Extramural recurrence of tracheal glomus tumour following resection by rigid bronchoscopy.

Glomus tumour of the trachea is very rare neoplasm that is generally benign and arises most commonly from the distal portion of the respiratory tree. This report presents the case of a 67-year-old man who was referred to our institute for excision of a tracheal mass that had been found incidentally, and subsequently recurred extramurally. Initial contrast-enhanced computed tomography images of the chest revealed a nodular lesion in the trachea, 2.5 cm above the carina, that demonstrated strong enhancement similar to blood vessels. The tumour was excised by rigid bronchoscopy, but an extramural tracheal lesion was detected 18 months later. Tracheal resection and end-to-end anastomosis were performed, and histopathological examination confirmed the extramural lesion as recurrence of the tracheal glomus tumour. The histologic features and treatment are discussed.

NOTCH1 and CREBBP co-mutations negatively affect the benefit of adjuvant therapy in completely resected EGFR-mutated NSCLC: translational research of phase III IMPACT study.

The phase III IMPACT study (UMIN000044738) compared adjuvant gefitinib with cisplatin plus vinorelbine (cis/vin) in completely resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Although the primary endpoint of disease-free survival (DFS) was not met, we searched for molecular predictors of adjuvant gefitinib efficacy. Of 234 patients enrolled in the IMPACT study, 202 patients were analyzed for 409 cancer-related gene mutations and tumor mutation burden using resected lung cancer specimens. Frequent somatic mutations included tumor protein p53 (TP53; 58.4%), CUB and Sushi multiple domains 3 (CSMD3; 11.8%), and NOTCH1 (9.9%). Multivariate analysis showed that NOTCH1 co-mutation was a significant poor prognostic factor for overall survival (OS) in the gefitinib group and cAMP response element binding protein (CREBBP) co-mutation for DFS and OS in the cis/vin group. In patients with NOTCH1 co-mutations, gefitinib group had a shorter OS than cis/vin group (Hazard ratio 5.49, 95% CI 1.07-28.00), with a significant interaction (P for interaction = 0.039). In patients with CREBBP co-mutations, the gefitinib group had a longer DFS than the cis/vin group, with a significant interaction (P for interaction = 0.058). In completely resected EGFR-mutated NSCLC, NOTCH1 and CREBBP mutations might predict poor outcome in patients treated with gefitinib and cis/vin, respectively.

Emergent airway recanalization of the left main bronchus due to obstructive adenoid cystic carcinoma enables achievement of radical resection.

Malignant airway obstruction is a life-threatening condition that can cause suffocation and recurrent infections due to lung atelectasis. Adenoid cystic carcinoma is a rare and slow-growing tumour of low-grade malignancy. We report the case of a 69-year-old female who presented with severe chest pain, orthopnea, and a 1-month history of progressively worsening difficulty in breathing. Emergent rigid bronchoscopy revealed a polypoid tumour originating in the proximal end of the left main bronchus that was obstructing the left main bronchus. Debulking of the tumour using rigid bronchoscopy was performed to restore ventilation to collapsed lung and obtain histopathological examination. Histological analysis revealed a diagnosis of adenoid cystic carcinoma. The patient underwent radical sleeve resection of the left main bronchus without sacrificing lung parenchyma via left posterolateral thoracotomy. No postoperative complications or disease recurrence was found at the 5-year follow-up. This case emphasizes the pivotal role of rigid bronchoscopic intervention in malignant central airway obstruction.

Lack of Association of Plasma Levels of Soluble Programmed Cell Death Protein 1, Programmed Death-Ligand 1, and CTLA-4 With Survival for Stage II to IIIA NSCLC After Complete Resection and Adjuvant Chemotherapy.

