Multiplex intraoperative rapid immunohistochemistry with non-contact antibody mixing for distinguishing the histologic phenotype of lung cancer.

INTRODUCTION: Determining a surgical strategy for early-stage lung cancer requires an accurate histologic diagnosis. Immunohistochemistry (IHC) enables reliable diagnosis of histological types but requires more time and more tumor tissue slides than hematoxylin and eosin staining. We aimed to assess the clinical validity of a new rapid multiplex IHC technique utilizing alternating current (AC) mixing for intraoperative lung cancer diagnosis. METHODS: Forty-three patients who underwent radical resection of lung cancers were enrolled in a retrospective observational study. Frozen sections were prepared from lung tumor samples, and rapid IHC employing AC mixing was implemented alongside a multiplex IHC protocol targeting thyroid transcription factor-1 + Cytokeratin 5, Desmoglein 3 + Napsin A, and p63 + tripartite motif containing 29. We then evaluated the concordance between intraoperative diagnoses derived from rapid multiplex IHC and final pathology. RESULTS: The concordance rate between the pathological diagnosis made with added rapid multiplex IHC and the final pathology was 93.0% (Cohen's 𝜅 coefficient = 0.860 and 95% CI 0.727-0.993). When considering only adenocarcinoma and squamous cell carcinoma, the diagnoses were in agreement for all cases. CONCLUSIONS: We suggest rapid multiplex IHC as a promising tool for determining surgical strategies for lung tumors.

Proximal ligation technique prevents thrombus formation in the pulmonary vein stump after lobectomy.

PURPOSE: To assess the risk factors for thrombosis in the pulmonary vein stump (PVT) and the efficacy of proximal ligation in preventing PVT after lobectomy. METHODS: In total, 649 surgical patients with lung cancer were retrospectively reviewed. To compare the clinical effectiveness of PV proximal ligation, the simple stapler group (290 patients) and the proximal ligation group (359 patients who underwent thread ligation at the pericardial reflection with/without a stapler) were analyzed. RESULTS: In the simple stapler group, 12 of 290 patients (4.1%) developed PVT. Among these, 9 of 58 underwent left upper lobectomy (LUL). In contrast, 5 of the 359 patients (1.4%) in the proximal ligation group developed PVT. All five patients received LUL. The incidence of PVT in the proximal ligation group was significantly lower than that in the simple stapler group (p = 0.0295) as well as in the analysis by LUL alone (p = 0.0263). A logistic regression analysis indicated that higher BMI and LUL were associated with the development of PVT (p = 0.0031, p < 0.0001), and PV proximal ligation reduced PVT (p = 0.0055). CONCLUSION: Proximal ligation of the PV has the potential to prevent PVT, especially after LUL.

The outcome and risk factors for recurrence and extended hospitalization of secondary spontaneous pneumothorax.

PURPOSE: Secondary spontaneous pneumothorax (SSP) is difficult to treat by itself and due to its association with serious underlying diseases. It has a high rate of recurrence and often requires extended hospitalization. Therefore, we evaluated the outcome and risk factors associated with recurrence and extended hospitalization. METHODS: We retrospectively examined 61 patients with SSP, and evaluated the patients' characteristics, underlying diseases, introduction of home oxygen therapy, Brinkman index, and X-ray imaging findings to determine the risk factors for recurrence and extended hospitalization. RESULTS: There were 28 patients (46.0%) with chronic obstructive pulmonary disease, 8 (13.1%) with interstitial pneumonia, 16 (26.2%) with massive emphysema, and 9 (14.8%) with other diseases. Adhesion and mediastinal shift visualized by X-ray imaging were observed in 37 (37.9%) and 25 patients (40.1%), respectively. Recurrence occurred in 25 patients (40.9%) and the average hospitalization duration was 14.5 days (±11.2). A multivariate analysis showed that adhesion on X-ray imaging was a significant risk factor for recurrence (odds ratio 4.90, 95% confidence interval 1.38-21.44) and mediastinal shift on X-ray imaging was a significant risk factor for extended hospitalization (odds ratio 6.05, 95% confidence interval 1.44-31.06). CONCLUSIONS: Findings from X-ray imaging, and not underlying diseases, are risk factors for recurrence and extended hospitalization.

[Antineutrophil Cytoplasmic Antibody (ANCA) Negative Limited-form Granulomatosis with Polyangiitis of the Lung Diagnosed by the Thoracoscopic Lung Biopsy].

