A proposal for a comprehensive risk scoring system for predicting postoperative complications in octogenarian patients with medically operable lung cancer: JACS1303.

OBJECTIVES: Although some retrospective studies have reported clinicopathological scoring systems for predicting postoperative complications and survival outcomes for elderly lung cancer patients, optimized scoring systems remain controversial. METHODS: The Japanese Association for Chest Surgery (JACS) conducted a nationwide multicentre prospective cohort and enrolled a total of 1019 octogenarians with medically operable lung cancer. Details of the clinical factors, comorbidities and comprehensive geriatric assessment were recorded for 895 patients to develop a comprehensive risk scoring (RS) system capable of predicting severe complications. RESULTS: Operative (30 days) and hospital mortality rates were 1.0% and 1.6%, respectively. Complications were observed in 308 (34%) patients, of whom 81 (8.4%) had Grade 3-4 severe complications. Pneumonia was the most common severe complication, observed in 27 (3.0%) patients. Five predictive factors, gender, comprehensive geriatric assessment75: memory and Simplified Comorbidity Score (SCS): diabetes mellitus, albumin and percentage vital capacity, were identified as independent predictive factors for severe postoperative complications (odds ratio = 2.73, 1.86, 1.54, 1.66 and 1.61, respectively) through univariate and multivariate analyses. A 5-fold cross-validation was performed as an internal validation to reconfirm these 5 predictive factors (average area under the curve 0.70). We developed a simplified RS system as follows: RS = 3 (gender: male) + 2 (comprehensive geriatric assessment 75: memory: yes) + 2 (albumin: <3.8 ng/ml) + 1 (percentage vital capacity: ≤90) + 1 (SCS: diabetes mellitus: yes). CONCLUSIONS: The current series shows that octogenarians can be successfully treated for lung cancer with surgical resection with an acceptable rate of severe complications and mortality. We propose a simplified RS system to predict severe complications in octogenarian patients with medically operative lung cancer. Trial Registration Number: JACS1303 (UMIN000016756).

A randomized phase II study to assess the effect of adjuvant immunotherapy using α-GalCer-pulsed dendritic cells in the patients with completely resected stage II-IIIA non-small cell lung cancer: study protocol for a randomized controlled trial.

BACKGROUND: As the toxicity associated with the α-GalCer-pulsed dendritic cell (DC) therapy could be considered to be negligible, its addition to postoperative adjuvant chemotherapy would be expected to greatly improve the therapeutic effect, and could result in prolonged survival. The aim of the present study is to compare the therapeutic efficacy of alpha-galactosylceramide-pulsed DC therapy in patients who have undergone a complete resection of stage II-IIIA non-small-cell lung cancer (NSCLC) followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to that in patients who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only). METHODS: Subsequent to the complete resection of NSCLC, followed by the administration of cisplatin plus vinorelbine dual-agent combination adjuvant chemotherapy, patients who satisfy the inclusion criteria will be randomly allocated to either the α-GalCer-pulsed DC immune therapy group, or the standard treatment group. In total, 56 patients will be included in the study. The primary endpoint is recurrence-free survival, and the secondary endpoints are natural killer T-cell-specific immune response, the frequency of toxic effects and safety, and overall survival. DISCUSSION: In order to determine the efficacy of α-GalCer-pulsed DC therapy, the present study compares patients with stage II-III NSCLC who underwent complete surgical resection followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to those who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only). TRIAL REGISTRATION: UMIN000010386 ( R000012145 ). Registered on 1 April 2013. UMIN-CTR is officially recognized as a registration site which satisfies ICMJE criteria.

The Outcomes of a Limited Resection for Non-Small Cell Lung Cancer Based on Differences in Pathology.

