Molecular testing for melanocytic tumors: a practical update

The work-up of melanocytic tumors has undergone significant changes in the last years following the exponential growth of molecular assays. For the practicing pathologist it is often difficult to sort through the myriad of different tests available currently for clinical use. The molecular tests used in melanocytic pathology can be broadly divided into 4 categories: (i) Tests useful in the differential diagnosis of nevus versus melanoma (primarily used as an aid in the diagnosis of histologically ambiguous melanocytic tumors), (ii) Tests that predict prognosis in melanoma, (iii) Tests useful in the classification of melanocytic tumors and (iv) Tests that predict response to systemic therapy in melanoma. This review will present an updated overview of major ancillary tests used in clinical practice.     

Assessment of dental implant surface stability at the nanoscale level

ObjectivesTo study the oxide layer stability of certified dental implants of system "P", made based on TiO₂ alloy with carbon coating. To perform a comparative statistical analysis of the obtained data with the available data for the dental implants of systems "A" and "B".MethodsX-ray microtomography and X-ray fluorescence analysis were used to study soft tissue biopsy specimens. Supernatants were studied by dynamic light scattering and transmission electron microscopy when simulating free emission of nanoscale metal oxide particles from the surface of dental implants as well as when simulating physical loading. A comparative analysis of three parameters of nanoscale particles was performed by statistical data analysis. The surface of the "P" system dental implant with surface treatment was analyzed by scanning electron microscopy.ResultsBoth free emission of nanoscale oxide layer particles and yield of nano- and microscale particles during simulation of physical load were confirmed. Statistically significant differences were noted in a comparative analysis of the size and frequency of occurrence of these particles in the supernatants obtained from the surfaces of three dental implant systems. The elemental composition of the particles and the composition and structure of the "P" system dental implants themselves were analyzed.SignificanceThe developed method of dynamic light scattering can be used to compare the stability of the oxide layer of standardized medical products manufactured on the basis of the TiO₂ alloy.     

近红外荧光成像技术在外科手术中的研究进展

作为术中导航的新兴领域,近红外荧光(near-infrared fluorescence,NIRF)成像技术能借助荧光探针对特定的生物组织进行显像,从而在外科手术中实时获取血管、淋巴管和特定组织的视觉信息,从而发现传统方法无法识别的微小灶,正确显示肿瘤切缘,帮助外科医生进行术中决策。该技术由于其操作简单,快速实时,安全无害,具有良好的应用前景。本文将就NIRF成像技术的基本原理,在实时引导肿瘤切除,前哨淋巴结定位,保护正常解剖结构等方面的临床进展进行综述,并且讨论了该技术的局限性和优势并展望其应用前景。     

Near-infrared fluorescence imaging improves the nodal yield in neck dissection in oral cavity cancer – A randomized study

IntroductionLymph node yield (LNY) in neck dissection has been identified as a prognostic factor in oral cavity cancer. The purpose of this study was to investigate the impact of additional use of optical imaging on LNY in therapeutic ND in oral cancer.MethodsConsecutive patients with oral squamous cell carcinoma with clinical neck metastasis planned for primary tumor resection were randomized to conventional neck dissection or near-infrared fluorescence (NIRF)-guided neck dissection, respectively. In the intervention group, patients were injected with ICG-Nanocoll prior to surgery. Intraoperatively, an optical hand-held camera system was used for lymph node identification. Also, NIRF imaging of the neck specimen was performed, and optical signals were pinned with needle markings to guide the pathological examination. The endpoint of the study was LNY per neck side in levels Ib-III.Results31 patients were included with 18 neck sides in the control group and 18 neck sides in the intervention group for evaluation. During NIRF-guided ND, individual lymph nodes could be identified by a bright fluorescent signal and individual tumor-related drainage patterns could be observed in the neck. The LNY in the intervention group was significantly higher compared to the control group (p = 0.032) with a mean of 24 LN (range: 12–33 LN in levels Ib-III compared to 18 LN (range: 10–36 LN) in the control group, respectively.ConclusionsNIRF-guided ND significantly improved the nodal yield compared to the control group. Intraoperative real-time optical imaging enabled direct visualization of tumor-related drainage patterns within the neck lymphatics.     

