Postoperative tegafur-uracil for stage I lung adenocarcinoma: first real-world data with an exploratory subgroup analysis.

PURPOSE: The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting. METHODS: A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects. RESULTS: After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort. CONCLUSIONS: The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years.

Randomized phase II study of daily and alternate-day administration of S-1 for adjuvant chemotherapy in completely-resected stage I non-small cell lung cancer: results of the Setouchi Lung Cancer Group Study 1301.

BACKGROUND: The aim of this multicenter, randomized phase II study was to analyze the feasibility and safety of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in patients with completely resected pathological stage I (tumor diameter > 2 cm) non-small cell lung cancer (NSCLC). METHODS: Patients were randomly assigned to receive adjuvant chemotherapy for 1 year comprising either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Group A) or a 2-week oral administration of S-1 (80 mg/m2/day) followed by 1 week of rest (Group B). The primary endpoint was feasibility, which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. RESULTS: Ninety-three patients were enrolled of whom 90 patients received S-1 treatment. Median follow-up was 66.9 months. The treatment completion rate based on an RDI of 70% or more for 6 months was 84.4% (95%CI; 70.5-93.5%) in group A and 64.4% (95%CI; 48.8-78.1%) in group B. There were no grade 4 adverse events in either group. Moderate or severe adverse events (grade 2 or grade 3) were significantly more frequent in group B (67%) compared with group A (29%, P = 0.001). The 5-year relapse-free survival rate was 87.0 and 80.9% for group A and B, respectively (P = 0.451). The 5-year overall survival rate for all patients (n = 93) was 100 and 89.4% for group A and B, respectively (P = 0.136). CONCLUSION: Alternate-day oral administration of S-1 for 1 year as adjuvant chemotherapy was demonstrated to be feasible with low toxicity in completely resected stage I (tumor diameter > 2 cm) NSCLC. TRIAL REGISTRATION: Trial registration number: UMIN000011994 . Date of registration: 10/8/2013.

The treatment and survival of patients with postoperative recurrent thymic carcinoma and neuroendocrine carcinoma: a multicenter retrospective study.

PURPOSE: There are few data available on the outcomes of postoperative recurrent thymic carcinoma (TC) and thymic neuroendocrine carcinoma (TNEC). The aim of this study is to evaluate the treatment and survival in patients with recurrent TC and TNEC after undergoing surgical resection. METHODS: A retrospective chart review was performed using our multicenter database to identify patients with a postoperative recurrence of TC and TNEC from 1995 to 2018. The clinicopathological factors were reviewed and the survival outcomes were analyzed. RESULTS: Sixty patients were identified among 152 patients who underwent resection of TC and TNEC. The median follow-up period from the first recurrence was 14.8 months (range 0-144). The 5-year post-recurrence survival was 23% for the whole cohort. According to a univariable analysis, advanced stage [hazard ratio (HR) 2.81, 95% confidence interval (CI) 1.09-9.54], interval between primary surgery and recurrence (HR 0.97, 95% CI 0.95-0.99), any treatment for recurrence (HR: 0.27, 95% CI 0.13-0.58) and chemotherapy for recurrence (HR: 0.46, 95% CI 0.22-0.95) were significant factors related to post-recurrence survival. CONCLUSIONS: Chemotherapy rather than surgery appears to be the mainstay treatment for managing patients with postoperative recurrent TC and TNEC and it may also be considered in multidisciplinary management. Further studies with a larger sample size are required to confirm our findings.

Survival outcomes after minimally invasive thymectomy for early-stage thymic carcinoma.

Minimally invasive surgery (MIS) has occasionally been used for selected patients with thymoma, but there is little information on the MIS approach for thymic carcinoma. The aim of this study was to evaluate survival outcomes after MIS for early-stage (Masaoka stage I-II) thymic carcinoma and thymic neuroendocrine carcinoma. A retrospective chart review of the cases recorded in our multi-institutional database was performed to identify patients who underwent resection for thymic carcinoma between 1995 and 2017. MIS thymectomy was performed in 17 cases (VATS, n = 14; RATS, n = 3. male, 41%; median age, 72 years). The median follow-up period was 32.7 (range 7.4-106) months. The five-year overall survival and relapse-free survival rates were 84.4% and 77.8%, respectively. The present study demonstrated encouraging preliminary results regarding MIS for the treatment of early-stage thymic carcinoma and thymic neuroendocrine carcinoma. Further studies with a larger sample size are required to evaluate the indications for this surgery.

