Cyclin D1 blocks the anti-proliferative function of RUNX3 by interfering with RUNX3-p300 interaction.

Transcriptional function of cyclin D1, whose deregulation is frequently observed in human cancers, has been suggested to contribute to cancer formation. In the present study, we show that cyclin D1 protein inhibits RUNX3 activity by directly binding to it and interfering with its interaction with p300 interaction in lung cancer cells. Cyclin D1 inhibits p300-dependent RUNX3 acetylation and negatively regulates cyclin-dependent kinase (cdk) inhibitor p21 expression. These transcriptional effects of cyclin D1 do not require cdk4/6 kinase activation. We propose that cyclin D1 provides a transcriptional switch that allows the tumor suppressor activity of RUNX3 to be repressed in cancer cells. Since RUNX3 plays tumor suppressive roles in a wide range of cancers, a non-canonical cyclin D1 function may be critical for neoplastic transformation of the epithelial cells in which RUNX3 regulates proliferation.

Impalpable pulmonary nodules with ground-glass opacity: Success for making pathologic sections with preoperative marking by lipiodol.

BACKGROUND: The developments in high-resolution CT scanning have increased the chance of detecting small bronchioloalveolar carcinoma (BAC) or atypical adenomatous hyperplasia (AAH) that appears as a ground-glass opacity (GGO). However, these lesions are not only difficult to localize during surgery, but they are also hard to make pathologic sections of because they are usually impalpable. Here, we report a method of making pathologic sections for impalpable GGO lesions. METHODS: Twenty-nine impalpable GGO lesions < 1 cm in size were marked by 0.4 to 0.5 mL of lipiodol under CT scan before surgery. The lesions were resected under C-arm fluoroscopy. The radiopaque areas marked by lipiodol within the formalin-fixed specimens were cut serially under conventional fluoroscopy for pathologic examinations. RESULTS: The mean (+/- SD) size of the lesions was 0.5 +/- 0.2 cm (range, 0.2 to 1 cm), and the mean depth from the pleural surface was 1.6 +/- 1.4 cm (range, 0.2 to 6 cm). The mean number of sections submitted for pathologic examinations was 2.3 +/- 1.7 per lesion (range, 1 to 7 per lesion). While 11 of the 29 lesions (38%) were invisible even on the cut surface of the specimens, all were demonstrated in hematoxylin-eosin sections. The pathologic diagnosis was BAC in 17 lesions, AAH in 10 lesions, and organized pneumonia in 2 lesions. The use of lipiodol did not affect the pathologic findings. CONCLUSIONS: The use of fluoroscopy to cut sections from resected specimens after preoperative marking with lipiodol was useful for making pathologic sections of impalpable GGOs < 1 cm in size.

Microscopic-sized "microthymoma" in patients with myasthenia gravis.

BACKGROUND: In 2005, Cheuk et al reported two patients with microscopic-sized thymomas and proposed the term microthymoma to distinguish it from the nodular hyperplasia of thymic epithelium, so-called microscopic thymoma. Here, we present microthymomas that were found in 196 patients with myasthenia gravis (MG) who had undergone thymectomy. MATERIALS AND METHODS: Thymic tissues in 196 patients with MG who underwent thymectomy or thymothymomectomy were examined. Of these patients, 73 patients had thymoma indicated by CT before surgery, and the other 123 patients had no mediastinal tumors. From the resected thymic tissues, an average of 14 hematoxylin-eosin-stained sections (range, 4 to 55 sections) were prepared for microscopic examination. The histologic type of the thymoma was classified according to the World Health Organization (WHO) classification. RESULTS: From the 196 patients, we found three microthymomas in 3 patients (1.5%). While these three tumors could not be seen grossly in pathology section, they were found microscopically (range, 2 to 4 mm). The histologic subtype according to the WHO classification system was B1 in one patient and B2 in two patients. CONCLUSION: Microthymoma was found in 3 of 196 patients (1.5%) with MG. Microthymoma might exist in thymus of patients with MG, even in patients who have no thymoma indicated by CT.

Three cases of multiple thymoma with a review of the literature.

Three cases of patients with synchronous multiple thymoma are reported. Two patients had two thymomas each and the remaining patient had three. The thymomas in each patient all displayed similar histological findings, of which the WHO histological classification were type B2, A and B1, respectively. With a modified Masaoka staging system, the thymomas were determined to be stages II-1 and I in patient 1, one of stage III and two of stage I in patient 2, and two of stage II-1 in patient 3. We reviewed nine reported cases of multiple thymoma in which histological findings were provided and discuss whether they developed from multi-centric origin or from intra-thymic metastasis.

