Mark Edward Puhaindran’s research while affiliated with National University Hospital - NUH and other places

» Tumors of the brachial plexus are uncommon and can present as a mass, with or without neurological symptoms. At times, asymptomatic tumors are also picked up incidentally when imaging is performed for other reasons. » Magnetic resonance imaging is the main imaging modality used to evaluate tumors of the brachial plexus. Other imaging modalities can be used as required. » Benign tumors that are asymptomatic should be observed. Excision can be considered for those that are found to be growing over time. » Biopsies of tumors of the brachial plexus are associated with the risk of nerve injury. Despite this, they should be performed for tumors that are suspected to be malignant before starting definitive treatment. » For malignant tumors, treatment decisions should be discussed at multidisciplinary tumor boards, and include both the oncology and peripheral nerve surgical team, musculoskeletal radiology, neuroradiology, and general radiology.

Artificial intelligence (AI) has witnessed significant advancements, reshaping various industries, including healthcare. The introduction of ChatGPT by OpenAI in November 2022 marked a pivotal moment, showcasing the potential of generative AI in revolutionising patient care, diagnosis and treatment. Generative AI, unlike traditional AI systems, possesses the ability to generate new content by understanding patterns within datasets. This article explores the evolution of AI in healthcare, tracing its roots to the term coined by John McCarthy in 1955 and the contributions of pioneers like John Von Neumann and Alan Turing. Currently, generative AI, particularly Large Language Models, holds promise across three broad categories in healthcare: patient care, education and research. In patient care, it offers solutions in clinical document management, diagnostic support and operative planning. Notable advancements include Microsoft’s collaboration with Epic for integrating AI into electronic medical records (EMRs), enhancing clinical data management and patient care. Furthermore, generative AI aids in surgical decision-making, as demonstrated in plastic, orthopaedic and hepatobiliary surgeries. However, challenges such as bias, hallucination and integration with EMR systems necessitate caution and ongoing evaluation. The article also presents insights from the implementation of NUHS Russell-GPT, a generative AI chatbot, in a hand surgery department, showcasing its utility in administrative tasks but highlighting challenges in surgical planning and EMR integration. The survey showed unanimous support for incorporating AI into clinical settings, with all respondents being open to its use. In conclusion, generative AI is poised to enhance patient care and ease physician workloads, starting with automating administrative tasks and evolving to inform diagnoses, tailored treatment plans, as well as aid in surgical planning. As healthcare systems navigate the complexities of integrating AI, the potential benefits for both physicians and patients remain significant, offering a glimpse into a future where AI transforms healthcare delivery. Level of Evidence: Level V (Diagnostic)

We analysed the differences in clinical presentation between proximal (above elbow) and distal (below elbow) upper limb metastases in a retrospective review of patients presenting to our centre from 2011 to 2019. There were 55 cases, 64% involving the humerus and 62% occurring in men. The median age at the time of diagnosis was 64 years. Thirty-one per cent of the cases were proximal lesions. Distal upper limb metastases were more likely to be soft tissue lesions (71%) compared with proximal lesions (8%). The median age of patients with distal lesions was significantly lower at 58 years compared with 65 years for proximal lesions. Overall, non-small cell lung carcinoma was the most common primary malignancy (25%), however haematological cancers were most common in the distal group (29%). Distal upper limb metastases have distinct features that distinguish them from proximal lesions. Level of evidence: IV

Background Peripheral Nerve Sheath Tumors (PNST) are a diverse group of mostly benign tumours uncommon in the general population. About 5–10% of PNSTs are hereditary, predominantly arising from germline variants in NF1, NF2, SMARCB1 , or LZTR1 gene. Methods We reviewed the clinical characteristics and genetic testing results of patients referred to the NCIS Adult Cancer Genetics Clinic for suspected hereditary PNST. Results 3,001 patients suspected to have various hereditary cancer syndromes were evaluated between year 2000 to March 2021. 13 (0.4%) were clinically diagnosed to have hereditary PNSTs. The majority were male (54%), with a median age at presentation to the genetics clinic of 29 years (range 19–48). 11/13 (85%) patients had multiple PNSTs, 12/13 (92%) had young onset PNSTs, 5/13 (38.5%) had personal and family history of PNST. 11/13 patients (85%) had clinical features of neurofibromatosis type 1 (NF1) including one patient who also fulfilled clinical criteria of neurofibromatosis type 2 (NF2); 2/13 (14%) had multiple schwannomas. Four patients underwent multi-gene panel testing, including one patient with clinical NF1, one patient who met both clinical NF1 and NF2 criteria, and two patients with multiple schwannomas. The patient with clinical features of NF1 was heterozygous for a pathogenic c. 2033dup variant in the NF1 gene. The patient with both NF1/NF2 features was heterozygous for a novel c.732 T > A nonsense variant in the NF2 gene. The two patients with multiple schwannomas were heterozygous for a pathogenic/likely pathogenic variant in the LZTR1 gene and are the first LZTR1 -positive schwannomatosis patients reported in Asia. Conclusion Hereditary PNSTs are rare referrals to an adult cancer genetics clinic. NF1 is the most common PNST seen. LZTR1 variants may be the underlying cause in Asian patients with multiple schwannomatosis.

