The Impact of Surgery on Circulating Malignant Tumour Cells in Oral Squamous Cell Carcinoma.

IMPORTANCE: The extent to which surgical management of oral squamous cell carcinoma (OSCC) disseminates cancer is currently unknown. OBJECTIVE: To determine changes in numbers of malignant cells released into systemic circulation immediately following tumour removal and over the first seven post-operative days. DESIGN: An observational study from March 2019 to February 2021. SETTING: This study was undertaken at Queen Mary University Hospital, Hong Kong. PARTICIPANTS: Patients with biopsy-proven oral SCC were considered for eligibility. Patients under 18 years of age, pregnant or lactating women and those unable to understand the study details or unable to sign the consent form were excluded. Twenty-two patients were enrolled (12 male and 10 female) with mean age of 65.5 years. INTERVENTION: Primary tumour management was performed in accord with multi-disciplinary team agreement. Anaesthesia and post-operative care were unaltered and provided in accord with accepted clinical practice. MAIN OUTCOMES AND MEASURES: Three types of malignant cells detected in peripheral blood samples were enumerated and sub-typed based on the presence of chromosomal aneuploidy and immunohistochemical characteristics. To test the hypothesis that malignant cells are released by surgery, the numbers of single circulating tumour cells (CTCs), circulating tumour microemboli (CTM) and circulating endothelial cells (CTECs) were recorded pre-operatively, upon tumour removal and the second and seventh post-operative days. RESULTS: Of a potential 88 data collection points, specimens were not obtainable in 12 instances. Tumour removal resulted in a statistically significant increase in CTCs and a non-statistically significant rise in CTMs. CTCs, CTMs and CTECs were detected in the majority of patients up to the seventh post-operative day. Individual patients demonstrated striking increases in post-operative CTCs and CTECs numbers. CONCLUSIONS/RELEVANCE: Surgical management of OSCC has a significant impact on the systemic distribution of cancer cells. Malignant cells persisted post-operatively in a manner independent of recognised staging methods suggesting differences in tumour biology between individuals. Further investigation is warranted to determine whether circulating malignant cell enumeration can be used to refine risk stratification for patients with OSCC.

A comparison of two methods for the detection of circulating tumour cells in patients with oral cavity cancer.

BACKGROUND: Circulating tumour cells (CTCs) detected in patient blood samples are relevant as diagnostic and prognostic markers offering insights into tumour behaviour and guiding treatment of cancer at an individualised level. The aim of this study was to ascertain the feasibility of detecting CTCs in oral squamous cell carcinoma (OSCC) using two different methods so as to determine the optimal method for the study of this cancer. METHODS: Comparison of the numbers of CTCs, circulating tumour micro-emboli (CTMs) and circulating tumour endothelial cells (CTECs), was undertaken in forty clinical samples of oral squamous cell carcinoma (OSCC) determined by filtration (ISET® ) and in situ fluorescent immunostaining (i-FISH, Cytelligen® ) immunostaining and in situ hybridisation. RESULTS: i-FISH detected CTCs in 80% of samples compared with 40% of samples analysed by microfiltration. i-FISH detected CTCs in a further 40% of samples in which microfiltration did not detect CTCs. No CTC clusters were detected by microfiltration while i-FISH detected CTM in 12.5% of samples. i-FISH analysis detected CTECs in 20/40 samples. CONCLUSION: These results highlight significant differences in detection of CTCs, CTM and CTECs between i-FISH and microfiltration when applied to OSCC samples, suggesting that technologies capable of detecting circulating aneuploid cells more accurately detect CTCs. i-FISH also detected CTM and CTEC not detected using ISET® . With proven prognostic relevance in adenocarcinomas, accurate enumeration of CTCs, CTMs and CTECs may be a clinically useful tool in the management of OSCC and may aid in the reduction of false-negative diagnoses.

The role of citrate, lactate and transferrin in determining titanium release from surgical devices into human serum.

The presence of ionic titanium in the serum of patients with titanium implants is currently unexplained. This is presumed due to corrosion, and yet the serum titanium concentration measured in patients is far greater than that predicted by its solubility. The binding of titanium ion as Ti(IV) to human transferrin (hTF) in serum indicates that Ti(IV) ions interact with human physiology. This is an intriguing finding since there is currently no known role for titanium ions in human physiology. Thus, understanding the factors that determine in vivo titanium ion release is relevant to further understanding this metal's interactions with human biochemistry. The present study sought to determine the extent of titanium ion release of into human serum in vitro, and the role of citrate, lactate and hTF in this process. It was found that, when surgical devices of commercially pure titanium were placed into human serum, citrate and lactate concentrations were the prime determinants of titanium release. Crystallography revealed Ti(IV) bound to hTF in the presence of citrate alone, signalling that citrate can act as an independent ligand for Ti(IV) binding to hTF. Based on these findings, a two-stage process of titanium ion release into human serum that is dependent upon both citrate and hTF is proposed to explain the ongoing presence of titanium ion in human subjects with implanted titanium devices.

Three-dimensional printing of patient-specific surgical plates in head and neck reconstruction: A prospective pilot study.

