Emerging from their burrow: Hedgehog pathway inhibitors for cancer

Introduction: Cancer treatment is moving away from conventional cytotoxic drugs and towards agents that target specific proteins and mechanisms important to cancer development or survival. The Hedgehog Pathway (HhP) is a signal transduction pathway and its constitutive activation is tumorigenic in basal cell carcinoma (BCC). The HhP enables phenotypic flexibility, and channels tumor-stroma interactions. As a result, it is over-expressed in numerous cancers as well as in the tumor microenvironment and may represent a promising therapeutic target.

Areas covered: In this article, we review the rationale for targeting HhP and its role as an oncogenic driver, in tumor epithelial-to-mesenchymal transition (EMT), and in the tumor microenvironment and describe the results of preclinical and clinical studies involving HhP inhibitors.

Expert opinion: HhP activation plays an important role in both the tumor microenvironment and tumor EMT which can lead to treatment resistance for a number of different malignancies. In addition to standard use in BCC, several HhP inhibitors are in preclinical, early, and mid-stage clinical development for other solid and hematologic malignancies.     

Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

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Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

A comparison of head injuries in male and female lacrosse participants seen in US emergency departments from 2005 to 2016

Introduction

In the United States there has been a large increase in participation in lacrosse for both males and females. The purpose of this study was to analyze the number of head injuries, injury rates (calculated using the reported number of participants) and types of head injuries that are seen in emergency departments in the United States.

Praying to win this battle: Cancer Metaphors in Latina and Spanish Women’s Narratives

ABSTRACT

This study closely examines 51 breast cancer narratives Latina and Spanish women wrote for other patients to illuminate how they conceptualize their health, with insights for addressing health disparities. Using discourse analysis of the role of language and culture in health care communication, this study focuses on the use of metaphors in the narratives. This provides revelations about the cultural and linguistic aspects of how the writers conceptualize their disease. Building on past research on metaphor use in cancer discourse in the English language, this study reveals the prevalence of metaphors comparing cancer to combat, or more generally, violence (e.g., “my battle against cancer”), or a journey (e.g., “my path with cancer”). Writers used this metaphorical language to offer advice to others with cancer and to mark their membership in a larger community of people with cancer. We also find that Spanish women use metaphors more frequently than Latinas and that they differed in their metaphorical portrayals of cancer. This research uncovers culturally embedded themes that are central to how women with cancer think about the disease, such as the prominence of spirituality in Latinas’ metaphorical constructions, a pattern not evident in Spanish women’s narratives.     

Five Year Trends in the Utilization of Robotic Bariatric Surgery Procedures,United States 2015–2019

Purpose

Robotic approaches have been steadily replacing laparoscopic approaches in metabolic and bariatric surgeries (MBS); however, their superiority has not been rigorously evaluated. The main goal of the study was to evaluate the 5-year utilization trends of robotic MBS and to compare to laparoscopic outcomes.

Methods

Retrospective analysis of 2015–2019 MBSAQIP data. Kruskal-Wallis test/Wilcoxon and Fisher’s exact/chi-square were used to compare continuous and categorical variables, respectively. Generalized linear models were used to compare surgery outcomes.

Results

The use of robotic MBS increased from 6.2% in 2015 to 13.5% in 2019 (N= 775,258). Robotic MBS patients had significantly higher age, BMI, and likelihood of 12 diseases compared to laparoscopic patients. After adjustment, robotic MBS patients showed higher 30-day interventions and 30-day readmissions alongside longer surgery time (26–38 min).

Conclusion

Robotic MBS shows higher intervention and readmission even after controlling for cofounding variables.

Graphical Abstract

     

Per‐oral transgastric abdominal surgery

Laparoscopic surgery has several advantages over traditional surgery because it has been shown to be less invasive. The next logical step in the evolution of minimally invasive surgery may be to eliminate all abdominal incisions. The natural orifices provide a port of entry via the gastrointestinal tract to the peritoneal cavity. This approach would require the creation of a perforation, which is considered to be a major complication of endoscopy with significant morbidity and mortality. However, there are several recent studies that have described the technical feasibility and safety of a per‐oral transgastric approach to the peritoneal cavity using conventional endoscopes. Theoretically, this approach could reduce postoperative abdominal wall pain, wound infection, hernia formation, and adhesions. This article aims to summarize the current status of transgastric surgery, currently referred to as natural orifice transluminal endoscopic surgery (NOTES), and to address some of its future challenges.     

Littoral‐cell angioma as a rare cause of splenomegaly

We report the case of a littoral‐cell angioma of the spleen, a recently described benign vascular tumour, whose imaging and pathological characteristics have been discussed only by a few authors. The diagnosis was made after elective splenectomy. The CT images, scintigraphy and histological specimens are presented, and differential diagnoses discussed.