Keiji Ohata

Evaluation of the new TNM staging system proposed by the International Association for the Study of Lung Cancer at a single institution

OBJECTIVE The seventh TNM Classification of Malignant Tumours will be published in 2009. The International Association for the Study of Lung Cancer has proposed a revision of the current pathologic staging system. We illustrated the effects of this new system and pointed out potential problems using a retrospective study of surgical cases of non-small cell lung cancer at our institution. METHODS Subjects were 1532 patients for whom current pathologic staging was possible. These data were migrated into the new staging system. The numbers of patients at various stages determined by using the current and new staging systems were, respectively, as follows: IA (n = 700, n = 700), IB (n = 338, n = 249), IIA (n = 49, n = 164), IIB (n = 129, n = 116), IIIA (n = 204, n = 234), IIIB (n = 77, n = 17), and IV (n = 35, n = 52). Prognoses were compared by using the current and the new systems. RESULTS By using the new staging system, 5-year survivals by T classifications were as follows: T1a, 82.6%; T1b, 73.3%; T2a, 63.5%; T2b, 50.1%; T3, 40.6%; and T4, 34.6%. There were significant differences between the new T1a and T1b (P = .0026), T1b and T2a (P = .0027), and T2a and T2b (P = .0062) classifications. In the current system 5-year survivals based on pathologic stages were as follows: IA, 84.8%; IB, 72.9%; IIA, 53.8%; IIB, 53.7%; IIIA, 31.8%; IIIB, 34.0%; and IV, 27.1%. There were significant differences between stages IA and IB (P < .0001) and stages IIB and IIIA (P = .0006). In the new system these were as follows: IA, 84.8%; IB, 75.2%; IIA, 62.4%; IIB, 52.1%; IIIA, 32.4%; IIIB, 15.2%; and IV, 30.6%. There were significant differences between stages IA and IB (P = .0004), IB and IIA (P = .0195), IIA and IIB (P = .0257), IIB and IIIA (P = .0040), and IIIA and IIIB (P = .0399). CONCLUSION Although the outcomes for stages IIIB and IV were reversed, the new pathologic staging system was considered valid based on our single-institution evaluation.

Postrecurrence survival in patients with stage I non-small cell lung cancer

OBJECTIVE Postoperative recurrence is a major obstacle to achieving a cure and long-term survival in patients with non-small lung cancer. However, prognostic factors and the efficacy of therapy after recurrence remain controversial. We evaluated the clinical outcomes of patients with resected lung cancer for postrecurrence prognostic factors. METHODS Patients who underwent complete resection with systematic lymph node dissection for stage I non-small cell lung cancer were selected. Cases of low-grade malignancy, preoperative therapy, history of previous malignancy or death within 30 days of operation were excluded. A total of 397 patients were retrospectively reviewed. RESULTS Out of 87 patients who had recurrence after surgery, 45 had symptoms at the initial recurrence. The initial recurrent site was local in 30 patients and distant in 57. Single-site recurrence was detected in 48 patients and multiple-site recurrence was seen in 39. The recurrent site was the ipsilateral thorax in 49 patients, the contralateral thorax in 32, the cervico-mediastinum in 15, brain in 12 and bone in 11. Surgery was performed in 20 patients, whereas non-surgical therapy was performed in 55 (chemotherapy, 16; radiation therapy, 33; chemo-radiation therapy, 6). Prognostic analysis of factors related to recurrent status demonstrated that symptoms at the initial recurrence, cervico-mediastinal metastasis, liver metastasis and postrecurrence therapy were significant prognostic factors in both univariate and multivariate analysis. CONCLUSIONS Symptoms at the initial recurrence, cervico-mediastinal metastasis and liver metastasis were worse prognostic factors after recurrence. Postrecurrence therapy for the initial recurrence may prolong survival after recurrence.

Surgical treatment for non-small cell lung cancer in octogenarians--the usefulness of video-assisted thoracic surgery.

