Expression of SATB2 in Neuroendocrine Carcinomas of the Lung: Frequent Immunopositivity of Large Cell Neuroendocrine Carcinoma with a Diagnostic Pitfall.

Small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC) are both classified as lung neuroendocrine carcinoma (NEC). It has recently been reported that the special AT-rich sequence-binding protein 2 (STAB2), known as a colorectal cancer marker, is also expressed in NECs occurring in various organs including the lung. However, few studies have examined any differences of SATB2 immunopositivity between SCLC and LCNEC. We investigated SATB2 expression in 45 SCLC and 14 LCNEC cases using immunohistochemistry as well as the expression of caudal-type homeobox 2 (CDX2) and keratin (KRT) 20. The LCNEC cases were more frequently positive for SATB2 (ten out of 14, 71%) than the SCLC ones (seventeen out of 45, 38%) with a statistically significance (P = 0.035). Furthermore, two LCNEC cases were positive for CDX2 while no positive findings were observed for any SCLC cases, the difference of which, however, was not statistically significant (P = 0.053). KRT20 was negative in all LCNEC and SCLC cases. These results require our attention when we use SATB2 and CDX2 as colorectal cancer markers because their expression in pulmonary NECs can lead to a misdiagnosis that the tumor is of metastatic colorectal adenocarcinoma, especially when the patient has a past history of colorectal cancer. Analyzing the relationship between the demographic/clinical variables and the SATB2 expression in the SCLC cases, just high Brinkman index (≥ 600) was significantly related to the positivity of SATB2 (P = 0.017), which is interesting considering the strong relationship between SCLC and smoking.

Inflammatory Risk Factors for Early Recurrence of Non-Small Cell Lung Cancer Within One Year Following Curative Resection.

BACKGROUND: Several inflammation-based scoring systems and nutritional indicators have been shown to have relevance to survival of patients with non-small cell lung cancer (NSCLC).The present study examined preoperative and pathological factors in patients who underwent curative resection for non-small cell lung cancer, with the aim to elucidate risk factors for early recurrence within 1 year of surgery. METHODS: Patients with NSCLC who underwent surgery from January 2009 to December 2014 were retrospectively investigated. Routine laboratory measurements including carcinoembryonic antigen were performed before surgery, and pathological information was collected after surgery. Patients with recurrence within 1 year after surgery were considered as early recurrence group (ERG), those with recurrence after 1 year were as late recurrence group (LRG), and those without recurrence were as no recurrence group (NRG). RESULTS: Multivariate analysis between ERG and LRG revealed Glasgow prognostic score (GPS) and CRP-to-albumin ratio (CAR) as independent risk factors for early recurrence. Multivariate analysis between ERG and LRG + NRG confirmed CAR, vascular invasion, and pathological stage as risk factors for early recurrence. CONCLUSION: These findings indicated that CAR and GPS were confirmed to be risk factors for early recurrence, in addition to pathological factors.

Validation of the Proposed cN2 Subclassification in the Eighth Edition of the IASLC Staging System: A Prospective Phase II Multicenter Study.

INTRODUCTION: Surgery for N2 stage IIIA NSCLC is not recommended in major guidelines. Nevertheless, it has been noted that single-station N2 may have a better prognosis than multistation N2 and that surgery can be performed as the main therapeutic option. METHODS: We conducted a prospective phase II study for single-station clinical N2 (cN2) NSCLC to evaluate the efficacy and safety of surgical resection without induction therapy. Complete resection with lobectomy, bilobectomy, or pneumonectomy followed by ipsilateral mediastinal lymphadenectomy was performed in 32 of 34 enrolled patients, whereas the remaining two patients underwent incomplete resection. Three-quarters of the patients underwent subsequent adjuvant chemotherapy. RESULTS: The 5-year overall survival rate was 58.5% (95% confidence interval: 41.9-75.4) for all 34 patients, and eight patients (23.5%) with pN0 or pN1 seemed to have been enrolled. The 5-year overall survival rates for single-station cN2 without and with hilar node enlargement were 81.3% and 37.5%, respectively (p = 0.025). Surgical mortality was 0% for all, and no considerable perioperative complications were noted; however, two patients died of interstitial pneumonia and unknown cause within 3 months after surgical resection. CONCLUSIONS: This is the very first prospective study on the surgical approach for cN2 NSCLC, and our result partially validated the proposed classification of the N descriptor in the new staging system. The treatment for single-station cN2 without hilar node enlargement would better if it were similar to that for cN1 disease. Induction chemotherapy or chemoradiotherapy may not be needed for such an entity.

