A pilot study of intraoperative localization of peripheral small pulmonary tumors by cone-beam computed tomography: sandwich marking technique.

Background: Intraoperative identification of small pulmonary nodules has been an important technical issue. We aimed to develop a new localization method which is much safer and simple procedure compared with conventional methods. Methods: This was a retrospective study including patients with resected peripheral pulmonary nodules between November 2017 and April 2021 at Teikyo University School of Medicine, and Saitama Cardiovascular and Respiratory Center. All surgical procedure was wedge resection, and the tumor size was equal to or less than 20 mm which were detected by cone-beam computed tomography (CBCT; Philips Allura Xper FD 20, Philips). Some metal clips were put on several places of visceral pleura, where the target lesion was sandwiched by marking clips (sandwich marking technique). CBCT detected both the target lesion and metal clips, and video-assisted thoracoscopic surgery (VATS) was performed. Radiological and pathological findings were analyzed, and the correlation coefficient of tumor size was examined among pre-, intra-, and post-operative tumor sizes. Results: The average age of 90 patients was 65.2 years, and 47 were male (52.2%). All procedure was wedge resection including twelve bi-wedge resections, and one hundred nine peripheral pulmonary lesions were obtained by sandwich marking technique. The detection rate was 100%, and there was no marking-related complication. Conclusions: All small peripheral pulmonary lesions were successfully detected and resected by using CBCT with no marking-related complication. Sandwich marking technique was demonstrated to provide safe, reliable, and simple localization procedure for small peripheral pulmonary lesions.

Loop-Mediated Isothermal Amplification as Point-of-Care Testing for EGFR-Mutated Lung Adenocarcinoma.

Liquid biopsy has been adapted as a diagnostic test for EGFR mutations in patients with advanced or metastatic non-small cell lung cancer (NSCLC). Loop-mediated isothermal amplification (LAMP) has been widely used for the rapid detection of pathogens through DNA amplification. This study investigated the efficacy of an EGFR-LAMP assay using plasma samples of patients with resected NSCLC tumors. The EGFR status was investigated using both LAMP and next-generation sequencing (NGS) assays in cases that met the following criteria: (1) pulmonary adenocarcinoma with EGFR mutation detected by the Therascreen EGFR PCR Kit and (2) preoperative plasma samples contained enough DNA for the LAMP and NGS experiments. Among 51 specimens from patients with EGFR-mutated tumors or metastatic lymph nodes, the LAMP assay detected 1 EGFR mutation that was also detected in the NGS assay. However, a plasma sample that demonstrated EGFR wild type in the LAMP assay showed an EGFR mutant status in NGS. The detection rates (1.9% in LAMP and 3.9% in NGS) were very low in both assays, demonstrating a similar performance in detecting EGFR mutations in NSCLC tumors; therefore, it could be a more suitable test for the advanced stage, not the early stage. Notably, the LAMP assay was more time-saving, cost-effective, and straightforward. However, further investigation is required to develop a more sensitive assay.

Left upper lobectomy for cancer of the left lung with a rare mediastinal left basal pulmonary artery.

We report a rare case wherein a mediastinal left basal pulmonary artery was detected during surgery. Intraoperative findings revealed mediastinal left lingular and basal segments of the pulmonary artery (A4+5 + A8-10) just dorsal to the superior pulmonary vein. The mediastinal left basal pulmonary artery is classified by its branching type, (1) complete type-wherein the entire that all basal pulmonary artery flow lies between the superior pulmonary vein and the left upper bronchus, as in like this case, (2) incomplete type-wherein that a part of the left basal pulmonary artery segment is on the flow mediastinal side. It is important to understand this rare aberration for undergoing safe surgery.

A novel loop­mediated isothermal amplification method for efficient and robust detection of EGFR mutations.

The activation of somatic mutations conferring sensitivity to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors has been widely used in the development of advanced or metastatic primary lung cancer therapy. Therefore, identification of EGFR mutations is essential. In the present study, a loop­mediated isothermal amplification (LAMP) method was used to identify EGFR mutations, and its efficiency was compared with the Therascreen quantitative PCR assay. Using LAMP and Therascreen to analyze surgically resected tissue samples from patients with pulmonary adenocarcinoma, EGFR mutations were observed in 32/59 tumor samples (LAMP) and 33/59 tumor samples (Therascreen). Notably, the LAMP assay identified one tumor as wild­type, which had previously been identified as a deletion mutation in exon 19 via the Therascreen assay (Case X). However, the direct sequencing to confirm the EGFR status of the Case X adhered to the results of the LAMP assay. Further experiments using Case X DNA identified this exon 19 deletion mutation using both methods. In addition, a novel deletion mutation in exon 19 of the EGFR was identified. Overall, the present study shows that the LAMP method may serve as a valuable alternative for the identification oncogene mutations.

Inter-tumor heterogeneity of PD-L1 expression in non-small cell lung cancer.

