Hyung-Eun Yoon

Inversely correlated expression of p16 and Rb protein in non‐small cell lung cancers: An immunohistochemical study

Cdk4‐mediated phosphorylation of Rb protein is inhibited by p16, a product of a possible tumor suppressor gene. We examined the expression of p16 and Rb protein by means of immunohistochemistry in 61 non‐small cell lung cancers and have demonstrated an inverse relationship between the expression of p16 and Rb protein: 28/30 specimens that did not stain for p16 stained for Rb and 21/31 p16‐positive specimens did not stain for Rb. Only 1 of the p16‐negative specimens had a mutation of exon 2 of the CDKN2 gene. Our results indirectly support the theory that p16 expression is negatively regulated by the functional Rb protein.

Clinical spectrum of congenital cystic disease of the lung in children

OBJECTIVES Congenital cystic lesions of the lung are uncommon but share similar embryologic and clinical characteristics. The purpose of this study is to review our institutional experience of congenital cystic lung disease, emphasizing the clinical spectrum of the disease related to age, and present some cases with unusual clinical manifestations. PATIENTS Between 1962 and 1996, 26 patients (9 females and 17 males) under 15 years old underwent evaluation and surgical treatment for congenital cystic lung disease. Seven patients were under 1 year old, and 19 were in over 1 year old. There were 13 bronchogenic pulmonary cysts, 6 pulmonary sequestrations, 4 congenital cystic adenomatoid malformations (CCAM), and 3 congenital lobar emphysemas. RESULTS All patients under 1 year old showed respiratory distress with mediastinal shift but no episodes of infection. In contrast, 13 of the 19 patients over 1 year old had symptoms of recurrent infection without respiratory distress. Five patients over 1 year old were entirely asymtomatic from birth. There were significant differences (P < 0.05) in the frequencies of respiratory distress and infection between the two groups (chi2-test). Lobectomy was performed in 21 patients, excision in 3 patients, segmentectomy in one patient, and exploration in one patient. There was no incident of postoperative mortality or morbidity except for one patient with CCAM complicated by reexpansion lung edema. Twenty-one patients at long-term follow-up from 2 to 30 years after surgery are doing well with no subsequent limitation of physical activities due to lung resection. CONCLUSIONS In patients under 1 year old, cystic lesions were discovered by respiratory distress; and in patients over 1 year old signs of infection were the most important clinical features. Early recognition of these relatively rare congenital cystic lung lesions would lead to the immediate, proper surgical intervention.

Disruption of the RB pathway and cell-proliferative activity in non-small-cell lung cancers.

The pathway consisting of retinoblastoma protein (pRB), cyclin D1 and p16 (RB pathway) which is involved in the phosphorylation of pRB plays an important role in G1/S progression. The disruption of this RB pathway has been reported in several types of human neoplasm. An immunohistochemical study of 101 non‐small‐cell lung cancers (NSCLCs) showed loss of p16 is in 47 tumors (46.5%) and loss of pRB in 42 tumors (41.6%). In 79 of 101 NSCLCs (78.2%), the expression of p16 and pRB was complementary (p < 0.0001). Methylation of the cdkn2 gene was detected in 50% of p16‐negative tumors and in 11% of p16‐positive tumors. Aberrant expression of cyclin D1 was found in 45 tumors (44.5%). The cyclin‐D1‐positive tumors had significantly higher Ki‐67 indices than the cyclin‐D1‐negative tumors irrespective of the tumor p16 or pRB expression. Thus, 91 (90%) of 101 NSCLCs showed disturbed expression of at least 1 of the 3 components of the RB pathway. Our results suggest that the disruption of the RB pathway plays an important role in tumorigenesis in NSCLCs and that increased cyclin‐D1 expression leads to strong proliferative activity which may over‐ride the suppressive effect of p16 and pRB. Int. J. Cancer (Pred. Oncol.) 79:111–115, 1998.© 1998 Wiley‐Liss, Inc.

Clinical Study on Lung Cancer as a Second Primary Cancer

This study evaluates the effect of a previous cancer on the clinical characteristics and the outcome of lung cancer patients. The 313 primary lung cancer patients operated on in the Osaka University Hospital during the period 1984-1993 were reviewed. Of those, 37 had a history of previous cancer. In the lung cancer patients with a history of previous cancer, 20 had adenocarcinomas, 14 had squamous cell carcinomas, while 3 had other cancers. The previous malignancies included 13 gastric cancers, 10 head and neck cancers, 6 colorectal cancers, and 8 others. The pathological stage was 17 stage I, 1 stage II, 15 stage IIIA, 1 stage IIIB, and 3 stage IV. The 5-year survival rate was 37.9%. In patients without a history of previous cancer, there were 139 adenocarcinomas, 100 squamous cell carcinomas, and 37 others. The pathological stage was 126 stage I, 33 stage II, 74 stage IIIA, 23 stage IIIB, and 20 stage IV. The 5-year survival rate was 43.3%. There were no significant differences in the cell type, stage, or survival between the lung cancers found as the first and second cancers. Lung cancer patients with a history of previous cancer are expected to respond to a resection as well as those with lung cancer appearing as their first cancer.

Non-small-cell lung cancer associated with non-thymomatous myasthenia gravis

A non-small-cell lung cancer without distant metastases was incidentally found in a 77-year-old man who had suffered from myasthenia gravis (MG) without thymoma. The patients condition was stabilized by oral pyridostigmine bromide which he had taken during the past 6 years. He simultaneously underwent thymectomy and left lower lobectomy with regional lymph node dissection. Although postoperative myasthenic crisis occurred, mechanical ventilation and intravenous steroid pulse relieved the patient and the symptoms improved thereafter. Cases of operable lung cancer with non-thymomatous MG have rarely been reported and the appropriate therapeutic strategy for such cases remains to be debated. Their causal association remains to be identified, whereas some studies have implied that immune disorder due to the abnormal thymus might possibly enhance the oncogenesis of extrathymic malignancies. Myasthenic crisis should also be taken into account in postoperative management of MG patients who simultaneously undergo thymectomy and lobectomy for synchronous lung cancer.

