Sakiko Tazawa

Clinical features and outcomes of aspiration pneumonia compared with non-aspiration pneumonia: A retrospective cohort study

Pneumonia is a leading cause of death among elderly patients. Although aspiration pneumonia (AP) commonly occurs with aging, its clinical features and outcomes are still uncertain. The aims of this study were to describe the clinical features and outcomes of AP and to assess whether presence of AP affects clinical outcomes in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). We retrospectively analyzed patients with CAP and HCAP hospitalized in our institution in Japan from October 2010 to March 2012. We compared clinical features and outcomes between AP and non-AP, and investigated risk factors for recurrence of pneumonia and death. Of 214 consecutive patients, 100 (46.7%) were diagnosed as having aspiration pneumonia. These patients were older and had lower body mass index, more comorbidities, and poorer Eastern Cooperative Oncology Group performance status (ECOG PS) than the patients with non-AP. Patients with AP had more severe disease, required longer hospital stays, and had a frequent recurrence rate of pneumonia and higher mortality. In multivariate analyses, AP, age, and ECOG PS were related to recurrence of pneumonia, and the prognostic factors were CURB-65 score and ECOG PS. AP was not a significant indicator for prognosis but was the strongest risk factor for recurrence of pneumonia. Clinical background and outcomes including recurrence and mortality of AP were obviously different from those of non-AP; therefore AP should be considered as a distinct subtype of pneumonia, and it is important to prevent the recurrence of pneumonia in the patients with AP.

Acquired resistance L747S mutation in an epidermal growth factor receptor-tyrosine kinase inhibitor-naïve patient: A report of three cases

The purpose of the present study was to report cases of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-naïve patients carrying a mutation associated with acquired resistance to the drug. Gene alterations in 77 lung carcinoma patients were analyzed by collecting and studying curette lavage fluid at the time of diagnosis. PCRs were performed to amplify mutation hotspot regions in EGFR genes. The PCR products were direct-sequenced and the mutations confirmed by resequencing using different primers. Case 1 was a 78-year-old Japanese male diagnosed with stage IB lung adenocarcinoma who was found to have two EGFR mutations, G719S and L747S. Case 2 was a 73-year-old Japanese male diagnosed with stage IV squamous cell lung carcinoma and bone metastasis who had the EGFR mutation, L747S. Case 3 was an 82-year-old Japanese male diagnosed with hyponatremia due to inappropriate secretion of antidiuretic hormone and stage IIIB small cell lung carcinoma (SCLC) who had the EGFR mutation, L747S. Thus, the EGFR mutation L747S associated with acquired EGFR-TKI resistance was detected in two non-small cell lung carcinoma (NSCLC) patients and one SCLC patient, none of whom had ever received EGFR-TKI. The patients were current smokers with stages at diagnosis ranging from IB to IV, and their initial tumors contained resistant clones carrying L747S. L747S may be associated with primary resistance. To the best of our knowledge, this study is the first report of an EGFR mutation associated with resistance to EGFR-TKI in SCLC patients. The early detection of EGFR-TKI resistance mutations may be beneficial in making treatment decisions for lung carcinoma patients, including those with SCLC.

CD200 Expression on Plasma Cell Myeloma Cells is Associated with the Efficacies of Bortezomib, Lenalidomide and Thalidomide

Plasma cell myeloma (PCM) is a devastating disease with a highly heterogeneous outcome, with survival ranging from a few months to longer than 10 years. Treatment of multiple myeloma has changed markedly in the past decade due to the development of new drugs such as bortezomib, lenalidomide and thalidomide, which have greatly improved the outcome of PCM. The clinical and prognostic value of immunophenotyping in PCM remains questionable. The aim of this study was to determine the diagnostic and prognostic significance of CD200 expression in newly diagnosed PCM. We retrospectively reviewed the records of 107 patients newly diagnosed with PCM at Showa University Hospital between January 2004 and September 2013. Expression of CD200 was studied by immunohistochemistry. Clinical and pathological parameters were compared between CD200-positive and CD200-negative cases. CD200-positive PCM cases had lower serum albumin (p = 0.0001) compared to those without CD200 expression. Our results showed no significant difference in median overall survival between patients with CD200-positive and CD200-negative PCM. However, there was a strong correlation between CD200 expression and serum albumin level. In the CD200-negative group, median overall survival was significantly longer in patients who received new drug treatment. These findings suggest that CD200 expression is a useful marker for evaluation of the severity of PCM and that lack of CD200 expression may improve the sensitivity of PCM to therapy with new drugs.

