Salvage surgery to treat tumor regrowth after stereotactic body radiotherapy in primary non-small cell lung cancer.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is considered to be an effective and safe treatment in patients with primary lung cancer. If local recurrence is confirmed following SBRT, surgical treatment is a possibility. The present study aimed to clarify the safety and survival outcomes of salvage surgery in primary lung cancer patients with local recurrence following SBRT. METHODS: All subjects were patients with primary lung cancer who underwent surgical treatment for local recurrence following SBRT during the period from July 2005 to July 2015. We evaluated the reason for SBRT selection, the surgical procedure, postoperative complications, and prognosis. RESULTS: Of 932 patients underwent SBRT as treatment for primary lung cancer, 48 patients (5.2%) had local recurrence alone and 19 patients (2.0%) underwent salvage surgery. SBRT was selected in eight medically operable patients who refused surgery, and in 11 patients considered medically inoperable by their pulmonologist. Lobectomy was performed in 15 patients. Postoperative complications were documented in 4 patients (21.1%). Incomplete resection was performed in 2 patients. Stage progression was confirmed in 7 patients (36.8%). The 5-year overall survival (OS) was 72.5% and the 5-year disease-free survival (DFS) was 65.2%. CONCLUSIONS: We evaluated patients who underwent salvage surgery due to local recurrence of lung cancer following SBRT. We found that salvage surgery could be performed safely without affecting SBRT outcomes. We further infer that cases of complete resection are likely to be associated with good prognosis, and that SBRT should be selected only after careful consideration because complete resection is not possible in all cases.

Impact of postoperative complications on outcomes of second surgery for second primary lung cancer.

PURPOSE: The best surgical approach for second primary lung cancer remains a subject of debate. The purpose of this study was to review the postoperative complications after second surgery for second primary lung cancer and to investigate the outcomes based on these complications. METHODS: The clinical data of 105 consecutive patients who underwent pulmonary resection for multiple primary lung cancers between January, 1996 and December, 2017, were reviewed according to the Martini-Melamed criteria. RESULTS: After the second surgery, low body mass index (BMI) (< 18.5 kg/m2) (P = 0.004) and high Charlson comorbidity index (CCI) (P = 0.002) were independent predictors of postoperative complications. Survival analysis revealed the 5-year overall survival rates of 74.5% and 61.4% for patients without postoperative complications and those with postoperative complications (P = 0.044), respectively, but the 5-year cancer-specific survival rates of 82.5% and 80.0% (P = 0.926), respectively. During this period, there were significantly more respiratory-related deaths of patients with complications than of those without complications (P = 0.011). CONCLUSION: Surgical intervention is feasible and potentially effective for second primary lung cancer but may not achieve positive perioperative and long-term outcomes for patients with a low BMI or a high CCI. Treatment options should be considered carefully for these patients.

Generation of Lungs by Blastocyst Complementation in Apneumic Fgf10-Deficient Mice.

The shortage of donor lungs hinders lung transplantation, the only definitive option for patients with end-stage lung disease. Blastocyst complementation enables the generation of transplantable organs from pluripotent stem cells (PSCs) in animal models. Pancreases and kidneys have been generated from PSCs by blastocyst complementation in rodent models. Here, we report the generation of lungs using mouse embryonic stem cells (ESCs) in apneumic Fgf10 Ex1mut/Ex3mutmice by blastocyst complementation. Complementation with ESCs enables Fgf10-deficient mice to survive to adulthood without abnormalities. Both the generated lung alveolar parenchyma and the interstitial portions, including vascular endothelial cells, vascular and parabronchial smooth muscle cells, and connective tissue, largely originate from the injected ESCs. These data suggest that Fgf10 Ex1mut/Ex3mutblastocysts provide an organ niche for lung generation and that blastocyst complementation could be a viable approach for generating whole lungs.

[Resection of Multiple Thymic Carcinomas of the Thymus].

