal and family history and 10 (5.7%) met the inclusion criteria for genetic sequencing. Pathogenic germline BRCA2 mutation [c.7480C>T (p.Arg2494*)] was identified in one male patient, resulting in a frequency of 10% for the risk-stratified patients and 0.6% for the unselected PDAC population. Two patients had germline BRCA2 variants of uncertain significance [c.1744A>C (p.Thr582Pro) and c.68-7T>A]. Conclusion Personal or family history of breast or ovarian cancers is a feasible, cost-effective risk categorization for screening germline BRCA mutations in Asian PDAC patients as 10% of this population had the pathogenic mutation herein. Future validation from a large, prospective cohort is needed.

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Anti-glomerular basement membrane glomerulonephritis following nintedanib for idiopathic pulmonary fibrosis: a case report

We report a previously unrecognized and unreported case of a patient with anti-glomerular basement membrane glomerulonephritis following nintedanib, an orally active small molecule tyrosine kinase inhibitor.

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Re: ASTRO consensus guideline for oropharyngeal cancer

Publication date: Available online 5 August 2017
Source:Practical Radiation Oncology
Author(s): Gary V. Walker, Pierre Blanchard, Adam S. Garden




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Response to ASTRO consensus guideline for oropharyngeal cancer

Publication date: Available online 5 August 2017
Source:Practical Radiation Oncology
Author(s): David J. Sher, David J. Adelstein, Gopal K. Bajaj, David M. Brizel, Ezra E. Cohen, Aditya Halthore, Louis B. Harrison, Charles Lu, Benjamin J. Moeller, Harry Quon, James W. Rocco, Erich M. Sturgis, Roy B. Tishler, Andy Trotti, John Waldron, Avraham Eisbruch




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Mortality, Geriatric, and Nongeriatric Surgical Risk Factors Among the Eldest Old: A Prospective Observational Study.

BACKGROUND: Preoperative risk and postoperative outcomes among the elderly are the subject of extensive debate. However, the eldest old, that is, the fastest-growing and most vulnerable group, are insufficiently studied; even their mortality rate is unclear. This prospective observational study was performed with the aim of determining the mortality rate of this population and establishing which preoperative conditions were predictors of which postoperative outcomes. The study was undertaken between 2011 and 2015 in a major tertiary care university hospital. METHODS: All patients aged >=85 years undergoing any elective procedure during the study period were included. Patients were followed up for 30 days postoperatively. The preoperative conditions studied were demographic data, grade of surgical complexity (1-3), preoperative comorbidities, and some characteristically geriatric conditions (functional reserve, nutrition, cognitive status, polypharmacy, dependency, and frailty). The outcome measures were 30-day all-cause mortality (primary end point), morbidity, prolonged length of stay, and escalation of care in living conditions. RESULTS: Of 139 eligible patients, 127 completed follow-up. The 30-day mortality was 7.9%; 95% confidence interval (CI), 3.2-12.6. It had 3 predictors: malnutrition (odds ratio [OR], 15; 95% CI, 3-89), complexity 3 (OR, 9.1; CI, 2-52), and osteoporosis/osteoporotic fractures (OR, 14.7; CI, 2-126). Significant predictors for morbidity (40%) were ischemic heart disease (OR, 3.9; CI, 1-11) and complexity 3 (OR, 3.6; CI, 2-9), while a nonfrail phenotype (OR, 0.3; CI, 0.1-0.8) was found to be protective. Only 2 factors were found to be predictive of longer admissions, namely complexity 3 (OR, 4.4; CI, 2-10) and frailty (OR, 2.7; CI, 2-7). Finally, risk factors for escalation of care in living conditions were slow gait (a surrogate for frailty, OR, 2.5; CI, 1-6), complexity 3 (OR, 3.2; CI, 1-7), and hypertension (OR, 2.9; CI, 1-9). CONCLUSIONS: The eldest old is a distinct group with a considerable mortality rate and their own particular risk factors. Surgical complexity and certain geriatric variables (malnutrition and frailty), which are overlooked in American Society of Anesthesiologists and most other usual scores, are particularly relevant in this population. Inclusion of these factors along with appropriate comorbidities for risk stratification should guide better decision making for families and doctors alike and encourage preoperative optimization of patients. (C) 2017 International Anesthesia Research Society

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The Technology of Processed Electroencephalogram Monitoring Devices for Assessment of Depth of Anesthesia.

