Cancer by Sfakianakis Alexandros: 04/15/18

Κυριακή 15 Απριλίου 2018

Prevalence of thyroid diseases in familial adenomatous polyposis: a systematic review and meta-analysis

Abstract

Thyroid cancer (TC) is a known extra-intestinal manifestation and contributes to the mortality and morbidity in patients with familial adenomatous polyposis (FAP). Its exact prevalence is not well established and recent studies have shown an increasing number of TC in this patient population. The prevalence of benign thyroid masses and endocrinologic thyroid disorders are also poorly described. We conducted a systematic review and meta-analysis by using a random-effects model to characterize TC and estimated the prevalence of thyroid diseases in FAP patients. Twelve studies (n = 9821) were included. Pooled prevalence of TC, benign thyroid masses, and endocrinologic thyroid disorders in FAP were 2.6% [95% confidence interval (CI) 1.3–4.8], 48.8% [95% CI 33.8–64.0], and 6.9% [95% CI 4.5–10.3] respectively. Subgroup analyses revealed higher prevalence of TC in studies with fewer participants, studies that used screening ultrasound to diagnose TC, and studies that were published after 2002. TC diagnosis preceded the diagnosis of FAP in 34% of the patients. The means age at diagnosis of FAP and TC were 29 and 31 years, respectively. 95% of the patients were female and the most common pathology was of papillary subtype (83.3%). Most mutations (79.2%) were located at the 5′ end of APC gene. In summary, benign thyroid disorders are common in FAP, yet, TC is an uncommon phenomenon. Certain patient subset, such as young female with APC mutation at the 5′ end, might benefit from routine surveillance ultrasound.

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Impact of Powered and Tissue-Specific Endoscopic Stapling Technology on Clinical and Economic Outcomes of Video-Assisted Thoracic Surgery Lobectomy Procedures: A Retrospective, Observational Study

Abstract

Introduction

Video-assisted thoracic surgery (VATS) lung resections are complex procedures with a critical role played by endoscopic staplers in the transection of vessels, bronchi, and lung tissue. This retrospective, observational study compared hospital resource use, costs, and complications of VATS lobectomy procedures for whom powered versus manual endoscopic surgical staplers were used.

Methods

Patients ≥ 18 years of age undergoing elective VATS lobectomy during an inpatient admission from January 1, 2012 to September 30, 2016 were identified from the Premier Healthcare Database (first admission = index admission). Use of either powered or manual endoscopic staplers during the index admission was identified from hospital administrative records. Multivariable regression analyses adjusting for patient, hospital, and provider characteristics and hospital-level clustering were carried out to compare the following outcomes between the powered and manual stapler groups: hospital length of stay (LOS), operating room time (ORT), hospital costs, complications (bleeding and/or transfusions, air leak complications, pneumonia, and infection), discharge status, and 30-, 60-, and 90-day all-cause readmissions.

Results

The powered and manual stapler groups comprised 659 patients (mean age 66.1 years; 53.6% female) and 3100 patients (mean age 66.7 years; 54.8% female), respectively. In the multivariable analyses, the powered stapler group had shorter LOS (4.9 vs. 5.9 days, P < 0.001), lower total hospital costs ($23,841 vs. $26,052, P = 0.009), and lower rates of combined hemostasis complications (bleeding and/or transfusions; 8.5% vs. 16.0%, P < 0.001) and transfusions (5.4% vs. 10.9%, P = 0.002), compared with the manual stapler group. Other outcomes did not differ significantly between the study groups. Similar trends were observed in subanalyses comparing devices across predominant manufacturers in each group, and in subanalyses of patients with comorbid chronic obstructive pulmonary disease.

Conclusion

In this analysis of VATS lobectomy procedures, powered staplers were associated with significant benefits with respect to selected types of hospital resource use, costs, and clinical outcomes when compared with manual staplers.

Funding

Johnson & Johnson.

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Impact of Powered and Tissue-Specific Endoscopic Stapling Technology on Clinical and Economic Outcomes of Video-Assisted Thoracic Surgery Lobectomy Procedures: A Retrospective, Observational Study

Abstract

Introduction

Methods

Results

Conclusion

Funding

Johnson & Johnson.

