[Radical surgery using modified open door method for anterior apical tumor].

The approach that should be used for an anterior apical tumor still remains controversial. Since a modified open door method was very useful for the widening of the surgical field in a recent patient with an anterior apical tumor, an outline of this case is reported. The patient was a 66-year-old male with squamous cell carcinoma of the anterior apical region of the right lung (suspected to be invading the thoracic wall, cT3N1M0). After a midline sternal incision with a right unilateral collar incision, the medial half of the right clavicle and a few cm of the right 1st rib on the sternal side were resected to sufficiently expose the area from the right brachiocephalic trunk to around the subclavicular artery and vein, where invasion was suspected. This treatment facilitated widening of the visual field around the site of tumor invasion and made safe right upper lobectomy + combined thoracic wall resection + ND2a possible. In this patient, anterolateral incision at the 4th intercostal level, which is made using the original open door method, could be avoided, probably minimizing surgical invasion.

[Median approach for the right upper lobe lung cancer patient with impaired pulmonary function].

We report the usefulness of a median approach to the right upper lobe lung cancer with impaired pulmonary function. Patient was a 68-year-old man with chronic obstructive pulmonary disease and primary right upper lobe (S1) lung cancer with suspected anterior mediastinal invasion (cT4N0M0). Thoracoscopy excluded mediastinal invasion, but a median sternal incision was made to avoid injuring respiratory muscles and postoperative respiratory complications. We successfully performed systematic mediastinal lymph node dissection (ND2a) after right upper lobectomy. The patient was discharged on the 10th postoperative day without any events. He eventually underwent additional chemotherapy because of the liver metastasis confirmed at 8 months after the operation. In right upper lobe lung cancer patients with impaired pulmonary function, a median approach seems useful for intraoperative respiratory management and the sparing of respiratory muscles which will reduce the possibility of postoperative respiratory complications.

[Surgical approach for histopathological determination of anterior mediastinal malignant lymphoma].

In a retrospective review of all patients who admitted our hospital between January 1992 and December 2006, we identified 9 with anterior mediastinal malignant lymphoma. They represented 6.8% of the 133 patients with mediastinal tumor. Histology revealed 3 cases of primary mediastinal large B-cell lymphoma, 2 of Hodgkin lymphoma, 2 of precursor T-lymphoblastic lymphoma and 2 of thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma. Careful attention should be paid to the relatively high incidence of malignant lymphoma in the anterior mediastinal tumors. It is highly important to differentiate of malignant lymphoma from other diseases that shape anterior mediastinal tumor to avoid unnecessary operation. Early and accurate diagnosis of these tumors is also important because some of these patients require immediate treatment by hematology specialists.

[Reoperation for left main bronchial stump fistula developing after pneumonectomy].

We report the case of a 71-year-old male patient who underwent reoperation for bronchial stump fistula developing after left pneumonectomy for adenocarcinoma of the left lung (clinical stage IIB). After surgery, he developed persistent, severe cough and chest X-ray films taken on the 23rd postoperative day showed a drop in the air-fluid level in the left lung field, which, along with bronchoscopic findings, strongly suggested the bronchial stump fistula and subsequent reoperation was performed. Both superior pulmonary vein and main pulmonary artery were dissected again proximally in pericardium, and the left main bronchus was separated from the surrounding tissue. Bronchial stump was closed with a stapler as close to the carina as possible, and additional resection was performed. After reoperation, the patient had an uneventful course, and was discharged in the second postoperative week. Shorter length of bronchial stump may be the most important factor to prevent the bronchial stump fistula developing after pneumonectomy.

[Median approach for upper lobe lung cancer patients with suspected anterior mediastinal invasion].

We report the usefulness of a median approach to the mediastinum for the treatment of lung cancer with possible mediastinal invasion. Patient was a 74-year-old man with left S3 squamous cell carcinoma suspected of anterior mediastinal invasion (cT4N0M0) because of hoarseness before surgery. A median sternotomy with partial collar incision was chosen for surgery. The tumor was widely adherent to the anterior mediastinum, invading the common carotid artery and the origin of the left subclavian artery. Left upper lobectomy with ND2a by incomplete resection of the invading portion followed by postoperative radiotherapy was performed. For upper lobe lung cancer with possible mediastinal invasion, a median approach seems to be useful, because it facilitates both easy approach to the anterior mediastinum and the management of invasion of large vessels.

