Pectoral nerve block1 versus modified pectoral nerve block2 for postoperative pain relief in patients undergoing modified radical mastectomy: a randomized clinical trial †

Abstract

Background. Pectoral nerve block1 (PEC1) given between pectoralis major and minor, and modified pectoral nerve block2 (mPEC2) performed between pectoralis minor and serratus anterior, can provide continuous analgesia after modified radical mastectomy (MRM) when catheters are placed before skin closure. This study was designed to compare PEC1 and mPEC2 block for providing postoperative pain relief after MRM.Methods. Sixty-two physically fit patients undergoing MRM were assigned into two groups (Group PEC1, n=31 and Group mPEC2, n=31). Before wound closure, epidural catheter was placed in the group designated muscle plane and 30ml of 0.25% bupivacaine was injected through the catheter after wound closure. Bupivacaine 15ml of 0.25% top up was given on patient's demand or whenever visual analogue scale (VAS) score was>4. Time for first analgesia (TFA), number of top ups and VAS was recorded at 0.5, 6, 12, 18, 24 h after surgery. Sensory blockade was assessed 30 min after extubation.Results. Analgesia was significantly prolonged in group mPEC2 [mean(SD)] 313.45(43.05) vs 258.87(34.71) min in group PEC1, P<0.001. Total pain experienced over 24 h was significantly less in group mPEC2 [mean(SD)] 9.77(6.93) than in group PEC1 24.19(10.81), P<0.0001. Consequently, top up requirements were significantly reduced in group mPEC2 than in group PEC1 [median(range)] 3(2-4) vs 4(3-5) respectively, P<0.001. Lateral pectoral (77.42% and 35.48%) and thoracodorsal nerves (93.55% and 48.39%) had higher incidence of sensory block in group mPEC2 than group PEC1, P<0.001.Conclusions. mPEC2 provides better postoperative analgesia than PEC1 when catheters are placed under direct vision after MRM.Clinical trial registration. CTRI/2017/02/007811 (REF/2015/11/010185).

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Beta-blockers in sepsis: time to reconsider current constraints?

New insights into the mechanisms of action of beta-blockers, and the potential consequences for clinical practice, are continually evolving. Originally, this class of drugs was targeted towards treatment or prevention of hypertension, arrhythmias and myocardial ischaemia. Their therapeutic potential then expanded towards the reduction of mortality after myocardial infarction and heart failure.¹ Although these indications are now widely accepted, they were not immediately apparent. So why may the use of beta-blockers be beneficial in patients already suffering from impaired myocardial contractility? Clinical observations suggested that the beneficial effect of beta-blockers was greater in patients with the worst cardiac performance.² Concurrent findings that chronic use of an oral beta-agonist was associated with increased mortality led to re-evaluation of the paradigm,³⁴ fuelled new research that unravelled the concept of maladaptive sympathetic overstimulation in heart failure,⁵ and changed clinical practice towards the use of beta-blockade.

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3D endothelial cell spheroid/human vitreous humor assay for the characterization of anti-angiogenic inhibitors for the treatment of proliferative diabetic retinopathy

Abstract

Proliferative diabetic retinopathy (PDR) represents a main cause of acquired blindness. Despite the recognition of the key role exerted by vascular endothelial growth factor (VEGF) in the pathogenesis of PDR, limitations to anti-VEGF therapies do exist. Thus, rapid and cost-effective angiogenesis assays are crucial for the screening of anti-angiogenic drug candidates for PDR therapy. In this context, evaluation of the angiogenic potential of PDR vitreous fluid may represent a valuable tool for preclinical assessment of angiostatic molecules. Here, vitreous fluid obtained from PDR patients after pars plana vitrectomy was used as a pro-angiogenic stimulus in a 3D endothelial cell spheroid/human vitreous assay. The results show that PDR vitreous is able to stimulate the sprouting of fibrin-embedded HUVEC spheroids in a time- and dose-dependent manner. A remarkable variability was observed among 40 individual vitreous fluid samples in terms of sprouting-inducing activity that was related, at least in part, to defined clinical features of the PDR patient. This activity was hampered by various extracellular and intracellular signaling pathway inhibitors, including the VEGF antagonist ranibizumab. When tested on 20 individual vitreous fluid samples, the inhibitory activity of ranibizumab ranged between 0 and 100% of the activity measured in the absence of the drug, reflecting a variable contribution of angiogenic mediators distinct from VEGF. In conclusion, the 3D endothelial cell spheroid/human vitreous assay represents a rapid and cost-effective experimental procedure suitable for the evaluation of the anti-angiogenic activity of novel extracellular and intracellular drug candidates, with possible implications for the therapy of PDR.

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Highly sensitive detection of ESR1 mutations in cell-free DNA from patients with metastatic breast cancer using molecular barcode sequencing

Abstract

Purpose

We aimed to develop a highly sensitive method to detect ESR1 mutations in cell-free DNA (cfDNA) using next-generation sequencing with molecular barcode (MB–NGS) targeting the hotspot segment (c.1600–1713).

Methods

The sensitivity of MB–NGS was tested using serially diluted ESR1 mutant DNA and then cfDNA samples from 34 patients with metastatic breast cancer were analyzed with MB–NGS. The results of MB–NGS were validated in comparison with conventional NGS and droplet digital PCR (ddPCR).

Results

MB–NGS showed a higher sensitivity (0.1%) than NGS without barcode (1%) by reducing background errors. Of the cfDNA samples from 34 patients with metastatic breast cancer, NGS without barcode revealed seven mutations in six patients (17.6%) and MB–NGS revealed six additional mutations including three mutations not reported in the COSMIC database of breast cancer, resulting in total 13 ESR1 mutations in ten patients (29.4%). Regarding the three hotspot mutations, all the patients with mutations detected by MB–NGS had identical mutations detected by droplet digital PCR (ddPCR), and mutant allele frequency correlated very well between both (r = 0.850, p < 0.01). Moreover, all the patients without these mutations by MB–NGS were found to have no mutations by ddPCR.

Conclusion

In conclusion, MB–NGS could successfully detect ESR1 mutations in cfDNA with a higher sensitivity of 0.1% than conventional NGS and was considered as clinically useful as ddPCR.

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Scrotoschisis: a case report

Scrotoschisis is a rare congenital anomaly of the scrotal wall with idiopathic etiology and unknown prevalence. This pathology is extremely rare. We report a new case and review the literature for relevant data.

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The role of the neural niche in brain metastasis

Abstract

Cancers with neurologic metastasis are a burdensome affliction. As primary cancer care improves, the incidence of metastatic cancer increases as a result of prolonged survival time. Because of this, advances in the understanding of the mechanisms of metastasis are important for the development of continuing management strategies. Knowing how metastatic tumor cells engage, survive, and proliferate in the central nervous system (CNS) is an important first step in developing treatment paradigms. The neural niche is the soil of the CNS that accommodates tumor cells, is a microenvironment of cell signaling that exists between the tumor cell and the native neural cellular network. Elements of the neural niche have been identified as acquaintances for metastatic tumor growth. As more is known about the neural niche, treatment strategies can be developed to target these networks of metastatic tumor progression.

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Pembrolizumab in the treatment of advanced urothelial cancer

Future Oncology, Ahead of Print.


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