Antineutrophil cytoplasmic antibody (ANCA) negative pulmonary limited-form granulomatous with polyangiitis (GPA) is a rare type of GPA. A 53-year-old female had been followed as the possible pulmonary infarction of bilateral lungs for 4 years without any therapy. Chest computed tomography(CT) examination of the patient showed newly appeared nodular lesions in the lungs, which were suspected as malignancy by positron emission tomography (PET) -CT. Thoracoscopic lung biopsy of the lesions was performed and histopathological diagnosis was GPA showing multiple granulomas with vasculitis. Since both C and P-ANCA were negative and no evidence of kidney involvement, we finally diagnosed the lung lesions as ANCA negative limited-form GPA.

Does clinical T1N0 GGN really require checking for distant metastasis during initial staging for lung cancer?

BACKGROUND: Accurate clinical staging is crucial for selection of optimal oncological treatment strategies in non-small cell lung cancer (NSCLC). Although brain MRI, bone scintigraphy and whole-body PET/CT play important roles in detecting distant metastases, there is a lack of evidence regarding the indication for metastatic staging in early NSCLCs, especially ground-grass nodules (GGNs). Our aim was to determine whether checking for distant metastasis is required in cases of clinical T1N0 GGN. METHODS: This was a retrospective study of initial staging using imaging tests in patients who had undergone complete surgical R0 resection for clinical T1N0 Stage IA NSCLC. RESULTS: A total of 273 patients with cT1N0 GGNs (n = 183) or cT1N0 solid tumors (STs, n = 90) were deemed eligible. No cases of distant metastasis were detected on initial routine imaging evaluations. Among all cT1N0M0 cases, there were 191 incidental findings on various modalities (128 in the GGN). Most frequently detected on brain MRI was cerebral leukoaraiosis, which was found in 98/273 (35.9%) patients, while cerebral infarction was detected in 12/273 (4.4%) patients. Treatable neoplasms, including brain meningioma and thyroid, gastric, renal and colon cancers were also detected on PET/CT (and/or MRI). Among those, 19 patients were diagnosed with a treatable disease, including other-site cancers curable with surgery. CONCLUSIONS: Extensive staging (MRI, scintigraphy, PET/CT etc.) for distant metastasis is not required for patients diagnosed with clinical T1N0 GGNs, though various imaging modalities revealed the presence of adventitious diseases with the potential to increase surgical risks, lead to separate management, and worsen patient outcomes, especially in elderly patients. If clinically feasible, it could be considered to complement staging with whole-body procedures including PET/CT.

Tracheal bifurcation repair for blunt thoracic trauma in a patient with COVID-19.

BACKGROUND: Tracheobronchial injury (TBI) is a rare but potentially life-threatening trauma that requires prompt diagnosis and treatment. We present a case in which a patient with COVID-19 infection was successfully treated for a TBI through surgical repair and intensive care with extracorporeal membrane oxygenation (ECMO) support. CASE PRESENTATION: This is the case of a 31-year-old man transported to a peripheral hospital following a car crash. Tracheal intubation was performed for severe hypoxia and subcutaneous emphysema. Chest computed tomography showed bilateral lung contusion, hemopneumothorax, and penetration of the endotracheal tube beyond the tracheal bifurcation. A TBI was suspected; moreover, his COVID-19 polymerase chain reaction screening test was positive. Requiring emergency surgery, the patient was transferred to a private negative pressure room in our intensive care unit. Due to persistent hypoxia and in preparation for repair, the patient was started on veno-venous ECMO. With ECMO support, tracheobronchial injury repair was performed without intraoperative ventilation. In accordance with the surgery manual for COVID-19 patients in our hospital, all medical staff who treated this patient used personal protective equipment. Partial transection of the tracheal bifurcation membranous wall was detected and repaired using 4-0 monofilament absorbable sutures. The patient was discharged on the 29th postoperative day without postoperative complications. CONCLUSIONS: ECMO support for traumatic TBI in this patient with COVID-19 reduced mortality risk while preventing aerosol exposure to the virus.

Inferior pulmonary ligament division during left upper lobectomy causes pulmonary dysfunction.