Treatment of a fractured ultraflex stent causing tracheal stenosis.

We report on a case of a fractured Ultraflex stent after placement for malignant tracheal stenosis. The patient was a 49-year-old female with adenoid cystic carcinoma of the trachea causing airway stenosis. She was treated by non-covered Ultraflex stent followed by chemoradiotherapy. Twenty months after stent placement, more than half of the distal end of the stent was fractured and caused airway stenosis, while there was no tumor regrowth. After dilation by balloon and bougienage using an endotracheal tube, an additional non-covered Ultraflex stent was placed within the first one, resulting in successful dilation. The patient is now well without any problem with the stent, 12 months after the second stent placement.

Omission of mediastinal lymph node dissection in lung cancer: its techniques and diagnostic procedures.

To reduce or omit a mediastinal lymph node dissection in the patients with clinical stage I non-small cell lung cancer (NSCLC), several authors examined the prevalence of metastatic sites of lymph nodes. Because lymphatic drainage usually heads for the upper mediastinum in upper lobe cancer and for the lower mediastinum in lower lobe cancer, upper and lower mediastinal lymph node dissection could be reduced in lung cancers of lower lobe and upper lobe. By using sentinel node (SN) navigation surgery, it is possible to omit mediastinal lymph node dissection. Radiological findings are also useful to determine reduction of mediastinal lymph node dissection. In clinical stage Ia adenocarcinomas that show ground glass opacity (GGO) findings on computed tomography (CT) or negative for fluorodeoxyglucose accumulation on positron emission tomography (PET), mediastinal lymph node dissection can be omitted, because these types of adenocarcinomas rarely metastasize to the lymph nodes. By using these procedures, mediastinal lymph node dissection can be reduced or omitted with little risk of local recurrence.

Kissing pleural metastases from metastatic osteosarcoma of the lung.

Two patients with osteosarcoma lung metastases of which migrated to the parietal pleura due to contact are reported. The first patient was a 16-year-old male who had a pleural metastasis in the diaphragm within an area in contact with a single lung metastasis. Both of the tumors were resected, followed by systemic chemotherapy. Nine months after the resection of the first metastases, two other lung metastases were found which were resected after chemotherapy. The patient is alive without recurrence 84 months after the first resection of the metastases. The second patient was an 11-year-old female with a pleural metastasis of osteosarcoma which was within an area in contact with a single lung metastasis, which had been resected 4 months before. We concluded (1) that a lung metastasis of osteosarcoma occasionally metastasizes to the pleura due to contact; and (2) that because this kissing metastases of osteosarcoma could be cured by a complete resection, the intrathoracic cavity should be thoroughly observed.

The efficacy of epidural analgesia after video-assisted thoracoscopic surgery: a randomized control study.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) is known to reduce the severity of pain after surgery. However, it has not yet been established whether epidural anesthesia/analgesia (EA) is necessary after VATS. We therefore conducted a randomized control study to examine whether or not EA is necessary for pain control after VATS. PATIENTS AND METHODS: Forty-six patients undergoing VATS were randomly allocated to one of 2 groups: 24 who were given EA after the procedure (EA group) and 22 who were not (NEA group). Patients in the EA group received a continuous infusion of fentanyl and bupivacaine via an epidural catheter for 2 days after VATS. The degree of postoperative pain was assessed on the total dose of additional analgesics administered, a visual analog scale (VAS), a verbal pain score at rest (VPS-R) and on movement (VPS-M), from the day of surgery to the 2nd postoperative day (2 POD). RESULTS: Additional use of rectal diclofenac sodium and intramuscular pentazocine was more frequent in the NEA group than in the EA group (p<0.05). The VAS, VPS-R, and VPS-M scores were significantly lower in the EA group than in the NEA group at 0 POD, from 0 to 1 POD, and from 0 to 2 POD, respectively (p<0.0001-0.05). Stepwise regression analysis revealed that EA was a significant independent variable of VPS-R and VPS-M from 0 to 1 POD (p<0.05). However, the incidence of nausea/vomiting in the EA group was 29%, which was more frequent than in the NEA group (5%) (p<0.05). CONCLUSION: While EA causes nausea/vomiting in some patients, it is effective for pain control until 1 POD after VATS, especially for pain on movements.

Changes in respiratory condition after thymectomy for patients with myasthenia gravis.