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BLU-667 Targets RET-Altered Cancers [News in Brief]

Investigational drug is safe, shows early promise in patients with medullary thyroid cancer and NSCLC.

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Adjuvant Therapy for Melanoma Prolongs RFS [News in Brief]

PD-1 inhibitor pembrolizumab reduces recurrence risk in patients with stage III disease.

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Precision Targeted Therapy With BLU-667 for RET-Driven Cancers [Research Articles]

The receptor tyrosine kinase, rearranged during transfection (RET), is an oncogenic driver activated in multiple cancers including non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC). No approved therapies have been designed to target RET; treatment has been limited to multi-kinase inhibitors (MKIs) which can have significant off-target toxicities and limited efficacy. BLU-667 is a highly potent and selective RET inhibitor designed to overcome these limitations. In vitro, BLU-667 demonstrated ≥10-fold increased potency over approved MKIs against oncogenic RET variants and resistance mutants. In vivo, BLU-667 potently inhibited growth of NSCLC and thyroid cancer xenografts driven by various RET mutations and fusions without inhibiting vascular endothelial growth factor receptor 2 (VEGFR-2). In first-in-human testing, BLU-667 significantly inhibited RET signaling and induced durable clinical responses in patients with RET-altered NSCLC and MTC without notable off target toxicity, providing clinical validation for selective RET targeting.

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Smoking is predictive of poorer distant metastasis-free and progression free-survival in soft tissue sarcoma patients treated with pre-operative radiotherapy or chemoradiotherapy

Abstract

Background

Soft tissue sarcomas (STS) are often treated with pre-operative radiation (RT), with or without chemotherapy, followed by wide local excision. Prognosis for these patients involves an interplay of tumor and patient characteristics. Known prognostic determinants include tumor size, grade, response to therapy, and patient characteristics such as age. While smoking is negatively correlated with outcomes in various malignancies, the impact on STS is unknown. We aimed to assess if smoking impacts overall (OS), distant metastasis-free (DMFS), and progression-free (PFS) survival in patients with STS treated with pre-operative RT.

Methods

Between 2000 and 2015, 166 patients with STS were identified from our prospective database. Patient variables were retrospectively reviewed. Smoking was defined as a ≥ 10 pack year history of current and former smokers. Survival was evaluated using the fisher exact test for univariate (UVA) and logistic regression for multivariate (MVA) analysis.

Results

Fifty-seven (34.3%) patients had smoking histories of ≥ 10 pack years. On UVA, smoking was associated with decreased DMFS (p = 0.0009) and PFS (p = 0.0036), but not OS (p = 0.05). Smoking held significance on MVA for both DMFS and PFS. Current smokers and patients with ≥ 24-month follow-up demonstrated decreased DMFS and PFS on UVA and MVA.

Conclusions

Current smokers and patients with a significant smoking history demonstrated decreased DMFS and PFS in STS patients treated with pre-operative RT. Smoking may cause immunologic compromise and therefore lead to higher rates of progression and distant metastasis.

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Editorial Board

Publication date: April 2018
Source:Cancer Genetics, Volumes 222–223

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Smoking is predictive of poorer distant metastasis-free and progression free-survival in soft tissue sarcoma patients treated with pre-operative radiotherapy or chemoradiotherapy

Abstract

Background

Methods

Results

Conclusions

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Spontaneous posterior rectus sheath hernia: a case report

Hernias of the posterior rectus sheath are very rare abdominal wall hernias with only a handful of cases reported in the literature to date. As an uncommon disease, it is important to recognize and report this...

