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Κυριακή 7 Αυγούστου 2022

Characterizing the epithelial–mesenchymal transition status of circulating tumor cells in head and neck squamous cell carcinoma

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Abstract

Background

Circulating tumor cells (CTCs), in particular those undergoing an epithelial–mesenchymal transition (EMT), are a promising source of biomarkers in head and neck squamous cell carcinoma (HNSCC). Our aim was to validate a protocol using microfluidic enrichment (Parsortix platform) with flow-cytometry CTC characterization.

Method

Blood samples from 20 treatment naïve HNSCC patients underwent Parsortix enrichment and flow cytometry analysis to quantify CTCs and identify epithelial or EMT subgroups—correlated to clinical outcomes and EMT gene-expression in tumor tissue.

Results

CTCs were detected in 65% of patients (mean count 4 CTCs/ml). CTCs correlated with advanced disease (p = 0.0121), but not T or N classification. Epithelial or EMT CTCs did not correlate with progression-free or overall survival. Tumor mesenchymal gene-expression did not correlate with CTC EMT expression (p = 0.347).

Discussion

Microfluidic enrichment and flow cytometry successfully characterizes EMT CTCs in HNSCC. The lack of association between tumor and CTC EMT profile suggests CTCs may undergo an adaptive EMT in response to stimuli within the circulation.

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Excessive mechanical stress induced temporomandibular joint osteoarthritis via osteoclasts‐mediated osteogenic differentiation of BMSCs

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Abstract

Background

Bone homeostasis is a dynamic process maintained by osteoblasts and osteoclasts, which may be regulated by excessive mechanical stress (EMS).

Objectives

Our study aims to explore the relationship between osteogenic differentiation of BMSCs and EMS-activated osteoclast differentiation of RAW 264.7 cells in order to optimize orthodontic treatment.

Methods

We established the model of EMS in vivo and in vitro. In vivo, HE, Safranin-O staining, micro-CT, and immunofluorescence double-labeling were utilized to assess the changes in condylar, the distributions of osteoblasts, osteoclasts and MAPKs. In vitro, the effects of EMS-activated osteoclast differentiation exerting on osteogenic differentiation of BMSCs were observed by Western Blot, qRT-PCR and Alizarin Red staining. Furthermore, the role of MAPKs in this progress was explored by using inhibitors of MAPKs and co-culture supernatants.

Results

In vivo, EMS led to the degradation of condylar cartilage and destruction of subchondral bone, diagnosed as temporomandibular joint osteoarthritis (TMJ OA). Osteoclasts and osteoblasts were both enriched in subchondral bone, but osteoclast predominated. The expressions of p-JNK, p-ERK1/2, and p-p38 were all activated in vitro and in vivo, which were localized mainly in the Trap+ area in subchondral bone. Interestingly, only the inactivation of p-ERK1/2 in osteoclasts significantly inhibited the osteogenic differentiation of BMSCs in vitro. This revealed that p-ERK1/2 played a key role in the osteoclasts-induced osteogenic differentiation of BMSCs.

Conclusion

Our results proved that EMS led to TMJ OA, in which up-regulated p-ERK1/2 in osteoclasts was mechanosensitive and facilitated the osteogenic differentiation of BMSCs.

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Πέμπτη 4 Αυγούστου 2022

COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection during Delta-dominant and Omicron-dominant periods in Japan: a multi-center prospective case-control study (FASCINATE study)

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Abstract
Background
Although several COVID-19 vaccines initially showed high efficacy, there have been concerns due to waning immunity and the emergence of variants with immune escape capacity.
Methods
A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period, compared to unvaccinated individuals.
Results
The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received mRNA-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% CI: 82-93) 14 days-3 months after dose 2 and 87% (95% CI: 38-97) 3-6 months a fter dose 2. During the Omicron-dominant period, VE was 56% (95% CI: 37-70) 14 days-3 months since dose 2, 52% (95% CI: 40-62) 3-6 months after dose 2, 49% (95% CI: 34-61) 6 + months after dose 2, and 74% (95% CI: 62-83) 14 + days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (i.e. mask-wearing/high-risk behaviors) yielded similar estimates, respectively.
Conclusions
In Japan where most are infection-naïve and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level.
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Prognostic capacity of the transcriptional expression of lactate dehydrogenase A in patients with head and neck squamous cell carcinoma

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Abstract

Background

To analyze the relationship between the transcriptional expression of lactate dehydrogenase A (LDHA) and the disease control in patients with a head and squamous cell carcinoma (HNSCC).

Methods

We determined the transcriptional expression of LDHA in 110 HNSCC patients treated with surgery.

Results

Five-year disease-free survival for patients with a high transcriptional expression of LDHA (n = 51) was 39.2% (95% confidence interval [CI]: 25.3%–53.1%), and for patients with a low expression (n = 59), it was 63.6% (95% CI: 51.1%–76.1%) (p = 0.004). According to the results of a multivariate analysis, patients with a high transcriptional expression of LDHA had a 3.4-fold increased risk of tumor recurrence. Patients with a high transcriptional expression of LDHA tended to show a higher intensity of immunohistochemical expression of LDHA at the tumor cells (p = 0.086).