The purpose of this study was to investigate whether surgical treatment for non-small cell lung cancer (NSCLC) confers a survival benefit in octogenarians, and whether video-assisted thoracic surgery (VATS) is effective in terms of postoperative morbidity, mortality, and quality of life (QOL). Among 1684 patients with primary NSCLC who underwent pathologically complete resection, 95 were octogenarians. Operation was performed by the VATS approach (VATS group, n=58) or the standard thoracotomy (ST group, n=37). Although postoperative cardiopulmonary complications occurred in 20 cases (21.1%), all were manageable. In the ST group cardiopulmonary complications occurred more frequently than in the VATS group (P=0.030). The overall 5-year survival rate of the 95 octogenarians, including deaths from all causes, was 54.4%. The overall 5-year survival rate of patients with stage IA disease was 65.2%. These outcome data were not significantly worse than those for patients aged 79 years or under (P=0.136). There was no significant difference in overall 5-year survival rates between the ST group and the VATS group (P=0.144). The VATS approach for pulmonary resection is recommended for octogenarians with NSCLC. Surgical resection is the optimal treatment for stage IA NSCLC, and therefore, advanced age is not a contraindication for curative resection.

Rapidly expanding extrapleural hematoma

We present a rare case of extrapleural hematoma due to chest trauma in an anticoagulated male patient. Chest computed tomography revealed multiple left rib fractures and a D-shaped opacity in the upper left side of the thorax suggesting extrapleural hematoma, which was caused from continuous bleeding. His past history included alcoholic liver cirrhosis, which caused thrombocytopenia and coagulopathy. Therefore, the hematoma was expanding, causing circulatory and ventilatory disturbance and severe anemia despite the difficulty of expanding in the extrapleural space. As the bleeding did not stop, even after intercostal artery angiography with embolization was performed, surgical treatment was undertaken to control the bleeding and evacuate the huge hematoma. The problems associated with the diagnosis and treatment of an extrapleural hematoma are discussed in the light of this case.

Inhibition of Toll-like receptor 4 signaling ameliorates lung ischemia-reperfusion injury in acute hyperglycemic conditions.

BACKGROUND Recent lung transplantation studies have shown that peri-operative hyperglycemia is an important factor affecting recipient survival; however, its underlying mechanisms are not well understood. We hypothesized that acute hyperglycemia exacerbates lung ischemia-reperfusion injury (IRI) through up-regulation of Toll-like receptor 4 (TLR4) signaling pathways. METHODS C57BL/6Ncr mice were divided into 3 treatment groups: sham; IRI; and IRI under acute hyperglycemic conditions (IRI+HG). Mice in the IRI and IRI+HG groups were exposed to IRI via clamping the left hilum for 1 hour, followed by reperfusion for 2 hours. Acute hyperglycemia was established by glucose injection. The severity of lung injury and TLR4 signaling pathway activity were assessed. Further, we performed a pharmacologic blockade of TLR4 signaling to determine the effect of TLR4 signaling inhibition on lung injury. RESULTS Compared with normoglycemic mice, hyperglycemic mice had 2-fold higher blood glucose levels (p < 0.001). Pulmonary compliance was significantly lower, and airway resistance was significantly higher, in the IRI+HG group than in the IRI group (p < 0.05). Levels of inflammatory cytokines in bronchoalveolar lavage fluid were significantly higher in the IRI+HG group than in the IRI group. Correspondingly, TLR4 signaling pathways were up-regulated in the IRI+HG group. Moreover, pharmacologic inhibition of TLR4 signaling significantly decreased lung injury markers under hyperglycemic conditions. CONCLUSIONS Acute hyperglycemia exacerbated lung IRI and was associated with up-regulation of TLR4 signaling pathways. Pharmacologic inhibition of TLR4 signaling ameliorated lung IRI with acute hyperglycemia. Targeting TLR4 appears to be a promising approach to managing coexisting pathologies in lung transplant recipients.

Pediculate mucinous cystadenoma difficult to differentiate from pleural tumor.

We present a case of benign pediculate mucinous cystadenoma in a 60-year-old man. The tumor, which was connected with the lung parenchyma, was difficult to distinguish from a pleural tumor radiographically. Initially, computed tomographic-guided needle aspiration biopsy was performed to confirm the diagnosis, but this was unsuccessful. Therefore, surgical resection was performed to diagnose and treat the tumor, and pathologic examination of the specimen revealed mucinous cystadenoma. The problems associated with the diagnosis and treatment of pediculate mucinous cystadenoma are discussed in light of this case.