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Real-world use, safety, and survival of ipilimumab in metastatic cutaneous melanoma in The Netherlands

Phase III trials with ipilimumab showed an improved survival in patients with metastatic melanoma. We evaluated the use and safety of ipilimumab, and the survival of all patients with metastatic cutaneous melanoma (N=807) receiving ipilimumab in real-world clinical practice in The Netherlands using data from the Dutch Melanoma Treatment Registry. Patients who were registered between July 2012 and July 2015 were included and analyzed according to their treatment status: treatment-naive (N=344) versus previously-treated (N=463). Overall, 70% of treatment-naive patients and 62% of previously-treated patients received all four planned doses of ipilimumab. Grade 3 and 4 immune-related adverse events occurred in 29% of treatment-naive patients and 21% of previously-treated patients. No treatment-related deaths occurred. Median time to first event was 5.4 months [95% confidence interval (CI): 4.7–6.5 months] in treatment-naive patients and 4.4 months (95% CI: 4.0–4.7 months) in previously-treated patients. Median overall survival was 14.3 months (95% CI: 11.6–16.7 months) in treatment-naive patients and 8.7 months (95% CI: 7.6–9.6 months) in previously-treated patients. In both patient groups, an elevated lactate dehydrogenase level (hazard ratio: 2.25 and 1.70 in treatment-naive and previously-treated patients, respectively) and American Joint Committee on Cancer M1c-stage disease (hazard ratio: 1.81 and 1.83, respectively) were negatively associated with overall survival. These real-world outcomes of ipilimumab slightly differed from outcomes in phase III trials. Although phase III trials are crucial for establishing efficacy, real-world data are of great added value enhancing the generalizability of outcomes of ipilimumab in clinical practice. *Anouk Jochems and Brenda Leeneman contributed equally to the writing of this article. Correspondence to Anouk Jochems, MD, MSc, Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands Tel: +31 71 5263486; fax: +31 71 5264036; e-mail: a.jochems@lumc.nl Received October 5, 2017 Accepted March 15, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Real-world use, safety, and survival of ipilimumab in metastatic cutaneous melanoma in The Netherlands

A Novel Technique of Ultrasound-Guided Selective Mandibular Nerve Block With a Lateral Pterygoid Plate Approach: A Cadaveric Study

Background and Objectives We aimed to describe a novel technique of ultrasound-guided selective mandibular nerve block with a lateral pterygoid plate (LPP) approach and to assess its feasibility and accuracy in a soft cadaver model. Methods Ten soft cadavers were studied. A curved array ultrasound transducer was applied over 1 side of the face of the cadaver, in an open-mouth position. The transducer was placed transversely below the zygomatic arch and tilted in the caudal-to-cranial direction to identify the boundary of the LPP. The needle was inserted in-plane, in an anterior-to-posterior direction, into the posterior border of the uppermost part of the LPP, and 3 mL of methylene blue was injected. Results Mandibular nerve block was successfully performed in all 10 cadavers using an LPP approach under ultrasound guidance. The mandibular nerve and its branches were seen to be stained with methylene blue in all cadaveric specimens. No accidental injection into the facial nerve or maxillary artery was observed. Conclusions This cadaveric study suggests that this novel technique, using an LPP approach under ultrasound guidance, is helpful for selective mandibular nerve block, with high accuracy and feasibility. Further studies are required to establish its safety and efficacy for clinical application. Clinical Trial Registration This study was registered at the Thai Clinical Trials Registry (ClinicalTrials.in.th), identifier TCTR20160601004. Accepted for publication November 20, 2017. Address correspondence to: Wirinaree Kampitak, MD, Department of Anesthesiology, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society and Faculty of Medicine, Chulalongkorn University, 1873, Rama 4 Road, Pathumwan, Bangkok, 10330, Thailand (e-mail: nutong127@yahoo.com). No external funding was received. The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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The Impact of Spinal Needle Selection on Postdural Puncture Headache: A Meta-Analysis and Metaregression of Randomized Studies

Background and Objectives Potentially broadened indications for spinal anesthesia require increased understanding of the risk factors and prevention measures associated with postdural puncture headache (PDPH). This review is designed to examine the association between spinal needle characteristics and incidence of PDPH. Methods Meta-analysis and metaregression was performed on randomized controlled trials to determine the effect of needle design and gauge on the incidence of PDPH after controlling for patient confounders such as age, sex, and year of publication. Results Fifty-seven randomized controlled trials (n = 16416) were included in our analysis, of which 32 compared pencil-point design with cutting-needle design and 25 compared individual gauges of similar design. Pencil-point design was associated with a statistically significant reduction in incidence of PDPH (risk ratio, 0.41; 95% confidence interval, 0.31–0.54; P

