Evaluation of flow dynamics in distal stent graft-induced new entry using 4D flow MRI.

Distal stent graft-induced new entry may occur after stent grafting for aortic dissection. Four-dimensional magnetic resonance imaging is useful for predicting outcomes, showing accelerated flow and increased wall shear stress, indicating further false lumen expansion.

Thoracic endovascular aortic repair for acute type B aortic dissection complicated by total occlusion of the abdominal aorta.

A 72-year-old man presenting with lower body malperfusion and complete paralysis was transferred for emergency treatment of a complicated acute type B aortic dissection. Enhanced computed tomography showed occlusion of the true lumen inside the abdominal aorta due to compression of the false lumen, accompanied by a Crawford extension type IV thoraco-abdominal aortic aneurysm. The primary entry tear was located at the level of the tenth thoracic vertebra above the aneurysm. Emergency thoracic endovascular aortic repair was performed to cover the entry tear and to regain perfusion of the lower body. Efforts to perform retrograde insertion of a guidewire from the femoral arteries to pass the occluded abdominal aorta were unsuccessful. A through-and-through guidewire technique between the left brachial artery and the right femoral artery was performed to deliver a Zenith TX-2 stent graft from the right femoral artery. After closure of the primary entry tear, complete recovery from the occlusion of the abdominal aorta was obtained 6 h after the onset. His paralysis recovered completely, and the postoperative course was uneventful without reperfusion injury.

Identification of Clonality through Genomic Profile Analysis in Multiple Lung Cancers.

In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. In this study, we investigated the differences between clinical/histopathological and genomic diagnoses to determine whether they are primary or metastatic. 37 patients with multiple lung cancers were enrolled in this study. Tumor cells were selected from tissue samples using laser capture microdissection. DNA was extracted from those cells and subjected to targeted deep sequencing. In multicentric primary lung cancers, the driver mutation profile was mutually exclusive among the individual tumors, while it was consistent between metastasized tumors and the primary lesion. In 11 patients (29.7%), discrepancies were observed between genomic and clinical/histopathological diagnoses. For the lymph node metastatic lesions, the mutation profile was consistent with only one of the two primary lesions. In three of five cases with lymph node metastases, the lymph node metastatic route detected by genomic diagnosis differed from the clinical and/or pathological diagnoses. In conclusion, in patients with multiple primary lung cancers, cancer-specific mutations can serve as clonal markers, affording a more accurate understanding of the pathology of multiple lung cancers and their lymphatic metastases and thus improving both the treatment selection and outcome.

Clinical Implications of Noncoding Indels in the Surfactant-Encoding Genes in Lung Cancer.

Lung cancer arises from the accumulation of genetic mutations, usually in exons. A recent study identified indel mutations in the noncoding region of surfactant-encoding genes in lung adenocarcinoma cases. In this study, we recruited 94 patients with 113 lung cancers (88 adenocarcinomas, 16 squamous cell carcinomas, and nine other histologies) who had undergone surgery in our department. A cancer panel was designed in-house for analyzing the noncoding regions, and targeted sequencing was performed. Indels in the noncoding region of surfactant-encoding genes were identified in 29/113 (25.7%) cases and represent the precise cell of origin for the lung cancer, irrespective of histological type and/or disease stage. In clinical practice, these indels may be used as clonal markers in patients with multiple cancers and to determine the origin of cancer of unknown primary site.

Genomic Characteristics of Invasive Mucinous Adenocarcinomas of the Lung and Potential Therapeutic Targets of B7-H3.

