[Superior Vena Cava Syndrome].

Superior vena cava(SVC)syndrome is a syndrome caused by impaired venous return due to stenosis of the SVC. Most of such cases are due to tumors(non-small cell lungcancer, small cell lungcancer, malignant lymphoma, etc), and the most common cause of SVC syndrome is lungcancer. Symptoms of SVC syndrome are caused by external compression of the SVC, direct invasion, internal thrombus or embolization. Increased venous pressure results in objective findings including edema of the face and neck, edema of the upper limbs, superficial precordial vein distension due to collateral circulation, and hoarseness and subjective symptoms includingcoug h, dyspnea, syncope, headache, and dizziness. SVC syndrome impair the patient's quality of life(QOL). Although there are cases of spontaneous remission, SVC syndrome is recognized as one of the oncologic emergencies because brain and laryngeal edema can be fatal and urgent care should be provided. Therapeutic modalities include radiotherapy, chemotherapy, stent placement and surgery. Treatment should be determined comprehensively based on the severity, histological type, standard therapy for the histological type and its sensitivity. It is necessary to make a definitive histopathological diagnosis as soon as possible and to cooperate with other departments to promptly select the most appropriate treatment.

[Surgery of Papillary Adenoma;Report of a Case].

A 59-year-old man consulted our hospital because of an abnormal shadow on a chest X-ray without any symptoms. A chest computed tomography (CT) revealed growing pulmonary nodule in the right lower lobe. Benign lung tumor was suspected and the patient underwent right lower lobe partial resection. Pathological examination demonstrated the tumor to be pulmonary papillary adenoma within round atelectasis.

Comparison of Acute Gene Expression Profiles of Islet Cells Obtained via Laser Capture Microdissection between Alloxan- and Streptozotocin-treated Rats.

To identify the molecular profiles of islets from alloxan (ALX)- and streptozotocin (STZ)-treated rats, a microarray-based global gene expression analysis was performed on frozen islets isolated via laser capture microdissection. At 6 weeks old, rats were injected with ALX (40 mg/kg) or STZ (50 or 100 mg/kg) and then euthanized 24 hr later. Histopathological analysis showed ß-cell necrosis, macrophage infiltration, and islet atrophy. The extent of these changes was more notable in the STZ groups than in the ALX group. Transcriptome analysis demonstrated a significant up- or downregulation of cell cycle arrest-related genes in the p53 signaling pathway. Cyclin D2 and cyclin-dependent kinase inhibitor 1A, mediators of G1 arrest, were remarkably altered in STZ-treated rats. In contrast, cyclin-B1 and cyclin-dependent kinase 1, mediators of G2 arrest, were remarkably changed in ALX-treated rats. Genes involved in the intrinsic mitochondria-mediated apoptotic pathway were upregulated in the ALX and STZ groups. Moreover, heat-shock 70 kDA protein 1A ( Hspa1a), Hsp90ab1, and Hsph1 were upregulated in ALX-treated rats, suggesting that ALX treatment injures ß cells via endoplasmic reticulum stress. These results contribute to a better understanding of gene expression in the pathogenesis of islet toxicity.

[Surgical Case of Pulmonary Enteric Adenocarcinoma].

A 59-year-old man consulted our hospital because of an abnormal shadow on a chest computed tomography, located in the right lower lobe. Fluorodeoxyglucose-positron emission tomography showed abnormal uptake in the tumor suggesting lung cancer and right lower lobectomy was performed. Pathological the tumor was diagnosed as lung cancer comprising tall columnar cells. Immunohistochemical staining was positive for TTF-1, CK-7 and CK-20. Postoperative screening of the abdomen revealed no suspicious primary lesion in the colon and the tumor was diagnosed as a pulmonary enteric adenocarcinoma.

[Pneumothorax Caused by Multiple Pulmonary Metastases of a Uterine Endometrial Stromal Sarcoma;Report of a Case].

A 53-year-old woman who had undergone hystero-oophorectomy for uterine endometrial stromal sarcoma in our hospital 9 months previously was referred to our hospital because of bilateral pneumothorax. Chest computed tomography scan on admission revealed multiple thin-walled cavity nodules in both lung and a bilateral pneumothorax, suggesting pulmonary metastases of the uterine endometrial stromal sarcoma. We surgically treated the pneumothorax and diagnosed the nodules as metastatic lesions. They were pathologically diagnosed as metastatic uterine endometrial stromal sarcoma.