BACKGROUND: The Dako PD-L1 immunohistochemistry (IHC) 22C3 pharmDx and the Dako 28-8 IHC pharmDx assays were approved by the US Food and Drug Administration, as a companion diagnostic test for pembrolizumab (Keytruda, Merk, Kenilworth, NJ, USA) and a complementary diagnostic test for nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY, USA) in non-small cell lung cancer (NSCLC), respectively. Increased PD-L1 expression levels can be associated with greater therapeutic efficacy of pembrolizumab relative to other anti-PD-1 agents. However, in treatment decision making, little is known about which tissue (primary or metastatic lesion) should be stained by 22C3 antibody. We investigated the relationship between PD-L1 expression in primary tumors and paired metastatic lymph nodes using the 22C3 assay, and evaluated the concordance between the 22C3 and 28-8 assays. METHODS: PD-L1 expression was evaluated in cells from primary tumors and paired metastatic lymph nodes using the 22C3 and 28-8 IHC assays. Total 35 patients with primary tumor and paired metastatic lymph node were enrolled into this study, and all samples were surgically resected, formalin-fixed, and paraffin-embedded NSCLC tissues. Tumor cells exhibiting complete or partial membrane staining, were considered as PD-L1 positive. On the basis of tumor proportion score (TPS), all samples were classified as no expression (TPS: <1%), low expression (TPS: 1-49%), or high expression (TPS: ≥50%). RESULTS: TPS distribution was markedly different between primary tumors and paired metastatic lymph nodes. In 22C3 IHC assay, TPS similar to that of metastatic lymph nodes was demonstrated in 10 primary tumors, and concordance rate between them was 28.6%. Concurrently, in 28-8 IHC assay, 11 primary tumors had TPS similar to that of metastatic lymph nodes, with a concordance rate of 31.4%. CONCLUSIONS: TPS concordance rates (for both 22C3 and 28-8 antibodies) between primary tumors and paired lymph nodes were low. Inter-tumor heterogeneity of PD-L1 expression is an important issue for clinical oncologists during treatment planning.

[Present Status and Future Issues of Multidisciplinary Treatment of Lung Cancer from the Viewpoint of a Respiratory Surgeon].

With the advent of molecular targeted therapeutic agents and immunity checkpoint inhibitors, lung cancer drug therapy has advanced. We cannot expect to improve the performance of surgical treatment without drug therapy. The problem of improving the performance of surgical treatment for lung cancer is:① the role of surgery in multidisciplinary treatment for c-stageⅢ N2 lung cancer, ② post-operative adjuvant therapy, ③ multidisciplinary treatment of post-operative recurrence, ④ salvage surgery, and ⑤ sublobar resection in high risk cases. We will describe each of these with reference to our own experiences and literature considerations.

A clinicopathological study of surgically resected lung cancer in patients with usual interstitial pneumonia.

BACKGROUND: The clinicopathological characteristics of lung cancer with concomitant usual interstitial pneumonia (UIP) are insufficiently understood. This study aimed to elucidate a characteristic pathological feature of lung cancer that develops in patients with UIP, with a focus on the location of its onset. METHODS: We reviewed surgically obtained specimens, including 547 tumors from 526 patients who underwent lobectomy for lung cancer. Surveyed patients were classified into three groups: patients with UIP (UIP group), patients with lung pathology other than UIP (non-UIP group), and patients without any associated lung pathology (normal group). The histology as well as the lobe and location of the onset of lung cancer were compared among these groups. The peripheral location was subdivided into subpleural, inner and tumor involved centrally secondary to extension. RESULTS: The UIP group comprised 82 patients (male, 71 [87%]; mean age, 71 years; smoking rate, 94%), the non-UIP group comprised 334 patients (male, 267 [80%]; mean age, 69 years; smoking rate, 81%), and the normal group comprised 110 patients (male, 33 [30%]; mean age, 63; smoking rate, 29%). No statistical differences were noted in sex, mean age, or smoking index between the UIP and non-UIP groups. Compared with the non-UIP group, the frequency of squamous cell carcinoma (63% vs. 32%), lower lobe origin (76% vs. 32%), and subpleural location (24% vs. 5%) were significantly higher in the UIP group. CONCLUSIONS: Lung cancers in patients with UIP show a predilection for the subpleural region, where UIP is also thought to originate.

Acute ischaemic lung injury due to pulmonary vascular obstruction.

AIMS: We have encountered cases of a distinctive myxomatous alveolar wall thickening around pulmonary infarctions, and have termed it 'acute ischaemic lung injury' (AILI). In this study we determined if pulmonary infarction is the only cause of AILI and have elucidated its histological features. METHODS AND RESULTS: We examined 2941 cases that underwent lobectomy, surgical lung biopsies for nodular lesions or autopsies between 1994 and 2014. Cases were divided into pulmonary infarction and non-infarction groups. The histological features of AILI sought were lobule-based alveolar wall thickening (myxomatous or fibrous) with epithelial metaplasia and negligible inflammation. In order to characterize AILI further, we performed immunohistochemical staining using several antibodies. Thirty-four of 69 cases in the infarction group (mean age 57.1 years, 30 males) had AILI, whereas only one (but with vascular obstruction) of the remaining 2872 in the non-infraction group had AILI. AILI was located around infarctions. Separation of the epithelial and endothelial basement membranes of the alveolar wall was observed in 75% of cases. CONCLUSIONS: AILI is associated almost exclusively with lung infarction, caused presumably by vascular obstruction. We consider AILI to represent a distinct lung lesion other than pulmonary haemorrhage and infarction.

