Cervical Neck Research Articles

Clinical Implication of Cervical Pain on Posture among Teaching Professionals Aged Between 25-35 Years- A Cross Sectional Study

Cervical pain is amongst the incessant musculoskeletal disorders having a prevalence of 30% up to 60 % among teaching professionals. Cervical pain also known as neck pain; have consequences which are very severe among several working populations. Primary objective of study was to find out consequences of cervical neck pain on scapula position. Present study will embrace us about clinical implications of cervical pain on static scapular position further significant positive result lead to formation of specific scapular rehabilitation program for teaching professionals keeping all risk factors and their work ergonomics. Cross-sectional Comparative study design was used to identify the effect of cervical pain over resting position of scapula position with respect to scapula protraction and scapula upward rotation among 107 school teachers further to mention it is an extension of research work of primary author on school teachers. Scapula protraction was assessed at three different positions i.e at rest, 45-degree shoulder flexion and 90-degree glenohumeral abduction and scapula upward rotation was examined with the help of baseline digital inclinometer at four different positions. Results exhibit changes in scapula protraction and upward rotation among school teachers keeping p value < 0.001. Since school teachers primarily work on computer screen for teaching and preparation of lesson plans, this executes enormous load on teachers as they have to work continuously in static cervical posture for long hours continuously which executes significant load on neck and scapulothoracic musculature and alters the mechanics cervical pain results in statistically significant changes in scapula position i.e., scapula protraction, and scapula upward rotation in primary school teachers in all examined positions.

The Necessity of a Locally Active Antidote in the Clinical Practice of Botulinum Neurotoxin Therapy: Short Communication.

Recently, it was demonstrated that copper complexes and 3,4-diaminopyridine can effectively reduce the activity of the botulinum neurotoxin light chain. The aim of the present study was to indicate that treatment with an antidote may have a major influence, not only on the extremely rare disease of botulism, but also on the much more frequently occurring side effects experienced during BoNT therapy. This was a retrospective chart review of patients who were regularly treated with BoNT for various indications. The percentage of patients with clinical signs of overdosing was determined. In patients with facial dystonia, double vision and ptosis occurred as side effects. In patients with cervical dystonia, neck weakness and dysphagia were observed as the most frequent side effects. In oromandibular and oropharyngeal dystonia, abnormal tongue movements and dysphagia occurred frequently. In writer’s cramp and mild post-stroke hand spasticity, severe paresis of the injected and non-injected finger muscles was observed. Additionally, in the BoNT treatment of pain syndromes (such as tension headaches or migraines), neck weakness may occur. Across all indications for clinical BoNT applications, clinical signs of BoNT overdosing may occur in up to 5% of the BoNT-treated patients. Therefore, the development of an antidote for BoNT overdoses would be very much appreciated and would have a major influence on the management of BoNT therapy.

Effectiveness of Ozone-Oxygen Mixture by Ultrasonography-Guided Facet Medial Branch Block in the Treatment of Cervicogenic Dizziness

Purpose: Among many central and peripheral causes of vertigo, one of the factors whose pathophysiology is not yet understood is cervicogenic dizziness (CD). There are studies reporting that CD may benefit from facet joint medial bundle branch block (MBB). The purpose of our study was to share our experiences of MBB application using ultrasonography (USG) in patients diagnosed with CD. Materials and Methods: After physical examination and necessary cervical imaging, C1, C2 and C3 cervical facet joint MBB and ozone injection were performed using USG for patients who had vertigo and accompanying cervical pathology and neck pain. In order to evaluate the effectiveness of the treatment, pain levels with the Visual Analog Scale (VAS) and the effect of vertigo on the quality of life with the “Dizziness Handicap Inventory (DHI)” Turkish validation questionnaire were documented. Results: Thirty-five patients who met the criteria were included in the study. The mean age of the patients was 50.8 ± 10.7. Of the 35 patients, 10 (28.6%) were male and 25 (71.4%) were female. There was a significant difference between the preoperative period and the postoperative 1st, 2nd, and 6th week VAS scores. A significant difference was found between the preoperative and the postoperative 2nd and 6th week DHI questionnaire survey results as well. Conclusions: In the follow-up after the procedures, it was observed that vertigo complaints of the patients decreased significantly.

