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The molecular mechanisms underlying the development of pulmonary fibrosis remain unknown, and effective treatments have not yet been developed. It has been shown that oxidative stress is involved in lung fibrosis. Oxidized diacylglycerol (DAG) produced by oxidative stress is thought to play an important role in lung fibrosis. This study assessed the effect of oxidized DAG in an animal model of pulmonary fibrosis induced by aspiration of bleomycin (BLM) into the lungs. The inhibitory effect of ebselen on pulmonary fibrosis was also investigated. In lung fibrotic tissue induced by BLM, an increase in lipid peroxides and collagen accumulation was observed. Moreover, the levels of oxidized DAG, which has strong protein kinase C (PKC) activation activity, were significantly increased over time following the administration of BLM. Western blotting showed that phosphorylation of PKCα and δ isoforms was increased by BLM. Oral administration of ebselen significantly suppressed the increase in oxidized DAG induced by BLM and improved lung fibrosis. PKCα and δ phosphorylation were also significantly inhibited. The mRNA expression of α-smooth muscle actin and collagen I (marker molecules for fibrosis), as well as the production of transforming growth factor-β and tumor necrosis factor-α(a potentially important factor in the fibrotic process), were increased by BLM and significantly decreased by ebselen. The administration of BLM may induce lipid peroxidation in lung tissue, while the oxidized DAG produced by BLM may induce overactivation of PKCα and δ, resulting in the induction of lung fibrosis.

ROS1 rearrangements are found in 1–2% of patients with non‐small‐cell lung cancer. The detection of the rearrangements is crucial since clinically effective molecular targeted drugs are available for them. We present a case of lung adenocarcinoma with a previously unknown ROS1‐CD74 fusion variant, CD74 exon 3 fused to ROS1 exon 34, which was not detected by a conventional RT‐PCR‐based test for ROS1 fusion gene detection but identified by hybrid capture‐based next‐generation sequencing. This tumor responded to crizotinib initially and to entrectinib after relapse with brain metastasis, indicating the oncogenic activity of this novel fusion variant., We present a case of lung adenocarcinoma with a novel ROS1‐CD74 fusion variant, CD74 exon 3 fused to ROS1 exon 34, which was not detected by a conventional RT‐PCR‐based testing but identified by hybrid capture‐based next‐generation sequencing. This tumor responded to crizotinib initially and to entrectinib after relapse with brain metastasis, indicating the oncogenic activity of this novel fusion variant.

Epithelial cells form epithelial tissue structures by joining together

Background Dermatomyositis is associated with malignant tumors including breast cancer, and inflammatory breast cancer is considered to have a poorer prognosis than most breast cancers. Case presentation A 74-year-old Asian woman, developed erythema on her face, back, and the back of her hands, 3 weeks before attending our department. At the same time, she had noticed a right breast mass and redness of the skin of the breast. The clinical findings and vacuum aspiration biopsy diagnosed inflammatory breast cancer and neoadjuvant chemotherapy was performed. The mass and enlarged axillary lymph nodes had shrunk, therefore a total mastectomy was performed. The sentinel lymph node biopsy was negative. She was discharged 7 days after surgery without any complications. She has received a postoperative aromatase inhibitor and is alive without recurrence. The dermatomyositis also began to improve with the start of her chemotherapy and has not recurred since the surgery. Conclusions Neoadjuvant chemotherapy was performed for inflammatory breast cancer with dermatomyositis, and tumor shrinkage was confirmed. A total mastectomy without axillary lymph node dissection was performed. Dermatomyositis and breast cancer have not recurred. Dermatomyositis may have been a paraneoplastic syndrome due to breast cancer.

