[The Significance of Surgical Biopsy in Case of the Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for the Treatment of Postoperative Recurrence of Lung Cancer].

To evaluate the clinical features of patients who developed resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) administered for postoperative recurrence of lung cancer, we assessed eight patients who underwent surgical biopsy or sampling for the detection of T790M mutation under general anesthesia from 2017 to 2019 in our hospital. All 8 patients had undergone lobectomy with nodal dissection for lung cancer of pathological stageⅠB/Ⅲ/Ⅳa (4/3/1 patients). The median disease-free survival was 29 months (range:11~110 months). The recurrence site was the lung in six patients including malignant pleural effusion in one of six, and two pleural disseminations. All eight patients received gefitinib as first-line treatment. The median age at surgical biopsy was 75 years (range:66~86 years). We performed pleural biopsy in 2 patients, partial lung resection in 5 patients, and pleural effusion sampling in 1 patient in whom our attempt to perform partial lung resection failed because of severe adhesion between the lung and chest wall. T790M mutation was observed in 7 patients( 85.7%) and the treatment by osimertinib in 6 patients was effective in 5 patients( 83.3%). Surgical biopsy is useful for detecting gene mutations in patients resistant to EGFR-TKIs.

[Lung Cancer Accompanied by Sarcoidosis with Mediastinal and Bilateral Hilar Lymphadenopathy;Report of a Case].

A 64-year-old woman with complete atrioventricular block caused by sarcoidosis was emergently placed a pacemaker. A 10 mm nodule in the left upper lobe of the lung and the mediastinal and bilateral hilar lymphadenopathy was detected through chest computed tomography. To establish the diagnosis, resection of the tumor and #4L was performed. By intraoperative pathology, the nodule was diagnosed as an adenocarcinoma and #4L was found to be a granuloma without metastasis of carcinoma. Subsequently, left upper lobectomy and lymph node dissection (ND2a-2) was conducted. Pathological stage was stageⅠA1 lung cancer. No recurrence has been noted for a year postoperatively and lymphadenopathy has improved by administering prednisolone medication.

[Anomalous systemic arterial supply to left basal lung with anomalous return of V6].

The patient was 52-year-old woman. Her chief compliant was bloody sputum. The computed tomography revealed an anomalous artery from descending aorta running into left lung basal segment and anomalous left V6 return to superior pulmonary vein. The bronchoscopic examination showed normal bronchial branches. Under the diagnosis of anomalous systemic arterial supply to left basal lung without sequestration, left lower lobectomy was performed. Microscopically, the pulmonary artery showed intimal thickening and alveolar collapse with interstitial fibrosis were seen. The postoperative course was uneventful and she discharged at 6th postoperative day.

[Patient with massive hemothorax due to blunt trauma saved by transcatheter arterial embolization (TAE)].

A 78-year-old man who fell from a step ladder was transported to our hospital by ambulance under the diagnosis of multiple rib fractures and right hemothorax. Since he was in shock on arrival, endotracheal intubation and tube thoracotomy were immediately performed. Though 2 liters of blood was evacuated, persistent hemorrhage was observed, requiring continuous rapid infusion and blood transfusion. Emergency thoracic arteriography revealed active bleeding from a branch of the right internal thoracic artery. Transcatheter arterial embolization (TAE) was performed using vascular embolization coils and porous gelatin particles. These procedures successfully controlled active hemorrhage from the chest. Intrathoracic hematoma was evacuated through the 2nd large chest tube. Chest tubes were removed on the 7th day. He was discharged on the 17th day without any complications.

[Right lower lobectomy with flap bronchoplasty for primary lung cancer].

