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.

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.

Primary pericardial synovial sarcoma.

A 57-year-old man was admitted to our hospital with cardiomegaly on a chest roentgenogram. A mediastinal tumor was observed during a chest computed tomographic scan and the patient was diagnosed with pericardial synovial sarcoma as a result of a tumor biopsy. Surgery, radiotherapy and chemotherapy were carried out, and although the tumor temporarily decreased in size, it subsequently increased and the patient died approximately 3 years following the initial medical examination. Most synovial sarcomas commonly occur in the vicinity of the joints of the extremities. Therefore, we herein report a rare case of synovial sarcoma which occurred in the pericardium.

[Required matters in the study enforcement and the publication].

We must confirm "instructions for authors" in a medical journal before we submit a manuscript to the journal. Human studies must conform to ethical standards, and be approved by the appropriate Institutional Review Board (IRB). Most "instruction for authors" require to obey "WMA Declaration of Helsinki-Ethical Principles for Medical Research Involving Human Subjects", "Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication" etc. The editors of journal are concerned about appropriate IRB review and informed consent. Lack of appropriate consent or documentation may be grounds for rejection, and we must understand the necessary guidelines before starting a study.

Cause and management of recurrent primary spontaneous pneumothorax after thoracoscopic stapler blebectomy.

BACKGROUND: As the number of patients treated by thoracoscopic stapler blebectomy increased, the postoperative recurrence rate had risen unexpectedly. We retrospectively investigated the cause and management of primary spontaneous pneumothorax recurrence after thoracoscopic stapler blebectomy. METHODS: From March 1992 to the end of December 2006, thoracoscopic stapler blebectomy was performed in 357 patients with primary spontaneous pneumothorax at the Nihon University Itabashi Hospital. The causes and management of recurrence were investigated in 30 patients with postoperative recurrence based on items such as the resurgical observations, preoperative chest computed tomography findings, previous operative notes. RESULTS: Among the patients with bilateral pneumothorax, young patients exhibited a higher tendency for postoperative recurrence. The most common cause was new bulla formation (28 slides, 16 of which were apparently related to the staple line and 12 of which were not related to the staple line). CONCLUSION: In thoracoscopic stapler blebectomy for primary spontaneous pneumothorax, the most common cause of recurrence was new bulla formation. It is necessary to establish additional procedures involving either the visceral pleura or the parietal pleura to reduce the recurrence rate.

Thoracoscopic resection of mediastinal bronchogenic cysts in adults.

OBJECTIVE: The aim of this study was to discuss the diagnosis and determine the optimal thoracoscopic surgical treatment of mediastinal bronchogenic cysts. METHODS: From May 1996 to April 2008, 13 consecutive patients with mediastinal bronchogenic cysts underwent thoracoscopic surgery at our institution. There were eight men and five women aged 16-74 years (mean age, 41.5 years). RESULTS: In the majority of patients (69.2%), there were no clinical symptoms and the lesions were found incidentally by chest radiography that was performed as part of physical screening. Lesions were found in the posterior mediastinum in five patients (38.5%) and in the upper mediastinum in four (30.8%). In the histopathological examinations, ciliary epithelium was observed in 13 patients (100.0%), bronchial cartilage in 7 patients (53.8%), bronchial glands in 6 patients (46.2%), and smooth muscle in 5 patients (38.5%). No serious postoperative complications were observed. In 3 patients (23.1%), conversion to open thoracotomy was necessary due to major pleural adhesions and intraoperative vascular injury. CONCLUSION: Thoracoscopic resection of mediastinal bronchogenic cyst is minimally invasive and has no serious postoperative complications, and should therefore be considered as the primary therapeutic option.

Preventing recurrence of spontaneous pneumothorax after thoracoscopic surgery: a review of recent results.