Correlation of Intensity of Pain, Functional Disability and Deep Neck Flexor Endurance in Individual with Chronic Non-Specific Neck Pain: An Observational Study

Background: Musculoskeletal deficits of the craniocervical region play an important role in causing various cervical disorders. Cervical disorders and neck pain are almost as prevalent as low back pain and like low back pain; in most of the cases it is difficult to determine the actual cause of neck pain hence it is regarded as “non-specific neck pain”. This study was conducted to determine the correlation between deep neck flexor endurance, the intensity of pain, and functional disability in individuals with chronic non-specific neck pain. Materials and methods: A cross-sectional observational study was conducted on twenty individuals with chronic non-specific neck pain. Numerical Pain Rating Scale (NPRS), Neck Disability Index (NDI), and Craniocervical Flexion Test (CCFT) were used to measure neck pain intensity, neck disability, and deep neck flexor endurance respectively. The correlation was found using the Pearson Correlation Coefficient test. Result: The results showed that there was a positive correlation found between NPRS and NDI, and CCFT has negative correlations with NPRS and NDI respectively. Conclusion: The findings suggest that the lesser deep neck flexor endurance corresponded to greater neck pain intensity and disability. Keywords: cervical spine, neck disability index, neck pain, craniocervical flexion test, deep neck flexors endurance, correlation.

64-Year-Old Woman With Aphasia and Troponin Elevation

64-Year-Old Woman With Aphasia and Troponin Elevation

Effectiveness of isometric exercises on disability and pain of cervical spondylosis: a randomized controlled trial

BackgroundNeck pain and disability is a significant public health problem with only very few evidence-based treatment option. The aim of this study was to evaluate the effect of isometric exercise on pain and disability of cervical spondylosis.MethodsTwenty four patients with cervical osteoarthritis and neck pain (22 females and 2 males; mean age, 46.70 ± 13.71 years) were recruited and randomly allocated into 2 arms: neck isometric exercises (n = 12) and conservative management without exercise (n = 12). The Neck Disability Index (NDI) and Neck Pain and Disability Scale (NPAD) were used to assess participants at baseline and after 4 weeks.ResultsBasic characteristics, NDI score and NPAD score were not significantly different between groups at baseline. The exercise arm demonstrated significantly lower scores regarding NDI (mean, 17.41 vs. 25.58; P-value = 0.035) and NPAD (mean, 25.33 vs. 66.67; P < 0.001), compared to the control arm after 4 weeks. The exercise arm also showed significant within group reduction considering NDI and NPAD scores after 4 weeks (Both, P < 0.001).ConclusionOur findings suggested that isometric exercises might be a beneficial treatment for improving pain and disability caused by cervical spondylosis.Trial registration This study was registered at irct.ir (Iranian Registry of Clinical Trials) with the code IRCT20220206053950N1, 07.05.2022, retrospectively registered.

Abstract CT241: ENVOY-001: A phase 1, multicenter, open-label study of SQZ-AAC-HPV as monotherapy and in combination with immune checkpoint inhibitors in HLA-A*02+ patients with HPV16+ recurrent, locally advanced, or metastatic solid tumors

