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.

Development of adoptive immunotherapy with KK-LC-1-specific TCR-transduced γδT cells against lung cancer cells.

The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer-specific CTLs to establish forceful cancer-specific adoptive immunotherapy. We cloned the TCRαß genes from CTLs showing HLA-B15 restricted recognition of Kita-Kyushu lung cancer antigen-1 (KK-LC-1), a cancer/germline gene antigen, identified in a lung adenocarcinoma case (F1121). The TCRαß and CD8 genes were transduced into γδT cells induced from PBLs of healthy volunteers stimulated with zoledronate and IL-2. The KK-LC-1-specific TCRαß-CD8 γδT cells showed cytotoxic activity against the KK-LC-1 positive lung cancer cell line F1121L and produced IFN-γ against F1121L and KK-LC-1 peptide-pulsed F1121 EBV-B cells. These responses were blocked by HLA class I and HLA-B/C antibodies. An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαß-CD8 transduced γδT cells (TCRαß-CD8 γδT cells) were intravenously injected. Growth inhibition of KK-LC-1+ , HLA-B15+ lung cancer cells was confirmed in mice with injection of the TCRαß-CD8 γδT cells from 1 wk after xenotransplantation of cancer cells but not in those treated 2 wk after xenotransplantation. The resected specimens of the tumor, 2 wk after xenotransplantation, highly expressed FasL but not programmed death ligand-1 (PD-L1) by immunohistochemical staining. FasL highly expressed cancer cells xenotransplanted 2 wk ago were resistant to TCRαß-CD8 γδT cells injection. These results suggested that apoptosis of Fas-positive TCRαß-CD8 γδT cells may be induced by a Fas-mediated signal after interacting with FasL-positive cancer cells.

[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.

Calcifying giant cell cardiomyopathy: a possible new entity: Images in Cardiovascular Pathology.

We demonstrated an extremely unusual case of an 83-year-old male's sudden death secondary to characteristic myocardial necrosis and fibrosis with calcification and multinucleated giant cells infiltration, possibly due to sepsis and Stage IV pulmonary pleomorphic carcinoma-induced cachexia after postmortem study. We propose that this calcifying giant cell cardiomyopathy (CGC) would be a new entity especially from the pathological viewpoints and should be considered in the classification of noninfectious myocarditis. Further prospective studies are needed to validate the presence and significance of CGC and the association with any triggers of somewhat microvascular dysfunction and/or toxic agents, after collecting and investigating a larger number of CGC cases examined.

[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.

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.

Results of surgical resection for patients with thymoma according to World Health Organization histology and Masaoka staging.

OBJECTIVES: Thymomas are relatively rare tumors. In this study, we investigated the clinical features of patients who underwent surgical resection for thymoma. PATIENTS AND METHODS: This study clinicopathologically evaluated 54 consecutive patients who underwent a surgical resection of thymoma in our department between 1994 and 2006. RESULTS: A complete resection was performed in 52 patients, while two patients underwent an incomplete resection due to pleural dissemination. Combined resection with adjacent organs was performed for the lung (n=6), pericardium (n=5), and large vessels (brachiocephalic vein in three, superior vena cava in two). The concomitant autoimmune diseases were observed in 20 patients (37%), and they included myasthenia gravis in 17 patients, macroglobulinemia in one, pemphigus vulgaris in one, and stiff person syndrome in one patient. The histologic types of the World Health Organization classification diagnosed as type A in four patients, type AB in 14, type B1 in eight, type B2 in 15, and type B3 in 11. There were 27, 17, eight, and two patients with Masaoka stages I, II, III, and IV, respectively. Four patients died, and the causes of death included recurrence of thymoma in two, gastric carcinoma in one, and respiratory failure due to myasthenia gravis in one patient. The overall survival rate at 10 years was 94.6% in patients with stages I and II disease and 77.1% in patients with stages III and IV disease. CONCLUSIONS: Long-term survival can be expected not only for patients at early stages, as well as for patients with stages III and IV disease if surgical resection is completed macroscopically.

Differences in sensitivity to tumor-specific CTLs between primary and metastatic esophageal cancer cell lines derived from the same patient.