Allergic inflammatory reaction is involved in necrosis of human pulmonary dirofilariasis.

AIMS: To determine whether, in view of the massive inflammatory cell infiltration and the rounded rather than wedge-shaped character of pulmonary lesions in dirofilariasis, the inflammatory response against the worm contributes to the coagulative necrosis, in addition to an ischaemic process. METHODS AND RESULTS: The histopathological features of 13 resected dirofilariasis cases with well-defined nodules ranged from 10 to 30 mm were analysed. On routine histology and using immunohistochemistry, the peripheral encapsulating wall showed mild to severe infiltration of eosinophils, lymphocytes and plasma cells and a histiocytic reaction in all cases, often with necrotic eosinophils seen within the necrosis (84.6%) and inflammatory changes in the adjacent lung (38.5%). The CD4+ lymphocyte count (80.8 +/- 33.4) was greater than that of CD8+ lymphocytes (24.5 +/- 16.9) in the central necrosis and vice versa in the wall. In the necrotic regions, disruption of the pulmonary artery (61.5%) and extravasation of the torn worm (23.1%) could be seen. CONCLUSIONS: These findings indicate that an allergic inflammatory reaction, mediated by eosinophils and lymphocytes, is involved in the formation of the dirofilarial necrotizing granuloma rather than infarction caused simply by embolism.

[Pulmonary actinomycosis developing diffuse phregmone after pneumonectomy].

The patient was a 75-year-old male who consulted the department of respiratory tract internal medicine in our hospital for left chest pain occurring from the beginning of December 2003. Chest X-ray indicated a tumorous shadow in the left lower lung field. A chest CT also revealed an irregularly shaped mass shadow in the left lower lobe. Since bronchoscopy failed to establish a definitive diagnosis, the patient was referred to our department for surgery to undertake thoracotomy. After left pneumonectomy being performed based on a suspicion of lung abscess, pathological examination of specimen from the resected left lung showed sulfur granules which led to the diagnosis of pulmonary actinomycosis. Because of the diffuse phregmone developing around the surgical wound, benzylpenicillin potassium administration was started, and was continued for a further 6 months on an outpatient basis. Pulmonary actinomycosis is a relatively rare chronic pulmonary infection. It is often difficult to distinguish pulmonary actinomycosis from other pulmonary disease such as lung cancer because of the similarity of their appearance on X-ray or CT, and almost all cases of pulmonary actinomycosis are diagnosed by thoracotomy.

[Large cell carcinoma with chest wall infiltration combined with contralateral giant bulla].

A 48-year-old male consulted the department of respiratory medicine for right precordial pain occurring from the beginning of May 2004. Chest X-ray indicated a tumorous shadow in the right upper lung field and a large left lung cyst. Although chest wall infiltration was suspected based on computed tomography (CT) demonstrating a mass lesion in the right S2, there was no significant swelling of the mediastinal lymph node. On the left side, the lung was markedly compressed by a large cyst in the left upper lobe. Since bronchoscopy failed to establish a definitive diagnosis, the patient was referred to our department for surgery based on a suspicion of malignant pulmonary tumor. Considering both the risk of perioperative complications due to the left cystic lesion at surgery for right lung lesion and the improvement of respiratory function by removing cystic lesion of the left lung, the left side operation was preceded by the right side. Although postoperative examinations of respiratory function did not demonstrate any particular improvement, the results of selective right pulmonary artery obstruction test supported the possibility of pulmonary lobectomy. Therefore, the right upper lobectomy and ND 2a mediastinal dissection combined with chest wall resection was subsequently performed. Postoperative pathological diagnosis revealed that the tumor was a stage IIB large cell carcinoma of pT3N0M0 with costal infiltration.