OBJECTIVE: A precise preoperative diagnosis of in situ or minimally invasive carcinoma may identify patients who can be treated by limited resection. Although some clinical trials of limited resection for lung cancer have started, it will take a long time before the results will be published. We have already reported a large-scale study of limited resection. We herein report the data for a subclass analysis according to differences in pathology. METHODS: Data from multiple institutions were collected on 1710 patients who had undergone limited resection (segmentectomy or wedge resection) for cT1N0M0 non-small cell carcinoma. The disease-free survival (DFS) and recurrence-free proportion (RFP) were analyzed. Small cell carcinomas and carcinoid tumors were excluded from this analysis. Adenocarcinomas were sub-classified into four groups using two factors, the ratio of consolidation to the tumor diameter (C/T) and the tumor diameter alone. RESULTS: The median patient age was 64 (20-75) years old. The mean maximal diameter of the tumors was 1.5 ± 0.5 cm. The DFS and RFP at 5 years based on the pathology were 92.2 and 94.7 % in adenocarcinoma (n = 1575), 76.3 and 82.4 % in squamous cell carcinoma (SqCC) (n = 100), and 73.6 and 75.9 % in patients with other tumors (n = 35). The prognosis of adenocarcinoma in both groups A (C/T ≤0.25 and tumor diameter ≤2.0 cm) and B (C/T ≤0.25 and tumor diameter >2.0 cm) was good. In SqCC, only segmentectomy was a favorable prognostic factor. In the groups with other pathologies, large cell carcinomas were worse in prognosis (the both DFS and RFP: 46.3 %). CONCLUSION: Knowing the pathological diagnosis is important to determine the indications for limited resection. Measurement of the tumor diameter and C/T was useful to determine the indications for limited resection for adenocarcinoma. Limited resection for adenocarcinomas is similar with a larger resection, while the technique should be performed with caution in squamous cell carcinoma and other pathologies.

Early and late recurrence after intentional limited resection for cT1aN0M0, non-small cell lung cancer: from a multi-institutional, retrospective analysis in Japan.

OBJECTIVES: In 2015, we reported the outcomes of patients undergoing intentional limited resection (ILR) for non-small-cell lung cancer (NSCLC) from a retrospective, multi-institutional large database in Japan. Here, we analyse the clinicopathological characteristics of the patients extracted from this database with late recurrence and compare them with those with early recurrence. METHODS: Of 1538 patients in the database with cT1aN0M0 NSCLC, 92 (6%) had recurrence. In this study, early recurrence was defined as recurrence within 5 years and late recurrence as recurrence beyond 5 years after surgery. We compared the clinicopathological characteristics and post-recurrence survival (PRS) between patients with early and late recurrence. RESULTS: Of the 92 patients with recurrence, 21 (23%) had late recurrence. Compared with the early recurrence group, there were significantly more adenocarcinomas and local recurrences in the late recurrence group (P = 0.04 for both). The 3- and 5-year PRS rates were 53 and 24%, respectively, and the median PRS period was 38 months. There were no significant differences in the PRS curves between patients with early and late recurrence (P = 0.12). Only 3 patients (0.2%) had recurrence more than 10 years after ILR. Of the 21 late-recurrence patients, 17 (81%) had tumours with a consolidation/tumour ratio (CTR) >0.25. CONCLUSIONS: Late recurrence occurred in 21 (23%) of 92 patients with recurrence after ILR for cT1aN0M0 NSCLC. Late recurrence was more likely to involve adenocarcinoma and local recurrence. It is thus considered reasonable to follow patients with a CTR >0.25 for 10 years after ILR.

Pulmonary hepatoid adenocarcinoma: report of a case.

Hepatoid adenocarcinoma (HAC) is a rare neoplasm with aberrant hepatocellular differentiation. HAC occurs in extrahepatic organs such as the gastrointestinal tract, testes, ovaries, and lungs and frequently produces alpha-fetoprotein. A 69-year-old patient was diagnosed clinically with T2aN0M0, stage IB, non-small cell lung carcinoma. Because the tumor showed tight adhesion to the chest wall, we performed left upper lobectomy, combined resection of the 3rd and 4th ribs, and lymph node dissection. Pathological examination confirmed the diagnosis of HAC of the lung (pathological T2aN0M0, stage IB), and four courses of cisplatin and gemcitabine were administered as adjuvant chemotherapy. Genetic analysis of the epidermal growth factor receptor showed wild type. Preoperative serum alpha-fetoprotein level, a useful marker of disease progression, was elevated to 4497 ng/ml, decreasing within the normal range by about 3 months postoperatively. The patient remains alive without recurrence as of 51 months after surgery.

Novel approach to pleurodesis with 50 % glucose for air leakage after lung resection or pneumothorax.