[Anaphylaxis Induced by Fibrin Glue During Surgery for Pneumothorax].

We report here our experience with a case of anaphylactic shock caused by fibrin glue. A 51-year-old male underwent a thoracoscopic surgery for refractory pneumothorax under local anesthesia. Bullae were revealed, and subsequently covered with fibrin glue and a polyglycolic acid sheet. Twenty-minutes after application of the fibrin glue, sudden drop of blood pressure less than 80 mmHg and a skin rash appeared. Since the patient was not administered any other drugs prior to the reduction in blood pressure, anaphylactic shock was considered to be caused by fibrin glue. The patient recovered after the treatment by dopamine and steroid.

Advanced Lung Cancer Inflammation Index Predicts Outcomes of Patients with Pathological Stage IA Lung Adenocarcinoma Following Surgical Resection.

PURPOSE: The correlation of advanced cancer with inflammation and/or nutrition factors is well known. Recently, the advanced lung cancer inflammation index (ALI) was developed as a new prognostic tool for patients with advanced lung cancer. In this study, we examined whether ALI results are correlated with prognosis of patients with early stage lung adenocarcinoma who undergo lung resection. METHODS: From January 2009 to December 2014, 544 patients underwent lung resection due to primary lung cancer at Dokkyo Medical University Hospital, of whom 166 with pathological stage IA lung adenocarcinoma were retrospectively investigated in this study. ALI was calculated as follows: Body Mass Index (BMI; kg/m2) × albumin (g/dL)/neutrophil-to-lymphocyte ratio (NLR). RESULTS: Multivariate analysis revealed that gender, red cell distribution width (RDW), NLR, and ALI were parameters significantly correlated with overall survival (OS). Patients with an ALI value less than 22.2 had an inferior 5-year OS rate as compared to those with a value of 22.2 or higher (p <0.001) as well as an inferior 5-year recurrence-free survival (RFS) rate (p <0.001). CONCLUSION: Low ALI was correlated with poor prognosis in patients with stage IA lung adenocarcinoma. Those with an ALI value less than 22.2 should be carefully followed regardless of cancer stage.

[Structural Deterioration of a Bovine Pericardial Valve in a Tricuspid Position 14 Years Postoperatively;Report of a Case].

Although nonstructural dysfunction of a bioprosthesis caused by pannus formation or native valve attachment has been well described, structural valve deterioration( SVD) caused by calcification or tear of a bioprosthesis, especially a bovine pericardial valve, is very rare in the tricuspid position. We report a case of redo tricuspid valve surgery for SVD 14 years after tricuspid valve replacement( TVR) using a Carpentier-Edwards Perimount (CEP) pericardial valve. A 71-year-old woman was referred to our hospital because of exertional dyspnea and pre-syncope. She had undergone mitral valve replacement with a St. Jude Medical mechanical valve and TVR with a CEP pericardial valve 14 years previously. Transthoracic echocardiography revealed tricuspid valve stenosis with a mean trans-tricuspid valve pressure gradient (TVPG) of 7.3 mmHg. Redo TVR using a CEP Magna Mitral Ease valve was performed under cardiac arrest. Severe calcification was observed on the ventricular side of the leaflets of the explanted valve. The mean TVPG decreased to 3.2 mmHg after surgery, and the patient's postoperative course was uneventful.

Nontuberculous mycobacterial and Aspergillus infections among cadaveric lung transplant recipients in Japan.