[Surgical Case of Pulmonary Blastoma;Report of a Case].

A 81-year-old man consulted our hospital because of an abnormal shadow on a chest radiography in the right lower field. Computed tomography of the chest showed a mass shadow measuring 41 mm in diameter in the lower lobe of the right lung. There was no lymph node swelling in the hilum or mediastinum. A diagnosis of the lung cancer was suspected and the patient underwent right lower lobectomy with standard nodal dissection. Microscopically, the tumor revealed the epithelial component mimicking fetal lung tissue and proliferative mesenchymal component consisting of immature and heteromorphic nuclear cells as well. The final diagnosis was pulmonary blastoma classified as pathological stage IIB. He was not scheduled for adjuvant chemotherapy due to his older age.

[Pulmonary Alveolar Proteinosis Observed in the Subpleural Area;Report of a Case].

A 39-year-old man consulted our hospital because of an abnormal shadow on a chest X-ray without any symptoms. A chest computed tomography revealed patchy peripheral ground-glass attenuation, in the subpleural area. Bronchoalveolar lavage fluid was clear and transbronchial lung biopsy findings were inconclutive. A video-assisted thoracic surgery-biopsy was performed. The specimens demonstrated accumulation of proteinaceous materials within alveolar spaces. The patient was given a diagnosis of pulmonary alveolar proteinosis.

[Emergency Surgery for Intercostal Lung Hernia after Right Upper Lobe Resection for Lung Cancer;Report of a Case].

We report an operative case of intercostal lung hernia after resection of a Lung cancer. A 60-year-old man with asthma consulted our hospital because of an abnormal shadow on a chest X-ray. A chest computed tomography revealed a tumor in the right upper lobe. A diagnosis of lung cancer was suspected and the patient underwent right upper lobectomy with standard nodal dissection from 4th intercostal space with right anterolateral incision. Intercostal space was directly closed by three stitches. A chest drain was removed on the 5th operative day. On the 6th operative day, the patient suddenly developed asthma attack and radiologically, the middle lobe was found to prolapse from the chest wall. An emergency surgery was performed, and the intercostal space was closed by approximating the ribs with 6 stitches. The patient was discharged from our hospital on the 26th postoperative day.

[Vacuum-assisted Closure for Mediastinitis Caused by Methicillin-resistant Staphylococcus aureus after Coronary Artery Bypass Grafting;Report of a Case].

A 78-year-old man underwent off-pump coronary artery bypass grafting in our hospital. Purulent discharge from a sternotomy wound appeared 8 days after the operation of sternal re-fixation for sternal fracture. Methicillin-resistant Staphylococcus aureus(MRSA) was identified by the culture of the wound exudate. He underwent a surgical revision with the removal of the sternal wires and necrotic tissues. After sufficient irrigation, vacuum-assisted closure therapy was adopted and finally the wound was naturally healed. Vacuum-assisted closure therapy was an effective treatment for MRSA mediastinitis after coronary artery bypass grafting.

Plasma miR-208 as a useful biomarker for drug-induced cardiotoxicity in rats.

Cardiotoxicity is one of the major safety concerns in drug development. Therefore, detecting and monitoring cardiotoxicity throughout preclinical and clinical studies is important for pharmaceutical companies. The present study was conducted in order to explore a plasma miRNA biomarker for cardiotoxicity in rats. As organ specificity is an important factor for a biomarker, we analyzed the miRNA microarray dataset in 55 organs/tissues in normal male rats. Based on this analysis, 5 miRNAs consisting of miR-208 (heart-specific), miR-1, miR-133a, miR-133b (heart and skeletal muscle-specific) and miR-206 (skeletal muscle-specific) were selected. Next, we evaluated the usefulness of those 5 miRNAs as circulating biomarkers in rats administered with single-dose isoproterenol or doxorubicin. Plasma miR-208 was consistently increased through 24 h after dosing in rats administered with isoproterenol, whereas plasma concentrations of cardiac troponin (cTn) showed transient elevation. In contrast, the plasma levels of miR-1, miR-133a, miR-133a and miR-206 were elevated after treatment with doxorubicin, probably as a result of skeletal muscle toxicity. Additionally, the plasma miR-208 level was elevated even after repeat-dose administration (once daily for 7 days) of isoproterenol under which the pathological condition proceeded to the sub-chronic phase such as fibrosis. Thus, our data suggest that miR-208 is a promising plasma biomarker for cardiotoxicity in rats. Monitoring of plasma miR-208 levels in rats may lead to more accurate evaluation of cardiotoxicity in preclinical studies.

