Is the Preoperative Prognostic Nutritional Index a Useful Marker for the Decision to Perform Limited Resection in High-risk Patients With Stage I Non-small Cell Lung Cancer?

BACKGROUND/AIM: The indications for limited resection in high-risk patients with stage I non-small cell lung cancer (NSCLC) remain controversial. The purpose of this study was to evaluate the prognostic impact of the preoperative prognostic nutritional index (PNI) in high-risk patients undergoing limited resection. PATIENTS AND METHODS: High-risk patients undergoing limited resection for stage I NSCLC in our institution from 2005 to 2020 were retrospectively reviewed. Patients with clinical/pathological Tis/minimally invasive adenocarcinoma and multiple NSCLC were excluded. A multivariate Cox regression analysis was conducted to identify factors associated with overall survival (OS). RESULTS: Ninety eligible patients were included in this study. Grade ≥2 postoperative complications were significantly more frequent in the low-PNI group (6 cases, 16.6% vs. 7 cases, 12.9%; p=0.03). The rate of death due to other diseases was significantly higher in the low-PNI group than in the high-PNI group (14 cases, 50.0% vs. 11 cases, 25.0%; p=0.002). The multivariate analysis showed that male sex, Brinkman index ≥400, preoperative low PNI and pathological T factor ≥T1c/T2a were independent prognostic factors for OS. CONCLUSION: In high-risk patients undergoing limited resection for stage I NSCLC, low PNI was a poor prognostic factor, especially in relation to death from other diseases and lung cancer. The results may support thoracic surgeons in decision-making in relation to the indications for surgery.

Prognostic Impact of the Histologic Lepidic Component in Pathologic Stage IA Adenocarcinoma.

INTRODUCTION: Because several articles have reported a prognostic association with the radiologic features of ground-glass opacity, we explored whether the histologic presence of a lepidic component had similar significance. METHODS: We retrospectively evaluated 380 consecutive surgically resected lung adenocarcinomas (ADCs) of pathologic (p)stage IA. The tumors were classified into lepidic-positive and lepidic-negative ADCs. Clinicopathologic characteristics, radiographic ground-glass opacity status, and disease-free survival were compared between lepidic-positive and lepidic-negative ADCs and between part-solid and solid nodules on computed tomography images. RESULTS: Of the 380 cases, 176 (46.3%) were lepidic-positive ADCs. Of the overall patients with pT1, lepidic-positive ADCs were found to have significantly better recurrence-free survival (5 y, 95.4% versus 87.0%, p = 0.005), but this significance was not reproduced in pT1 subcategories (pT1a, pT1b, and pT1c). Furthermore, the presence of the lepidic component was not an independent prognostic factor in the multivariate analysis (hazard ratio = 0.46 [95% confidence interval: 0.19-1.14], p = 0.09). We also analyzed the extent of the lepidic component with 10% incremental valuables. Although we found that a 10% or greater extent of lepidic component made the recurrence-free survival difference the largest, a clear prognostic impact was not obtained with this cutoff point. CONCLUSIONS: Although lepidic-positive ADCs tended to have a favorable outcome, the lepidic component was not a clear independent prognostic factor in pstage I ADC.

Cryobiopsy as a reliable technique for the preoperative identification of micropapillary/solid components in early-stage lung adenocarcinoma.

OBJECTIVES: Micropapillary (MIP) and solid (SOL) subtypes of early-stage lung adenocarcinomas are associated with lymph node metastasis and local recurrence after limited resection. Preoperative identification of these components may influence the decisions of treatment strategy, additional lymph node evaluation, indication for limited resection, and extent of lymph node dissection. However, conventional biopsy specimens are insufficient for identifying these subtypes, especially MIP components. Cryobiopsy can collect larger tissue samples with fewer crush artifacts than conventional forceps biopsy, which would be helpful for detecting MIP/SOL components. Thus, this study aimed to analyze the feasibility of using cryobiopsy for MIP/SOL subtype detection. MATERIAL AND METHODS: Consecutive patients who underwent surgery for clinical IA lung cancer following a preoperative diagnosis of adenocarcinoma by cryobiopsy at our institution between October 2017 and July 2019 were retrospectively examined. The concordance rate of MIP/SOL subtypes between the specimens obtained by cryobiopsy and surgery was investigated. RESULTS: In total, 115 patients were evaluated. There were 26 (22.6%) and 14 (12.2%) patients with MIP and SOL subtypes, respectively. For concordance of MIP/SOL subtypes, the sensitivity was 65.7% (95% confidence interval [CI]: 57.7-65.7%). For the primary or secondary predominant patterns, a more satisfactory concordance rate of 72.2% (95% CI: 52.6-86.2%) was obtained. On assessing each subtype, high sensitivity was noted in SOL-predominant patterns (85.7%, 95% CI: 56.5%-96.0%) and MIP-secondary predominant patterns (83.3%, 95% CI: 45.8-97.0%). However, SOL-secondary predominant patterns revealed low sensitivity (0%, 95% CI, 0-38.2%). Overall, the MIP subtypes had higher sensitivity than the SOL subtypes (65.4% vs. 50.0%). CONCLUSION: Cryobiopsy could be reliable for identifying MIP/SOL components, especially the MIP component, in clinical stage IA adenocarcinomas.