Fluorescence ureteral navigation during laparoscopic surgery for clinically suspected stage T4 colorectal cancer: A cohort study

BackgroundApproximately 15% of patients with colorectal cancer present with locally advanced tumors (T4 stage). Laparoscopic surgery for stage T4 disease has not yet been established.The near-infrared ray catheter fluorescent ureteral catheter (NIRFUC) is a new device that uses near-infrared fluorescence resin.We examined the utility of fluorescence ureteral navigation (FUN) with the NIRFUC during laparoscopic surgery for stage T4 colorectal cancer.Materials and methodsPatients with stage T4 colorectal cancer (n = 143, from January 2017 to March 2021) were divided into a T4FUN + group, in which the NIRFUC was used (n = 21), and a T4FUN- group, in which the NIRFUC was not used (n = 122). Short-term outcomes were compared between the groups.Next, the laparoscopic surgery rate and incidence of ureteral injury from January 2017 to March 2021 were compared between the T4FUN- group and the non-stage T4FUN- group (n = 434, from January 2017 to March 2021), in which fluorescence ureter navigation was not used.ResultsRectal cancer, stage T4b disease, and invasion into the urinary tract were observed more often in the T4FUN + group than in the T4FUN- group.In the comparisons of the T4FUN + versus T4FUN- groups, the operative time was 398 (161–1090) vs. 256 (93–839) minutes, the blood loss was 10 (1–710) vs. 25 (0–1360) ml, and the ratio of laparoscopic surgery to open surgery was 21:0 vs. 79:43. Postoperative complications (Clavien-Dindo grade ≥ III) were present in 2 (10%; 0 ureteral injury) patients in the T4FUN + group and 13 (11%; 2 ureteral injury) patients in the T4FUN- group.In the T4FUN + group, the operative time was longer (p < 0.0001), but the laparoscopic ratio was higher (p = 0.0002), and the blood loss volume and incidence of ureteral injury tended to be lower.In the comparisons of the T4FUN- versus non-stage T4FUN- groups, the ratio of laparoscopic surgery to open surgery was 79:43 vs. 384:50, the incidence of open conversion was 8 (6.6%) vs. 15 (3.5%), and the incidence of ureteral injury was 2 (1.6%) vs. 0 (0%). In the T4FUN- group, the open surgery rate (<0.0001), open conversion rate (p = 0.0205) and incidence of ureteral injury (p = 0.0478) were high, with a significant difference observed between the groups.ConclusionPatients with stage T4 disease have an increased risk of ureteral injury and are more likely to be converted to open surgery.FUN can help to safely increase the laparoscopic surgery rate while safely visualizing the ureter. FUN is recommended for laparoscopic surgery in patients with stage T4 colorectal cancer.Clinical trial registrationExamination of fluorescence navigation for laparoscopic colorectal cancer surgery; Research Ethics Committee of the Kawaguchi Municipal Medical Center (Saitama, Japan) approval number: 2020-3. https://kawaguchi-mmc.org/wp-content/uploads/clinical research-r02.pdf;     

Single-dose combination nanovaccine induces both rapid and durable humoral immunity and toxin neutralizing antibody responses against Bacillus anthracis

Bacillus anthracis, the causative agent of anthrax, continues to be a prominent biological warfare and bioterrorism threat. Vaccination is likely to remain the most effective and user-friendly public health measure to counter this threat in the foreseeable future. The commercially available AVA BioThrax vaccine has a number of shortcomings where improvement would lead to a more practical and effective vaccine for use in the case of an exposure event. Identification of more effective adjuvants and novel delivery platforms is necessary to improve not only the effectiveness of the anthrax vaccine, but also enhance its shelf stability and ease-of-use. Polyanhydride particles have proven to be an effective platform at adjuvanting the vaccine-associated adaptive immune response as well as enhancing stability of encapsulated antigens. Another class of adjuvants, the STING pathway-targeting cyclic dinucleotides, have proven to be uniquely effective at inducing a beneficial inflammatory response that leads to the rapid induction of high titer antibodies post-vaccination capable of providing protection against bacterial pathogens. In this work, we evaluate the individual contributions of cyclic di-GMP (CDG), polyanhydride nanoparticles, and a combination thereof towards inducing neutralizing antibody (nAb) against the secreted protective antigen (PA) from B. anthracis. Our results show that the combination nanovaccine elicited rapid, high titer, and neutralizing IgG anti-PA antibody following single dose immunization that persisted for at least 108 DPI.     

