[Securing and Treatment of Interlobar Pulmonary Artery in Severe Insufficient Interlobar Fissure of the Lung].

There are 2 surgical approaches to secure and treat interlobar pulmonary artery in severe insufficient interlobar fissure of the lung. One is an interlobar approach which is called "fissure first technique". This approach is standard, but sometimes difficult to secure interlobar artery safely. So, lung parenchyma injury and accidental bleeding from the pulmonary artery become troublesome problems. On the other hand, hilar approach without contacting to interlobar fissure which called "hilar first technique" is very useful to avoid lung parenchyma injuries. There are some knack and pitfalls in every lobe of the lung. The key of this approach is to be familiar with the anatomical position of pulmonary artery running by confirming preoperative 3-dimensional computed tomography( 3D-CT). In the final step of this technique cutting the interlobar line exactly is more important to prevent atelectasis and congestion of residual lung. It is very important for thoracic surgeons to know the details of both approaches in the surgical treatment of severe insufficient interlobar fissure of the lung.

Podoplanin expression in cancer-associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma.

AIMS: Podoplanin expression in cancer-associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early-stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expression in patients with pathological stage (p-stage) IA lung adenocarcinoma as categorised by the 8th edition of the tumour-node-metastasis classification for lung cancer. METHODS AND RESULTS: Immunohistochemical analyses using anti-podoplanin antibody were performed on resected specimens from 158 patients with p-stage IA lung adenocarcinoma. When more than 10% of cancer cells or CAFs showed immunoreactivity with podoplanin, the specimens were classified as podoplanin-positive. Podoplanin-positive status in cancer cells (n = 8) was not correlated with clinicopathological factors or with patient prognosis. Podoplanin-positive status in CAFs (n = 41) was correlated significantly with poorer tumour differentiation (P < 0.001), the presence of lymphatic invasion (P < 0.001) and high-grade (solid and/or micropapillary) components constituting ≥1% of the entire tumour (P < 0.001). The log-rank test showed that podoplanin-positive status in CAFs was associated significantly with shorter disease-free survival (DFS) (P < 0.001) and disease-specific survival (P = 0.015). In Cox's multivariate analysis, podoplanin-positive status in CAFs had the most significant effect on shorter DFS [hazard ratio (HR) = 4.411, P = 0.004], followed by the presence of high-grade components (HR = 3.581, P = 0.013). CONCLUSIONS: Podoplanin expression in CAFs could be an independent predictor of increased risk of recurrence in patients with p-stage IA lung adenocarcinoma.

[Robot-Assisted Thoracoscopic Surgery for Lung Cancer].

In addition to conventional video-assisted thoracic surgery(VATS)as minimallyinvasive surgeryfor lung cancer, medical insurance system of robot-assisted thoracoscopic surgery(RATS)byusing da Vinci Surgical System®(DVSS)is just adapted from this spring. Although VATS is widelydiffused in clinical practice, it is recommended as grade C1(considerable)in the latest lung cancer medical guideline. On the other hand, it has been noticed that RATS is attractive and expected to cover the disadvantages of conventional VATS. In the comparison of both VATS and RATS lobectomyfor lung cancer, theyhave been reported to be comparable in safetyand efficacy, but RATS is superior at the viewpoint of good operabilityand faster learning curve. However, high costs and the longer operative time in RATS are of a concern. Experience of RATS is still in the initial phase, however from now on RATS is graduallyinfiltrating and expected to demonstrate the improvement of perioperative outcome. Especially, manyinstitutes have just began to introduce robotic surgeryin general thoracic field after the adaption of medical insurance. So, safetyand sure spread of RATS is an urgent and important issue in our field. Of course, while coexisting with VATS, it is important to verifythe efficacyof RATS.

Simplified comorbidity score for elderly patients undergoing thoracoscopic surgery for lung cancer.

