1
Review
Anticancer Drugs
. 2019 Oct;30(9):879-885. doi: 10.1097/CAD.0000000000000832.
A review of canakinumab and its therapeutic potential for non-small cell lung cancer
Kara M Schenk 1, Joshua E Reuss 1, Karin Choquette 2 3, Alexander I Spira 1 2 3
Affiliations expand
PMID: 31503012
DOI: 10.1097/CAD.0000000000000832
Abstract
Inflammation is essential for our innate and adaptive immunity, but chronic inflammation can also be detrimental, playing a role in tumor development and subversion of host immunity. A multitude of proteins and cytokines are involved in chronic inflammation; interleukin-1β, in particular, has been recognized as a critical pro-inflammatory cytokine that can trigger a cascade of inflammatory mediators, promoting angiogenesis, tumor invasiveness, and metastasis. The inhibition of interleukin-1β with the antibody canakinumab was recently highlighted in a large-scale trial studying the effects of the inflammatory modulating antibody in heart disease. In this study, a marked decrease in the incidence of lung cancer (a 67% relative risk reduction) was observed in a high-risk population. Although a number of preclinical studies have demonstrated that canakinumab inhibits interleukin-1β and reduces inflammation, the question remains whether these actions positively affect both cancer incidence and recurrence. This review will summarize the role of inflammation in cancer propagation and development, discuss the biological rationale for targeting interleukin-1β in lung cancer, advocate for further investigation of the anti-inflammatory antibody canakinumab as a new attractive mechanism for future lung cancer therapy, and discuss future and ongoing trials.
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2
JMIR Mhealth Uhealth
. 2019 Dec 3;7(12):e14919. doi: 10.2196/14919.
Medical Videography Using a Mobile App: Retrospective Analysis
Julia C Cambron 1, Kirk D Wyatt 2, Christine M Lohse 3, Page Y Underwood 4, Thomas R Hellmich 5
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PMID: 31793894
PMCID: PMC6918202
DOI: 10.2196/14919Free PMC article
Abstract
Background: As mobile devices and apps grow in popularity, they are increasingly being used by health care providers to aid clinical care. At our institution, we developed and implemented a point-of-care clinical photography app that also permitted the capture of video recordings; however, the clinical findings it was used to capture and the outcomes that resulted following video recording were unclear.
Objective: The study aimed to assess the use of a mobile clinical video recording app at our institution and its impact on clinical care.
Methods: A single reviewer retrospectively reviewed video recordings captured between April 2016 and July 2017, associated metadata, and patient records.
Results: We identified 362 video recordings that were eligible for inclusion. Most video recordings (54.1%; 190/351) were captured by attending physicians. Specialties recording a high number of video recordings included orthopedic surgery (33.7%; 122/362), neurology (21.3%; 77/362), and ophthalmology (15.2%; 55/362). Consent was clearly documented in the medical record in less than one-third (31.8%; 115/362) of the records. People other than the patient were incidentally captured in 29.6% (107/362) of video recordings. Although video recordings were infrequently referenced in notes corresponding to the clinical encounter (12.2%; 44/362), 7.7% (22/286) of patients were video recorded in subsequent clinical encounters, with 82% (18/22) of these corresponding to the same finding seen in the index video. Store-and-forward telemedicine was documented in clinical notes in only 2 cases (0.5%; 2/362). Videos appeared to be of acceptable quality for clinical purposes.
Conclusions: Video recordings were captured in a variety of clinical settings. Documentation of consent was inconsistent, and other individuals were incidentally included in videos. Although clinical impact was not always clearly evident through retrospective review because of limited documentation, potential uses include documentation for future reference and store-and-forward telemedicine. Repeat video recordings of the same finding provide evidence of use to track the findings over time. Clinical video recordings have the potential to support clinical care; however, documentation of consent requires standardization.
Keywords: medical informatics applications; photography; telemedicine; video recording.
©Julia C David Cambron, Kirk D Wyatt, Christine M Lohse, Page Y Underwood, Thomas R Hellmich. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 03.12.2019.
Conflict of interest statement
Conflicts of Interest: All coauthors are students (JCC and KDW) and/or employees (KDW, TRH, and CML) at Mayo Clinic. Mayo Clinic developed and owns intellectual property rights for the PhotoExam app; however, the app is currently only being used internally and is not being licensed or sold.
16 references
6 figures
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3
Breast Cancer Res Treat
. 2020 Jan;179(1):241-249. doi: 10.1007/s10549-019-05441-3. Epub 2019 Sep 30.
Optimized immunohistochemical detection of estrogen receptor beta using two validated monoclonal antibodies confirms its expression in normal and malignant breast tissues
John R Hawse 1, Jodi M Carter 2, Kirsten G M Aspros 3, Elizabeth S Bruinsma 3, Justin W Koepplin 2, Vivian Negron 4, Malayannan Subramaniam 3, James N Ingle 5, Karen L Rech 2, Matthew P Goetz 5 6
Affiliations expand
PMID: 31571071
PMCID: PMC6989344 (available on 2021-01-01)
DOI: 10.1007/s10549-019-05441-3
Abstract
Purpose: Significant controversy exists regarding the expression patterns of estrogen receptor beta (ERβ) in normal and diseased breast tissue. To address this issue, we have validated two ERβ antibodies, optimized the IHC protocols for both antibodies and now report the expression patterns of ERβ in normal and malignant breast tissues.
Methods: ERβ antibody specificity was determined using western blot and IHC analysis. ERβ protein expression patterns were assessed via IHC in normal breast tissue and invasive breast carcinoma. Further, we report the detailed protocol of the ERβ IHC assay developed in our CAP/CLIA certified laboratory to provide a standardized method for future studies.
Results: We have confirmed the specificity of two independent ERβ monoclonal antibodies, one that detects total (i.e., full length plus splice variants 2-5, which do not include the ligand binding domain) ERβ protein (PPZ0506) and one that detects only the full-length form, which includes the ligand binding domain, of ERβ (PPG5/10). Using these two antibodies, we demonstrate that ERβ is highly expressed in normal human breast tissue as well as in 20-30% of invasive breast cancers. Further, these two antibodies exhibited similar staining patterns across multiple different tissues and were highly concordant with regard to determining ERβ positivity in breast cancers.
Conclusions: ERβ protein was shown to be abundant in the majority of normal breast epithelial cells and is present in 20-30% of breast cancers. Use of these two antibodies, along with their standardized IHC protocols, provide a reference for future studies aimed at determining the utility of ERβ as a prognostic and/or predictive biomarker in various tissues of benign or malignant states.
Keywords: Antibody; Breast; Breast cancer; Estrogen receptor beta.
Conflict of interest statement
Conflict of interest:
M.P.G. reports personal fees from Genomic Health, consulting fees from Lilly, Biovica, Novartis, Sermonix, Context Pharm, Pfizer and Biotheranostics and grant funding from Pfizer and Lilly for efforts that are outside the context of the present study. All other authors declare that they have no conflicts of interest.
Cited by 4 articles
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4
Eur J Oncol Nurs
. 2020 Feb;44:101710. doi: 10.1016/j.ejon.2019.101710. Epub 2019 Dec 5.
Ways of understanding the ability to have children among young adult survivors of childhood cancer - A phenomenographic study
Jenny Nilsson 1, Marta Röing 2, Johan Malmros 3, Jeanette Winterling 4
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PMID: 31837594
DOI: 10.1016/j.ejon.2019.101710
Abstract
Purposes: The aim was to explore the ways young adult survivors of childhood cancer with risk of being infertile understand their ability to have children.
Method: The study has a qualitative design with a phenomenographic approach. Interviews with a purposeful sample of 19 childhood cancer survivors who did not have children (age range 17-27) were carried out and analysed.
Results: We identified four qualitatively different ways in which young adult survivors of childhood cancer understand their ability to have children: difficulty in having children is not as important as surviving cancer, having a biological child may be a complicated procedure, having children may be affected by hereditary concerns, having children in the future is a difficult topic to deal with.
Conclusions: The four different ways in which young adult childhood cancer survivors understand their ability to have children did not appear to be solely related to information they had or had not received during treatment but appeared to reflect their current life situation and how they were coping with their cancer experience. Using survivors' understandings of their ability to have children is recommended as a starting point when healthcare personnel initiate communication about fertility issues in survivorship care. Some survivors need psychosocial support for the acceptance and management of both cancer and fertility problems.
Keywords: Cancer survivors; Childhood cancer; Fertility; Phenomenography; Sweden; Young adults.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Declaration of competing interest None declared.
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5
Mycoses
. 2020 Apr;63(4):343-351. doi: 10.1111/myc.13047. Epub 2020 Jan 20.
Quantifying guideline adherence in mucormycosis management using the EQUAL score
Philipp Koehler 1 2, Sibylle C Mellinghoff 1 2, Jannik Stemler 1 2 3, Felix Otte 4, Ariana Berkhoff 4, Nedim Beste 4, Sofia Budin 4, Florian B Cornely 4 5, Johanna M Evans 4, Frieder Fuchs 6, Luca Pesch 4, Arvid W Rebholz 4, Omer Reiner 4, Marius Schmitt 4, Julien Schuckelt 4, Arlene Spiertz 4, Jon Salmanton-García 1, Florian Kron 1 7, Oliver A Cornely 1 2 3 8
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PMID: 31876327
DOI: 10.1111/myc.13047
Abstract
Objectives: Mucormycosis is a difficult-to-diagnose life-threatening disease with high morbidity and mortality. Adherence to guidelines that lead through complex management and support clinical decisions is however rarely reported. By applying the EQUAL Score, our study evaluates the management of mucormycosis at the University Hospital of Cologne, Germany.