Abstract Background: AAC-HPV consists of autologous RBCs engineered using Cell Squeeze® technology to deliver synthetic long peptides (SLP) of HPV16 E6, E7 and the adjuvant, poly I:C. After intravenous (IV) administration, the AACs are designed to be phagocytosed by endogenous antigen presenting cells (APCs) and the E6 and E7 antigens presented on the APC’s major histocompatibility complexes (MHCs). The concurrent delivery of antigen and adjuvant to the APCs is designed to elicit a potent antitumor T cell response to drive HPV16+ tumor killing. Preclinical experiments demonstrated that post IV administration of mouse AAC-HPV in a HPV16 E7-expressing TC-1 mouse model, E7 specific CD8+ T cells are recruited to the tumor, inhibiting tumor growth, prolonging survival, and forming immunological memory. Murine AAC-HPV treatment was also shown to be synergistic with cisplatin combinations. In vitro studies with human volunteer derived SQZ-AAC-HPV demonstrated to be endocytosed by dendritic cells and drive IFN-gamma production by T cell clones specific to human E7. The Phase 1/2 study’s biomarker program investigates whether pharmacodynamic effects observed in nonclinical studies correlate with potential clinical benefit. Immunogenic and pharmacodynamic endpoints include quantification and characterization of TILs and tumor microenvironment, changes in numbers and functions of circulating blood cells. In addition, cytokine responses and cell-free HPV16 DNA will be measured. Methods: ENVOY-001 (NCT04892043) is open for enrollment to HLA A*02+ patients with HPV16+ recurrent, locally advanced, or metastatic solid tumors and includes escalation cohorts for monotherapy and in combination with anti-PD-1 and anti-CTLA-4 checkpoint inhibitors. The study is divided in two parts, the first will assess the safety in monotherapy dose-escalation following a Bayesian Optimal Interval approach. The second part of the study will assess the safety of SQZ-AAC-HPV when combined with nivolumab 360 mg q3w and/or ipilimumab 3 mg/kg q3w x4 or 1 mg/kg q6w when combined with nivolumab. The cycle length is 3 weeks, and patients will receive SQZ-AAC-HPV for up to 1 year or until available autologous drug product is exhausted. Eligible patients including but not limited to anal, cervical and head and neck tumors will undergo a 200 mL whole blood collection at the study site. The manufacturing process takes less than 24 hours to produce multiple cryopreserve patient doses and this therapy does not necessitate pre-conditioning. The vein-to-vein time for the 1st administration is approximately one week. Patients must have a lesion that can be biopsied with acceptable clinical risk and agree to have a fresh biopsy at Screening and on study. A Data Monitoring Committee is in place. No formal statistical hypothesis testing will be performed. Results: N/A Conclusions: N/A Citation Format: Victoria Villaflor, Rajwanth Veluswamy, Elena Garralda, Richard Maziarz, Emese Zsiros, Anthony Shields, Mariano Ponz-Sarvise, Martijn Lolkema, Mehdi Brahmi, Julia Jennings, Nathan Miselis, Lindsay Moore, Katarina Blagovic, Rui-Ru Ji, Scott Loughhead, Ricardo Zwirtes, Sandip Patel. ENVOY-001: A phase 1, multicenter, open-label study of SQZ-AAC-HPV as monotherapy and in combination with immune checkpoint inhibitors in HLA-A*02+ patients with HPV16+ recurrent, locally advanced, or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT241.

Robot-Assisted Total Thyroidectomy with or without Robot-Assisted Neck Dissection in Pediatric Patients with Differentiated Thyroid Cancer.

Pediatric thyroid cancer more frequently develops cervical node metastasis than adult thyroid cancer, even in differentiated thyroid carcinoma (DTC). Thus, cervical neck dissection often needs to be performed simultaneously with thyroidectomy in pediatric patients. Herein, we describe our experience with robot-assisted total thyroidectomy with/without robot-assisted neck dissection in pediatric patients compared with the conventional operated group. A total of 30 pediatric patients who underwent thyroidectomy for DTC between July 2011 and December 2019 were retrospectively reviewed. Among them, 22 underwent robot-assisted operation, whereas 8 underwent conventional operation. There was no statistical difference in the mean operation times, blood loss, drainage amounts, and hospital stay length between the robot-assisted and conventional operation groups; however, the operation time was less in the retroauricular approach subgroup (robot-assisted operation group) with better satisfaction on cosmesis. No postoperative complications, such as seromas, hemorrhages, or hematomas were observed. Our experience suggested that robot-assisted thyroidectomy with or without neck dissection through the retroauricular approach is a feasible and safe alternative treatment, producing outstanding esthetic results compared to the conventional approach, especially in pediatric patients with DTC.

APOBEC3: Friend or Foe in Human Papillomavirus Infection and Oncogenesis?

Human papillomavirus (HPV) infection is a causative agent of multiple human cancers, including cervical and head and neck cancers. In these HPV-positive tumors, somatic mutations are caused by aberrant activation of DNA mutators such as members of the apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytidine deaminases. APOBEC3 proteins are most notable for their restriction of various viruses, including anti-HPV activity. However, the potential role of APOBEC3 proteins in HPV-induced cancer progression has recently garnered significant attention. Ongoing research stems from the observations that elevated APOBEC3 expression is driven by HPV oncogene expression and that APOBEC3 activity is likely a significant contributor to somatic mutagenesis in HPV-positive cancers. This review focuses on recent advances in the study of APOBEC3 proteins and their roles in HPV infection and HPV-driven oncogenesis. Further, we discuss critical gaps and unanswered questions in our understanding of APOBEC3 in virus-associated cancers.