Commercial brain function monitors for depth of anesthesia have been available for more than 2 decades; there are currently more than 10 devices on the market. Advances in this field are evidenced by updated versions of existing monitors, development of new monitors, and increasing research unveiling the mechanisms of anesthesia on the brain. Electroencephalography signal processing forms an integral part of the technology supporting the brain function monitors for derivation of a depth-of-anesthesia index. This article aims to provide a better understanding of the technology and functionality behind these monitors. This review will highlight the general design principles of these devices and the crucial stages in electroencephalography signal processing and classification, with a focus on the key mathematical techniques used in algorithm development for final derivation of the index representing anesthetic state. We will briefly discuss the advantages and limitations of this technology in the clinical setting as a tool in our repertoire used for optimizing individualized patient care. Also included is a table describing 10 available commercial depth-of-anesthesia monitors. (C) 2017 International Anesthesia Research Society

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Atlas of Peripheral Regional Anesthesia Anatomy and Techniques, 3rd edition.

No abstract available

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Perioperative Drill-Based Crisis Management.

No abstract available

http://ift.tt/2vaCCoy

Reduction in Operating Room Plasma Waste After Evidence-Based Quality Improvement Initiative.

Anesthesiologists request units of plasma in anticipation of transfusion. The amount of plasma transfused intraoperatively is less than that issued (requested, thawed, and sent). We presented institutional-specific data on plasma usage including anesthesiologist-specific ratios of plasma issued-to-transfused. In month-to-month comparisons from the year before the presentation (June-December 2015) to 7 months after (June-December 2016), plasma issued to the operating room was reduced from 434.9 +/- 81 to 327.3 +/- 65 units, a change of 107.6 units per month (95% confidence interval [CI], 22-193); plasma discarded by the blood bank was reduced from 109.7 +/- 48 units to 69.1 +/- 9 units, a change of 40.6 units per month (95% CI, 0.2-81); and plasma transfused went from 188.4 +/- 42 units to 160.7 +/- 52 units, a nonsignificant change of 27.7 units per month (95% CI, -27 to 83). (C) 2017 International Anesthesia Research Society

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An Appraisal of the Carlisle-Stouffer-Fisher Method for Assessing Study Data Integrity and Fraud.

Data fabrication and scientific misconduct have been recently uncovered in the anesthesia literature, partly via the work of John Carlisle. In a recent article in Anaesthesia, Carlisle analyzed 5087 randomized clinical trials from anesthesia and general medicine journals from 2000 to 2015. He concluded that in about 6% of studies, data comparing randomized groups on baseline variables, before the given intervention, were either too similar or dissimilar compared to that expected by usual sampling variability under the null hypothesis. Carlisle used the Stouffer-Fisher method of combining P values in Table 1 (the conventional table reporting baseline patient characteristics) for each study, then calculated trial P values and assessed whether they followed a uniform distribution across studies. Extreme P values targeted studies as likely to contain data fabrication or errors. In this Statistical Grand Rounds article, we explain Carlisle's methods, highlight perceived limitations of the proposed approach, and offer recommendations. Our main findings are (1) independence was assumed between variables in a study, which is often false and would lead to "false positive" findings; (2) an "unusual" result from a trial cannot easily be concluded to represent fraud; (3) utilized cutoff values for determining extreme P values were arbitrary; (4) trials were analyzed as if simple randomization was used, introducing bias; (5) not all P values can be accurately generated from summary statistics in a Table 1, sometimes giving incorrect conclusions; (6) small numbers of P values to assess outlier status within studies is not reliable; (7) utilized method to assess deviations from expected distributions may stack the deck; (8) P values across trials assumed to be independent; (9) P value variability not accounted for; and (10) more detailed methods needed to understand exactly what was done. It is not yet known to what extent these concerns affect the accuracy of Carlisle's results. We recommend that Carlisle's methods be improved before widespread use (applying them to every manuscript submitted for publication). Furthermore, lack of data integrity and fraud should ideally be assessed using multiple simultaneous statistical methods to yield more confident results. More sophisticated methods are needed for nonrandomized trials, randomized trial data reported beyond Table 1, and combating growing fraudster sophistication. We encourage all authors to more carefully scrutinize their own reporting. Finally, we believe that reporting of suspected data fraud and integrity issues should be done more discretely and directly by the involved journal to protect honest authors from the stigma of being associated with potential fraud. (C) 2017 International Anesthesia Research Society

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Perioperative Considerations for the Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes.

