Mitsuaki Sakai

Preoperative lymphocyte count is an independent prognostic factor in node-negative non-small cell lung cancer

A number of prognostic factors have been reported in non-small cell lung cancer (NSCLC). Although lymph node metastasis is the most poorly predictive value in completely resected NSCLC, a significant number of patients have a fatal recurrence even in node-negative curative NSCLC. Recently inflammatory response has been shown as a predictive value in NSCLC. Neutrophils and lymphocytes play an important role in cancer immune response. In this study, we retrospectively examined the impact of preoperative peripheral neutrophil and lymphocyte counts on survival, and investigated the relationships of these factors to clinicopathological factors in node-negative NSCLC. A total 237 patients were evaluated. When the cut-off value of neutrophil count was 4500 mm(-3) with a maximum log-rank statistical value, overall 5-year survival rates were 79.7% for the low-neutrophil-count group and 69.5% for the high-neutrophil-count group (P=0.04). When the cut-off value of lymphocyte count was 1900 mm(-3) with a maximum log-rank statistical value, overall survival rates were 67.9% for the low-lymphocyte group and 87.7% for the high-lymphocyte group (P<0.001). High-neutrophil-counts were associated with tumor size (P=0.002) and pleural invasion (P<0.001). Low-lymphocyte-counts were correlated with vascular invasion (P=0.018) and recurrence of NSCLC (P=0.01). Multivariate analysis showed that the lymphocyte count was an independent prognostic factor (hazard ratio: 3.842; 95% confidence interval: 1.827-8.078; P<0.001), but the neutrophil count was not (P=0.185). We conclude that a peripheral lymphocyte count, which is associated with vascular invasion, is an independent prognostic factor in node-negative NCSLC.

Carcinomatous meningitis from non-small-cell lung cancer responding to gefitinib.

The prognosis for carcinomatous meningitis remains poor, and focal neurological dysfunctions usually do not improve despite the available treatment options. We report a case of carcinomatous meningitis from non-small-cell lung cancer treated with gefitinib, which brought about a sustained clinical response. A 40-year-old Japanese man was diagnosed with adenocarcinoma in the right lower lobe of the lung, and with multiple pulmonary and brain metastases. Six courses of carboplatin and paclitaxel chemotherapy and gamma-knife radiosurgery induced a near complete response in all lesions. However, 2 months later, cauda equina syndrome and left oculomotor paralysis from carcinomatous meningitis developed rapidly. Magnetic resonance imaging of the brain and spinal cord revealed the enhancement of leptomeningeal disseminations. The patient was treated with 250 mg/day gefitinib. All his neurological symptomatology disappeared within 2 weeks. The shrinkage of the leptomeningeal disseminations was confirmed by follow-up magnetic resonance imaging. The patient is currently doing well and is able to work. Cancer relapse was not observed at 4 months after the initiation of gefitinib. Although the survival benefit is controversial, gefitinib may have a role in the treatment of carcinomatous meningitis from non-small-cell lung cancer to improve neurological dysfunctions.

Pathologic Radioresponse of Preoperatively Irradiated Invasive Thymomas

Background: We have been applying preoperative radiotherapy (RT) to Masaoka stage III thymomas intending to make surgical resection more complete by reducing mass volume, to prevent possible dissemination caused by surgical manipulation and to get better survival as a result. However, the radioresponses vary from tumor to tumor. We hypothesized that thymoma is a variable radioresponsive tumor depending on pretreatment histology. Materials and Methods: Twenty-one of stage III thymomas underwent preoperative RT plus surgery followed by postoperative RT between 1982 and 2004. Reduction ratios, histopathologic changes according to WHO histologic criteria, resectability, long-term survival, and disease control, by preoperative RT were analyzed. Results: Pretreatment WHO subtypes were type AB (n = 1), B1 (5), B2 (6), B3 (4), and unclassified (5). Sixteen tumors (76.2%) decreased in size after preoperative RT with a mean (median) reduction ratio of 30.8% (27.0%). Type B1or B2 group had higher reduction ratio than type B3 group (mean value of 39.7%, 31.8%, and 21.0%, respectively, p < 0.01). Histopathologically, lymphocyte diminished markedly in type B1 thymoma, and both lymphocyte and epithelial cells diminished in type B2, whereas none of the B3 tumors showed any histologic change. The values of all the cases is 90.5% in complete resection, 19.0% in no combined resection of the adjacent organs, and 77.6% and 83.6% in overall and disease-free 10-year survival, respectively, and these value do not differ according to the WHO histologic criteria. Conclusions: This modality at modest doses was macroscopically and histopathologically effective on tumors particularly in WHO B1 and B2 thymomas than WHO B3 thymoma. The therapeutic benefit of preoperative RT followed by surgery and postoperative RT for stage III thymomas should be defined thoroughly.

