Clinicopathological and Molecular Characteristics Promoting PD-L1 Expression in Early-stage Lung Adenocarcinoma and Squamous Cell Carcinoma.

BACKGROUND/AIM: Lung adenocarcinoma and lung squamous cell carcinoma represent the most prevalent subtypes of non-small cell lung cancer eligible for surgery in the early stages. The emergence of immune checkpoint inhibitors as adjuvant therapy has shown promising potential in improving the postoperative prognosis of patients with lung cancer. Hence, a comprehensive understanding of the clinicopathological and molecular features of programmed cell death ligand-1 (PD-L1) expression in lung adenocarcinoma and squamous cell carcinoma is crucial. PATIENTS AND METHODS: In this retrospective study, we conducted a comparative analysis of clinicopathological features associated with the expression of PD-L1, stratifying patients who underwent surgical resection into two distinct groups: 289 patients with lung adenocarcinoma and 66 with lung squamous cell carcinoma. Furthermore, we investigated the associations between the expression of PD-L1 and genetic alterations in well-established oncogenic driver mutations. RESULTS: Among the cases, 52.9% exhibited negative PD-L1 expression, 32.9% had low PD-L1 expression, and 12.3% had high PD-L1 expression in adenocarcinoma, while the PD-L1 expression in squamous cell carcinoma showed a near-even distribution. Notably, male sex, smoking history, the presence of invasive pathological factors, and disease progression significantly influenced PD-L1 expression in adenocarcinoma, whereas none of these factors were associated with PD-L1 expression in squamous cell carcinoma. Additionally, the distribution of PD-L1 expression varied based on the type of specific driver gene mutation in adenocarcinoma. CONCLUSION: The present study revealed clinicopathological and molecular differences between lung adenocarcinoma and squamous cell carcinoma patients promoting the expression of PD-L1.

Close-to-lesion transbronchial biopsy: a novel technique to improve suitability of specimens for genetic testing in patients with peripheral pulmonary lesions.

Bronchoscopy with radial-probe endobronchial ultrasound, a guide sheath, and electromagnetic navigation can improve the diagnostic yield of peripheral lung nodules. However, the suitability of specimens for genetic analysis remains unsatisfactory. We hypothesized that a transbronchial biopsy performed after closely approaching the bronchoscope tip to the lesion might provide more suitable specimens for genetic analysis. We enrolled 155 patients with peripheral pulmonary lesions who underwent bronchoscopy with a thin or ultrathin bronchoscope. Bronchoscopy was performed using virtual bronchoscopic navigation and radial-probe endobronchial ultrasound with a guide sheath. The bronchoscope tip was placed closer to the lesion during bronchoscopy to collect larger specimens with higher malignant cell content. The patients who underwent a close-to-lesion biopsy had higher rates of overall diagnostic yield, histopathological diagnostic yield, and specimen quality for genetic testing than those who did not. The significant determinants of the specimen's suitability were the close-to-lesion approach, within-the-lesion image, the use of standard 1.9-mm-forceps, and the number of cancer-cell-positive specimens. The significant predictors of the specimen's suitability for genetic analysis were close-to-lesion biopsy and the number of malignant cell-positive tissue samples. This study demonstrates that the close-to-lesion transbronchial biopsy significantly improves the suitability of bronchoscopic specimens for genetic analysis.

Survival benefits of salvage surgery for primary lung cancer based on routine clinical practice.