Pulmonary invasive mucinous adenocarcinoma (IMA) is considered a variant of lung adenocarcinomas based on the current World Health Organization classification of lung tumors. However, the molecular mechanism driving IMA development and progression is not well understood. Thus, we surveyed the genomic characteristics of IMA in association with immune-checkpoint expression to investigate new potential therapeutic strategies. Tumor cells were collected from surgical specimens of primary IMA, and sequenced to survey 53 genes associated with lung cancer. The mutational profiles thus obtained were compared in silico to conventional adenocarcinomas and other histologic carcinomas, thereby establishing the genomic clustering of lung cancers. Immunostaining was also performed to compare expression of programmed death ligand 1 (PD-L1) and B7-H3 in IMA and conventional adenocarcinomas. Mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS) were detected in 75% of IMAs, but in only 11.6% of conventional adenocarcinomas. On the other hand, the frequency of mutations in epidermal growth factor receptor (EGFR) and tumor protein p53 (TP53) genes was 5% and 10%, respectively, in the former, but 48.8% and 34.9%, respectively, in the latter. Clustering of all 78 lung cancers indicated that IMA is distinct from conventional adenocarcinoma or squamous cell carcinoma. Strikingly, expression of PD-L1 in ≥1% of cells was observed in only 6.1% of IMAs, but in 59.7% of conventional adenocarcinomas. Finally, 42.4% and 19.4% of IMAs and conventional adenocarcinomas, respectively, tested positive for B7-H3. Although currently classified as a variant of lung adenocarcinoma, it is also reasonable to consider IMA as fundamentally distinct, based on mutation profiles and genetic clustering as well as immune-checkpoint status. The immunohistochemistry data suggest that B7-H3 may be a new and promising therapeutic target for immune checkpoint therapy.

Lymph node cancer of the mediastinum with a putative necrotic primary lesion in the lung: a case report.

BACKGROUND: Although mediastinal lymph node cancer is presumed to originate in the lung, the primary site is usually unidentified, so the pathological course remains unclear. We recently encountered a case of mediastinal lymph node cancer having a putative primary lesion remaining in the lung as a necrotic focus. CASE PRESENTATION: The patient was a 56-year-old man who visited our department because computed tomography screening had revealed a nodular shadow in the lingular segment. However, on positron emission tomography, fluorine-18 deoxyglucose accumulation was detected in a subcarinal lymph node and not in the nodule in the lingular segment. Biopsy of the lung tumor and the lymph node was performed via minimal thoracotomy. Intraoperative pathologic examination showed necrosis alone and no malignant findings in the lung tumor. By contrast, carcinoma was detected in the lymph node. Additional subcarinal lymph node dissection was performed. Results of postoperative histopathologic examination indicated poorly differentiated adenocarcinoma of the subcarinal lymph node. Meanwhile, the nodule in the lingular segment was speculated to be a spontaneously resolved primary focus of lung cancer. CONCLUSIONS: In this case, the primary lung cancer focus resolved spontaneously after lymph node metastasis, explaining the pathogenesis underlying mediastinal lymph node cancer of unknown primary site. For similar cases of malignancy, aggressive treatment, including surgery, is effective.

New therapeutic targets for pulmonary sarcomatoid carcinomas based on their genomic and phylogenetic profiles.

OBJECTIVES: Pulmonary sarcomatoid carcinomas are rare and generally aggressive tumors composed of carcinomatous and sarcomatous components; however, the evolution of sarcomatoid cancer has not been elucidated. Here, we aimed to evaluate the mutational profiles and phylogeny of sarcomatoid carcinomas using next generation sequencing and in-silico analysis to facilitate the development of novel therapies. METHODS: Four patients who underwent surgery for sarcomatoid cancer were enrolled. Cancer cells were collected from carcinomatous and sarcomatous components in each tumor by laser capture microdissection. Next-generation sequencing was performed in each component, and the mutation profiles were compared. For further inference of phylogenies, phylogenetic and PyClone analyses were performed. Mismatch repair disturbance and programmed death ligand-1 (PD-L1) expression were also evaluated. RESULTS: Comparative genetic analysis of different histological areas revealed that the separate components shared several common mutations, which showed relatively high cellular prevalence in the PyClone statistical inference. Phylogenetic analysis showed that the sarcomatous component had ramified from the carcinomatous component in the early phase of the evolution process and accumulated a number of mutations that were different from those of the carcinomatous component. Moreover, microsatellite instability was detected in a case of sarcomatoid cancer and PD-L1 was strongly positive (≥ 50%) in all sarcomatoid cancers. CONCLUSIONS: Our data suggest that sarcomatoid carcinoma evolves from a common ancestral clone, and its phylogenetic features may reflect high-grade malignancy in pulmonary sarcomatoid carcinoma. High tumor mutation burden and strong PD-L1 staining may provide a rationale for the use of targeted immunotherapies in pulmonary sarcomatoid carcinomas.