Immunohistochemical CD73 expression status in gastrointestinal neuroendocrine neoplasms: A retrospective study of 136 patients

The WHO 2010 classification divides gastrointestinal neuroendocrine neoplasms (GI-NENs) into neuroendocrine tumor (NET) G1, NET G2, neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) groups. A total of 136 cases of GI-NENs diagnosed at our hospitals as gastrointestinal carcinoids, endocrine cell carcinomas and NENs over the last 11 years, using the WHO 2010 classification were assessed. Among the 136 cases, 88.2% (120/136) were classified into the NET group (NET G1/G2) and 11.8% (16/136) were classified into the NEC group (NEC/MANEC). The incidences of lymphatic and venous invasions were higher in the NEC group compared with in the NET group (P<0.0001 and P=0.0021, respectively). The immunohistochemical staining of cluster of differentiation 73 (CD73) was evaluated in GI-NENs. CD73 is a potentially useful molecule in tumor immunity. In general, CD73 on the tumor cell membrane converts adenosine monophosphate to adenosine, which restrains the production of interferon-γ and cytocidal activity. Although the association between stem cells of pancreatic NENs and CD73 has been reported, few studies have reported on CD73 expression in GI-NENs. Immunohistochemical CD73 expression on the cytomembrane of neuroendocrine cells was detected in 27.2% (37/136) of the GI-NENs. The positive ratio of CD73 was significantly higher in the NEC group compared with in the NET group (P=0.0015). CD73 is also considered as a potential biomarker of anti-programmed death-1 (PD-1) therapy. The expression of programmed death-ligand 1 (PD-L1) on the cytomembrane of GI-NENs was assessed. The positive ratio of PD-L1 was higher in the NEC group compared with in the NET group (P=0.0011). Furthermore, CD73 expression status was significantly correlated with PD-L1 expression (P<0.0001). These results indicate that CD73 may be an interesting candidate for a biomarker for certain prognostic factors and therapeutics concerning PD-1 therapy.

The role of microvessel density, lymph node metastasis, and tumor size as prognostic factors of distant metastasis in colorectal cancer

Angiogenesis is essential for tumor growth and metastasis. CD105 is reportedly a specific marker for tumor angiogenesis. It has been demonstrated that monoclonal antibodies to CD105 have high affinity for activated endothelial cells. A relationship between metastasis and microvessel density (MVD), as an indicator of neovascularization, has been identified in patients with colorectal cancer as shown by the presence of monoclonal antibodies to CD105. However, data on potentially confounding factors such as lymphatic and vascular infiltration and tumor size are lacking. We further investigated the relationship between MVD and distant metastasis, along with potentially confounding clinicopathological factors, to more precisely characterize this relationship. In this retrospective study, we analyzed colorectal cancer specimens surgically or endoscopically resected from January to September 2009. We defined MVD as the number of microvessels stained by monoclonal antibodies to CD105 per ×400 field. Selected clinicopathological factors were analyzed and stepwise multivariate logistic regression was performed to identify independent risk factors for distant metastasis. We analyzed 129 lesions. The median follow-up time was 34 months (range, 6-85 months) in patients with distant metastasis and 61 months (range, 60-86 months) in those without distant metastasis. At the time of resection or during subsequent follow-up, 32 patients had distant metastases. The MVD was significantly greater in patients with than without distant metastases (mean ± standard deviation: 10.4±4.9 vs. 7.6±3.3, P=0.008; Welchs t-test). Stepwise multivariate logistic regression indicated that MVD, regional lymph node metastasis, and tumor size were independent risk factors for distant metastases. Combining assessment of monoclonal antibodies to CD105-positive MVD with assessment of regional lymph node metastasis and tumor size may help to identify patients who need more intensive surveillance after surgery for colorectal cancer.