Background: Color matching is a critically important part of, and by far, also the most challenging aspect of producing esthetic silicone prosthesis. There is a knowledge gap in the literature and a lack of opportunities for training in the expertise, particularly regarding color-matching techniques. Objective: This article details a color-matching technique that is able to achieve life-like coloration in esthetic prosthesis. Technique: Each prosthesis is molded in an outer and inner layers of silicone tinted to different shades and opacities incorporating an intermediate touch-up layer to reproduce the detailed coloration of the hand (because of the presence of veins, finger joint/dermal pigmentations, a vascularized nail bed, and pinkish palm). This method of color-matching prosthesis combining intrinsic and extrinsic techniques simulates the layered anatomy and optical properties of the human skin to effectively replicate its esthetic and life-like coloration. Technical tips for achieving an accurate color match to the patient's skin, including pigment formulation adjustments for a tanned vs. a fair skin, and for painting the touch-up details are discussed. Methods for modifying the color tones of completed prosthesis and for minimizing metameric color differences when the prosthesis is viewed under different light sources are also presented. Discussion: The technique is instrumental in achieving good outcomes for life-likeness and esthetic coloration in the prostheses fitted at our center. Studies previously published that investigated patients' evaluation of important esthetic characteristics of their prosthesis after a period of adjustment to fitting have shown a generally high level of patient satisfaction.

Background: Pediatric osteosarcoma outcomes among developed and developing countries have not been previously compared. Countries in Southeast Asia (SEA) have a wide variety of socioeconomic statuses. A multi-institutional retrospective study was conducted to determine the prognostic factors and outcomes for pediatric osteosarcoma in SEA. Methods: Pediatric patients with osteosarcoma treated between 1998 and 2017 in 4 SEA pediatric oncology centers were studied. Countries were classified using the World Bank Atlas method. Kaplan-Meier method and Cox's Proportion Hazard Model were applied to estimate survival outcomes and identify prognostic factors. Results: In all, 149 patients with osteosarcoma with a mean age of 12.48±3.66 years were enrolled. The localized to metastatic disease ratio was 1.5:1. The 5-year overall survival (OS) and event-free survival (EFS) were 53.8% and 42%, respectively. Prognostic factors associated with outcomes were country, stage of disease, MTX-containing regimens, and surgery type (p-value <0.05). In patients with localized disease, EFS was superior with limb-salvage surgery (62%) than amputation or rotationplasty (40%) (p-value 0.009). MTX-containing chemotherapies provided higher OS (45.3%) and EFS (37.9%) than non-MTX regimens (12.3% and 10.7%, respectively) among metastatic patients (p-value 0.004 and 0.005, respectively). Metastatic disease was an independent prognostic factor for death but not relapse outcome. Conclusion: The disease outcomes in SEA were acceptable compared to developed countries. The stage of disease was the only independent prognostic factor. MTX-containing regimens and limb-salvage surgery should be considered where possible.

Purpose Upper limb masses are one of the most common presentations in the outpatient setting. However, there is a paucity of information in the literature regarding the epidemiology of upper-extremity masses in the pediatric population. The aim of this study was to determine the differential diagnoses and clinical characteristics in children aged ≤18 years presenting with upper limb masses. Methods A retrospective review of patients aged ≤18 years managed at our institution over a 5-year period was performed. We obtained information on patient demographics, clinical features, radiological investigations, intraoperative features, and histology. We also evaluated the correlation between the clinical and histopathological diagnoses in patients who underwent surgery. Results There were 141 upper limb masses in our series. The mean age at presentation was 12 years (SD, 5 years). The most common presenting complaints were asymptomatic swelling, pain, and paresthesia. The majority (128; 91%) of tumors were benign; there were 5 locally aggressive tumors and 6 malignant tumors. The dominant hand was involved in 60 patients. Of 140 patients, 43 (31%) patients had surgery. The procedures included incisional biopsy, excisional biopsy, wide resection, and reconstruction. One patient required a below elbow amputation for an osteosarcoma. Conclusions Ten percent of cases represented malignant or locally aggressive disease. We have used our observations to develop a clinical algorithm that can assist clinicians in evaluating and managing children and adolescents presenting with upper-extremity masses. Type of study/level of evidence Prognostic IV.

Background: As a high-grade neoplasm of connective tissues, de-differentiated liposarcoma (DDLPS) is featured by genomic amplification of MDM2, CDK4 and JUN. Super-enhancer-driven master transcription factors (RUNX1, FOSL2 and MYC) establish a core feed-forward transcriptional circuit underpinning the DDLPS malignancy. However, an important question remains unanswered: how do genomic insults interact with epigenetic dysregulation in this disease? Methods: We performed ChIP-seq analysis to map loading of transcription factors and histone marks on chromatin in DDLPS cells. Functional assays following genetic manipulation of target genes were conducted to explore their disease relevance. Results: Genomic activation of JUN represents a promising prognostic marker for DDLPS. Meanwhile, JUN locus engaged excessive H3K27ac signals in both DDLPS tissues and cells, while a markedly lower level of H3K27ac deposition was observed in normal adipose tissues, adipocytes and MSCs. JUN formed a complex with FOSL2 and other co-factors in active chromatin, especially super-enhancers. Silencing of either JUN or its co-factors disrupted the core regulatory circuitry, which was accompanied by strong deleterious impacts on both cell viability and tumorigenicity. As BET bromodomain proteins dictate transcriptionally active chromatin, targeted degradation of BET proteins by PROTAC compounds exerted potent inhibitory effects on both JUN cistrome and DDLPS development. Conclusion: Our study reveals that amplification and overexpression of JUN contribute to DDLPS development. DDLPS-associated genomic abnormalities collaborate with BET proteins to fuel disease-driving core regulatory circuitry. Citation Format: Ye Chen, Pushkar Dakle, Tuan Zea Tan, Ruby Yu-Tong Lin, Mark E. Puhaindran, Sigal Gery, Liang Xu, Phillip H. Koeffler. Genetic activation of JUN fuels the core regulatory circuitry of de-differentiated liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2438.