[Usefulness of Nutritional Enforcement by Percutaneous Gastrostomy in Successful Omentoplasty for Empyema with Fistula].

Omentoplasty has been accepted as an effective surgical procedure for fistulated empyema. However, it is difficult for patients with poor nutritional status because their omental volume is often too poor to be applied for omentoplasty. Percutaneous endoscopic gastrostomy(PEG) is useful for long-term nutritional management. There is no report on safety and usefulness of PEG before omentoplasty. We report a case of omentoplasty that was successfully performed after nutritional enforcement by using percutaneous endoscopic gastrostomy in a patient of postoperative empyema with fistula.

[Nutritional treatment for bronchopleural fistula-promising effect of arginine as a pharmaconutrient].

Pharmaconutrition, which is a supportive nutritional care of surgical patients, has been proven to shorten hospital stay, decrease the incidence of infection, and reduce hospital costs in selected groups of patients. Arginine, one of the most essential pharmaconutrients, has also been proven to enhance would healing process. In severely malnourished patients like bronchopleural fistula with resultant empyema, aggressive nutritional approach should be mandatory. And management of the fistula is also important in stabilizing the ongoing infection. Our hypothesis was that basic nutritional support enhanced with arginine would be effective in not only improving the general condition including nutritional status but also in healing the fistula. We report a case of major bronchopleural fistula in which arginine-supplemented diet as well as aggressive nutritional support could accelerate the postoperative recovery after open thoracic window, ultimately leading to the healing of the fistula.

Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201.

BACKGROUND: It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC. METHODS: Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. RESULTS: We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11). CONCLUSION: Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. TRIAL REGISTRATION: Unique ID issued by UMIN: UMIN000007819 (Date of registration: Apr 25, 2012) https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009128. Trial ID issued by jRCT: jRCTs061180089 (Date of registration: Mar 22, 2019, for a shift toward a "specified clinical trial" based on Clinical Trials Act in Japan) https://jrct.niph.go.jp/en-latest-detail/jRCTs061180089.

Outcomes and pulmonary function in living lobar lung transplant donors.

Successful living-donor lobar lung transplantation (LDLLT) largely depends on donor outcome; however, there are few studies that have assessed outcomes of LDLLT donors, particularly pulmonary function. We investigated the outcomes and pulmonary function after donor lobectomy in LDLLT donors. Retrospective evaluation of consecutive 33 LDLLT donors was performed. Preoperative characteristics and perioperative and postoperative variables were investigated. Evaluation of pulmonary function 3, 6 and 12 months after donor lobectomy was performed prospectively. All donors were well alive after donor lobectomies. Morbidity was found in five donors (15%). Postoperative complications consisted of re-accumulation of pleural effusion requiring readmission in three donors and prolonged air leakage in two donors. Sacrifice of pulmonary arteries was performed in 20 donors (61%) with 1.4 ± 0.6 branches. Forced vital capacity was 77.8 ± 6.1%, 84.8 ± 6.0% and 89.4 ± 6.6% of the preoperative value 3, 6 and 12 months after donor lobectomy, respectively. Forced expiratory volume in 1 s was 80.5 ± 7.8%, 85.6 ± 8.9% and 89.3 ± 8.7% of the preoperative value 3, 6, and 12 months postoperatively. Living-donor lobectomy was performed with low morbidity. Pulmonary function even after lobectomy was better preserved than expected.

Short-term outcome in living donors for lung transplantation: the role of preoperative computer tomographic evaluations of fissures and vascular anatomy.