BACKGROUND: Anesthesia without muscle relaxants has been reported to be effective for early extubation after thymectomy, but postoperative respiratory status of the patients has not been studied intensively. METHODS: Fifty-two consecutive patients undergoing thymectomies for myasthenia gravis (MG) were evaluated. RESULTS: Forty-two (81%) of the 52 patients were extubated in the operating room, and 49 (94%) patients were extubated within 24 hours. However, 6 (12%) patients required subsequent reintubation for respiratory support. There was a sudden increase in the respiratory rate (RR) and PaCO(2). The mean value of the increase in PaCO(2) at the time of reintubation was 23 mmHg (12-58 mmHg). The mean value of the increase in RR above the preoperative level at the time of reintubation was 16/min (7-30/min). In univariate analysis, vital capacity (VC), %VC, the preoperative pyridostigmine dose and the duration of surgery correlated with reintubation, but with multivariate analyses, the pyridostigmine dose was the only significant factor related to reintubation. CONCLUSION: The patients who received at least or more than 240 mg of pyridostigmine should be monitored carefully after tracheal extubation.

Diaphragm perforation after radio-frequency ablation for metastatic lung cancer.

A case of diaphragm perforation after radio-frequency ablation (RFA) for lung metastasis from uterine cervical cancer is reported. The patient developed pelvic recurrence and solitary lung metastasis after a radical hysterectomy for uterine cervical cancer. Pelvic radiation and RFA for lung metastasis were performed. Metastasis was located in the laterobasal segment of the lower lobe of the right lung. RFA was repeatedly performed in September 2005 and August 2006. In May 2008, ¹8F-fluoro-deoxy-glucose (FDG) positron emission tomography-computed tomography showed evidence of local recurrence of the lung metastasis. A solid lesion with FDG accumulation accompanying a cystic lesion was observed in the lung base. The patient underwent a wedge resection of the lung in June 2008, during which a perforated area of the diaphragm (3 cm in diameter) was identified under the cystic lesion, which was not herniated. The perforation in the diaphragm was closed with a simple continuous suture.

A case of sclerosing hemangioma evaluated with diffusion-weighted magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography.

A 33-year-old female patient was referred to our hospital for further examination of an abnormal shadow evident on a chest X-ray film. Chest computed tomography (CT) revealed a solid nodule 1.9 cm in diameter in the hilum of the upper lobe of the left lung. Positron emission tomography showed high 18F-fluorodeoxyglucose accumulation in the nodule with a maximal standardized uptake value of 4.5, which favored a malignant lesion. Diffusion-weighted magnetic resonance imaging (DWI), which shows differences in the diffusion of water molecules and can discriminate between malignant and benign lesions, indicated that the nodule had a minimum apparent diffusion coefficient of 1.7 × 10-3 mm2/sec, which was higher than the cutoff value of 1.1 × 10-3 mm2/sec for discriminating between malignant and benign diseases; i.e., values equal to or lower than 1.1 × 10-3 mm2/sec favor malignant disease. The results of a CT-guided needle biopsy of the nodule favored sclerosing hemangioma. During surgery, the tumor did not appear to be invasive, and lymph node metastasis and dissemination were not apparent. On the basis of gross appearance, location, preoperative histological diagnosis, and DWI findings, the tumor was enucleated from the pulmonary parenchyma. Seven months after surgery, the patient was alive and had no evidence of recurrent disease.

Three young osteosarcoma patients with small adenocarcinoma or atypical adenomatous hyperplasia of the lung.

Three young osteosarcoma patients with adenocarcinoma (AD) or atypical adenomatous hyperplasia (AAH) of the lung are reported. A 14-year-old male patient with femoral osteosarcoma had solitary AD (case 1); a 23-year-old female patient with femoral osteosarcoma had AAH and lung metastasis (case 2); and a 17-year-old male patient with humeral osteosarcoma had AD and lung metastasis of osteosarcoma (case 3). They have been the youngest patients with lung cancer or AAH in our hospital. The maximum diameter of each lung tumor on computed tomography (CT) was 0.5, 0.6, and 0.5 cm, respectively. On immunohistochemical analyses, the p53 was positive in both AD and osteosarcoma and negative in both AAH and osteosarcoma. On genomic analyses, p53 mutation was detected in only one osteosarcoma (case 3). Epidermal growth factor receptor (EGFR) mutations, short in-frame deletion in exon 19, and insertion in exon 20 were found in AD, but not in AAH or osteosarcoma. There was no apparent genomic relationship between AD/AAH and osteosarcoma in the young patients in this study. Advances in CT and its applications to osteosarcoma patients as a method of assessing lung metastasis might contribute in large part to the detection of AD/AAH in patients younger than 30.

The distribution of parenchyma, follicles, and lymphocyte subsets in thymus of patients with myasthenia gravis, with special reference to remission after thymectomy.