Methods: We performed a retrospective chart review of patients with mucormycosis at the University Hospital of Cologne. Data collection comprised items for quality assessment in mucormycosis management according to the EQUAL Mucormycosis Score and economics.
Results: Of 29 patients identified, 27 were documented retrospectively. Eight patients of 18 with neutropenia (>10 days) or receiving allogeneic stem cell transplantation (44.4%) received mould active prophylaxis. Chest CT was done in 21 patients (77.8%), while BAL and direct microscopy of BAL fluid was performed in 22 patients (81.5%), culture in 22 (81.5%) and fungal PCR in 24 (88.9%). First-line treatment was liposomal amphotericin B in 19 patients (70.4%). Isavuconazole or posaconazole with therapeutic drug monitoring was used in four (14.8%) and in one patient (3.7%), respectively. In our cohort, crude mortality was 51.9% (n = 14) with a median survival time of 113 days. During the management of the 27 patients, 450 points (53.8%) of the maximum EQUAL Mucormycosis Score were achieved (median 15 points, range 6-30).
Conclusions: We observed management of mucormycosis aligning with current guidelines and hope to encourage other groups to use the EQUAL Score in routine clinical settings. Future studies will evaluate whether guideline adherence in mucormycosis management improves patient outcome.
Keywords: diagnosis; follow-up; isavuconazole; liposomal amphotericin B; mucorales; posaconazole; treatment; zygomycosis.
© 2019 The Authors. Mycoses published by Blackwell Verlag GmbH.
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6
Clinical Trial
Biosci Rep
. 2019 Oct 30;39(10):BSR20192091. doi: 10.1042/BSR20192091.
Effects of the MAML2 genetic variants in glioma susceptibility and prognosis
Ming Zhang 1, Yonglin Zhao 2, Junjie Zhao 3, Tingqin Huang 1, Xiaoye Guo 3, Xudong Ma 3, Yuan Wu 4
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PMID: 31652449
PMCID: PMC6822528
DOI: 10.1042/BSR20192091Free PMC article
Abstract
Background: Abnormal expression of the mastermind-like transcriptional co-activator 2 (MAML2) gene is oncogenic in several human cancers, including glioma. However, the relevance of MAML2 variants with glioma remains unknown. We aimed to investigate the role of MAML2 polymorphisms in glioma risk and prognosis among the Chinese Han population.
Methods: Seven MAML2 single-nucleotide polymorphisms (SNPs) were genotyped using Agena MassARRAY system among 575 patients with glioma and 500 age- and gender-matched healthy controls. Logistic regression was used to estimate the association between MAML2 polymorphisms and glioma risk by calculating odds ratios (ORs) and 95% confidence intervals (CI). Kaplan-Meier survival analysis and univariate, multivariate Cox proportional hazard regression analyses for hazard ratios (HRs) and 95% CIs were performed to evaluate the contribution of MAML2 polymorphisms to glioma prognosis.
Results: MAML2 rs7938889 and rs485842 polymorphisms were associated with the reduced risk of glioma (OR = 0.69, P=0.023; and OR = 0.81, P=0.032, respectively). Rs7115578 polymorphism had a lower susceptibility to glioma in males (OR = 0.68, P=0.034), while rs4598633 variant with a higher risk in females (OR = 1.66, P=0.016). Additionally, rs7115578 AG genotype represented a poorer prognosis of glioma (HR = 1.24, P=0.033) and astrocytoma (log-rank P=0.037, HR = 1.31, P=0.036). Furthermore, rs11021499 polymorphism had lower overall survival (OS) and progression-free survival (PFS) in patients with low-grade glioma.
Conclusion: We provided some novel data suggesting MAML2 polymorphisms might contribute to glioma risk and prognosis. Future studies are warranted to validate these findings and characterize mechanisms underlying these associations.
Keywords: Glioma; MAML2; prognosis; susceptibility.
© 2019 The Author(s).
Conflict of interest statement
Written informed consent was obtained from all of the subjects before participating.
The protocol of the present study was approved by the institutional Ethnics Committee of both the People’s Hospital of Xinjiang Uygur Autonomous Region and Northwest University, and carried out in accordance with the World Medical Association Declaration of Helsinki.
The authors declare that there are no competing interests associated with the manuscript.
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7
Psychooncology
. 2020 Sep 15. doi: 10.1002/pon.5547. Online ahead of print.
Pediatric Psycho-Oncology in Russia: Caregiver mental health and sleep outcomes on the oncology wardss
M A Burns 1 2, M Aralova 3, S Ellis 1 2, K S Aslanyan 4, T Egorkina 1 2, C E Wakefield 1 2
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PMID: 32935374
DOI: 10.1002/pon.5547
Abstract
Objectives: Caregivers are at risk of poor sleep and elevated distress during their child's cancer treatment. Russia is currently underrepresented in the international psycho-oncology field, with no identified psychosocial standards of care, and limited or inconsistent psychological service provision, particularly for caregivers. This study aimed to determine the prevalence of Russian caregivers' psychological distress and identify factors associated with caregiver sleep duration when staying on the pediatric oncology ward.
Methods: We recruited 74 caregivers of children with cancer and 74 comparison caregivers in Rostov-on-Don, Russia. Participants completed a survey assessing clinical outcomes, sleep (St Mary's Hospital Sleep Questionnaire), and psychological distress (Depression Anxiety Stress Scales, 21; DASS-21).
Results: Caregivers of children with cancer reported significantly higher scores for all DASS-21 subscales and higher depression (48.6 vs 24.6%), anxiety (47.3 vs 12.3%) and stress (45.9 vs 0%) scores from "moderate" to "extremely severe". Caregivers of children with cancer reported significantly shorter sleep duration (5.82hours vs 7.49hours, t(143)=-6.22,p=.002), more night-time awakenings (3.20 vs 1.25, t(135)=6.94,p<.001) and worse sleep quality (46.5 vs 9.6%; x2 (1)=24.4,p<0.001) than comparison caregivers. Caregivers with a higher total DASS-21 score (B=-1.32,p=.032) and those who were closer to diagnosis (B=-1.53,p=.012) reported shorter sleep duration.
Conclusions: Russian caregivers of children with cancer experience high rates of psychological distress and poor sleep on the oncology ward. These findings provide an important target for future research and culturally relevant clinical interventions to improve caregivers' mental health and capacity for care. This article is protected by copyright. All rights reserved.
Keywords: Anxiety; Cancer; Caregivers; Mental Health; Neoplasm; Oncology; Parent; Psycho-Oncology; Russia; Sleep.
This article is protected by copyright. All rights reserved.
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8
Sci Rep
. 2019 Mar 1;9(1):3209. doi: 10.1038/s41598-019-39965-x.
Mutational profile of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations
Letícia Ferro Leal 1, Flávia Escremim de Paula 2, Pedro De Marchi 3, Luciano de Souza Viana 3, Gustavo Dix Junqueira Pinto 3, Carolina Dias Carlos 2, Gustavo Noriz Berardinelli 2, José Elias Miziara 4, Carlos Maciel da Silva 4, Eduardo Caetano Albino Silva 5, Rui Pereira 6 7, Marco Antonio de Oliveira 8, Cristovam Scapulatempo-Neto 5, Rui Manuel Reis 9 10 11 12
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PMID: 30824880
PMCID: PMC6397232
DOI: 10.1038/s41598-019-39965-xFree PMC article
Abstract
Lung cancer is the deadliest cancer worldwide. The mutational frequency of EGFR and KRAS genes in lung adenocarcinoma varies worldwide per ethnicity and smoking. The impact of EGFR and KRAS mutations in Brazilian lung cancer remains poorly explored. Thus, we investigated the frequency of EGFR and KRAS mutations in a large Brazilian series of lung adenocarcinoma together with patients' genetic ancestry, clinicopathological and sociodemographic characteristics. The mutational frequency of EGFR was 22.7% and KRAS was 20.4%. The average ancestry proportions were 73.1% for EUR, 13.1% for AFR, 6.5% for AME and 7.3% for ASN. EGFR mutations were independently associated with never-smokers, high-Asian ancestry, and better performance status. KRAS mutations were independently associated with tobacco exposure and non-Asian ancestry. EGFR-exon 20 mutations were associated with worse outcome. The Cox regression model indicated a worse outcome for patients whose were older at diagnosis (>61 y), solid histological subtype, loss of weight (>10%), worse performance status (≥2), and presence of KRAS mutations and EGFR mutational status in TKi non-treated patients. In conclusion, we assessed the clinicopathological and ethnic impact of EGFR and KRAS mutations in the largest series reported of Brazilian lung adenocarcinomas. These findings can support future clinical strategies for Brazilian lung cancer patients.