Successful living-donor lobar lung transplantation (LDLLT) largely depends on donor outcome. We reviewed our experiences with LDLLT and focused on preoperative computed tomographic evaluations of donors. Twenty-five LDLLTs were performed in Kyoto University. As a routine preoperative assessment, high-resolution chest computed tomography (CT), and three-dimensional (3D)-CT angiography were performed. Preoperative evaluations, surgical procedures, and early postoperative outcomes were reviewed in 43 consecutive LDLLT donors. All donors were discharged home after the donor lobectomies. Severely incomplete fissures were intraoperatively identified in two donors, whose interlobar fissures were mostly not identified by high resolution CT preoperatively. Preoperative 3D-CT angiography was effective for the identification of the branches of the pulmonary artery and vein. Pulmonary arterioplasties were performed with auto pericardial patches in three left donors. The bilateral donors had to be exchanged because of an anomaly of the pulmonary veins in one donor. Small pulmonary arterial branches to the remaining lobes were to be sacrificed in 23 donors (53%). Early postoperative complications were ascertained in seven donors, and five of them presented air leak-related complications. Living donor lobectomies were safely performed with low morbidities in our institution. Preoperative computer tomographic evaluations might be useful in donor lobectomies.

Therapeutic effect of surfactant inhalation during warm ischemia in an isolated rat lung perfusion model.

Warm ischemia-reperfusion injury related to donation after cardiac death donors is a crucial and inevitable issue. As surfactant function is known to deteriorate during warm ischemia, we hypothesized that surfactant inhalation during warm ischemia would mitigate warm ischemia-reperfusion injury. We used an isolated rat lung perfusion model. The rats were divided into three groups: sham, control, and surfactant. In the control and surfactant groups, cardiac arrest was induced by ventricular fibrillation. Ventilation was restarted 110 min later; subsequently, the lungs were flushed, and heart and lung block was recovered. In the surfactant group, a natural bovine surfactant Surfacten(®) was inhaled for 3 min at the end of warm ischemia. Then, the lungs were reperfused for 80 min. Surfactant inhalation significantly improved graft functions, effectively increased lung tissue ATP levels, and significantly decreased mRNA levels of IL-6 and IL-6/IL-10 ratio at the end of reperfusion. Histologically, lungs in the surfactant group showed fewer signs of interstitial edema and hemorrhage, and significantly less neutrophilic infiltration than those in the control group. Our results indicated that surfactant inhalation in the last phase of warm ischemia maintained lung tissue energy levels and prevented cytokine production, resulting in the alleviation of warm ischemia-reperfusion injury.

Antibody-mediated rejection of a unilateral donor lung in bilateral living-donor lobar lung transplantation: report of a case.

We report a case of antibody-mediated rejection (AMR) of a unilateral donor lung in the presence of newly formed donor-specific antibodies, 10 months after living-donor lobar lung transplantation (LDLLT). Of note is that the AMR occurred in the unilateral lung. Furthermore, the lung graft was from her husband and HLA analysis on the recipient's daughter revealed the same donor-specific HLA antigens, which strongly suggested pre-sensitization before lung transplantation. Fortunately, we could perform direct crossmatch even 1 year after lung transplantation because of the living donors.

[Perioperative nutritional support with immune-enhancing diet for surgical closure of open thoracic window].

Immunonutrition, which is a therapeutic approach to modulate acute surgical or medical conditions, has been proven to decrease surgical site complications in patients undergoing major elective surgery for upper gastrointestinal and esophageal malignancy. For immunonutrition to be carried out effectively, specific nutrients called pharmaconutrients are quite important. In our case, to enhance the perioperative nutritional status of the patient, special formulas supplemented with specific pharmaconutrients, which are arginine and omega-3 fatty acids, were orally administered. The open thoracic window for chronic empyema caused by postoperative bronchopleural fistula was successfully closed. Perioperative immunonutrition is likely to have beneficial effect in decreasing postoperative infectious complications in high-risk malnourished thoracic surgical patients.

Epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma: a multi-institutional retrospective study.