Introduction: Perioperative treatment in NSCLC has gained marked attention with the introduction of immune checkpoint inhibitors. Such a paradigm shift has given us additional opportunities to evaluate potential biomarkers in patients with these curable disease stages. Methods: This study (WJOG12319LTR) was designed as a biomarker study to evaluate whether soluble immune markers were prognostic or predictive on relapse-free survival in patients with stage II to IIIA NSCLC who underwent complete resection and adjuvant chemotherapy with cisplatin plus S-1, which is an oral fluoropyrimidine formulation that consists of tegafur, gimeracil, and oteracil, or S-1 alone in the previous WJOG4107 study. Archived plasma samples were assayed for soluble (s) forms of programmed cell death protein 1 (sPD-1), programmed death-ligand 1(sPD-L1), and CTLA-4 (sCTLA-4) with the highly sensitive HISCL system. Using time-dependent receiver operating characteristic curve analysis, the area under the curves were derived and optimal cutoff values were determined. Using the cutoff values, whether the marker was prognostic or predictive was assessed by survival analysis. Results: A total of 150 patients were included in the study. The time-dependent receiver operating characteristics analysis revealed that the area under the curves for sPD-1, sPD-L1, and sCTLA-4 were 0.54, 0.51, and 0.58, respectively. The survival analysis did not reject that hazard ratios were 1 in terms of the soluble immune marker and the treatment-marker interaction for all three markers. Conclusions: There was no proof that circulating concentrations of sPD-1, sPD-L1, and sCTLA-4 were prognostic or predictive factors of the outcome for adjuvant chemotherapy after complete resection in patients with NSCLC.

Prospective, Multi-Institutional Observational Study of Deterioration in Activities of Daily Living in Elderly Patients After Lung Cancer Surgery.

Introduction: To determine the rate of deteriorating activities of daily living (ADL) and to investigate predictive factors in elderly patients undergoing surgery for NSCLC. Methods: Patients with NSCLC aged 75 years or older who underwent curative surgical resection were evaluated using the Tokyo Metropolitan Institute of Gerontology Index of Competence Instrumental ADL (TMIG-IADL) and the Japanese version of EuroQol 5-dimensions 5-level (EQ-5D-5L) quality-of-life scale administered at baseline and at 6 months postoperative. The primary end point was the rate of living patients without substantial deterioration of TMIG-IADL, defined as a decline greater than or equal to three points. Multivariable logistic regression was performed to determine risk factors for deteriorating ADL. Results: Between May 2019 and May 2020, 876 of the 986 screened patients enrolled from 47 institutions were eligible and included in the analysis. TMIG-IADL and EQ-5D-5L scores were obtained from 96.0% and 92.6% of the patients, respectively. At 6 months postoperative, 745 patients (85.1%, 95% confidence interval: 82.5%-87.3%) reported no significant ADL deterioration, and 96 of 841 patients (11.4%) with postoperative score data reported significant deterioration. The social domain was the most frequently affected activity. In multivariable analysis, poor performance status, low G8 geriatric screening score, segmentectomy (versus wedge resection), and surgery lasting less than 3 hours were associated with deteriorating ADL. Worsening EQ-5D-5L scores by minimally important difference or more were observed in 22.1% of the patients. Changes in TMIG-IADL and EQ-5D-5L scores were poorly correlated. Conclusions: Approximately 15% of elderly patients with NSCLC experienced significant ADL deterioration at 6 months postoperative.

Segmentectomy for ground-glass-dominant lung cancer with a tumour diameter of 3 cm or less including ground-glass opacity (JCOG1211): a multicentre, single-arm, confirmatory, phase 3 trial.

BACKGROUND: Although segmentectomy is a widely used surgical procedure, lobectomy is the standard procedure for resectable non-small-cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and safety of segmentectomy for NSCLC up to 3 cm in size, including ground-glass opacity (GGO) and predominant GGO. METHODS: A multicentre, single-arm, confirmatory phase 3 trial was conducted across 42 institutions (hospitals, university hospitals, and cancer centres) in Japan. Segmentectomy with hilar, interlobar, and intrapulmonary lymph node dissection was performed as protocol surgery for patients with a tumour diameter of up to 3 cm, including GGO and dominant GGO. Eligible patients were those aged 20-79 years with an Eastern Cooperative Oncology Group performance score of 0 or 1 and clinical stage IA tumour confirmed by thin-sliced CT. The primary endpoint was 5-year relapse-free survival (RFS). This study is registered with the University Hospital Medical Information Network Clinical Trials (UMIN000011819), and is ongoing. FINDINGS: A total of 396 patients were registered from Sept 20, 2013, to Nov 13, 2015, of whom 357 underwent segmentectomy. At a median follow-up of 5·4 years (IQR 5·0-6·0), the 5-year RFS was 98·0% (95% CI 95·9-99·1). This finding exceeded the 87% of the pre-set threshold 5-year RFS and the primary endpoint was met. Grade 3 or 4 early postoperative complications occurred in seven patients (2%), but no grade 5 treatment-related deaths occurred. INTERPRETATION: Segmentectomy should be considered as part of standard treatment for patients with predominantly GGO NSCLC with a tumour size of 3 cm or less in diameter, including GGO even if it exceeds 2 cm. FUNDING: National Cancer Centre Research and Development Fund and Japan Agency for Medical Research and Development.

