Triple-negative expression (ALDH1A1-/CD133-/mutant p53-) cases in lung adenocarcinoma had a good prognosis.

Cancer stem cells (CSCs) are major contributors to the malignant transformation of cells because of their capacity for self-renewal. Aldehyde dehydrogenase1A1 (ALDH1A1) and CD133 are promising candidate of CSC markers in non-small cell lung cancer (NSCLC). Furthermore, TP53 is frequently mutated in lung cancer, and the loss of its function is associated with malignant characteristics. However, the relationship between CSCs and mutant p53 in lung adenocarcinoma is not well-established. We examined the expression of ALDH1A1, CD133, and mutant p53 in lung adenocarcinoma patients and conducted a clinicopathological study. Triple-negative cases without ALDH1A1, CD133, and mutant p53 expression in lung adenocarcinoma were shown to have a much better prognosis than others. Our present results suggest that detection of CSC markers and mutant p53 by immunohistochemical staining may be effective in therapeutic strategies for lung adenocarcinoma.

Paraneoplastic limbic encephalitis due to lung squamous cell carcinoma.

Paraneoplastic limbic encephalitis (PLE) is one of paraneoplastic neurological syndrome (PNS). We herein report a case of PLE due to lung squamous cell carcinoma. A 80-year-old woman visited because of several neurological symptoms. Brain magnetic resonance imaging revealed hyperintense signals at the splenium of the corpus callosum, suggesting limbic encephalitis. Chest X-ray and computed tomography showed a 17 × 14 mm tumor in the left lung field, suggesting lung cancer. Surgical examination revealed T1bN0M0 lung squamous cell carcinoma. She died 50 days after surgery due to the rapid progression of encephalitis. PLE is an extremely rare disorder, and even a case in the early stage of cancer shows poor prognosis. We should doubt a possibility of PLE, and detailed brain examination should be performed in case of consciousness disorder with rapid progression in the cancer patient.

Association Between CD133 Expression and Prognosis in Human Lung Adenocarcinoma.

BACKGROUND/AIM: CD133 is a promising candidate marker for cancer stem cells. However, clinical studies on CD133 expression in human lung adenocarcinoma have not yet been conducted. We hypothesized that CD133 expression in lung adenocarcinoma is a poor prognostic factor. PATIENTS AND METHODS: CD133 expression in lung adenocarcinoma was examined clinicopathologically. Then, clinicopathological parameters and patient prognosis were investigated. Moreover, CD133 expression was examined via immunohistochemical staining, and the relationship between CD133 expression and clinicopathological parameters was explored. RESULTS: Approximately 48.0% (49/102) of patients had CD133-positive cells. Based on a subgroup analysis, the CD133-positive group with pStage I+II disease had a significantly worse disease-free interval than the CD133-negative group (p<0.05). CONCLUSION: CD133 expression may be a poor prognostic factor in lung adenocarcinoma.

Ingenuity of minimally invasive thoracoscopic lobectomy for undiagnosed pulmonary tumour.

A 51-year-old man was referred to our hospital, with a dumbbell-shaped nodule measuring 40 mm in the right upper lobe of the lung. He was a current smoker with diabetes mellitus and bronchial asthma. The transbronchial biopsy was performed. However, definitive diagnosis was not obtained from the excised specimens. Bacterial culture of bronchial lavage fluid also yielded negative results, including for tuberculosis. After eight months of observation, the tumour had slightly increased in size. Surgery was planned to resect the tumour for definitive diagnosis. Because of the size of the tumour, a lobectomy of the lung was scheduled with the patient's consent. Four small incisions, each less than 1.2 cm long, were made in the chest wall for thoracoscopic surgery. To remove the specimen, we made a 3-cm longitudinal incision 1 cm below the xiphisternal joint. The patient complained of no chest pain after surgery. The post-operative course was uneventful.

[Prediction of Pleural Adherence Area Used by Ultrasound Sonography].

Video-assisted thoracoscopic surgery has been used to treat lung cancer. However, pleural adhesions may increase the risk of lung injury while making the access port. We report a case of lung cancer in which preoperative lung ultrasound sonography was used to predict the pleural adherence area. An octogenarian man had undergone chest surgery for right spontaneous pneumothorax 20 years ago. He was recently diagnosed with a right middle lobe carcinoma and thoracoscopic surgery was scheduled. On preoperative lung ultrasound sonography, adhesion in the area surrounding the previous incision line was predicted to be strong. However, a sliding lung sign was observed in the pleura on the caudal side, where no adhesions were expected. The thoracoscopic findings during the operation revealed that adhesions were present in the upper and middle regions of the pleural cavity in the locations and to the extent predicted before surgery, but no adhesion was observed on the caudal side. We were able to make an access port avoiding the adherence area in the pleural cavity. Lung ultrasound sonography was useful for detection of the adherence area between the parietal and visceral pleura in this case.