Association of Local Intrapulmonary Production of Antibodies Specific to Donor Major Histocompatibility Complex Class I With the Progression of Chronic Rejection of Lung Allografts

Background Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA. Methods Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats. Rats that underwent allogeneic lung transplantation were subsequently administered cyclosporine until day 14 (short immunosuppression) or day 35 (long immunosuppression). The lung grafts and spleens of recipient animals were tissue cultured for 4 days, and the titer of antibody against donor major histocompatibility complex molecules was assayed by flow cytometry. Explanted lung grafts were also evaluated pathologically. Results By day 98, DSA titers in supernatants of lung graft (P = 0.0074) and spleen (P = 0.0167) cultures, but not serum, from the short immunosuppression group were significantly higher than titers in syngeneic controls. Cultures and sera from the long immunosuppression group showed no production of DSA. Microscopically, the lung grafts from the short immunosuppression group showed severe bronchiole obliteration and parenchymal fibrosis, along with lymphoid aggregates containing T and B cells, accompanying plasma cells. These findings suggestive of local humoral immune response were not observed by days 28 and 63. Conclusions DSA can be locally produced in chronically rejected lung allografts, along with intragraft immunocompetent cells. Clinical testing of DSA in serum samples alone may underestimate lung allograft dysfunction.

Novel thermographic detection of regional malperfusion caused by a thrombosis during ex vivo lung perfusion

OBJECTIVES Although ex vivo lung perfusion (EVLP) has been clinically applied as a novel rig to evaluate marginal donor lungs, no parameters have been reported to objectively detect regional lung damage during EVLP. The aim of this study was to investigate whether regional donor lung malperfusion-related damage caused by a thrombus could be detected by thermography during EVLP. METHODS Lewis rats were divided into two groups: the Thrombosis group and the Control group (n = 6 in each group). All rats were heparinized and the lungs were flushed with 20 ml of Steen solution. In the Thrombosis group, a 30-mg artificial thrombus was inserted into the left main pulmonary artery. All the lungs were perfused and ventilated using the EVLP system. Perfusion flow was increased every 2 min up to 10 ml/min. The lungs were evaluated by collecting thermographical and physiological data during EVLP. RESULTS Pulmonary artery pressure was higher and lung compliance was lower in the Thrombosis group compared with those in the Control group (P = 0.0005 and <0.0001, respectively). Macroscopically, no differences were seen between the perfused area and the malperfused area, whereas significant differences were detected between them by thermography. The surface temperature of both lungs in the Control group and the right lungs in the Thrombosis group rose with increasing perfusion flow, whereas the surface temperature of the left lungs in the Thrombosis group did not rise (P < 0.0001). CONCLUSIONS Although physiological data could possibly imply the existence of thrombi in the Thrombosis group, it could not reveal which area was obstructed by thrombi; however, thermography could detect a malperfused region. Thermographical evaluation may become a promising strategy to detect regional damage in donor lungs.

Thoracoscopic Bronchoplasty Using Continuous Sutures in Complete Monitor View

Thoracoscopic sleeve lobectomy in a complete monitor view is rarely reported. In thoracoscopic bronchoplasty, the insertion of a needle to the optimal point at the appropriate angle is difficult because of the restricted movement, and the limitation of monitor visualization complicates the creation of extraluminal ligations for anastomosis of the deep part of the bronchus. We report a case of sleeve resection of the right upper lobe with continuous sutures in a complete monitor view. Anastomosis with continuous sutures, which requires only three knots, is thought to be useful for bronchoplasty in thoracoscopic surgical procedures.

Rib chondrosarcoma with intramedullary progression completely resected by magnetic resonance imaging: useful short inversion time inversion recovery sequence

Chondrosarcoma is the second most common bone sarcoma, for which complete resection is the only effective treatment. Herein, we report a case of completely resected rib chondrosarcoma protruding through the bone marrow. An intramedullary lesion was revealed with magnetic resonance imaging using short inversion time inversion recovery sequence (STIR-MRI), but was not depicted by computed tomography. STIR-MRI is highly sensitive for the detection of bone tumors due to the suppression of peritumoral soft tissue signals, and is critical for radical resection of chondrosarcoma.