Assessment of a 4-chemokine signature in prediction of T-cell inflammation and response to immune checkpoint inhibition across tumor types.

2558 Background: Immune checkpoint inhibitors (ICI) are highly effective in select cancers. Novel predictors of T cell-inflammation may identify a broader subset of tumors with ICI responsiveness. Our group has identified four chemokines (CCL4, CCL5, CXCL9, CXLC10) able to predict a T cell-inflamed phenotype in primary and metastatic pancreatic tumors. Here, we test whether this 4-chemokine signature can predict T cell-inflammation across additional tumor types and response to ICI. Methods: Using matched genomic and transcriptomic data from 6,455 patients spanning 25 tumor types from The Cancer Genome Atlas, we searched for associations between the 4-chemokine signature and metrics of antitumor immunity. Further, we tested the association of this signature with markers of DNA damage repair deficiency. We also investigated the ability of this signature to predict response to immunotherapy using real-world data from a pan-cancer cohort of 82 patients in the Personalized OncoGenomics Program who had received ICI. Results: The majority of tumor types displayed sub-populations with high expression of the 4-chemokines (4-chemokinehi) and transcriptional hallmarks of the cancer-immunity cycle. Testicular germ cell tumors, cervical squamous cell carcinomas, and head and neck squamous cell carcinomas were the strongest expressors of the signature. Immunomodulatory genes, including PD-L1, PD-1, TIM3, LAG3, TIGIT, CTLA-4, and FASLG, were significantly overexpressed (p&lt;0.05) in the 4-chemokinehi cohorts. Genesets of processes involved in the cancer-immunity cycle, including MHC I expression and cytolytic activity, were upregulated in the 4-chemokinehi cohorts (p&lt;0.05). While a global relationship between tumor mutation burden (TMB) and 4-chemokine expression across tumor histological type was seen (rho=0.42, p=0.02), high TMB was associated with only a subset of 4-chemokinehi tumors. Among patients treated with ICIs, those with 4-chemokinehi tumors had a longer median time to progression (104 versus 71 days, p=0.013) and overall survival (391 versus 195 days, p=0.016). The 4-chemokine signature outperformed TMB for overall survival prediction. Conclusions: Sub-populations of T cell-inflamed patients exist across tumor types and may therefore respond favourably to ICI. The 4-chemokine signature has the potential to select a wider spectrum of patients that may benefit from ICIs. [Table: see text]

Phase I study of HFB200301, a first-in-class TNFR2 agonist monoclonal antibody in patients with solid tumors selected via Drug Intelligent Science (DIS).

TPS2670 Background: Tumor necrosis factor receptor-2 (TNFR2) is expressed on effector CD8+ T cells, CD4+ T cells, T regulatory cells, natural killer cells, and myeloid cells. Targeting TNFR2 is anticipated to yield effective anti-tumor immunity by stimulating T-cell and NK-cell activation and proliferation in the tumor microenvironment. HFB200301 is a first-in-class anti-TNFR2 agonistic monoclonal antibody that triggers both innate and adaptive immune stimulation by binding to a specific epitope on TNFR2. HFB200301 has demonstrated dose-dependent anti-tumor activity in human TNFR2 knock-in mice bearing MC38 and Hepa1-6 syngeneic tumors. Methods: HFB200301 is being evaluated in a first-in-human, open-label, multi-center, dose escalation and expansion study in adult patients with advanced solid tumors. A single-cell immune profiling platform, DIS, was deployed to identify unique tumor-infiltrating T cell signatures that could help optimize patient selection for HFB200301 treatment. It is hypothesized that the presence of an effector T cell subpopulation that express both TNFR2 and CD8A in solid tumors may represent a tumor microenvironment favorable to TNFR2 agonism. The following cancer indications have been identified based on the prevalence of a TNFR2 high/CD8 high signature: Epstein-Barr Virus positive (EBV+) gastric cancer, clear cell renal cell carcinoma (ccRCC), cutaneous melanoma, testicular germ cell tumor (TGCT), soft tissue sarcoma (STS), and PD-L1+ cancers: cervical cancer, pleural mesothelioma, lung adenocarcinoma, and head and neck squamous cell carcinoma (HNSCC). The escalation portion of the study explores increasing doses in cohorts of up to six patients, utilizing mTPI-2 design to determine recommended dose(s) for expansion (RDE(s)). Based on pharmacokinetic modeling to maximize HFB200301 activity, 60-minute intravenous infusions of HFB200301 are administered every 4 weeks. Once RDE(s) is determined, expansion into three indication-specific cohorts is planned to determine the recommended phase 2 dose (RP2D). Key eligibility criteria include histologically documented advanced or metastatic solid tumors in the above listed indications. Patient enrollment opened in February 2022 in the USA, with plans for additional clinical sites in Spain and China. The primary objective is to identify the RDE, characterize safety and tolerability of HFB200301, and determine RP2D. Secondary objectives include pharmacokinetic parameters, preliminary evidence of anti-tumor efficacy (e.g., ORR, DCR, DOR) and pharmacodynamic evaluation (e.g., T cell subsets) in the blood and in the tumor. Furthermore, a potential predictive biomarker signature derived based on the DIS single-cell immune profiling approach will be investigated retrospectively. Clinical trial information: NCT05238883.