The Clinical Significance of Cancer Stem Cell Markers ALDH1A1 and CD133 in Lung Adenocarcinoma.

BACKGROUND/AIM: Aldehyde dehydrogenase-1A1 (ALDH1A1) and CD133 have been identified as markers of cancer stem cells (CSCs). We investigated the expression of these markers and their clinical significance in lung adenocarcinoma. MATERIALS AND METHODS: An immunohistochemical analysis of ALDH1A1 and CD133 expression of 92 lung adenocarcinomas was performed. The association between the expression of both markers and cancer-related death and recurrence was determined. RESULTS: Cancer-related death and tumor recurrence were observed in 15 and 17 cases, respectively. The expression of CD133, but not ALDHA1A, was significantly associated with poorer overall survival (p<0.0001) and shorter disease-free interval (DFI) (p<0.0001). Multivariate analysis revealed that double negativity was independently associated with increased survival (hazard ratio(HR)=16.1, p=0.0004) and a longer DFI (HR=9.5, p=0.0007). CONCLUSION: We propose that as a functional marker, ALDH1A1 positivity may influence the viability of CSCs. The findings suggest that it is important to evaluate the expression of both markers.

[Endobronchial Watanabe Spigot in Treating Pleural Empyema with Fistula].

For pleural empyema with fistula, fenestration and subsequent omental plombage, and thoracoplasty are frequently necessary. A 57-year-old man was transported by ambulance because of impaired consciousness and septic shock due to pleural empyema on the right caused by a ruptured lung abscess. We performed empyema curettage urgently, drained 800 ml of purulent pleural effusion, and inserted 3 chest tubes. Postoperative air leakage from the ruptured lung abscess of the middle lobe was noted, and respiratory failure was prolonged. We inserted an Endobronchial Watanabe Spigot (EWS) into bronchus B5b on postoperative day 11. The air leak stopped, and the inflammatory response was gradually reduced. Computed tomography revealed decrease in free air space. We removed the chest tubes on postoperative day 35, and was able to wean off the ventilator on postoperative day 60. He was discharged on postoperative day 102. Bronchial plombage with EWS is a procedure of choice in treating pleural empyema with fistula caused by pulmonary abscess rupture, and can avoid fenestration in these patients.

The diagnosis of primary cardiac lymphoma was facilitated by computed tomographic coronary angiography.

Primary cardiac lymphoma (PCL) is a rare entity that leads to fatal symptoms such as serious arrhythmia. The present case was an 80-year-old female with severe dyspnea caused by 30 bpm bradycardia. Computed tomography revealed a tumor invading to the right inferior myocardium. A computed tomographic coronary angiography (CTCA) study revealed the right coronary artery penetrating the tumor with no invasion by the surrounding tumor. Because a percutaneous biopsy was unsuccessful, video-assisted thoracic surgery (VATS) was performed. The final pathological diagnosis was diffuse large B cell lymphoma. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy reduced the size of the tumor, and the symptoms thereafter improved. An observation of the coronary artery penetrating the tumor without tumor invasion may be a characteristic finding of PCL. CTCA is useful to detect this finding. When a percutaneous biopsy is unavailable, VATS should be considered as a minimally invasive procedure to obtain a reliable diagnosis of PCL.

Subglottic granuloma after aortic replacement: resection via flexible bronchoscopy after an emergency tracheostomy.

A subglottic granuloma is one of the late-phase complications that can occur after intubation. It can cause a life-threatening airway obstruction; therefore, a rapid diagnosis and appropriate treatment plan is necessary. A 62-year-old male had undergone an emergency total arch replacement for acute aortic dissection. Postoperative ventilation support had been performed until the 15th postoperative day (POD). He was discharged from the hospital on POD 30. On POD 50, he was brought to our hospital by an ambulance with severe dyspnea. A large subglottic granuloma occupying the trachea was identified by flexible bronchoscopy. After an emergency tracheostomy, resection of the granuloma with argon plasma coagulation via flexible bronchoscopy was performed safely. Physicians should suspect a post-intubation subglottic granuloma when patients who have undergone intubation report feeling throat discomfort. Resection via flexible bronchoscopy after tracheostomy is a safe and feasible procedure that may shorten the duration of therapy and hospital stay.

[A case of lung adenocarcinoma with uncontrollable myocardial metastasis and pericardial effusion].