We reported a surgical case of methotrexate-associated lymphomatoid granuloma. A 69-year-old female had been treated with methotrexate for rheumatoid arthritis for 35 months. The patient underwent partial resection of the right upper pulmonary lobe for lung cancer when she was 67 years old. A nodule was detected in the left lung field on a chest radiograph performed during the postoperative follow-up period. Computed tomography revealed a 28-mm nodule in the lower left pulmonary lobe. A transbronchial biopsy examination did not lead to a diagnosis. The pulmonary nodule subsequently increased in size. We suspected a malignant tumor and performed lower left lobectomy. A pathological examination revealed lymphomatoid granuloma. Finally, the patient was diagnosed with methotrexate-associated lymphomatoid granuloma based on her history of oral methotrexate treatment.

Pathological stage is the most important prognostic factor in patients with lung cancer, and is defined according to the tumor node metastasis classification system. The present study aimed to investigate the clinicopathological significance of lymphatic invasion in 103 patients who underwent surgical resection of lung squamous cell carcinoma (SqCC). The patients were divided into two groups, according to the degree of lymphatic invasion: Those with no or mild lymphatic invasion (ly0-1) and those with moderate or severe lymphatic invasion (ly2-3). Ly2-3 was associated with tumor size (P=0.028), lymph node metastasis (P

Background Advanced unresectable pulmonary adenocarcinoma with the epidermal growth factor receptor ( EGFR ) exon 21 L858R point mutation (Ex21) is associated with a poor prognosis. However, for early-stage resectable adenocarcinoma, Ex21 tumors have a lower-grade malignancy than exon 19 deleted (Ex19) tumors. We therefore investigated the effect of EGFR mutations on the prognosis in patients with completely resected pN1-N2 adenocarcinoma. Methods Five-year disease-free survival (DFS) and overall survival (OS) were analyzed in 202 pN1-N2 pulmonary adenocarcinoma patients, 100 of whom had EGFR mutations, comprising Ex21 in 41 (20.3%), Ex19 in 55 (27.2%), and Ex18 in 4 (2%). Results Patients with and without EGFR mutations had similar DFS (26.2% vs 24.6%, respectively; p = 0.280) and OS (64.9% vs 54.2%, respectively; p = 0.564). Patients with Ex19 tumors had significantly better DFS (38.8% vs 11.8%, p = 0.001) and tended to have better OS (78.3% vs 48.3%, p = 0.123) than those with Ex21 tumors. For pN1, patients with Ex19 tumors had a longer disease-free interval (54.0 vs 22.3 months, p = 0.003) and median survival time (81.0 vs 50.6 months, p = 0.022) than those with Ex21 tumors. For pN2, patients with Ex19 tumors had longer disease-free interval than those with Ex21 tumors (43.6 vs 30.1 months, p = 0.109). Multivariate analysis showed Ex21 was a prognosticator of poor DFS (hazard ratio, 2.25; 95% confidence interval, 1.21 to 4.20). Conclusions For pN1-N2 pulmonary adenocarcinoma, Ex21 mutation was associated with poorer prognosis than Ex19 mutation. Thus, EGFR mutation status should be considered when predicting prognosis.

A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy followed by the administration of decreasing doses of oral steroids. Nivolumab, an immune checkpoint inhibitor, is known to induce various neurological adverse events. However, this is the first report of acute cerebellar ataxia associated with nivolumab treatment.

A 44-year-old man experiencing repeated episodes of epistaxis and respiratory aspiration was diagnosed with nasopharyngeal cancer. Although the tumor completely disappeared after chemoradiation, six pulmonary nodules developed in the right lower lobe within a year. Right lower lobectomy was performed. All nodules were metastases of the nasopharyngeal cancer. Surgery was performed despite a poor prognosis, and there has been no recurrence 12 years postoperatively. Aerogenous metastases were suggested owing to right lower lobe localization and the patient's symptoms and prolonged survival. The possibility of aerogenous spread and the efficacy of local therapy should be further studied.