A dramatic course after the resection of an SMARCA4-deficient undifferentiated tumour.

Thoracic SMARCA4-deficient undifferentiated tumours are ordinarily found as a huge mass with systemic metastasis, and the prognosis is poor. The potential of immunotherapy for these unresectable tumours has been reported. An asymptomatic 68-year-old man with a smoking history had a left lung mass without distant metastasis and underwent complete resection. Two months after surgery, with no adjuvant therapy, he developed multiple distant metastases with aphasia and died 4 months after surgery. Adjuvant treatment may be necessary with immune checkpoint inhibitors, with a closer follow-up to detect recurrence without symptoms.

Desquamation of the subpleural lung parenchyma caused by empyema after pulmonary embolism: A case report.

Subpleural peripheral lung regions are mainly nourished by pulmonary arteries. Herein, we report a case in which pleural infection after pulmonary embolism caused circulation failure in the subpleural lung parenchyma (SLP) and massive desquamation of the SLP.

Extracutaneous neutrophilic infiltration of the spleen and lung associated with pyoderma gangrenosum of the skin.

We describe a patient with extracutaneous pyoderma gangrenosum (PG), who presented with chest pain. Histological examination showed extracutaneous neutrophilic infiltration of the spleen and lung, with later findings of PG.

Laparoscopic liver resection with open partial resection of the thoracoabdominal wall for cancer along the transhepatic biliary drainage tract: A case report.

INTRODUCTION AND IMPORTANCE: Recently, laparoscopic liver resection has been established as a standard procedure for a certain group of hepatic resections; its indications and procedures have been expanding. CASE PRESENTATION: A 67-year-old woman was referred with a chief complaint of left subcostal pain. Eight years and nine months before, she underwent pancreatoduodenectomy for cancer of the ampulla of Vater after endoscopic retrograde biliary drainage for obstructive jaundice. A trans-anastomotic internal-external retrograde transhepatic biliary drainage (RTBD) catheter was placed intraoperatively. Based on radiological findings, intrahepatic cholangiocarcinoma, or local recurrence of cancer of the ampulla of Vater, invading the anterior thoracoabdominal wall, diaphragm, and pericardium, without distant metastasis, were considered. Laparoscopic lateral segmentectomy of the liver combined with open en bloc resection of the invaded portion of the anterior thoracoabdominal wall with costal cartilage, diaphragm, and pericardium was performed. The postoperative course was uneventful, and the patient was discharged 17 days post-surgery. The patient died of cancer recurrence 46 months later. CLINICAL DISCUSSION: The cancer invaded along the RTBD tract. Although the mechanisms of carcinogenesis remain unclear, transhepatic biliary drainage is a risk factor for cancer invasion along the tract. Laparoscopic liver resection before open thoracoabdominal wall resection ensured clear delineation of the cancer margins invading the thoracoabdominal wall and minimized the defect of the thoracoabdominal wall. CONCLUSION: Laparoscopic liver resection for hepatic cancer invading adjacent structures or organs would be feasible and useful in selected patients, even if resection of the invaded area is performed by open surgery.

Rapid Progression of Tracheoesophageal Fistula Caused by Immunotherapy Administered after Tracheal Stent Placement.