OBJECTIVE: We sought to examine the distribution of parenchyma, follicles, and lymphocyte subsets in the thymus of patients with myasthenia gravis and to identify determinants of remission after thymectomy. METHODS: Sixty patients with myasthenia gravis who underwent thymectomy were examined. The thymus was divided into upper, middle, and lower parts. The upper part was defined as the superior horn, the lower part as the inferior horn, and the middle part as tissue located between the 2 horns. The percentage of parenchyma was measured morphometrically. The degree of follicular hyperplasia was classified into 5 grades. The densities of CD3+, CD4+, and CD8+ lymphocytes were classified into 5 grades. The remission of myasthenia gravis after thymectomy was examined with those variables in each part of the thymus. RESULTS: The middle part had the highest percentage of parenchyma, the highest grade of follicular hyperplasia, and the highest density of CD3+, CD4+, and CD8+ lymphocytes among the 3 parts (P < .001-.05). The grades of follicular hyperplasia in the middle and lower parts were significantly higher in patients with improvement of myasthenia gravis than in those without (P < .05). The densities of CD3+, CD4+, and CD8+ lymphocytes in the cortex of the middle part were significantly higher in patients with improvement than in those without improvement (P < .01-.05). CONCLUSIONS: The thymus has a heterogeneous distribution of parenchyma, follicles, and lymphocyte subsets. The middle part had the largest parenchyma, the highest grade of follicular hyperplasia, and the highest densities of CD3+, CD4+, and CD8+ lymphocytes among the 3 parts of the thymus. The grade of follicular hyperplasia and the density of these lymphocyte subsets are predictive of improvement in myasthenia gravis after thymectomy.

Successful steroid treatment for fibrosing mediastinitis and sclerosing cervicitis.

The use of steroids to successfully treat a 75-year-old woman with fibrosing mediastinitis and sclerosing cervicitis causing a stricture of the left common carotid artery is reported. Biopsy specimens showed collagenous fibers and fibroblasts with moderate infiltration of lymphocytes. The mediastinal and neck lesions were significantly reduced, with almost complete resolution of arterial stricture, 3 months after initiating administration of prednisolone at 20 mg/d.

Sentinel node navigation segmentectomy for clinical stage IA non-small cell lung cancer.

OBJECTIVE: Intraoperative frozen section examination of sentinel lymph nodes was conducted to determine the final indication for segmentectomy for clinical T1 N0 M0 non-small cell lung cancer. METHODS: Between April 2005 and July 2006, 52 patients with clinical T1 N0 M0 non-small cell lung cancer were prospectively treated by segmentectomy with sentinel node identification. The day before surgery, technetium-99m tin colloid was injected into the peritumoral region. After segmentectomy and lymph node dissection, sentinel nodes identified by measuring radioactive tracer uptake were examined for intraoperative frozen sections, which were serially cut 2 to 3 mm in thickness. When sentinel node metastasis was observed, segmentectomy was converted to lobectomy. RESULTS: Sentinel nodes were identified in 43 (83%) patients. The average number of sentinel nodes was 1.6 +/- 0.9 (range: 1-5) per patient. Of 3 patients with metastatic sentinel lymph nodes, 2 underwent lobectomy and 1 larger segmentectomy. None of the other 40 patients had metastatic sentinel lymph nodes and therefore they were treated with segmentectomy. Pathologic staging with permanent sections was N0 in all of the 40 patients. On the other hand, in 9 patients whose sentinel nodes could not be identified, intraoperative frozen sections were required for 5.4 +/- 2.3 lymph nodes, which was significantly more than 1.6 +/- 0.9 in the 43 patients with sentinel node identification (P < .001). CONCLUSION: Sentinel node identification is useful to determine the final indication of segmentectomy for clinical T1 N0 M0 non-small cell lung cancer by targeting the lymph nodes needed for intraoperative frozen section diagnosis.

Sentinel node identification in clinical stage Ia non-small cell lung cancer by a combined single photon emission computed tomography/computed tomography system.