PURPOSE: We investigated the efficiency of the Simplified Comorbidity Score (SCS) for predicting postoperative complications and prognosis in elderly patients undergoing video-assisted thoracoscopic surgery (VATS) for lung cancer. METHODS: We reviewed 216 patients aged 75 years or older, who underwent pulmonary resection by VATS for lung cancer between January, 2005 and December, 2012. The SCS assigns different scores to patients' comorbidities; namely, smoking (n = 7); diabetes mellitus (n = 5); renal insufficiency (n = 4); and respiratory, neoplastic, and cardiovascular comorbidities or alcoholism (n = 1 each). Patients were divided into a high SCS group (SCS ≥ 9; n = 154) and a low SCS group (<9; n = 62), for a comparative analysis of differences in perioperative factors and prognoses. RESULTS: Limited resection was more frequent in the high SCS group (58 %) than in the low SCS group (40 %; P = 0.02). Postoperative complications were more frequent in the high SCS group (45 %) than in the low SCS group (15 %; P < 0.01). A logistic regression analysis revealed that a high SCS was significantly predictive of postoperative complications (odds ratio 2.7; P = 0.02). The 5-year overall survival rate was 79 % for the low SCS group and 52 % for the high SCS group (P < 0.01). CONCLUSIONS: The SCS can predict the likelihood of postoperative complications and prognosis of elderly patients with VATS-treated lung cancers.

[Two Surgical Cases of Müllerian Cyst Arising From the Posterior Mediastinum].

We experienced 2 cases of Müllerian cyst. Case 1 was a 48-year-old woman with a paravertebral cystic tumor. The tumor grew from 23 to 31 mm in diameter for the 3 years. She underwent video-assisted thoracic surgery(VATS) for the excision of the tumor. Case 2 was a 40-year-old woman with a paravertebral cystic tumor, who underwent VATS. The Histological finding showed that the tumors of both cases were the cysts lined by non-stratified cuboidal to columnar epithelium and epithelial cells were positive in the nucleus with estrogen receptor immunohistochemically. The resected cysts were finally diagnosed as Müllerian cyst. Twenty four published cases of Müllerian cyst were reported before, including symptomatic and growing cases. There were some reports of malignant transformation in cases of pelvic origin.

Cytoplasmic expression of maspin predicts unfavourable prognosis in patients with squamous cell carcinoma of the lung.

AIMS: Maspin is known to be a tumour suppressor protein, and its prognostic significance in patients with several types of cancer, including lung squamous cell carcinoma (SCC), has been reported. However, its prognostic impact on lung SCC has been controversial. We explored the prognostic value of maspin expression with particular reference to its subcellular localization in patients with lung SCC. METHODS AND RESULTS: Paraffin-embedded tissue samples from 101 curatively resected patients with lung SCC were analysed immunohistochemically using an antibody for maspin. Maspin positivity was defined as strong expression in only the cytoplasm and observed in 25 patients (24.6%). It correlated significantly with the presence of lymph node metastasis (P = 0.006) and higher pathological stage (P = 0.003). The patients were followed-up for 2-119 months (median: 50 months), and the maspin-positive group had shorter disease-free survival (DFS) and disease-specific survival (DSS) by log-rank test (P = 0.002, P = 0.016, respectively). Multivariate analysis revealed that the status of maspin was the only independent prognostic factor for DFS and DSS (P = 0.017, P = 0.047, respectively). CONCLUSIONS: Cytoplasmic expression of maspin could be an independent unfavourable prognostic indicator in patients with lung SCC.

Distribution and Prevalence of Locoregional Recurrence after Video-Assisted Thoracoscopic Surgery for Primary Lung Cancer.