Objectives Cachexia has been shown to be related to mortality in patients with advanced cancers and chronic obstructive pulmonary disease. Smokers receiving surgery for lung cancer are thought to be at risk of developing cachexia postoperatively. We aimed to investigate whether 2 surrogate variables for cachexia, body mass index (BMI) and C-reactive protein (CRP) level, are predictive of mortality in smokers after complete resection of non-small-cell lung cancer. Methods We retrospectively examined 678 patients who underwent curative lobar resection for non-small-cell lung cancer at our hospital. Associations between clinicopathological factors and overall survival were assessed in smokers ( N = 421) and never smokers ( N = 257). Results Multivariate analysis of the smokers group showed that preoperative BMI ≤ 20.6 kg/m 2 and CRP ≥ 0.13 ng/ml were risk factors for poorer prognosis, independent of age and pathological stage. In never smokers, BMI and CRP were not significantly associated with survival. Smokers in the high-risk group, defined based on preoperative BMI and CRP, had shorter survival after recurrence, although they did not have an elevated recurrence rate. Despite the absence of recurrence, they died more frequently of pneumonia or other cancers. These observations are consistent with the idea that the poor postoperative prognosis could have resulted from the progression of cachexia. Conclusions In smokers with non-small-cell lung cancer, preoperative low BMI and elevated CRP are predictive factors for poor prognosis after complete resection, probably as a result of cachexia progression. The effective treatment of cachexia might improve postoperative prognosis.

Cell polarity and cell-cell adhesion play a critical role in the regulation of normal tissue architecture and function. Disruption of cell adhesion and cell polarity is often associated with neoplastic tumors. Loss of apical-basal polarity in epithelial cells is one of the hallmarks of aggressive and invasive cancers. Several polarity proteins including atypical protein kinase C (aPKC), Par 6, Par 3, and Lethal giant larvae (Lgl, the human homologues of which are called Hugl 1 and Hugl 2) are localized at the leading edge of migrating cells, and play critical roles during directional migration. Herein, we investigated the expression of aPKC, Par 6, Par 3, Hugl 1, and Hugl 2 in lung squamous cell carcinoma (SqCC). An inverse correlation was observed between the expression of Hugl 1 and lung SqCC progression. Results of immunohistochemistry and real-time RT-PCR analyses showed that reduced expression of Hugl 1 predicts poor survival in lung SqCC patients. The expression of Hugl 1 was inversely correlated with both overall survival rate and tumor stage. On the other hand, no associations were observed between the expressions of Hugl 2, Par 6, and Par 3 and lung SqCC progression. These findings indicate that the reduced expression of Hugl 1 could be considered as a poor prognostic factor in human lung cancers.

To evaluate the long-term functional outcome of colonic J-pouch reconstruction after low anterior resection (LAR) for rectal cancer in a prospective study. We compared the functional outcome of 46 patients who underwent J-pouch reconstruction (J-group) and 49 patients who underwent straight anastomosis (S-group) after LAR for rectal cancer. We evaluated clinical function using a 17-item questionnaire about different aspects of bowel function. Physiologic reservoir function was evaluated by manovolumetry. Among the patients with an ultralow anastomosis (≤4 cm from the anal verge), those in the J-group had fewer bowel movements during the day and at night, and less urgency, soiling, protective pad use, incontinence, and dissatisfaction with bowel function than those in the S-group. Among the patients with a low anastomosis (5–8 cm from the verge), those in the J-group had fewer bowel movements at night, and less urgency and soiling than those in the S-group. Moreover, reservoir function (reflected by the maximum tolerable volume, threshold volume, and compliance) was better in the J-group than in the S-group in both the ultralow and low anastomosis groups. J-pouch reconstruction after low anterior resection creates a better stool reservoir than straight anastomosis, especially when the anastomosis is less than 4 cm from the anal verge, resulting in a better quality of life 3 years after rectal cancer resection.

