Zainal Ariff Abdul Rahman

Injecting Realism in Surgical Training—Initial Simulation Experience With Custom 3D Models

UNLABELLED The traditionally accepted form of training is direct supervision by an expert; however, modern trends in medicine have made this progressively more difficult to achieve. A 3-dimensional printer makes it possible to convert patients imaging data into accurate models, thus allowing the possibility to reproduce models with pathology. This enables a large number of trainees to be trained simultaneously using realistic models simulating actual neurosurgical procedures. The aim of this study was to assess the usefulness of these models in training surgeons to perform standard procedures that require complex techniques and equipment. METHODS Multiple models of the head of a patient with a deep-seated small thalamic lesion were created based on his computed tomography and magnetic resonance imaging data. A workshop was conducted using these models of the head as a teaching tool. The surgical trainees were assessed for successful performance of the procedure as well as the duration of time and number of attempts taken to learn them. FINDINGS All surgical candidates were able to learn the basics of the surgical procedure taught in the workshop. The number of attempts and time taken reflected the seniority and previous experience of each candidate. DISCUSSION Surgical trainees need multiple attempts to learn essential procedures. The use of these models for surgical-training simulation allows trainees to practice these procedures repetitively in a safe environment until they can master it. This would theoretically shorten the learning curve while standardizing teaching and assessment techniques of these trainees.

Neurosurgical endoscopic training via a realistic 3- dimensional model with pathology.

Introduction Training in intraventricular endoscopy is particularly challenging because the volume of cases is relatively small and the techniques involved are unlike those usually used in conventional neurosurgery. Present training models are inadequate for various reasons. Using 3-dimensional (3D) printing techniques, models with pathology can be created using actual patient’s imaging data. This technical article introduces a new training model based on a patient with hydrocephalus secondary to a pineal tumour, enabling the models to be used to simulate third ventriculostomies and pineal biopsies. Methods Multiple models of the head of a patient with hydrocephalus were created using 3D rapid prototyping technique. These models were modified to allow for a fluid-filled ventricular system under appropriate tension. The models were qualitatively assessed in the various steps involved in an endoscopic third ventriculostomy and intraventricular biopsy procedure, initially by 3 independent neurosurgeons and subsequently by 12 participants of an intraventricular endoscopy workshop. Results All 3 surgeons agreed on the ease and usefulness of these models in the teaching of endoscopic third ventriculostomy, performing endoscopic biopsies, and the integration of navigation to ventriculoscopy. Their overall score for the ventricular model realism was above average. The 12 participants of the intraventricular endoscopy workshop averaged between a score of 4.0 to 4.6 of 5 for every individual step of the procedure. Discussion Neurosurgical endoscopic training currently is a long process of stepwise training. These 3D printed models provide a realistic simulation environment for a neuroendoscopy procedure that allows safe and effective teaching of navigation and endoscopy in a standardized and repetitive fashion.

The creation and verification of cranial models using three-dimensional rapid prototyping technology in field of transnasal sphenoid endoscopy.

BACKGROUND Surgical navigation systems have been used increasingly in guiding complex ear, nose, and throat surgery. Although these are helpful, they are only beneficial intraoperatively; thus, the novice surgeon will not have the preoperative training or exposure that can be vital in complex procedures. In addition, there is a lack of reliable models to give surgeons hands-on training in performing such procedures. METHODS A technique using an industrial rapid prototyping process by three-dimensional (3D) printing was developed, from which accurate spatial models of the nasal cavity, paranasal sinuses (sphenoid sinus in particular), and intrasellar/pituitary pathology were produced, according to the parameters of an individual patient. Image-guided surgical (IGS) techniques on two different platforms were used during endoscopic transsphenoidal surgery to test and validate the anatomical accuracy of the sinus models by comparing the models with radiological images of the patient on IGS. RESULTS It was possible to register, validate, and navigate accurately on these models using commonly available navigation stations, matching accurately the anatomy of the model to the IGS images. CONCLUSION These 3D models can be reliably used for teaching/training and preoperative planning purposes.Background Surgical navigation systems have been used increasingly in guiding complex ear, nose, and throat surgery. Although these are helpful, they are only beneficial intraoperatively; thus, the novice surgeon will not have the preoperative training or exposure that can be vital in complex procedures. In addition, there is a lack of reliable models to give surgeons hands-on training in performing such procedures. Methods A technique using an industrial rapid prototyping process by three-dimensional (3D) printing was developed, from which accurate spatial models of the nasal cavity, paranasal sinuses (sphenoid sinus in particular), and intrasellar/pituitary pathology were produced, according to the parameters of an individual patient. Image-guided surgical (IGS) techniques on two different platforms were used during endoscopic transsphenoidal surgery to test and validate the anatomical accuracy of the sinus models by comparing the models with radiological images of the patient on IGS. Results It was possible to register, validate, and navigate accurately on these models using commonly available navigation stations, matching accurately the anatomy of the model to the IGS images. Conclusion These 3D models can be reliably used for teaching/training and preoperative planning purposes.

