Shivani Modi

Colorectal cancer (CRC) develops through both conventional adenoma–carcinoma and serrated neoplasia pathways, yet noninvasive screening still under-detects the advanced precursor lesions that enable true cancer prevention. Stool-based screening reduces CRC mortality, but its preventive impact remains constrained by limited detection of advanced precancerous lesions (APLs), including advanced adenomas and sessile serrated lesions. Next-generation multitarget stool DNA assays (mt-sDNA; e.g., Cologuard Plus) have established high sensitivity for CRC and specificity approaching 94%, leaving improved APL detection as the principal opportunity for innovation. This review presents a consensus framework for a multi-omic stool screening paradigm that integrates host epigenetic markers (DNA methylation) with gut microbiome features using artificial intelligence (AI). Multi-omics capture complementary layers of early tumor biology: epithelial shedding and field effects reflected in host methylation signals together with luminal ecological and inflammatory changes represented by microbial features. Evidence from cross-cohort microbiome studies indicates that microbial signatures provide an additive—rather than standalone—axis of information for CRC and its precursor lesions. Because microbiome-based models are highly susceptible to batch effects arising from collection devices, extraction chemistry, sequencing platforms, and bioinformatic pipelines, practical mitigation strategies are outlined, including harmonized pre-analytics, batch-aware study design, leakage-resistant validation, and computational harmonization. A translational roadmap linking analytical validity, locked-model development, and prospective colonoscopy-verified clinical validation is proposed, aligned with TRIPOD + AI, STARD, PROBAST-AI, SPIRIT-AI, CONSORT-AI, and DECIDE-AI reporting standards. Scenario modeling using BLUE-C prevalence estimates suggests that improving APL sensitivity from approximately 43% to 55–65% at ~94% specificity could translate to detecting roughly 13–23 additional advanced precancerous lesions per 1000 individuals screened, highlighting the potential prevention impact of a multi-omic approach. This framework aims to guide developers and clinical investigators toward next-generation stool tests capable of materially improving precursor-lesion detection while maintaining clinically acceptable specificity.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of malignancies characterized by varying degrees of aggressiveness and clinical behavior. Despite advancements in treatment, including targeted therapies such as sunitinib and everolimus, peptide receptor radionuclide therapy with [177Lu]Lu-DOTATATE, and chemotherapy regimens like capecitabine plus temozolomide, the advanced GEP-NETs remain largely incurable. The limited efficacy of current treatments highlights the urgent need for novel therapeutic strategies. Recent years have seen a rise in several landmark clinical trials aimed at exploring new agents and combinations to improve patient outcomes in GEP-NETs. This literature review focuses on the ongoing clinical trials that hold promise for advancing the treatment landscape of GEP-NETs. We include some industry- and cooperative group-sponsored, phase II-III, randomized, and comparative trials in our review. We analyze the design, rationale, objectives, and preliminary findings of these trials, with a particular emphasis on those with pending results that may offer new insights into potential therapeutic targets. By examining these trials, we aim to provide a comprehensive overview of the evolving strategies in the management of GEP-NETs and underscore the importance of continued research innovation in addressing the challenges posed by the heterogeneity of GEP-NETs and in the pursuit of more effective and potentially curative treatment options.

Insulin resistance (IR) is a prevalent metabolic condition characterized by reduced cellular responsiveness to insulin and consequent hyperinsulinemia, and it is a key component of type 2 diabetes and metabolic syndrome. A growing body of evidence suggests IR is a critical accomplice in the pathogenesis of various cancers. This review synthesizes evidence on underlying molecular mechanisms, including the integrated roles of the insulin/IGF system, chronic inflammation, metabolic reprogramming, and mitochondrial dysfunction. This review proposes that metabolic dysregulation should be viewed as a modifiable oncogenic force. This perspective illuminates new pathways for understanding cancer development and offers promising avenues for prevention and therapeutic intervention.