OBJECTIVES: The aim of this study was to analyse the long-term survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma. METHODS: Using a multi-institutional database, we performed a retrospective chart review to identify all patients who had undergone complete resection of stage I-III EGFR-mutated lung adenocarcinoma at 11 acute care hospitals between 2009 and 2016 and had received first-line EGFR-TKI treatment for postoperative recurrence. Adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using Kaplan-Meier analysis. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for PFS and OS. RESULTS: The study sample comprised 154 patients with a median age of 69. The total numbers of events were 101 for PFS and 60 for OS. The median PFS and OS were 26.1 and 55.4 months, respectively. In the multivariable analysis, EGFR ex 21 L858R mutation (HR: 1.71, 95% CI: 1.15-2.55) and shorter disease-free intervals (HR: 0.98, 95% CI: 0.96-0.99) were significantly associated with shorter PFS. Age (HR: 1.03, 95% CI: 1.00-1.07), smoking history (HR: 2.31, 95% CI: 1.35-3.94) and pathological N2 disease at the initial surgery (HR: 2.30, 95% CI: 1.32-4.00) were significantly associated with shorter OS. CONCLUSIONS: First-line EGFR-TKI treatment was generally associated with favourable survival outcomes in patients with postoperative recurrent EGFR-mutated lung adenocarcinoma. EGFR ex 21 L858R mutation may be an important prognostic factor for shorter PFS.

A novel technique for Endobronchial Watanabe Spigot placement for bronchopleural fistula: a traction method.

Empyema with bronchopleural fistula is a challenging condition that often requires open-window thoracostomy. Bronchial occlusion with Endobronchial Watanabe Spigot is an effective and less invasive procedure to close the fistula; however, delivering a spigot into the target bronchus requires high technical skills. Herein, we report a case of bronchopleural fistula occluded with a spigot using a new 'traction method' in which the spigot is tied as an anchor to a guidewire and pulled into the target bronchus. Our method allows selective and steady placement of the spigot for patients who undergo open-window thoracostomy for the treatment of bronchopleural fistula.

Multicentre, prospective, observational study investigating the most appropriate surgical option that can prevent the recurrence of primary spontaneous pneumothorax after surgery: the PATCH study, protocol.

INTRODUCTION: Thoracoscopic surgery is performed for refractory or recurrent primary spontaneous pneumothorax (PSP). To reduce postoperative recurrence, additional treatment is occasionally adopted during surgery after bulla resection. However, the most effective method has not been fully elucidated. Furthermore, the preference for additional treatment varies among countries, and its efficacy in preventing recurrence must be evaluated based on settings tailored for the conditions of a specific country. The number of registries collecting detailed data about PSP surgery is limited. Therefore, to address this issue, a prospective multicentre observational study was performed. METHODS AND ANALYSIS: This multicentre, prospective, observational study will enrol 450 participants aged between 16 and 40 years who initially underwent PSP surgery. Data about demographic characteristics, disease and family history, surgical details, and CT scan findings will be collected. Follow-up must be conducted until 3 years after surgery or in the event of recurrence, whichever came first. Patients without recurrence will undergo annual follow-up until 3 years after surgery. The primary outcome is the rate of recurrence within 2 years after surgery. A multivariate analysis will be performed to compare the efficacy of different surgical options. Then, adverse outcomes correlated with various treatments and the feasibility of treatment methods will be compared. ETHICS AND DISSEMINATION: This study was approved by the local ethics committee of all participating centres. The findings will be available in 2025, and they can be used as a basis for clinical decision-making regarding appropriate options for the initial PSP surgery. TRIAL REGISTRATION NUMBER: NCT04758143.

Perioperative assessment of oversized lobar graft downsizing in living-donor lobar lung transplantation using three-dimensional computed tomographic volumetry.

A 15-year-old boy with bronchiolitis obliterans after bone marrow transplantation successfully underwent bilateral living-donor lobar lung transplantation (LDLLT) with segmentectomy of the superior segment of an oversized right lower lobe graft. As the recipient was small for his age, the predicted value of his functional vital capacity of the recipient was difficult to determine preoperatively. Three-dimensional computed tomography (CT) volumetry revealed that the ratio of donor graft volume to recipient hemithorax volume was 159% on the right side and 82% on the left side. The patient is alive and well 7 months after transplantation, and three-dimensional CT volumetry revealed that the right and left donor lungs were still compressed to 73% and 84% of the original size, respectively. In LDLLT, segmentectomy of the superior segment of the lower lobe is a useful option for downsizing an oversized graft and three-dimensional CT volumetry can provide meaningful data for size matching.

Forced oscillation technique as a non-invasive assessment for lung transplant recipients.