Background The aim of this study is to evaluate cases with locoregional recurrence after video-assisted thoracoscopic surgery (VATS) for primary lung cancer. Methods We reviewed 248 patients with primary lung cancer who underwent lobectomy or segmentectomy with mediastinal lymph node dissection by VATS between January 2005 and December 2011. Locoregional recurrence is defined as per its occurrence in (1) bronchial stump or lung parenchymal cut end, (2) ipsilateral pleura, and (3) ipsilateral hilar and mediastinal lymph nodes, and we analyzed recurrence rate and significant associated factors for locoregional recurrence by logistic regression analysis. Results There were 47 cases of postoperative recurrence, which consisted of 26 distant, 6 locoregional and distant, and 15 locoregional recurrences. The locoregional recurrence rate was 6.0%. Of the 15 locoregional recurrence cases, there were two cases of bronchial stump and lung parenchyma cut end (0.4%), five cases of ipsilateral pleura (2.0%), and eight cases of ipsilateral hilar and mediastinal lymph nodes (3.2%). Pleural and lymphovascular invasion and advanced stages were significant associated factors in univariate analysis. Multivariate analysis revealed that advanced stages were only a significant associated factor for locoregional recurrence (p < 0.01, odds ratio: 3.3). Conclusion Although locoregional recurrence rates of our surgical treatments for primary lung cancer by VATS might be acceptable, we should explore more effective modalities against pathologically proven local advanced lung cancer for preventing not only distant but also locoregional recurrences.

[Robot-assisted Thoracoscopic Surgery for Lung Cancer].

As surgical robots have widely spread, verification of their usefulness in the general thoracic surgery field is required. The most favorable advantage of robotic surgery is the markedly free movement of joint-equipped robotic forceps under three-dimensional high-vision. Accurate operation makes complex procedures straightforward and may overcome weak points of previous thoracoscopic surgery. Robotic surgery for lung cancer has been safely introduced and initial results have shown favorable. It is still at the stage of clinical research, but is expected to take its usefulness in the procedure of hilar exposure, lymph node dissection and the suturing of lung parenchyma or bronchus. The evidence is insufficient for robotic thoracic surgery, and also safety management, education and significant cost are larger problems. Now, urgent issues are to carry out clinical trial for advanced medical care and insurance acquisition.

Cytoplasmic maspin expression is a predictor of poor prognosis in patients with lung adenocarcinoma measuring <3 cm.

AIMS: Maspin is known to be a tumour suppressor protein, and few studies focused upon its prognostic significance in patients with small-size lung adenocarcinoma have been reported; however, its clinical significance remains controversial. We explored the prognostic value of maspin with particular reference to its subcellular localization in patients with resected lung adenocarcinoma measuring <3 cm. METHODS AND RESULTS: Immunohistochemical analyses were performed on resected 110 specimens of lung adenocarcinoma measuring <3 cm. Maspin positivity was defined as strong expression in only the cytoplasm and was observed in 27 patients (24.5%). It correlated significantly with the presence of lymph node metastasis (P = 0.009) and micropapillary component (P < 0.001). The patients were followed-up for 6-88 months (median: 71 months), and the maspin-positive group had shorter disease-free survival (DFS) and overall survival (OS) by log-rank test (P < 0.001, P < 0.001, respectively). Using Cox's multivariate analysis, the status of maspin was an independent prognostic factor for DFS and OS (P = 0.004, P = 0.022, respectively), as well as lymph node metastasis. CONCLUSIONS: Cytoplasmic maspin expression could be an independent poor prognostic indicator of patients with lung adenocarcinoma measuring <3 cm.

[Operation-assisted robot·da Vinci (lung)].

The most favorable advantage of robotic surgery is the markedly free movement of joint-equipped robotic forceps under 3-dimensional high-vision. Accurate operation makes complex procedures straightforward and may overcome weak points of previous thoracoscopic surgery. The efficiency and safety improves with acquiring skills. However, the spread of robotic surgery in the general thoracic surgery field has been delayed compared to those in other fields. The surgical indications include primary lung cancer, thymic diseases, and mediastinal tumors, but it is unclear whether technical advantages felt by operators are directly connected to merits for patients. Moreover, problems concerning the cost and education have not been solved. Although evidence is insufficient for robotic thoracic surgery, it may be an extension of thoracoscopic surgery, and reports showing its usefulness for primary lung cancer, myasthenia gravis, and thymoma have been accumulating. Now, important thing is to carry out clinical trial for advanced medical care and insurance acquisition. Although it is necessary to solve important problems such as safety, education, training, the cost for the future development, advancing robot technology has a possibility to markedly change general thoracic surgery.