Post-transfusion purpura (PTP) is a rare, immune-mediated disorder characterised by severe thrombocytopaenia occurring 5–12 days after a blood transfusion. It occurs in approximately from 1 out of 24 000 to 1 out of 100 000 transfusions. It occurs when the immune system attacks transfused platelets, particularly those with the human platelet antigen-1 a (HPA-1a), which the body recognises as foreign if the person has been previously exposed to it. This antigenic reaction is more likely in individuals with a history of pregnancies or transfusions involving platelets expressing HPA-1a. Patients who has anti-HPA- 1a antibodies after having being exposed to platelets which contains HPA-1a antigens following pregnancy or blood transfusion are at risk of PTP. The management of PTP typically involves transfusing platelets lacking this antigen, immunosuppression, plasmapheresis to remove antibodies and close monitoring. This case report highlights a rare and life-threatening complication of PTP—the first documented occurrence of diffuse alveolar haemorrhage (DAH) in an elderly patient with a remote history of immune thrombocytopaenic purpura. The patient developed respiratory distress, diffuse petechiae and profound thrombocytopaenia 8 days after receiving a blood transfusion for symptomatic chronic anaemia. A comprehensive diagnostic workup, including bronchoscopy, confirmed the presence of DAH. Prompt recognition and management, involving specialised blood products, immunosuppression and close monitoring, led to a successful outcome in this complex clinical scenario. This case underscores the challenges in diagnosing and managing PTP, especially in elderly patients with multiple comorbidities and a history of blood disorders. It highlights the critical importance of swift identification and intervention to prevent life-threatening complications in such patients.

Introduction and importance: Renal cell carcinoma (RCC) represents 90% of renal malignancies with rising global incidence. While the classic triad includes hematuria, flank pain, and palpable masses, paraneoplastic hypercalcemia occurs in 17% of cases and indicates aggressive disease behavior. This case documents severe hypercalcemia as the initial manifestation of metastatic RCC. Case presentation: A 64-year-old male presented with malaise, bloating, and weight loss. Laboratory evaluation revealed severe hypercalcemia (15.1 mg/dL), suppressed parathyroid hormone (4.2 pg/mL), and elevated parathyroid hormone-related peptide (83 pg/mL). Imaging identified a 5.5 × 5.0 × 5.3 cm left renal mass with metastases to lungs, brain, and possibly bone. Biopsy confirmed metastatic clear-cell RCC. Management comprised aggressive hydration, zoledronic acid, combined immunotherapy (pembrolizumab/lenvatinib), and palliative radiation for cerebral lesions. Clinical discussion: This case illustrates PTHrP-mediated humoral hypercalcemia of malignancy in metastatic RCC. The pathophysiology differs from alternative mechanisms such as calcitriol-mediated hypercalcemia or cytokine-driven osteoclast activation. Diagnostic markers demonstrated a classic humoral pattern with PTHrP elevation (83 pg/mL) and PTH suppression (4.2 pg/mL). The multimodal imaging protocol effectively delineated primary tumor dimensions, vascular invasion, and metastatic burden. Treatment efficacy was objectively measured through serial calcium levels and documented radiographic regression of primary and metastatic lesions. This aligns with recent data on combination immunotherapy (anti-PD-1) with tyrosine kinase inhibition in advanced RCC, supporting current therapeutic paradigms for PTHrP-mediated hypercalcemia in metastatic disease. Conclusion: Prompt recognition of paraneoplastic hypercalcemia in RCC facilitates timely intervention. This case demonstrates the value of comprehensive diagnostic evaluation and multidisciplinary management combining supportive care with targeted immunotherapy. Further prospective studies are needed to optimize therapeutic strategies for patients presenting with metabolic derangements suggestive of underlying malignancy.