Development of a tracheoesophageal fistula (TEF) is a serious complication of treatment for esophageal or lung cancer, especially following radiation therapy. However, development of a TEF as a complication of chemotherapy or tracheal stenting after surgical debulking is quite uncommon. We herein report a rare case involving a patient with advanced adenocarcinoma invading the mediastinum who rapidly developed a TEF after placement of a tracheal stent and administration of nivolumab immunotherapy. A 55-year-old heavy ex-smoker was diagnosed with lung adenocarcinoma with mediastinal invasion. Nine months after first-line therapy (chemotherapy and radiation therapy), he underwent treatment with nivolumab (3 mg/kg) as fourth-line therapy. Two weeks after the first dose, he underwent mechanical debulking of the tumor with tracheal stenting because of the rapid development of paraesophageal lymph node swelling and severe tracheal stenosis. He received a second dose of nivolumab 2 weeks later; however, imaging studies 12 days after this second dose revealed a huge fistula between the upper trachea and esophagus through a metastatic lymph node. Neither an additional stent nor replacement of the stent was considered because of the fistula site expansion and suffocation risk. Despite further treatment, the patient died of his primary disease 2 months later. Our findings will be of great interest to the readers, especially those involved in the clinical treatment of patients with advanced lung cancer treated by immunotherapy. The knowledge of potentially devastating TEF formation in the presence of transmural tracheal metastasis/invasion will allow clinicians to provide the best possible care for their patients.

[Long-Term Survival after Multidisciplinary Treatment for Resected Pancreatic Adenocarcinoma with Recurrence of Pulmonary Metastases - A Case Report].

Recent studies indicated that isolated pulmonary metastases could define a favorable subgroup in metastatic pancreatic cancer. We report a case of isolated pulmonary metastases after curative resection of pancreas head cancer treated with chemotherapy and pulmonary metastasectomy survived for 79 months after recurrence. A 72-year-old male underwent pancreatoduodenectomy for pancreas head cancer. Adjuvant chemotherapy was done with gemcitabine hydrochloride (GEM)for 6 months and then S-1 for 2 months. Twenty-seven months after surgery, 2 small metastatic nodules in the left lung was detected. Chemotherapy with GEM was performed but the lesions grew larger very slowly. A new metastatic nodule was detected in the right lung 40 months after surgery and pleural effusion was detected 52 months after surgery. Then combination chemotherapy with GEM and S-1 was performed for 3 months followed chemotherapy with S-1 alone. Seventytwo months after surgery, chemotherapy with GEM was performed again because of patient's intolerance to S-1. Ninety months after initial surgery, pulmonary metastasectomy of the right lung was performed because of its resistance to chemotherapy. Chemotherapy with GEM was started again 4 months after pulmonary metastasectomy but serum levels of tumor markers remained increase. Combination chemotherapy with GEM and nab-paclitaxel was started 8 months after pulmonary metastasectomy but the patient died 16 months after pulmonary metastasectomy.

Surgical outcome of patients with lung cancer involving the left atrium.

BACKGROUND: Pulmonary and left atrial resection is not yet an established treatment for patients with primary lung cancer involving the left atrium. We investigated the clinical course of patients with primary lung cancer involving the left atrium who were treated with pulmonary resection and partial atrial resection. METHODS: From January 1996 to December 2013, 51 patients underwent extended resection for lung cancer that invaded the surrounding organs. Of these, we focused on 12 patients who underwent surgical treatment for lung cancer involving the left atrium. The clinical course of each of these patients was investigated retrospectively. RESULTS: The most common histological subtype was squamous cell carcinoma. Pneumonectomy was performed in nine patients, and right middle and lower lobectomy was performed in three patients. Complete resection was performed in 11 patients (92 %). Postoperative complications were observed in four patients (33 %)-prolonged air leakage in two patients, broncho-pleural fistula in one patient, and empyema in one patient. There were no surgical deaths. This study involved seven patients with pathological N0-1 disease and five patients with pathological N2 disease. The postoperative 5-year survival rate was 46 % in all patients. The 5-year survival rates in patients with pathological N0-1 disease and N2 disease were 67 and 20 %, respectively. CONCLUSION: Because treatment-related death was not observed and outcome was fair in patients with N0-1 disease, surgical resection for primary lung cancer involving the left atrium may be acceptable in selected patients. Further investigations are required to improve the outcome of surgical treatment for patients with primary lung cancer involving the left atrium.

Efficacy of Surgical Airway Plasty for Benign Airway Stenosis.