A 73-year-old Japanese man visited a local hospital due to palpitations and dyspnea. He was diagnosed as having lung cancer (adenocarcinoma, cT1aN2M1b (BRA), stage Ⅳ), but he did not want to receive any anticancer medications, and was simply being observed. Several months later, he was referred to our hospital due to exacerbation of the dyspnea. His chest computed tomography revealed massive pericardial effusion, therefore he was diagnosed as having cardiac tamponade due to carcinomatous pericarditis and was immediately hospitalized. Upon admission, pericardial fenestration was firstly applied in order to drain pericardial effusion, and intraoperative cardiac findings showed suspicion of myocardial and pericardial metastasis. Immediately after the pericardiotomy, he suffered from cardiac arrest caused by shock. In lung cancer patients with pericardial effusion, even though it is rare, myocardial metastasis in addition to carcinomatous pericarditis and pericardial metastasis should be kept in mind.

Pulmonary dirofilariasis in a 59-year-old man.

We present a case of a human pulmonary dirofilariasis in a 59-year-old man. At the medical examination, a chest computed tomography (CT) revealed a mass, measuring 18 × 15 mm in diameter, with an irregular margin on the bottom of the right lower lobe. We could not neglect the possibility of a primary lung cancer, and therefore, a lung partial resection was performed under video-assisted thoracoscopic surgery. The intra-operative pathological findings revealed inflammatory granuloma with coagulation necrosis and no malignant cells. The permanent pathological examination showed occlusion of the peripheral pulmonary artery by worms and formation of a necrotic mass surrounded by reactive inflammation and hemorrhage. Human pulmonary dirofilariasis is an extremely rare zoonotic infection, and sometimes it is difficult to distinguish it from a primary lung cancer on radiographic findings.

Cytochrome P450 in non-small cell lung cancer related to exogenous chemical metabolism.

The occurrence of lung cancer is associated with smoking, which exposes smokers to a series of carcinogenic chemicals. CYP (cytochrome P450) usually metabolizes carcinogens to their inactive derivatives, but occasionally convert the chemicals to more potent carcinogens. In addition to the metabolism of carcinogenic compounds, CYP also participates in the activation and/or inactivation of anti-carcinogenic agents, suggesting that the local CYP expression in lung cancer and surrounding tissues could be an important determinant of efficacy of anticancer drugs. Furthermore, CYP19 (aromatase), estrogen synthase P450, expressed in more than 80 percent of non-small cell lung cancers. It suggests an association between estrogens and cancer development, which makes aromatase an attractive therapeutic target for the treatment of lung cancer. 1alpha,25-Dihydroxyvitamin D3 has an inhibitory effect on the proliferation of cancer tissues, and is converted to its inactive 24-hydroxylated derivatives by CYP24, which is frequently expressed in lung cancer tissues. Therefore, understanding the CYP expression in tumor tissues is important in developing better therapies for lung cancer, and may lead us to standardized, tailor-made therapies for individuals.

Successful treatment of lung adenocarcinoma in an 18-year-old man.

Primary lung cancer is an extremely rare neoplasm in young adults. We report a case of a primary lung adenocarcinoma in an 18-year-old man who presented for examination of a solitary nodule located in the right lower lobe of the lung. A right lower lobectomy was performed with an incomplete resection because of pleural dissemination (pT4N2M0 stage IIIB adenocarcinoma). Intrathoracic chemotherapy (cisplatin, 50 mg/body) was administered initially, followed by systemic chemotherapy (carboplatin + paclitaxel). A bronchopleural fistula occurred 2 months postoperatively and was successfully treated with conservative therapy, including thoracic drainage, intrathoracic fibrin glue administration, and transbronchial superglue administration. Thereafter, a total of five courses of systemic chemotherapy with minor changes in the administration regimen were performed. The patient was alive and with no evidence of recurrence at his 5-year follow-up.

A randomized phase II trial of adjuvant chemotherapy with bi-weekly carboplatin plus paclitaxel versus carboplatin plus gemcitabine in patients with completely resected non-small cell lung cancer.