[Current status and future prospects of robotic surgery for lung cancer].

As the use of robotic surgery has widely spread, its usefulness in the field of general thoracic surgery needs to be verified. The biggest advantage of robotic surgery is the remarkably free movement of joint-equipped robotic forceps under 3-dimensional high vision. An accurate operation makes complex procedures straightforward and may overcome the disadvantages of previous thoracoscopic surgery. Robotic surgery for lung cancer has been safely introduced, and the initial results have been favorable. While still at the stage of clinical research, it is expected to be useful in hilar exposure, lymph node dissection, and suturing of lung parenchyma or bronchus. We considered robotic surgery for lung cancer surgery because of its ability to facilitate both thoracotomy and minimally invasive video-assisted thoracic surgery. Robotic thoracic surgery has not been sufficiently examined for its usefulness, and other major issues such as safety management, education, and significant cost need to be addressed. However, it may become an extension of thoracoscopic surgery, and studies showing its usefulness for primary lung cancer have been increasing. Two urgent issues are its use in advanced medical care and national heal th insurance coverage.

An adult case of primary rhabdomyosarcoma of the trachea with resection of seven cartilage rings and primary reconstruction.

A 74-year-old female consulted a local clinic with bloody sputum and dyspnea. Bronchoscopy revealed a tumor with ∼80% stenosis in the trachea. She was referred to our hospital. Biopsy findings suggested primary rhabdomyosarcoma of the trachea. Cervical computed tomography (CT) revealed a tumor involving the 3rd to 9th tracheal cartilages. Tubular resection of the 3rd to 9th tracheal cartilages and tracheal reconstruction were performed. Finally, a pathological diagnosis of rhabdomyosarcoma was made. Primary rhabdomyosarcoma of the trachea is extremely rare.

Diagnostic value of recombinant nanoluciferase fused Toxoplasma gondii antigens in Luciferase-linked Antibody Capture Assay (LACA) for Toxoplasma infection in pigs.

Toxoplasmosis is a widespread protozoan zoonosis. Since ingesting undercooked meat harboring Toxoplasma gondii cyst is considered one of the major transmission routes to humans, the screening of T. gondii in meat-producing animals can reduce the risk of food-borne toxoplasmosis in humans. Among serological diagnostic methods, Luciferase-linked Antibody Capture Assay (LACA) has been found to be a promising platform with high sensitivity and specificity. In this study, we aimed to evaluate recombinant nanoluciferase fused-T. gondii antigens (rNluc-GRA6, rNluc-GRA7, rNluc-GRA8 and rNluc-BAG1) for their potential use in LACA for pigs. As a result, the sensitivity of GRA6-, GRA7-, GRA8- and BAG1-LACA were 70.0%, 80.0%, 80.0% and 30.0% with specificity 87.0%, 81.5%, 74.1% and 50.0%, respectively. The cocktail LACA using a mixture of rNluc-GRA6, rNluc-GRA7 and rNluc-GRA8 indicated higher sensitivity (90.0%) and a similar specificity (96.3%) in comparison with the commercial ELISA kit. Compared to the Dye-Test as a reference test, cocktail LACA showed strong agreement (kappa value=0.811) when we assessed pig sera collected at the slaughterhouse. In addition, we also successfully established the rapid LACA format for the detection of Toxoplasma infection in pigs (called Rapid-LACA) in which the test could be performed within 30 min. In Rapid-LACA, the protein A pre-coated/blocked plates could be preserved at -30°C, 4°C or room temperature conditions for at least two months without compromising on the quality of assay.

Spatial distribution of anti-Toxoplasma gondii antibody-positive wild boars in Gifu Prefecture, Japan.