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Selective Suprascapular and Axillary Nerve Block Versus Interscalene Plexus Block for Pain Control After Arthroscopic Shoulder Surgery: A Noninferiority Randomized Parallel-Controlled Clinical Trial

Background and Objectives This randomized trial aimed to assess if a combined suprascapular-axillary nerve block (SSB) is noninferior (margin = 1.3 on a 0- to 10-point scale) to interscalene block (ISB) in treating pain after arthroscopic shoulder surgery. Secondary end points included opioid consumption, dyspnea, discomfort associated with muscle weakness, and patient satisfaction. Methods One hundred patients undergoing arthroscopic shoulder surgery were randomized to receive ultrasound-guided ISB (n = 50) or SSB (n = 50). Pain intensity at rest, dyspnea, and discomfort were recorded upon arrival in the recovery room, discharge to the ward, and at 4, 8, and 24 hours after surgery. Piritramide consumption was recorded for the first 24 hours. Patient satisfaction was assessed on the second postoperative day. Results During the first 4 hours after surgery, the difference in mean pain score between SSB and ISB was higher than 2.5 (±0.8). The difference gradually decreased to 1.1 (±1.0) at 8 hours before resulting in noninferiority during the night and at 24 hours. Piritramide consumption was significantly higher in the SSB group in the first 8 hours. The incidence of dyspnea and discomfort was higher after ISB. Treatment satisfaction was similar in both groups. Conclusions Suprascapular-axillary nerve block is inferior to ISB in terms of analgesia and opioid requirement in the immediate period after arthroscopic shoulder surgery but is associated with a lower incidence of dyspnea and discomfort. The difference in pain and opioid consumption gradually decreases as the blocks wear off in order to reach similar pain scores during the first postoperative night and at 24 hours. Clinical Trial Registration This study was registered at ClinicalTrials.gov, identifier NCT02415088. Accepted for publication December 30, 2017. Address correspondence to: Björn Stessel, MD, PhD, Department of Anesthesiology and Pain Treatment, Jessa Hospital, Virga-Jesse Campus, Stadsomvaart 11, 3500 Hasselt, Belgium (e-mail: bjornstessel@hotmail.com). This study is part of the Limburg Clinical Research Program (LCRP) UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk, Province of Limburg, Flemish Government, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. The authors declare no conflict of interest. Authors' contributions: A.N. was responsible for the study design, data collection, and writing of the paper. B.S. was responsible for the study design, data interpretation, table creation, and writing of the paper. P.F.W. was responsible for the data interpretation and writing of the paper. C.D. was responsible for the study design and the writing of the paper. W.C. provided statistical expertise and was responsible for the statistical analyses and figure creation. J.-P.O., I.A., L.J., and J.D. were responsible for the writing of the paper. D.S. conceived of the study and was responsible for the study design, the literature search, execution of all regional blocks, and writing of the paper. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Clotting-Factor Concentrations 5 Days After Discontinuation of Warfarin