BACKGROUND: The benefits of adjuvant chemotherapy for completely resected non-small cell lung cancer (NSCLC) have been demonstrated using mainly cisplatin (CDDP)-based chemotherapeutic regimens. However, treatment-related deaths sometimes occur. Therefore, the development of a safer regimen is necessary. PATIENTS AND METHODS: The patients were randomized to either carboplatin (CBDCA) area under the curve (AUC) 3 and paclitaxel (PTX) 90 mg/m(2) (PCb arm) or CBDCA (AUC3) plus gemcitabine (GEM) (1000 mg/m(2)) (GCb arm) every 2 weeks for 8 cycles after surgery. The primary endpoint was the compliance with the regimen, while the secondary endpoints were safety and toxicity. RESULTS: A total of 75 patients were enrolled in a multi-institutional study. Twenty-one out of 39 patients (54%) in the PCb arm and 25 of 36 patients (69%) in the GCb arm completed 8 cycles, and 59% in the PCb arm and 81% in the GCb arm completed ≥6 cycles. The predominant toxicity was neutropenia. Non-hematological adverse effects were infrequent and no treatment-related death was registered. The estimated disease-free survival and overall survival at 2 years were 70.8% and 66.3% in the PCb and 91.4% and 79.1% in the GCb arm, respectively. CONCLUSION: This adjuvant bi-weekly scheduled chemotherapy resulted in good compliance in both arms, and the regimen was feasible, with acceptable levels of toxicity in completely resected Japanese NSCLC patients. Therefore, these regimens represent a new treatment option suitable for outpatients with completely resected NSCLC.

Surgical treatment for chest wall invasion due to the local recurrence of breast cancer.

OBJECTIVE: In this study, we investigated the surgical results for chest wall invasion of local recurrence of breast cancer. PATIENTS AND METHODS: We reviewed eight patients who underwent a chest wall resection for local recurrence of breast cancer in our department between 1986 and 2004. RESULTS: All of the patients had local recurrence without any distant metastasis. All of them had skin ulcers with blood oozing. The operation procedures were Bt + Ax + Ic + Mj + Mn (Halsted mastectomy) in four patients, Bt + Ax + Ic + Mn (Patey procedure) in two patients, Bt + Ax + Ic (muscle-preserving mastectomy) in one patient, and Bt + Ax (Auchincloss procedure) in one patient. The intervals from the primary operation ranged from 14 months to 20 years. The maximum and minimum areas of the chest wall defect were 18 x 16 cm and 4.5 x 3.5 cm, respectively. Reconstruction of the chest wall was performed using a flap of the rectus abdominis muscle with polypropylene (Marlex) mesh in four patients, a flap of the rectus abdominis muscle combined with sandwich prosthesis of polypropylene mesh and methylmethacrylate in one patient, a flap of latissimus dorsi muscle in one patient, polypropylene mesh with pectoralis major muscle in one patient, and by direct closure in one patient. A survival of more than 3 years was achieved in seven patients and only one patient died 1 year and 2 months after the chest wall resection. CONCLUSION: In patients with the chest wall recurrence of breast cancer without distant metastasis, a surgical resection of the chest wall may be effective both for relieving pain and for control of the local hemorrhage. Seven out of the eight patients survived more than 3 years, suggesting that this surgical treatment could facilitate home health care and maintain a good quality of life for patients with breast cancer.

Mechanism of the action of didecyldimethylammonium chloride (DDAC) against Escherichia coil and morphological changes of the cells.

The antibacterial activity of a disinfectant with geminated twin long-chain alkyl groups, didecyldimethylammonium chloride (DDAC), was investigated. The minimum inhibitory concentration (MIC) value of DDAC against Eschrichia coil was revealed to be a small value, 1.3 mg/L, by using the specific growth rates, mu, obtained from the cultivation in a liquid nutrient broth (NB) medium. The relationship between the leakage of proteins or beta-galactosidase and the DDAC concentration showed that the leakage of intracellular macromolecules occurs at around 3 - 4 mg/L DDAC. Furthermore, the effect of DDAC on the enhancement of membrane fluidity was examined by using liposomes labeled with a fluorescent probe. It was shown that the phase transition occurs at around 3 mg/L DDAC. The bleb formation of E. coli cells in the presence of DDAC was also examined by use of scanning electron microscopy (SEM) and transmission electron microscopy (TEM). However, bleb formation was not observed at around 3 mg/L DDAC but at concentrations higher than 50 mg/L. These results suggested that the action of DDAC toward the cell membrane causes the leakage of the intracellular molecules and the subsequent death of the cells. Thus the bleb formation seemed to be a result of the action of the DDAC toward the cell membrane but not to be a reason for the death of the cells.

Expression of FHIT in esophageal epithelium and carcinoma: reference to drinking, smoking and multicentric carcinogenesis.