Spontaneous pneumothorax (SP) is now commonly treated with thoracoscopic surgery, which is associated with less pain and a shorter hospital stay than thoracotomy; however, in its initial stages, thoracoscopic stapled bullectomy resulted in an unexpectedly high incidence of postoperative SP recurrence. Thus, new thoracoscopic procedures, designed to be performed in addition to stapled bullectomy, were developed, which resulted in a gradual decline in the postoperative recurrence rate. We review the recent literature on SP recurrence after thoracoscopic surgery with these other surgical procedures. Pleurectomy and pleural abrasion have been performed for a long time with low recurrence rates; however, they cause the lung to adhere to the parietal pleura, often resulting in complications such as postoperative bleeding. Other surgical procedures that may be recommended to minimize the risk of recurrence are reinforcement of the staple lines using fleece-coated glue or an absorbable sheet. These procedures are now considered to be the thoracoscopic treatment of choice for SP.

[Treatment with S-1 and radiation therapy for advanced lung cancer invading chest wall].

The patient was a 63-year-old man, who had been suffering from lung cancer with left chest wall invasion and contralateral pulmonary metastases. Due to the severe pain caused by this advanced lung cancer with poor performance status (PS), oxycodone was administered for treatment. Radiotherapy was used for local tumor control and oral S-1 was given as systemic chemotherapy. The local control rate (near CR) and the PS were improved effectively by this combination of palliative treatment. As a result, he was allowed to return home and followed as an outpatient. Our experience suggests that positive palliative treatment improves the quality of life (QOL) of patients and provides survival benefits.

Surgical treatment of catamenial pneumothorax.

OBJECTIVE: To discuss the aetiology and determine the optimal surgical treatment of catamenial pneumothorax. METHODS: Between January 1980 and December 2007, 17 patients with catamenial pneumothorax were treated at our institution. Regarding the surgical approach, thoracotomy was performed until 1991, and thoracoscopic surgery was performed from 1992 onward. RESULTS: Pneumothorax was on the right side in all but two patients. Surgery was performed on 15 of the 17 patients. The surgical procedure was a diaphragm resection plus a partial bleb resection in eight patients, a diaphragm resection in two patients, a diaphragm resection plus an absorbable polyglycolic acid sheet in four patients, and a partial bleb resection in one patient. Five patients demonstrated a postoperative recurrence (33.0%). However, no recurrence has been observed thus far in the four patients with an absorbable polyglycolic sheet placed on the diaphragmatic surface. CONCLUSION: Although the postoperative recurrence rate of patients undergoing surgical procedures remains high, there were some patients with no postoperative recurrence. Placement of an absorbable sheet on the diaphragmatic surface may therefore prevent recurrence of catamenial pneumothorax.

Isoflurane protects renal function against ischemia and reperfusion through inhibition of protein kinases, JNK and ERK.

Isoflurane has a pharmacological preconditioning effect against ischemia in the heart and brain, but whether this also occurs in the kidney is unclear. In this study, we investigated pharmacological preconditioning by isoflurane in the rat kidney. In the isoflurane preconditioning group (1.5% isoflurane for 20 min before renal ischemia) serum creatinine (1.2 +/- 0.7 and 1.1 +/- 0.2 mg/dL) and blood urea nitrogen (99 +/- 29 and 187 +/- 31 mg/dL) were significantly smaller at 24 and 48 h after reperfusion than in the nonpreconditioning group (creatinine; 2.4 +/- 1.2 and 2.9 +/- 0.9 mg/dL, urea; 62 +/- 19 and 79 +/- 20 mg/dL). We also investigated the intracellular signal transduction involved in isoflurane preconditioning in the kidney. The activities of the stress protein kinases, JNK and ERK but not p38, were significantly less in the kidneys of the preconditioning group than in those of the nonpreconditioning group (P < 0.05). We conclude that isoflurane has a preconditioning effect against renal ischemia/reperfusion injury when administered before ischemia. Inhibition of the protein kinases, JNK and ERK, might be involved in the mechanisms of isoflurane preconditioning.

Effect of cyclooxygenase-2 inhibitor pretreatment on gas exchange after hydrochloric acid aspiration in rats.

