Tatsuya Kato

Background: Early detection of lung adenocarcinoma remains challenging despite advances in low-dose computed tomography (LDCT) screening. Urinary microRNAs (miRNAs) represent a non-invasive biomarker modality, but their clinical utility in early-stage disease remains unclear. This study aimed to identify urinary miRNA candidates associated with early-stage lung adenocarcinoma and to explore whether urinary miR-574-5p may provide complementary diagnostic information beyond established clinical risk factors. Methods: We conducted an exploratory case-control study using urinary samples from the J-CAN cohort, a prospective biomarker study. Small RNA sequencing was performed to profile miRNAs. Candidate miRNAs were identified using edgeR and the Wilcoxon rank-sum test. Associations with lung cancer status were evaluated using multivariable Firth logistic regression adjusted for age, sex, smoking status, and urinary creatinine. Model performance was assessed using the area under the curve (AUC), and internal validation was performed using bootstrap resampling. Results: A total of 77 participants (33 early-stage lung adenocarcinoma (stage 0–IA2) and 44 healthy controls) were included in the primary analysis. Among candidate miRNAs, miR-574-5p showed the most consistent overall signal. Urinary miR-574-5p expression was significantly decreased in patients with early-stage adenocarcinoma and remained independently associated with lung cancer status after adjustment [odds ratio (OR) 0.15, 95% confidence interval (CI): 0.02–0.53, PConclusions: Urinary miR-574-5p was decreased in early-stage lung adenocarcinoma and was independently associated with disease status. Although its incremental diagnostic value was modest, urinary miR-574-5p may provide limited complementary information beyond established clinical risk factors. Further validation in independent and prospective cohorts is warranted.

Background: Lung cancer continues to be associated with a dismal prognosis, despite the recent development of multiple therapeutic modalities. Consequently, there remains an urgent need for the advancement of novel and more efficacious treatment strategies. Cluster of Differentiation 44 (CD44), a cell surface marker associated with cancer stem cells, has been implicated in tumor progression, metastasis, and resistance to therapy, thereby representing a compelling target for oncologic intervention. Near-infrared photoimmunotherapy (NIR-PIT) is an emerging cancer treatment modality that integrates the high specificity of monoclonal antibodies with cytotoxic effects induced by a photosensitizer upon exposure to NIR light. In the present study, we evaluated the therapeutic efficacy of CD44-targeted NIR-PIT utilizing an orthotopic lung cancer mouse model established via transtracheal tumor cell injection, which more faithfully recapitulates the tumor microenvironment compared to conventional subcutaneous models. Methods: An antibody–photoabsorber conjugate was synthesized by conjugating an anti-CD44 monoclonal antibody (IM7) with IRDye700DX (IR700). The cytotoxic effects of CD44-targeted NIR-PIT were assessed in vitro using CD44-expressing lung cancer cell lines. Therapeutic efficacy was subsequently evaluated in an orthotopic lung cancer mouse model established by transtracheal injection of tumor cells. Tumor progression was monitored by bioluminescence imaging, and survival and histopathological changes were analyzed following treatment. Results: In vitro experiments employing CD44-expressing cell lines demonstrated that CD44-targeted NIR-PIT induces cytotoxicity in a light dose-dependent manner. The in vivo therapeutic efficacy was subsequently assessed using the orthotopic lung cancer mouse model. Following CD44-targeted NIR-PIT, bioluminescence imaging revealed a marked reduction in tumor burden, accompanied by an exploratory difference in survival in a small cohort. Histological analysis further demonstrated tumor cell elimination and intratumoral hemorrhage in the treated lesions. Conclusions: CD44-targeted NIR-PIT demonstrated potent antitumor activity in an orthotopic lung cancer model. These findings support the potential clinical translation of CD44-targeted NIR-PIT as a novel therapeutic strategy for lung cancer. Further studies are warranted to optimize clinically feasible light-delivery methods and establish the long-term safety of this approach.