PURPOSE: Pleurodesis is performed in patients demonstrating air leakage after lung resection and in those with pneumothorax who must avoid surgery. However, there have so far been very few reports of pleurodesis with 50 % glucose. We herein examined the feasibility and effectiveness of this novel pleurodesis technique. METHODS: Thirty-five patients after lung resection and 11 pneumothorax patients without surgery were treated with pleurodesis using 50 % glucose. Approximately, 200 mL of 50 % glucose solution was injected into the pleural space and repeated until the air leakage stopped. Cases in which the air leakage did not stop after three injections were considered to be unsuccessful and subsequently treated with conventional pleurodesis using OK-432. RESULTS: Thirty-nine patients were successfully treated with 50 % glucose, although 7 patients required further treatment with OK-432. The unsuccessful group had some pulmonary comorbidities (P < 0.001), and the pleural effusion volume after pleurodesis was less than that in the successful group (P < 0.001). Although the air leakage did not stop in unsuccessful patients, the amount of air leakage markedly decreased. A temporary elevation of the blood sugar level was observed in 20 patients, but no other side effects had appeared. CONCLUSIONS: Pleurodesis with 50 % glucose is an easy, safe, and effective treatment modality. It is therefore considered to be a useful alternative method for pleurodesis.

Survival of 1737 lobectomy-tolerable patients who underwent limited resection for cStage IA non-small-cell lung cancer.

OBJECTIVES: A precise preoperative diagnosis of 'very early' lung carcinoma may identify patients who can undergo curative surgery with limited resections. METHODS: Data from a multi-institutional project were collected on 1737 patients who had undergone limited resections (segmentectomy or wedge resection) for T1N0M0 non-small-cell carcinomas. As it was expected, this study was predominantly including ground glass nodules. Computed tomography was used to obtain the ratio of consolidation to the maximal tumour diameter to determine invasive potential of the tumours. Overall and disease-free survivals and recurrence-free proportions were analysed. RESULTS: Median age was 64 years. Mean maximal diameter of the tumours was 1.4±0.5 cm. Overall and recurrence-free survivals after limited lung resection were 94.0 and 91.1% at 5 years, respectively. Recurrence-free proportions were 93.7% at 5 years. Unfavourable prognostic factors in overall survival were lymph node metastasis, interstitial pneumonia, male gender, older age, comorbidities (cardiac disease, diabetes etc.) and consolidation/tumour ratio (C/T)≤0.25. C/T≤0.25 predicted good outcomes especially in cT1aN0M0 disease. In a subclass analysis of cT1N0M0 squamous cell carcinomas, wedge resection was the only unfavourable prognostic factor in both overall and disease-free survivals. CONCLUSIONS: If the patient was 75 years old or younger and was judged fit for lobectomy, limited resection for cStage I non-small-cell lung cancer (NSCLC) showed excellent outcomes and was not inferior to the reported results of lobectomy for small-sized NSCLC. The carcinomas with C/T≤0.25 rarely recur and are especially good candidates for limited resection.

Multiple lung adenocarcinomas associated with von hippel-lindau disease.

Lung adenocarcinoma has never before been reported to be associated with von Hippel-Lindau (VHL) disease. Here, we report a case of VHL disease in a patient who had metachronous multiple lung adenocarcinomas. The patient is a 64-year-old-woman with VHL disease. She underwent surgical resection of one adenocarcinoma and one atypical adenomatous hyperplasia. A second lung adenocarcinoma developed metachronously. A point mutation in the VHL gene was confirmed in DNA from a blood sample, and loss of heterozygosity at the VHL locus was detected in the lung adenocarcinoma. The VHL dysfunction may have a role in the development of multiple lung adenocarcinomas.

Aberrant methylation and silencing of IRF8 expression in non-small cell lung cancer.