症例は53歳の女性で, 2001年10月に検診で便潜血反応陽性を指摘され, 直腸診で肛門縁から5cmに下縁を有する2cm大の腫瘍を触知した. カルチノイドの診断で側方郭清を伴う低位前方切除術および肝S7にみられた5mm大の転移巣に対する肝部分切除術を施行した. 原発巣の壁深達度はmpで, 251番・左262番リンパ節に転移が認められ, 組織学的に根治度Bであった. 肝動注による補助化学療法を行っていたところ, 術後5か月目に肝S2・S7に転移巣が認められたため, 経皮的にラジオ波焼灼療法 (radiofrequency ablation; 以下, RFAと略記) を施行した. 2005年9月まで, 計20か所の肝転移巣に対して経皮的RFA を施行し, 肝転移のコントロ-ルは良好で他の転移・再発は認められない. RFAは両葉に多発する小さな肝転移巣に対して有効な局所療法と考えられた.

Few reports on the long-term functional outcome of colonic J-pouch reconstruction have been published, and data comparing J-pouch and straight reconstruction are contradictory. This prospective study compares the functional outcome of colonic J-pouch and straight anastomosis five years after low anterior resection for rectal cancer. Functional outcome was compared in 46 patients with J-pouch reconstruction (J-group) and 48 patients with straight anastomosis (S-group). Clinical status was evaluated with a 17-item questionnaire inquiring about different aspects of bowel function. Reservoir function was evaluated by manovolumetry. The Fisher’s exact test and Wilcoxon’s rank-sum test were used to compare categoric and quantitative data, respectively. Among patients with an ultralow anastomosis (≤4 cm from the anal verge), the number of bowel movements during the day (≥5, 4.3 vs. 29.2 percent; P = 0.028) and at night (>1/week, 4.3 vs. 33.3 percent; P = 0.013) and urgency (4.3 vs. 33.3 percent; P = 0.013) and soiling (21.7 vs. 50.0 percent; P = 0.043) were less in the J-group than in the S-group. Among patients with a low anastomosis (5 to 8 cm from the verge), patients in the J-group had fewer bowel movements at night (>1/week, 0 vs. 20.8 percent; P = 0.028) and less urgency (0 vs. 20.8 percent; P = 0.028). Reservoir function was better in the J-group than in the S-group in both the ultralow (maximum tolerable volume (mean), 101.7 vs. 76.3 ml; P = 0.004; threshold volume (mean), 46.5 vs. 30.4 ml; P < 0.001; compliance (mean), 4.9 vs. 2.5 ml/cm H2O; P < 0.001) and low-anastomosis (maximum tolerable volume, 120.4 vs. 97.9 ml; P < 0.001; threshold volume, 58.3 vs. 40.8 ml; P < 0.001; compliance, 5.2 vs. 3.1 ml/cm H2O; P < 0.001) groups. J-pouch reconstruction increased reservoir function and provided better functional outcome than straight anastomosis, even five years after surgery, especially in patients whose anastomosis is less than 4 cm from the anal verge.

To avoid the complications of internal pneumatic stabilization for flail chest, we performed stabilization of the chest wall with a metal bar using the Nuss procedure. Here, we used a highly elastic lightweight biocompatible titanium alloy Chest Way (Solve Corporation, Kanagawa, Japan), enabling magnetic resonance imaging. The patient was a 37-year-old man who sustained injuries in a car crash. Gradually increasing subcutaneous emphysema was present. Bilateral pleural drainage and tracheal intubation were conducted on the scene, and a peripheral venous line was established. The patient was then transferred to our hospital by helicopter. A titanium alloy Chest Way was inserted to manage his flail chest accompanied by multiple rib fractures on the left side. Two days later, artificial respiration was no longer required.