[Retracted] Analysis of YAP1 and TAZ expression by immunohistochemical staining in malignant mesothelioma and reactive mesothelial cells

[This retracts the article DOI: 10.3892/ol.2018.8225.].

Expression of matrix metalloproteinase-7 correlates with the invasion of T1 colorectal carcinoma

T1 colorectal carcinomas (CRCs) are an initial site of metastatic spread. Various risk factors for lymph node metastasis have been investigated in T1 CRCs. However, the major step in the entire process of metastasis remains unclear. In terms of carcinoma invasion and metastasis, matrix metalloproteinases (MMPs) have recently gained increasing attention. Notably, MMP-7 is frequently overexpressed in CRCs, but its implication has not been determined in T1 CRCs yet. The present study aimed to clarify the associations between the pathological risk factors of T1 CRCs and MMP-7. In the current study, 211 lesions of T1 CRC that were resected endoscopically or surgically at Showa University Northern Yokohama Hospital (Yokohama, Japan) between April 2008 and December 2009 were retrospectively analyzed. MMP-7 was immunostained and evaluated by its frequency of expression. Pathological factors of T1 CRCs were analyzed in association with MMP-7 expression. Furthermore, the ultrastructural alterations of carcinoma invasion were examined using low vacuum-scanning electron microscopy (LV-SEM). MMP-7 expression was associated with venous invasion (P=0.005), and LV-SEM revealed the disappearance of the normal structure of collagen and elastic fibers of veins invaded by tumor cells expressing MMP-7. At the invasive front, MMP-7 has a vital role in carcinoma invasion, correlating with venous invasion of T1 CRCs.

Analysis of YAP1 and TAZ expression by immunohistochemical staining in malignant mesothelioma and reactive mesothelial cells Retraction in /10.3892/ol.2018.9405

Gene mutations are involved in the development of malignant mesothelioma. Important mutations have been identified in the genes for cyclin-dependent kinase inhibitor 2A (p16) alternative reading frame, breast cancer-associated protein 1 (BAP1) and neurofibromatosis type 2 (NF2). Previously, the utility of detecting the loss of BAP1 by immunohistochemistry (IHC) and p16-deletion by fluorescence in situ hybridization has been identified in several studies. However, NF2-associated examinations have not been performed. The present study aimed to evaluate the expression of yes-associated protein 1 (YAP1) and tafazzin (TAZ) protein, which are associated with NF2 gene mutations, in malignant mesothelioma (MM) and reactive mesothelial cells (RMCs). Formalin-fixed paraffin-embedded tissues from 31 MM and 33 RMC samples were analyzed. The expression of YAP1 and TAZ protein were examined by IHC. Positivity for YAP1 was identified 27/31 MM and 15/33 RMC samples. Positivity for TAZ was identified in 28/31 MM and 18/33 RMC samples. Using the optimal cutoff points determined by the receiver operating characteristic curve, a positive IHC result for YAP1 and TAZ was 74% sensitive and 94% specific for detecting MM. The results indicate that increased expression of YAP1 and TAZ may be associated with mesothelial tumorization, and aid in the diagnosis of MM.

A solitary bronchial squamous cell papilloma with increased 18-fluorodeoxyglucose uptake and high serum levels of squamous cell carcinoma antigen

Squamous cell papillomas are the most common benign tumors of the larynx (1). A solitary bronchial squamous cell papilloma (BSCP) was first reported in 1954 (2). BSCP is a benign tumor originating from squamous cell epithelium cells, and it accounts for 0.38% of all lung tumors (3). There are two primary clinical features of bronchial papillomas. First, BSCP has a tendency to spread to multiple sites within the bronchial tree.