[A Case of Recurrent Lung Adenocarcinoma with Right Aortic Arch Treated with Pembrolizumab].

Only a few cases of primary lung cancer associated with the right aortic arch have been reported. A treatment report of recurrent lung cancer with the right aortic arch is rare. A woman in her late 70s was diagnosed with lung cancer associated with the right aortic arch. A 3.4-cm tumor was detected in the right middle lobe on CT performed before a knee joint surgery. The tumor was diagnosed as lung adenocarcinoma and categorized as cT2aN0M0 with cStage ⅠB. Subsequently, a right middle lobectomy was performed. Histopathological study revealed pT1cN1M0 with pStage ⅡB tumor. Molecular analysis revealed 85% expression of programmed death-ligand 1(PD-L1). One year after surgery, mediastinal lymph nodes recurred with multiple lung metastases. The number of metastatic lymph nodes reduced after pembrolizumab was administered, followed by the disappearance of lung metastasis. The outcome was recorded as a partial response. She has been alive 2 years after surgery.

[A Case of Recurrent Thymoma Treated with Pembrolizumab as the Fifth-Line Chemotherapy].

The option of chemotherapy for recurrent thymoma is limited. Postoperative adjuvant therapy has yet to be established. A 71-year-old male underwent extended thymectomy for thymoma with Masaoka stage Ⅲ, and subsequently, radiation was performed as adjuvant therapy in 2012. Since recurrence was detected in 2014, multidisciplinary treatment was performed for 4 years. An increase of intrathoracic dissemination was detected in 2018. Tumor tissue samples by re-biopsy showed 70% expression of programmed death-ligand 1(PD-L1). Pembrolizumab was administered as fifth-line chemotherapy every 4 weeks at a dosage of 200 mg. After 3 courses, the lesions had remarkably decreased. This suggests that pembrolizumab for thymoma with high PD-L1 expression is efficacious.

[Nivolumab Therapy for Synchronous Double Primary Lung and Gastric Cancers].

A 70-year-old man who was diagnosed with a cStage ⅣA lung adenocarcinoma was in a stable condition for a long time after the first chemotherapy with gefitinib. However, 2 years 4 months later, the lung cancer progressed, and he was diagnosed with Stage Ⅲ gastric cancer. Since the administration of afatinib as the second-line chemotherapy was ineffective, nivolumab was administered as the third-line chemotherapy. The lung cancer showed a partial response to nivolumab treatment, but the gastric cancer remained unresponsive. We report a rare case of immune checkpoint inhibitor administration for synchronous double primary cancers.

'Lung age' predicts post-operative complications and survival in lung cancer patients.

BACKGROUND AND OBJECTIVE: The Japanese Respiratory Society recently proposed 'lung age' as an easily understood concept of respiratory function. In this study, we evaluated whether 'lung age' could be a useful predictor of post-operative respiratory complications and survival patients with lung cancer treated surgically. METHODS: The study recruited 308 patients who underwent surgery for primary non-small-cell lung cancer. All patients had preoperative pulmonary function testing. 'Lung age' was determined using the methods advocated by the Japanese Respiratory Society. Based on the difference between 'real age' (R) and 'lung age' (L), patients were classified into five groups: group A: R-L > 15 (n = 37), B: 5 < R-L R-L (n = 94). Clinicopathological factors, post-operative respiratory complications and survival were compared between the groups. RESULTS: Gender, smoking status and index, histology, operative approach and FEV(1) were significantly associated with the group classification. The incidence of complications was significantly higher in group E compared with other groups (P = 0.003). Multivariate analysis showed that the group classification by 'lung age' was an independent predictor of post-operative respiratory complications (P = 0.02). Overall survival differed significantly between the groups (P = 0.03). CONCLUSIONS: 'Lung age' could be useful for the prediction of post-operative respiratory complications and survival in patients with lung cancer treated surgically.