OBJECTIVES: The division of inferior pulmonary ligament (IPL) during upper lobectomy (UL) was believed to be mandatory to dilate the remaining lung sufficiently. However, the benefits, especially postoperative pulmonary function, remain controversial. This study aimed to evaluate whether IPL division leads to pulmonary dysfunction. METHODS: This retrospective study included 213 patients who underwent UL between 2005 and 2018. They were categorized into an IPL division group (D group, n = 106) and a preservation group (P group, n = 107). Postoperative dead space at the lung apex, pulmonary function and complications were assessed using chest X-rays and spirometry. Changes in bronchial angle, cross-sectional area and circumference of the narrowed bronchus on the excised side were measured on three-dimensional computed tomography. RESULTS: There was no significant difference in the postoperative complication rate, the dead space area, forced vital capacity (FVC), or forced expiratory volume in 1 s (FEV1) between the 2 groups after right UL (FVC; P = 0.838, FEV1; P = 0.693). By contrast, after left UL pulmonary function was significantly better in the P than in the D group (FVC; P = 0.038, FEV1; P = 0.027). Changes in bronchial angle did not significantly differ between the 2 groups. The narrowed bronchus's cross-sectional area (P = 0.021) and circumference (P = 0.009) were significantly smaller in the D group than in the P group after left UL. CONCLUSIONS: IPL division during left UL caused postoperative pulmonary dysfunction and airflow limitation due to bronchial kinking. IPL preservation may have a beneficial impact on postoperative pulmonary function.

Rapid intraoperative Ki-67 immunohistochemistry for lung cancer using non-contact alternating current electric field mixing.

OBJECTIVES: Locoregional recurrence of non-small cell lung cancer (NSCLC) occurs even among patients with stage I disease, as a result of tumor proliferative activity. The aim of this study was to evaluate the clinical reliability of a new rapid immunohistochemistry (IHC) technique for assessing malignant potential through detection of tumoral Ki-67 expression. MATERIALS AND METHODS: The rapid IHC method uses non-contact alternating current (AC) mixing to achieve more rapid/stable staining within 20 min during surgery. First, to investigate the association between clinical outcomes and tumoral Ki-67 labeling with rapid IHC, 21 pairs of surgical patients treated between 2012 and 2020 for pStage IA1-3 NSCLC with/without recurrence were retrospectively reviewed. Second, 40 frozen section (FS) samples in patients with NSCLC for whom radical surgery was planned between April 2021 and February 2022 were deemed eligible for comparison of the clinical performance of conventional IHC and intraoperative rapid Ki-67 IHC with FS. RESULTS: Detection of tumoral Ki-67 expression using rapid IHC with formalin-fixed, paraffin-embedded (FFPE) blocks was significantly associated with clinical outcomes in R0 pStage IA NSCLC surgical patients, including overall and recurrence-free survival (P = 0.0043 and P < 0.0001, respectively). Levels of Ki-67 expression among resectable NSCLC patients detected using rapid IHC with FS significantly correlated with those detected using conventional FFPE-IHC (p < 0.001). An intraoperative cut-off of > 7.5 % tumor cell Ki-67 positivity accurately predicted pathological stage more advanced than IA3 [P = 0.0185, Odds ratio = 20.477, 95 % confidence interval (CI): 1.660-252.55]. CONCLUSION: Rapid Ki-67 IHC with AC mixing could potentially serve as a clinical tool for intraoperative determination of tumor malignancy status. The present study suggests that segmentectomy for early small NSCLCs is oncologically safe and a reasonable alternative to lobectomy, but only when there is adequate intraoperative selection for primary tumors with low-grade malignancy, which could be verified using intraoperative rapid Ki-67 IHC with FS.

Case of advanced pulmonary squamous cell carcinoma cured by resection through preoperative induction of immune checkpoint inhibitor.

The options for lung cancer treatment have increased due to the development of immune checkpoint inhibitors, but there has been no report of inoperable cases whereby the treatment effects rendered the case operable, an operation was subsequently performed, and histological assessment of the surgical specimen was carried out. Here, we report a 67-year-old man who was given pembrolizumab for T3N0 lung squamous cell carcinoma suspected of pericardial infiltration and judged inoperable. Treatment effect was evaluated after four courses. Computed tomography indicated a partial response, and operability was feasible. Therefore, thoracoscopic left upper lobectomy was performed after six courses of pembrolizumab, and histological assessment of the treatment effect was determined to be Ef 3, a complete response. The postoperative course was uneventful and he was discharged on the third postoperative day. We encountered a case that could be surgically treated after pembrolizumab administration. This treatment was safe and effective for advanced lung cancer.