BACKGROUND: Lung transplantation is an effective treatment modality for respiratory failure. Chronic lung infections, including infections caused by nontuberculous mycobacteria (NTM) and Aspergillus, are difficult to control, and uncontrolled infections are relative contraindications for lung transplantation. However, few reports have documented the incidence and outcome of these infections in lung transplant recipients. METHODS: To quantify the incidence and outcomes of colonization and disease caused by NTM and aspergillosis in recipients before and after lung transplantation, we reviewed the medical records and microbiology data from 240 consecutive cadaveric lung transplant recipients between 2000 and 2014. RESULTS: Before lung transplantation, NTM and Aspergillus species were isolated from five (2.1%) and six (2.5%) patients, respectively, out of the total 240 recipients. All patients with NTM infection received treatment, resulting in culture conversion. They had no recurrence after lung transplantation. All patients with aspergillosis received treatment, one of whom had recurrence after lung transplantation. Over a median follow-up period of 3.3 years, NTM species were isolated after transplantation from eight of 240 patients (3.3%). Five of these patients met the criteria for NTM disease, and four of them received treatment. Four patients survived without a worsening of NTM disease. Over the same median follow-up period, Aspergillus species were isolated from seven of 240 patients (2.9%), six of whom received treatment. CONCLUSIONS: Isolation of NTM or Aspergillus species from lung transplant recipients is uncommon. Adequate pre-transplant control and post-transplant management of NTM and Aspergillus infections allows for safe lung transplantation.

Molecular biological analysis in a patient with multiple lung adenocarcinomas.

The utility of molecular biological analysis in lung adenocarcinoma has been demonstrated. Herein we report a rare case presenting as multiple lung adenocarcinomas with four different EGFR gene mutations detected in three lung tumors. After opacification was detected by routine chest X-ray, the patient, a 64-year-old woman, underwent chest computed tomography which revealed a right lung segment S4 ground-glass nodule (GGN). Follow-up computed tomography revealed a 42 mm GGN nodule with a 26 mm nodule (S6) and a 20 mm GGN (S10). Histopathology of resected specimens from the right middle and lower lobes revealed all three nodules were adenocarcinomas. Four EGFR mutations were detected; no three tumors had the same mutations. Molecular biological analysis is a promising tool for the diagnosis of primary tumors in patients with multiple lung carcinomas of the same histotype, enabling appropriate treatment.

Inflammation-Based Prognostic Score Predicts Postoperative Survival of Patients with Interstitial Pneumonia After Undergoing Lung Cancer Resection.

OBJECTIVES: Idiopathic interstitial pneumonias (IIPs) are associated with an increased risk of lung cancer. Glasgow prognostic score (GPS), which uses serum C-reactive protein (CRP) and albumin levels to indicate systemic inflammatory response and nutrition level, has been reported to be a predictor of overall survival in patients with various types of cancer. We evaluated the usefulness of GPS for prediction of survival of patients with both lung cancer and IIPs following a lung resection procedure. METHODS: Patients with IIPs who underwent lung cancer resection from January 2006 through December 2015 were investigated. Routine laboratory measurements, including serum CRP and albumin for determining GPS, were performed before the operation. Univariate and multivariate analyses with a COX proportional hazards regression model were used to identify independent risk factors for overall survival (OS), relapse-free survival (RFS), cancer-specific survival (CSS), and other disease-specific survival (ODSS). RESULTS: A total of 135 patients underwent lung resection during the study period. Multivariate analysis selected sublobar resection (p = 0.035), UIP pattern (p = 0.025), and GPS of 1-2 (p = 0.042) as predictive factors associated with OS, while GPS of 1-2 (p = 0.039) was shown to be a predictive factor associated with RFS. Multivariate analysis also revealed pTNM (p < 0.001), usual interstitial pneumonia pattern (p = 0.006), and GPS of 2 (p = 0.003) as predictive factors associated with CSS, while univariate analysis indicated pTNM (p = 0.042), GPS of 1 (p = 0.044), and %DLCO (p = 0.038) as predictive factors associated with ODSS. CONCLUSION: GPS is an independent prognostic factor of OS and RFS in lung cancer patients with IIPs undergoing a lung resection procedure. Furthermore, a GPS of 2 was found to be associated with CSS following lung cancer resection, while a score of 1 was associated with ODSS.