Background The American Society of Regional Anesthesia and Pain Medicine guidelines recommend discontinuation of warfarin and an international normalized ratio (INR) of 1.2 or less before a neuraxial injection. The European and Scandinavian guidelines accept an INR of 1.4 or less. We evaluated INR and levels of clotting factors (CFs) II, VII, IX, and X 5 days after discontinuation of warfarin. Methods Patients who discontinued warfarin for 5 days and had an INR of 1.4 or less had activities of factors II, VII, IX, and X measured. The primary outcome was the frequency of subjects with CF activities of less than 40%. Results Twenty-three patients were studied; 21 (91%) had an INR of 1.2 or less. In these 21 patients, the median (interquartile range) activities of factors II, VII, IX, and X were 66% (52%–80%), 114% (95%–132%), 101% (84%–121%), and 55% (46%–63%), respectively. Ninety-five percent (99% confidence interval, 69%–99%) had CF activities of greater than 40%. The patient who did not CF activities greater than 40% had end-stage renal disease. Two subjects had an INR of greater than 1.2; the activities of factor II, VII, IX, and X were 37% and 46%, 89% and 105%, 66% and 78%, and 20% and 36%, respectively. Neither patient had CF activities of greater than 40%. Conclusions Based on 40% activity of CFs, patients with INRs of 1.2 or less can be considered to have adequate CFs to undergo neuraxial injections. The number of patients with an INR of 1.3 and 1.4 is too small to make conclusions. Accepted for publication January 30, 2018. Address correspondence to: Honorio T. Benzon, MD, Department of Anesthesiology, 251 E. Huron, St, Feinberg Pavilion, 5–704, Chicago, IL 60611 (e-mail: h-benzon@northwestern.edu). L.V. is retired. This work is attributed to the Departments of Anesthesiology and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. Funding support for this study was provided by the Department of Anesthesiology, Northwestern University Feinberg School of Medicine (departmental sources only). The study was presented at Anesthesiology 2016, the annual meeting of the American Society of Anesthesiologists, October 22 to 25, 2016, Chicago, IL. The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Cancers, Vol. 10, Pages 118: Roles of Polyploid/Multinucleated Giant Cancer Cells in Metastasis and Disease Relapse Following Anticancer Treatment

Cancers, Vol. 10, Pages 118: Roles of Polyploid/Multinucleated Giant Cancer Cells in Metastasis and Disease Relapse Following Anticancer Treatment

Cancers doi: 10.3390/cancers10040118

Authors: Razmik Mirzayans Bonnie Andrais David Murray

Tumors and tumor-derived cell lines contain polyploid giant cells with significantly elevated genomic content, often with multiple nuclei. The frequency of giant cells can increase markedly following anticancer treatment. Although giant cells enter a dormant phase and therefore do not form macroscopic colonies (aggregates of ≥50 cells) in the conventional in vitro colony formation assay, they remain viable and metabolically active. The purpose of this commentary is to underscore the potential importance of polyploid/multinucleated giant cells in metastasis and cancer recurrence following exposure to anticancer agents. We also discuss the possibility that most preclinical (cell-based and animal model) drug discovery approaches might not account for delayed responses that are associated with dormant giant cells.

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Cancers, Vol. 10, Pages 118: Roles of Polyploid/Multinucleated Giant Cancer Cells in Metastasis and Disease Relapse Following Anticancer Treatment

Cancers, Vol. 10, Pages 118: Roles of Polyploid/Multinucleated Giant Cancer Cells in Metastasis and Disease Relapse Following Anticancer Treatment

Cancers doi: 10.3390/cancers10040118

Authors: Razmik Mirzayans Bonnie Andrais David Murray

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[Radiation therapy in patients with inflammatory bowel disease. A review].

[Radiation therapy in patients with inflammatory bowel disease. A review].

Bull Cancer. 2018 Apr 10;:

Authors: Jmour O, Pellat A, Colson-Durand L, To NH, Latorzeff I, Sargos P, Sobhani I, Belkacemi Y

Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, are multifactorial diseases characterized by a chronic intestinal inflammation. Abdominal and pelvic irradiation can result in acute or chronic digestive toxicity. A few old studies on small population samples have suggested an increase of gastro-intestinal toxicities in patients with IBD in case of irradiation. Nevertheless, the physiopathology is unknown. More recent studies, including new irradiation techniques, have shown less toxicity events in these patients with IBD. There are no recommendations for irradiation in patients with IBD. This review aims to report recent data on this topic and discuss them regarding radiation parameters.