Conclusion

In HNSCC patients treated with surgery, a high transcriptional expression of LDHA was associated with a significant decrease in disease-free survival.

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Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta‐analysis

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Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta-analysis

The aim of this systematic review and meta-analysis was to determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer. We demonstrated that TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines.


Objective

To determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer.

Methods

PubMed/MEDLINE, Cochrane Library, and Scopus databases were searched. English language, original studies investigating oncological outcomes of TLM in adult patients with recurrent laryngeal cancer were included. Data were pooled using a distribution-free approach for estimating summary local control (LC), disease-specific survival (DSS), and overall survival (OS) curves with random effects.

Results

Two hundred and thirty-five patients underwent salvage TLM after primary (chemo)radiotherapy. The mean follow-up time was 60.8 months (95% CI: 32.7–88.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 74.2% (61.7–89.4), 53.9% (38.5–75.3), and 39.1% (25.2–60.8). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 88.4% (82.0–95.3), 67.8% (50.9–90.3), and 58.9% (42.7–81.1). Two hundred and seventy-one patients underwent TLM after primary laser treatment. The mean follow-up time was 70.9 months (95% CI: 36.9–104.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 72.2% (64.7–80.6), 53.2% (42.2–66.9), and 40.4% (29.6–55.2). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 92.1% (85.5–99.1), 77.0% (64.4–92.0), and 67.1% (51.6–87.3).

Conclusions

TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines.

Level of Evidence

NA Laryngoscope, 2022

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Survival and complications of implant‐supported cantilever fixed dental prostheses with zirconia and metal frameworks: A retrospective cohort study

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Abstract

Background

Current evidence about long-term survival of all-ceramic implant-supported cantilever fixed dental prostheses (cFDP) is limited.

Purpose

To evaluate the survival and complication rates of all-ceramic and metal–ceramic implant-supported cFDPs located in anterior and posterior sites, under consideration of risk factors.

Methods of study

The retrospective analysis compared an experimental group (75 implant-supported cFDPs among 48 patients [mean age 60.47 ± 9.25 years; 21 men]; mean observation period 3.56 years) with a control group (300 implant-supported non-cantilever FDPs [ncFDP] among 241 patients [mean age 62.85 ± 10.72 years; 109 men]; mean observation period 7.25 years). Kaplan–Meier estimates were used to describe the long-term survival and success of both groups. Log-rank tests were used for group comparisons. Mixed-effects Cox proportional hazards regression models were used to examine the effects of restoration- and site-specific risk factors. A random intercept was included in the models to take multiple FDPs per patient into account.

Results

Five-year cumulative survival until loss of restoration was 97.1% (95% confidence interval [CI] 0.93–1.00) for cFDPs and 97.0% (95% CI 0.95–0.99) for ncFDPs. Ten-year survival was 93.7% (95% CI 0.86–1.00) for cFDPs and 92.8% (95% CI 0.87–0.98) for ncFDPs, no difference between the survival curves of these groups was observed. Success differed between cFDPs and ncFDPs (p Log  = 0.002), zirconia and metal frameworks (p Log  < 0.001), and provisional and definitive cements (p Log  = 0.025). The effects of the variables "framework material" and "attachment method" were confirmed in a mixed-effects Cox regression model. Loss of retention was the predominant complication for both cFDPs and ncFDPs and usually affected provisionally cemented FDPs.

Conclusions

cFDPs do not differ from ncFDPs with regard to long-term failure, whereas additional complications were higher for cFDPs. Fewer complications were observed for zirconia frameworks without occlusal veneers and definitive cemented FDPs.

Clinical trial registration: the trial has no registration number because it commenced before January 31, 2017.

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Does the presence of third molars during sagittal split mandibular ramus osteotomy favour complications? Systematic review and meta-analysis

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The aim of this systematic review and meta-analysis was to assess whether the presence of inferior third molars during sagittal split mandibular ramus osteotomy increases the risk of intraoperative and postoperative complications. The PRISMA protocol was followed in this study, and the review was registered in the PROSPERO database (CRD42020147642). A search was conducted in the MEDLINE (PubMed), Web of Science, Cochrane Central, and Scopus databases on November 1, 2021. Nineteen articles were included, and the variables analysed were unfavourable fractures, infection, neurosensory disturbance, removal of osteosynthesis material, and duration of surgery. (Source: International Journal of Oral and Maxillofacial Surgery)
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Τετάρτη 3 Αυγούστου 2022

Long‐Term Outcomes of End‐Flexible‐Rigidscopic Transoral Surgery for Pharyngolaryngeal Cancer

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Objective

End-flexible-rigidscopic transoral surgery (E-TOS) is a new and minimally invasive transoral surgery for resection of Tis-selected T3 pharyngolaryngeal cancers. We evaluated long-term oncological outcomes and whether postoperative voice and swallowing function were preserved following E-TOS.

