Wilmer Rene Cujilema Guillin

Cutaneous oncology has entered a new phase defined by the integration of early detection strategies, molecular risk stratification, and biologically guided systemic therapies. Melanoma, although less frequent than keratinocyte cancers, remains the most lethal form of skin cancer, while basal cell carcinoma and Merkel-cell carcinoma contribute significantly to global oncologic burden. This review analyzes the contemporary transformation of cutaneous oncology within the precision medicine framework, focusing on three core domains: stage-based prognosis, genomic characterization, and targeted and immune-based therapeutic interventions. Evidence from landmark clinical trials demonstrates that BRAF-mutated melanoma benefits from combined BRAF/MEK inhibition, while immune checkpoint blockade—particularly PD-1–based regimens—achieves durable survival in advanced disease. Long-term survival data confirm sustained benefit in a subset of patients, redefining expectations for metastatic melanoma outcomes. In addition, immunotherapy has shown meaningful activity in other aggressive cutaneous malignancies such as Merkel-cell carcinoma. The integration of staging systems, molecular diagnostics, and systemic therapies illustrates a dual therapeutic paradigm in which tumor genotype and immune context guide treatment selection. From an international perspective, including healthcare systems in Mexico, Colombia, and Ecuador, the implementation of precision oncology requires structured integration of early detection, standardized pathology, essential genomic testing, and multidisciplinary therapeutic access. Cutaneous oncology in the precision era is therefore characterized by coordinated biological insight and clinical application, forming the basis for advanced academic instruction and evidence-based oncologic practice.

Chronic pain represents a major challenge in internal medicine due to its persistent nature, heterogeneous presentation, and frequent dissociation from identifiable tissue damage. Contemporary evidence indicates that chronic pain should be conceptualized as a multisystem condition sustained by interacting mechanisms of peripheral sensitization, neuropathic remodeling, and central sensitization, rather than as a linear extension of acute nociception. This narrative integrative review synthesizes key findings from pain neuroscience, clinical research, and contemporary classification systems to examine how these mechanisms contribute to pain persistence, symptom amplification, and functional impairment. The analysis highlights the clinical relevance of pain phenotyping—nociceptive, neuropathic, nociplastic, and mixed—using observable clinical features commonly encountered in internal medicine practice. Patterns such as widespread pain, disproportionate symptom intensity, sleep disturbance, fatigue, cognitive complaints, and autonomic manifestations are discussed as indicators of central-dominant mechanisms. The review further explores how differential therapeutic responsiveness across phenotypes supports a mechanism-based approach to management, emphasizing the limitations of uniform analgesic strategies and the value of interdisciplinary care, including pharmacologic modulation, rehabilitation, and pain education. By integrating mechanistic understanding with diagnostic reasoning, this review provides an educational framework aimed at improving clinical decision-making in internal medicine. Recognizing chronic pain as a condition with modifiable neurobiological drivers supports more individualized, effective, and patient-centered care across diverse healthcare settings.

Immunologic and inflammatory skin disorders have undergone a profound conceptual transformation over the past two decades. Conditions such as psoriasis, atopic dermatitis, autoimmune blistering diseases, and cutaneous lupus erythematosus are now understood as immune-mediated entities driven by specific pathogenic pathways rather than solely morphologic diagnoses. This review synthesizes contemporary high-impact literature to analyze emerging diagnostic and therapeutic paradigms, emphasizing the transition from broad immunosuppression to mechanism-informed precision targeting. Particular attention is given to the IL-23/Th17 axis in psoriasis, type 2 inflammation in atopic dermatitis, and autoantibody-mediated mechanisms in blistering disorders. The review further compares cytokine-specific biologics with intracellular pathway modulators such as JAK inhibitors, highlighting distinctions in monitoring requirements, breadth of immunologic impact, and practical considerations. A structured therapeutic sequencing model is proposed, integrating clinical severity, immunologic alignment, safety monitoring, and healthcare feasibility. Special consideration is given to implementation in diverse international contexts, including Mexico, Colombia, and Ecuador. The findings support a unified framework in which diagnosis remains clinically grounded but conceptually reinforced by immunopathogenesis, and treatment selection is increasingly guided by targeted immune modulation. This paradigm reflects the broader evolution of translational medicine and underscores the necessity of adaptable, evidence-based strategies in inflammatory dermatology.