The patient was a 70-year-old woman who was found to have 2 mediastinal tumors on chest computed tomography(CT). One was located in the anterior mediastinum, and the other was in the upper mediastinum. Based on previous imaging studies, it was revealed that the 2 tumors had been increasing in size for 5 years. Thymectomy via median sternotomy was performed. Histopathologically, 3 tumors revealed to be in the thymus without direct invasion of the adjacent organs. All were thymic squamous cell carcinomas of 3.0×1.8×1.6 cm, 2.5×1.6×1.2 cm and 0.7 cm in size. No lymphatic invasion was observed and all tumors were pathologically stage I. Thus, we considered the 3 tumors were multi-centric primary tumors.

[Dedifferentiated Liposarcoma of the Anterior Mediastinum;Report of a Case].

A 69-year-old man was pointed out the anterior mediastinal mass on chest computed tomography (CT). Since the thymoma was suspected, thymectomy was performed through median sternotomy. The tumor was encapsulated and did not directly invade adjacent organs. The tumor was 8.3×5.3×8.2 cm in size. Histological examination of the resected specimen showed a large mucinous component and a small fibrous component, both containing many atypical spindle cells and multinuclear giant cells, and fat cells and atypical lipoblasts observed in a small part of the specimen. The postoperative pathological diagnosis was dedifferentiated liposarcoma. No relapse is observed without adjuvant therapy at 1 year after surgery.

Early and mid-term outcomes of simultaneous thoracic endovascular stent grafting and combined resection of thoracic malignancies and the aortic wall.

OBJECTIVES: To aim of this study was to clarify the safety of simultaneous thoracic aortic endografting and combined resection of the aortic wall and thoracic malignancy in a one-stage procedure over the early and mid-term periods. METHODS: From March 2013 to December 2017, 6 patients underwent aortic endografting followed by one-stage en bloc resection of the tumor and aortic wall. Thoracic surgeons and cardiovascular surgeons discussed predicted tumor invasion range and resection site, stent placement position, stent length and size, and the surgical procedure, taking into account the safe margin. RESULTS: The proximal site of aortic endografting was the: aortic arch in 2 cases (subclavian artery (SCA) occlusion in one, and SCA fenestration in one); distal arch just beneath the SCA in 2; descending aorta in 2. Pulmonary resection involved lobectomy in 2 patients, pneumonectomy in 2, and completion pneumonectomy in 1. Aortic resection was limited to the adventitia in 2 cases, extended to the media in 3, and extended to the intima in 1. An endograft-related complication, external iliac artery intimal damage requiring vessel repair, was observed in one case. No complications associated with aortic resection were observed. Two postoperative complications of atrial fibrillation and chylothorax developed. There were no surgery-related deaths. During follow-up, no late endograft-related complications such as migration or endoleaks occurred. CONCLUSIONS: Early and mid-term outcomes of stent graft-related complications are acceptable. Simultaneous thoracic aortic endografting and combined resection of the aortic wall and thoracic malignancies are feasible in one stage on the same day.

Trachea Engineering Using a Centrifugation Method and Mouse-Induced Pluripotent Stem Cells.