BACKGROUND: Surgical plates have been extensively used in head and neck reconstruction and conventional plates are mass-produced with universal configurations. To overcome disadvantages of conventional surgical plates, we have been exploring patient-specific surgical plates using the three-dimensional (3D) printing technology. We hypothesized that the application of 3D-printed patient-specific surgical plates in head and neck reconstruction is feasible, safe and precise. METHODS: We are conducting a prospective clinical trial to assess the feasibility, safety and accuracy of applying 3D-printed patient-specific surgical plates in head and neck reconstruction. The primary endpoint was the intraoperative success rate. Secondary endpoints included the incidence and severity of postoperative adverse events within six months postoperatively. The accuracy of surgical outcomes was also explored by comparing the planned and final positions of the maxilla, mandible and grafted bone segments. RESULTS: From December 2016 to October 2017, ten patients were enrolled and underwent head and neck reconstruction using 3D-printed patient-specific surgical plates. The patient-specific surgical plates adapted to bone surface precisely and no plate-bending was performed. The intraoperative success rate was 100%. The average follow-up period was 6.5 months. No major adverse events were observed. The mean absolute distance deviation of integral mandible or maxilla was 1.40 ±â€¯0.63 mm, which showed a high accuracy of reconstruction. CONCLUSIONS: The 3D printing of patient-specific surgical plates could be effective in head and neck reconstruction. Surgical procedures were simplified. The precise jaw reconstruction was achieved with high accuracy. Long-term results with a larger sample size are warranted to support a final conclusion. The study protocol has been registered in ClinicalTrials.gov with a No. of NCT03057223.

Extranodal lymphoma arising within the maxillary alveolus: a case report.

OBJECTIVE: Extranodal lymphomas affecting the head and neck arise infrequently within the bones of the jaws. This is a report of a symptom-free patient whose general dentist detected a radiolucency as an incidental finding on conventional radiography. STUDY DESIGN: The conventional radiography of lesions in the maxilla displayed "floating teeth" indicative of malignancy. This case was then imaged by cone beam computed tomography (CBCT), multidetector computed tomography (MDCT), and magnetic resonance imaging (MRI). The lymphoma grew rapidly in less than a week between the MDCT and the MRI. All the above cross-sectional modalities elicited a provisional diagnosis of a squamous cell carcinoma (SCC). CONCLUSIONS: Evaluation of the extent of the lesion and its encroachment on adjacent structures is limited by conventional radiography. Nevertheless, conventional radiography can display features that are suggestive of malignant disease. Although cross-sectional imaging of lesions within the anatomically-complex-maxilla has generally taken the form of MDCT and MRI, CBCT has a role. In hindsight, the absence of central necrosis should have directed the inclusion of "extranodal lymphoma arising within the maxillary alveolus" in the provisional diagnosis.

Are clinical findings of systemic titanium dispersion following implantation explained by available in vitro evidence? An evidence-based analysis.

Although the presence of titanium wear particles released into tissues is known to induce local inflammation following the therapeutic implantation of titanium devices into humans, the role that titanium ions play in adverse tissue responses has received little attention. Support that ongoing titanium ion release occurs is evidenced by the presence of ionic titanium bound to transferrin in blood, and ongoing excretion in the urine of patients with titanium devices. However, as reports documenting the presence of titanium within tissues do not distinguish between particulate and ionic forms due to technical challenges, the degree to which ionic titanium is released into tissues is unknown. To determine the potential for titanium ion release into tissues, this study evaluates available in vitro evidence relating to the release of ionic titanium under physiological conditions. This is a systematic literature review of studies reporting titanium ion release into solutions from titanium devices under conditions replicating the interstitial pH and constituents. Inclusion and exclusion criteria were defined. Of 452 articles identified, titanium ions were reported in nine media relevant to human biology in seventeen studies. Only one study, using human serum replicated both physiological pH and the concentration of constituents while reporting the presence of titanium ions. While there is insufficient information to explain the factors that contribute to the presence of titanium ions in serum of humans implanted with titanium devices, currently available information suggests that areas of future inquiry include the role of transferrin and organic acids.

An Australian retrospective study to evaluate the prognostic role of p53 and eIF4E cancer markers in patients with head and neck squamous cell carcinoma (HNSCC): study protocol.

Complete surgical resection of the primary tumour is a crucial predictive step for head and neck squamous cell carcinoma (HNSCC), because incomplete resection may lead to increase in the recurrence rate. Molecular cancer markers have been investigated as potential predictors of prognosis marker, to identify patients who are at high risk of local recurrence. This retrospective study aimed to determine the prognostic correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival. Forty eight HNSCC patients were selected between 2006 and 2009 diagnosed at the Royal Darwin Hospital, Darwin, Northern Territory, Australia. Out of 48, only those 24 with negative surgical margins with hematoxylin and eosin (HandE) were chosen for further analysis. A total of 77 surgical margins were obtained and subsequently analysed by immunohistochemical (IHC) staining with monoclonal p53 and polyclonal eIF4E antibodies. Contingency table and χ2-test were used to investigate the correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival of the HNSCC patients. The follow up period was 74 months (range 1-74 months). The Kaplan-Meier method was used to generate recurrence and survival curves. This is a first retrospective study of Northern Territory patients, including Indigenous and non-Indigenous Australians. Molecular study of surgical margins could help to identify patients with and without clear margins after surgery and help in choice of the most appropriate adjuvant treatment for HNSCC patients.