[Conservative therapy for recurrent bronchial stump fistula occurred after surgery for lung cancer with cerebrovascular disease].

BACKGROUND: Although pyrothorax caused by bronchial stump fistula is 1 of the most severe respiratory complications frequently encountered after surgery for lung cancers, it is very difficult to prevent the development of pyrothorax. However, conservative treatment for bronchial stump fistula occurred after surgery for lung cancer was successfully performed in 1 of our elderly lung cancer patients with a history of cerebrovascular events. CASE: Patient was a 74-year-old man who developed cerebral infarction in October 2000, and was continuously undergoing rehabilitation for left hemiplegia. Chest computed tomography (CT) demonstrated a tumorous lesion in the right S6. Clinical diagnosis of stage IA squamous cell carcinoma was made. His performance status (PS) was degree IV, and he required complete assistance. In addition, since several abnormal florae were detected by preoperative examinations of sputum, the development of postoperative respiratory complications was suspected. In April 2001, thoracoscopy-assisted right inferior lobectomy and nodal dissection 1 (ND 1) were performed. Although the patient developed bronchial stump fistula on the 6th hospital day, it was successfully treated by conservative procedures after second surgery. CONCLUSION: Conservative therapy under nutritional management mainly consisting of central venous nutrition may be useful for some surgically treated lung cancer patients with bronchial stump fistula when they have mild inflammation and the reduction of pyrothorax cavity can be expected by re-expansion of the residual lobes of the lung.

The immunohistochemical localization of Fas and Fas ligand in jaw bone and tooth germ of human fetuses.

The cellular localization and roles of bone morphogenetic protein (BMP)-2 and apoptosis-associating factors in human orofacial development remain unclear. In this study, BMP-2, osteocalcin, and TGF-beta, which are bone-differentiating markers, apoptosis-associating factors (i.e., Bcl-2, Bax, Fas, and Fas ligand), apoptotic cells detected by the in situ 3'-end labeling method (TUNEL), and proliferating cell nuclear antigen (PCNA) were immunohistochemically examined in the heads (in particular, the jaw bone and tooth germs) of human fetuses of 11-week pregnancy. BMP-2 was positive in osteoblasts and newly formed osteoid of the incisive and palatal bone of the maxilla and the mandible, which indicated that BMP-2 was exclusively involved in intramembranous ossification in the human fetal head. Fas was positive in the cytoplasm of osteocytes and a few osteoblasts. In contrast, Fas ligand was positive in the cytoplasm of osteoblasts and abundant in the stroma of the osteoblastic layer, periosteum, and perichondrium. The Fas ligand in the stroma was recognized as the soluble form, which was possibly produced by osteoblasts. TUNEL-positive apoptotic cells were found in a few osteocytes and a few osteoblastic cells in new bone, and in monocytes of degenerate Meckel's cartilage. The induction of apoptosis observed in monocytes seems to be caused via a Fas-Fas ligand cell death system, because some of these monocytes were Fas-positive, and most of them were Fas ligand-positive. Interestingly, the abundant soluble Fas ligand observed in the periosteum probably protects the bone-formative zone from the invasion of the activated lymphocytes by binding to Fas expressing in these lymphocytes and killing these cells. Fas and Fas ligand were focally positive in the dental lamina and inner enamel epithelium and cusps of the enamel organ, nevertheless, the presence of TUNEL-positive cells was very rare. Bcl-2 was clearly and Bax was weakly positive in the cells throughout the dental lamina and enamel organ. These findings indicated that Fas-mediated apoptosis was inhibited by the Bcl-2 family in the development of teeth.

Genetic variants of IL-13 signalling and human asthma and atopy.