[Surgically Treated Clear Cell Carcinoma of the Lung; Report of a Case].

We report an operative case of primary clear cell carcinoma of the lung. A 47-year-old man consulted our hospital because of back pain and an abnormal shadow on a chest computed tomography(CT). A chest CT revealed a nodule in the lung cyst. A diagnosis of lung cancer was suspected and the patient underwent right upper lobectomy with standard nodal dissection. Pathological findings are the lung cancer spreading along the cysts' inner walls. Most of the tumor cells were characterized as having large clear cytoplasm. Screening of the abdomen performed pre- and post-operatively revealed no suspected primary lesion in the kidney, and the tumor was diagnosed as clear cell carcinoma of the lung. Postoperative adjuvant chemotherapy with cisplatin and vinorelbine ditartrate was performed. Patient is well without reccurence 3 years after surgery.

[Lung Abscess Diagnosed as Adenocarcinoma by Needle Biopsy;Report of a Case].

We report a case of lung abscess misdiagnosed as adenocarcinoma based on cytologic findings of the sample obtained from needle biopsy. A 45-year-old man consulted our hospital because of fever, wet cough and an abnormal shadow on a chest X-ray film. A chest computed tomography revealed gradually enlarging pulmonary mass in the left S6 infiltrating the S5. A diagnosis of lung cancer was suspected and surgery was performed. Pathological findings of the specimen showed atypical cells with a large nucleus and a gross papillary neoplasm by needle biopsy. The patient underwent left lower lobectomy and partial resection of upper lobe with standard nodal dissection. The final diagnosis was a lung abscess with pneumonia without evidence of malignancy. When an indeterminate pulmonary tumor must be diagnosed during an operation, we should perform partial resection if possible.

Combinatorial measurement of CDKN1A/p21 and KIF20A expression for discrimination of DNA damage-induced clastogenicity.

In vitro mammalian cytogenetic tests detect chromosomal aberrations and are used for testing the genotoxicity of compounds. This study aimed to identify a supportive genomic biomarker could minimize the risk of misjudgments and aid appropriate decision making in genotoxicity testing. Human lymphoblastoid TK6 cells were treated with each of six DNA damage-inducing genotoxins (clastogens) or two genotoxins that do not cause DNA damage. Cells were exposed to each compound for 4 h, and gene expression was comprehensively examined using Affymetrix U133A microarrays. Toxicogenomic analysis revealed characteristic alterations in the expression of genes included in cyclin-dependent kinase inhibitor 1A (CDKN1A/p21)-centered network. The majority of genes included in this network were upregulated on treatment with DNA damage-inducing clastogens. The network, however, also included kinesin family member 20A (KIF20A) downregulated by treatment with all the DNA damage-inducing clastogens. Downregulation of KIF20A expression was successfully confirmed using additional DNA damage-inducing clastogens. Our analysis also demonstrated that nucleic acid constituents falsely downregulated the expression of KIF20A, possibly via p16 activation, independently of the CDKN1A signaling pathway. Our results indicate the potential of KIF20A as a supportive biomarker for clastogenicity judgment and possible mechanisms involved in KIF20A downregulation in DNA damage and non-DNA damage signaling networks.

Durvalumab plus carboplatin-etoposide treatment in a patient with small-cell lung cancer on hemodialysis: a case report and literature review.

Little is known about the efficacy and safety of durvalumab plus carboplatin-etoposide treatment in patients with extensive-disease (ED) small-cell lung cancer (SCLC) on hemodialysis. Here, we present a case of a 67-year-old man with pleuroperitoneal communication on continuous ambulatory peritoneal dialysis who was diagnosed with ED-SCLC based on a cytological analysis of the peritoneal fluid. He was switched from peritoneal dialysis to hemodialysis and received durvalumab (1500 mg/body on day 1) plus carboplatin (area under the concentration-time curve = 5, 125 mg on day 1) and etoposide (50 mg/m2 on days 1 and 3) as first-line therapy. During the first cycle, grade 2 anemia, grade 3 neutropenia, and grade 3 upper gastrointestinal bleeding occurred; therefore, durvalumab and reduced doses of carboplatin and etoposide were administered. No other severe adverse events occurred, and a partial response was observed after four cycles. Our findings indicate that durvalumab plus carboplatin-etoposide treatment is safe and effective even in patients on hemodialysis.

