Toshiteru Tokunaga

Sublobar Resection Provides an Equivalent Survival After Lobectomy in Elderly Patients With Early Lung Cancer

BACKGROUND Sublobar resection is indicated for early-stage non-small cell lung cancer in patients with a perioperative risk associated with impaired medical conditions. This study was conducted to investigate the clinical impact of this procedure in the elderly. METHODS The patients who underwent complete resection for stage IA non-small cell lung cancer from 1990 and 2007 were enrolled (n = 764). Two age groups were defined as elderly (≥75 years) and younger (<75 years) patients. The 5-year survival, recurrence, and postoperative complications after sublobar resection were compared with those after standard lobectomy according to age group. RESULTS There were 133 elderly patients (79 standard lobectomies and 54 sublobar resections) and 631 younger patients (539 standard lobectomies and 92 sublobar resections). While the 5-year survival after sublobar resection was significantly inferior to that after standard lobectomy in the younger group (64.0% and 90.9%, respectively, p < 0.0001), however, no substantial difference was observed in the elderly (67.6% and 74.3%, p = 0.92). Locoregional recurrence rates were higher in patients after sublobar resection than those after standard lobectomy in both the elderly (11.1% vs 1.3%) and the younger (12.0% vs 1.5%) groups. No significant difference in postoperative complications was observed between the types of surgery in the elderly. CONCLUSIONS Sublobar resection for stage IA is considered to be an appropriate treatment in the elderly patients as this procedure provides an equivalent long-term outcome in comparison with lobectomy. A larger scale study with matching patients is necessary to confirm the noninferiority of sublobar resection in comparison with standard lobectomy in this population.

Occult mediastinal lymph node metastasis in NSCLC patients diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT: Risk factors, pattern, and histopathological study

BACKGROUND Integrated F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is widely used for mediastinal lymph node (MLN) staging in patients with non-small cell lung cancer (NSCLC). However, FDG-PET/CT has certain limitations. Prediction of occult MLN metastasis could allow selection of candidates for preoperative cervical mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration. This study defined risk factors for occult MLN metastasis in patients with NSCLC patients who were diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT. METHODS Consecutive patients with NSCLC who underwent staging using integrated FDG-PET/CT as an adjunct to CT prior to lung resection from October 2006 to September 2009 were evaluated retrospectively. The prevalence of MLN metastasis in patients diagnosed as clinical N0-1 was analyzed according to clinicopathological factors such as tumor location, tumor size, histology, and FDG uptake by the primary tumor. Risk factors for occult MLN metastasis were defined by multivariate analysis. Patterns of occult MLN metastasis were also analyzed and the involved MLNs were further examined histopathologically. RESULTS The incidence of MLN metastasis was 11% (24 patients of 224). Multivariate analysis identified adenocarcinoma (P=0.04), tumors located in upper or middle lobe (P=0.02), tumor size >3 cm (P=0.01), and SUV(max) of primary tumor >4.0 g/ml (P=0.04) as significant risk factors for MLN metastasis. The pattern of occult MLN metastasis was typical for NSCLC cases. The size of metastatic foci were small, with 68% of foci smaller than 4.0mm. CONCLUSIONS The present study demonstrated that adenocarcinoma, tumors located in the upper or middle lobe, tumor size >3 cm, and SUV(max) of primary tumor >4.0 g/ml are risk factors for occult MLN metastasis in patients with NSCLC who were diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT. Patients with tumors located in the right upper or middle lobe are considered candidates for cervical mediastinoscopy because the involved metastatic mediastinal lymph nodes are easily accessible by these modalities.

Long-term results of surgical resection for pulmonary metastasis from renal cell carcinoma: a 25-year single-institution experience

OBJECTIVE Despite the report of new treatment options, surgery remains the best treatment for pulmonary metastases from renal cell carcinoma (RCC). Repeat resection is also an effective means for recurrent pulmonary metastases. The aim of the present study was to define the prognostic factors for survival after pulmonary metastasectomy from RCC based on a 25-year single-centre experience. METHODS Between 1973 and 2008, 59 thoracotomies on 48 patients (38 men, 10 women) were performed in our hospital. Repeat resections were performed in eight patients. The clinicopathological and surgical data of these patients obtained from the medical records were analysed. The time interval between lung resection and death, or latest follow-up, ranged from 3 to 177 months (median 39 months). Survival analysis was conducted by the Kaplan-Meier method and log-rank test. Multivariate analysis was performed using the Cox multivariate proportional hazard model. RESULTS The cumulative 3-, 5- and 10-year survival rates were 60%, 47% and 18%, respectively. Multivariate analysis identified disease-free interval (DFI) (≥ 2 years) and complete resection as significant prognostic factors for survival. Among eight patients, who underwent repeat resection, two remain alive with no evidence of disease. These two patients had long DFI and long DFI-2 (time from first pulmonary metastasectomy to diagnosis of recurrent pulmonary metastasis). CONCLUSIONS The results showed that (1) surgical resection of pulmonary metastasis from RCC has a favourable outcome in selected patients, (2) DFI and completeness of resection are prognostic markers for survival after pulmonary metastasectomy and (3) repeat lung resection for metastatic RCC is a safe procedure that provides satisfactory patient outcomes.