BACKGROUND: Long-term patency is required during treatment for benign airway stenosis. This study investigated the effectiveness of surgical airway plasty for benign airway stenosis. METHODS: Clinical courses of 20 patients, who were treated with surgical plasty for their benign airway stenosis, were retrospectively investigated. RESULTS: Causes of stenosis were tracheobronchial tuberculosis in 12 patients, post-intubation stenosis in five patients, malacia in two patients, and others in one patient. 28 interventional pulmonology procedures and 20 surgical plasty were performed. Five patients with post-intubation stenosis and four patients with tuberculous stenosis were treated with tracheoplasty. Eight patients with tuberculous stenosis were treated with bronchoplasty, and two patients with malacia were treated with stabilization of the membranous portion. Anastomotic stenosis was observed in four patients, and one to four additional treatments were required. Performance status, Hugh-Jones classification, and ventilatory functions were improved after surgical plasty. Outcomes were fair in patients with tuberculous stenosis and malacia. However, efficacy of surgical plasty for post-intubation stenosis was not observed. CONCLUSION: Surgical airway plasty may be an acceptable treatment for tuberculous stenosis. Patients with malacia recover well after surgical plasty. There may be untreated patients with malacia who have the potential to benefit from surgical plasty.

Randomized Phase II Study of Adjuvant Chemotherapy with Long-term S-1 versus Cisplatin+S-1 in Completely Resected Stage II-IIIA Non-Small Cell Lung Cancer.

PURPOSE: The aims of this study were to evaluate the efficacy and safety of S-1 versus cisplatin (CDDP)+S-1 in patients with completely resected stage II and IIIA non-small cell lung cancer, and to identify predictive biomarkers whose expression in the tumors was significantly associated with patient outcome. EXPERIMENTAL DESIGN: A total of 200 patients were randomly assigned to receive either S-1 (40 mg/m(2) twice per day) for 2 consecutive weeks repeated every 3 weeks for 1 year (S group) or CDDP (60 mg/m(2)) on day 1 plus oral S-1 (40 mg/m(2) twice per day) for 2 consecutive weeks repeated every 3 weeks for four cycles (CS group) within 8 weeks after surgery. The primary endpoints were relapse-free survival (RFS) at 2 years and identification of predictive biomarkers whose expressions have been reported to be associated with CDDP or fluoropyrimidine sensitivity. RESULTS: The RFS rate at 2 years was 65.6% (95% confidence intervals; CI, 55.3-74.0%) in the S group and 58.1% (95% CI, 47.7-67.2%) in the CS group. The only gene with interaction of P < 0.05 was uridine monophosphate synthase (UMPS; P = 0.0348). The benefit that members of the S group had over members of the CS group was higher expression of UMPS. In vitro and in vivo experiments confirmed that overexpression of UMPS enhanced the antitumor effect of fluoropyrimidine. CONCLUSIONS: Adjuvant S-1 monotherapy might be preferable to CDDP+S-1 for patients with completely resected NSCLC. UMPS expression may define a patient subset that would benefit from long-term postoperative S-1 monotherapy.

[Thoracic Drainage Using Nasal Airway for Postoperative Broncho-pleural Fistula].

A 61-year-old man with right lung cancer underwent right lower lobectomy. He suffered from postoperative broncho-pleural fistula, which was treated with thoracic drainage. After disappearance of air leakage, a drainage tube was removed. Forty days later, severe back pain, cough and fever were observed. Chest computed tomography showed enlarged thoracic cavity around the bronchial stump. Bronchoscopical examination revealed complete dehiscence of the bronchial stump. Because thoracic cavity was localized and located dorsal to the bronchial stump, a fenestration surgery was difficult. We placed a nasal airway from the dorsal to directly thoracic cavity, followed by disappearance of the symptoms. Thoracic cavity around the bronchial stump was gradually decreased and a nasal airway was successfully removed. Because a nasal airway was soft enough to keep supine position, we chose it as a drainage tube. Thoracic drainage using nasal airway may be a suitable therapeutic approach for localized small thoracic cavity.

Surgical reconstruction for tuberculous airway stenosis: management for patients with concomitant tracheal malacia.