Conflict of interest statement
The authors declare no competing interests.
Cited by 7 articles
47 references
3 figures
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9
Urol Oncol
. 2019 Oct;37(10):659-671. doi: 10.1016/j.urolonc.2019.05.021. Epub 2019 Jun 27.
The role of adjuvant radiotherapy after surgery for upper and lower urinary tract urothelial carcinoma: A systematic review
Takehiro Iwata 1, Shoji Kimura 2, Mohammad Abufaraj 3, Florian Janisch 4, Pierre I Karakiewicz 5, Veronika Seebacher 6, Morgan Rouprêt 7, Yasutomo Nasu 8, Shahrokh F Shariat 9
Affiliations expand
PMID: 31255542
DOI: 10.1016/j.urolonc.2019.05.021
Abstract
Objectives: The role of adjuvant radiotherapy (ART) in patients with bladder cancer (BCa) and upper tract urothelial carcinoma (UTUC) is controversial. We systematically evaluated the oncologic efficacy of ART and its associated toxicity in patients treated with surgery and ART for BCa and UTUC.
Materials and method: We performed a literature search on December 2018 using MEDLINE, Web of Science, Cochrane databases and Scopus according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Fourteen BCa studies and 14 UTUC studies were included in this systematic review. The data were too scarce and heterogeneous for meta-analytical analysis.
Results: The quality and quantity of the data on ART in BCa and UTUC patients are limited. The combination of ART and chemotherapy appears to be beneficial in patients with locally advanced BCa or UTUC. The early and late adverse effects of ART are decreasing reflecting the progress in radiation technology.
Conclusions: According to the currently available literature, there is no clear benefit of ART after radical surgery in BCa and UTUC. Future efforts should focus on evaluating multimodal approach using ART with chemotherapy. Until that time comes, ART should be used carefully in patients with BCa and UTUC on a case-by-case basis.
Keywords: Adjuvant radiotherapy; Bladder cancer; Recurrence; Upper tract urothelial carcinoma.
Copyright © 2019 Elsevier Inc. All rights reserved.
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10
Review
Environ Res
. 2020 Sep 13;110211. doi: 10.1016/j.envres.2020.110211. Online ahead of print.
Biomarkers of Metabolic Disorders and Neurobehavioral Diseases in a PCB- Exposed Population: What We Learned and the Implications for Future Research
Jyothirmai J Simhadri 1, Christopher A Loffredo 2, Tomas Trnovec 3, Lubica Palkovicova Murinova 4, Gail Nunlee-Bland 1, Janna G Koppe 3, Greet Schoeters 5, Siddhartha Sankar Jana 6, Somiranjan Ghosh 7
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PMID: 32937175
DOI: 10.1016/j.envres.2020.110211
Abstract
Polychlorinated biphenyls (PCBs) are one of the original twelve classes of toxic chemicals covered by the Stockholm Convention on Persistent Organic Pollutants (POP), an international environmental treaty signed in 2001. PCBs are present in the environment as mixtures of multiple isomers at different degree of chlorination. These compounds are manmade and possess useful industrial properties including extreme longevity under harsh conditions, heat absorbance, and the ability to form an oily liquid at room temperature that is useful for electrical utilities and in other industrial applications. They have been widely used for a wide range of industrial purposes over the decades. Despite a ban in production in 1979 in the US and many other countries, they remain persistent and ubiquitous in environment as contaminants due to their improper disposal. Humans, independent of where they live, are therefore exposed to PCBs, which are routinely found in random surveys of human and animal tissues. The prolonged exposures to PCBs have been associated with the development of different diseases and disorders, and they are classified as endocrine disruptors. Due to its ability to interact with thyroid hormone, metabolism and function, they are thought to be implicated in the global rise of obesity diabetes, and their potential toxicity for neurodevelopment and disorders, an example of gene by environmental interaction (GxE). The current review is primarily intended to summarize the evidence for the association of PCB exposures with increased risks for metabolic dysfunctions and neurobehavioral disorders. In particular, we present evidence of gene expression alterations in PCB-exposed populations to construct the underlying pathways that may lead to those diseases and disorders in course of life. We conclude the review with future perspectives on biomarker-based research to identify susceptible individuals and populations.
Keywords: Biomarkers; Exposure; Gene Validation; Gene expression; Polychlorinated Biphenyls (PCBs).
Copyright © 2020 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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11
Can Respir J
. 2020 Sep 5;2020:1401053. doi: 10.1155/2020/1401053. eCollection 2020.
Tuberculosis and COVID-19: Lessons from the Past Viral Outbreaks and Possible Future Outcomes
Radu Crisan-Dabija 1, Cristina Grigorescu 2, Cristina-Alice Pavel 3, Bogdan Artene 4, Iolanda Valentina Popa 5 6, Andrei Cernomaz 7, Alexandru Burlacu 4 6
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PMID: 32934758
PMCID: PMC7479474
DOI: 10.1155/2020/1401053Free PMC article
Abstract
Background: The threat of contagious infectious diseases is constantly evolving as demographic explosion, travel globalization, and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies.
Methods and results: The PubMed electronic database was systematically searched for relevant articles linking TB, influenza, and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (focusing on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from past outbreaks (other coronaviruses) and influenza pandemic/seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection.
Conclusions: Because viral respiratory infections and TB impede the host's immune responses, it can be assumed that their lethal synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead. The trial is registered with NCT04327206, NCT01829490, and NCT04121494.
Copyright © 2020 Radu Crisan-Dabija et al.
Conflict of interest statement
The authors declare that there are no conflicts of interest regarding the publication of this article.
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12
Review
Cancer
. 2020 Sep 15. doi: 10.1002/cncr.33205. Online ahead of print.
Clinical trial design: Past, present, and future in the context of big data and precision medicine
Allen Li 1, Raymond C Bergan 1
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PMID: 32931022
DOI: 10.1002/cncr.33205
Abstract
Clinical trials are fundamental for advances in cancer treatment. The traditional framework of phase 1 to 3 trials is designed for incremental advances between regimens. However, our ability to understand and treat cancer has evolved with the increase in drugs targeting an expanding array of therapeutic targets, the development of progressively comprehensive data sets, and emerging computational analytics, all of which are reshaping our treatment strategies. A more robust linkage between drugs and underlying cancer biology is blurring historical lines that define trials on the basis of cancer type. The complexity of the molecular basis of cancer, coupled with manifold variations in clinical status, is driving the individually tailored use of combinations of precision targeted drugs. This approach is spawning a new era of clinical trial types. Although most care is delivered in a community setting, large centers support real-time multi-omic analytics and their integrated interpretation by using machine learning in the context of real-world data sets. Coupling the analytic capabilities of large centers to the tailored delivery of therapy in the community is forging a paradigm that is optimizing service for patients. Understanding the importance of these evolving trends across the health care spectrum will affect our treatment of cancer in the future and is the focus of this review.
Keywords: big data; clinical trial; clinical trial protocol; precision medicine.
© 2020 American Cancer Society.
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13
Review
Cancer Metastasis Rev
. 2020 Sep 14. doi: 10.1007/s10555-020-09931-5. Online ahead of print.
Current methods in translational cancer research
Michael W Lee 1 2 3, Mihailo Miljanic 2 3, Todd Triplett 2 3, Craig Ramirez 2 3, Kyaw L Aung 2 3, S Gail Eckhardt 2 3, Anna Capasso 4 5
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PMID: 32929562
DOI: 10.1007/s10555-020-09931-5
Abstract
Recent developments in pre-clinical screening tools, that more reliably predict the clinical effects and adverse events of candidate therapeutic agents, has ushered in a new era of drug development and screening. However, given the rapid pace with which these models have emerged, the individual merits of these translational research tools warrant careful evaluation in order to furnish clinical researchers with appropriate information to conduct pre-clinical screening in an accelerated and rational manner. This review assesses the predictive utility of both well-established and emerging pre-clinical methods in terms of their suitability as a screening platform for treatment response, ability to represent pharmacodynamic and pharmacokinetic drug properties, and lastly debates the translational limitations and benefits of these models. To this end, we will describe the current literature on cell culture, organoids, in vivo mouse models, and in silico computational approaches. Particular focus will be devoted to discussing gaps and unmet needs in the literature as well as current advancements and innovations achieved in the field, such as co-clinical trials and future avenues for refinement.
Keywords: Cancer; GEMMs; PDX; Translational research; Xenograft; tumor immunology.
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14
Review
Oncology
. 2020;98(9):593-602. doi: 10.1159/000507959. Epub 2020 Jun 30.
A Fragile Balance: The Important Role of the Intestinal Microbiota in the Prevention and Management of Colorectal Cancer
Daniela Toumazi 1, Constantina Constantinou 2
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PMID: 32604093
DOI: 10.1159/000507959
Abstract
Background: Colorectal cancer is the second leading cause of cancer-related death worldwide. In recent years, researchers have focussed on the role of the intestinal microbiota in both the prevention and the treatment of colorectal cancer.