Association of Perioperative Redox Balance on Long-Term Outcome in Patients Undergoing Lung Resection.

PURPOSE: We examined whether redox balance during the perioperative period is associated with long-term survival of patients after undergoing lung resection. METHODS: Patients who underwent surgery for lung cancer from January to June 2013 at our institution were investigated. Serum was collected during the operation, and on postoperative day (POD) 3 and 7, and the levels of derivatives of reactive oxygen metabolites (d-ROMs) and biologic antioxidant potential (BAP) were measured. RESULTS: In all, 21 patients (69 ± 7 years old) were enrolled, of whom 9 underwent video-assisted thoracoscopic surgery. Comorbidities in the patients included chronic obstructive pulmonary disease in eight and idiopathic pulmonary fibrosis in five. d-ROM values on POD 3 and 7 were significantly increased as compared to those obtained during the operation (p <0.001), whereas BAP did not change after surgery. Patients with a value below a d-ROM cutoff value of 327 during the operation showed significantly superior 3-year overall survival as compared to those with a value above the cutoff (87.5% vs. 20.0%, p <0.001). CONCLUSION: In the present patients, surgical stress caused an increase in d-ROM during the postoperative course. The d-ROM value obtained during the operation was correlated with long-term survival following resection for lung cancer.

Epidermal Growth Factor Receptor Gene Mutation in Pleural Lavage Cytology Findings of Primary Lung Adenocarcinoma Cases.

PURPOSE: In the present study, we examined the relationship between intraoperative pleural lavage cytology findings and presence of epidermal growth factor receptor (EGFR) gene mutations. METHODS: We investigated 160 patients who underwent surgical treatment for primary lung adenocarcinoma at our hospital from January 2011 to December 2013 to determine the presence of EGFR gene mutations and pleural lavage cytology. RESULTS: In all, 52 subjects (31.5%) were positive EGFR gene mutations, of whom 38 were found to possess the Exon 21 L858R mutation. Intraoperative pleural lavage cytology examinations were performed in 160 subjects and 12 had positive results, of whom 6 were positive for EGFR gene mutations, which was the Exon 21 L858R mutation in all. In a comparison between subjects possessing the Exon 21 L858R mutation and those negative for EGFR gene mutations, lavage cytology-positive (p = 0.02) and vascular infiltration-negative (p = 0.01) were characteristics of the Exon 21 L868R mutation-positive group. CONCLUSION: Subjects positive for the EGFR Exon 21 L858R mutation had a higher positive rate of intraoperative pleural lavage cytology than those not possessing EGFR mutations.

[Successful Combined Modality Therapy for an Advanced Malignant Mediastinal Non-seminomatous Germ Cell Tumor in an Elderly Female].

A 69-year-old woman was diagnosed with a germ cell tumor in the anterior mediastinum. Following 3 years follow-up, she experienced chest pain and an enlarging of the anterior mediastinal tumor and bilateral lung metastases were detected by chest X-ray. The tumor was diagnosed as a primary malignant mediastinal non-seminomatous germ cell tumor by needle biopsy. After initial radiotherapy (12 Gy/4 Fr), she was subsequently treated with EP chemotherapy which achieved a partial response. Complete resection of the residual tumors in the mediastinum and right lung was performed. No recurrence has been noted for 5 years post-operatively.

[Salvage Surgery Following Chemoradiotherapy for Thymic Basaloid Cell Carcinoma].

We performed salvage surgery after chemoradiotherapy(CRT) in a patient with thymic basaloid cell carcinoma. A 46-year-old man with an abnormal chest shadow on X-ray findings was referred to our hospital. Computed tomography revealed a partially solid tumor along with a multilocular cyst in the anterior mediastinum with mediastinal lymph node swelling infiltrating to the superior vena cava(SVC). Positron emission tomography revealed FDG accumulation (SUVmax 7.94)in the tumor. Pathological findings of a tumor biopsy specimen obtained by thoracoscopy led to a diagnosis of thymic basaloid cell carcinoma. Following CRT (ADOC+RT:60 Gy), a complete resection (R0)with replacement of the SVC was performed. The postoperative course was uneventful, and the patient was alive at 20 months after surgery with metastasis to the cervical lymph nodes and bone.