Fluorescence imaging of dental restorations using the VistaCam intra-oral camera

Optical fluorescence imaging methods have a range of forensic applications. The VistaCam system (Dürr Dental) is an existing intra-oral fluorescence camera, which was designed to aid detection of dental caries using 405 nm wavelength light generated by light emitting diodes (LEDs). This study assessed whether this fluorescence imaging device could also be used to recognize dental restorative materials, which is essential for accurate dental charting of deceased persons who are unidentified. The effect of body fluids (saliva and blood) on performance was also assessed. The VistaCam was used on the bench to assess 55 extracted human teeth with restorations, and samples of restorative materials. Readings were first taken in the moist state and then after the application of human saliva or venous blood. Fluorescence scores were compared using one-way ANOVA. Human enamel gave lower fluorescence than restorations. Different tooth-coloured restorative materials gave similar strong fluorescence scores, without statistically significant differences between them. Fluorescence scores were not affected by the presence of ambient fluids (saliva or blood). Using violet 405 nm light to elicit fluorescence may aid in the recognition of dental restorative materials.     

基于荧光定量PCR技术的当归不同炮制品中大肠埃希菌数量测定方法开发及比较研究

目的对当归不同炮制品中大肠埃希菌变化进行定量分析。方法建立荧光定量PCR方法,对当归不同炮制品、不同产地、不同收集企业、不同储藏时间的大肠埃希菌进行定量分析。结果不同炮制品中大肠埃希菌数量变化为生当归土炒当归酒当归;在不同产地的当归中以甘肃岷县地区所含的大肠埃希菌的数量最少;与零售企业相比,生产销售企业的当归和酒当归中大肠埃希菌的数量较少;不同储藏时间对当归和酒当归中大肠埃希菌数量有一定影响,随储藏时间的增加,大肠埃希菌的数量也在增加。对部分代表性样品进行平板计数法与荧光定量PCR法比较时发现,平板计数法结果多呈阴性,荧光定量PCR结果均呈阳性。结论所建立的荧光定量PCR法特异性、灵敏度、可靠性以及报告周期均优于平板计数法,可为当归不同炮制品中大肠埃希菌的快速、准确定量检测提供有效手段。     

LacdiNAc-Glycosylated Prostate-specific Antigen Density is a Potential Biomarker of Prostate Cancer

BackgroundSerum LacdiNAc-glycosylated prostate-specific antigen (LDN-PSA) and LDN-PSA density together with PSA and PSA density (PSAD) were measured as a diagnostic tool for prostate cancer (PCa).Patients and MethodsWe included 150 patients with PCa without hormonal therapy and 41 patients without PCa obtained from the Kyoto University Hospital between 2012 and 2017. LDN-PSA levels were measured through a WFA–anti-PSA antibody sandwich immunoassay using a highly sensitive surface plasmon field-enhanced fluorescence spectroscopy (SPFS) system. Diagnostic performance of serum LDN-PSA and LDN-PSAD was evaluated by measuring the area under the receiver-operating characteristic curve (AUC).ResultsThe AUCs of LDN-PSA, LDN-PSAD, and PSAD levels (0.780, 0.848, and 0.835, respectively) detected in patients with PCa were significantly higher (P = .0001, P < .0001, and P < .0001, respectively) than that of PSA (0.590). Moreover, among 143 patients with PCa who received radical prostatectomy (RP), the AUCs of LDN-PSA, LDN-PSAD, and PSAD levels (0.750, 0.812, and 0.769, respectively) detected in patients with a pathologic Gleason grade group ≥ 2 were significantly higher (P = .0170, P = .0028, and P = .0003, respectively) than that of PSA (0.578). In the group comprising 35 patients who received RP with a Gleason grade group 1-graded biopsy, the LDN-PSA, LDN-PSAD, and PSAD levels were significantly different (P = .0097, P = .0024, and P = .0312, respectively). However, PSA alone could not discriminate cases with adverse features (P = .454).ConclusionsLDN-PSAD is a potential marker for detecting PCa and selecting candidates for RP.