We usually use spirometry for the medical follow-up of respiratory mechanics after lung transplantation. However, especially in the first few post-operative weeks, it is easily affected by postoperative pain and the patient's co-operation during forced breathing effort. To avoid missing out on assessing pulmonary function, we perform non-invasive forced oscillation techniques on the patients who cannot perform forced breathing maneuvers. In this paper, we discuss the application of forced oscillation techniques on a patient with suspicion of acute lung rejection, whose spirometry could not be correctly performed and seemed to be unreliable. The respiratory impedance measurements had good correlation with the patient's clinical symptoms before and after steroid therapy. Thus, postoperative pulmonary function follow-up using forced oscillation technique was useful in assessing peripheral airway condition in critically ill patients, and may be able to detect acute rejection.

Age-related changes in the trachea in healthy adults.

To investigate age-related changes in the shape of trachea, normal male volunteers (n = 83, mean +/- SD: 47.7 +/- 20.2 years old) underwent inspiratory CT scans at full inspiration and lung function tests. Subjects who showed VC < 80% predicted or FEV1 < 80% predicted on lung function tests were excluded. The CT data, which is located at 2.0 cm above the aortic arch, were transferred to a personal computer. The tracheal area (St) and two parameters, Tracheal index (Ti) and Circularity (Ci) indicating the shape of the trachea, were automatically calculated. Ti was defined the ratio of the coronal to the sagittal diameter of the trachea, and the Ci (Ci = 4piS/L2, S: tracheal area, L: tracheal perimeter) was used to indicate the roundness of the trachea. A Ci value of less than 1 indicated the distortion of the roundness. Both St and St/BSA (body surface area) showed a significant correlation with age (r = 0.37, r = 0.52; p = 0.0006, p < 0.0001). Ti was not correlated with age (r = -0.20; p = 0.0697), whereas Ci was significantly correlated with age (r = -0.32; p = 0.00364). There were measurable age related changes of the trachea both in the area and the shape. Aging results in the increased tracheal area and a distortion of the roundness.

Congenital partial pericardial defect confirmed based on spontaneous pneumothorax: A case report and literature review.

INTRODUCTION: Congenital pericardial defects are rare but can cause fatal complications. Most cases are asymptomatic and incidentally detected during a thoracic surgery or autopsy. We report a case of a partial pericardial defect confirmed based on spontaneous pneumothorax. PRESENTATION OF CASE: A 16-year-old boy with left spontaneous pneumothorax showed pneumopericardium on chest X-ray. Chest computed tomography revealed a partial pericardial defect. Video-assisted thoracoscopic surgery was performed, and a small pericardial defect was confirmed at the level of the upper pulmonary hilum. We did not reconstruct the defect because of the improbability of cardiac herniation. DISCUSSION: Pneumopericardium combined with pneumothorax suggests the existence of a pericardial foramen. Partial pericardial defects could cause cardiac herniation or strangulation, and pneumothorax may worsen the protruding of the heart. Video-assisted thoracic surgery is an effective method to prevent the recurrence of pneumothorax and determine whether reconstruction of the defect is required. CONCLUSION: Video-assisted thoracic surgery should be performed in the case of a pericardial defect combined with pneumothorax.

Solitary Pulmonary Hematoma Radiographically Indistinguishable from Mediastinal Tumor.

Solitary pulmonary hematoma is a rare consequence of blunt chest trauma. Moreover, there has been no reported case of solitary pulmonary hematoma radiographically diagnosed as a posterior mediastinal tumor. We present the case of a 63-year-old man who was referred for an oval-shaped opacity at the left paraspinal area on a chest X-ray. Chest computed tomography showed a well-circumscribed posterior mediastinal tumor on the left paraspinal lesion with extrapleural sign and callus formation on the left ribs posteriorly (7th to 11th ribs). The tumor was thoracoscopically confirmed to be a subpleural pulmonary tumor of the left lower lobe, and wedge resection was performed. Histological examination confirmed the diagnosis of pulmonary hematoma. On reviewing the callus formation of the ribs, which was suggestive of rib fractures, the pulmonary hematoma was determined to be traumatic in origin. The postoperative course was uneventful. We reviewed a rare case of pathologically proven traumatic solitary pulmonary hematoma. The rarity of this case is enhanced because the hematoma initially appeared to be a posterior mediastinal tumor.