High-dose concurrent chemo–proton therapy for Stage III NSCLC: preliminary results of a Phase II study

The aim of this report is to present the preliminary results of a Phase II study of high-dose (74 Gy RBE) proton beam therapy (PBT) with concurrent chemotherapy for unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients were treated with PBT and chemotherapy with monthly cisplatin (on Day 1) and vinorelbine (on Days 1 and 8). The treatment doses were 74 Gy RBE for the primary site and 66 Gy RBE for the lymph nodes without elective lymph nodes. Adapted planning was made during the treatment. A total of 15 patients with Stage III NSCLC (IIIA: 4, IIIB: 11) were evaluated in this study. The median follow-up period was 21.7 months. None of the patients experienced Grade 4 or 5 non-hematologic toxicities. Acute pneumonitis was observed in three patients (Grade 1 in one, and Grade 3 in two), but Grade 3 pneumonitis was considered to be non-proton-related. Grade 3 acute esophagitis and dermatitis were observed in one and two patients, respectively. Severe ( ≥ Grade 3) leukocytopenia, neutropenia and thrombocytopenia were observed in 10 patients, seven patients and one patient, respectively. Late radiation Grades 2 and 3 pneumonitis was observed in one patient each. Six patients (40%) experienced local recurrence at the primary site and were treated with 74 Gy RBE. Disease progression was observed in 11 patients. The mean survival time was 26.7 months. We concluded that high-dose PBT with concurrent chemotherapy is safe to use in the treatment of unresectable Stage III NSCLC.

Limited thymectomy for stage I or II thymomas

BACKGROUND Once an anterior mediastinal tumor has been diagnosed as a thymoma, complete excision including the thymic gland and perithymic fat is currently the procedure of choice. However, little is known about the clinical outcome of grossly encapsulated thymomas excised only with the surrounding tissue while leaving a part of the thymic gland. METHODS A retrospective historical comparative study was conducted on 79 patients who had received surgery for stage I (n=25) or stage II (n=54) thymomas. Total thymectomy was performed in 61 patients (Total Thymectomy Group), whereas resection of tumors with only the surrounding tissue was carried out in 18 (Limited Thymectomy Group). The follow-up interval was longer in the Limited Thymectomy Group because these patients were treated longer ago (104.2+/-58.1 months vs 67.3+/-54.8 months, p<0.05). RESULTS One case in the Limited Thymectomy Group showed postoperative myasthenia gravis (5.6%). Two patients with multiple thymomas (2.5%) were treated with total thymectomy. One case in the Limited Thymectomy Group, which had been diagnosed as Masaoka stage II and WHO type B3 at initial surgery, recurred. None died of tumor progression in this study. Disease free survival rates at 10 years did not differ between the Limited Thymectomy and Total Thymectomy Groups (85.7% and 82.0%, respectively). There were no statistical differences in the incidence of postoperative myasthenia gravis and disease free survival between the two groups. CONCLUSION Resection of thymomas with surrounding tissue instead of total thymectomy can be indicated for stage I or II thymomas in light of disease free and overall survival, post-operative onset of MG, and the incidence of multiple lesions.