The aim of the present study was to investigate the aberrant methylation and altered expression of the interferon regulatory factor 8 (IRF8) gene in non-small cell lung cancer (NSCLC). Pyrosequencing assays were performed on 191 tumor specimens from NSCLC patients. The changes in IRF8 mRNA expression, prior to and following treatment with a demethylating agent and methylation itself, were examined in 13 lung cancer cell lines by quantitative polymerase chain reaction (qPCR) and pyrosequencing. IRF8 protein expression was examined in 94 of the 191 NSCLC specimens by immunohistochemical analysis. The IRF8 methylation level was significantly higher in the tumor tissues than in matched non-malignant lung tissues (P<0.0001). IRF8 was more frequently methylated in tumor tissues compared with matched non-malignant lung tissues, as defined by a predetermined cut-off value (P<0.0001). The IRF8 methylation level was strongly correlated with the change in mRNA expression in lung cancer cell lines and with the protein expression level in primary tumors. The IRF8 gene was more frequently methylated in patients without an epidermal growth factor receptor (EGFR) mutation than in patients with an EGFR mutation (P=0.015). IRF8 methylation correlated with recurrent prognosis in adenocarcinomas (log-rank test, P=0.048). IRF8 protein expression was frequently silenced in males, smokers, patients with non-adenocarcinoma or with wild-type EGFR, or in an advanced stage. IRF8 is often silenced by its methylation, which is a frequent event in NSCLC and, therefore, methylation of IRF8 may act as a prognostic marker for recurrence. Analysis of IRF8 methylation status may provide novel opportunities for improved prognosis and therapy of resected NSCLC.

Association of a genetic variant of CYP19A1 with multicentric development of lung adenocarcinomas.

BACKGROUND: The detection rate of multiple lung adenocarcinomas, which display multiple ground glass opacity nodules in the peripheral lung, is increasing because of advances in high resolution computed tomography. The genetic backgrounds of multiple nodules and the mechanisms that underlie their multicentric development are unknown. In this study, we examined single nucleotide polymorphisms (SNPs) of the cytochrome P450 19A1 gene to determine if they are associated with multiple adenocarcinomas risk. METHODS: Fifty-one cases of multiple adenocarcinomas with lepidic growth, 62 cases of a single adenocarcinoma with lepidic growth, and 126 control cases were analyzed. Three SNPs were analyzed by using a 5' nuclease assay with TaqMan minor-groove-binder probe. The expression level of CYP19A1 in the noncancerous lung was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: A minor allele of SNP rs3764221, which is located in the CYP19A1 gene, was significantly associated with multiple adenocarcinomas risk (adjusted odds ratio = 3.06; P = 0.006). Other polymorphisms of CYP19A1 were not significantly associated with the risk of multiple adenocarcinomas. A minor allele of SNP rs3764221 was also associated with a higher level of CYP19A1 messenger RNA expression (P = 0.03). CONCLUSIONS: SNP rs3764221 contributes to the development of multicentric adenocarcinomas in the peripheral lung by causing higher levels of CYP19A1 expression.

A case of desmoid-type fibromatosis arising after thoracotomy for lung cancer with a review of the english and Japanese literature.

Chest wall desmoid-type fibromatoses are rare, locally aggressive tumors that occasionally arise from previous thoracotomy sites. Tumors arising from previous sites of thoracotomy to treat malignant disease should be discriminated from the pleural dissemination of the previous malignancy. In this study, we report a case of desmoid-type fibromatosis arising from a site for thoracotomy to treat lung cancer. Additionally we reviewed 15 reported cases of desmoid-type fibromatosis following thoracotomy and summarized their features. A 62-year-old woman was found to have a tumor on computed tomography (CT) at a 1-year routine checkup for lung cancer. The tumor (diameter, 3.4 cm) was located at the previous thoracotomy site. Positron emission tomography (PET) revealed mild (18)F-fluorodeoxyglucose (FDG) accumulation in the tumor, with a maximal standardized uptake value (SUVmax) of 1.9. CT-guided biopsy revealed only fibrous tissue. Eighteen months after the biopsy, CT revealed apparent tumor growth, and a biopsy revealed the same histology observed previously. The tumor was removed and diagnosed as desmoid-type fibromatosis. Currently, the patient is alive without recurrence 4 years after desmoid surgery.

Long interspersed nucleotide element 1 hypomethylation is associated with poor prognosis of lung adenocarcinoma.