Survival after surgery for pathologic stage IA non-small cell lung cancer associated with idiopathic pulmonary fibrosis.

BACKGROUND: Many problems exist in regard to the treatment of lung cancer patients with idiopathic pulmonary fibrosis (IPF), but few reported studies have investigated the long-term prognosis after pulmonary resection in such patients. The purpose of the present study was to determine the postoperative survival of patients with pathologic stage IA non-small cell lung cancer (NSCLC) and IPF. METHODS: We retrospectively reviewed 350 patients with pathologic stage IA NSCLC who underwent pulmonary resections at our institution between September 1994 and December 2007. We analyzed and compared 28 of these patients, who had simultaneous lung cancer and IPF, with the remaining 322 lung cancer patients without IPF. RESULTS: The 5-year survival rates were 54.2% in pathologic stage IA lung cancer patients with IPF and 88.3% in those without IPF (p < 0.0001). Univariate analyses showed that age, sex, Brinkman Index, limited resection, operation time, adenocarcinoma, and IPF were significant prognostic factors for survival (p < 0.10). By multivariate analysis, however, only IPF was a significant prognostic factor for survival (p = 0.007). Propensity score-matching analysis confirmed that only IPF was significant prognostic factor (p = 0.043). CONCLUSIONS: The 5-year survival rate of patients with pathologic stage IA NSCLC and IPF is 54.2%. IPF has independent, adverse effects on survival of pathologic stage IA NSCLC patients treated with pulmonary resection.

Isolation of Candida species is an important clue for suspecting gastrointestinal tract perforation as a cause of empyema.

BACKGROUND: Empyema due to Candida species is a rare entity, and the significance of isolation of Candida species from the pleural effusion is not fully understood. OBJECTIVE: To elucidate the clinical features of Candida empyema. METHODS: We retrospectively reviewed the cases of 128 patients with culture-positive empyema. RESULTS: These 128 patients included 7 whose cause of empyema was esophago- or gastropleural fistula. Empyema was due to Candida species in 5 of the 7 patients. Primary diseases of these 5 patients were spontaneous esophageal rupture in 3 patients, esophageal rupture due to lung cancer invasion in 1 patient, and gastric ulcer perforation in 1 patient. None of these 5 patients had esophageal candidiasis. Among the 121 other patients with empyema not due to esophago- or gastropleural fistula, no patient had empyema due to Candida. CONCLUSION: We believe that the empyema in these 5 patients was caused by normal commensal Candida species entering the pleural cavity when the fistula between the gastrointestinal tract and pleural cavity was formed. Isolation of Candida species can be an important clue for suspecting gastrointestinal tract perforation as a cause of empyema.

Spontaneous hemorrhage of a thymic cyst in an adult: report of a case.

Mediastinal cysts account for about 19% of all mediastinal masses, and thymic cysts represent only about 1.5% of anterior mediastinal masses. Thymic cysts do not usually cause symptoms and are often found incidentally on routine chest radiography. We report the case of a thymic cyst that hemorrhaged into the mediastinum and the right pleural cavity, causing chest pain. The patient, a 55-year-old man, underwent emergency surgical resection and recovered uneventfully.

Placental transmogrification of the lung presenting as a small solitary nodule.

Placental transmogrification of the lung is a rare cystic lesion of the lung, which has some histologic resembling to placental tissue. Placental transmogrification of the lung has been considered a variant of unilateral bullous emphysema, but in our case, the patient was a 47-year-old man who had no coexisting emphysema of the lung. Histologically our case showed an interstitial proliferation of clear cells with cystic change interpreted as secondary; we also agree with our colleagues that this proliferation may be the primary event pathogenetically. Surgical resection of this lesion seems to be curative.

Second primary digestive cancer after resection of lung cancer.

PURPOSE: We evaluated the clinical findings of patients with second primary digestive cancers (SPDC) after the resection of lung cancer. METHODS: Among 772 patients who underwent resection of primary lung cancer at Saitama Cardiovascular and Respiratory Center between 1993 and 2002, 10 (1.3%) were diagnosed with SPDC during follow-up. These ten patients were classified into two groups based on whether the SPDC was incidentally (group I) or symptomatically (group S) diagnosed. RESULTS: The median interval to the detection of SPDC was 17 months in group I and 66 months in group S, and the disease was at an earlier stage in group I than in group S ( P = 0.008). Comparing body weight at the time of lung resection to that at the time of abdominal surgery, significant weight loss was evident in group S ( P = 0.009). The postoperative disease-specific survival rate was 100% in group I. No long-term survivor died of lung cancer. CONCLUSION: Special attention must be paid to the possibility of SPDC after the resection of lung cancer to improve the prognosis of patients with lung cancer.