Postoperative Follow-Up for Patients with Non-Small Cell Lung Cancer

Background: It is unclear whether postoperative follow-up by thoracic surgeons or chest physicians for non-small cell lung cancer (NSCLC) alters survival. Patients and Methods: The charts of 1,398 NSCLC patients, diagnosed between 1980 and 2008, were reviewed. Prognostic factors contained therein were evaluated using univariate and multivariate analyses. Patients were divided into 2 groups according to the doctor in charge of their postoperative follow-up: the thoracic surgeon group and the chest physician group. The doctors in charge of following up the patients were also analyzed for prognostic significance. Results: In the univariate and multivariate analyses, age 65 years or younger, female sex, early pathological stage, Charlson Index score of 0–1, absence of adjuvant therapy, and follow-up by a chest physician were significantly favorable prognostic factors. Exam-ined overall, NSCLC patients in the chest physician group had longer survival than those in the thoracic surgeon group. The difference in survival of patients with advanced disease was also statistically significant between these 2 groups. Conclusions: Our results indicate that early detection of asymptomatic disease by regular follow-up including chest computed tomography scan may improve the chance of treatment with curative intent and thus may increase survival, irrespective of the doctor in charge of follow-up.

New method for evaluation of lung lymph flow rate with intact lymphatics in anaesthetized sheep

Aim:  Lung lymph has commonly been studied using a lymph fistula created by tube cannulation into the efferent duct of the caudal mediastinal node in sheep. In this method, the tail region of the caudal mediastinal node is resected and the diaphragm is cauterized to exclude systemic lymph contamination, and cannulation is performed into one of the multiple efferent ducts originating from the caudal mediastinal node. Moreover, the pumping activity of lymphatics might be diminished by cannulation. Therefore, the purpose of the study was to evaluate the flow rate of lung lymph with maintenance of intact lymphatic networks around the caudal mediastinal node to the thoracic duct in sheep.

Observational study on the efficacy and safety of erlotinib in patients with non-small cell lung cancer

To evaluate the efficacy and safety of erlotinib for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The study involved 307 patients treated with erlotinib at 14 sites (17 departments) in Ibaraki (Japan) between December 2007 and December 2010. The tumor response and disease control rates were 11.1 and 46.3% in all patients, respectively. The median time to treatment failure and survival time were 1.6 months (95% confidence interval, 41–57 days) and 5.3 months (134–181 days) in all patients, respectively. Survival was significantly prolonged in EGFR mutation-positive patients compared with negative patients. EGFR mutation-negative patients who presented with a skin rash had significantly prolonged survival compared with those without a skin rash. The most common adverse event was skin disorder, followed by diarrhea. Although 45.6% of the patients in this study received erlotinib as a fourth-line or subsequent treatment, the results from this study were similar to those of clinical studies. We deduce that erlotinib is effective against NSCLC and is tolerated in clinical practice.

Video-Assisted Thoracoscopic Conservative Repair of Postoperative Lobar Torsion

Postoperative lobar torsion is a rare and life-threatening complication. Several previous cases have been treated with completion lobectomy. We report successful surgical repair of middle lobar torsion after upper lobectomy. On postoperative day 4, the middle lobe was rotated approximately 150 degrees counterclockwise. The surface of the middle lobe appeared congestive, but its surface color, elasticity, and compliance improved 1 h after detorsion. We preserved the middle lobar function and prescribed warfarin for pulmonary vein thrombosis. When preserving a twisted lobe, it is important to consider the damage to the twisted lung, risk of thrombosis, and residual pulmonary function.

Increased Fluorodeoxyglucose-Uptake in Positron Emission Tomography with an Endobronchial Schwannoma Occluding the Left Main Stem Bronchus

A 48-year-old woman suffering from left-side back pain and a 3-year history of coughing was found to have a submucosal lesion occluding the left main bronchus by chest computed tomographic scanning and bronchoscopy. The lesion showed a high standardized uptake value of 3.9 in positron emission tomography with fluorine-18 labeled fluorodeoxyglucose scanning (FDG-PET). The tumor was resected with the posterior wall of the left main bronchus through a postrolateral thoracotomy, and a large defect in the membranous portion was reconstructed in the manner of wedge bronchoplasty, preserving the lung parenchyma. Pathological findings confirmed the diagnosis of schwannoma with no malignant cells. Schwannoma should be included in the differential diagnosis of endobronchial tumors with high standardized uptake values in FDG-PET.