Spontaneous regression of lung adenocarcinoma: Report of a case.

This report presents a rare case of lung adenocarcinoma accompanied by partial spontaneous regression (SR). A 69-year-old woman with an abnormal shadow on chest X-ray was admitted to the hospital. She was diagnosed to have lung adenocarcinoma with right adrenal metastasis based on a thorough examination. However, a month after the diagnosis, the primary and metastatic lesions markedly shrank on the following computed tomography scan and (18)F-fluorodeoxyglucose positron emission tomograph. This was thought to be a partial SR of the cancer, and she was treated with a surgical procedure. She has since remained free of disease for 14 months after the surgery.

['Lung age' predicts post-operative complications and survival in lung cancer patients].

The Japanese Respiratory Society (JRS) recently proposed 'lung age' as an easily understood concept of respiratory function. In this study, we evaluated whether 'lung age' could be a useful predictor of post-operative respiratory complications and survival patients with lung cancer treated surgically. The study recruited 308 patients who underwent surgery for primary non-small cell lung cancer. All patients had pre-operative pulmonary function testing. 'Lung age' was determined using the methods advocated by the JRS. Based on the difference between real age' (R) and 'lung age' (L), patients were classified into five groups: group A: R-L > 15 (n = 37), B: 5 < R-L < or = 15 (n = 50), C: -5 < or = R-L < or = 5 (n = 73), D: -15 < or = R-L < -5 (n = 54), E: -15 > R-L (n = 94). Clinicopathological factors, post-operative respiratory complications and survival were compared between the groups. Gender, smoking status and index, histology, operative approach and FEV1 were significantly associated with the group classification. The incidence of complications was significantly higher in group E compared with other groups (p < 0.01). Multivariate analysis showed that the group classification by 'lung age' was an independent predictor of postoperative respiratory complications (p = 0.02). Overall survival differed significantly between the groups (p = 0.03). 'Lung age' could be useful for the prediction of post-operative respiratory complications and survival in patients with lung cancer treated surgically.

Immunohistochemical expression of geminin in colorectal cancer: Implication of prognostic significance.

DNA should be duplicated precisely once per cell cycle to maintain genome integrity. After DNA replication, geminin binding to Cdt1 inhibits uploading of the minichromosome maintenance (MCM) complex as DNA helicase onto chromatin and prevents DNA re-replication in the same cell cycle. Expression of geminin indicates poor prognosis in some malignancies, such as breast and renal cell carcinoma. We evaluated the expression of geminin to clarify its pathobiological and prognostic significance in colorectal cancer, compared with expression of MCM7 and Ki-67. We performed Western blot analyses of 5 human colorectal cancer cell lines and immunohistochemistry on 191 surgically removed specimens of Dukes' B and C stage colorectal cancer. Double-labeling immunofluorescence was also carried out to identify co-expression of geminin, MCM7 and Ki-67. Geminin proteins were detected in all the 5 cell lines examined. Geminin, MCM7 and Ki-67 were co-expressed and cells that stained only for geminin were not detected. Mean labeling indices (LIs) for geminin, MCM7 and Ki-67 were 26.3, 58.2 and 40.8%, respectively. Patients with high geminin LIs had significantly unfavorable prognosis in stage II and III colorectal cancer (P=0.04). Patients with a tumor with a higher proliferating nature (i.e. high LIs for three markers) showed significantly unfavorable prognosis in multivariate Cox analysis. Our results indicate that assessment of geminin, MCM7 and Ki-67 may be useful for predicting prognosis in patients with colorectal cancer.

Minichromosome maintenance protein 7 in colorectal cancer: implication of prognostic significance.