Summary: The evidence in the literature supports that there is a fragile balance between different species of bacteria in the human gut. A disturbance of this balance towards increased levels of the bacteria Fusobacterium nucleatum and Bacteroides fragilis is associated with an increased risk of colorectal cancer. The mechanisms involved include the release of toxins which activate inflammation and the regulation of specific miRNAs (with an increase in the expression of oncogenic miRNAs and a decrease in the expression of tumour suppressor miRNAs), thereby increasing cell proliferation and leading to tumorigenesis. On the other hand, Lactobacillus and Bifidobacterium have a protective effect against the development of colorectal cancer through mechanisms that involve an increase in the levels of anticarcinogenic metabolites such as butyrate and a decrease in the activity of proinflammatory pathways. Even though preliminary studies support that the use of probiotics in the prevention and management of colorectal cancer is promising, more research is needed in this field. Key Message: The association between the intestinal microbiota, diet and colorectal cancer remains an active area of research with expected future applications in the use of probiotics for the prevention and management of this significant disease.
Keywords: Colorectal cancer; Intestinal microbiota; Prevention; Probiotics; Treatment.
© 2020 S. Karger AG, Basel.
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15
Cancer Med
. 2019 Dec;8(18):7728-7740. doi: 10.1002/cam4.2633. Epub 2019 Oct 23.
Exosomal miRNA-1231 derived from bone marrow mesenchymal stem cells inhibits the activity of pancreatic cancer
Song Shang 1, Jinfeng Wang 1, Shilin Chen 1, Renyun Tian 2, Hui Zeng 3, Liang Wang 3, Man Xia 4, Haizhen Zhu 2, Chaohui Zuo 1
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PMID: 31642612
PMCID: PMC6912060
DOI: 10.1002/cam4.2633Free PMC article
Abstract
Pancreatic cancer (PC) is a highly malignant tumor with increased morbidity and mortality, which is difficult to diagnose and cure in the clinic. Through secreting exosomes containing biological molecules, including diverse RNAs and proteins, bone marrow mesenchymal stem cells (BM-MSCs) influence the immunity, inflammation, tumor environment, and cancer metastasis. In this study, low expression of miRNA-1231 (miR-1231) in exosomes derived from the peripheral blood was significantly correlated with the TNM stage of PC, suggesting the potential inhibitory effect of exosomal miR-1231 on PC occurrence and development. The proliferation, migration, invasion, and adhesion to the matrix of PC cells BxPC-3 and PANC-1 were negatively regulated by exosomes derived from the supernatants of BM-MSCs that transfected with miR-1231 oligonucleotides. Simultaneously, tumor growth in vivo was seriously restrained in BALB/C nude mice by tail vein injection with exosomes originated from BM-MSCs that transfected with miR-1231 mimics. The exosomes extracted from BM-MSCs with high level of miR-1231 inhibit the activity of PC, providing the potential application for developing new and efficient medicine for cancer therapy, especially for PC treatment. The exosomal miR-1231 of peripheral blood may also be a potential indicator for PC diagnosis in the future.
Keywords: BM-MSCs; exosomes; miR-1231; oncogenic activity; pancreatic cancer.
© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Conflict of interest statement
The authors have declared that there are no conflicts of interest.
Cited by 5 articles
51 references
5 figures
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16
Editorial
Int J Radiat Oncol Biol Phys
. 2020 Oct 1;108(2):491-495. doi: 10.1016/j.ijrobp.2020.06.048.
Scholarly Publishing in the Wake of COVID-19
Robert C Miller 1, C Jillian Tsai 2
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PMID: 32890542
PMCID: PMC7462968
DOI: 10.1016/j.ijrobp.2020.06.048Free PMC article
Abstract
The speed at which the COVID-19 pandemic spread across the globe and the accompanying need to rapidly disseminate knowledge have highlighted the inadequacies of the traditional research/publication cycle, particularly the slowness and the fragmentary access globally to manuscripts and their findings. Scholarly communication has slowly been undergoing transformational changes since the introduction of the Internet in the 1990s. The pandemic response has created an urgency that has accelerated these trends in some areas. The magnitude of the global emergency has strongly bolstered calls to make the entire research and publishing lifecycle transparent and open. The global scientific community has collaborated in rapid, open, and transparent means that are unprecedented. The general public has been reminded of the important of science, and trusted communication of scientific findings, in everyday life. In addition to COVID-19-driven innovation in scholarly communication, alternative bibliometrics and artificial intelligence tools will further transform academic publishing in the near future.
Copyright © 2020 Elsevier Inc. All rights reserved.
23 references
3 figures
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17
Review
Nat Rev Clin Oncol
. 2020 Sep 15. doi: 10.1038/s41571-020-0426-7. Online ahead of print.
Exploring the NK cell platform for cancer immunotherapy
Jacob A Myers 1, Jeffrey S Miller 2
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PMID: 32934330
DOI: 10.1038/s41571-020-0426-7
Abstract
Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system that are capable of killing virally infected and/or cancerous cells. Nearly 20 years ago, NK cell-mediated immunotherapy emerged as a safe and effective treatment approach for patients with advanced-stage leukaemia. Subsequently, the field of NK cell-based cancer therapy has grown exponentially and currently constitutes a major area of immunotherapy innovation. In general, the development of NK cell-directed therapies has two main focal points: optimizing the source of therapeutic NK cells for adoptive transfer and enhancing NK cell cytotoxicity and persistence in vivo. A wide variety of sources of therapeutic NK cells are currently being tested clinically, including haploidentical NK cells, umbilical cord blood NK cells, stem cell-derived NK cells, NK cell lines, adaptive NK cells, cytokine-induced memory-like NK cells and chimeric antigen receptor NK cells. A plethora of methods to augment the cytotoxicity and longevity of NK cells are also under clinical investigation, including cytokine-based agents, NK cell-engager molecules and immune-checkpoint inhibitors. In this Review, we highlight the variety of ways in which diverse NK cell products and their auxiliary therapeutics are being leveraged to target human cancers. We also identify future avenues for NK cell therapy research.
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18
Comment
Future Oncol
. 2020 Sep;16(25):1875-1878. doi: 10.2217/fon-2020-0307. Epub 2020 Aug 5.
ENLIVEN study: Pexidartinib for tenosynovial giant cell tumor (TGCT)
William Tap 1
Affiliations expand
PMID: 32755241
DOI: 10.2217/fon-2020-0307
Abstract
Pexidartinib is the first approved medication in the USA for people with tenosynovial giant cell tumor (TGCT). The drug was approved based on the ENLIVEN study, which looked at pexidartinib (brand name, Turalio™), a medication taken by mouth (orally) for people with TGCT (also known as giant cell tumor of the tendon sheath [GCTTS] and pigmented villonodular synovitis [PVNS]) who are not able to have surgery because of the location and/or the size of the tumor. The study showed that pexidartinib is effective in treating people with TGCT because it shrunk the size of their tumors and improved their symptoms and their ability to function. In general, people treated with pexidartinib had side effects that were mostly mild that went away after treatment with pexidartinib was stopped. The most common side effects were hair color changes and tiredness (fatigue). Pexidartinib was also associated with liver problems (or hepatotoxicity), which started within the first 2 months of treatment. Due to the risk of liver problems, which may be severe and potentially life threatening, the researchers closely monitored participants' blood liver function tests before, during, and after participants in the study took pexidartinib. To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF. Clinical Trial Registration: NCT02371369 (ClinicalTrials.gov).
Keywords: clinical trial; lay summary; patient education handbook; pexidartinib; pigmented villonodular synovitis; tenosynovial giant cell tumour; treatment.
Comment on
Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial.
Tap WD, Gelderblom H, Palmerini E, Desai J, Bauer S, Blay JY, Alcindor T, Ganjoo K, Martín-Broto J, Ryan CW, Thomas DM, Peterfy C, Healey JH, van de Sande M, Gelhorn HL, Shuster DE, Wang Q, Yver A, Hsu HH, Lin PS, Tong-Starksen S, Stacchiotti S, Wagner AJ; ENLIVEN investigators.Lancet. 2019 Aug 10;394(10197):478-487. doi: 10.1016/S0140-6736(19)30764-0. Epub 2019 Jun 19.PMID: 31229240 Free PMC article. Clinical Trial.
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19
Review
Oncol Lett
. 2020 Nov;20(5):137. doi: 10.3892/ol.2020.11997. Epub 2020 Aug 20.
ZBED1/DREF: A transcription factor that regulates cell proliferation
Yarong Jin 1 2, Ruilei Li 2, Zhiwei Zhang 2 3, Jinjin Ren 1, Xin Song 2, Gong Zhang 1
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PMID: 32934705
PMCID: PMC7471704
DOI: 10.3892/ol.2020.11997Free PMC article
Abstract
Maintenance of genomic diversity is critically dependent on gene regulation at the transcriptional level. This occurs via the interaction of regulatory DNA sequence motifs with DNA-binding transcription factors. The zinc finger, BED-type (ZBED) gene family contains major DNA-binding motifs present in human transcriptional factors. It encodes proteins that present markedly diverse regulatory functions. ZBED1 has similar structural and functional properties to its Drosophila homolog DNA replication-related element-binding factor (DREF) and plays a critical role in the regulation of transcription. ZBED1 regulates the expression of several genes associated with cell proliferation, including cell cycle regulation, chromatin remodeling and protein metabolism, and some genes associated with apoptosis and differentiation. In the present review, the origin, structure and functional role of ZBED1 were comprehensively assessed. In addition, the similarities and differences between ZBED1 and its Drosophila homolog DREF were highlighted, and future research directions, particularly in the area of clinical cancer, were discussed.
