The efficacy of cryosurgery for skin cancers is believed to depend on thaw time, which may be influenced by the presence of adrenaline in local anaesthetics due to its vasoconstrictive effects. This is the first study to perform detailed, non-invasive temperature measurements using infrared (IR) thermography during cryosurgery for basal cell carcinomas (BCCs), evaluating the impact of adrenaline on thaw time. A total of 15 patients with eyelid BCCs underwent cryosurgery with local anaesthetics both with and without adrenaline. Thawing was continuously monitored using a high-resolution IR camera and compared with the surgeon's visual assessment. No significant difference in thaw time was observed between anaesthetics with and without adrenaline. Thermographic mapping revealed a triphasic thawing curve. The surgeon's visual assessment of thawing corresponded well with the point at which tissue temperatures rose above 0°C, likely indicating the onset of reperfusion, thus providing a clinical margin beyond the actual phase transition. This is the first study to use IR thermography to monitor cryosurgery of BCCs, demonstrating that adrenaline in local anaesthetics does not affect thaw time. The findings suggest that deeper tissue perfusion during BCC treatment may counteract superficial vasoconstriction, supporting the effective use of cryosurgery regardless of adrenaline use.

Allogeneic hematopoietic cell transplantation (allo-HCT) offers curative potential for acute myeloid leukemia (AML) through its graft-versus-leukemia (GVL) effects, but this same alloreactivity can cause graft-versus-host disease (GVHD), making separation of these effects a central challenge. Proposed mechanisms of post-allo-HCT immune evasion by AML cells include HLA loss via 6p loss of heterozygosity, epigenetic HLA class II silencing, upregulation of immune-suppressive ligands on AML cells, and persistence of leukemia stem cells (LSCs) after transplantation. In addition, donor T-cell exhaustion and an immunosuppressive tumor microenvironment may contribute to post-transplant relapse. We summarize emerging strategies to ameliorate GVHD without attenuating GVL, including intensified local therapy, selective trafficking blockade, S1PR modulators that limit pathogenic T-cell migration, and tissue-protective agents that enhance epithelial regeneration and prevent the establishment of inflammatory memory. We also outline maintenance approaches designed to restore leukemia immunogenicity without exacerbating GVHD, including inhibition of MDM2, EZH2, menin, and FLT3-ITD; IFN-α-based immune modulation; hypomethylating agents; and minor histocompatibility antigen-directed vaccines intended to selectively elicit anti-leukemia alloresponses. Finally, optimization of calcineurin inhibitor timing in post-transplant cyclophosphamide-based allo-HCT may help balance GVHD prevention and GVL preservation. Collectively, these growing mechanistic and clinical insights are making functional separation of GVL from GVHD increasingly feasible.

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are driven by recurrent driver mutations and evolve through the stepwise accumulation of additional genetic alterations and clonal evolution. Some large cohort studies have demonstrated that individual additional mutations significantly influence prognosis, leukemic transformation, and progression to myelofibrosis. Furthermore, certain mutations frequently co-occur with other adverse mutations and may act as molecular hubs that amplify clinical impact. Based on these findings, mutation-integrated scoring systems have been developed to improve risk stratification and refine therapeutic decision-making. However, despite the recent adoption of comprehensive genomic testing in clinical practice, there is still limited evidence to guide treatment selection or determine the optimal timing of therapeutic intervention based on mutational profiles or molecular monitoring results. A deeper understanding of clonal evolution, grounded in genomic abnormality data, will be essential for establishing more rational and biology-driven therapeutic strategies.

An 80-year-old man was diagnosed with acute myeloid leukemia (AML), and molecular analysis identified FLT3-ITD, TKD mutations. Induction chemotherapy with daunorubicin plus cytarabine achieved hematological complete remission; however, extramedullary infiltration was detected in the skin and central nervous system. Due to this extramedullary disease, treatment with mitoxantrone plus high-dose cytarabine was administered, leading to systemic complete remission. Two cycles of the same regimen were then added. The patient relapsed 5 months later, at which time FLT3 mutations were no longer detectable by a companion diagnostic test. However, targeted sequencing analysis identified a novel FLT3-ITD positive minor clone. Treatment with venetoclax plus azacitidine was then started. The patient achieved complete remission and has remained relapse-free for more than 2 years. In this case, the FLT3 mutation companion diagnostic test result became spontaneously negative without FLT3-directed treatment, and the response to venetoclax plus azacitidine was favorable. This case highlights the importance of molecular testing not only at diagnosis but also at relapse for appropriate treatment selection.