BACKGROUND: Genome-wide DNA hypomethylation is known to play important roles in genomic instability and carcinogenesis. Methylation in long interspersed nucleotide element 1 (LINE-1) is a good indicator of the global DNA methylation level within a cell. The aim of this study was to evaluate prognostic significance of LINE-1 hypomethylation in lung adenocarcinoma. METHODS: A consecutive series of 211 lung adenocarcinoma patients who underwent curative resections without any preoperative chemotherapy or radiotherapy at Kumamoto University Hospital between April 2010 and December 2012 were included. The LINE-1 methylation levels were quantified in tumor and noncancerous tissue by Pyrosequencing assay. RESULTS: Higher histologic grade and positive findings for vascular invasion were significantly associated with lower methylation levels. The disease-free survival in the hypomethylation group was significantly shorter than that of the non-hypomethylation group. The prognostic difference was more obvious in advanced cases (stage II, III) than in stage I cases. CONCLUSIONS: The LINE-1 methylation level is associated with histologic grade and vascular invasion of lung adenocarcinoma. Additionally, LINE-1 hypomethylation is a useful biomarker to predict early recurrence of lung adenocarcinoma.

Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer.

Genome-wide DNA hypomethylation and gene hypermethylation play important roles in instability and carcino-genesis. Methylation in long interspersed nucleotide element 1 (LINE-1) is a good indicator of the global DNA methylation level within a cell. Slit homolog 2 (SLIT2), myelin and lymphocyte protein gene (MAL) and insulin-like growth factor binding protein 7 (IGFBP7) are known to be hypermethylated in various malignancies. The aim of the present study was to assess the precise methylation levels of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer (NSCLC) using a pyrosequencing assay. Methylation of all regions was examined in 56 primary NSCLCs using a pyrosequencing assay. Changes in mRNA expression levels of SLIT2, MAL and IGFBP7 were measured before and after treatment with a demethylating agent. Methylation of these genes was also examined in 9 lung cancer cell lines using RT-PCR and a pyrosequencing assay. Frequencies of hypomethylation of LINE-1 and hypermethylation of SLIT2, MAL and IGFBP7, defined by predetermined cut off values, were 55, 64, 46 and 54% in NSCLCs, respectively and exhibited tumor-specific features. The hypermethylation of all genes was well correlated with changes in expression. The methylation level and frequency of MAL were significantly higher in smokers and in patients without EGFR mutations. Through accurate measurement of methylation levels using pyrosequencing, hypomethylation of LINE-1 and hypermethylation of SLIT2, MAL and IGFBP7 were frequently detected in NSCLCs and associated with various clinical features. Analysis of the methylation profiles of these genes may, therefore, provide novel opportunities for the therapy of NSCLCs.

[Esophageal fish bone migrating to the lung; report of a case].

A 55-year-old female felt a transient chest pain soon after a fish meal. Sixteen days later she presented a local clinic with fever of 38°C. After chest computed tomography( CT) and upper gastrointestinal endoscopy showed fish bone embedded in the wall of the middle portion of the esophagus, she referred to our hospital 22 days after the meal. Thirty days after the meal ,endoscopic removal of the fish bone was challenged bygastroentenologists in vain. Chest CT after the attempt showed migration of the fish bone to the lung adjacent to the right inferior pulmonary vein. The fish bone which stuck out from the lung after division of the pulmonary ligament was removed successfully under thoracoscopic surgery. The patient is well 26 months after the surgery.

Segmentectomy for selected cT1N0M0 non-small cell lung cancer: a prospective study at a single institute.

BACKGROUND: To examine whether segmentectomy is radical for cT1N0M0 non-small cell lung cancer (NSCLC), a prospective single-arm study was performed at a single institution. METHODS: The criteria for segmentectomy were as follows: (1) peripheral-type cT1N0M0 NSCLC; (2) intraoperative frozen sections of sentinel nodes identified with isotope showing no metastasis; (3) surgical margins greater than 2 cm; (4) patient choice for segmentectomy; and (5) exclusion of right middle lobe tumors. From 2005 to 2009, of 245 patients with cT1N0M0 NSCLC, 195 (80%) were enrolled in the present study. Of these 195 patients, 179 ultimately underwent segmentectomy with systematic lymph node dissection. Of these 179 patients, 134 (75%) had tumors 2 cm or smaller, and 45 (25%) had tumors 2.1 cm to 3 cm. The median follow-up period was 43 months. RESULTS: All 181 tumors from 179 patients were stage pN0. Of the 179 patients, 6 developed distant site recurrence and 3 local recurrence (ie, 1 developed pulmonary metastases within the same lobe 21 months after segmentectomy and 2 developed local recurrence at the surgical margin 60 and 62 months after segmentectomy, respectively). The 5-year overall survival was 94% for patients with tumors 2 cm or smaller and 81% for those with 2.1-cm to 3-cm tumors. Postoperative pulmonary function was preserved at 90% ± 12% of preoperative levels. CONCLUSIONS: Segmentectomy with systematic lymph node dissection with a sufficient surgical margin could be a radical treatment for selected cT1N0M0/pN0 NSCLC while preserving pulmonary function. The surgical margin should be monitored for the development of local recurrence for a long period after segmentectomy.