Circulating Virus-Host Chimera DNAs in the Clinical Monitoring of Virus-Related Cancers.

Simple SummaryCell-free tumor DNA (ctDNA), the DNA released into circulation from tumors, is a promising tumor marker with versatile applications. The associations of the amount, somatic mutation frequency, and epigenetic modifications of ctDNA with the tumor burden, tumor behavior, and prognosis have been widely investigated in different types of tumors. However, there are still some challenging issues to be resolved before ctDNA can complement or even replace current serum tumor markers. We propose employing exogenous viral DNA integration that produces unique virus–host chimera DNA (vh-DNA) at junction sites. Cell-free vh-DNA may become a new biomarker because it overcomes background interference detection problems, takes advantage of virus tropism to localize the tumor, and acts as a universal marker for monitoring clonal expansion or tumor loads in tumors related to oncogenic viruses.The idea of using tumor-specific cell-free DNA (ctDNA) as a tumor biomarker has been widely tested and validated in various types of human cancers and different clinical settings. ctDNA can reflect the presence or size of tumors in a real-time manner and can enable longitudinal monitoring with minimal invasiveness, allowing it to be applied in treatment response assessment and recurrence monitoring for cancer therapies. However, tumor detection by ctDNA remains a great challenge due to the difficulty in enriching ctDNA from a large amount of homologous non-tumor cell-free DNA (cfDNA). Only ctDNA with nonhuman sequences (or rearrangements) can be selected from the background of cfDNA from nontumor DNAs. This is possible for several virus-related cancers, such as hepatitis B virus (HBV)-related HCC or human papillomavirus (HPV)-related cervical or head and neck cancers, which frequently harbor randomly integrated viral DNA. The junction fragments of the integrations, namely virus–host chimera DNA (vh-DNA), can represent the signatures of individual tumors and are released into the blood. Such ctDNA can be enriched by capture with virus-specific probes and therefore exploited as a circulating biomarker to track virus-related cancers in clinical settings. Here, we review virus integrations in virus-related cancers to evaluate the feasibility of vh-DNA as a cell-free tumor marker and update studies on the development of detection and applications. vh-DNA may be a solution to the development of specific markers to manage virus-related cancers in the future.

Localization of Ectopic Mediastinal Parathyroid Adenomas Using Indigo Carmine Injection for Surgical Management: A Preliminary Report.

An ectopic parathyroid adenoma (EPA) is a rare entity. The aim of this study was to report our experience in the preoperative localization and surgical management of EPAs. This was a multicenter retrospective study involving patients diagnosed with an EPA (three males and seven females) from January 2005 to November 2021. The clinical features, preoperative management, and surgical procedures were analyzed. A cervical neck ultrasound was performed in all patients and showed a focus in eight patients. Cervicothoracic enhanced computed tomography was performed in all patients and showed a focus in nine patients. The 99mTc-MIBI scintigraphy was performed in eight patients and showed uptake in six of them. We performed a neck dissection and thoracotomy in one patient, a thoracoscopy in one patient, surgery with a focused approach in seven patients, four of whom were injected with indigo carmine blue, and surgery with a bilateral approach in one patient. 1 h following the parathyroidectomy, the parathyroid hormone (PTH) concentration was decreased to 40–80% of the baseline value. Establishing a preoperative diagnosis of an EPA is challenging for the surgeon, despite the progress in the morphologic assessment. An intraoperative PTH assay and injection of indigo carmine have been shown to be valuable tools in the appropriate surgical management of an EPA.