Poroid hidradenocarcinoma is a rare malignant sweat gland neoplasm. Although primary nodal hidradenoma has been reported, primary nodal poroid hidradenocarcinoma has not been described. We report a case of a 56-year-old man presenting with a nontender 5.5 cm mass within the axillary lymph node, and no identifiable primary cutaneous lesion on clinical examination or imaging. Histopathologic examination of the axillary lymph node dissection revealed involvement of 1 of 42 lymph nodes by a multinodular, solid and cystic neoplasm composed of poroid and cuticular cells with ductal differentiation, consistent with a background poroid hidradenoma. There was an abrupt transition to malignant areas with marked cytologic atypia, nuclear pleomorphism, increased mitotic activity, elevated Ki-67 proliferation index and necrosis, supporting the diagnosis of poroid hidradenocarcinoma. Tumor cells were positive for CK5 and CK7. Molecular analysis identified a YAP1::NUTM1 fusion and oncogenic mutations in EGFR exon 20 and FBXW7. At 30 months of follow-up after axillary lymph node dissection and chemoradiation, there was no evidence of disease progression. This case represents the first report of primary nodal poroid hidradenocarcinoma, expanding its clinicopathologic spectrum. Awareness of this entity is important to avoid misdiagnosis as metastatic carcinoma and to prevent potential overtreatment.

Colon cancer is one of the most prevalent cancers globally, characterized by the abnormal growth of cells in the intestines. Numerous studies have explored the effects of pomegranate-derived products, such as pomegranate seed oil (PSO), as anti-proliferative, anti-invasive, and pro-apoptotic agents against various cancer cell lines. Additionally, previous research has highlighted the anti-cancer properties of low-frequency electromagnetic fields (LF-EMF). In the present study, we investigated the combined effects of these two factors on the expression of the Caspase 3, Caspase 9, BAX, and Bcl2 genes. Human colon cancer cells of the HT29 line were sourced from the Pasteur Institute of Iran cell bank and maintained in a complete culture medium. The cells were categorized into four groups: control, PSO, EMF, and PSO+EMF. To assess cell viability and the type of cell death, MTT and Annexin V-FITC assays were employed. Changes in the expression levels of Caspase 3, Caspase 9, BAX, and Bcl2 were analyzed using Real-Time PCR. The results from the MTT and Annexin V-FITC assays indicated that both PSO and EMF reduced cell viability and promoted apoptosis in colon cancer cells. The Real-Time PCR results showed an upregulation of Caspase 3, Caspase 9, and BAX genes, along with a downregulation of Bcl2 expression in the treatment groups compared to the control group. This study demonstrated that the combination of PSO and EMF enhances apoptotic gene expression, thereby diminishing the proliferation and viability of cancer cells. Based on these findings, both PSO and LF-EMF exhibit cytotoxic effects on colon cancer cells, suggesting their potential as candidates for future research in the field of colon cancer.

The cGAS/STING pathway is a central innate immune DNA-sensing system that links aberrant DNA species to innate immune and stress-response transcriptional programs and has emerged as a key regulator of tumor-immune interactions. In cancer, pathway outputs are shaped by interconnected downstream signaling modules, including type I IFN, NF-κB, autophagy, and stress-metabolic checkpoints, as well as by stringent spatial and biochemical regulation of both cGAS and STING. When activation is acute and appropriately compartmentalized, cGAS/STING signaling promotes antitumor immunity across multiple cellular compartments in the tumor microenvironment, supporting DC cross-priming and cytotoxic lymphocyte responses. In contrast, chronic or dysregulated activation rewires downstream signaling toward stress-adaptive and inflammatory programs that promote tumor progression, metastasis, and immune dysfunction, including deleterious effects in lymphocytes and the induction of suppressive myeloid and B cell populations. Here, we examine how context determines the consequences of cGAS/STING activation in cancer, review emerging therapeutic strategies that modulate this pathway, and discuss how its antitumor potential can be maximized while minimizing systemic toxicity and immune dysregulation.