Keywords: DREF; ZBED1; proliferation; transcription factor; transposable element.
Copyright: © Jin et al.
81 references
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20
Review
Ann Surg
. 2020 Aug;272(2):277-283. doi: 10.1097/SLA.0000000000003586.
Casting A Wide Net On Surgery: The Central Role of Neutrophil Extracellular Traps
Jules H Eustache 1, Samer Tohme 2, Simon Milette 1, Roni F Rayes 1, Allan Tsung 3, Jonathan D Spicer 1
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PMID: 32675540
PMCID: PMC7373444
DOI: 10.1097/SLA.0000000000003586Free PMC article
Abstract
: Since their discovery, neutrophil extracellular traps (NETs) have been implicated in a broad array of functions, both beneficial and detrimental to the host. Indeed, NETs have roles in infection, sepsis, wound healing, thrombotic disease, and cancer propagation, all of which are directly implicated in the care of surgical patients. Here we provide an updated review on the role of NETs in the perioperative period with specific emphasis on perioperative infections, wound healing, vascular complications, cancer propagation, as well as discussing ongoing, and future therapeutic targets. Surgeons will benefit from understanding the latest discoveries in neutrophil biology and how these novel functions affect the care of surgical patients. Furthermore, novel anti-NET therapies are being developed which may have profound effects on the care of surgical patients.
Conflict of interest statement
The authors report no conflicts of interest.
75 references
1 figure
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21
Cell Stem Cell
. 2020 Sep 2;S1934-5909(20)30401-X. doi: 10.1016/j.stem.2020.08.005. Online ahead of print.
Hydrogel Network Dynamics Regulate Vascular Morphogenesis
Zhao Wei 1, Rahel Schnellmann 1, Hawley C Pruitt 1, Sharon Gerecht 2
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PMID: 32931729
DOI: 10.1016/j.stem.2020.08.005
Abstract
Matrix dynamics influence how individual cells develop into complex multicellular tissues. Here, we develop hydrogels with identical polymer components but different crosslinking capacities to enable the investigation of mechanisms underlying vascular morphogenesis. We show that dynamic (D) hydrogels increase the contractility of human endothelial colony-forming cells (hECFCs), promote the clustering of integrin β1, and promote the recruitment of vinculin, leading to the activation of focal adhesion kinase (FAK) and metalloproteinase expression. This leads to the robust assembly of vasculature and the deposition of new basement membrane. We also show that non-dynamic (N) hydrogels do not promote FAK signaling and that stiff D- and N-hydrogels are constrained for vascular morphogenesis. Furthermore, D-hydrogels promote hECFC microvessel formation and angiogenesis in vivo. Our results indicate that cell contractility mediates integrin signaling via inside-out signaling and emphasizes the importance of matrix dynamics in vascular tissue formation, thus informing future studies of vascularization and tissue engineering applications.
Keywords: cell contractility; integrin clustering; stress-relaxation; vasculogenesis.
Copyright © 2020 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of Interests The authors declare no competing interests.
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22
Ann Emerg Med
. 2020 Sep;76(3S):S64-S72. doi: 10.1016/j.annemergmed.2020.08.013.
A Survey-Based Needs Assessment of Barriers to Optimal Sickle Cell Disease Care in the Emergency Department
Elizabeth A Linton 1, Dania A Goodin 2, Jane S Hankins 3, Julie Kanter 4, Liliana Preiss 5, Jena Simon 6, Kimberly Souffront 7, Paula Tanabe 8, Robert Gibson 9, Lewis L Hsu 10, Allison King 11, Lynne D Richardsona 12, Jeffrey A Glassberg 1, Sickle Cell Disease Implementation Consortium
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PMID: 32928465
DOI: 10.1016/j.annemergmed.2020.08.013
Abstract
Study objective: Guided by an implementation science framework, this needs assessment identifies institutional-, provider-, and patient-level barriers to care of sickle cell disease (SCD) in the emergency department (ED) to inform future interventions conducted by the multicenter Sickle Cell Disease Implementation Consortium.
Methods: The consortium developed and implemented a validated needs assessment survey administered to a cross-sectional convenience sample of patients with SCD and ED providers caring for them. In total, 516 adolescents and adults with SCD and 243 ED providers from 7 and 5 regions of the United States, respectively, responded to the ED care delivery for SCD survey.
Results: Survey results demonstrated that 84.5% of respondents with SCD have an outpatient provider who treats many patients with SCD. In the ED, 54.3% reported not receiving care fast enough and 46.0% believed physicians did not care about them and believed similarly of nurses (34.9%). Consequently, 48.6% of respondents were "never" or "sometimes" satisfied with their ED care. Of surveyed ED providers, 75.1% were unaware of the National Heart, Lung, and Blood Institute recommendations for vaso-occlusive crises, yet 98.1% were confident in their knowledge about caring for patients with SCD. ED providers identified the following factors as barriers to care administration: opioid epidemic (62.1%), patient behavior (60.9%), crowding (58.0%), concern about addiction (47.3%), and implicit bias (37.0%).
Conclusion: The results underscore that many patients with SCD are dissatisfied with their ED care and highlight challenges to optimal care on the practice, provider, and patient levels. Exploring these differences may facilitate improvements in ED care.
Copyright © 2020 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
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23
Review
Oncol Lett
. 2020 Nov;20(5):126. doi: 10.3892/ol.2020.11985. Epub 2020 Aug 19.
Challenges surrounding postoperative adjuvant chemotherapy for T2N0 gastric cancer
Ke-Kang Sun 1 2, Qing-Hua Wang 1, Yong-You Wu 2
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PMID: 32934695
PMCID: PMC7471739
DOI: 10.3892/ol.2020.11985Free PMC article
Abstract
Determining the requirement for adjuvant chemotherapy in patients with stage IB gastric cancer (GC), and particularly for those with stage T2N0 (muscularis propria) disease, remains challenging. Patients with stage II/III disease benefit from postoperative adjuvant therapy; however, the randomized trials examining whether such therapy affords any survival benefit to patients with T2N0 disease are not sufficient. Current evidence suggests that not all patients with T2N0 disease should undergo such treatment, but only those with a high risk. To date, a number of retrospective studies have attempted to identify factors that are predictive of increased risk in an effort to guide adjuvant therapy-related clinical decision making. The National Comprehensive Cancer Network and the Chinese Society of Clinical Oncology have published guidelines regarding factors associated with increased patient risk. As a result, treatment decisions for patients with stage T2N0 disease are currently determined on an individualized basis, in light of risk factors and the potential benefits of treatment. The present review surveyed current evidence related to the treatment of patients with high-risk GC and highlighted the potential avenues for future investigated.
Keywords: T2; adjuvant chemotherapy; gastric cancer; muscularis propria; prognosis.
Copyright © 2020, Spandidos Publications.
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24
ChemMedChem
. 2019 Dec 4;14(23):1995-2004. doi: 10.1002/cmdc.201900415. Epub 2019 Nov 7.
Ligand- and Structure-Based Approaches of Escherichia coli FabI Inhibition by Triclosan Derivatives: From Chemical Similarity to Protein Dynamics Influence
Thales Kronenberger 1 2, Philipe de Oliveira Fernades 3 4, Isabella Drumond Franco 3, Antti Poso 1 2, Vinícius Gonçalves Maltarollo 3
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PMID: 31670463
PMCID: PMC6916556
DOI: 10.1002/cmdc.201900415Free PMC article
Abstract
Enoyl-acyl carrier protein reductase (FabI) is the limiting step to complete the elongation cycle in type II fatty acid synthase (FAS) systems and is a relevant target for antibacterial drugs. E. coli FabI has been employed as a model to develop new inhibitors against FAS, especially triclosan and diphenyl ether derivatives. Chemical similarity models (CSM) were used to understand which features were relevant for FabI inhibition. Exhaustive screening of different CSM parameter combinations featured chemical groups, such as the hydroxy group, as relevant to distinguish between active/decoy compounds. Those chemical features can interact with the catalytic Tyr156. Further molecular dynamics simulation of FabI revealed the ionization state as a relevant for ligand stability. Also, our models point the balance between potency and the occupancy of the hydrophobic pocket. This work discusses the strengths and weak points of each technique, highlighting the importance of complementarity among approaches to elucidate EcFabI inhibitor's binding mode and offers insights for future drug discovery.
Keywords: chemical similarity models; enoyl-acyl carrier protein reductase (FabI); molecular dynamics; triclosan.
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
Conflict of interest statement
The authors declare no conflict of interest.
64 references
6 figures
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25
Review
Int J Gynecol Cancer
. 2020 Sep 14;ijgc-2020-001789. doi: 10.1136/ijgc-2020-001789. Online ahead of print.