BACKGROUND: Premeditated induction chemotherapy followed by surgical resection is accepted as safe and effective. Studies on salvage surgery in patients with incompletely cured lung cancer are lacking. This study aimed to demonstrate the safety and efficacy of salvage surgery. METHODS: We conducted a retrospective multi-institutional cohort study on patients who underwent salvage surgery for advanced (stage III and IV) non-small cell lung cancer (NSCLC) between January 2005 and December 2016 at the 14 hospitals of the Chubu Lung Cancer Surgery Study Group. A total of 37 patients were assigned to the salvage surgery group; a lobectomy with mediastinal lymph node dissection was performed. The survival benefit was assessed using the Kaplan-Meier method and the Cox proportional hazard model. RESULTS: Although postoperative complications were observed in 11 patients (29.7%), surgery-related death occurred in only one patient (mortality rate: 2.7%) resulting from respiratory failure caused by interstitial pneumonia exacerbation. Postoperative recurrence was observed in 22 patients (61.1%), the incidence of brain metastasis being high (nine patients: 40.9%). The five-year survival rate from the first day of treatment was 60%. The survival of the postoperative pathological stage (s'-stage) I group was significantly better (five-year survival rate: 80.9%) than that of the other groups (p < 0.05). S'-stage was the most significant factor (p < 0.01) associated with long-term survival. CONCLUSIONS: Salvage surgery is a feasible therapeutic modality for advanced lung cancer. Downstaging to s'-stage I with previous treatment was most important for survival. Complete resection (R0) should be the goal because surgical procedures were tolerated despite intense treatment.

[Rapidly Growthing Mediastinal Cystic Teratoma with Suggestive Perforation by Infection in Pregnancy].

The patient was a 34-year-old female and was 32 weeks pregnant. She was admitted to our department because of mediastinal cyst with infection. She complained of chest pain. Chest computed tomography(CT) revealed the rapid growth of anterior mediastinal tumor. The pain increased after 2 days and magnetic resonance imaging (MRI) suggested the rupture of teratoma. After delivery by Caesarean section, we performed abscess drainage, to stabilize the patient's condition and thereafter the resection of mediastinal teratoma with partial resection of right lung was performed. Histological findings showed a mature teratoma.

[Atypical Pulmonary Carcinoid Tumor with Elevated Serum ProGRP;Report of a Case].

We report a case of an atypical pulmonary carcinoid with high serum ProGRP. A 78-year-old man was found to have an abnormal shadow by a chest X-ray. Chest computed tomography (CT) revealed a solitary pulmonary nodule in the right middle lobe, which was homogeneous, well demarcated, and round. The level of serum ProGRP was elevated to 104.6 pg/ml (normal<81 pg/ml). The nodule was suspected to be a pulmonary carcinoid tumor, and a right middle lobectomy with mediastinal lymph node dissection was performed. Histopathological diagnosis was an atypical pulmonary carcinoid. Pro-GRP decreased to be normal level 5 month after operation.

[Mediastinal Bronchial Artery Aneurysm Associated with Bronchiectasis;Report of a Case].

The patient was a 66-year-old man who had treated with bronchiectasis. He was admitted to our hospital because of hemoptysis. A chest plain computed tomography (CT) showed bronchiectasis in the left lower lobe and nodular lesion in the mediastinum. Chest contrast CT revealed a left bronchial artery aneurysm, and hyperplastic left bronchial arteries dilating and winding toward the left lower lobe. We performed selective angiography of the bronchial artery, revealing an aneurysm, and we performed 3 times of bronchial arterial embolization( BAE). He was performed surgery at 7th day following BAE. After postoperative empyema treatment, he was discharged on the 124th postoperative day.

[Successful Primary Endovascular Repair for Aortoesophageal Fistula due to Ruptured Tuberculous Pseudoaneurysm of the Thoracoabdominal Aorta;Report of a Case].

We report a successful case of 50-year-old woman with aortoesophageal fistula due to tuberculous pseudoaneurysm of the thoracoabdominal aorta. We underwent endovascular repair with stent graft. Her clinical course improved without additional surgical repair or postoperative complications. The patient remains well at 3-year follow-up.

[Hemothorax complicated with celiac artery compression syndrome (CACS); report of a case].

We report a case of hemothorax complicated with celiac artery compression syndrome (CACS). A 43-year-old man presented with a sudden onset left back pain. Computed tomography (CT) showed its hemothorax, esophageal artery aneurysm and severe stenosis of the celiac truncus with its anterior compression by median accurate ligament, and a diagnosis of CACS associated with rupture of the aneurysm was made. Emergent transcatheter arterial embolization of the aneurysm resulted in a technical failure, although the patient's condition was stable and performed esophageal artery ligation through video-assisted thoracoscopic surgery on day 5 after onset. After surgery, the patient recovered without significant incidents. A cause of this aneurysmal development was supposed to be a significantly increased esophageal arterial blood flow with its luminal dilation to compensate a decreased celiac blood flow. Segmental arterial mediolysis could not be excluded as another cause.