Normal and Abnormal Development of Left Vertebral Artery and its Implications in Cervical Region Surgery

Anomalies occur in branches arising from the aortic arch (AA) in approximately 3‐5% of cadaveric cases (Lazaridis et al. 2018; Natsis et al. 2021), and these atypical branches remain a point of discussion in cervical neck surgery. Here, we describe a 73‐year‐old Caucasian female who died of renal failure following a complicated urinary tract infection whose left vertebral artery (VA) originated from the AA between the left common carotid and subclavian arteries. The preforaminal part of the left VA was 3.5 mm in diameter and entered the C5 transverse foramen while the right VA arising from the right subclavian artery was 4.2 mm in diameter and entered the C5 transverse foramen normally. Embryologically, the VAs are formed during weeks 4 through 8 by development of longitudinal anastomoses linking the cervical intersegmental arteries (ISA). The ISA regresses except the seventh, which becomes the proximal subclavian artery, the point of origin of the adult VA. Persons with left VAs that arise from the AA may be asymptomatic; however, secondary dilatation of the right VA may be implicated in the development of cerebrovascular disorders and atherosclerotic changes due to increased blood flow. Additionally, the recognition of the anomalous origin and anatomical positioning of a left VA is important when considering an anterior approach for cervical spine surgery (Tardieu et al. 2017) and other head‐neck procedures when soft structures such as arteries, veins and muscles are retracted to reach the cervical spine.

Integrating BRAFV600E mutation, ultrasonic and clinicopathologic characteristics for predicting the risk of cervical central lymph node metastasis in papillary thyroid carcinoma

BackgroundThe advantages of prophylactic central lymph node dissection (CLND) for clinically node-negative patients remained a great deal of controversies. Our research was aimed to analyze the relationship between cervical central lymph node metastasis (CLNM) and BRAFV600E mutation, ultrasonic and clinicopathologic characterizes in papillary thyroid carcinoma (PTC).Methods and materialsIn current study, a total of 112 consecutive PTC patients who experienced thyroidectomy plus cervical central neck dissection were included in our research. All PTC were pre-operatively analyzed by ultrasonic features, including tumor size, multifocality or not, tumor location, internal components, echogenicity, microcalcification, margins, orientation, taller than wide shape, and internal vascularity. The presence of clinicopathologic factors, including age, sex, T stage, Hashimoto’s thyroiditis, and BRAFV600E mutation was then investigated. Univariate and multivariate analysis were conducted to check into the relationship between predictive factors and cervical CLNM in PTC patients, and then a predictive model was also established.ResultsPathologically, 58.0% (65/112) of the PTC patients harbored cervical CLNM. Univariate and multivariate analysis were conducted to identify age < 55 years, tumor size > 10 mm, microcalcification, non-concomitant Hashimoto’s thyroiditis and BRAFV600E mutation were predictive factors for cervical CLNM in PTC. The risk score for cervical CLNM in PTC patients was calculated: risk score = 1.284 × (if age < 55 years) + 1.241 × (if tumor size > 10 mm) + 1.143 × (if microcalcification) – 2.097 × (if concomitant Hashimoto’s thyroiditis) + 1.628 × (if BRAFV600E mutation).ConclusionAge < 55 years old, PTC > 10 mm, microcalcification, non-concomitant Hashimoto’s thyroiditis and BRAFV600E mutation are predictive factors for cervical CLNM. BRAFV600E mutation by pre-operative US-FNA technology synergized with clinicopathologic and ultrasonic features is expected to guide the appropriate surgical management for PTC patients.