PURPOSE: MHC antigens and adhesion molecules, such as the intracellular adhesion molecule (ICAM-I), play an important role in cellular immune response. We examined the expression patterns of these molecules in both primary and metastatic esophageal carcinoma cells from the same patient and evaluated the cellular immune responses against these cells. MATERIALS AND METHODS: In the esophageal cancer patient (H122), tumor cell lines were established from primary and subcutaneous metastatic lesions. We compared the expression of cell surface molecules on the metastatic tumor cell line (H122SC) with that on the primary tumor cell line (H122ESO) using flow cytometry. Moreover, we analyzed the differences in cellular immune responses against these cell lines, which expressed similar levels of the Tara antigen, using the Tara antigen-specific CTL clone. RESULTS: H122SC ICAM-1 expression was significantly lower in H122ESO, and the Tara antigen-specific CTL clone produced lower levels of TNF in response to H122SC than H122ESO. ICAM-1 transfection into the H122SC rendered these cells as sensitive to the CTL clone as the H122ESO. CONCLUSION: The metastatic tumor cells displayed lower regulated ICAM-1 expression levels and were less sensitive to specific CTLs. ICAM-1 downregulation may be one mechanism by which tumor cells escape immunologic surveillance.

[Clinical analysis of esophageal cancer associated with other primary cancers].

This study aims to investigate the therapeutic and prognostic implications of esophageal cancer in patients with other primary cancer. Between April 1992 and December 2008, in 83 patients underwent surgery for esophageal cancer at our department. Among them, 24 patients (28.9%) had medical history of additional primary cancer. There were 16 metachronous cancers and 8 synchronous cancers. Six patients had antecedent other primary cancers, and subsequent primary cancers developed in 10 patients. The other primary cancers included head and neck cancer in 8 patients, gastric cancer in 8, lung cancer in 6, colorectal cancer in 3, and other cancer in 3. The patients with other primary cancers were both heavy smokers and heavy drinkers in comparison to those without other primary cancers. The post-operative 5-year survival rate in patients with subsequent cancers, antecedent cancers, and synchronous cancers were 100%, 70.0%, and 46.9%. The 5-year survival rate was 33.4% in patients without other primary cancers. A high incidence of multiple primary cancers was observed in patients with esophageal carcinoma but the prognosis of these patients with metachronous cancers are better than that of patient with synchronous cancers and patients without other primary cancers. Post-operative follow up is considered to be necessary for early detection of multiple occurrences of carcinoma, especially in the upper aerodigestive tract.

Limited pulmonary resection for peripheral small-sized adenocarcinoma of the lung.

BACKGROUND: It was recently reported that a limited pulmonary resection (segmentectomy or wedge resection) was not inferior to a lobectomy in the management of peripheral small-sized adenocarcinoma (tumor ≦ 20 mm) of the lung. METHODS: We retrospectively analyzed patients undergoing a lobectomy (n = 114) and a limited resection (n = 35) for peripheral small-sized adenocarcinoma of the lung during a 7-year period from April 2001 to March 2008. Our criteria for the limited resection of lung cancer were as follows: (1) adenocarcinoma of 10 mm or less in diameter and (2) adenocarcinoma of 11-20 mm in diameter, in which the ratio of the ground glass opacity is 50% or more, without pleural indentation on computed tomography. Additionally, the frozen sections of the tumors were intraoperatively diagnosed as Noguchi type A or B. The survival and clinical outcomes were analyzed. RESULTS: The 5-year survival rates of the lobectomy group and limited resection groups were 89.2% and 100%, respectively. No recurrence was seen in the limited resection group. CONCLUSIONS: Our results suggest that our criteria for limited resection were adequate for the management of small-sized adenocarcinoma of the lung.

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.

[Treatment recommendations for adrenal metastasis of non-small cell lung cancer].

To evaluate the optimum treatment strategy for metastatic adrenal tumors derived from non-small cell lung cancer (NSCLC), we retrospectively analyzed 17 consecutive cases (8 resection cases: 4 synchronous and 4 metachronous: 9 non-resection cases: 3 synchronous and 6 metachronous) who received surgical resection for NSCLC. The patients included 12 males and 5 females with a mean age of 63.9 years. Of these, 9, 3, 2, 2, and 1 patient (s) were diagnosed as having adenocarcinoma, squamous cell carcinoma, pleomorphic carcinoma, large cell carcinoma, and adenosquamous cell carcinoma, respectively. The mean interval after lung resection and treatment of metachronous adrenal metastasis was 9.9 months. The mean time to progression from treatment of metachronous adrenal metastasis to disease progression was 8.9 months. A survival analysis showed no significant prognostic difference between the patient age, gender, pathological stage, synchronous/metachronous classification, CEA, and site of metastases. However, patients who received an adrenalectomy had a more favorable prognosis. The 2-year survival of patients following resection versus those who did not undergo a resection for adrenal metastasis was 62.5 and 22.8%, respectively. These data indicate that metastatic adrenal tumors should be resected if the patient can tolerate surgery after appropriate selection.