Minichromosome maintenance (MCM) proteins are essential components for DNA replication, and also prognostic markers for various human tumors. MCM-positive but Ki67-negative cells (e.g. primary oocytes) are thought to be licensed non-proliferating populations, and are significantly correlated with the clinicopathological profiles of some human tumors. In the present study, we evaluated the expression levels of MCM7, MCM2 and Ki67 in colorectal cancer to clarify their pathobiological significance. We carried out Western blot analyses of 5 human colorectal cancer cell lines and performed immunohistochemistry on 202 surgically removed colorectal cancers of Dukes' B and C stages. Double-labeling immunofluorescence was also carried out on the cancer specimens to identify MCM-positive but Ki67-negative tumor cells. MCM proteins were detected in all the 5 cell lines examined. MCM7 and MCM2 were coexpressed in almost the same populations of tumor cells, whereas MCM7-negative but Ki67-positive tumor cells were absent in the double-labeled specimens, except for mitotic cells. The mean positive tumor labeling indexes (LIs) for MCM7, MCM2 and Ki67 were 58.1, 57.1 and 40.6%, respectively. The mean LI for MCM7-positive but Ki67-negative tumor cells was 17.6%, and significantly correlated with the N status (P=0.01), distant metastasis (P=0.01) and UICC stage (P=0.02). The high LI of >58.1% for MCM7 were independent prognostic factors in multivariate Cox regression analysis (relative risk = 2.12; P=0.02). Our results indicate that MCM7 expression is an independent prognostic factor for human colorectal cancer, and MCM7-positive but Ki67-negative tumor cells are correlated with tumor metastases.

CD1a expression in PEComas.

According to the World Health Organization classification, neoplasms with perivascular epithelioid cell differentiation (PEComas) are mesenchymal tumors composed of histologically and immunohistochemically distinctive PEC. Generally, nearly all PEComas have immunoreactivity for both melanocytic (HMB-45 and/or melan A) and smooth muscle (actin (SMA) and/or desmin) markers. Recently the authors reported that benign clear cell sugar tumor of the lung, one of the PEComas, expressed CD1a. Therefore the purpose of the present study was to investigate the relationship between PEComas and CD1a expression. Nineteen PEComas were obtained, which included angiomyolipoma of the kidney or liver, lymphangiomyomatosis of the uterus or lung and clear cell sugar tumor of the lung. Eighteen tumors had alpha-SMA and HMB-45 expression and 16 had melan A expression. In contrast, all 19 tumors had CD1a expression. The present study confirms CD1a expression in many cases of PEComa. These data suggest that CD1a expression can be an additional new marker for PEComas and also supports the distinct and integrated disease entity of PEComas.

Pulmonary arteriovenous fistula with cerebral infarction successfully treated by video-assisted thoracic surgery.

We experienced a case in which a pulmonary arteriovenous fistula was found due to the occurrence of cerebral infarction. The patient was a 65-year-old female who had seen a local doctor for lightheadedness occurring upon rising in the morning. She underwent a cerebral MRI and was diagnosed to have a cerebral infarction. Upon closer examination, a chest radiograph revealed an abnormal shadow and a three-dimensional computed tomography (3D-CT) chest angiography detected a pulmonary arteriovenous fistula 32x30 mm in size with the feeder blood vessel A10 and drainer blood vessel V10 in the left inferior lobe S10, which was considered to be the cause of the cerebral infarction. Video-assisted thoracic surgery (VATS) was conducted for a segmental resection of the basal segment of the left lung. The patient's postoperative progress was good and there was no reoccurrence of the cerebral infarction. The rate of occurrence of cerebral infarction along with pulmonary arteriovenous fistula is considered to be 11.4%; however, cerebral infarction may be an early indicator of pulmonary arteriovenous fistula, and therefore, due attention must be paid.

Primary adenocarcinoma of the trachea resected using percutaneous cardiopulmonary support (PCPS).