198: ROBOTIC ASSISTED TRANS CERVICAL ESOPHAGECTOMY (RACE PROCEDURE): DESCRIPTION OF THE SURGICAL TECHNIQUE AND PRELIMINARY RESULTS

Abstract Background and aim A combined trans-hiatal and transcervical approach to perform esophagectomy has been described in the literature for patients who are not candidates for a transthoracic approach. In this context, the technical limitations of conventional laparoscopy might be overcome by the application of robotic systems such as the DaVinci Xi. We aimed at describing the technical details and the feasibility of our technique for the robotic-assisted trans-cervical esophagectomy (RACE) and a preliminary case series. Methods In the abdominal phase the DaVinci Xi is docked using the standard 5-trocar configuration used for Ivor-Lewis esophagectomy. After gastric mobilization, tubulization and D2 lymphadenectomy, the dissection is advanced trans-hiatally until the tracheal carina. Infra-tracheal lymph-node dissection is normally feasible from the abdomen. A left cervical incision and neck lymph node dissection are performed, the esophagus is encircled. The robot is docked at the neck using a gel port with a 3-trocar configuration and an assistant-trocar for suction. The upper mediastinal preparation starts by dissecting the esophagus from the mediastinal pleura bilaterally, the pars membranacea anteriorly and the aortic arch proceeding caudally. Dissection of the left recurrent laryngeal nerve (l-RLN) lymph nodes can be achieved; care should be taken to avoid nerve injuries. Proceeding caudally, the tracheal dissection is advanced to the left bronchus. The azygos vein is encountered at the right tracheobronchial angle. Dissection of bronchial lymph nodes is performed bilaterally, the plane is connected to the previous abdominal plane. After retrieval of the specimen an end-to-side circular stapled anastomosis is performed at the neck. Results The procedure was completed in 4 patients with mid-esophageal squamous cell carcinoma who were not candidate for a trans-thoracic approach due to cardio-pulmonary comorbidities. Median hospital stay was 14 (9–18) days, median ICU stay was 4 (1–6) days. Left vocal cord palsy requiring rehabilitation therapy occurred in 2 patients (50%). No postoperative mortality was recorded. R0 resection was achieved in all patients with a median of 19 (15–22) retrieved lymph nodes. Conclusion RACE using the robotic system is feasible and provides an adequate surgical radicality. The procedure is safe, although the rate of RLN injury is higher.

Improving Patients' Life Quality after Radiotherapy Treatment by Predicting Late Toxicities.

Simple SummaryOver 50% of patients with cancer will receive radiotherapy treatment. Five to ten percent of patients who received radiotherapy will develop side effects. Identifying these patients before treatment start would allow for treatment modification to minimize these effects and improve the life quality of these patients. Our team developed a test, which allows predicting these secondary effects before starting the treatment. This will help in proposing personalized treatments to improve the outcome. This review presents how this test is performed, its results, as well as its modification in order to be used in hospitals.Personalized treatment and precision medicine have become the new standard of care in oncology and radiotherapy. Because treatment outcomes have considerably improved over the last few years, permanent side-effects are becoming an increasingly significant issue for cancer survivors. Five to ten percent of patients will develop severe late toxicity after radiotherapy. Identifying these patients before treatment start would allow for treatment adaptation to minimize definitive side effects that could impair their long-term quality of life. Over the last decades, several tests and biomarkers have been developed to identify these patients. However, out of these, only the Radiation-Induced Lymphocyte Apoptosis (RILA) assay has been prospectively validated in multi-center cohorts. This test, based on a simple blood draught, has been shown to be correlated with late radiation-induced toxicity in breast, prostate, cervical and head and neck cancer. It could therefore greatly improve decision making in precision radiation oncology. This literature review summarizes the development and bases of this assay, as well as its clinical results and compares its results to the other available assays.