The outcomes of tracheal transplantation for the treatment of airway stenosis are unsatisfactory. We investigated the feasibility of regeneration of the trachea using a rat decellularized tracheal scaffold and mouse-induced pluripotent stem (iPS) cells for in vivo transplantation. The rat trachea was first decellularized using a detergent/enzymatic treatment method. We successfully established a centrifugation method that can transplant cells onto the luminal surface of the decellularized rat tracheal scaffold circumferentially. Two types of mouse iPS cells were differentiated into definitive endoderm cells and transplanted onto the luminal surface of the decellularized tracheal matrix scaffold using this centrifugation method. For in vivo study, normal rat tracheas, no-cell rat tracheal scaffolds, or rat tracheal scaffolds recellularized with rat tracheal epithelial cells (EGV-4T) were orthotopically transplanted on F344 rats, and rat tracheal scaffolds recellularized with mouse iPS cells were transplanted on F344/NJc1-rnu/rnu rats. Rats transplanted with no-cell scaffolds or scaffolds recellularized with EGV-4T survived for 1 month, although airway stenosis was observed. One of the F344/NJc1-rnu/rnu rats transplanted with rat trachea regenerated using mouse iPS cells survived over 5 weeks. Histological analysis indicated the cause of death was airway stenosis due to colonic cellular proliferation of undifferentiated iPS cells. Re-epithelialization with numerous ciliated epithelial cells was observed in one of the rats transplanted with trachea bioengineered using iPS cells. In this study, we present a simple and efficient tracheal tissue engineering model using a centrifugation method in a small-animal model. Tissue-engineered trachea using decellularized tracheal scaffolds and iPS cells is potentially applicable for tracheal transplantation.

Survival after repeated surgery for lung cancer with idiopathic pulmonary fibrosis: a retrospective study.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) have a high risk of developing lung cancer, but few studies have investigated the long-term outcomes of repeated surgery in such patients. The purpose of this study was to evaluate the surgical outcomes of repeated lung cancer surgery in patients with IPF. METHODS: From January 2001 to December 2015, 108 lung cancer patients with IPF underwent pulmonary resection at two institutions; 13 of these patients underwent repeated surgery for lung cancer, and their data were reviewed. RESULTS: The initial procedures of the 13 patients were lobectomy in 8, segmentectomy in 2, and wedge resection in 3. The subsequent procedures were wedge resection in 10 and segmentectomy in 3. The clinical stage of the second tumor was stage IA in 12 and stage IB in 1. Postoperatively, 3 patients (23.1%) developed acute exacerbation (AE) of IPF and died. The rate of decrease in percent vital capacity was significantly higher in patients with AE than in those without AE (p = 0.011). The 3-year overall survival rate was 34.6%. The causes of death were cancer-related in 7, AE of IPF in 3, and metachronous lung cancer in 1. CONCLUSIONS: Despite limited resection, a high incidence of AE was identified. The early and long-term outcomes of repeated surgery in lung cancer patients with IPF were poor because of the high risk of AE of IPF and lung cancer recurrence. Long-term intensive surveillance will be required to determine whether surgical intervention is justified in patients with multiple primary lung cancers and IPF.

Characteristics and timing of recurrence during postoperative surveillance after curative resection for lung adenocarcinoma.

PURPOSE: To establish the most effective methods of postoperative surveillance to detect early recurrence of lung adenocarcinoma. METHODS: The subjects of this retrospective study were 485 patients with p-stage I-III lung adenocarcinoma, who underwent postoperative surveillance. We examined the sites and detection modes of recurrence and calculated the recurrence-free probabilities. Patients with stage I disease were divided into low- and high-risk recurrence groups using a risk score calculated by assigning points proportional to risk factor regression coefficients. RESULTS: Of the 112 patients with recurrence, 86 had intrathoracic recurrence. Routine computed tomography (CT) revealed recurrence in 60 patients. The recurrence-free probability curves showed that 95% of recurrences were identified within the first 4 years after resection in patients with stage II/III disease. In patients with stage I disease, the predictors of recurrence included male sex, positive pleural lavage cytology, moderate-to-poor differentiation, and visceral pleural invasion. Postoperative recurrences were detected throughout the follow-up period in the high-risk group. CONCLUSIONS: Routine chest CT plays an important role in the postoperative surveillance of lung adenocarcinoma. We recommend intensive follow-up during the early post-resection period for patients with advanced stage disease and long-term follow-up for high-risk patients with stage I disease.

[Fatal Respiratory Failure Developed during Chemotherapy for Diffuse Large B Cell Lymphoma that Occurred Late after Lung Transplantation].