We encountered one very rare case of primary adenocarcinoma of the trachea. The patient was a 72-year-old woman who was hospitalized immediately following significant dyspnea and mental confusion. A computed tomography scan of her chest revealed a 14x13x11 mm tumor in the trachea. After establishing artificial respiration, a tracheal tubular resection was immediately performed using percutaneous cardiopulmonary support (PCPS). A postoperative pathological examination led to the patient being diagnosed with primary adenocarcinoma of the trachea, and she was treated with adjuvant chemotherapy. Since then, for approximately 1 year and 6 months we have detected no relapse.

Desmoid tumor requiring differentiation from port-site relapse after surgery for lung cancer.

Thoracoscopic left lower lobectomy with lymph node dissection for lung cancer was performed in a 76-year-old man. The diagnosis was pT2aN2M0 adenocarcinoma. Sixteen months after surgery, CT revealed a pleural tumor measuring 38 mm at the surgical port wound. CT-guided biopsy revealed fibroma. However, the tumor size increased 4 months after biopsy, and surgery was performed. An intraoperative diagnosis revealed benign fibroma. Thoracoscopic tumorectomy was conducted. The pathological diagnosis was desmoid tumor. As the margins of the resected specimen were positive, radiotherapy was performed. During the 16-month follow-up period, there has been no relapse. Pleural desmoid tumors must be differentiated from port-site relapse.

Radiation-induced synovial sarcoma of the lung diagnosed by gene analysis after the surgical resection of chondrosarcoma arising from the scapula.

The patient was a 62-year-old male who underwent wide resection and radiotherapy for right scapular chondrosarcoma 12 years ago. An abnormal shadow was detected in the right upper lung field included in the irradiated field on chest X-ray. Since the nodule tended to enlarge, a malignant lung tumor was suspected, and surgery was performed. On histological examination, spindle cells densely proliferated in a bundle pattern. Vimentin, bcl-2 protein, and CD99 were positive, and CD34, cytokeratin, AE1/AE3, and EMA were partially positive on immunohistochemical staining. The SYT-SSX (synaptotagmin- synovial sarcoma X) fusion gene was detected employing RT-PCR, based on which primary synovial sarcoma of the lung was diagnosed. The findings also matched the diagnostic criteria of radiation-induced sarcoma, suggesting radiation-induced primary synovial sarcoma of the lung. Primary synovial sarcoma of the lung is a rare tumor. It is difficult to diagnose based on cellular findings, and immunohistochemical and genetic investigations are essential. Radiation-induced sarcoma may develop through a long-term course, as seen in this patient, for which long-term follow-up after radiotherapy is important.

A successful case of robotic bronchoplastic lobectomy for lung cancer.

We performed robotic bronchoplastic upper lobectomy for squamous cell carcinoma of the right hilum of the lung. The patient was a 56-year-old male and surgery was performed using 3 robotic arms and 1 assistance. Deeply wide wedge resection and interrupted suture were applied to the bronchus of the upper lobe. The pathological stage was pT1bN1M0, IIA. Chest drain tube was removed on postoperative day 2 and no postoperative respiratory complication occurred. The key for success of this procedure is accustoming to robotic manipulation, especially suturing technique because of the absence of a tactile sense.

Thymic metastasis of breast cancer 22 years after surgery: a case report.

We report a rare case of thymic metastasis of breast cancer. A 68-year-old woman, who had undergone surgery for cancer in her right breast and had been free of recurrence for 22 years, was noted to have an abnormal shadow on a chest X-ray at a regular medical checkup. Further workup, including chest CT, revealed a 22 × 18-mm mass in the anterior mediastinum. Fluorine-18-fluorodeoxyglucose-PET showed increased fluorine-18-fluorodeoxyglucose uptake that was highly suggestive of thymoma. Thoracoscopic thymothymectomy was performed. The tumor had invaded the pericardium, which was also resected. A small nodule was found in the right lung, and it was also resected. The intraoperative frozen-section diagnosis was breast cancer metastasis to the thymus and lung. The pathological diagnosis was luminal A solid tubular carcinoma (strongly estrogen receptor and progesterone receptor positive, HER2 negative) with an MIB-1 index of less than 5%. After surgery, the patient was treated with an aromatase inhibitor. As of August 2013, she has been free of recurrence for more than 36 months. It is extremely rare for breast cancer to metastasize to the thymus more than 20 years after surgery.