Toxoplasma gondii is a globally wide-spread parasite that infects almost all species of mammals and birds, including humans. We studied the spatial distribution of individual T. gondii-seropositive wild boar in Gifu Prefecture (10,621 km2), Japan. Altogether, 744 wild boars were captured at 663 points around human settlements in Gifu Prefecture. Serum samples were collected after recording the exact capture locations, along with each wild boar's body length and sex. We then used a commercial enzyme-linked immunosorbent assay kit for swine to measure anti-T. gondii antibodies in these animals. Among the 744 wild boars, 169 tested positive for T. gondii (22.7%). No significant difference in T. gondii seroprevalence was observed between the mountainous northern region with high winter snow cover and the mild-wintered geographical plain of the southern part of the prefecture. In contrast, 8 of the 11 wild boars that were captured in a public park surrounded by residential areas showed T. gondii seropositivity (72.7%), a value significantly higher than those of the wild boar populations in the other prefecture areas. This in-depth analysis, which spans the big city suburbs and rural areas of a whole prefecture, explains the seroprevalence of zoonotic T. gondii in wild boar and has public health implications.

'Lung age' predicts post-operative complications and survival in lung cancer patients.

BACKGROUND AND OBJECTIVE: The Japanese Respiratory Society recently proposed 'lung age' as an easily understood concept of respiratory function. In this study, we evaluated whether 'lung age' could be a useful predictor of post-operative respiratory complications and survival patients with lung cancer treated surgically. METHODS: The study recruited 308 patients who underwent surgery for primary non-small-cell lung cancer. All patients had preoperative pulmonary function testing. 'Lung age' was determined using the methods advocated by the Japanese Respiratory Society. Based on the difference between 'real age' (R) and 'lung age' (L), patients were classified into five groups: group A: R-L > 15 (n = 37), B: 5 < R-L R-L (n = 94). Clinicopathological factors, post-operative respiratory complications and survival were compared between the groups. RESULTS: Gender, smoking status and index, histology, operative approach and FEV(1) were significantly associated with the group classification. The incidence of complications was significantly higher in group E compared with other groups (P = 0.003). Multivariate analysis showed that the group classification by 'lung age' was an independent predictor of post-operative respiratory complications (P = 0.02). Overall survival differed significantly between the groups (P = 0.03). CONCLUSIONS: 'Lung age' could be useful for the prediction of post-operative respiratory complications and survival in patients with lung cancer treated surgically.

Spontaneous regression of lung adenocarcinoma: Report of a case.

This report presents a rare case of lung adenocarcinoma accompanied by partial spontaneous regression (SR). A 69-year-old woman with an abnormal shadow on chest X-ray was admitted to the hospital. She was diagnosed to have lung adenocarcinoma with right adrenal metastasis based on a thorough examination. However, a month after the diagnosis, the primary and metastatic lesions markedly shrank on the following computed tomography scan and (18)F-fluorodeoxyglucose positron emission tomograph. This was thought to be a partial SR of the cancer, and she was treated with a surgical procedure. She has since remained free of disease for 14 months after the surgery.

['Lung age' predicts post-operative complications and survival in lung cancer patients].

The Japanese Respiratory Society (JRS) recently proposed 'lung age' as an easily understood concept of respiratory function. In this study, we evaluated whether 'lung age' could be a useful predictor of post-operative respiratory complications and survival patients with lung cancer treated surgically. The study recruited 308 patients who underwent surgery for primary non-small cell lung cancer. All patients had pre-operative pulmonary function testing. 'Lung age' was determined using the methods advocated by the JRS. Based on the difference between real age' (R) and 'lung age' (L), patients were classified into five groups: group A: R-L > 15 (n = 37), B: 5 < R-L < or = 15 (n = 50), C: -5 < or = R-L < or = 5 (n = 73), D: -15 < or = R-L < -5 (n = 54), E: -15 > R-L (n = 94). Clinicopathological factors, post-operative respiratory complications and survival were compared between the groups. Gender, smoking status and index, histology, operative approach and FEV1 were significantly associated with the group classification. The incidence of complications was significantly higher in group E compared with other groups (p < 0.01). Multivariate analysis showed that the group classification by 'lung age' was an independent predictor of postoperative respiratory complications (p = 0.02). Overall survival differed significantly between the groups (p = 0.03). 'Lung age' could be useful for the prediction of post-operative respiratory complications and survival in patients with lung cancer treated surgically.