Esophageal cancer is a highly lethal cancer with notable global variations in incidence and risk factors. In the U.S., it ranks as the fifth most common gastrointestinal cancer, with around 16,940 new cases annually, while globally, it is the sixth most common cancer. Significant regional disparities are highlighted by the "esophageal cancer belt" across northern Iran, southern Russia, central Asia, and northern China, where squamous cell carcinoma (SCC) dominates, comprising 90% of cases. In contrast, the U.S. has seen a rise in esophageal adenocarcinoma, primarily due to obesity and gastroesophageal reflux disease, with SCC rates declining as tobacco and alcohol use decrease. Key trials have shaped current treatment approaches. The CROSS trial (2012) showed a survival advantage with neoadjuvant chemoradiotherapy (carboplatin/paclitaxel with radiotherapy) plus surgery over surgery alone, extending median overall survival (OS) from 24 to 49.4 months. The FLOT4 trial (2017) established perioperative FLOT chemotherapy as superior to ECF/ECX, with median OS increasing from 35 to 50 months. The Neo-AEGIS trial (2020) found comparable OS between the CROSS and perioperative chemotherapy regimens, supporting treatment flexibility. Recently, the ESOPEC trial (ASCO 2024) demonstrated a median OS benefit with perioperative FLOT (66 months) over CROSS (37 months) in resectable esophageal adenocarcinoma, positioning FLOT as the preferred strategy. These findings highlight the value of tailored, multimodal therapies in enhancing survival and quality of life for esophageal adenocarcinoma patients. Future research will explore immunotherapy's role and the potential to omit surgery in patients achieving a complete pathological response.

This case report presents the first known instance of pembrolizumab-induced autoimmune encephalitis in a 41-year-old female patient with stage IIIc triple-negative breast cancer. The patient developed expressive aphasia three days after starting pembrolizumab in combination with chemotherapy, prompting comprehensive evaluations that ruled out infectious or metastatic causes. A diagnosis of pembrolizumab-associated autoimmune encephalitis was established following a lumbar puncture and MRI. After discontinuing the immune checkpoint inhibitors (ICI) and initiating high-dose corticosteroids (methylprednisolone), the patient's symptoms significantly improved within days. This case highlights the importance of recognizing and managing neurological immune-related adverse events (irAEs) associated with ICIs, as their incidence can be variable but potentially severe. Clinicians must maintain a high index of suspicion for neurological irAEs, especially with new neurological symptoms, as early diagnosis and intervention are crucial for optimizing patient outcomes while balancing effective cancer treatment. Ongoing research is essential to elucidate the mechanisms and management strategies for ICI-related autoimmune encephalitis.

Immune checkpoint inhibitors (ICIs), including programmed cell death protein 1 (PD-1) inhibitors, such as nivolumab, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, such as ipilimumab, have revolutionized cancer treatment, particularly in metastatic melanoma. However, these therapies can cause immune-related adverse events (irAEs), including myositis, a rare but significant complication characterized by elevated creatine kinase (CK) and muscle weakness. We present the case of a 79-year-old male with a history of metastatic melanoma to the brain, previously treated with nivolumab and ipilimumab, who was admitted after an unwitnessed fall. Initial laboratory tests revealed significantly elevated CK levels (5277 U/L) and mildly elevated liver function tests (LFTs). Despite the absence of muscle pain or weakness upon presentation, the patient developed proximal muscle weakness and myalgias during hospitalization. Extensive workup, including negative autoimmune panels and imaging, raised suspicion of immune-related myositis given the recent ICI therapy. The patient was treated with prednisone, which resulted in a rapid decrease in CK levels and improvement of symptoms, supporting the diagnosis of ICI-related myositis.

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, characterized by abnormal growth of mature B cells in the blood, bone marrow, and lymphoid tissues. Although CLL primarily affects the hematopoietic system and lymph nodes, renal involvement is exceptionally rare and presents diagnostic and treatment challenges. Potential causes of renal failure in CLL patients include sepsis, dehydration, tumor lysis syndrome (TLS), compression of the ureter by enlarged lymph nodes, and side effects of cancer therapy. This report presents a case of CLL with renal infiltration leading to severe renal failure, discussing the clinical presentation, diagnostic workup, and management of this condition.