The new world of poly-(ADP)-ribose polymerase inhibitors (PARPi) used in the treatment of gynecological cancers
Anca Chelariu-Raicu 1, Graziela Zibetti Dal Molin 2, Robert L Coleman 3 4
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PMID: 32928926
DOI: 10.1136/ijgc-2020-001789
Abstract
The clinical development of poly-(ADP)-ribose polymerase inhibitors (PARPi) began with the treatment of ovarian cancer patients harboring BRCA1/2 mutations and continues to be expanded to other gynecological cancers. Furthermore, The Cancer Genome Atlas (TCGA) analysis of endometrial and cervical cancers offered rationale that PARPi may be an option for treatment based on the molecular profiles of these cancer types. This review summarizes the current indications of PARPi, such as its role in the treatment and maintenance of recurrent ovarian cancer and for first-line maintenance therapy in advanced ovarian cancer. We also outline new concepts for PARPi therapy in other gynecological cancers such as endometrial and cervical cancers based on recent clinical data. Finally, we present potential future directions to continue exploring the world of PARPi resistance and combining PARPi with other therapies.
Keywords: BRCA1 protein; BRCA2 protein; homologous recombination; ovarian cancer; uterine cancer.
© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Conflict of interest statement
Competing interests: RLC has clinical research funding from Merck, AstraZeneca/Medimmune, Genentech/Roche, Novartis, Clovis Oncology, Abbvie, and Janssenpharmaceuticals. RLC receives consulting fees from Genmab, Tesaro, Agenus, OncoMed, Novocure, Oncoquest, Merck, AstraZeneca/Medimmune, Genentech/Roche, Novartis, Clovis Oncology, Abbvie, Janssen pharmaceuticals, aravive, and OncoSec. These disclosed companies and grant funding sources had no input into the design, conduct, or preparation of the manuscript.
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26
Meta-Analysis
PLoS One
. 2020 Jul 28;15(7):e0235887. doi: 10.1371/journal.pone.0235887. eCollection 2020.
Laparoscopic vs. open mesorectal excision for rectal cancer: Are these approaches still comparable? A systematic review and meta-analysis
Maria Conticchio 1, Vincenzo Papagni 1, Margherita Notarnicola 1, Antonella Delvecchio 1, Umberto Riccelli 1, Michele Ammendola 2, Giuseppe Currò 2, Patrick Pessaux 3, Nicola Silvestris 4 5, Riccardo Memeo 6
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PMID: 32722694
PMCID: PMC7386630
DOI: 10.1371/journal.pone.0235887Free PMC article
Abstract
Background: To analyze pathologic and perioperative outcomes of laparoscopic vs. open resections for rectal cancer performed over the last 10 years.
Methods: A systematic literature search of the following databases was conducted: Cochrane Central Register of Controlled Trials, MEDLINE (through PubMed), EMBASE, and Scopus. Only articles published in English from January 1, 2008 to December 31, 2018 (i.e. the last 10 years), which met inclusion criteria were considered. The review only included articles which compared Laparoscopic rectal resection (LRR) and Open Rectal Resection (ORR) for rectal cancer and reported at least one of the outcomes of interest. The analyses followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement checklist. Only prospective randomized studies were considered. The body of evidence emerging from this study was evaluated using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. Outcome measures (mean and median values, standard deviations, and interquartile ranges) were extracted for each surgical treatment. Pooled estimates of the mean differences were calculated using random effects models to consider potential inter-study heterogeneity and to adopt a more conservative approach. The pooled effect was considered significant if p <0.05.
Results: Five clinical trials were found eligible for the analyses. A positive involvement of CRM was found in 49 LRRs (8.5%) out of 574 patients and in 30 ORRs out of 557 patients (5.4%) RR was 1.55 (95% CI, 0.99-2.41; p = 0.05) with no heterogeneity (I2 = 0%). Incorrect mesorectal excision was observed in 56 out of 507 (11%) patients who underwent LRR and in 41 (8.4%) out of 484 patients who underwent ORR; RR was 1.30 (95% CI, 0.89-1.91; p = 0.18) with no heterogeneity (I2 = 0%). Regarding other pathologic outcomes, no significant difference between LRR and ORR was observed in the number of lymph nodes harvested or concerning the distance to the distal margin. As expected, a significant difference was found in the operating time for ORR with a mean difference of 41.99 (95% CI, 24.18, 59.81; p <0.00001; heterogeneity: I2 = 25%). However, no difference was found for blood loss. Additionally, no significant differences were found in postoperative outcomes such as postoperative hospital stay and postoperative complications. The overall quality of the evidence was rated as high.
Conclusion: Despite the spread of laparoscopy with dedicated surgeons and the development of even more precise surgical tools and technologies, the pathological results of laparoscopic surgery are still comparable to those of open ones. Additionally, concerning the pathological data (and particularly CRM), open surgery guarantees better results as compared to laparoscopic surgery. These results must be a starting point for future evaluations which consider the association between ''successful resection" and long-term oncologic outcomes. The introduction of other minimally invasive techniques for rectal cancer surgery, such as robotic resection or transanal TME (taTME), has revealed new scenarios and made open and even laparoscopic surgery obsolete.
Conflict of interest statement
The authors declare no competitive interests.
41 references
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27
Eur J Surg Oncol
. 2020 Aug 25;S0748-7983(20)30716-2. doi: 10.1016/j.ejso.2020.08.024. Online ahead of print.
Frailty assessment tools and geriatric assessment in older patients with hepatobiliary and pancreatic malignancies
Siri Rostoft 1, Barbara van Leeuwen 2
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PMID: 32933803
DOI: 10.1016/j.ejso.2020.08.024
Abstract
Background: The majority of patients with hepatobiliary and pancreatic (HBP) malignancies are older than 65 years. Due to the heterogeneity of this older population, decisions regarding surgical treatment cannot rely solely on treatment guidelines, but have to take into account patient frailty, geriatric impairments and resilience as well as patient preferences. In the few studies of older patients with HBP malignancies that have included a preoperative geriatric assessment (GA), frailty and elements from the GA such as reduced functional status have emerged as powerful predictors of postoperative morbidity and mortality, length of stay, type of treatment received and survival. A GA is a systematic evaluation of functional status, comorbidities, polypharmacy, cognition, nutritional status, emotional status, and social support.
Materials and methods: A Pubmed search identifying clinical studies investigating the association between frailty, GA and outcomes in patients with HBP malignancies.
Results: A total of 20 studies were included in this review. For HBP malignancies, the evidence linking frailty and GA variables to negative outcomes is limited, but generally shows that frailty, functional dependency, comorbidity, and sarcopenia predict postoperative complications and survival.
Conclusion: Although scarcely investigated, frailty and elements from a GA seem to be associated with negative short- and long-term treatment outcomes in older patients with HBP malignancies. Future studies should investigate the impact of geriatric interventions and prehabilitation on outcomes.
Keywords: Assessment tools; Cancer; Frailty; Geriatric assessment; Hepatobiliary disorders; Older adults; Preoperative assessment.
Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors have no conflicts of interest to declare.
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28
Oncogene
. 2020 Sep 14. doi: 10.1038/s41388-020-01454-1. Online ahead of print.
Combined inhibition of JAK2-STAT3 and SMO-GLI1/tGLI1 pathways suppresses breast cancer stem cells, tumor growth, and metastasis
Daniel Doheny 1, Sherona Sirkisoon 1, Richard L Carpenter 1 2, Noah Reeve Aguayo 1, Angelina T Regua 1, Marlyn Anguelov 1, Sara G Manore 1, Austin Arrigo 1, Sara Abu Jalboush 1, Grace L Wong 1, Yang Yu 1, Calvin J Wagner 1, Michael Chan 3 4, Jimmy Ruiz 3 5, Alexandra Thomas 3 5, Roy Strowd 3 6, Jiayuh Lin 7, Hui-Wen Lo 8 9
Affiliations expand
PMID: 32929154
DOI: 10.1038/s41388-020-01454-1
Abstract
Triple-negative breast cancer (TNBC) and HER2-positive breast cancer are particularly aggressive and associated with unfavorable prognosis. TNBC lacks effective treatments. HER2-positive tumors have treatment options but often acquire resistance to HER2-targeted therapy after initial response. To address these challenges, we determined whether novel combinations of JAK2-STAT3 and SMO-GLI1/tGLI1 inhibitors synergistically target TNBC and HER2 breast cancer since these two pathways are concurrently activated in both tumor types and enriched in metastatic tumors. Herein, we show that novel combinations of JAK2 inhibitors (ruxolitinib and pacritinib) with SMO inhibitors (vismodegib and sonidegib) synergistically inhibited in vitro growth of TNBC and HER2-positive trastuzumab-resistant BT474-TtzmR cells. Synergy was also observed against breast cancer stem cells. To determine if the combination is efficacious in inhibiting metastasis, we treated mice with intracardially inoculated TNBC cells and found the combination to inhibit lung and liver metastases, and prolong host survival without toxicity. The combination inhibited orthotopic growth, VEGF-A expression, and tumor vasculature of both TNBC and HER2-positive trastuzumab-refractory breast cancer. Lung metastasis of orthotopic BT474-TtzmR xenografts was suppressed by the combination. Together, our results indicated that dual targeting of JAK2 and SMO resulted in synergistic suppression of breast cancer growth and metastasis, thereby supporting future clinical testing.
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29
Expert Rev Hematol
. 2020 Sep 15;1-12. doi: 10.1080/17474086.2020.1819785. Online ahead of print.