Is completion lobectomy merited for unanticipated nodal metastases after radical segmentectomy for cT1 N0 M0/pN1-2 non-small cell lung cancer?

OBJECTIVE: To examine the role of radical segmentectomy, defined as a segmentectomy with extensive hilar/mediastinal lymph node dissection and a sufficient surgical margin, for local control in cT1 N0 M0/pN1-2 non-small cell lung cancer (NSCLC), we examined the following: (1) whether metastases were observed in specimens additionally resected by completion lobectomy undertaken after segmentectomy because of pN1-2 disease and (2) prognostic outcome in patients whose operations were completed with segmentectomy regardless of pN1-2. METHODS: Of 275 patients with cT1 N0 M0 NSCLC who were scheduled to undergo radical segmentectomy, 15 (6%) had a diagnosis of pN1 or N2 disease. Of these patients, 10 were additionally treated with completion lobectomy, whereas the operations of the remaining 5 were completed with segmentectomy. RESULTS: None of the 10 patients who underwent completion lobectomy showed residual metastases in the specimens additionally resected by completion lobectomy. Two of the 5 patients whose operations were completed with segmentectomy, regardless of N1 or N2 disease, had tumor recurrence, but their first recurrence was not local. CONCLUSIONS: Radical segmentectomy, with extensive hilar/mediastinal lymph node dissection and a sufficient surgical margin, may play a role in local control in patients with cT1 N0 M0/pN1-2 NSCLC.

Two lung adenocarcinomas in the same lobe: multiple primaries or intrapulmonary metastasis?

Abnormal nodules were found in the left lung of a 52-year-old woman in segments 6 and 10 on a chest CT. These nodules showed no changes for 18 months, and we discontinued follow-up. Almost 5 years later, an abnormal shadow was found in her left lower lung field on a medical check-up chest X-ray. Chest CT revealed that the left segments 6 and 10 nodules had grown. We diagnosed these lesions as synchronous double primary lung cancers in the same lobe based on the disease history and performed a left lower lobectomy and lymph node dissection. Pathological examination of both tumors revealed adenocarcinoma of a mixed subtype with papillary and bronchioloalveolar carcinoma. Epidermal growth factor receptor gene mutations were examined, and the 2 lesions shared an L858R mutation. Although we expected EGFR gene mutation analysis would help us distinguish the 2 lesions from each other, it was of little help. Disease history can be more important in evaluating multiple pulmonary cancers.

Comparison of postoperative pulmonary function and air leakage between pleural closure vs. mesh-cover for intersegmental plane in segmentectomy.

BACKGROUND: To prevent postoperative air leakage after lung segmentectomy, we used two methods for the intersegmental plane: closing it by suturing the pleural edge (pleural closure), or opening it with coverage using polyglycolic acid mesh and fibrin glue (mesh-cover). The preserved forced expiratory volume in one second (FEV1) of each lobe and the postoperative air leakage were compared between the two groups. METHODS: For 61 patients who underwent pleural closure and 36 patients who underwent mesh-cover, FEV1 of the lobe before and after segmentectomy was measured using lung-perfusion single-photon-emission computed tomography and CT (SPECT/CT). The groups' results were compared, revealing differences of the preserved FEV1 of the lobe for several segmentectomy procedures and postoperative duration of chest tube drainage. RESULTS: Although left upper division segmentectomy showed higher preserved FEV1 of the lobe in the mesh-cover group than in the pleural closure one (p = 0.06), the other segmentectomy procedures showed no differences between the groups. The durations of postoperative chest drainage in the two groups (2.0 ± 2.5 vs. 2.3 ± 2.2 days) were not different. CONCLUSIONS: Mesh-cover preserved the pulmonary function of remaining segments better than the pleural closure method in left upper division segmentectomy, although no superiority was found in the other segmentectomy procedures. However, the data include no results obtained using a stapler, which cuts the segment without recognizing even the intersegmental plane and the intersegmental vein. Mesh-cover prevented postoperative air leakage as well as the pleural closure method did.