An Alert to Possible False Positives With a Commercial Assay for MET Exon 14 Skipping.

INTRODUCTION: Because molecular-targeted drugs against MET exon 14 (METex14) skipping have been approved, molecular testing of the alteration has added to clinical guidelines. There are several such assays, but methodological issues have been reported. METHODS: METex14 skipping results from three assays (Oncomine DxTT, ArcherMET, and laboratory-developed reverse-transcriptase polymerase chain reaction test [LDT RT-PCR]) were compared in a relatively small series of the specimens diagnosed as advanced NSCLC (n = 50). RESULTS: The ArcherMET and LDT RT-PCR results were identical for all 50 samples, but eight samples had discordant results between Oncomine DxTT and the other two assays. All eight samples had METex14 skipping with Oncomine DxTT and wild-type signals with ArcherMET and LDT RT-PCR. The discordance might be caused by the homopolymeric error of the splice donor site with Oncomine DxTT, and false positives could be distinguished by relatively low read counts. CONCLUSIONS: Although the caution in detecting METex14 skipping focuses on false negatives in the literature, false positives were first noted at a relatively high frequency (8 of 26, 30.8%) in this study. According to the results of previous clinical trials using the other tyrosine kinase inhibitors, it could be surmised that MET inhibitor treatment in patients without METex14 skipping is detrimental. Clinicians need to be alert to the false positives that can lead to harmful treatments.

Visualization of Intratumor Pharmacokinetics of [fam-] Trastuzumab Deruxtecan (DS-8201a) in HER2 Heterogeneous Model Using Phosphor-integrated Dots Imaging Analysis.

PURPOSE: We assessed the intratumor pharmacokinetics of [fam-] trastuzumab deruxtecan, T-DXd (known as DS-8201a), a novel HER2-targeted antibody-drug conjugate, using phosphor-integrated dots (PID)-imaging analysis to elucidate its pharmacologic mechanism. EXPERIMENTAL DESIGN: We used two mouse xenograft models administered T-DXd at the concentration of 4 mg/kg: (i) a heterogeneous model in which HER2-positive and HER2-negative cell lines were mixed, and (ii) a homogeneous model in which both cell types were transplanted separately into the same mouse. PID imaging involved immunostaining using novel high-intensity fluorescent nanoparticles. The distribution of T-DXd was assessed by PID imaging targeting the parent antibody, trastuzumab, and the payload, DXd, in serial frozen sections, respectively. RESULTS: After T-DXd administration in the heterogeneous model, HER2 expression tended to decrease in a time-dependent manner. The distribution of trastuzumab and DXd was observed by PID imaging along the HER2-positive area throughout the observation period. A detailed comparison of the PID distribution between trastuzumab and DXd showed that trastuzumab matched almost perfectly with the HER2-positive area. In contrast, DXd exhibited widespread distribution in the surrounding HER2-negative area as well. In the HER2-negative tumor of the homogeneous model, the PID distribution of trastuzumab and DXd remained extremely low throughout the observation period. CONCLUSIONS: Our results suggest that T-DXd is distributed to tumor tissues via trastuzumab in a HER2-dependent manner and then to adjacent HER2-negative areas. We successfully visualized the intratumor distribution of T-DXd and its mechanism of action, the so-called "bystander effect."

Feasibility of next-generation sequencing (Oncomine™ DX Target Test) for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients.

BACKGROUND: The Oncomine™ Dx Target Test based on next-generation sequencing has been approved for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients. METHODS: We assessed the tissue sample factors that affect the success rate of Oncomine™ Dx Target Test companion diagnostics and the feasibility of using biopsy specimens for Oncomine™ Dx Target Test companion diagnostics in advanced non-small-cell lung cancer patients. RESULTS: Ninety-nine biopsy samples were subjected to genetic testing using the Oncomine™ Dx Target Test companion diagnostics to detect v-raf murine sarcoma viral oncogene homologue B1 mutations (Cohort 1), and 136 biopsy samples were examined using Oncomine™ Dx Target Test companion diagnostics for the detection of multiple oncogenic mutations (Cohort 2) between July 2018 and April 2020. We retrospectively collected clinical and pathological data, including tissue size and tumour cell content. The success rate was 77% (76/99) in Cohort 1 and 93% (127/136) in Cohort 2. In Cohort 1, the success rate was significantly associated with the tumour cell content: the success rate was 63% for samples with a tumour cell content of <20%, whereas it was 83% for samples with a tumour cell content of 20% or higher (P = 0.0446). The tissue size also affected the success rate: a success rate of 57% was obtained for tissue sizes <4 mm2, whereas a success rate of 95% was obtained for tissue sizes of 4 mm2 or larger (P < 0.0001). In Cohort 2, the success rate was 100% when tumour specimens with a tissue size of 4 mm2 or larger were used. CONCLUSIONS: Tissue size and tumour cell content were significantly associated with the success rate of Oncomine™ Dx Target Test companion diagnostics.