Postoperative pyothorax a risk factor for acute exacerbation of idiopathic interstitial pneumonia following lung cancer resection.

OBJECTIVE: Acute exacerbation (AE) of idiopathic interstitial pneumonia (IP) is a potentially fatal postoperative complication following lung cancer resection. Postoperative pyothorax (PP) following development of a bronchopleural fistula (BPF) after lung surgery induces continuous inflammation and may affect the occurrence of AE. We investigated the relationship between AE and PP in patients who underwent pulmonary resection for lung cancer. METHODS: A total of 941 patients who underwent lung resection due to primary lung cancer from 2006 to 2015 at our hospital were investigated. RESULTS: Of the 941 enrolled patients, 137 (14.6 %) had idiopathic IP and were predominantly male (p < 0.01). Pathological stage Ia and adenocarcinoma were observed at significantly high rates in the non-IP group (p < 0.01). Patients with IP showed a tendency for a higher percentage of PP (p = 0.054). Of the 137 patients with IP, 17 (12.4 %) showed postoperative AE. Furthermore, PP was observed in three cases in the AE(+) group and two in the AE(-) group. PP had a correlation with a significantly higher incidence of AE (p = 0.007). CONCLUSION: PP was found to be a significant risk factor for postoperative AE in lung cancer patients undergoing a pulmonary resection. Since IP itself is likely a risk factor for PP, prevention of BPF is important for patients with IP, as it can lead to PP.

Tumor-related gene expression levels in pulmonary pleomorphic carcinoma.

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a rare type of non-small-cell lung cancer that belongs to the family of sarcomatoid carcinomas and is associated with poor prognosis. We investigated the expressions of tumor-related genes in resected PPC specimens. METHODS: Specimens resected from patients with PPC from July 2006 through April 2012 were investigated. Tumor segments were collected from the specimens by micro-dissection to extract mRNA, then RT-PCR was performed according to Dannenberg's tumor profile method for semi-quantitation of tumor-related gene mRNA. To compare with other types of lung cancer, data from stage-matched adenocarcinoma (AC) and squamous cell carcinoma (SCC) cases in our database were also examined. RESULTS: The gene expression levels of thymidylate synthase were significantly higher in PPC and SCC as compared to the AC specimens (p < 0.001). The levels of dihydropyrimidine dehydrogenase and thymidine phosphorylase mRNA in PPC showed a similar tendency to those in SCC, in contrast to AC. Furthermore, the expression level of excision repair cross-complementation group 1 mRNA in PPC specimens was similar to that reported in NSCLC, while the level of vascular endothelial growth factor (VEGF) expression was higher as compared to that reported for colorectal cancer. CONCLUSIONS: Although gene expression of tumor cannot be directly correlated to its sensitivity for anti-cancer drugs, it is likely that PPC tumors are not sensitive to anti-metabolic drugs. Anti-VEGF therapy may be a candidate for PPC, while cisplatin also remains a viable option.

Preoperative saline-filled computed tomography thoracography for awake video-assisted thoracic surgery: report of three cases.

Awake video-assisted thoracic surgery (VATS) is a therapeutic option for patients with intractable secondary spontaneous pneumothorax (SSP) complicated by impaired pulmonary function. The preoperative identification of air leak points is one of the keys to the success of this procedure. We describe how we performed saline-filled computed tomography (CT) thoracography to detect pleural fistulae in three patients with intractable SSP. Saline-filled CT thoracography showed bubble signs in two patients and an air-water level in bulla in one patient. The preoperative identification of air leak points resulted in successful awake VATS for all three patients. Our experience demonstrates that saline-filled CT thoracography is a useful diagnostic tool for SSP, especially when used in preparation for awake VATS when minimally invasive procedures are desirable.

[Pulmonary Clear Cell Type Squamous Cell Carcinoma that Required Differential Diagnosis from Metastatic Ureter Cancer;Report of a Case].