Ventilatory muscle recruitment and work of breathing in patients with respiratory failure after thoracic surgery

OBJECTIVES Increased work of breathing (WOB) and respiratory muscle weakness have been identified as major causes of respiratory failure after thoracic surgery. This study was undertaken firstly to characterize the mechanical impairment in patients with respiratory failure after cardio-thoracic surgery, and secondly, to determine how diaphragmatic paralysis affects deterioration in the ventilatory mechanics. METHODS We evaluated the respiratory mechanics of 24 patients following cardiac and thoracic surgery. Ten patients without respiratory problems were examined as control subjects. There were nine patients with phrenic nerve injury and five patients without phrenic nerve injury who required mechanical ventilation for more than 7 days. Phrenic nerve injury was assessed with a phrenic nerve stimulation test. We measured the respiratory variables, the esophageal, gastric and transdiaphragmatic pressure swing (deltaPes, deltaPga and deltaPdi, respectively), and the work of breathing during quiet tidal breathing. RESULTS Both the groups requiring mechanical ventilation exhibited abnormally negative deltaPga/deltaPes values, compared with the control subjects. A significant increase in WOB with the normal generation of deltaPdi was seen in the patients without phrenic nerve injury. In contrast, the poor generation of deltaPdi with a slight increase in work of breathing was noted in patients with phrenic nerve injury. CONCLUSIONS These results demonstrated two different types of respiratory failure in thoracic surgery patients, focusing on the impact of phrenic nerve paralysis. Diaphragmatic dysfunction should not be overlooked in postoperative care, and the amelioration of this compromise in respiratory mechanics is an important aspect of good patient management.

Assessment of ALK gene rearrangement in lung cancer using a new rapid automated SureFISH (Dako Omnis) assay

The ALK fluorescence in situ hybridisation (FISH) method is the examination essential for pathological diagnosis and choice of molecular-targeted therapy in ALK-rearranged lung cancer. Here, for detection of ALK gene rearrangement in patients with lung cancer, we evaluated the rapid FISH technology (ALK SureFISH), a newly developed assay for the automated staining platform Dako Omnis, using 21 formalin-fixed paraffin-embedded (FFPE) samples. All cases could be evaluated with the SureFISH method. SureFISH provided excellent quality signals without any background staining. The SureFISH assay was able to offer a rapid turnaround time (approximately 3.5 hours) and was 100% concordant with prior Vysis FISH results in our laboratory.

Small calcifying fibrous pseudotumor of the heart confined to the epicardium

A calcifying fibrous pseudotumor (CFPT) is a rare benign lesion that often presents in the upper and lower extremities of children and young adults. In the present report, we describe a case of a small CFPT arising from the epicardium (visceral pericardium) in a 32-year-old woman. The tumor presented as a 25-mm polypoid mass protruding into the pericardial cavity, without extending into the myocardium. A complete resection was performed, and the patient has not experienced any relapse for more than 2 years. On histological examination, the lesion contained densely hyalinized collagen with psammomatous and dystrophic calcifications, as well as patchy chronic inflammatory infiltrate. The localization in the epicardium with no involvement of the myocardium was confirmed by the elastic stain. Amyloid was negative by the Congo red stain. On immunohistochemical analysis, the lesional cells indicated diffuse positive staining for vimentin and factor XIIIa and focal positive staining for CD34, but did not indicate positive staining for other pertinent antigens such as cytokeratins, calretinin, desmin, α-smooth muscle actin, ALK, and estrogen and progesterone receptors as well as IgG4 in plasma cells. To our knowledge, only three cases of CFPT in the heart have been reported in the literature, all of which developed in young females as a large mass involving the epicardium; the lesion also extended to the parietal pericardium in two cases. Moreover, all cases presented with few symptoms, despite the large lesion. In the present case, the CFPT developed also in a young woman, but the lesion was much smaller than those previously published and was localized in the visceral serous membrane of the heart. The findings of this case suggest a potential preferable site of origin of CFPTs of the heart.

Life-threatening and Rapidly Growing Teratoma in the Anterior Mediastinum.

This report describes the case of a 23-year-old man with a mediastinal teratoma. Five months before admission, a chest radiograph during a routine health checkup was normal. Four months before admission, the patient developed sudden onset of mild right-sided chest pain. He gradually developed dyspnea and was admitted to our hospital. Computed tomography revealed a giant tumor that was markedly compressing the right atrium. Urgent surgery was performed, and a ruptured, benign mature teratoma was diagnosed. Mature mediastinal teratomas are benign tumors, but they can rupture and have the potential to grow rapidly, potentially leading to life-threatening complications.

Preoperative Identification of Anomalous Drainage Vein for Posterior Segment of Right Upper Lobe

A 62-year-old man had a small nodule in the right upper lobe, which was diagnosed as adenocarcinoma by transbronchial biopsy analysis. Preoperative three-dimensional (3D) angiography with contrastenhanced images obtained using multi detector-row computed tomography (CT) revealed a 3-mm diameter vein for the posterior segment of the right upper lobe running posterior to the right hilum that drained directly to the left atrium, and independent of both the superior and inferior pulmonary veins (Fig 1, arrows). A corresponding small vessel located dorsal to the right bronchus intermedius was seen in axial CT sections. We performed a thoracoscopic right upper lobectomy along with mediastinal lymph node dissection. Intraop-