Hinokitiol Dysregulates Metabolism of Carcinoma Cell Lines and Induces Downregulation of HPV16E6 and E7 Oncogenes and p21 Upregulation in HPV Positive Cell Lines

Background: Hinokitiol (β-thujaplicin), isolated from the wood of Chamaecyparis taiwanensis, has a wide variety of biological properties including anti-inflammatory, anti-microbial, and anti-tumor effects. Therefore, hinokitiol has become a frequent additive in oral and other healthcare products. Objectives: Our goal was to determine the anti-tumor activity of hinokitiol on human papillomavirus (HPV) positive (n = 3) and negative (n = 2) cell lines derived from cervical or head and neck squamous cell carcinoma (HNSCC) and keratinocyte cell lines (n = 3) transformed spontaneously or with HPV16E6 and E7 oncogenes. Methods: The cell-lines were exposed to hinokitiol at different concentrations (0–200 µM) for 24 h. Cell metabolism, proliferation, and the cell cycle distribution were assessed by MTT- and 3H-thymidine incorporation and flow cytometry. Expressions of p21 and on HPV16E6 and E7 oncogenes were assessed by qPCR. Results: In all carcinoma cell lines, hinokitiol treatment declined the metabolic activity irrespective of the HPV status. This decline was statistically significant, however, only in HPV-positive cell lines CaSki and UD-SCC-2 when exposed to hinokitiol concentrations at 100 and 200 µM, respectively (p &lt; 0.05). Immortalized cell lines, HMK and HPV-positive IHGK, were more sensitive as a similar metabolic effect was achieved at lower hinokitiol concentrations of 3.1, 6.25, and 50 µM, respectively. Hinokitiol blocked DNA synthesis of all carcinoma cell lines without evident association with HPV status. G1 cell cycle arrest and p21 upregulation was found in all cell lines after hinokitiol treatment at higher concentration. However, when the p21 results of all HPV-positive cells were pooled together, the increase in p21 expression was statistically significantly higher in HPV-positive than in HPV-negative cell lines (p = 0.03), but only at the highest hinokitiol concentration (200 µM). In HPV-positive cell lines hinokitiol declined the expression of HPV16E7 and E6 along the increase of p21 expression. The dose-dependent inverse correlation between p21 and E7 was statistically significant in SiHa cells (r = −0.975, p-value = 0.03) and borderline in UD-SCC-2 cells (r = −0.944, p-value = 0.06), in which p21 and E6 were also inversely correlated (r = −0.989). Conclusions: Our results indicate that hinokitiol might have potential in preventing the progress of immortalized cells toward malignancy and the growth of malignant lesions. Hinokitiol can also influence on the progression of HPV-associated lesions by downregulating the E6 and E7 expression.

Challenges in managing the isolated cervical lymphadenopathy in absence of thyroid nodule

Differentiated thyroid cancer make up the vast majority of thyroid cancers with papillary thyroid cancer representing 84% of all thyroid cancer diagnoses. Papillary carcinoma of the thyroid presenting primarily as lateral neck swelling is rare. In the absence of thyroid swelling further evaluation should be done to exclude the primary tumors of scalp and head and neck region. Diagnosis of this condition is made by ultrasound guided FNAC. Surgery is the main treatment modality of choice. Here, we reported a case of an adult female who presented with isolated cervical lymphadenopathy and FNAC revealed metastatic papillary carcinoma of thyroid. Total thyroidectomy with central and posterolateral cervical neck dissection was done, with histology confirming as papillary thyroid carcinoma with local lymphnode metastasis.

Comparison of cervical neck strain in common otolaryngology surgeries

BackgroundCervical neck strain and surgical ergonomics is an increasingly important topic being addressed in this time and age. With new technologies, visualizations, and approaches to surgeries, there are now different strains and duration of strains to the cervical neck. Recently the effect of chronic cell phone use has been described as “text neck.” In a similar fashion we understand that certain otolaryngology surgeries can also impart chronic strain to the cervical neck. We aim to quantitatively describe strain for different types of surgeries by looking at posture, duration of surgery, and anatomic ergonomics of specific surgeries. MethodsLateral photo documentation of posture during 6 common otolaryngology procedures, used to estimate cervical neck angle and calculate force and impulse to cervical neck. ResultsSix common otolaryngology procedures show various cervical neck angles ranging from around 0° to 60° of neck flexion, with subsequent forces ranging from 16 lb to 60 lb of force. When accounting for surgical time, bigger differences arose with impulses ranging from 270,000 N∗s to 3,300,000 N∗s. Noticeably, thyroidectomy and cleft palate showed much higher impulses than the other four types of surgeries. ConclusionBoth cervical neck flexion and duration of surgery play important roles in total neck theoretical strain. Variance exists between neck strains of common otolaryngology surgeries. There is a necessity for continued study and improvement in surgical ergonomics.