COVID-19 in benign hematology: emerging challenges and special considerations for healthcare professionals
Peter Noun 1, Ahmad Ibrahim 2 3, Mohammad Hassan Hodroj 4, Rayan Bou-Fakhredin 5, Ali T Taher 5
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PMID: 32931348
DOI: 10.1080/17474086.2020.1819785
Abstract
Introduction: Many patients with inherited or acquired benign hematological disorders are at increased risk of developing severe complications from COVID-19. These patients, therefore, require specific advice regarding isolation and changes to their usual treatment schedules. Their disease can also be associated with significant burden, and they necessitate life-long and regular access to therapy, and regular follow-up consultations and hospital visits. The current COVID-19 pandemic is therefore presenting many challenges for these patients, their families, and health-care professionals.
Areas covered: This review provides an overview of the reported COVID-19 cases in the literature in patients with certain benign hematological disorders including thalassemia, sickle cell disease, hemophilia, immune thrombocytopenia, venous thromboembolism, and aplastic anemia. The review also outlines some recommendations on how to manage these patients if they are infected with SARS-CoV-2. To review the literature on benign hematological disorders and COVID-19, a bibliographic search was performed using PubMed for articles published between January 2020 and June 2020.
Expert opinion: International efforts must be made to continue reporting and better understanding the effects of SARS-CoV-2 infection in these patients and accordingly develop a set of recommendations to optimize the treatment of future infected patients.
Keywords: COVID-19; benign hematology; bleeding disorders; coagulopathy; hemoglobin disorders; platelet disorders; sars-CoV-2.
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30
Expert Rev Anticancer Ther
. 2020 Sep 15. doi: 10.1080/14737140.2020.1810572. Online ahead of print.
Patient selection and risk factors in the changing treatment landscape of metastatic renal cell carcinoma
Ehab Abdou 1, Ravi M Pedapenki 2, Mohamed Abouagour 1, Abdul R Zar 3, Emad Anwar 4, Dalia Elshourbagy 5, Humaid Al-Shamsi 4, Enrique Grande 6
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PMID: 32930617
DOI: 10.1080/14737140.2020.1810572
Abstract
Introduction: The approval of combination treatments for metastatic renal cell carcinoma (mRCC) represents a major change in the clinical management of this malignancy. Updated treatment guidelines differentiate first-line mRCC treatment by patient risk group as defined by prognostic models and the number of risk factors.
Areas covered: Current prognostic models, with a focus on the International Metastatic RCC Database Consortium and the Memorial Sloan-Kettering Cancer Center models, the heterogeneity of the intermediate risk group, and first- and second-line mRCC treatment outcomes according to patient risk group are discussed. Consideration is given to the future direction of treatment selection strategies including refinement of prognostic factors, genetic biomarkers and gene signatures.
Expert opinion: Current prognostic models require updating, but initial data suggests they are effective in stratifying patients treated with immune checkpoint inhibitors or combination therapy. Treatment selection for patients with 1-2 risk factors may require further consideration due to the heterogeneous nature of the intermediate risk group. Future prognostic models may benefit from inclusion of gene signatures and stratification by molecular subtype. Prognostic risk factors are not the only consideration in treatment selection; tumor burden, location of metastases, and comorbidities, among other factors, should also be considered.
Keywords: Combination therapy; immune checkpoint inhibitor; prognostic model; renal cell carcinoma; risk factors; targeted therapy; tyrosine kinase inhibitor.
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31
Histol Histopathol
. 2020 Sep 16;18260. doi: 10.14670/HH-18-260. Online ahead of print.
Nephronectin is a prognostic biomarker and promotes gastric cancer cell proliferation, migration and invasion
Di Mei 1 2, Bochao Zhao 1, Jiale Zhang 1, Huimian Xu 1, Baojun Huang 3
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PMID: 32935851
DOI: 10.14670/HH-18-260
Abstract
Gastric cancer (GC) is a malignant disease with high incidence and mortality rates worldwide. Nephronectin (NPNT) was found to be dysregulated in some kinds of cancer. The goal of our study was to explore the expression profile of NPNT based on large numbers of GC samples with detailed clinicopathological and prognostic data from our institution and the data from a public database. A total of 117 GC samples and 73 corresponding non-tumorous adjacent tissues (NATs) were obtained from GC patients and used to detect expression of NPNT through immunohistochemistry. Western blot and qRT-PCR were performed to examine expression of NPNT in GC cell lines. Our results found that the positive expression ratio of NPNT in GC tissues is significantly higher than that in NATs (p<0.001). Chi-squared analysis results showed positive expression ratio of NPNT was significantly associated with depth of tumor invasion (p=0.049) and TNM stage (p=0.017). Kaplan-Meier survival and cox analysis results showed that patients with positive NPNT protein expression tend to have poorer prognosis than those with negative NPNT expression (p=0.0032) and NPNT expression was independent prognostic factor. High expression level was seen in GC cell lines. Furthermore, through a series of cancer cell proliferation, invasion and migration associated experiments, we found that NPNT could evidently promote GC cell proliferation, invasion and migration, as well as epithelial-mesenthymal transition. In summary, NPNT was evidently overexpressed in GC and had an oncogenic role. In the future, NPNT could serve as a promising therapeutic target for treating GC patients.
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32
Review
Cancers (Basel)
. 2020 Sep 11;12(9):E2598. doi: 10.3390/cancers12092598.
Multimodality Treatment in Metastatic Gastric Cancer: From Past to Next Future
Alessandro Parisi 1 2, Giampiero Porzio 1 2, Corrado Ficorella 1 2
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PMID: 32932914
DOI: 10.3390/cancers12092598Free article
Abstract
Gastric cancer (GC) still remains an incurable disease in almost two-thirds of the cases. However, a deeper knowledge of its biology in the last few years has revealed potential biomarkers suitable for tailored treatment with targeted agents. This aspect, together with the improvement in early supportive care and a wiser use of the available cytotoxic drugs across multiple lines of treatment, has resulted in incremental and progressive survival benefits. Furthermore, slowly but surely, targeted therapies and immune checkpoint inhibitors are revising the therapeutic scenario even in metastatic GC and especially in particular subgroups. Moreover, important study results regarding the possible role of an integrated approach combining systemic, surgical, and locoregional treatment in carefully selected oligometastatic GC patients are awaited. This review summarizes the state-of-the-art and the major ongoing trials involving a multimodal treatment of metastatic GC.
Keywords: advanced gastric cancer; chemotherapy; immunotherapy; locoregional treatment; supportive care; surgical treatment; targeted therapy.
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33
Cancer Epidemiol Biomarkers Prev
. 2020 Sep 14;cebp.0520.2020. doi: 10.1158/1055-9965.EPI-20-0520. Online ahead of print.
Racial and ethnic differences in sarcoma incidence are independent of census-tract socioeconomic status
Brandon J Diessner 1, Brenda J Weigel 2, Paari Murugan 3, Lin Zhang 4, Jenny N Poynter 5, Logan G Spector 6
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PMID: 32928933
DOI: 10.1158/1055-9965.EPI-20-0520
Abstract
Background: Epidemiological analyses of sarcoma are limited by the heterogeneity and rarity of the disease. Utilizing population-based surveillance data enabled us to evaluate the contribution of census tract-level socioeconomic status (CT-SES) and race/ethnicity on sarcoma incidence rates.
Methods: We utilized the Surveillance, Epidemiology and End Results program to evaluate associations between CT-SES and race/ethnicity on the incidence rates of sarcoma. Incidence rate ratios (IRR) and 99% confidence intervals (CI) were estimated from quasi-Poisson models. All models were stratified by broad age groups (pediatric: < 20 years, Adult: 20 - 65 years, Older adult: 65 + years) and adjusted for sex, age and year of diagnosis. Within each age group, we conducted analyses stratified by somatic genome (fusion positive and fusion negative sarcomas) and for subtypes with > 200 total cases. A p-value less than 0.01 was considered statistically significant.
Results: We included 55,415 sarcoma cases in 35 sarcoma subtype-age group combinations. Increasing CT-SES was statistically significantly associated with 11 subtype-age group combinations, primarily in the older age group strata (8 subtypes), while malignant peripheral nerve sheath tumors in adults were associated with decreasing CT-SES. Nearly every sarcoma subtype-age group combination displayed racial/ethnic disparities in incidence that were independent of CT-SES.
Conclusions: We found race/ethnicity to be more frequently associated with sarcoma incidence than CT-SES. Our findings suggest that genetic variation associated with ancestry may play a stronger role than area-level SES-related factors in the etiology of sarcoma.
Impact: These findings provide direction for future etiologic studies of sarcomas.
Copyright ©2020, American Association for Cancer Research.
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34
Review
Mol Biol Rep
. 2020 Sep 14. doi: 10.1007/s11033-020-05826-4. Online ahead of print.
Do tumor exosome integrins alone determine organotropic metastasis?