Detection of tumor-derived DNA dispersed in the airway improves the diagnostic accuracy of bronchoscopy for lung cancer.

The diagnostic accuracy of bronchoscopy for detecting lung cancer, especially peripheral lung cancer with lesions outside the endoscopically visible range, remains unsatisfactory. The aim of this study was to perform next-generation sequencing on bronchoscopic specimens to determine whether this improves the accuracy of bronchoscopy for diagnosing lung cancer and to identify factors influencing sensitivity. The bronchoscopic sensitivity for diagnosing lung cancer was initially evaluated in 191 patients who underwent lobectomy after bronchoscopy at our hospital. Sputum, bronchial wash fluid, and resected lung cancer specimens were subsequently collected from 18 patients with peripheral small cell lung cancer for genomic analysis. DNA was extracted from formalin-fixed, paraffin-embedded surgical tissue specimens and the supernatant and cell fractions of sputum and bronchial wash fluid. Deep sequencing was performed using a lung cancer panel covering all exons of 53 lung cancer-related genes. The bronchoscopic sensitivity for diagnosing lung cancer at our hospital was 60.7%. Multivariate analysis revealed that this was influenced by tumor size and location, but not histological type or lymph node metastasis. The sensitivity was the highest for biopsy followed by curettage and bronchial wash specimens. DNA mutations homologous to those identified in the primary lesions were detected in the bronchial wash fluid of 10 patients (55.6%), while only 2 patients (11.1%) were diagnosed with lung cancer based on conventional cytological examinations. In conclusion, the addition of genomic analysis to routine pathological examinations improves the diagnostic accuracy of bronchoscopy.

Distribution of circulating tumor DNA in lung cancer: analysis of the primary lung and bone marrow along with the pulmonary venous and peripheral blood.

Circulating tumor DNA (ctDNA), extracted from plasma, is a non-invasive surrogate biomarker. However, the distribution of ctDNA in the body still remains to be elucidated. In this study, resected lung tumors, with simultaneous blood and bone marrow samples, were analyzed to elucidate the distribution of ctDNA. Rib bone marrow, pulmonary venous blood (Pul.V) and peripheral blood (Peri.B) were obtained from 30 patients. The liquid samples were divided into cell pellets and supernatant by centrifugation; a total of 212 DNA samples were subjected to massively parallel sequencing. ctDNA was detected in 5 patients. Given that the frequency of mutations in the primary tumor was considered to be 100%, those in the other specimens were as follows; Pul.V plasma 20%, Peri.B plasma 11%, and the other samples 0%. Furthermore, ctDNA reflected the predominant mutations in the primary lesion. Clinically, the presence of ctDNA was associated with significantly poorer survival. These results suggest ctDNA "spill over" into an immediate outflow tract (Pul.V), and from there is disseminated to the entire body. Thus, it can be inferred that ctDNA reflects the cancer progression and could function as a prognostic marker.

Elucidation of radiation-resistant clones by a serial study of intratumor heterogeneity before and after stereotactic radiotherapy in lung cancer.