Asthma and atopy show epidemiological association and are biologically linked by T-helper type 2 (T(h)2) cytokine-driven inflammatory mechanisms. IL-4 operates through the IL-4 receptor (IL-4R, a heterodimer of IL-4Ralpha and either gammac or IL-13Ralpha1) and IL-13 operates through IL-13R (a heterodimer of IL-4Ralpha and IL-13Ralpha1) to promote IgE synthesis and IgE-based mucosal inflammation which typify atopy. Recent animal model data suggest that IL-13 is a central cytokine in promoting asthma, through the stimulation of bronchial epithelial mucus secretion and smooth muscle hyper-reactivity. We investigated the role of common genetic variants of IL-13 and IL-13Ralpha1 in human asthma, considering IgE levels. A novel variant of human IL-13, Gln110Arg, on chromosome 5q31, associated with asthma rather than IgE levels in case-control populations from Britain and Japan [peak odds ratio (OR) = 2.31, 95% CI 1.33-4.00]; the variant also predicted asthma and higher serum IL-13 levels in a general, Japanese paediatric population. Immunohistochemistry demonstrated that both subunits of IL-13R are prominently expressed in bronchial epithelium and smooth muscle from asthmatic subjects. Detailed molecular modelling analyses indicate that residue 110 of IL-13, the site of the charge-modifying variants Arg and Gln, is important in the internal constitution of the ligand and crucial in ligand-receptor interaction. A non-coding variant of IL-13Ralpha1, A1398G, on chromosome Xq13, associated primarily with high IgE levels (OR = 3. 38 in males, 1.10 in females) rather than asthma. Thus, certain variants of IL-13 signalling are likely to be important promoters of human asthma; detailed functional analysis of their actions is needed.

Three cases of primary pulmonary amyloidosis.

In three cases of primary pulmonary amyloidosis the chief complaint was hemosputum. The diagnosis of amyloidosis was made using histochemical analysis of bronchial wall biopsy in all cases; multiple nodular lesions were observed in trachea and bronchi on flexible fiberoptic bronchoscopy. The surface of the tracheobronchial mucosa was smooth but bled easily. In one patient, chest X-ray film showed a solitary nodular shadow in the left lower lung field. These three cases were tracheobronchial amyloidosis, and one case was combined with nodular parenchymal type amyloidosis.

[An autopsy case of a ruptured cerebral aneurysm treated with interlocking detachable coils].

We described an autopsy case of a ruptured aneurysmal subarachnoid hemorrhage treated with endovascular embolization by interlocking detachable coils. An 85-year-old male presented with sudden onset of severe subarachnoid hemorrhage. Cerebral angiogram revealed a right internal carotid-posterior communicating artery aneurysm. Post-operative angiogram revealed complete obliteration of the aneurysm, except for its orifice. Following the embolization of the aneurysm, tissue plasminogen activator was intrathecally perfused for anti-vasospasm treatment. Follow-up angiogram showed stable obliteration of the aneurysm, and no particular findings of cerebral vasospasm. The patient had been recovering without any neurological deficits, but died from pneumonia on the 25th day after the embolization. Autopsy findings revealed the disappearance of the subarachnoid hemorrhage, and no visible finding of cerebral infarction or edema. The inner lumen of the aneurysm was occupied by a mixture of the coils and the clots. The surface of the embolized coils was directly observed through the orifice of the aneurysm without any membranous substance from the inner lumen of the internal carotid artery. This pathological finding is different from the previously reported animal models in which the surface of the embolized coils was covered with endothelial membrane 2 weeks after embolization. Further examinations are required to clarify the pathogenesis of the endothelial regrowth.

[Relation between the sialic acid/fucose ratio in airway secretions and the degree of airway remodeling in bronchial asthma--reversibility of airflow limitation by beta-agonists and airway remodeling in bronchial asthma].

Airway remodeling caused by inflammation is believed to affect both airway hyperresponsiveness and the reversibility of airflow limitation. Airway remodeling entails changes in the bronchial secretion system. Mucin, one of the glycoprotein components of airway secretions, is a major product of submucosal glands and goblet cells. Airway remodeling causes both qualitative and quantitative changes in much production. We evaluated the relationship of airway remodeling, estimated by the change in glycoprotein in sputum, to airway hyperresponsiveness and to reversibility in patients with bronchial asthma. The %FEV1 after inhalation of a beta agonist was less in patients with severe asthma than in those with mild asthma. The sialic acid/fucose ratio in sputum correlated significantly with the slope of the dose-response curve during inhalation challenge, and with the %FEV1 after beta-agonist inhalation. These results suggest that the sialic acid/ fucose ratio in airway secretions reflects the degree of the airway remodeling in bronchial asthma.