Functioning pancreatic neuroendocrine carcinoma (pNEC) is relatively less common. Here, we report a middle-aged lady, initially diagnosed as primary ductal carcinoma of the breast with multiple metastases, who was managed with excision biopsy of the breast tumor and palliative chemotherapy elsewhere. She later developed recurrent episodes of hypoglycemia following chemotherapy and was found to have hyperinsulinemic hypoglycemia, clearly suggestive of insulinoma. Ga-68 DOTANOC PET-CT scan showed DOTA-avid primary lesion in pancreas with intense uptake in several sites, including liver, bilateral adnexa, and intra-abdominal lymph nodes, favoring a probable functioning pancreatic neuroendocrine tumor (pNET) with distant metastases. Histopathology of her breast lesion was then re-examined, which showed features of neuroendocrine carcinoma (NEC) that was confirmed with immunohistochemistry (IHC), thus establishing the diagnosis of functioning pNEC. She was treated conservatively with octreotide and diazoxide for recurrent and refractory level 2 and 3 hypoglycemia. She was later discharged at her request on octreotide in a relatively stable condition, but died a week later. Despite being rare, diagnosing insulin-secreting pNEC is quite challenging. However, the diagnosis can be established based on radiological clues, somatostatin receptor expression based on functional imaging, and careful histopathological examination with appropriate IHC.

A 74-year-old man presented with leg edema and was found to have nephrotic-range proteinuria. Renal biopsy revealed AL amyloidosis. Subsequent bone marrow examination demonstrated an increase in monoclonal plasma cells accounting for 13% of nucleated cells. Right-sided pleural effusion developed and was confirmed to be chylothorax. Although treatment with daratumumab, lenalidomide, and dexamethasone (DLd regimen) was initiated, the pleural effusion continued to increase. Lymphangiography using ethiodized oil identified a leakage point in the anterior mediastinum. A chest drain was inserted on the following day, and approximately 4 l of chylous fluid was drained. The tube was removed one week later, and pleural effusion did not recur thereafter. Although a hematologic response was achieved, the nephrotic syndrome persisted, and the patient ultimately died. Chylothorax associated with AL amyloidosis is rare and difficult to treat. This case suggests that lymphangiography using ethiodized oil may be both diagnostic and therapeutic.

Respite care, particularly short-stay services, is essential for maintaining the quality of life in children and adults with severe motor and intellectual disabilities (SMID) and their caregivers. This study evaluated the impact of the COVID-19 pandemic on short-stay service utilization by children and adults with SMID.

A retrospective study of individuals (N = 54) who received short-stay services at a medical-type residential facility in Japan between January 2017 and December 2025 was conducted. Utilization was compared across three phases: pre-pandemic (January 2017-December 2019), pandemic (January 2020-April 2023), and post-pandemic (May 2023-December 2025). Participants were categorized into Care and Non-care groups according to their need for intensive home medical care (e.g., ventilator, suctioning).

The total number of utilization days per month was significantly decreased during the pandemic phase (49.4 ± 15.6 days; p < 0.001), but dramatically increased in the post-pandemic phase (92.1 ± 16.3; p < 0.001), compared to pre-pandemic levels (62.1 ± 10.9 days). During the pandemic, the proportion of utilization days in the Care group was significantly increased (91.4% vs. 85.9% pre-pandemic; p = 0.001), indicating persistent and high demand among medically fragile cases. Intra-ward COVID-19 outbreaks were associated with temporary declines in utilization.

The pandemic dynamically altered respite care utilization patterns. The relative maintenance of utilization by the Care group during the pandemic underscores the indispensable nature of these services for families of individuals with high medical needs. The post-pandemic surge suggests accumulated caregiver exhaustion, highlighting the need for robust institutional capacity and infection control to ensure service continuity during future pandemics.