[Bronchial Occlusion with Endobronchial Watanabe Spigot for Massive Pulmonary Hemorrhage during Heart Surgery;Report of a Case].

Massive pulmonary hemorrhage, although rare, is a potentially life-threatening complications during heart surgery. We herein present 1 such case successfully treated by selective bronchial occlusion using an Endobronchial Watanabe Spigot (EWS). The 82-year-old female underwent mitral valve replacement, tricuspid annuloplasty, and maze procedure. An hour and a half after cessation of cardiopulmonary bypass, the patient suffered a massive pulmonary hemorrhage. A subsequent bronchoscopy identified the hemorrhage site at the right middle lobe bronchus (B5b), and an EWS was then selectively deployed into this bronchus to block the hemorrhage. The following day, bronchial arterial embolization was performed, enabling the removal of the spigot on the next day. The patient's respiratory condition gradually improved, allowing for extubation on the 21st postoperative day. By preventing bleeding into neighboring bronchi, which, in turn, avoids the risk of exacerbating hypoxia, bronchial occlusion with EWSs is highly effective in managing massive pulmonary hemorrhage during heart surgery.

[Congenitial Pulmonary Airway Malformation in an Adult with Pneumonia].

Congenitial pulmonary airway malformation (CPAM) most commonly present respiratory distress in the prenatal or neonatal period, but may rarely be asymptomatic and is incidentally found in adult patients with acute or recurrent pneumonia. Herein, we report a case of a 26-year-old asymptomatic adult male patient with pneumonia of the right lower lobe. He was also found to have multiple cystic lesions in the same lobe which was suspected to be CPAM, and the right lower lobectomy was performed.

[Bronchial Typical Carcinoid Tumor Treated with Two-stage Resection;Report of a Case].

A 45-year-old woman, who had been treated for bronchial asthma, was referred to our hospital with symptoms of dyspnea. Upon examination, we found the right main bronchus to be almost completely occluded by an endobronchial tumor. For the purpose of diagnosis and relieving the dyspnea, we performed a rigid bronchoscopic tumor resection with a high frequency snare. The tumor was pathologically diagnosed as a typical bronchial carcinoid, and a right upper lobectomy and wedge resection of the right main bronchus was carried out 1 month later.

Is bipolar thermofusion an acceptable option for unseparated interlobar fissure division in pulmonary lobectomy?

OBJECTIVES: This study aimed to review the safety of a reusable sealing instrument, BiClamp(®), as an alternative to the mechanical stapler for interlobar fissure division in pulmonary lobectomy. METHODS: A retrospective review was conducted of 95 patients who underwent pulmonary lobectomy performed by a single surgeon between November 2005 and March 2010. The patients were divided into two groups according to the period before and after introduction of the BiClamp(®): 29 patients who underwent fissure division with staples only (staple group) and 66 patients who underwent the same procedure mainly with the instrument (BiClamp(®) group). RESULTS: There were 60 (63.2%) male and 35 (36.8%) female patients, with a mean ± SD age of 67.5 ± 10.8 years. Comparison of the characteristics of the two groups revealed that the BiClamp(®) group included significantly more cases of lobectomy by video-assisted thoracic surgery and far fewer completely lobulated lungs; 6 of 66 patients (9.1%) compared with 9 of 29 (31.0%) of the staple group. Except for 18 patients who underwent division using staples owing to thick parenchyma of the interlobar fissure, we attempted to divide the fissure of 42 patients in the BiClamp(®) group. Solo use of the BiClamp(®) was possible for 25 of 60 patients (41.7%) with an incomplete fissure. Eight patients (13.3%) needed one staple cartridge in combination with BiClamp(®), five (8.3%) needed two cartridges and four (6.7%) patients needed three (combined use). In most cases, except for right upper or middle lobectomy, the division of the interlobar fissure could be performed by sole use of the BiClamp(®). Incidence rates of prolonged air leakage and pneumonia were not significantly different between the two groups (respectively, 6.9 and 3.4% in the staple group vs 10.6 and 9.1% in the BiClamp(®) group). CONCLUSIONS: The study results demonstrate that the division of the interlobar fissure in pulmonary lobectomy with BiClamp(®) is safe and feasible in most cases. While the results point out the limitation that division of the right upper or middle lobe may still be a challenge, they show the potential benefit of staple reduction. Less use of staples results in reduced medical costs and carbon dioxide emission, contributing to 'ecosurgery', which ultimately conserves the global environment.