Transformation from adenocarcinoma to squamous cell carcinoma associated with long-term administration of EGFR-TKIs.

Although patients with non-small cell lung cancer exhibiting EGFR mutations generally respond to tyrosine kinase inhibitors (TKIs), the majority of patients acquire resistance ~1 year after treatment. EGFR T790M mutations, MET or HER2 amplifications and phenotypic transformations contribute to the mechanism of EGFR-TKI resistance. The transformation of small cell lung cancer frequently occurs, although few convert to squamous cell carcinoma associated with the administration of EGFR-TKIs. The current study reports a case of EGFR-mutated adenocarcinoma of the lung that transitioned to squamous cell carcinoma in association with long-term EGFR-TKIs administration.

Suppression of inflammatory genes expression in the injured host intestinal wall during Mesocestoides vogae tetrathyridium larvae migration.

Mesocestoides vogae is a cestode parasite of the family Mesocestoididae (order Cyclophyllidea). Its larvae, tetrathyridium, are approximately 1 mm long and 300 µm wide and infect a wide range of host species including humans. Tetrathyridium migrate through the intestinal wall to invade the peritoneal cavity. Despite intestinal penetration by such a large-sized parasite, symptomatic intestinal disorders are not common during the migration period. In this study, the dynamics of tetrathyridia migration and their pathogenicity towards intestinal tissues were examined in mice infected orally with these parasites. Most tetrathyridia were found to migrate through the intestinal wall, moving into the peritoneal cavity or liver 24 to 48 hours after the oral infections. Next, the pathogenicity of tetrathyridium in the intestinal wall was histopathologically evaluated, and tissue injury from tetrathyridium migration was confirmed. Inflammatory foci were observed as tetrathyridium migration tracks from 48 hours after oral infection; however, the number of inflammatory foci had decreased by half more than 48 hours later. Therefore, we examined the gene expression levels of the macrophage driving cytokine, IL-1ß, and the eosinophil recruiting chemokine, CCL11, by quantitative reverse-transcriptase PCR. The expression levels of these genes in the infected group were significantly lower than those of the non-infected group at 48 hours post-infection. Although the immunomodulating ability of the excretory-secretory products released from tetrathyridium has been previously shown by in vitro assays, the significance of this ability in their lifecycle has remained unclear. In this study, we discovered that tetrathyridium causes temporal inflammation in the intestinal wall during penetration and large-scale migration in this organ, but tetrathyridium simultaneously suppresses the host's inflammatory gene expression, might to be a strategy that reduces inflammatory responses and increases survival of the parasite.

Comparison of medium-term survival outcomes between robot-assisted thoracoscopic surgery and video-assisted thoracoscopic surgery in treating primary lung cancer.

OBJECTIVES: Robot-assisted thoracoscopic surgery (RATS) for primary lung cancer has been spreading rapidly in Japan. While RATS has various technical advantages over video-assisted thoracoscopic surgery (VATS), the quality of surgery from an oncologic viewpoint must be maintained, and the evaluation of medium- to long-term survival outcomes is momentous. METHODS: This study included 299 patients with primary lung cancer (VATS, n = 246; RATS, n = 53) who underwent lobectomy and mediastinal lymph node dissection at our hospital. We reviewed and compared perioperative factors, the number of dissected lymph nodes, and postoperative recurrence between the VATS and RATS groups. We also compared the postoperative survival rates among 98 patients (49 patients in each group) whose background factors were adjusted by propensity score matching (PSM). RESULTS: After PSM, a significant difference was found in the total operative time between the two groups (p < 0.01); however, no difference was found between the RATS console time and VATS total operative time (p = 0.68). Postoperative recurrence was not significantly different between the groups (VATS, 14%; RATS, 6%; p = 0.18). The 3-year recurrence-free survival rate was not significantly different between the groups (VATS, 91.7%; RATS, 91.2%; p = 0.21). CONCLUSIONS: RATS had promising survival results, which were similar to those of VATS even after PSM. Further case series and longer observation periods are needed to determine what technical benefits of RATS may affect the prognosis of lung cancer.