Clinical features of primary lung cancer adjoining pulmonary bulla.

A few investigators have suggested a possible association between lung cancer and a pulmonary bulla. But its correlation is not yet fully understood. Five hundred and forty-five cases with primary lung cancer were studied retrospectively by re-evaluation of their chest computed tomography (CT)-scans. Cancer adjoined a bulla in 19 cases. In these instances, each case's clinical course, pathological findings and surgical results were investigated. All cases were men and were heavy smokers. Three of them were under 50 years of age. Bulla/cancer incidence was 3.5%. Initial symptoms were common respiratory symptoms in five cases (26.3%) and hemosputa and hoarseness in one case (5.3%), respectively. In comparison with the control group, a ratio of squamous cell carcinoma (SCC) and large cell carcinoma was significantly high (P<0.05) and differentiation of the carcinoma was poor (P<0.001). Although the pathological staging and lung function data revealed no statistical difference, the survival curve of bulla/cancer group was significantly worse (P<0.01). Primary lung cancer adjoining pulmonary bulla tends to be poor in prognosis, even if it was small in size. A low-density mass shadow adjoining the bulla should be frequently examined by CT-scans and should proceed to an exploratory thoracotomy if it have increased in size.

A case report of 20 lung radiofrequency ablation sessions for 50 lung metastases from parathyroid carcinoma causing hyperparathyroidism.

A 47-year-old man presented with multiple lung metastases from parathyroid carcinoma that caused hyperparathyroidism and refractory hypercalcemia. Lung radiofrequency (RF) ablation was repeated to decrease the serum calcium and parathyroid hormone levels and improve general fatigue. Pulmonary resection was combined for lung hilum metastases. The patient is still alive 4 years after the initial RF session. He has received 20 RF sessions for 50 lung metastases during this period.

Surgical treatment for chronic lung and thoracic cavity infection.

To avoid the complication of aspiration pneumonia, we attempted a new anterior approach of extrapleural pneumonectomy combined with thoracoplasty in four patients with chronic empyema, a bronchopleural fi stula, and severely destroyed lung. The thoracic cage was exposed by an L-shaped parasternal incision making a muscle-skin flap of the anterior chest. The anterior portions of ribs were removed at fi rst, and exfoliation was started in the mediastinal area. After detaching the lung from the mediastinum, an extrapleural pneumonectomy was completed. The backside ribs were then resected by way of the thoracic cavity. The muscle-skin flap was sutured to close the thoracic cavity completely. The procedure was tolerable for three cases. One patient died from accidental rupture of the descending aorta owing to atherosclerotic degeneration. Of the three successful outcomes, recurrence was observed in one case, although it was recurrence of malignant lymphoma associated with chronic empyema.

Pulmonary histoplasmosis as an example of imported mycoses in Japan.

As travel increases, histoplasmosis as an imported mycosis that has the potential to increase abruptly in Japan. A 56-year-old Japanese man who had been in Bolivia for 2 years complained of a dry cough. Chest computed tomography revealed multiple lesions in the right and left lower lobes of his lung that were difficult to diagnose and differentiate from advanced lung cancer. We performed surgical resection for biopsy by video-assisted thoracoscopic surgery. An intraoperative histopathological examination suggested a diagnosis of tuberculoma, but Mycobacterium tuberculosis DNA was not detected in the tumor tissue. Further histopathological examination, however, strongly suggested a diagnosis of histoplasmosis because multiple small, round yeast foci were observed after Grocott staining. The serological test was positive for anti-Histoplasma capsulatum and confirmed the diagnosis of pulmonary histoplasmosis. The postoperative course was uneventful, and fluconazole was administrated for 90 days after the operation. Concerning imported mycoses, physicians should be keep abreast of updated and detailed information.

Limited operation for lung cancer in combination with postoperative radiation therapy.