Combined subsegmentectomy: postoperative pulmonary function compared to multiple segmental resection.

BACKGROUND: For small peripheral c-T1N0M0 non-small cell lung cancers involving multiple segments, we have conducted a resection of subsegments belonging to different segments, i.e. combined subsegmentectomy (CSS), to avoid resection of multiple segments or lobectomy. Tumor size, location of tumor, and forced expiratory volume in 1 second (FEV1) of each preserved lobe were compared among the CSS, resection of single segment, and that of multiple segments. METHODS: FEV1 of each preserved lobe were examined in 17 patients who underwent CSS, 56 who underwent resection of single segment, and 41 who underwent resection of multiple segments, by measuring pulmonary function and lung-perfusion single-photon-emission computed tomography and computed tomography before and after surgery. RESULTS: Tumor size in the CSS was significantly smaller than that in the resection of multiple segments (1.4±0.5 vs. 2.0±0.8 cm, p=0.002). Tumors in the CSS were located in the right upper lobe more frequently than those in the resection of multiple segments (53% vs. 5%, p<0.001). Postoperative of FEV1 of each lobe after the CSS was higher than that after the resection of multiple segments (0.3±0.2 vs. 0.2±0.2 l, p=0.07). Mean FEV1 of each preserved lobe per subsegment after CSS was significantly higher than that after resection of multiple segments (0.05±0.03 vs. 0.03±0.02 l, p=0.02). There was no significant difference of these factors between the CSS and resection of single segment. CONCLUSIONS: The CSS is effective for preserving pulmonary function of each lobe, especially for small sized lung cancer involving multiple segments in the right upper lobe, which has fewer segments than other lobes.

Peptides derived from human insulin-like growth factor-II mRNA binding protein 3 can induce human leukocyte antigen-A2-restricted cytotoxic T lymphocytes reactive to cancer cells.

Insulin-like growth factor-II mRNA binding protein 3 (IMP-3) is an oncofetal protein expressed in various malignancies including lung cancer. This study aimed to identify immunogenic peptides derived from IMP-3 that can induce tumor-reactive and human leukocyte antigen (HLA)-A2 (A*02:01)-restricted cytotoxic T lymphocytes (CTL) for lung cancer immunotherapy. Forty human IMP-3-derived peptides predicted to bind to HLA-A2 were analyzed to determine their capacity to induce HLA-A2-restricted T cells in HLA-A2.1 (HHD) transgenic mice (Tgm). We found that three IMP-3 peptides primed HLA-A2-restricted CTL in the HLA-A2.1 Tgm. Among them, human CTL lines reactive to IMP-3 (515) NLSSAEVVV(523) were reproducibly established from HLA-A2-positive healthy donors and lung cancer patients. On the other hand, IMP-3 (199) RLLVPTQFV(207) reproducibly induced IMP-3-specific and HLA-A2-restricted CTL from healthy donors, but did not sensitize CTL in the HLA-A2.1 Tgm. Importantly, these two IMP-3 peptide-specific CTL generated from healthy donors and cancer patients effectively killed the cancer cells naturally expressing both IMP-3 and HLA-A2. Cytotoxicity was significantly inhibited by anti-HLA class I and anti-HLA-A2 monoclonal antibodies, but not by the anti-HLA-class II monoclonal antibody. In addition, natural processing of these two epitopes derived from the IMP-3 protein was confirmed by specific killing of HLA-A2-positive IMP-3-transfectants but not the parental IMP-negative cell line by peptide-induced CTL. This suggests that these two IMP-3-derived peptides represent highly immunogenic CTL epitopes that may be attractive targets for lung cancer immunotherapy.