OBJECTIVE: A gamma probe can identify sentinel nodes before nodal dissection in the mediastinum but not in the hilum, owing to high radioactivity from primary tumors. We evaluated the utility of fused single photon emission computed tomography/computed tomography (SPECT/CT) images for the identification of sentinel nodes in the hilum for patients with clinical stage Ia non-small cell lung cancer. METHODS: Technetium-99m tin colloid was injected into the peritumoral region approximately 18 hours before surgery in 63 patients with clinical stage Ia non-small cell lung cancer. On the morning of the operation, approximately 16 hours after administration of tin colloid, sentinel nodes were identified by fused SPECT/CT; this was followed by intraoperative sentinel node identification in the dissected lymph nodes by gamma probe. Because the gamma probe is a standard method for sentinel node identification, the sensitivity of fused SPECT/CT images was examined on the basis of the data of the gamma probe. RESULTS: Fused SPECT/CT images could identify sentinel nodes at segmental and lobar lymph nodes with a sensitivity of 0.87 and 0.74, both of which were significantly higher than 0.40 in the mediastinum (P < .001 and P = .012, respectively). In 5 patients with pathologic N1 or N2 disease, both SPECT/CT and the gamma probe could identify sentinel nodes with metastases. CONCLUSIONS: SPECT/CT could identify sentinel nodes of the hilum especially in segmental and lobar lymph nodes but not in the mediastinum. Because the gamma probe can identify sentinel nodes before nodal dissection in the mediastinum but not in the hilum, a combination of SPECT/CT and the gamma probe can be used to identify sentinel nodes before nodal dissection in both the hilum and the mediastinum, which will enable sentinel node navigation surgery in non-small cell lung cancer.

Extrapleural pneumonectomy via a lower door open thoracotomy with reconstruction of the diaphragm and pericardium using autologous materials for mesothelioma.

We performed extrapleural pneumonectomy (EPP) with combined resection of the diaphragm and pericardium via a lower door open (LDO) thoracotomy to treat right malignant pleural mesothelioma (MPM) in a 57-year-old man. Specifically, we extended the standard posterolateral thoracotomy skin incision along the anterior costal arch, and performed the thoracotomy by cutting into the 6th to 9th costal cartilage. The resulting defect of the diaphragm and pericardium were reconstructed with a reversed latissimus dorsi (LD) muscle flap and a fascia lata graft, respectively. The patient had an uneventful postoperative course without dyspnea or dysfunction of the extremities. The LDO thoracotomy provided a good operative field, especially for the costo- and cardiophrenic angles, allowing a complete resection of the diaphragm to be performed easily. Furthermore, the reversed LD muscle flap and fascia lata graft proved to be ideal autologous materials for reconstruction of both the diaphragm and the pericardium.

Sparganum mansoni parasitic infection in the lung showing a nodule.

Reported herein is a 57-year-old man infected by Sparganum mansoni, a kind of tapeworm, showing a solitary nodule of the middle lobe of the right lung. Because a transbronchial biopsy could not diagnose the nodule, a right middle lobectomy was performed on suspicion of malignant tumor. The lesion was diagnosed as sparganosis by histological and immuno-serological examinations. Histological examination revealed granulomatous inflammation with neutrophil and eosinophil infiltration around the worm and interstitial pneumonia surrounding the nodule. Moreover, vasculitis with foreign body giant cell was seen around the lesion. To the authors' knowledge this is the second case of sparganosis limited in the lung, and the current report presents the first detailed histological description of a pulmonary sparganosis case.

Size of metastatic and nonmetastatic mediastinal lymph nodes in non-small cell lung cancer.

OBJECTIVE: To determine the optimum selection of mediastinal lymph nodes for biopsy in non-small cell lung cancer (NSCLC), lymph nodes with or without metastasis at each mediastinal station were ranked in size in patients with pathological N2 disease. METHODS: Twenty-five NSCLC patients with pathological N2 disease who underwent pulmonary resection with complete mediastinal lymph node clearance were examined. Of 114 mediastinal lymph node stations dissected, 47 had metastases and 67 did not. The sizes of 259 nodes in the 47 positive lymph node stations were measured. Of these 259 nodes, 137 had metastases and 122 did not. The short- and long-axis diameters of the 259 lymph nodes were ranked in each lymph node station. RESULTS: Mean short- and long-axis diameters of lymph nodes with metastases were significantly greater than those without (p < 0.001). In 47 metastatic lymph node stations, the short- and long-axis diameters were greatest in a metastatic node in 44 (94%) and 42 (89%) respectively, whereas in the remaining 3 (6%) and 5 (11%), the second largest but not the largest node was positive. None of the largest lymph nodes with metastasis were smaller than the second largest lymph node at each station. Four of the 10 patients with adenocarcinoma (40%) had metastasis in the second largest but not in the largest node measured by long-axis diameter, a significant difference from one in eight (12.5%) among the squamous cell carcinoma cases (p = 0.04). CONCLUSION: For mediastinal lymph node biopsy, both the largest and the second largest node at each station should be sampled, especially in adenocarcinoma. If only the largest lymph node is selected, false-negative results will occur at a rate of about 10%.