A 59-year-old man was referred to our hospital for further investigation of an abnormal chest shadow. A chest computed tomography( CT) revealed a tumor shadow originating in the superior segment( S6)of the right lower lobe. Bronchoscopy showed no visible tumor, but adenocarcinoma cells were detected in brush cytology samples. We diagnosed primary lung cancer, classified as cT2aN0M0, and planned a radical operation. Intraoperatively, since the tumor had invaded the outer wall of intermediate bronchus, we considered a flap bronchoplasty to preserve the middle lobe. The right lower lobectomy and partial resection of intermediate bronchus were made with preserving unaffected ventral wall of lower bronchus. The lower bronchus remnant was used as a flap to cover the defect in the intermediate bronchus. The postoperative course was uneventful, and bronchoscopic findings revealed good healing of the suture line and sufficient airway patency.

[Giant malignant solitary fibrous tumor successfully resected via clamshell incision and lower door open thoracotomy].

We report a case of a giant intrathoracic tumor successfully resected via clamshell incision and lower door open thoracotomy. A 62-year-old woman presented with cough and dyspnea on exertion. A chest computed tomography (CT) revealed a giant mass occupying nearly whole of the right hemithorax. Since the tumor infiltrated deeply into the lung parenchyma, we performed a right pneumonectomy. The 1st thoracotomy was performed at 4th intercostal clamshell incision. Then we divided lower sternum vertically and opened the right lower chest wall laterally. These procedures provided wide operative view from the apex to the diaphragm and excellent access to hilar constructions, and enabled enbloc resction of giant tumor with the right lung. The resected specimen was 25×19×12 cm in size, 2,830 g in weight, and histologically diagnosed as a malignant solitary fibrous tumor. We conclude that this approach is effective for excision of giant intrathoracic tumor.

[Thymic carcinoid associated with multiple endocrine neoplasia type 1].

We report a case of a thymic carcinoid associated with multiple endocrine neoplasia type 1( MEN-1). A 37-year-old man was referred to our hospital for further examination of an abnormal chest shadow. A chest computed tomography (CT) showed an anterior mediastinal mass measuring 6.5 cm in diameter. A pathological diagnosis of thymic carcinoid was made from a CT-guided needle biopsy specimen. Preoperative workup including endocrinological examination revealed a pituitary adenoma and hyperparathyroidism, and MEN-1 was clinically diagnosed. We performed total parathyroidectomy with autotransplantation and thymectomy with lymph node dissection through cervical collar incision and median sternotomy. The diagnosis of MEN-1 was confirmed by the genomic analysis postoperatively. Since 25% of thymic carcinoids are MEN-1 related and 95% of MEN-1 patients develop hyperparathyroidism, it should be kept in mind that this condition can be treated by thymectomy and concurrent parathyroidectomy.

[Reconstruction of the superior vena cava by artificial graft bypass between right brachiocephalic vein and right atrial appendage preserving azygos vein circulation for mediastinal non-seminomatous germ cell tumor].

A 24-year-old man was admitted to our hospital for surgical resection of mediastinal non-seminomatous germ cell tumor after 4 courses of BEP therapy (cisplatin, bleomycin, etoposide). Although it became markedly smaller after chemotherapy, the tumor invaded the superior vena cava (SVC) and the left brachiocephalic vein (LBCV). Venogram demonstrated SVC obstruction above the azygos vein and missing LBCV. A blood return from the left upper limb was shown through thoracodorsal vein, intercostal vein, and accessory hemi-azygos continuation. Excision of residual tumor with SVC and LBCV was done through a median sternotomy. Vascular reconstruction was performed between the right brachiocephalic vein and the right atrial appendage with ringed polytetrafluoroethylene graft. SVC was sutured just above the azygos vein to preserve collateral circulation. LBCV reconstruction was abandoned because distal end of LBCV was entirely surrounded by postchemotherapy scar tissue. Venous occlusive symptoms were not seen in both intraoperative and postoperative period.

[Sleeveresection of the left main bronchus for bronchogenic carcinoid for preserving lung parenchyma].