PURPOSE: Combination therapy of lung wedge resection and postoperative radiation was performed to confirm the procedure's feasibility as a curative therapeutic modality. PATIENTS AND METHODS: Among the patients with clinical stage I lung cancer, who could not undergo a standard lobectomy due to their poor pulmonary function, six cases were studied, who agreed with the experimental trial after the informed consent. One patient of clinical N0 with chest wall invasion (T3) was also included in combination with intraoperative chest wall radiation therapy. At first, a wedge lung resection was performed using an auto-suture technique or manual suturing. Two weeks after the surgery, concomitant radiation therapy of the area including the remnant lung around the cancer and the hilum was initiated. Total dose was 40-50 Gy. All of the patients were followed up for more than five years. RESULTS: All cases tolerated the procedure and survived more than five years. Six were cancer-free. Cancer recurred in only one case. Its manifestation was pleuritis carcinomatosa. Pleural dissemination, which was undetectable at the time of operation, was presumed to be the cause of the recurrence. CONCLUSION: This procedure was tolerated and feasible, preventing local recurrence following the limited surgery.

Toll-like receptor 4 mediates lung ischemia-reperfusion injury.

BACKGROUND: We have previously reported that nuclear factor (NF)-kappaB activation and inflammatory cytokine expression were involved in the development of lung ischemia-reperfusion injury (LIRI). Because Toll-like receptor 4 (TLR4) activates NF-kappaB-dependent transcription of inflammatory cytokine genes during myocardial ischemia-reperfusion injury, we examined whether absence of TLR4 in TLR4-deficient mice protects against LIRI. METHODS: Left lungs of wild-type (C57BL/6J) mice or TLR4-null (TLR4-/-) mice were made ischemic for 60 minutes and then reperfused for 180 minutes. Response to injury was quantified by tissue myeloperoxidase activity, vascular permeability ([125I]-bovine serum albumin extravasation), and leukocyte and inflammatory mediator accumulation in bronchoalveolar lavage expression. Lung homogenates were also analyzed for activation of mitogen-activated protein kinases and nuclear translocation of the transcription factors NF-kappaB and activator protein-1. RESULTS: After LIRI, lungs from TLR4-/- mice demonstrated a 52.4% reduction in vascular permeability (p = 0.001), a 52.6% reduction in lung myeloperoxidase activity (p = 0.006), and a marked reduction in bronchoalveolar lavage leukocyte accumulation when compared with lungs from wild-type mice. The TLR4-/- mice lungs, subjected to LIRI, also demonstrated marked reductions in amounts of several proinflammatory cytokines/chemokines in bronchoalveolar lavage samples. Phosphorylation of c-Jun NH2-terminal kinase, and activation of NF-kappaB and activator protein-1 were also significantly reduced in homogenates of lungs from TLR4-/- mice injured by ischemia and reperfusion (p < 0.05). CONCLUSIONS: These data suggest that TLR4 plays a role in LIRI. Thus, TLR4 may be a potential therapeutic target to minimize ischemic-reperfusion-induced tissue damage and organ dysfunction.

Role of dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine against non-small cell lung cancer--in correlation with the tumoral expression of thymidylate synthase and dihydropyrimidine dehydrogenase.

5-Fluorouracil (5-FU) and its derivatives have been used worldwide for the treatment of several malignancies in solid organs. The effectiveness of these drugs is well proven in gastrointestinal malignancy, and has been reported upon the inverse correlation with the tumoral expression of dihydropyrimidine dehydrogenase (DPD). However, the significance of DPD expression in 5-FU based chemotherapy has not been well investigated in non-small cell lung cancer (NSCLC). We examined enzymatic activities and immunohistochemical expression of thymidylate synthase (TS) and DPD in 84 cases of NSCLC. In vitro sensitivity for 5-FU was tested in 53 cases of them to evaluate these predictive values for effectiveness of 5-FU. Efficacy of 5-chloro-2,4-dihydroxypyridine (CDHP), potent DPD inhibitor, was also examined in 27 cases of them. There was a reversal correlation between protein expression of DPD and sensitivity to 5-FU (r = -0.65; p < 0.001). Six (33.3%) of 18 cases with strong expression of DPD showed 10% or more increment of the anti-tumor effect by adding CDHP to 5-FU. DPD inhibitory fluoropyrimidine and examination of the tumoral expression of DPD might be a promising chemotherapeutic strategy in NSCLC.