Anomalous internal carotid artery-anterior cerebral artery anastomosis associated with fenestration and cerebral aneurysm.

A 69-year-old female presented with a ruptured aneurysm at the distal tip of a fenestrated anomalous artery which originated in the ophthalmic segment of the internal carotid artery (ICA), passed between the optic nerves, ascended along the midline, and formed the fenestration before dividing into the bilateral pericallosal arteries. The anomalous artery manifested as subarachnoid hemorrhage. Four days later, she died from severe pulmonary edema. The angiographic finding was confirmed by postmortem examination. Numerous perforating vessels from the anomalous artery and the distal ICA supplied the optic nerves and chiasm. This finding supports the idea that this anomalous vessel may be an extreme developmental variation of the prechiasmal arterial plexus.

Comparison of surface antigens on eosinophils from patients with eosinophilia.

Recent studies have suggested that there may be heterogeneity among human eosinophils. To study this further, surface antigens on blood eosinophils from patients with eosinophilia (23 bronchial asthma, 6 eosinophilic pneumonia, 1 Kimura's disease and 1 adult T-cell leukemia) and from 8 control subjects were examined using a new direct method for fluorescence detection of eosinophils. HLA-DR+ and CD4+ eosinophil counts were higher in patients with bronchial asthma and adult T-cell leukemia (ATL) than in patients from other groups and in control subjects. CD11b+ eosinophil counts in Kimura's disease and ATL were smaller than those in the other groups. CD45RO+ eosinophil counts in bronchial asthma and eosinophilic pneumonia were significantly higher (p < 0.05) compared with Kimura's disease, ATL and control subjects. CD44+ eosinophil counts in eosinophilic pneumonia were significantly higher (p < 0.05) compared with the other groups and control subjects. These results suggest the existence of functional heterogeneity in the different eosinophilic diseases, with eosinophils in bronchial asthma and eosinophilic pneumonia being more highly activated in migration, activation and immunoregulation. On the other hand, eosinophils in Kimura's disease and ATL might be functionally down-regulated. This heterogeneity of eosinophils may reflect differences in the pathogenesis of various eosinophilic diseases.

Surface antigens on eosinophils in bronchial asthma and eosinophilic pneumonia.

Surface antigens on peripheral blood eosinophils from 23 patients with bronchial asthma, 6 with eosinophilic pneumonia and 8 controls were examined using a new direct method. Peripheral blood eosinophils in bronchial asthma and eosinophilic pneumonia showed higher complexity and/or granularity than those from controls. The percentage expression of HLA DR, CD4 and CD45RO on peripheral blood eosinophils from patients with bronchial asthma were increased compared with those from patients with eosinophilic pneumonia and from the controls. These results suggest that peripheral blood eosinophils in bronchial asthma may play a role in immunoregulation via the expression of human leukocyte antigens, such as HLA-DR, CD4 and CD45RO, that interact with lymphocytes, and may function as antigen-presenting cells. Furthermore this study suggests that there may be different phenotypes of eosinophils with differing surface antigens and intercellular reactions between eosinophils and lymphocytes.

Hypersensitivity pneumonitis induced by inhalation of mushroom (Pholiota nameko) spores.

We describe the hypersensitivity pneumonitis of a 49-year-old woman who had been cultivating the edible mushroom 'Pholiota nameko' for three years. Her clinical manifestations and laboratory findings including transbronchial lung biopsy (TBLB) and bronchoalveolar lavage fluid (BALF) were consistent with those of other forms of hypersensitivity pneumonitis. Counter-immunoelectrophoresis determined the causative antigen to be the spores of Pholiota nameko. The indoor cultivation method appeared to play a major role in the occurrence of the hypersensitivity pneumonitis.