No abstract available

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Cadaveric Study of the Articular Branches of the Shoulder Joint.

Background and Objectives: This cadaveric study investigated the anatomic relationships of the articular branches of the suprascapular (SN), axillary (AN), and lateral pectoral nerves (LPN), which are potential targets for shoulder analgesia. Methods: Sixteen embalmed cadavers and 1 unembalmed cadaver, including 33 shoulders total, were dissected. Following dissections, fluoroscopic images were taken to propose an anatomical landmark to be used in shoulder articular branch blockade. Results: Thirty-three shoulders from 17 total cadavers were studied. In a series of 16 shoulders, 16 (100%) of 16 had an intact SN branch innervating the posterior head of the humerus and shoulder capsule. Suprascapular sensory branches coursed laterally from the spinoglenoid notch then toward the glenohumeral joint capsule posteriorly. Axillary nerve articular branches innervated the posterolateral head of the humerus and shoulder capsule in the same 16 (100%) of 16 shoulders. The AN gave branches ascending circumferentially from the quadrangular space to the posterolateral humerus, deep to the deltoid, and inserting at the inferior portion of the posterior joint capsule. In 4 previously dissected and 17 distinct shoulders, intact LPNs could be identified in 14 (67%) of 21 specimens. Of these, 12 (86%) of 14 had articular branches innervating the anterior shoulder joint, and 14 (100%) of 14 LPN articular branches were adjacent to acromial branches of the thoracoacromial blood vessels over the superior aspect of the coracoid process. Conclusions: Articular branches from the SN, AN, and LPN were identified. Articular branches of the SN and AN insert into the capsule overlying the glenohumeral joint posteriorly. Articular branches of the LPN exist and innervate a portion of the anterior shoulder joint. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

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Focused Cardiac Ultrasound for the Regional Anesthesiologist and Pain Specialist.

This article in our point-of-care ultrasound (PoCUS) series discusses the benefits of focused cardiac ultrasound (FoCUS) for the regional anesthesiologist and pain specialist. Focused cardiac US is an important tool for all anesthesiologists assessing patients with critical conditions such as shock and cardiac arrest. However, given that ultrasound-guided regional anesthesia is emerging as the new standard of care, there is an expanding role for ultrasound in the perioperative setting for regional anesthesiologists to help improve patient assessment and management. In addition to providing valuable insight into cardiac physiology (preload, afterload, and myocardial contractility), FoCUS can also be used either to assess patients at risk of complications related to regional anesthetic technique or to improve management of patients undergoing regional anesthesia care. Preoperatively, FoCUS can be used to assess patients for significant valvular disease, such as severe aortic stenosis or derangements in volume status before induction of neuraxial anesthesia. Intraoperatively, FoCUS can help differentiate among complications related to regional anesthesia, including high spinal or local anesthetic toxicity resulting in hemodynamic instability or cardiac arrest. Postoperatively, FoCUS can help diagnose and manage common yet life-threatening complications such as pulmonary embolism or derangements in volume status. In this article, we introduce to the regional anesthesiologist interested in learning FoCUS the basic views (subcostal 4-chamber, subcostal inferior vena cava, parasternal short axis, parasternal long axis, and apical 4-chamber), as well as the relevant sonoanatomy. We will also use the I-AIM (Indication, Acquisition, Interpretation, and Medical decision making) framework to describe the clinical circumstances where FoCUS can help identify and manage obvious pathology relevant to the regional anesthesiologist and pain specialist, specifically severe aortic stenosis, hypovolemia, local anesthetic systemic toxicity, and massive pulmonary embolism. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

http://ift.tt/2v8S9Xy