We report here a case of fatal respiratory failure developed during chemotherapy for diffuse large B cell lymphoma that occurred late after lung transplantation. 25-year- old man underwent lung transplantation from brain death donor for respiratory failure due to interstitial pneumonia at the age of 16 years old. Two years after transplantation, his respiratory function decreased gradually. Chronic lung allograft dysfunction including bronchiolitis obliterans( BOS) and restrictive allograft syndrome was suspected and immunosuppression was enhanced. Nine years after transplantation, he had abdominal pain and physical examination suggested intestinal obstruction. Small intestine endoscopy revealed an ulcer at jejunum and diffuse large B cell lymphoma( DLBCL) was finally diagnosed by biopsy. Chemotherapy was planned for lymphoma, but respiratory failure progressed just before chemotherapy. Chest computed tomography showed infiltrative shadow in right lung, so we suspected presence of lymphoma and chemotherapy was carried out. After chemotherapy, abnormal shadow in the right lung disappeared. Although chemotherapy was effective, respiratory failure progressed and he died. Pathological examination from autopsy showed mixture of BOS, diffuse alveolar damage, invasion of aspergillus and acute fibrinoid organizing pneumonia but no residual DLBCL was found in the lung.

Resection of a large ectopic parathyroid adenoma: A case report.

INTRODUCTION: Parathyroid adenomas are the most common cause of primary hyperparathyroidism. However, cases of parathyroid adenomas greater than 4cm with osteitis fibrosa cystica are extremely rare. Herein, we report a case of resection of a large ectopic mediastinal parathyroid adenoma. CASE PRESENTATIONS: A 46-year-old female with chief complaints of bone pain and gait disturbance was referred to our hospital. Physical examination revealed many mobile teeth in her oral cavity, distortion of the vertebral body, and bowlegs. Laboratory tests showed hypercalcemia, hypophosphatemia, and elevated serum levels of intact parathyroid hormone. Chest CT revealed a 42-mm well-defined, enhancing mass in front of the left-sided tracheal bifurcation. Her findings were diagnosed as primary hyperparathyroidism due to an ectopic mediastinal parathyroid tumor. We performed a median sternotomy and resected the tumor. The tumor was a solid, yellowish-brown mass measuring 42×42 mm. Pathologically, the tumor consisted mainly of chief cells with some oxyphil cells; there were no necrotic areas or nuclear atypia, and few mitotic figures. We diagnosed the tumor as an ectopic mediastinal parathyroid adenoma. Eight months after the resection, her serum calcium, phosphorus, and intact PTH levels were normal. DISCUSSION AND CONCLUSIONS: Parathyroid adenomas and parathyroid carcinomas have disparate natural histories, but they can be difficult to differentiate on the basis of preoperative clinical characteristics. We believe that long-term follow-up of these cases is required because there have been few reports on the postoperative natural history of large parathyroid adenomas.

Lobectomy Versus Segmentectomy in Radiologically Pure Solid Small-Sized Non-Small Cell Lung Cancer.

BACKGROUND: The indication for limited resection of radiologically pure solid non-small cell lung cancer (NSCLC) is controversial owing to its invasive pathologic characteristics. This study was performed to compare the outcomes after lobectomy and segmentectomy in these NSCLC patients. METHODS: We retrospectively reviewed 251 patients with radiologically pure solid cT1a N0 M0 NSCLC who underwent lobectomy or segmentectomy, and the preoperative characteristics of the patients treated with the two operative techniques were matched using propensity score methods. Overall survival (OS) and disease-free survival (DFS) curves were compared using the log rank test, and differences in survival were also evaluated by the McNemar test. The preoperative factors and surgical procedure were analyzed with the multivariate Cox proportional hazards regression model to identify independent predictors of poor OS and DFS. RESULTS: In the propensity score matched lobectomy and segmentectomy groups (87 patients per group), the 5-year and 10-year OS rates were 85% versus 84% and 66% versus 63%, respectively; and the 5-year and 10-year DFS rates were 80% versus 77% and 64% versus 58%, respectively. There were no significant differences between the two groups in OS or DFS by the log rank test, and also no significant differences in 3-year, 5-year, or 7-year OS or DFS by the McNemar test. Although age, smoking status, pulmonary function, and carcinoembryonic antigen were identified as significant predictors of both OS and DFS, the surgical procedure was not identified. CONCLUSIONS: Similar oncologic outcomes after lobectomy and segmentectomy were indicated among patients with radiologically pure solid small-sized NSCLC.