Tumor adaptation and therapeutic resistance remain central challenges in modern oncology despite significant advances in targeted therapy and immunotherapy. Contemporary evidence indicates that resistance is not an isolated pharmacologic failure but an emergent property of evolving tumor ecosystems characterized by intratumoral heterogeneity, clonal selection, immune modulation, and tumor microenvironmental support. This review synthesizes landmark mechanistic and translational studies to construct an integrated framework linking evolutionary dynamics, signaling plasticity, immune escape, and precision oncology implementation. Across targeted therapies, resistance frequently develops through pathway reactivation, bypass signaling, and adaptive rewiring under selective pressure. In immunotherapy, resistance involves immune editing, checkpoint regulation complexity, impaired antigen presentation, and stromal-mediated immune exclusion. The tumor microenvironment further stabilizes therapy-tolerant populations through niche protection and cytokine-driven suppression. Genome-driven oncology provides a translational pathway for personalization; however, effective precision strategies must be dynamic and iterative, accounting for tumor evolution rather than relying on static baseline profiling. This integrative perspective supports improved therapeutic reasoning, multidisciplinary decision-making, and context-adapted implementation in diverse healthcare systems, including emerging oncology infrastructures in Latin America. Understanding resistance as an evolutionary and ecological phenomenon strengthens both clinical strategy design and advanced oncology education.

Tumor adaptation and therapeutic resistance represent major limitations to sustained treatment efficacy in modern oncology. Despite advances in targeted therapies and personalized approaches, disease progression and relapse remain frequent, reflecting the intrinsic biological complexity of malignant tumors. This review synthesizes high-impact evidence addressing the mechanisms that drive tumor adaptation under therapeutic pressure, with particular emphasis on intratumoral heterogeneity, evolutionary dynamics, and cellular plasticity. The analyzed literature supports the view of cancer as a dynamic and evolving ecosystem composed of genetically and phenotypically diverse subpopulations that respond heterogeneously to treatment. Resistance emerges as a predictable consequence of Darwinian selection, shaped by both genetic alterations and non-genetic adaptive processes, including reversible drug-tolerant states and microenvironmental influences. The findings further highlight the limitations of static, single-time-point molecular profiling in capturing tumor complexity and guiding long-term therapeutic decisions. Evolution-informed strategies, such as adaptive therapy and rational treatment sequencing, are discussed as biologically grounded approaches that may improve disease control by managing, rather than attempting to eradicate, heterogeneous tumor populations. This integrative perspective is particularly relevant for diverse healthcare settings, including those in Latin America, where conceptual frameworks can support clinical decision-making in variable resource contexts. Overall, understanding tumor adaptation and resistance as emergent evolutionary phenomena provides a coherent foundation for advancing personalized oncology, improving clinical reasoning, and strengthening oncology education

The skin frequently reflects internal pathological processes, making cutaneous manifestations valuable indicators of systemic disease. This narrative integrative review analyzes current scientific evidence on dermatologic findings that function as early or concurrent markers of underlying systemic disorders. The study synthesizes peer-reviewed literature addressing renal–metabolic, inflammatory–immune, malignancy-related, and vascular–calcific conditions, emphasizing recognizable cutaneous patterns and their clinical context. Results demonstrate that paraneoplastic dermatoses are commonly described as early indicators that may precede the diagnosis of internal malignancy, whereas renal–metabolic and vascular–calcific manifestations are more frequently reported as concurrent expressions of established systemic disease. Inflammatory and immune-mediated dermatoses exhibit variable timing, reflecting heterogeneous triggers and systemic associations. Across categories, cutaneous findings consistently mirror immune dysregulation, metabolic imbalance, vascular injury, or neoplastic activity. This review highlights the diagnostic and educational relevance of dermatologic examination in general medical practice, particularly in settings where access to advanced diagnostic resources may be limited. Integrating systematic skin assessment into routine clinical evaluation can strengthen diagnostic reasoning, support earlier recognition of systemic illness, and promote a more holistic approach to patient care.