PMID: 29653817 [PubMed - as supplied by publisher]

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Advanced cutaneous squamous cell carcinoma: A retrospective analysis of patient profiles and treatment patterns—Results of a non-interventional study of the DeCOG

Publication date: June 2018
Source:European Journal of Cancer, Volume 96
Author(s): Uwe Hillen, Ulrike Leiter, Sylvie Haase, Roland Kaufmann, Jürgen Becker, Ralf Gutzmer, Patrick Terheyden, Albrecht Krause-Bergmann, Hans-Joachim Schulze, Jessica Hassel, Nina Lahner, Uwe Wollina, Fabian Ziller, Jochen Utikal, Christine Hafner, Jens Ulrich, Hans-Günther Machens, Carsten Weishaupt, Axel Hauschild, Peter Mohr, Claudia Pföhler, Jan Maurer, Patrick Wolff, Christine Windemuth-Kieselbach, Dirk Schadendorf, Elisabeth Livingstone
BackgroundAdvanced cutaneous squamous cell carcinoma (aSCC) is an area of unmet medical need and no treatment standards are established. Recently, an anti-PD-1 inhibitor received FDA breakthrough therapy designation. The aim of the study was to describe the clinical course, therapeutic management and prognosis of aSCC under real-life conditions.Patients and methodsIn a retrospective study performed in 24 German and Austrian hospitals and doctor's offices, patient and tumour characteristics of patients diagnosed with aSCC between January 1, 2010 and December 31, 2011 and their disease course was documented. Advanced SCC comprised either locally advanced SCCs (laSCC) or metastatic SCCs (mSCC) with any kind of metastatic spread.ResultsData of 190 patients with aSCC were analysed. Median age at time of diagnosis of aSCC was 78 years. LaSCC was diagnosed in 76 patients (40%), 114 patients (60%) had mSCC. Once diagnosed with laSCC, most patients (59%) did not receive any therapy, whereas in 92% of mSCC patients at least one type of therapy was performed. Only 32 patients (29 mSCC, 3 laSCC) received systemic antitumour therapies, mostly EGFR inhibitor-based regimens. Mean duration of response was short (17-months laSCC patients, 3-months mSCC patients). Only 2 patients achieved a complete response, 27% had a partial response, 43% disease stabilisation. At diagnosis of aSCC, ECOG status was 0–1 in most patients. Non-malignant comorbidities influenced the decision on SCC-specific therapy in 39 patients (21%).ConclusionsOur data show the high medical need for efficient and tolerable antitumour therapies and demonstrate that despite older age and comorbidities, most patients can be expected to be fit for treatment. This study provides a historical context for emerging aSCC treatments.

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Mental health insurance access and utilization among childhood cancer survivors: a report from the childhood cancer survivor study

Abstract

Purpose

To describe and compare the prevalence of mental health access, preference, and use among pediatric cancer survivors and their siblings. To identify factors associated with mental health access and use among survivors.

Methods

Six hundred ninety-eight survivors in the Childhood Cancer Survivor Study (median age = 39.4; median years from diagnosis = 30.8) and 210 siblings (median age = 40.4) were surveyed. Outcomes included having mental health insurance coverage, delaying care due to cost, perceived value of mental health benefits, and visiting a mental health provider in the past year.

Results

There were no differences in mental health access, preferences, and use between survivors and siblings (p > 0.05). Among respondents with a history of distress, most reported not having seen a mental health provider in the past year (80.9% survivors vs. 77.1% siblings; p = 0.60). Uninsured survivors were more likely to defer mental health services due to cost (24.6 vs. 8.4%; p < 0.001). In multivariable models, males (OR = 2.96) and survivors with public (OR = 6.61) or employer-sponsored insurance (ESI; OR = 14.37) were more likely to have mental health coverage.

Conclusions

Most childhood cancer survivors value having mental healthcare benefits; however, coverage and use of mental health services remain suboptimal. The most vulnerable of survivors, specifically the uninsured and those with a history of distress, are at risk of experiencing challenges accessing mental health care.

Implications for Cancer Survivors

Childhood cancer survivors are at risk for experiencing high levels of daily life stress that is compounded by treatment-related sequelae. Integrative, system-based approaches that incorporate financial programs with patient education about insurance benefits can help reduce some of the financial barriers survivors face.

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