Endoscopic skull base training using 3D printed models with pre-existing pathology.

Endoscopic base of skull surgery has been growing in acceptance in the recent past due to improvements in visualisation and micro instrumentation as well as the surgical maturing of early endoscopic skull base practitioners. Unfortunately, these demanding procedures have a steep learning curve. A physical simulation that is able to reproduce the complex anatomy of the anterior skull base provides very useful means of learning the necessary skills in a safe and effective environment. This paper aims to assess the ease of learning endoscopic skull base exposure and drilling techniques using an anatomically accurate physical model with a pre-existing pathology (i.e., basilar invagination) created from actual patient data. Five models of a patient with platy-basia and basilar invagination were created from the original MRI and CT imaging data of a patient. The models were used as part of a training workshop for ENT surgeons with varying degrees of experience in endoscopic base of skull surgery, from trainees to experienced consultants. The surgeons were given a list of key steps to achieve in exposing and drilling the skull base using the simulation model. They were then asked to list the level of difficulty of learning these steps using the model. The participants found the models suitable for learning registration, navigation and skull base drilling techniques. All participants also found the deep structures to be accurately represented spatially as confirmed by the navigation system. These models allow structured simulation to be conducted in a workshop environment where surgeons and trainees can practice to perform complex procedures in a controlled fashion under the supervision of experts.

Three-dimensional anatomical accuracy of cranial models created by rapid prototyping techniques validated using a neuronavigation station

In neurosurgery and ear, nose and throat surgery the application of computerised navigation systems for guiding operations has been expanding rapidly. However, suitable models to train surgeons in using navigation systems are not yet available. We have developed a technique using an industrial, rapid prototyping process from which accurate spatial models of the cranium, its contents and pathology can be reproduced for teaching. We were able to register, validate and navigate using these models with common available navigation systems such as the Medtronic StealthStation S7®.

An oral cancer biobank initiative: a platform for multidisciplinary research in a developing country

Identification of diagnostic markers for early detection and development of novel and therapeutic agents for effective patient management are the main motivation for cancer research. Biological specimens from large cohort and case-control studies which are crucial in providing successful research outcomes are often the limiting factor that hinders research efforts, especially in developing countries. Therefore, the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS) were established to systematically collect large number of samples with comprehensive sociodemographic, clinicopathological, management strategies, quality of life and associated patient follow-up data to facilitate oral cancer research in Malaysia. The MOCDTBS also promotes sharing among researchers and the development of a multidisciplinary research team. The following article aims to describe the process of setting-up and managing the MOCDTBS.

Genetically-defined novel oral squamous cell carcinoma cell lines for the development of molecular therapies

Emerging biological and translational insights from large sequencing efforts underscore the need for genetically-relevant cell lines to study the relationships between genomic alterations of tumors, and therapeutic dependencies. Here, we report a detailed characterization of a novel panel of clinically annotated oral squamous cell carcinoma (OSCC) cell lines, derived from patients with diverse ethnicity and risk habits. Molecular analysis by RNAseq and copy number alterations (CNA) identified that the cell lines harbour CNA that have been previously reported in OSCC, for example focal amplications in 3q, 7p, 8q, 11q, 20q and deletions in 3p, 5q, 8p, 18q. Similarly, our analysis identified the same cohort of frequently mutated genes previously reported in OSCC including TP53, CDKN2A, EPHA2, FAT1, NOTCH1, CASP8 and PIK3CA. Notably, we identified mutations (MLL4, USP9X, ARID2) in cell lines derived from betel quid users that may be associated with this specific risk factor. Gene expression profiles of the ORL lines also aligned with those reported for OSCC. By focusing on those gene expression signatures that are predictive of chemotherapeutic response, we observed that the ORL lines broadly clustered into three groups (cell cycle, xenobiotic metabolism, others). The ORL lines noted to be enriched in cell cycle genes responded preferentially to the CDK1 inhibitor RO3306, by MTT cell viability assay. Overall, our in-depth characterization of clinically annotated ORL lines provides new insight into the molecular alterations synonymous with OSCC, which can facilitate in the identification of biomarkers that can be used to guide diagnosis, prognosis, and treatment of OSCC.