Stereotactic radiotherapy (SRT) for inoperable stage I non-small cell lung cancer has shown promising results and is now an alternative therapy for this disease. Several reports have detailed changes in mutation profiles after treatment with chemotherapy; however, such changes after SRT for lung cancer have not been reported. A patient who received SRT for lung cancer developed local recurrence 9 months after treatment and underwent surgery in our department. Using bronchoscopically biopsied and surgically resected specimens, we performed targeted sequencing of 53 lung cancer-related genes and compared the tumor mutation profiles before and after SRT. Identical mutations were detected from tumor specimens collected before and after SRT, and the specimens were confirmed to be clonal. However, the number of mutations decreased after SRT, suggesting that it induced mutation selection. Analyses of the statistical inference of clonal population structure showed that this evolving heterogeneous genomic landscape may be caused by heterogeneous responsiveness to SRT.

Combined analgesic treatment of epidural and paravertebral block after thoracic surgery.

In pulmonary surgical practice, appropriate pain management after thoracotomy is essential for patient recovery and the prevention of complications. Although epidural analgesia (EPI) has been established for chest surgery, it has some limitations and contraindications. Recently, paravertebral block (PVB) was reported as a good alternative method with fewer side effects. Despite the significant effects of these two treatments, postoperative pain remains among the greatest patient burdens. In our institution, we apply a combination of epidural and PVBs after thoracic surgery to reduce pain more effectively. The purpose of this study was to demonstrate the safety and feasibility of our method. This study included patients who underwent thoracic surgery and analgesic treatment in our institution between November 2014 and December 2016. Per our method of PVB induction, the parietal pleura was peeled off with a metal suction tube and an extrapleural pocket was created. An epidural catheter was inserted into this pocket and used to inject local anesthetics continuously after surgery. The catheters for analgesia were removed on the 4th postoperative day. In total, 368 patients received the combined epidural and PVBs. No severe complication was observed. The rate of rescue medication use in this study was lower than that in the historical control before adoption of this combination method; the incidence of pneumonia and length of hospital stay after surgery were not significantly different in this study from those in the historical control. In conclusion, our study demonstrated the safety and feasibility of the combination method of EPI and PVB. Acute pain after thoracic surgery may be adequately controlled using double analgesic regimens, including EPI and PVBs, suggesting an alternative to conventional modalities of EPI alone or PVB alone.

Surgical treatment for mediastinal abscess induced by endobronchial ultrasound-guided transbronchial needle aspiration: a case report and literature review.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a useful and less invasive procedure for the definitive diagnosis of mediastinal and hilar lymph nodes. However, infectious complications can occur after EBUS-TBNA, although they are extremely rare. CASE PRESENTATION: A 66-year-old man with necrotic and swollen lower paratracheal lymph nodes underwent EBUS-TBNA. A mediastinal abscess developed 9 days post-procedure. Surgical drainage and debridement of the abscess were performed along with lymph node biopsy followed by daily washing of the thoracic cavity. Surgical treatment was effective, leading to remission of the abscess. Biopsy revealed that the tumor was squamous cell carcinoma with no radiologically detected cancer elsewhere in the body. Mediastinal lung cancer was thus confirmed. Subsequent chemoradiotherapy led to the remission of the tumor. CONCLUSIONS: Mediastinitis after EBUS-TBNA is rare but should be considered, particularly if the target lymph nodes are necrotic. Mediastinitis can lead to serious and rapid deterioration of the patient's condition, for which surgical intervention is the treatment of choice.

Debulking surgery for venous hemangioma arising from the epicardium: report of a case.

BACKGROUND: Cardiac hemangiomas are rare benign vascular tumors that can occur in any cardiac layer: endocardium, myocardium, or epicardium. Histologically, cardiac hemangiomas may be classified as capillary, cavernous, or arteriovenous; venous hemangiomas are extremely rare. CASE PRESENTATION: A 46-year-old man reported experiencing precordial discomfort. Computed tomography revealed a massive tumor adjacent to the right ventricle. The right coronary artery was found to be located at the center of the tumor. Cardiovascular angiography showed that the artery was completely encased by the tumor without any obstruction and that the right ventricular lumen was compressed by the tumor. Surgical debulking of the tumor was performed under cardiopulmonary bypass, and the frozen section led to a diagnosis of benign hemangioma. The tumor was debulked as much as possible until the right coronary artery appeared. For decompression of the heart, the pericardium was left open to the thoracic cavity and unsutured. Histopathologic examination revealed a diagnosis of epicardial venous hemangioma. CONCLUSIONS: Cardiac hemangioma should be included in the differential diagnosis of mediastinal tumor in reference to the location and flow of the coronary artery. Surgical resection, or at least tumor debulking, is required to confirm the diagnosis and prevent further complications and has a favorable clinical outcome.