Marfan syndrome (MFS) is a hereditary connective tissue disorder characterized by cardiovascular and skeletal abnormalities. While cardiovascular pathology is well described, the microscopic features of peripheral vasculature remain poorly characterized. We report a case of perioperative pulmonary arterial rupture in a patient with FBN1 ‐related MFS. A 17‐year‐old woman underwent bullectomy for spontaneous pneumothorax. Although the procedure was initially uneventful, unexpected bleeding developed beneath the staple line immediately after reinflation for the post‐bullectomy air‐leak test, necessitating additional wedge resection. Histologically, a ruptured pulmonary arterial branch was identified adjacent to the staple line. Patchy foci of hyperacute vascular injury with hemostatic plugs were identified on the luminal surface, and the surrounding airspaces were filled with fresh blood. The affected arterial wall showed mucoid extracellular matrix accumulation and disorganization of smooth muscle bundles. Furthermore, the medial layer demonstrated an aberrant distribution of elastic fibers, deviating from the normal architecture of muscular arteries. These findings highlight previously underrecognized microscopic features of peripheral arterial involvement in FBN1 ‐related MFS, characterized by latent structural fragility associated with abnormal vascular patterning. Surgery‐associated hemodynamic changes, including perioperative reinflation for an air‐leak test, which would be tolerated under normal conditions, may precipitate vascular injury and rupture.

Background: Percutaneous radiofrequency ablation (RFA) is a widely accepted, minimally invasive treatment for hepatic tumors. However, it can rarely cause severe complications, including visceral and diaphragmatic perforation leading to acute empyema. Such complex scenarios, particularly in patients with underlying liver cirrhosis and malignancy, require a highly specialized management strategy. We report a successful treatment case utilizing a staged, multidisciplinary approach prioritizing source control. Case Description: A 76-year-old man with Child-Pugh B cirrhosis, previously treated for descending colon cancer and liver metastases, presented with fever and malaise 90 days after his third RFA session. Imaging revealed a right subphrenic abscess contiguous with the transverse colon and right pleural space, suggesting a delayed iatrogenic perforation caused by thermal injury. We diagnosed acute empyema secondary to pleuro-colonic communication. Given the severe infection and extensive adhesions, we executed a three-stage therapeutic strategy. Stage 1 involved thoracic infection control via drainage and thoracoscopic debridement. Stage 2 addressed the abdominal source; a diverting ileostomy was created to mitigate contamination, followed later by a right hemicolectomy and diaphragmatic repair using a Gerota’s fascia patch. Stage 3 managed the residual refractory empyema and persistent air leak through an open window thoracostomy, followed by bronchial occlusion using endobronchial Watanabe spigots. The patient fully recovered, was discharged on day 162, and remains recurrence-free at the 15-month follow-up. Conclusions: Delayed colonic and diaphragmatic perforation is a rare but life-threatening complication of hepatic RFA. A rigorous staged, multidisciplinary approach focused on definitive source control and management of chronic pleural complications is essential for a favorable outcome in such complex cases.

Purpose Serum levels of cardiovascular markers, including brain natriuretic peptide (BNP), are associated with the prognosis of cancer patients. This study examined the relationship between the preoperative blood BNP level and the long-term prognosis after curative lung cancer resection. Methods Patients who underwent radical resection for lung cancer at our institution between January 2012 and June 2019 were divided into the high- (≥ 18.5 pg/ml) and low- (< 18.5 pg/ml) BNP groups. Kaplan–Meier curves were used to analyze the postoperative overall survival (OS) and relapse-free survival (RFS). The cumulative incidence function (CIF) was analyzed using the Gray’s test. Univariate and multivariate Cox proportional hazards models were used to identify independent predictors of the OS. Results The postoperative OS was significantly worse in the high-BNP group than in the low-BNP group (p = 0.03), but there was no statistically significant difference in the RFS (p = 0.09). A CIF analysis indicated that non-cancer-related deaths had a greater impact on the RFS than cancer recurrence. Blood BNP levels possibly affected the OS independently (hazard ratio, 1.50). Conclusions Preoperative BNP levels in patients with lung cancer may indicate a potentially compromised condition and can be associated with the postoperative OS. However, the link between the BNP level and lung cancer severity remains unclear.

