Aim : Near-infrared photoimmunotherapy (NIR-PIT) is a new, highly selective tumor treatment that employs a NIR phthalocyanine dye, IRDye 700DX (IR700), conjugated to a monoclonal antibody (mAb). Although NIR light exposure leads to immediate, target-selective necrotic cell death, actual tumor shrinkage occurs several days afterwards. Therefore, it is difficult to detect the immediate therapeutic effects by measuring tumor size. This study investigated IR700 fluorescence changes by means of fluorescence endoscopy as a potential real-time biomarker for monitoring cytotoxic effects during NIR-PIT.
Methods : In vivo mouse experiments were conducted with a human epidermal growth factor receptor type 2-expressing, green fluorescence protein (GFP)-expressing, gastric cancer cell line (N87-GFP). IR700 as a photosensitizer was conjugated to trastuzumab. The effects of NIR-PIT were evaluated in a flank xenograft model as well as in a disseminated peritoneal cancer model by GFP and IR700 real-time fluorescence imaging. Fluorescence intensity was compared before and after NIR-PIT for calculations of relative decreasing of fluorescence intensity (DFI).
Results : Tumor growth was significantly reduced and survival was significantly improved in the IR700 DFI ≤25％ group compared with the IR700 DFI >25％ group in Pearl images (p<0.05) in the flank xenograft model. In the disseminated peritoneal cancer model, an effective NIR-PIT therapeutic response was observed in the IR700 DFI ≤50％ group on fluorescence endoscopy.
Conclusion : IR700 fluorescence signal decrease during NIR-PIT may be a potential immediate indicator of the therapeutic effects of mAb-IR700-based NIR-PIT prior to the onset of tumor shrinkage.

View full abstract

Background : Cardiac surgery-associated acute kidney injury (CS-AKI) following pediatric cardiac surgery is associated with increased postoperative mortality and prolonged pediatric intensive care unit (PICU) stay. Early diagnosis and intervention are therefore essential. We retrospectively evaluated whether CS-AKI could be predicted using perioperative blood parameters, cardiopulmonary bypass (CPB) data, and postoperative furosemide responsiveness.
Methods : This retrospective study included 238 patients admitted to the PICU of Nagano Children's Hospital between April 2020 and March 2024. Age, body surface area (BSA), preoperative and postoperative serum creatinine (sCr), blood urea nitrogen (BUN), sodium, potassium, chloride, albumin, postoperative bicarbonate, lactate, serum osmolality, CPB time, and postoperative furosemide responsiveness were compared between AKI and non-AKI groups. Variables showing significant differences were analyzed to identify predictors of AKI onset.
Results : Significant differences between the AKI and non-AKI groups were observed in age, BSA, ΔCr (postoperative sCr-preoperative sCr), ΔK, CPB time, time to furosemide administration, and urine volume in response to furosemide. Logistic regression analysis identified CPB time, ΔCr, and furosemide-induced urine output as the most relevant predictors. In contrast, furosemide administration timing, BSA, ΔK, and age were less predictive. Highly relevant data were assigned a score of 2, and others a score of 1. A total score ≥6 predicted AKI onset with 90.8％ sensitivity and 90.5％ specificity.
Conclusion : Perioperative clinical and laboratory parameters can predict CS-AKI within 24 hours after pediatric cardiac surgery. Integrating these findings with established AKI biomarkers may further enhance prediction accuracy.

View full abstract

A 57-year-old women, foreigner residing in Japan, admitted to our hospital because of right lower abdominal pain. Whole computed tomography revealed a mass in the terminal ileum and oral intestinal distention without any pulmonary abnormal findings. Endoscopic examination of the lower digestive tract showed an irregularshaped mass in the terminal ileum causing stenosis. The pathological findings revealed the epithelioid cell granuloma accompanied by caseous necrosis. Although smear, PCR and culture for tuberculosis using the tissue were negative, interferon-gamma releasing assay was positive. Thus, the therapeutic diagnosis of intestinal tuberculosis was made and anti-tuberculosis therapy was initiated. The therapy had continued for one year, resulted in the complete remission in terminal ileum. Primary intestinal tuberculosis is extremely rare, however, physicians should be aware of the presence even in subjects without pulmonary involvement and immunodeficiency.

View full abstract