Mutational analysis of multiple lung cancers: Discrimination between primary and metastatic lung cancers by genomic profile.

In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. Treatment selection varies depending on such features, and this discrimination is critically important in predicting prognosis. The present study was undertaken to determine the efficacy and validity of mutation analysis as a means of determining whether multiple lung cancers are primary or metastatic in nature. The study involved 12 patients who underwent surgery in our department for multiple lung cancers between July 2014 and March 2016. Tumor cells were collected from formalin-fixed paraffin-embedded tissues of the primary lesions by using laser capture microdissection, and targeted sequencing of 53 lung cancer-related genes was performed. In surgically treated patients with multiple lung cancers, the driver mutation profile differed among the individual tumors. Meanwhile, in a case of a solitary lung tumor that appeared after surgery for double primary lung cancers, gene mutation analysis using a bronchoscopic biopsy sample revealed a gene mutation profile consistent with the surgically resected specimen, thus demonstrating that the tumor in this case was metastatic. In cases of multiple lung cancers, the comparison of driver mutation profiles clarifies the clonal origin of the tumors and enables discrimination between primary and metastatic tumors.

A novel technique for chest drain removal using a two layer method with triclosan-coated sutures.

In thoracic surgery, a thoracic drain is always inserted after the surgical procedure. Repair of the wound after removal of the thoracic tube is performed postoperatively, but no universally standard methods currently exists for this tube removal. Here we report a technique using triclosan-coated sutures that is used in thoracic surgery in our hospital. There are several advantages of this technique. First, there is no need for stitches removal on follow-up. Second, it prevents the leakage of pleural exudate because of the tight two-layer sutures. In addition, it was observed to be superior in terms of both wound healing and cosmetic aspects, due to the layer-to-layer sutures. The use of triclosan-coated sutures helps prevent infection and empyema is quite unlikely to occur as the result of the tight ligating of the muscular layer using these sutures. We applied this method in 168 patients over a period of 24 months. There were no complications on removal of the chest tube such as infection, fluid leakage or opening of the surgical wound.

Report of a case with a spontaneous mesenteric hematoma that ruptured into the small intestine.

INTRODUCTION: A spontaneous mesenteric hematoma is a rare condition. Furthermore, it is extremely rare that the mesenteric hematoma caused gastrointestinal bleeding with an unknown etiology. We experienced a case with a spontaneous mesenteric hematoma that ruptured into the jejunum. PRESENTATION OF CASE: A 75-year-old man was referred to our hospital because of anal bleeding and anemia. Abdominal computed tomography (CT) showed a low density mass measuring 3.0cm in diameter, including an enhanced spot. This finding suggested that a pseudo-aneurysm or mesenteric hematoma caused active bleeding into the jejunum. He underwent emergent laparotomy and partial resection of the jejunum and the mesentery including the tumor. A histological examination of the jejunum indicated no pathogenic findings causing active bleeding. And there were no findings suggesting the mesenteric aneurysm had developed. The patient had no history related to the development of a mesenteric hematoma, such as trauma, labor, surgery, or anticoagulant treatment. Therefore, we finally diagnosed that a spontaneous mesenteric hematoma had ruptured into the jejunum. DISCUSSION AND CONCLUSION: We reported extremely rare condition that the mesenteric hematoma was developed and ruptured into the jejunum without definitive etiology.