Genome Wide Analysis of Chromosomal Alterations in Oral Squamous Cell Carcinomas Revealed over Expression of MGAM and ADAM9

Despite the advances in diagnosis and treatment of oral squamous cell carcinoma (OSCC), mortality and morbidity rates have not improved over the past decade. A major drawback in diagnosis and treatment of OSCC is the lack of knowledge relating to how genetic instability in oral cancer genomes affects oral carcinogenesis. Hence, the key aim of this study was to identify copy number alterations (CNAs) that may be cancer associated in OSCC using high-resolution array comparative genomic hybridization (aCGH). To our knowledge this is the first study to use ultra-high density aCGH microarrays to profile a large number of OSCC genomes (n = 46). The most frequently amplified CNAs were located on chromosome 11q11(52%), 2p22.3(52%), 1q21.3–q22(54%), 6p21.32(59%), 20p13(61%), 7q34(52% and 72%),8p11.23–p11.22(80%), 8q11.1–q24.4(54%), 9q13–q34.3(54%), 11q23.3–q25(57%); 14q21.3–q31.1(54%); 14q31.3–q32.33(57%), 20p13–p12.3(54%) and 20q11.21–q13.33(52%). The most frequently deleted chromosome region was located on 3q26.1 (54%). In order to verify the CNAs from aCGH using quantitative polymerase chain reaction (qPCR), the three top most amplified regions and their associated genes, namely ADAM5P (8p11.23–p11.22), MGAM (7q34) and SIRPB1 (20p13.1), were selected in this study. The ADAM5P locus was found to be amplified in 39 samples and deleted in one; MGAM (24 amplifications and 3 deletions); and SIRPB1 (12 amplifications, others undetermined). On the basis of putative cancer-related annotations, two genes, namely ADAM metallopeptidase domain 9 (ADAM9) and maltase-glucoamylase alpha-glucosidase (MGAM), that mapped to CNA regions were selected for further evaluation of their mRNA expression using reverse transcriptase qPCR. The over-expression of MGAM was confirmed with a 6.6 fold increase in expression at the mRNA level whereas the fold change in ADAM9 demonstrated a 1.6 fold increase. This study has identified significant regions in the OSCC genome that were amplified and resulted in consequent over-expression of the MGAM and ADAM9 genes that may be utilized as biological markers for OSCC.

The utilization of cranial models created using rapid prototyping techniques in the development of models for navigation training

INTRODUCTION Navigation in neurosurgery has expanded rapidly; however, suitable models to train end users to use the myriad software and hardware that come with these systems are lacking. Utilizing three-dimensional (3D) industrial rapid prototyping processes, we have been able to create models using actual computed tomography (CT) data from patients with pathology and use these models to simulate a variety of commonly performed neurosurgical procedures with navigation systems. AIM To assess the possibility of utilizing models created from CT scan dataset obtained from patients with cranial pathology to simulate common neurosurgical procedures using navigation systems. METHODOLOGY Three patients with pathology were selected (hydrocephalus, right frontal cortical lesion, and midline clival meningioma). CT scan data following an image-guidance surgery protocol in DIACOM format and a Rapid Prototyping Machine were taken to create the necessary printed model with the corresponding pathology embedded. The ability in registration, planning, and navigation of two navigation systems using a variety of software and hardware provided by these platforms was assessed. RESULTS We were able to register all models accurately using both navigation systems and perform the necessary simulations as planned. CONCLUSION Models with pathology utilizing 3D rapid prototyping techniques accurately reflect data of actual patients and can be used in the simulation of neurosurgical operations using navigation systems.

Genome-wide analysis of oral squamous cell carcinomas revealed over expression of ISG15, Nestin and WNT11

BACKGROUND Multistep pathways and mechanisms are involved in the development of oral cancer. Chromosomal alterations are one of such key mechanisms implicated oral carcinogenesis. Therefore, this study aims to determine the genomic copy number alterations (CNAs) in oral squamous cell carcinoma (OSCC) using array comparative genomic hybridization (aCGH) and in addition attempt to correlate CNAs with modified gene expression. MATERIALS AND METHODS Genome-wide screening was performed on 15 OSCCs using high-density aCGH. On the basis of pathway analysis, three genes (ISG15, Nestin and WNT11) which mapped to CNA regions were selected for further evaluation of their mRNA expression using quantitative reverse transcriptase PCR (qRT-PCR). RESULTS Copy number alterations were observed on multiple genomic regions, including amplifications on 1p, 3q, 5p, 6p, 7p, 8q, 9q, 11q, 12q, 16p, 18p and deletions on 3p, 7q, 8p, 11q, 19q and 20q. Among the three selected genes, ISG15 had the highest mRNA expression level with a 22.5-fold increase, followed by Nestin with a 4.5-fold increase and WNT11 with a 2.5-fold increase. CONCLUSIONS This study has identified several major CNAs in oral cancer genomes and indicated that this correlates with over expression of the ISG15, WNT11, and Nestin genes.