Narayana Subramaniam

Early-onset cancers (diagnosed before age 45) are rising globally and demonstrate distinct biological characteristics compared to late-onset malignancies. While epidemiological trends are well-documented, the immune mechanisms for different disease trajectories in young adults remain poorly characterized. This review synthesizes and compares immune landscapes across early-onset cancers, identifying common immunological features and their interactions with non-immune factors including host genetics, tumor-intrinsic alterations, and microbiome dysbiosis. Young patients frequently exhibit preserved or elevated immune cell infiltration alongside functionally suppressed adaptive responses with TLS presence but without concurrent functional enhancement, impaired antigen presentation, and enhanced immunosuppressive cell populations. This creates a functionally “cold” tumor microenvironment in most cancer types that is fundamentally different from late-onset tumors. Concurrently, systemic immunity is characterized by altered T-cell subsets, metabolic shifts, and elevated inflammatory cytokines, though the existing literature remains limited and fragmented, representing a critical knowledge gap hindering peripheral biomarker development. Importantly, immune profiles are often driven more by molecular subtype, sex, and hormonal context than by age alone, underscoring the necessity for multi-level stratification. Notably, this immunosuppressive profile does not consistently translate to inferior responses to immune checkpoint inhibitor therapy, though young patients experience higher toxicity rates. Future studies must prioritize comprehensive systemic immune profiling, multi-omic signature development, and mechanistic investigations into functional immunosuppression despite immune infiltration. Prospective biomarker-guided trials with age- and molecular-stratified designs are essential to develop precision immunotherapies tailored to the unique immunobiology of young adults, ultimately improving outcomes in this increasingly affected population.

Cervical lymph node metastases are major prognostic determinants in head and neck squamous cell carcinoma (HNSCC), and neck dissection (ND) has long been central to regional control. As ND has evolved from radical to selective procedures, immune checkpoint inhibitors (ICIs) have emerged as a fourth treatment pillar, reframing tumor-draining lymph nodes (TDLNs) as active immune organs rather than passive conduits of metastatic spread. This narrative review synthesizes surgical, immunologic, and translational evidence on how ND and cervical irradiation interact with immunotherapy. It also examines the historical development of ND, the immunologic structure and function of cervical TDLNs, and the use of neoadjuvant, perioperative, and recurrent/metastatic immunotherapy in HNSCC. Preclinical and early clinical observations suggest that ablating or heavily irradiating non-involved nodal basins may attenuate ICI efficacy by disrupting antigen presentation, progenitor exhausted CD8⁺ T (Tpex) cell pools, and effector recirculation, supporting the conceptual model of an “immune desert neck.” The review critically appraises timing (pre- versus post-immunotherapy ND), response-adapted or de-escalated surgery, and imaging, tissue-based, and circulating biomarkers to guide individualized management. Current evidence does not support abandoning elective or therapeutic ND, but does highlight the need for biomarker-driven, lymphatic-sparing trials to redefine when ND is essential, modifiable, or potentially avoidable in immunotherapy-treated HNSCC.

Objectives To evaluate the effectiveness of the chimeric Free Anterolateral Thigh (FALT) and vastus lateralis muscle (VLM) flap for reconstructing extensive defects in advanced oral squamous cell carcinoma (OSCC), particularly those involving the infratemporal fossa (ITF) and masticator space. Methods A retrospective study was conducted at Sri Shankara Cancer Hospital, Bangalore, from January 2023 to June 2024. It included 22 patients with T4a and T4b OSCC who underwent curative ablative surgery, ITF clearance, and reconstruction using the chimeric FALT-VLM flap. The surgical technique involved harvesting a skin paddle based on a single perforator and a separate vastus lateralis muscle from the same donor site. The reconstruction aimed to provide oral cavity lining, oro-cervical separation, and ITF obliteration. Results Patient age ranged from 38 to 76 years (mean 53.6). The majority had buccal mucosa (54.5%) and retromolar trigone (36.3%) cancers. The FALT skin paddle size varied from 94.2 to 408.2 cm², with muscle bulk between 201.0 and 391.9 cm³. Complications included seroma and hematoma in 9.1% of cases, with 81.8% showing no complications. No donor site morbidity was noted. Post-operative mouth opening ranged between 2.5 and 3.5 cm. Most patients (72.7%) received adjuvant radiotherapy. All maintained local-regional control status. Conclusion The chimeric FALT-VLM flap is a robust technique for reconstructing complex oral cancer defects, effectively addressing both functional and aesthetic needs. This approach, combining skin and muscle components with independent vascular supplies, represents a significant advancement in reconstructive surgery for advanced OSCC.

Large language models (LLMs) have rapidly emerged as transformative tools across multiple domains, including healthcare. The ability of LLMs to process vast amounts of data and generate human-like responses has facilitated their integration into patient care, particularly in enhancing communication, improving patient satisfaction, and streamlining administrative processes. Despite this potential, there are concerns regarding their accuracy, reliability, and ethical use in clinical settings. This scoping review aims to investigate and map the current literature on the use of LLMs in improving provider–patient experience and interaction efficiency. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, we conducted a systematic search of Ovid MEDLINE, PubMed, and Google Scholar databases to identify relevant articles published between January 2015 and June 2024. Of the 3568 articles initially screened, 47 satisfied the inclusion criteria. These articles spanned 13 countries and encompassed diverse healthcare settings. Thematic areas of LLM utilization included improving communication between patients and healthcare providers, resolving patient inquiries, enhancing patient education, and increasing operational efficiency. Although numerous studies have yielded positive outcomes, significant challenges related to data accuracy, hallucinations, bias, and ethical concerns remain. LLMs can considerably improve patient experience in healthcare, particularly in areas of communication, education, and administrative efficiency. However, concerns regarding accuracy, ethical implications, and the need for rigorous safeguards to prevent misinformation impede their widespread adoption. Future research should focus on developing context-specific LLMs tailored to healthcare environments and addressing the identified limitations to optimize their implementation in clinical practice.

Introduction In the Indian subcontinent where tobacco chewing is rampant, composite 'bite' defects are common after oral cancer ablation, which comprise buccal mucosa, maxilla and mandible with or without skin. These are often reconstructed with soft tissue flaps like anterolateral thigh flaps, which provide ample soft tissue replacement. A common problem is palatal dehiscence where these flaps are inset, due to the dynamics of speaking and chewing, as well as the gravitational pull on the flap. Materials and Methods We describe our technique of combining an early custom obturator for these patients in the post operative period, which helps support the palatal inset and prevent dehiscence. We describe in detail the indications and workflow for this technique, mechanism of action and outcomes. Results We show the successful result of use in a single patient with an early dehiscence and how it can be incorporated into standard workflow in selected patients at risk of dehiscence. Conclusions This is a useful technique to prevent dehiscence in patients undergoing extensive buccal resections involving the maxilla. It allows for early oral intake and function while preventing dehiscence and dealyed wound healing, which is often costly.