OBJECTIVES: Surgical reconstruction is commonly recommended for the treatment of tuberculous airway stenosis. The clinical conditions underlying tuberculous airway stenosis often involve both cicatricial stenosis and malacia. Surgical reconstruction alone may not improve the respiratory symptoms of patients with both types of airway stenosis. This study retrospectively reviewed patients who underwent surgical reconstruction for tuberculous airway stenosis to investigate the most appropriate treatment for this complicated condition. METHODS: Twelve patients with tuberculous airway stenosis underwent surgical reconstruction at our institute from January 2003 to December 2013. The clinical courses of these patients were retrospectively reviewed. RESULTS: The 12 patients were 2 men and 10 women with a mean age of 36 years (range 17-61 years). The site of stenosis was the left main bronchus in six patients, trachea in four patients, and right main bronchus in two patients. The procedure performed was sleeve lobectomy in five patients, bronchial resection in four patients, and tracheal resection in three patients. Additional airway stenting was performed in two patients with concomitant malacia of the lower trachea. The performance status and Hugh-Jones classification improved postoperatively in all patients. The forced expiratory volume in 1 s as a percent of forced vital capacity and percent of forced expiratory volume in 1 s improved significantly. CONCLUSION: Surgical reconstruction is an acceptable treatment for tuberculous airway stenosis. Additional airway stenting may be needed in patients with symptomatic malacia.

Sequential stenting for extensive malignant airway stenosis.

PURPOSE: Malignant airway stenosis extending from the bronchial bifurcation to the lower lobar orifice was treated with airway stenting. We herein examine the effectiveness of airway stenting for extensive malignant airway stenosis. METHODS: Twelve patients with extensive malignant airway stenosis underwent placement of a silicone Dumon Y stent (Novatech, La Ciotat, France) at the tracheal bifurcation and a metallic Spiral Z-stent (Medico's Hirata, Osaka, Japan) at either distal side of the Y stent. We retrospectively analyzed the therapeutic efficacy of the sequential placement of these silicone and metallic stents in these 12 patients. RESULTS: The primary disease was lung cancer in eight patients, breast cancer in two patients, tracheal cancer in one patient, and thyroid cancer in one patient. The median survival period after airway stent placement was 46 days. The Hugh-Jones classification and performance status improved in nine patients after airway stenting. One patient had prolonged hemoptysis and died of respiratory tract hemorrhage 15 days after the treatment. CONCLUSION: Because the initial disease was advanced and aggressive, the prognosis after sequential airway stent placement was significantly poor. However, because respiratory distress decreased after the treatment in most patients, this treatment may be acceptable for selected patients with extensive malignant airway stenosis.

Resection of a second primary lung cancer in a lobe where small-cell lung cancer was previously treated with chemoradiotherapy: report of a case.

There are few reports of resected cases of second primary lung cancer in post-treatment survivors of small-cell lung cancer. Here, we report a surgical case of a 62-year-old female with second primary lung adenocarcinoma after chemoradiotherapy against small-cell lung cancer. She had been treated for small-cell lung cancer 2 years earlier, and achieved complete response after the treatment. A new nodular lesion was detected at a different segment in the right lower lobe. We performed a right lower lobectomy accompanied with systemic mediastinal nodal dissection. Histopathological findings revealed that the new nodular lesion was a second primary lung adenocarcinoma. No metastatic tumor was seen in the dissected lymph node; the initial tumor had disappeared completely. The postoperative course was uneventful, and she was discharged on day 10 after the operation. Ten months after the operation, she was free of recurrent tumor.

Ectopic bone formation in a subsegmental bronchus.

A 48-year-old man with fever and dry cough was admitted to our hospital. Imaging examinations revealed a mass lesion with calcification in the right B(3)b bronchus and atelectasis in the distal lung area. Subsequently, right S(3) segmentectomy was performed. There was a hard polypoid mass completely obstructing the right B(3)b bronchus. Histopathological findings suggested a metaplastic bone formation with mature bone marrow tissue leading to the primary bronchial cartilage. A case of ectopic bone formation in subsegmental bronchus has never been reported thus far. The resident fibroblasts might transform into osteoblasts under appropriate environmental conditions and induce bone formation.