Genomic biomarkers for cardiotoxicity in rats as a sensitive tool in preclinical studies.

The development of safer drugs is a high priority for pharmaceutical companies. Among the various toxicities caused by drugs, cardiotoxicity is an important issue because of its lethality. In addition, cardiovascular toxicity leads to the attrition of many drug candidates in both preclinical and clinical phases. Although histopathological and blood chemistry examinations are the current gold standards for detecting cardiotoxicity in preclinical studies, the large number of withdrawals from clinical studies owing to safety problems indicate that a more sensitive tool is required. We recently identified 32 genes that were candidate genomic biomarkers for cardiotoxicity in rats. Based on their functions, the present study focused on 8 of these 32 genes (Spp1, Fhl1, Timp1, Serpine1, Bcat1, Lmcd1, Rnd1 and Tgfb2). Diagnostic accuracy for the genes was determined by a receiver-operating characteristic (ROC) analysis using more cardiotoxic and non-cardiotoxic compounds. In addition, an optimized support vector machine (SVM) model that was composed of Spp1 and Timp1 was newly constructed. This new multi-gene model exhibited a much higher diagnostic accuracy than that observed for plasma cardiac troponin I (cTnI), which is one of the most useful plasma biomarkers for cardiotoxicity detection. Furthermore, we determined that this multi-gene model could predict potential cardiotoxicity in rats in the absence of any cardiac histopathological lesions or elevations of plasma cTnI. Overall, this multi-gene model exhibited advantages over classic tools commonly used for cardiotoxicity evaluations in rats. Our current results suggest that application of the model could potentially lead to the production of safer drugs.

Correction to: Vitiligo and tumor response in a patient with amelanotic melanoma undergoing nivolumab treatment.

[This corrects the article DOI: 10.1007/s13691-021-00515-w.].

Vitiligo and tumor response in a patient with amelanotic melanoma undergoing nivolumab treatment.

Vitiligo, an acquired depigmenting disorder of the skin that reacts against normal melanocytes, sometimes occurs as an immune-related adverse event in the treatment of melanoma with immune checkpoint inhibitors. It has been known that the occurrence of vitiligo is associated with a favorable therapeutic response in patients with melanoma, but it is not yet clear whether the association also applies to amelanotic melanoma, a minor subtype of melanoma with little or no melanin pigmentation. We report a patient with amelanotic melanoma of the esophagus who responded well to nivolumab treatment. Shortly after the tumor response, vitiligo was found on the patient's forearms. This case suggests that the occurrence of vitiligo is associated with a favorable response to nivolumab treatment for amelanotic melanoma.

Prediction model of potential hepatocarcinogenicity of rat hepatocarcinogens using a large-scale toxicogenomics database.

The present study was performed to develop a robust gene-based prediction model for early assessment of potential hepatocarcinogenicity of chemicals in rats by using our toxicogenomics database, TG-GATEs (Genomics-Assisted Toxicity Evaluation System developed by the Toxicogenomics Project in Japan). The positive training set consisted of high- or middle-dose groups that received 6 different non-genotoxic hepatocarcinogens during a 28-day period. The negative training set consisted of high- or middle-dose groups of 54 non-carcinogens. Support vector machine combined with wrapper-type gene selection algorithms was used for modeling. Consequently, our best classifier yielded prediction accuracies for hepatocarcinogenicity of 99% sensitivity and 97% specificity in the training data set, and false positive prediction was almost completely eliminated. Pathway analysis of feature genes revealed that the mitogen-activated protein kinase p38- and phosphatidylinositol-3-kinase-centered interactome and the v-myc myelocytomatosis viral oncogene homolog-centered interactome were the 2 most significant networks. The usefulness and robustness of our predictor were further confirmed in an independent validation data set obtained from the public database. Interestingly, similar positive predictions were obtained in several genotoxic hepatocarcinogens as well as non-genotoxic hepatocarcinogens. These results indicate that the expression profiles of our newly selected candidate biomarker genes might be common characteristics in the early stage of carcinogenesis for both genotoxic and non-genotoxic carcinogens in the rat liver. Our toxicogenomic model might be useful for the prospective screening of hepatocarcinogenicity of compounds and prioritization of compounds for carcinogenicity testing.

Penetrating nail-gun injury of the thoracic descending aorta.

Penetrating injury of the descending aorta due to accidental discharge of a nail gun.