Thoracoscopic resection with intraoperative use of methylene blue to localize mediastinal parathyroid adenomas.

We report a case of thoracoscopic resection of mediastinal parathyroid adenomas using methylene blue to localize the tumors during the operation. After methylene blue 4 mg/kg was injected intravenously, we easily identified methylene blue-stained parathyroid glands and successfully resected them with sufficient surgical margins. The use of methylene blue for detection of parathyroid adenoma is a useful technique.

Squamous cell carcinoma of the lung invaded to esophagus: a case report of successful surgical treatment after preoperative transesophageal echographic evaluation.

We describe a successful surgical case of a 78-year-old man with a squamous cell carcinoma of the lung invaded to the esophagus. Chest computed tomography on admission showed a tumor mass shadow in the left lower lobe (S(6)). The tumor was adjacent to the esophagus, which was a strongly suspected lung cancer with esophageal invasion. We performed the transesophageal endoscopic ultrasound (EUS) for a detailed evaluation of the degree of invasion, and we obtained the findings of localized tumor invasion into the muscular coat of the esophagus. The tumor invaded to the esophagus perioperatively, and we could remove all the involved area with enough surgical margin. We believe that the preoperative evaluation using EUS is a useful procedure, if we suspect the lung cancer with esophageal invasion.

First experience of robotic extended thymectomy in Japan for myasthenia gravis with thymoma.

We performed robot (da Vinci)-assisted thoracoscopic extended thymectomy (rThx) for myasthenia gravis with thymoma. The patient was a 66-year-old woman who complained of palpebral heaviness. Robotic operation was performed in the supine position by placing four ports in the right chest wall under 10 mmHg CO(2) insufflation using three arms and one assist port. Compared with conventional video-assisted thoracic surgery (VATS), the bilateral upper horns, fat around the diaphragm, and aortopulmonary window could be resected more easily. The tumor measured 41 mm maximum diameter and was diagnosed as type AB noninvasive thymoma. The operating time was 298 min, console operating time was 203 min, and the amount of bleeding was small. The postoperative course was uneventful with no complications. This is a report of the first Japanese case of rThx for myasthenia gravis. rThx is a promising technique, and further improvement in the procedure is expected.

Thoracoscopic resection of a thoracic duct cyst that developed during follow-up for a thymic cyst.

A 29-year-old man had been diagnosed with an anterior mediastinal cyst 6 years earlier and was undergoing follow-up. At a follow-up visit, a newly developed cystic lesion was found in the middle mediastinum; therefore, the anterior mediastinal cyst and the middle mediastinal cyst were resected by thoracoscopic surgery. It was observed that the middle mediastinal cyst originated from the thoracic duct, and the thoracic duct was clipped. Pathologically, the diagnosis was a thymic cyst of the anterior mediastinum and a thoracic duct cyst of the middle mediastinum. The patient developed chylothorax after surgery, and a second thoracoscopic operation was performed. It revealed that part of the clipping of the caudal thoracic duct was incomplete, and leakage of chyle was observed. Hence, the clipping was performed again. The course after the second surgery was good. Thoracic duct cysts are rare even among mediastinal cysts and thus require caution due to their tendency to expand.

Sister Mary Joseph's nodule that originated from lung adenocarcinoma.

Umbilical metastasis of cancer, known as Sister Mary Joseph's nodule (SMJN), is a rare phenomenon. It is usually due to intraabdominal malignancies and is quite rare from lung cancer. Here we describe a case of SMJN that originated from advanced lung adenocarcinoma. SMJN should be noted as an important sign of some hidden malignancy including lung cancer.