UNLABELLED: We performed bronchoplasty for a bronchogenic tumor of low-grade malignancy without lung parenchyma resection. A 69-year-old man visited our hospital in March 2008 because of cough. Chest computed tomography (CT) revealed atelectasis of the entire left upper lobe and a 2-cm mass with strong contrast enhancement in the lumen of the left main bronchus. Bronchoscopy identified a polypoid mass in the left main bronchus, about 3 cm distal to carina, obstructing the lumen. Biopsy led to a diagnosis of typical carcinoid tumor. Surgery : Thoracotomy showed complete atelectasis of the left upper lobe. After lymph node dissection, resection of the left main bronchus including the site of tumor origin was performed. From the extent of expansion, the left upper lobe was decided to be possible to be spared, and end-to-end anastomosis of the bronchus was performed. Postoperative respiratory rehabilitation resulted in improved aeration of the left upper lobe and markedly improved respiratory function. CONCLUSION: The judgment of whether the long-standing atelectatic left upper lobe could be spared or not was a key in choosing this procedure.

Progesterone receptor in non-small cell lung cancer--a potent prognostic factor and possible target for endocrine therapy.

A possible involvement of gender-dependent factors has been postulated in development of human non-small-cell lung cancers (NSCLC), but its details remain unclear. In this study, we examined biological significance of progesterone receptor in NSCLCs. Progesterone receptor immunoreactivity was detected in 106 of 228 NSCLCs (46.5%). Progesterone receptor-positive NSCLC was frequently detected in female and adenocarcinoma, and was inversely associated with tumor-node-metastasis stage and histologic differentiation. Progesterone receptor status was also associated with better clinical outcome of the patients, and a multivariate analysis revealed progesterone receptor status as an independent prognostic factor. Progesterone-synthesizing enzymes were detected in NSCLCs, and tissue concentration of progesterone was higher in these cases (n = 42). Immunoblotting analyses showed the presence of progesterone receptor in three NSCLC cell lines (A549, LCSC#2, and 1-87), but not in RERF-LC-OK or PC3. Transcriptional activities of progesterone receptor were increased by progesterone in these three progesterone receptor-positive NSCLC cells by luciferase assays. Cell proliferation was inhibited by progesterone in these progesterone receptor-positive NSCLC cells in a dose-dependent manner, which was inhibited by progesterone receptor blocker. Proliferation of these tumor cells injected into nude mice was also dose-dependently inhibited by progesterone, with a concomitant increase of p21 and p27 and a decrease of cyclin A, cyclin E, and Ki67. Results of our present study suggested that progesterone receptor was a potent prognostic factor in NSCLCs and progesterone inhibited growth of progesterone receptor-positive NSCLC cells. Therefore, progesterone therapy may be clinically effective in suppressing development of progesterone receptor-positive NSCLC patients.

Estrogen inhibits cell proliferation through in situ production in human thymoma.

PURPOSE: We showed previously estrogen receptor (ER) alpha as an independent prognostic marker in human thymoma. Estrogen sulfotransferase (EST), steroid sulfatase (STS), 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and aromatase are considered to play important roles in hormone metabolism of estrogen-dependent tumors. EXPERIMENTAL DESIGN: We examined estrogen production using primary cultures of human thymoma epithelial cells (TEC), intratumoral estradiol (E(2)) concentrations, and status of these enzymes above using immunohistochemistry or semiquantitative reverse transcription-PCR. We then correlated these findings with clinicopathologic variables and/or clinical outcome in 132 patients. RESULTS: E(2) inhibited cell proliferation via ERalpha in TEC, which synthesized estrone and E(2). Intratumoral E(2) concentrations were inversely correlated with EST, positively correlated with STS or 17beta-HSD type 1, and significantly higher in lower-grade or early-stage thymoma. EST status was positively correlated with tumor size, clinical stage, histologic differentiation, and Ki-67 labeling index and significantly associated with adverse clinical outcome and turned out to be a potent independent prognostic factor. STS and/or 17beta-HSD type 1 status was inversely correlated with Ki-67 labeling index and associated with lower histologic grade or early clinical stages. CONCLUSIONS: E(2) inhibits proliferation of TEC through ERalpha, which suggests that E(2) may be effective in treatment of thymoma, especially inoperable tumor, possibly through suppressing its cell proliferation activity. EST status is a potent prognostic factor in thymoma through inactivating estrogens. In situ estrogen synthesis through intracrine mechanism therefore may play important roles in tumorigenesis and/or development of thymoma through regulation of cell proliferation in an intracrine manner.