Clinicopathologic characteristics of mucinous carcinoma of the breast.

The mucinous carcinoma of breast cancer is a relatively rare malignant tumor. This study investigated the clinical and pathologic features of mucinous carcinoma. The medical records of 237 patients with invasive breast cancer who underwent surgery between 1995 and 2006 were reviewed. These cases included 10 patients (4.2%) with mucinous carcinoma. The age of the patients ranged from 43 to 71 years (mean, 55.5 years). The tumor size was T1 in 5 patients and T2 in 5 patients. Lymph node metastasis was diagnosed as being negative in 9 patients and positive in 1 patient. Six patients (60%) were positive both for estrogen and progesterone receptor. The 10-year survival rates of mucinous carcinoma and other types of invasive breast cancer were 87.5% and 80.7%, respectively. Mucinous carcinoma showed a lower incidence of lymph node metastasis than other types of invasive breast cancer. Mucinous carcinoma tended to have a better prognosis in comparison with other types of invasive breast carcinoma.

Correlation between HLA alleles and EGFR mutation in Japanese patients with adenocarcinoma of the lung.

INTRODUCTION: The identification of activating mutations in the epidermal growth factor receptor (EGFR) gene is one of the most intriguing recent discoveries in the field of lung cancer research, and they are more commonly found in adenocarcinoma occurring in females, never/light smokers, and East Asian patients. Why such certain patients are susceptible to the development of EGFR-mutant tumors is currently unknown. METHODS: This study evaluated the medical records of 437 patients with adenocarcinoma of the lung who underwent a surgical resection. The genetic status of the EGFR gene was investigated by polymerase chain reaction-based analyses. The serological typing of histocompatibility leukocyte antigen (HLA) class I was performed using a microcytotoxicity test of lymphocytes or polymerase chain reaction-sequence-specific oligonucleotides, and the correlation between the EGFR mutation and HLA alleles was analyzed. RESULTS: An EGFR mutation was found more frequently in females and never/former smokers than their counterpart. In females, the incidences of EGFR mutation were 61.0% and 41.7% in HLA-A2 (+) and A2 (-) patients with adenocarcinoma of the lung, respectively (p = 0.008). The EGFR mutation was found more frequently in female patients with HLA-A2. However, no significant correlation was identified between the frequencies of other HLA alleles and EGFR mutations in the same patients group. CONCLUSIONS: EGFR: mutations are associated with HLA-A2 in female patients with adenocarcinoma of the lung. Further research was needed to elucidate the other relevant factors in the histogenesis of lung cancer with an EGFR mutation.

Association between lymphangiogenesis-/micrometastasis- and adhesion-related molecules in resected stage I NSCLC.

BACKGROUND: The purpose of this study was to clarify the role and clinical significance of lymphangiogenesis/micrometastases and adhesion molecules in resected stage I non-small cell lung cancer (NSCLC). METHODS: Immunohistochemical (IHC) staining was used to analyze the protein expression of vascular endothelial growth factor-C (VEGF-C), VEGF, E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin in paraffin-embedded tumor samples from 117 well-characterized stage I NSCLC patients and to compare the protein expression, clinical variables and survival outcome. As a micrometastatic parameter in lymph nodes (LNs), cytokeratin (CK) staining was performed. RESULTS: The positive expression of VEGF-C and VEGF were detected in 54 (48.7%) and 86 (73.5%), respectively. We identified micrometastatic tumor cells in pathological N0 LNs in 34 (29.1%) of 117 patients. E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin were identified in 70 (59.8%), 41 (35.0%), 83 (70.9%), and 61 (52.1%) specimens, respectively. The VEGF-C expression was found more frequently in squamous cell carcinoma (SQ) and in the tumors with negative expression of beta-catenin than counter features. The VEGF expression was found more frequently in the tumors with a negative expression of E-cadherin. Micrometastasis was found more frequently in a pathological T2 status and in the tumors with a negative expression of alpha-catenin. Beta-catenin and gamma-catenin expressions were found less and more frequently in SQ, respectively. A univariate and multivariate survival analysis demonstrated that old age, pathological T2 status, and micrometastasis were independently associated with an increased risk of poor survival in the patients who underwent a surgical resection of stage I NSCLC. CONCLUSIONS: Complicated relationships exist between lymphangiogenesis/micrometastases and adhesion molecules with a specific histology. The detection of lymph nodal micrometastasis by CK may therefore be a useful marker for predicting a poor prognosis in patients who undergo a complete resection of stage I NSCLC.