Local IL-17 production and a decrease in peripheral blood regulatory T cells in an animal model of bronchiolitis obliterans.

Background. Recently, it has been reported that Th17 contributes to allograft rejection after transplantation. We investigated the alteration of Th17 and regulatory T cells (Treg) distribution in an animal model of bronchiolitis obliterans following ectopic tracheal transplantation model. Methods. Tracheal grafts from B6 mice transplanted into subcutaneous sites of C3H mice. Allografts were histologically evaluated, and expressions of CD4, CD8, CD25, CD28, CD127, CD152 and Foxp3, and intracellular interleukin (IL)-4, -6, -17, and interferon-&ggr;, in peripheral blood lymphocytes were analyzed. Tracheal graft IL-6 and -17 mRNA expression was assessed using a quantitative reverse-transcriptase polymerase chain reaction. All the data in allogenic transplantation was compared with those in isograft controls. In addition, the effect of IL-6 neutralization on the allograft was evaluated with histopathology and the IL-17 mRNA expression. Results. Treg was significantly lower in peripheral blood of allogenic mice, whereas no significant difference in Th17 in the CD4+ T-cell population was observed after allogenic or isogenic transplantation. Locoregional histologic examination revealed the presence of IL-6-producing lymphocytes and endothelium in the allograft, and the luminal obliteration by fibroblast proliferation. Both IL-6 and IL-17 mRNA levels were elevated in the allograft. Severity of tracheal obliteration and IL-17 mRNA level was significantly suppressed in the IL-6 neutralized allografts. Conclusions. After allograft in a mouse bronchiolitis obliterans model, IL-17 production increases locally without an alteration in peripheral blood Th17 cells, whereas peripheral Tregs decreases. Th17 cells, which can be regulated by IL-6 stimulation, may play a role in posttransplantation rejection of the allograft.

Outcome of surgical resection for recurrent pulmonary metastasis from colorectal carcinoma.

BACKGROUND The outcomes after repeat pulmonary resection for colorectal cancer (CRC) and the factors associated with the prognosis of these patients remain uncharacterized. METHODS Data on 156 patients who underwent curative resection of pulmonary metastasis from CRC were reviewed. Repeat pulmonary resection was performed in 25 patients; the present study examined the outcomes and factors associated with prognosis after repeat pulmonary resection. RESULTS The 5-year survival rate after the first pulmonary resection was 56.2%. A multivariate analysis identified a histological type other than well-differentiated adenocarcinoma, a high prethoracotomy serum carcinoembryonic antigen (CEA) level, and the presence of hilar or mediastinal lymph node metastasis as poor prognostic factors for the first pulmonary resection. The 5-year survival rate after repeat pulmonary resection was 42.1%. Hilar or mediastinal lymph node metastasis at the time of the repeat resection was significantly associated with poor survival. CONCLUSIONS Repeat pulmonary resection for metastatic CRC provides satisfactory outcomes. Hilar or mediastinal lymph node involvement is consistently associated with a poor prognosis after the first and repeat pulmonary resections.

Outcome of surgical resection of pulmonary metastasis from urinary tract transitional cell carcinoma

There is little information on pulmonary metastasectomy of urinary tract transitional cell carcinoma (TCC). In this study, we examined the long-term outcome and the factors associated with long-term survival after pulmonary metastasectomy of urinary tract TCC based on a 20-year single center experience. Between 1984 and 2005, 18 patients (12 men, six women) underwent pulmonary metastasectomy of the urinary tract TCC in our hospital. The clinicopathological and surgical data of these patients obtained from the medical records were analyzed in this retrospective study. The time interval between lung resection and death, or latest follow-up ranged from two to 200 months (median 52). Survival analysis was conducted by the Kaplan-Meier method and log-rank test. The cumulative three- and five-year survival rates were 59.8% and 46.5%, respectively. The number of resected metastatic tumors (solitary vs. multiple) was associated with long-term survival (P<0.05). The five-year survival rate of patients with solitary metastasis was 85.7% while that of patients with multiple metastases was 20.0%. Pulmonary metastasectomy of urinary tract TCC is associated with a favorable outcome, and solitary metastasis is associated with long-term survival. Aggressive management of solitary pulmonary metastasis from a urinary tract TCC is feasible in selected patients.