Sex steroid hormone receptors in human thymoma.

In this study we examined the immunohistochemical localization of sex steroid receptors for estrogen alpha (ER alpha) and ER beta, progesterone-A (PR-A) and PR-B, and androgen (AR) in human thymoma (n = 132) and correlated these findings with various clinicopathological parameters. We used RT-PCR and real-time PCR to further study the expression of these receptors in 20 thymoma cases. Immunoreactivity for all sex steroid receptors was detected in the nuclei of thymoma epithelial cells. The percentage of immunopositive cases and the H-score values for each receptor (mean +/- SD) were: ER alpha, 66% and 85.8 +/- 80.2; ER beta, 7% and 7.2 +/- 8.7; PR-A, 4% and 2.7 +/- 4.9; PR-B, 49% and 55.8 +/- 68.3; and AR, 15% and 14.1 +/- 11.7, respectively. The results of real-time PCR were consistent with those of immunohistochemistry, especially results for ER alpha, PR-B, and AR. A significant positive correlation was detected between immunoreactivity for ER alpha and PR-B. ER alpha immunoreactivity was inversely correlated with tumor size, clinical stage, WHO classification, and Ki-67 labeling index. In addition, the status of ER alpha immunoreactivity was significantly associated with a better clinical outcome in thymoma patients. Results from our study suggest that estrogens may inhibit thymoma growth via ER alpha, and that ER alpha immunoreactivity may act as a prognostic factor in human thymoma.

Computed tomographic image comparison between mediastinal and lung windows provides possible prognostic information in patients with small peripheral lung adenocarcinoma.

OBJECTIVES: The purpose of this study was to determine whether the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image can be a prognostic factor of small peripheral lung adenocarcinoma. METHODS: We studied the computed tomographic images of 143 patients with primary peripheral lung adenocarcinoma of 30 mm or less in maximum diameter. Two groups were categorized according to the tumor's ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image (tumor's area in the mediastinal computed tomographic image/tumor's area in lung computed tomographic image x 100%), both faint density-type (<50%) and solid-type images (>/=50%). Clinical factors and prognoses of the 2 groups were analyzed. RESULTS: There were 58 patients with the solid-type tumor image and 85 patients with the faint density-type tumor image. The number of patients with tumor size of less than 20 mm in the faint density-type tumor group (n = 30) was significantly higher than that in the solid-type tumor group (n = 8, P =.008). The 5-year survival of patients with faint density-type tumors was 74.1%, whereas that in patients with solid-type tumors was 54.2% (P =.013). Furthermore, the survival curve of patients with the solid-type computed tomographic image combined with ground-glass opacity was similar to that of patients with the faint density-type image. Multivariate analysis revealed the prognostic influence of the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image on survival (P =.029, relative risk = 0.48) and showed to be of second highest influence after the N factor. CONCLUSIONS: It is suggested that the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image can be a prognostic factor in patients with small peripheral lung adenocarcinoma.

A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery.

OBJECTIVE: A prospective randomized trial was performed to investigate the prognostic advantage of postoperative adjuvant chemotherapy in patients with resected stage I-II non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From March 1992 to December 1994, 221 patients with completely resected stage I-II primary NSCLC were enrolled and randomly assigned to two groups, as follows: 2-year oral administration of Uracil plus Tegafur (UFT) (adjuvant group, 109 patients), and surgical treatment alone (control group, 110 patients). RESULTS: The overall 5-year survival rates were 79% for the adjuvant group and 75% for the control group, and there was no statistical significance. The 5-year disease-free survival rates were 78% for the adjuvant group and 71% for the control group, and there was also no statistical significance. There have been seen no severe complications in the adjuvant group. The mean total dosages of UFT were about 75% of maximum basic amount. CONCLUSIONS: The UFT regimen was feasible. However, we have not observed any survival benefit in the adjuvant group. Larger trials are needed to confirm the effect of UFT to patients with resected NSCLC.