Urethral reconstruction remains a complex challenge in contemporary urology, particularly in patients with long-segment defects, recurrent strictures, or significant systemic comorbidities. Conventional techniques such as buccal mucosa graft urethroplasty provide reliable functional outcomes but are limited by donor-site morbidity and variable long-term durability. Advances in tissue engineering have introduced regenerative strategies aimed at restoring urethral structure while preserving physiological function, sexual health, and reproductive potential. This review synthesizes current experimental and clinical evidence on tissue-engineered urethral reconstruction, integrating a clinical urology perspective with considerations relevant to internal medicine. A structured narrative analysis of peer-reviewed studies was performed, focusing on scaffold design, cellularization strategies, functional urinary outcomes, complication profiles, reintervention burden, and patient-centered sexual and reproductive outcomes. The available evidence indicates that tissue-engineered urethral constructs are clinically feasible and capable of achieving sustained urethral patency in selected patients. Cell-seeded tubular scaffolds demonstrate favorable durability in carefully selected cohorts, while tissue-engineered buccal mucosa grafts reduce donor-site morbidity but show greater variability in long-term outcomes. Across all reconstructive strategies, reintervention rates increase with extended follow-up, reflecting the chronic nature of urethral stricture disease. Sexual and reproductive function is generally preserved, with trends favoring regenerative approaches, although these outcomes remain inconsistently reported. Overall, tissue-engineered urethral reconstruction represents a promising complementary strategy to conventional techniques, with its optimal application dependent on construct design, patient selection, and systemic health factors. Continued refinement and standardized outcome reporting are essential to support broader clinical adoption.

Type 2 diabetes mellitus (T2DM) in non-obese individuals represents a growing clinical challenge, particularly in regions where metabolic risk is not adequately captured by body mass index alone. In recent years, metabolic surgery has gained attention as a potential therapeutic option for selected non-obese patients, based on evidence suggesting that its benefits extend beyond weight reduction and involve sustained endocrine modulation. This narrative review analyzes the evolving role of metabolic surgery in non-obese patients with T2DM, focusing on emerging selection criteria and reported endocrine outcomes. The review synthesizes international literature and conceptual frameworks of chronic disease management to identify consistent patterns in patient selection, underlying physiological mechanisms, and clinically relevant outcomes. Across the reviewed evidence, selection criteria increasingly prioritize beta-cell reserve, disease duration, metabolic phenotype, and glycemic refractoriness over anthropometric thresholds. Reported outcomes predominantly emphasize sustained glycemic control, reduction in pharmacologic treatment burden, and improvements in insulin sensitivity, while remission is described as a variable outcome dependent on baseline metabolic capacity and follow-up duration. The findings support the interpretation of metabolic surgery as a durable endocrine-modifying intervention that requires careful patient selection and structured long-term follow-up. This perspective is particularly relevant for Latin American healthcare systems, including those in Mexico, Colombia, and Ecuador, where chronic disease management is influenced by system-level factors such as continuity of care and access to multidisciplinary monitoring.

Glaucoma is a chronic and progressive optic neuropathy in which sustained reduction of intraocular pressure (IOP) remains the most important modifiable factor to slow disease progression and prevent irreversible visual loss. Although topical hypotensive therapy is the standard first-line approach, its real-world effectiveness is frequently limited by poor adherence, variable drug bioavailability, and long-term tolerability issues. Long-acting implantable drug delivery systems have emerged as an alternative strategy designed to provide continuous intraocular drug exposure while reducing dependence on daily patient-administered treatment. This review synthesizes current evidence on long-acting implantable drug delivery systems for glaucoma, integrating pathophysiological rationale, technological characteristics, and clinical outcomes. High-impact peer-reviewed literature addressing sustained ocular drug delivery, biodegradable implants, and prostaglandin analog–based intraocular systems was analyzed, including experimental studies, clinical trials, and real-world data. The available evidence indicates that sustained-release intraocular implants achieve clinically meaningful reductions in IOP comparable to conventional topical therapy, with improved treatment persistence and reduced reliance on patient adherence. Dose–response analyses demonstrate effective pressure lowering across implant strengths, with a tendency toward a therapeutic plateau at higher doses, supporting individualized treatment optimization. Longitudinal findings further suggest durable IOP control over extended follow-up periods, including prolonged intervals without the need for additional IOP-lowering interventions. Overall, long-acting implantable drug delivery systems represent a significant advancement in glaucoma management by combining pharmacologic efficacy with controlled and sustained delivery, addressing key limitations of topical therapy and offering a promising complementary approach for long-term disease control in diverse international healthcare settings.