Biological implications of thymectomy for myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies to the striated muscle tissue. It is often treated by thymectomy. We review recent studies to investigate the biological implications of thymectomy. In anti-acetylcholine receptor antibody (anti-AchR Ab)-positive patients without a thymoma, abnormal germinal center formation in the thymus seems to play an essential role in the pathogenesis of MG. Specific differentiation of B cells producing anti-AchR Ab takes place uniquely in the thymus, and thymectomy is thought to assist in terminating the provision of high-affinity anti-AchR antibody-producing cells to peripheral organs. Thymectomy is not indicated for anti-AchR Ab-negative MG patients who are antimuscle specific kinase antibody (anti-MuSK Ab)-positive, although some anti-MuSK Ab-negative patients may benefit from the procedure. A thymoma can be considered as an acquired thymus with insufficient function of negative selection. The resection of a thymoma is thought to terminate the production of selfreactive T cells. Thus, the biological implications of thymectomy for MG have been partially revealed. Nevertheless, additional studies are needed to elucidate the ontogeny of T cells that recognize AchR and the mechanism of the activation of anti-AchR antibodies producing B cells.

Esophageal Schwannoma: Report of a Case

We report a case of esophageal schwannoma in a 46-year-old woman who presented with rapidly progressive dyspnea and dysphagia. Chest computed tomography showed a large mediastinal mass, which was extrinsically compressing the trachea, widely adjacent to the upper thoracic esophagus. We performed an axillary right thoracotomy to enucleate the tumor, which was located in the esophageal muscle layer. A definite diagnosis of esophageal schwannoma was made from the pathologic findings, which included positive immunohistochemical staining for S-100 protein and negative staining for c-kit and CD34.

Bilateral ovarian metastasis of non-small cell lung cancer with ALK rearrangement

The discovery of a distinct subtype of non-small cell lung cancer (NSCLC) positive for rearrangement of the anaplastic lymphoma kinase gene (ALK) has had a substantial impact on personalized therapy for this disease. The clinical features associated with metastasis in individuals with ALK rearrangement-positive NSCLC remain to be fully characterized, however. We now describe a case of ovarian metastasis from NSCLC with ALK rearrangement. A 39-year-old woman underwent a right middle lobectomy for acinar-type adenocarcinoma of the lung (pT2aN2M0, stage IIIA). Fluorescence in situ hybridization (FISH) analysis of the resected tumor tissue revealed the presence of an ALK rearrangement. Twenty months later, a large intrapelvic mass was detected in the patient at follow-up. She underwent both left salpingo-oophorectomy and right ovarian cystectomy. Histological examination of the ovarian tumors showed acinar adenocarcinoma, and FISH analysis revealed the presence of ALK rearrangement, confirming a diagnosis of ALK rearrangement-positive NSCLC with ovarian metastasis. Although the ovary is an uncommon site for metastasis from lung cancer, physicians should be aware of the possibility for such metastasis during follow-up for female patients with ALK rearrangement-positive NSCLC. Further investigation is warranted to clarify the incidence of ovarian metastasis in NSCLC patients with ALK rearrangement.

Differences in chemosensitivity between primary and paired metastatic lung cancer tissues: In vitro analysis based on the collagen gel droplet embedded culture drug test (CD-DST)

BACKGROUND To elucidate the differences in chemosensitivity to anticancer drugs between primary and metastatic lesions in non-small cell lung cancer (NSCLC) patients, we examined the in vitro chemosensitivities of surgically resected NSCLC tissues. METHODS A total of 32 specimens were enrolled: 26 specimens of primary lesions paired with metastases in the lymph node, 3 specimens of primary lesions paired with metastases in the adrenal gland, and 3 specimens of primary lesions paired with metastases in the lung. The collagen gel droplet embedded culture drug test (CD-DST) was applied to examine the sensitivity of the tissues to anticancer drugs, including cisplatin, gemcitabine, vinorelbine, docetaxel and 5-fluorouracil. RESULTS The degree of in vitro sensitivity to each anticancer drug varied between the primary and metastatic lesions. The sensitivity of the paired metastatic lesions was significantly lower than that of the primary lesions only for gemcitabine (P=0.029), vinorelbine (P=0.012), and docetaxel (P=0.009). The incidence of cases diagnosed as CD-DST-sensitive among the paired metastatic lesions was significantly lower than that for the primary lesions for vinorelbine (P=0.035) or docetaxel (P=0.022). The difference in the sensitivity to gemcitabine between the primary and paired non-lymphatic metastases was clearer than that between the primary lesion and paired lymph node metastases. CONCLUSIONS The sensitivities of the paired metastatic lesions to some anticancer drugs were significantly lower than those of the primary lesions. When performing chemotherapy based on CD-DST data using primary tumors from patients with postoperative recurrence, an appropriate regimen can be selected by carefully considering these differences.