Ki-67 is a nuclear protein that is expressed during the G1, S, G2 and M phases of the mitotic cell cycle. A previous study categorized tumor infiltration patterns (INF), of which INFc indicated cancer nests exhibiting infiltrative growth and an unclear boundary between tumor tissue and surrounding healthy tissue. The present study used the Ki‑67 labeling index (Ki‑67 LI) as an indicator of cell proliferation, in order to examine the factors affecting INF in lung squamous cell carcinoma (SqCC). SqCC specimens (89) were classified into two groups: High‑grade cell proliferation (Ki‑67 LI ≥30%) and low‑grade cell proliferation (Ki‑67 LI

Atypical protein kinase C lambda/iota (aPKC λ/ι) is expressed in several human cancers; however, the correlation between aPKC λ/ι localization and cancer progression in human lung adenocarcinoma (LAC) remains to be clarified. We found that patients with a high level of aPKC λ/ι expression in LAC had significantly shorter overall survival than those with a low level of aPKC λ/ι expression. In addition, localization of aPKC λ/ι in the apical membrane or at the cell-cell contact was associated with both lymphatic invasion and metastasis. The intercellular adhesion molecule, E-cadherin, was decreased in LACs with highly expressed aPKC λ/ι at the invasion site of tumor cells. This result suggested that the expression levels of aPKC λ/ι and E-cadherin reflect the progression of LAC. On double-immunohistochemical analysis, aPKC λ/ι and Lgl2, a protein that interacts with aPKC λ/ι, were co-localized within LACs. Furthermore, we found that Lgl2 bound the aPKC λ/ι-Par6 complex in tumor tissue by immune-cosedimentation analysis. Apical membrane localization of Lgl2 was correlated with lymphatic invasion and lymph node metastasis. These results thus indicate that aPKC λ/ι expression is altered upon the progression of LAC. This is also the first evidence to show aPKC λ/ι overexpression in LAC and demonstrates that aPKC λ/ι localization at the apical membrane or cell-cell contact is associated with lymphatic invasion and metastasis of the tumor.

We prospectively compared changes in function between colonic J-pouch and straight anastomoses from 1 to 5 years after low anterior resection for rectal cancer.At 1, 3, and 5 years after surgery, functional outcome was compared between 48 patients with J-pouch reconstruction (J group) and 51 with straight anastomosis (S group), using a 17-item questionnaire (overall best, 0; overall worst, 26). Reservoir function was evaluated manovolumetrically.At 5 years, patients with ultralow anastomoses (or =4 cm from anal verge) had fewer bowel movements during day or night, and less urgency and soiling in the J than S group. At that time, patients with low anastomoses (5 to 8 cm above the verge), had fewer bowel movements at night and less urgency in the J than S group. Manovolumetric results were better in the J than S group for both anastomotic levels. Functional scores improved significantly over time for both anastomotic levels, especially in the S group. Mean scores with ultralow anastomoses were J-group, 5.6 at 1 year vs. 5.3 at 3 years (P = 0.0304) vs. 3.7 at 5 years (P0.0001); and S group, 10.2 at 1 year vs. 9.6 at 3 years (P = 0.0063) vs. 7.3 at 5 years (P0.0001). Mean scores with low anastomoses were J group, 3.4 at 1 year vs. 3.1 at 3 years (P = 0.0052) vs. 2.1 at 5 years (P = 0.0003); and S group, 5.2 at 1 year vs. 3.8 at 3 years (P0.0001) vs. 2.7 at 5 years (P0.0001). Manovolumetric results improved overtime in both groups.Functional outcome improved in the J and especially the S group over 5 years. However, function was better in the J than S group at all time points.

One of the unresolved issues related to immunotherapy for cancers is how to predict the degree of growth of tumor stroma at the periphery of the tumor. We examined the feasibility of predicting stromal growth by measuring the glutathione (GSH) level in monocytes as an indicator of the local redox state of cancer, reflecting anti-tumor immune responses.Blood was drawn preoperatively from 21 patients with colorectal cancer. Monocytes were isolated from each blood sample and observed under a fluorescent microscope after fluorescent dye staining. The chromatic responses were rated on a three-grade scale: strongly positive, moderately positive and weakly positive. The monocytes were counted in each grade, and the GSH score was calculated. After surgery, pathology specimens of resected tissue were observed under a microscope to measure the percentage of the surface area of stroma in a given visual field at a magnification of x200. The percentage of stromal surface area was measured for three visual fields (near the deepest area of the tumor) to calculate the stroma score.The mean GSH score was 290.2. The mean stroma score was 60.8. There was a significant correlation between the GSH score and the stroma score (r = 0.421, p0.05).The monocyte GSH level may serve as a predictor of stromal growth.