A Case of Ectopic ACTH-Producing Pulmonary Carcinoid Arising in an Extralobar Pulmonary Sequestration.

Ectopic adrenocorticotrophic hormone (ACTH)-producing bronchopulmonary carcinoid arising in a bronchopulmonary sequestration is extremely rare. The case of a 67-year-old woman with a 1.7-cm nodule in the mediastinal side of the left lower lobe is presented. At 52 years of age, she was diagnosed as having ACTH-dependent Cushing's syndrome (CS). However, no ectopic source of ACTH-secretion was detected. Seven years later, she underwent a bilateral adrenalectomy because of aggravation of her health condition. This time, tumor excision was performed by thoracoscopic surgery. The tumor adhered sparsely to the mediastinal pleura and the left lower lobe and was bluntly separated from these tissues. Pathologically, the tumor was a typical carcinoid arising in an extralobar pulmonary sequestration. Immunohistochemical staining confirmed the secretion of ACTH by bronchopulmonary carcinoid tumor cells. After surgery, the serum ACTH level was almost normalized, and the dexamethasone (1 mg) suppression test showed significant suppression of ACTH.

[Surgical treatment for 2nd primary lung cancer originated close to the initial surgical margin for bronchioloalveolar carcinoma (BAC); report of a case].

77-year-old man was treated by wedge resection for bronchioloalveolar carcinoma (BAC) of right upper lobe 6 years before. Follow up computed tomography (CT) performed 5 years later revealed partial thickening of the resected line of the initial surgery which was diagnosed as adenocarcinoma with bronchoscopic cytology. Thoracoscopic right upper lobectomy and nodal dissection was performed. Histological diagnosis was papillary adenocarcinoma, which was thought to be a 2nd primary lung cancer.

Factors influencing long-term survival and surgical indications for pulmonary metastasectomy for metastases from colorectal cancer.

BACKGROUND: This study examined the prognostic factors and surgical indications for pulmonary metastasectomy for metastases from colorectal cancer. METHODS: We retrospectively reviewed 142 patients treated between 1985 and 2005 who had undergone complete resections of pulmonary metastases from colorectal cancer. RESULTS: Overall 5-year and 10-year survival rates were 42.4% and 32.0%, respectively. The 5-year survival rate for patients with a solitary metastasis was 55.1%, compared with 24.0% for patients with multiple metastases (P= 0.013). The 5-year survival rate for patients with a disease-free interval (DFI) ≥ 1000 days was 55.1%, compared with 31.6% for patients with a DFI < 1000 days (P= 0.008). No significant differences in survival rate according to the location of the primary lesion, maximum tumor size, preoperative serum carcinoembryonic antigen level, or surgical procedure were observed. Prior resection for liver metastases and repeated resection for recurrent pulmonary metastases did not influence the survival rate. A multivariate analysis demonstrated that the number of metastases was an independent, significant prognostic factor for survival. The survival rate of patients with three or more metastases was significantly lower than that of patients with two or fewer metastases. CONCLUSIONS: The number of metastases is an independent prognostic factor after pulmonary metastasectomy for metastases from colorectal cancer. Patients with a solitary pulmonary metastasis benefit the most from pulmonary metastasectomy. The pulmonary resection of three or more metastases is associated with a reduced survival rate. Pulmonary metastasectomy is recommended even for patients with a prior hepatic metastasectomy or patients with recurrent pulmonary metastases.