BACKGROUND: Both alcohol consumption and cigarette smoking are risk factors for esophageal cancer. The purpose of this study was to clarify whether the fragile histidine triad (FHIT) is their target gene in esophageal carcinogenesis as well as in multicentric carcinogenesis. PATIENTS AND METHODS: The expression of FHIT was immunohistochemically examined in the squamous cell carcinoma as well as in the normal esophageal epithelium of 55 cases with esophageal cancer. RESULTS: The median drinking indices (DIs) were 546 and 1092 (p<0.01) in cases with positive FHIT expression and those with a diminished expression in the esophageal epithelium, respectively. Furthermore, the incidences of intra-esophageal multiple cancer were 44% and 13%, respectively (p<0.05). Regarding the expression in cancer lesions, the median DIs were 280 and 721 in positive and diminished cases, respectively (p=0.081). CONCLUSION: A loss of FHIT expression is associated not only with alcohol-induced esophageal carcinogenesis, but also with multicentric carcinogenesis.

Epidermal growth factor receptor mutations are associated with gefitinib sensitivity in non-small cell lung cancer in Japanese.

The protein-kinase family is the most frequently mutated gene family found in human cancer. Gefitinib, an ATP-competitive inhibitor of epidermal growth factor receptor (EGFR), also appears to be particularly effective in adenocarcinoma of the lung and in patients without smoking history. To determine whether lung tumors sensitive to gefitinib contained mutations within the tyrosine kinase (TK) domain of EGFR, we screened exons 18-23 of EGFR of tumors in 20 patients with non-small cell lung cancer (NSCLC) who had been treated with gefitinib. Nine (45%) tumors had TK domain mutations. All mutations were observed in adenocarcinoma. Seven (77.8%) of 9 cases with mutated types showed sensitivity to gefitinib, while no cases of 11 with wild type showed gefitinib sensitivity. Such mutations were more frequently observed in patients who had never smoked (5/8 or 62.5%) than in smokers (4/12 or 33.3%). The patients with mutations of EGFR to have a more favorable prognosis than those with wild type (p=0.033). These data show that adenocarcinomas from patients who had never smoked comprise a specific subset of patients with NSCLC sensitive to gefitinib treatment.

Y-box-binding protein-1 expression is not correlated with p53 expression but with proliferating cell nuclear antigen expression in non-small cell lung cancer.

Transcription factor Y-box-binding protein 1 (YB-1), which binds to the inverted CCAAT box, is not only involved in the transcription of various genes, but also in cell proliferation and DNA repair. The aim of this study was to detect YB-1 and p53 expression and their relationship to proliferating cell nuclear antigen (PCNA) in non-small cell lung cancer (NSCLC) using immunohistochemical (IHC) staining, and to evaluate the relationship between their expression levels and the prognosis of patients with NSCLC. Positive expressions of YB-1, p53 and PCNA were detected in NSCLC cells in 43 (45.7%), 33 (35.0%) and 45 (47.9%) out of 94 patients, respectively. No significant differences were observed between YB-1 expression and the patients' gender, age at surgery, pathological stage, pathological T status, pathological N status, or pathological M status. The mean PCNA-labelling index (LI) for cells was 40.7+/-2.6. Also, a significant correlation between YB-1 and PCNA-LI was found (p<0.01), but none was found between p53 expression and PCNA. The positive expression of YB-1 was associated with squamous cell carcinoma and large cell carcinoma, compared with adenocarcinomas (p<0.01), and higher levels of PCNA-LI were associated with large cell carcinoma compared with adenocarcinomas and squamous cell carcinoma (p<0.01). These results suggest that YB-1 expression is correlated with PCNA expression in NSCLC. In addition, the DNA repair pathway and tumor proliferation mediated by YB-1 linking to PCNA may be responsible for controlling the growth of NSCLC.

Expression of deltaNp63 in squamous cell carcinoma of the esophagus.

BACKGROUND: The p63 gene is present as two isoforms, namely TAp63 and deltaNp63. The biological role of deltaNp63 in the progression of esophageal cancer is still controversial. PATIENTS AND METHODS: The expression of deltaNp63, as well as that of p63, was immunohistochemically examined in 61 resected specimens of squamous cell carcinoma of the esophagus. RESULTS: The incidences of a positive deltaNp63 expression were 32 and 64% in carcinomas with and without adventitial invasion, respectively, and 37 and 65% in those with and without lymph node metastasis, respectively (p<0.05). The prognosis was significantly better in the positive deltaNp63 group than in the negative group (p<0.01). However, a multivariate analysis revealed deltaNp63 not to be an independent prognostic factor. Regarding p63, diminished expression was more frequently observed in advanced carcinomas, however, there were no statistically significant differences. CONCLUSION: The impaired deltaNp63 reflects the progression of squamous cell carcinoma of the esophagus.