Background Metastasis to regional lymph nodes from colon cancer is an important prognostic factor. In the TNM classification, node metastases are classified into three grades based on the number of metastatic nodes. In the Japanese General Rules for Clinical and Pathologic Studies on Cancer of the Colon, Rectum, and Anus (JGR), node metastases are classified into four grades based on the distribution of metastatic nodes. Study design Based on the findings of node metastases in 164 patients with colon cancer obtained by the clearing method, node classifications by the JGR and TNM classifications were compared. Results The case distribution by the JGR grading was 41.5% in n (−), 29.3% in n1 (+), 18.3% in n2 (+), and 11.0% in n3 (+) disease. In the TNM classification, the distribution was 23.8% in pN1 and 34.8% in pN2 disease. The 5-year survival rate by the JGR was 98.4% in n (−), 74.3% in n1 (+), 51.2% in n2 (+), and 30.0% in n3 (+) disease; in TNM classification, this rate was 76.0% in pN1 and 45.0% in pN2 disease. Conclusions In the classification of regional node metastases from colon cancer, the JGR classification showed a wider range in distribution and 5-year survival rate compared with the TNM system.

Bowel function after low anterior resection for rectal cancer with colonic J-pouch reconstruction is more normal than after conventional straight anastomosis. However, few reports have examined the function of colonic J-pouch reconstruction in the elderly. Good function would obviate the need for colostomy, which is sometimes performed because of concern about fecal incontinence, which increases with age. This study evaluated the function of colonic J-pouch reconstruction in elderly patients aged 75 years or older. Functional outcome was compared in 20 patients aged 75 years or older (older group) and 27 patients aged 60 to 74 years (old group) and 60 patients aged 59 years or younger (young group), 3 years after colonic J-pouch reconstruction, using a functional scoring system with a 17-item questionnaire (score range, 0 (overall good) to 26 (overall poor)). The functional scores in the three age groups were satisfactory and similar. Among patients with anastomoses 1 cm to 4 cm from the anal verge, all 17 categories on the questionnaire in the three age groups were similar. Among patients with anastomoses 5 cm to 8 cm from the anal verge, only the use of laxatives or glycerine enemas was more common in the older group than in the old and young group (90 vs. 38.5 percent and 43.3 percent; P = 0.01). Low anterior resection with colonic J-pouch reconstruction provides excellent functional outcome, including continence, for elderly patients. Colonic J-pouch reconstruction is a highly preferable alternative to permanent colostomy in elderly patients undergoing low anterior resection.

Oxidation behavior of Fe-20Cr-4Al-S (185ppm) alloys with hafnium was studied in dry air at 1273K for 3600ks by mass change measurements, macro-morphology of oxidized surface, X-ray diffraction and scanning electron microscopy. The mass change of the alloy containing only 185ppmS was of 0.67×10-2kg/m2. The mass changes of all the alloys increased in the order of the 900ppmHf

Plexiform schwannoma is an infrequent variant of schwannoma characterized grossly and microscopically by multi-nodular growth. Although plexiform schwannoma has such growth patterns, it is a benign tumor as well as a conventional schwannoma. It rarely infiltrates adjacent organs or arises from the organ itself. In this report, we describe a case in which plexiform schwannoma involved the tracheal wall and left recurrent laryngeal nerve to a great extent. As it was expected to be difficult to achieve complete resection even if the longer tracheal resection were performed, we preserved the trachea and resected as much of the tumor as possible. This report is thought to be the first to describe plexiform schwannoma infiltrating or growing from the trachea. Although the treatment decisions we made might be controversial, we believed we could make an accurate diagnosis and adequate treatment decision through surgery. Electronic supplementary material The online version of this article (doi:10.1186/s40792-015-0070-0) contains supplementary material, which is available to authorized users.