E S Grigoryeva 1, O E Savelieva 2, N O Popova 3, N V Cherdyntseva 4, V M Perelmuter 2
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PMID: 32929649
DOI: 10.1007/s11033-020-05826-4
Abstract
Metastasis is the most life-threatening event in cancer patients, so the key strategy to treat cancer should be preventing tumor spread. Predicting the site of probable hematogenous metastasis is important for determining the therapeutic algorithm that could prevent the spread of tumor cells. Certain hopes for solving this problem appeared owing to study showing the association between specific integrins on tumor exosomes surface and the site of future metastasis. Numerous experimental data indicate the ability of exosomes to transfer various phlogogenic factors to the target organ, which can lead to the formation of inflammatory foci. Studies of T-lymphocytes homing show that expression of various adhesion molecules including ligands for integrins highly increases on the endothelium during inflammation. Such a mechanism underlies not only in leukocyte transvasation, but, apparently, in the accumulation of bone marrow precursor cells and the formation of a premetastatic niche. This review summarizes the most significant data on the role exosomes to induce inflammation, which leads to the recruiting of bone marrow precursors and the establishment of premetastatic niches.
Keywords: Carcinoma; Exosomes; Integrins; Organotropic metastasis; Premetastatic niche.
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35
Sci Adv
. 2020 May 20;6(21):eaba5996. doi: 10.1126/sciadv.aba5996. Print 2020 May.
Engineered algae: A novel oxygen-generating system for effective treatment of hypoxic cancer
Yue Qiao 1 2, Fei Yang 1, Tingting Xie 2, Zhen Du 2, Danni Zhong 2, Yuchen Qi 2, Yangyang Li 2, Wanlin Li 2 3, Zhimin Lu 2, Jianghong Rao 3, Yi Sun 4 5, Min Zhou 6 2 5 7
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PMID: 32937294
DOI: 10.1126/sciadv.aba5996Free article
Abstract
Microalgae, a naturally present unicellular microorganism, can undergo light photosynthesis and have been used in biofuels, nutrition, etc. Here, we report that engineered live microalgae can be delivered to hypoxic tumor regions to increase local oxygen levels and resensitize resistant cancer cells to both radio- and phototherapies. We demonstrate that the hypoxic environment in tumors is markedly improved by in situ-generated oxygen through microalgae-mediated photosynthesis, resulting in notably radiotherapeutic efficacy. Furthermore, the chlorophyll from microalgae produces reactive oxygen species during laser irradiation, further augmenting the photosensitizing effect and enhancing tumor cell apoptosis. Thus, the sequential combination of oxygen-generating algae system with radio- and phototherapies has the potential to create an innovative treatment strategy to improve the outcome of cancer management. Together, our findings demonstrate a novel approach that leverages the products of photosynthesis for treatment of tumors and provide proof-of-concept evidence for future development of algae-enhanced radio- and photodynamic therapy.
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
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36
Review
J Exp Clin Cancer Res
. 2020 Sep 14;39(1):187. doi: 10.1186/s13046-020-01700-0.
Natural antisense transcripts in the biological hallmarks of cancer: powerful regulators hidden in the dark
Shanshan Zhao 1, Xue Zhang 2, Shuo Chen 3, Song Zhang 4 5
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PMID: 32928281
DOI: 10.1186/s13046-020-01700-0Free article
Abstract
Natural antisense transcripts (NATs), which are transcribed from opposite strands of DNA with partial or complete overlap, affect multiple stages of gene expression, from epigenetic to post-translational modifications. NATs are dysregulated in various types of cancer, and an increasing number of studies focusing on NATs as pivotal regulators of the hallmarks of cancer and as promising candidates for cancer therapy are just beginning to unravel the mystery. Here, we summarize the existing knowledge on NATs to highlight their underlying mechanisms of functions in cancer biology, discuss their potential roles in therapeutic application, and explore future research directions.
Keywords: Cancer; Hallmarks of cancer; NATs; Natural antisense transcripts.
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37
Biomed Rep
. 2020 Nov;13(5):42. doi: 10.3892/br.2020.1349. Epub 2020 Aug 27.
RNA sequencing-based identification of potential targets in acute myeloid leukemia: A case report
Omar S El-Masry 1, Ali M Al-Amri 2, Ahlam Alqatari 3, Khaldoon Alsamman 1
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PMID: 32934815
PMCID: PMC7469581
DOI: 10.3892/br.2020.1349Free PMC article
Abstract
Acute myeloid leukemia (AML) refers to heterogenous types of blood cancer which possess a complicated genomic landscape, and multiple novel mutational alterations are frequently being reported. Herein, a case report of a 37-year old AML patient is presented, who was diagnosed following laboratory investigation after admission. The patient had thrombocytopenia, and three consecutive blast counts of 40, 30 and 41%, respectively. A blood sample was collected for whole-genome RNA sequencing to understand the transcriptomic profile at the time of diagnosis and compared with a matched female control. Gene expression was quantified using the RSEM software package. Bioinformatics analysis revealed a significant number of differentially expressed genes in the patient, suggesting a marked change in the transcriptomic landscape in this patient. By mining the bioinformatics data and screening the highly expressed genes with ≥80% probability of gene expression, four novel genes were highlighted that may serve as potential future targets in AML patients; Rh associated glycoprotein, succinate receptor 1, transmembrane-4 L-six family member-1 and ADGRA3, although further validation of their value is required.
Keywords: ADGRA3; RNA sequencing; Rh associated glycoprotein; acute myeloid leukemia; succinate receptor 1; transmembrane-4 L-six family member-1.
Copyright: © El-Masry et al.
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2 figures
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38
Am Surg
. 2020 Sep 15;3134820951451. doi: 10.1177/0003134820951451. Online ahead of print.
The Future Liver Remnant : Definition, Evaluation, and Management
Matthew Dixon 1, Jeffrey Cruz 1 2 3, Nabeel Sarwani 2, Niraj Gusani 1 3 4
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PMID: 32931301
DOI: 10.1177/0003134820951451
Abstract
When considering patients for a major hepatectomy, one must carefully consider the volume of liver to be left behind and if additional procedures are necessary to augment its volume. This review considers the optimal volume of the future liver remnant (FLR) and analyzes the techniques of augmenting this volume, the various growth parameters to assess adequate growth of the FLR, as well as further management when there has been inadequate growth of the FLR.
Keywords: future liver remnant; hepatectomy; portal vein embolization.
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39
Cancers (Basel)
. 2020 Sep 10;12(9):E2577. doi: 10.3390/cancers12092577.
A Modern Approach to Endometrial Carcinoma: Will Molecular Classification Improve Precision Medicine in the Future?
Simone Marnitz 1 2, Till Walter 1 2, Birgid Schömig-Markiefka 2 3, Tobias Engler 4, Stefan Kommoss 4, Sara Yvonne Brucker 4
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PMID: 32927671
DOI: 10.3390/cancers12092577Free article
Abstract
Endometrial cancer has been histologically classified as either an estrogen-dependent cancer with a favorable outcome or an estrogen-independent cancer with a worse prognosis. These parameters, along with the clinical attributions, have been the basis for risk stratification. Recent molecular and histopathological findings have suggested a more complex approach to risk stratification. Findings from the Cancer Genome Atlas Research Network established four distinctive genomic groups: ultramutated, hypermutated, copy-number low and copy-number high prognostic subtypes. Subsequently, more molecular and histopathologic classifiers were evaluated for their prognostic and predictive value. The impact of molecular classification is evident and will be recognized by the upcoming WHO classification. Further research is needed to give rise to a new era of molecular-based endometrial carcinoma patient care.
Keywords: L1CAM; MMRd; POLE; adjuvant radiation; brachytherapy; endometrial cancer; molecular classification; risk classification; risk stratification; uterus carcinoma.
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40
Future Oncol
. 2020 Sep 15. doi: 10.2217/fon-2020-0320. Online ahead of print.
Afatinib for the first-line treatment of EGFR mutation-positive NSCLC in China: a review of clinical data
Hai-Yan Tu 1, Yi-Long Wu 1
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PMID: 32927981
DOI: 10.2217/fon-2020-0320
Abstract
Mutations in the EGFR gene are particularly prevalent among Chinese patients with non-small-cell lung carcinoma. Six EGFR tyrosine kinase inhibitors are approved for the first-line treatment of EGFR mutation-positive non-small-cell lung carcinoma in China, which poses questions about which agent is most suitable for a particular patient. In this article, we review available clinical trial and real-world data with afatinib in Chinese patients. We assess its efficacy and safety in key patient subgroups such as those with uncommon mutations or brain metastases. We also consider possible subsequent therapies following afatinib. Encouragingly, available data suggest that sequential afatinib and osimertinib confer prolonged overall time to failure of almost 4 years in Asian patients, and represents a viable option in this setting.
Keywords: Chinese; EGFR mutation; NSCLC; afatinib; first-line.
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41
Br J Surg
. 2020 Sep 16. doi: 10.1002/bjs.11828. Online ahead of print.
Surgical outcomes of major hepatectomy following "radiation lobectomy" for hepatic malignancies and insufficiently functional future liver remnant: initial experience
D Andel 1, M G Dassen 2, M T M Reinders-Hut 2, N A Peters 1, O W Kranenburg 1, M G E H Lam 2, J Hagendoorn 1, I H M Borel Rinkes 1
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PMID: 32936446
DOI: 10.1002/bjs.11828
No abstract available
5 references
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