The present study was carried out to determine the effect of cyclooxygenase-2 (COX-2) inhibitor on acid aspiration-induced lung injury in rats. Rats were allocated into one of four groups. Group H received intratracheal instillation of HCl. Group S received saline intratracheally. Group HC received COX-2 inhibitor (celecoxib) 10 mg/kg intravenously 30 min before intratracheal instillation of HCl. Group C underwent bronchoalveolar lavage (BAL) only. All rats were mechanically ventilated for 30 min before BAL. Arterial blood gas analysis was done immediately before BAL. Groups H, S, and HC were subdivided to each two groups. Groups H-1, S-1, and HC-1 underwent BAL 1 h after instillation, whereas groups H-8, S-8, and HC-8 underwent BAL 8 h after instillation. The BAL fluid was used to measure the prostaglandin E2 (PGE2) concentration. Intratracheal HCl resulted in impaired oxygenation. COX-2 inhibitor attenuated the impairment of oxygenation 8 h after instillation but not after 1 h. Intratracheal HCl caused an increase in PGE2 concentration. COX-2 inhibitor attenuated an increase in PGE2 concentration 8 h after instillation but not after 1 h. The results show that COX-2 inhibitor attenuates the oxygenation impairment and the increase in alveolar PGE2 concentration during the inflammatory phase of acid aspiration-induced lung injury in rats.

Ropivacaine inhibits neurite outgrowth in PC-12 cells.

Peripheral nerve injury often leads to neuropathic pain, which might involve sympathetic postganglionic nerve fiber sprouting in the dorsal root ganglion. Recent studies suggest the effectiveness of ropivacaine in blocking neuropathic pain. To determine if ropivacaine affects sympathetic sprouting, we used pheochromocytoma (PC-12) cells, which differentiate into neurons on exposure to nerve growth factor (NGF). PC-12 cells were precultured in the presence of 50 ng/mL of NGF for 4 days. Neurite outgrowth was quantified as neurite extension after 24-, 48-, and 72-h exposure to ropivacaine at doses ranging from 10 to 200 microg/mL. Ropivacaine inhibited the neurite outgrowth in a dose-dependent manner. The inhibitory effect of ropivacaine was completely reversible because the NGF-stimulated neurite outgrowth was recovered to control level after washing out ropivacaine. Ropivacaine, therefore, may exert its therapeutic action on neuropathic pain, at least in part, by suppressing sympathetic sprouting.

Droperidol attenuates contractile and phosphatidylinositol responses of rat trachea.

Droperidol attenuates airway smooth muscle contraction. However, the intracellular mechanisms involved in the droperidol-induced attenuation of airway smooth muscle contraction are not fully understood. We examined the effects of droperidol on contractile and phosphatidylinositol responses of the rat trachea. Droperidol dose dependently attenuated carbachol (CCh) induced tracheal ring contractions. The IC(50) of droperidol on CCh-induced tracheal ring contraction was 13 +/- 2 micromol/l. Droperidol attenuated CCh and aluminum fluoride stimulated inositol monophosphate accumulation. These results suggest that droperidol inhibits G protein coupled phospholipase C, resulting in attenuation of CCh-induced phosphatidylinositol response and subsequent attenuation of contractions of the rat trachea.

Effects of fentanyl on cardiovascular response during rapid sequence induction in hypertensive patients.

This study was carried out to evaluate the effects of fentanyl on cardiovascular and catecholamine responses during rapid sequence induction (RSI) in hypertensive patients. Twenty-eight patients were allocated into one of 3 groups: group 1 (n=7) consisted of normotensive patients receiving no fentanyl, group 2 (n=10) consisted of normotensive patients receiving fentanyl, and group 3 (n=11) consisted of hypertensive patients receiving fentanyl. RSI was performed with thiamylal (4mg·kg-1) and succinylcholine (2mg·kg-1) for all groups. In groups 2 and 3, fentanyl (4 µg·kg-1) was given prior to induction. Measurements including systolic arterial pressure (SAP) and heart rate (HR) were made at preinduction (T1), preintubation (T2), 1 min after intubation (T3), and 3 min after intubation (T4). Simultaneously, plasma concentrations of epinephrine (E) and norepinephrine (NE) were measured at T1 and T3. Group 1 showed significant increases in SAP, HR, and NE at T3 as compared to T1. Group 2 showed a significant increase in HR at T3 but not in SAP or catecholamines. Group 3 showed no increase in SAP, HR, or catecholamines throughout the time course. The results suggest that fentanyl is useful to suppress sympathoadrenal and cardiovascular responses to RSI in hypertensive patients as well as normotensive patients.