Methods

In this retrospective single-center study, 154 patients treated with E-TOS using a curved retractor, flexible-tip rigid endoscope, and thin curved instruments were included. Their survival rate, larynx preservation rate, and disease control rate were estimated using the Kaplan–Meier method. Postoperative voice function was evaluated using both objective and subjective tests. Postoperative swallowing function was assessed using the Hyodo score and the functional outcome swallowing scale.

Results

The 3-year and 5-year overall survival, disease-specific survival, disease-free survival, laryngectomy-free survival, local control, and loco-regional control rates post E-TOS were 89.8% and 82.2%, 95.6% and 92.3%, 78.5% and 70.3%, 87.2% and 80.9%, 93.9% and 92.5%, and 87.2% and 85.7%, respectively. Both objective and subjective postoperative voice and swallowing function tests were within normal limits in more than 90% of the patients.

Conclusion

E-TOS is an effective, safe, low-cost, and minimally invasive transoral surgery for Tis-selected T3 pharyngolaryngeal cancer; it also preserves postoperative voice, larynx, and swallowing function.

Level of Evidence

4 Laryngoscope, 2022

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Extrarenal Wilms tumor with hypertension and dilated cardiomyopathy in an infant: A report of an unusual case

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Abstract

While Wilms tumors are the most frequently detected kidney cancer type in children, extrarenal Wilms tumors (ERWTs) remain rare. This report is the first to describe hypertension and dilated cardiomyopathy in a patient with an ERWT. A 6-month-old male infant presented with an abdominal mass and paroxysmal hypertension; echocardiography revealed dilated cardiomyopathy with an ejection fraction of 34%, as well as substantially increased plasma renin activity. Pathology yielded a definitive diagnosis of ERWT. Cardiac function and blood pressure gradually returned to normal after tumorectomy. The early diagnosis of such a tumor together with efficient oncologic treatment are vital to optimal patient outcomes.

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Non‐carious cervical lesions (NCCLs): morphology and progression, prevalence, etiology, pathophysiology, and clinical guidelines for restoration

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Abstract

Purpose

: To synthesize the literature regarding non-carious cervical lesions (NCCLs) and propose clinical guidelines when lesion restoration is indicated.

Material and Methods

: A PubMed search was performed related to NCCL morphology, progression, prevalence, etiology, pathophysiology, and restoration.

Results

: NCCLs form as either rounded (saucerlike) depressions with smooth, featureless surfaces that progress mainly in height or as V-shaped indentations that increase in both height and depth. Prevalence ranges from less than 10% to over 90% and increases with age. Common locations are the facial surfaces of maxillary premolars. They have a multifactorial etiology due to personal habits such as excessive horizontal toothbrushing and consumption of acidic foods and drinks. Occlusal factors have been identified as contributing to the prevalence of NCCLs in some studies whereas other studies indicate there is no relationship. The concept of abfraction has been proposed whereby mechanical stress from occlusal loading plays a role in the development and progression of NCCLs with publications supporting the concept and others indicating it lacks the required clinical documentation. Regardless of the development mechanism, demineralization occurs and they are one of the most common demineral ization diseases in the body. Treatment should be managed conservatively through preventive intervention with restorative treatment delayed until it becomes necessary due to factors such as lesion progression, impact on patient's quality of life, sensitivity, poor esthetics, and food collection may necessitate restoration. Composite resins are commonly used to restore NCCLs although other materials such as glass ionomer and resin-modified glass ionomer are also used. Sclerotic dentin does not etch like normal dentin and therefore it has been recommended to texture the dentin surface with a fine rotary diamond instrument to improve restoration retention. Some clinicians use mechanical retention to increase retention. Beveling of enamel is used to increase the bonding area and retention as well as enhance the esthetic result by gradually creating a color change between the restoration and tooth. Both multi-step and single-step adhesives have been used. Dentin etching should be increas ed to 30 seconds due to the sclerotic dentin with the adhesive agent applied using a light scrubbing motion for 20 seconds but without excessive force that induces substantial bending of a disposable applicator. Both flowable and sculptable composite resins have been successfully used with some clinicians applying and polymerizing a layer of flowable composite resin and then adding an external layer of sculptable composite resin to provide enhanced resistance to wear. When caries is present, silver diamine fluoride has been used to arrest the caries rather than restore the lesion.

Conclusions

: Non-carious cervical lesions (NCCLs) form as smooth saucerlike depressions or as V-shaped notches. Prevalence values as high as 90% and as low as 10% have been reported due to habits such as excessive toothbrushing and an acidic diet. Occlusal factors have been proposed as contributing to their presence but it remains controversial. Publications have both supported and challenged the concept of abfraction. They are one of the most common demineralization diseases in the body. Conservative treatment through prevention is recommended with restorative treatment delayed as long as possible. When treatment is needed, composite resins are commonly used with proposed restorative guidelines including texturing the sclerotic dentin, beveling the enamel, potential use of mechanical retention, 30 seconds of acid etching, and use of either multi-step or single-step adhesives in conjunction with a light scrubbing motion for 20 seconds without excessive force placed on disposable applicators.

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