A 71-year-old woman was referred to our department for a nodular lesion in the left lung. She had been followed by urology department in our hospital for 6 years since right nephrectomy for ureter cancer. Chest X-ray and computed tomography (CT) scan demonstrated a small nodular shadow in the left lower lobe. The lung tumor was removed by wedge resection, and pathologically diagnosed during the operation as a metastasis from the ureter cancer. The lung tumor consisted of clear cells similar to the ureter cancer. However, the final pathological diagnosis changed to a primary lung cancer based on the findings of stratified differentiation and cancer cell nests in the tumor. Immunohistochemical staining for ureter epithelium-related antigens confirmed the diagnosis. Although we recommended left lower completion lobectomy, the patient refused additional surgery. She is suspected to have local recurrence in the left lower lobe 18 months after the surgery.

Remission of newly diagnosed immune thrombocytopenia after lung cancer resection.

Secondary immune thrombocytopenia is a rare paraneoplastic syndrome of lung cancer. We report a case of pulmonary pleomorphic carcinoma with newly diagnosed secondary immune thrombocytopenia. On referral, the patient's complete blood cell count was normal; however, it showed marked thrombocytopenia after 1 month. Blood biochemistry and bone marrow puncture showed normal findings. We speculated that he had immune thrombocytopenia associated with the lung cancer and planned lung resection. Sleeve middle and lower lobectomy was successfully performed with preoperative intravenous immunoglobulin and intraoperative platelet transfusion. His platelet count was restored and maintained a normal level at 8 months after the operation.

A prospective study of surgical procedures for patients with oligometastatic non-small cell lung cancer.

BACKGROUND: Purely localized, oligometastatic, and widely metastatic tumors are likely to require different therapeutic strategies. Although surgical procedures for isolated pulmonary, brain, or adrenal metastases from lung cancer have been extensively evaluated, most data are from retrospective studies; accordingly, we conducted a prospective multicenter trial. METHODS: Patients were eligible if they had previously untreated clinical T1-2N0-1 lung cancer with single-organ metastasis, or single-organ metachronous metastasis after complete resection of pathologic T1-2N0-1 lung cancer. Metastatic lesions were classified into three groups: group A included metastasis in single organs other than brain or lung; group B included synchronous brain metastasis; and group C included pulmonary metastasis. The treatment intervention was surgical resection of metachronous metastasis or of both synchronous metastasis and primary lung cancer. RESULTS: From December 2002 through June 2011, 36 patients were enrolled. Two patients were ineligible, and the remaining 34 were analyzed; 6 (18%) had a benign lesion and no metastasis, 5 patients (15%) underwent incomplete resection of primary lung cancer, and 20 patients (59%) underwent complete resection of both primary lung cancer and metastasis. The 5-year survival rate for these 20 cases was 44.7%. CONCLUSIONS: Clinical T1-2N0-1 lung cancer with a single-organ metastatic lesion was a good candidate for surgical resection. A 5-year survival rate of about 40% can be expected, which could be comparable with that for stage II non-small cell lung cancer.

Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan.

BACKGROUND: An outbreak of cholangiocarcinoma occurred among workers in the offset color proof-printing department at a printing company in Japan. The aim of this study was to clarify the characteristics of the patients with cholangiocarcinoma. METHODS: This was a retrospective study conducted in 13 Japanese hospitals between 1996 to 2013. The clinicopathological findings of cholangiocarcinoma developed in 17 of 111 former or current workers in the department were investigated. Most workers were relatively young. RESULTS: The cholangiocarcinoma was diagnosed at 25-45 years old. They were exposed to chemicals, including dichloromethane and 1,2-dichloropropane. The serum γ-glutamyl transpeptidase activity was elevated in all patients. Dilated intrahepatic bile ducts without tumor-induced obstruction were observed in five patients. The cholangiocarcinomas arose from the large bile ducts. The precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile ducts, as well as non-specific bile duct injuries, such as fibrosis, were observed in various sites of the bile ducts in all eight patients for whom operative specimens were available. CONCLUSIONS: The present results showed that cholangiocarcinomas occurred at a high incidence in relatively young workers of a printing company, who were exposed to chemicals including chlorinated organic solvents.