Recent advancements in lung cancer treatment, including molecular targeted therapies and immune checkpoint inhibitors, have significantly improved patient outcomes and extended survival. However, the efficacy and safety of salvage surgery for lesions resistant to targeted therapy like osimertinib remain poorly understood. This report highlights a case of salvage surgery performed on a patient with epidermal growth factor receptor (EGFR)-mutant lung cancer resistant to osimertinib. A 60-year-old woman was diagnosed with lung adenocarcinoma (cT1cN3M0, cStage IIIB) harboring an EGFR exon 19 deletion (L747-A750>P). Initial treatment with afatinib yielded a favorable tumor response for 18 months, but disease progression ensued. Osimertinib was subsequently initiated after detection of the EGFR T790M mutation, demonstrating initial efficacy. Nineteen months later, regrowth of a lung lesion was observed, although radiographic evaluation showed no lymph node enlargement, with disease confined to the right upper lobe. A robot-assisted right upper lobectomy with lymph node dissection was successfully performed. During surgery, the patient experienced refractory atrial fibrillation, which was successfully managed with defibrillation. Pathological analysis confirmed metastasis to the right upper mediastinal lymph nodes. The EGFR exon 19 deletion mutation was detected in the resected tumor, while the T790M mutation was absent. The patient has remained disease-free for 10 months without additional treatment. Salvage surgery following molecular targeted therapy for lung cancer has been reported to be effective for selected patients. However, the mechanisms of resistance to osimertinib are diverse, and the efficacy of salvage surgery for patients with osimertinib resistance is not well understood. In this case, although the postoperative observation period is still short, salvage lung resection suggests the possibility of leading to favorable disease control. With a thorough evaluation of surgical indications and appropriate management of several complications associated with the prior treatment, salvage surgery can be a valuable and viable option for selected patients.

Background: Good’s syndrome is a rare immunodeficiency disorder associated with thymomas and hypogammaglobulinemia. Although thymectomy is needed to prevent local invasion and metastasis, the prognosis of patients can be poor owing to repeated severe infection-related complications. Recently, robotic-assisted thoracoscopic surgery (RATS) is increasingly performed for resection of thymomas. At our institution, we have treated seven surgical cases of Good’s syndrome from 2007 to 2023 including three RATS cases. Here, we discuss the ideal surgical treatment for Good’s syndrome. Case Description: All seven patients had preoperative infectious complications such as candidiasis, and received intravenous immunoglobulin. Median sternotomy was performed for two patients, video-assisted thoracoscopic surgery (VATS) was conducted for other two cases, and remaining three cases received RATS. Intraoperative blood loss was less than 10 mL in RATS cases, smaller than that in the other surgical cases. Early postoperative infectious complications were not observed in the three patients who underwent RATS. In all cases, surgical complete resection was achieved and recurrence of thymoma has not been noted. However, no cases showed improvement of hypogammaglobulinemia, and interestingly three including one RATS case developed pure red cell aplasia following thymectomy. Of the two patients who underwent VATS, one died of severe cytomegalovirus infection 8 years after thymectomy and the other died of lung adenocarcinoma 5 years postoperatively. Several reports revealed that RATS for thymectomy has some advantages including reduced blood loss and fewer perioperative infectious complications compared with median sternotomy. RATS enables earlier ambulation, and thus decreases the risk of pneumonia as well as sternal osteomyelitis. Moreover, some studies have reported that the R0 resection rate of robotic thymectomy is equivalent to that of median sternotomy even for large thymomas. The present study suggested these advantages of RATS, although the number of cases is small. Conclusions: RATS can be a feasible surgical treatment for Good’s syndrome that ensures reduced blood loss, lower risk of postoperative infection, and complete resection of thymoma. However, hypogammaglobulinemia and accompanying autoimmune manifestations might not be improved even after surgery, and careful perioperative management is essential.

Background: L-carnitine is essential in lipid metabolism and reportedly has preventive effects for arrhythmia. Our objective was to examine the incidence of postoperative atrial fibrillation (POAF) and changes in serum biomarker levels following perioperative L-carnitine administration in patients with lung cancer. Methods: Thirteen patients undergoing a lobectomy with preoperative serum brain natriuretic peptide levels >24 pg/mL were perioperatively administered L-carnitine for 5 days (3 g/3×). Accurate 95% confidence intervals (CI) for POAF incidence were calculated. Serum biomarkers for POAF in lung cancer and target proteins for L-carnitine were evaluated by using open-source data from proteomic analysis. Results: The incidence of POAF was 38.5% (95% CI 13.9%–68.4%). Fatty acid-binding protein 4 (FABP4) was selected as a candidate biomarker from 1472, 63, and 26 proteins related to lung cancer, L-carnitine, and AF, respectively. A positive correlation was observed between the predicted POAF incidence rate and preoperative FABP4 levels (Pearson’s r = 0.5183). The mean change in serum FABP4 after L-carnitine administration for 5 days was −2.9 ng/mL (95% CI −4.9 to −0.89 ng/mL). Conclusions: The incidence of POAF after a lobectomy was 38.5% after the perioperative administration of L-carnitine for patients at a high risk of POAF. The serum FABP4 level demonstrates potential as a candidate biomarker for POAF prediction.