A prospective trial of systematic nodal dissection for lung cancer by video-assisted thoracic surgery: can it be perfect?

BACKGROUND: There have been no reports evaluating the completeness of systematic nodal dissection with video-assisted thoracic surgery (VATS). In order to elucidate the completeness of the dissection, we have conducted a prospective trial with patients having primary lung cancer. METHODS: Patients with clinical stage I lung cancer were the candidates for this study. Thoracotomy was performed with a small skin incision of 7 cm to 8 cm in length. Through these small wounds and two trocars, pulmonary resection was performed and then hilar and mediastinal lymph nodes were dissected. After that, a standard thoracotomy was carried out by another surgeon to complete systematic nodal dissection. RESULTS: Video-assisted thoracic surgery lobectomy with lymph node dissection was accomplished in 17 right lung cancer patients and 12 left lung cancer patients. On the right side, the average numbers of resected lymph nodes by VATS and remnant lymph nodes were 40.3 and 1.2, respectively. The average weights of dissected tissues by VATS and remnant tissues were 10.0 g and 0.2 g, respectively. On the left side, there were 37.1 and 1.2 lymph nodes and 8.3 g and 0.2 g of weight of dissected tissues. No nodal involvement was observed in the remnant lymph nodes. CONCLUSIONS: The lymph node dissection with VATS was technically feasible and the remnant ("missed" by VATS) lymph nodes and tissues were 2% to 3%, which seems acceptable for clinical stage I lung cancer.

Primary intrapulmonary thymoma successfully resected with vascular reconstruction.

Primary intrapulmonary thymomas are defined as intrapulmonary tumors without an associated mediastinal component and are very rare. We report a resected case of primary intrapulmonary thymoma with dissection of mediastinal lymph nodes and vascular reconstruction. Because the tumor directly invaded the right brachiocephalic vein, the vein was reconstructed with a graft, and then adjuvant radiation was performed postoperatively. The tumor was diagnosed as a lymphocyte dominant thymoma and B2 type thymoma in the WHO classification. There has been no evidence of recurrence in 6 years. Complete resection of the tumor with vascular reconstruction and adjuvant radiation should be considered in invasive intrapulmonary thymoma.

A rare case of a pulmonary granular cell tumor presenting as a coin lesion.

A 38-year-old man was found to show a well-defined oval-shaped homogeneous dense mass (20 x 30 mm) in the left upper lung field on chest X-ray. Left upper divisionectomy was performed under video-assisted thoracic surgery. Histology showed that the tumor cells had abundant eosinophilic granular cytoplasm, and were immunopositive for neuron-specific enolase, CD56, S-100 protein, and chromogranin. The proportion of Ki-67 positive cells was < 1%. An electron-microscopic examination showed many membrane-bound whorls in the cytoplasm. Although this was a very rare case presenting as an asymptomatic coin lesion, the histological features were the same as those demonstrated for granular cell tumor at common sites.

Non-circumferential tracheal resection with muscle flap reconstruction for adenoid cystic carcinoma.

Circumferential airway resection with primary anastomosis has been widely adopted as a treatment for adenoid cystic carcinoma (ACC) of the trachea. However, carinal resection is a complicated procedure with high mortality and morbidity rates. We describe a technique of non-circumferential tracheal resection performed to treat ACC arising from the lower membranous trachea adjacent to the carina. The tumor was resected while preserving the tracheo-carinal cartilage. A silicone Y-stent was placed at the bifurcation to ensure airway patency before closing the defect. The airway defect, measuring 4 × 2.5 cm, was closed using an autologous pericardial patch and pedicled latissimus dorsi muscle flap. These procedures were technically easy, and no postoperative airway complication occurred.