Prognostic impact of surgical treatment for high-grade neuroendocrine carcinoma of the lung: a multi-institutional retrospective study.

Background: High-grade neuroendocrine carcinoma (HGNEC) of the lung, which includes small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), is an aggressive form of lung cancer. Although lobectomy followed by adjuvant chemotherapy is regarded as the standard therapy for this disease, it would be an uphill struggle for HGNEC patients to receive that multidisciplinary therapy perfectly. This study aimed to examine recurrence and survival outcomes in surgically treated patients with HGNEC of the lung. Methods: The medical records of 104 HGNEC patients who underwent surgical treatment in five institutions were retrospectively analyzed. Standard treatment (ST) was defined as lobectomy, bilobectomy, or pneumonectomy with mediastinal lymph node dissection followed by adjuvant platinum-doublet chemotherapy with more than two cycles. Results: Patients in the ST group (n=31; 30%) were younger and had fewer respiratory complications than those in the non-standard treatment (NST) group (n=73; 70%). A significantly higher proportion of patients in the NST group developed ipsilateral lymph node recurrence (21% vs. 3%; P=0.035) and ipsilateral or contralateral lung recurrence (15% vs. 0%; P=0.031). Five-year overall survival (OS) was 64.2% in the ST group and 38.3% in the NST group (P=0.038). NST was independently associated with worse OS in multivariate analysis (hazard ratio, 2.044; 95% confidence interval, 1.016-4.113; P=0.045). Conclusions: Surgically treated HGNEC patients who received ST had a more favorable outcome than those who received NST. Patients who receive NST may require additional treatment.

Pure high-grade fetal adenocarcinoma of the lung: a case report.

BACKGROUND: Pure high-grade fetal adenocarcinoma of the lung (H-FLAC) is a very rare tumor. CASE PRESENTATION: An annual check-up revealed an abnormal shadow in the left middle lung field of a 63-year-old Japanese man. Chest computed tomography (CT) showed a 3.6 × 2.8 cm pulmonary lesion with clear boundary in the left upper lobe. A transbronchial lung biopsy revealed non-small cell carcinoma. A left upper lobectomy and mediastinal lymph node dissection were performed. Histologically, the tumor consisted of solid proliferation of atypical cell with clear cytoplasm. Another histological component and morulae were not contained. Immunohistochemically, the tumor was focally positive for alpha-fetoprotein (AFP) and beta-catenin in the cell membrane. Accordingly, we made the diagnosis of pure H-FLAC, pT2aN2M0, stage IIIA. Two courses of adjuvant chemotherapy (cisplatin and vinorelbine) were administered but then the treatment was discontinued due to the patient's adverse reaction. At 25 months after the surgery, the patient had relapsed. CONCLUSIONS: We report a very rare case of pure H-FLAC. This histology has been considered to predict an extremely poor prognosis; therefore, the elucidation of genetic abnormalities and effective treatment is awaited.

Podoplanin expression in cancer-associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma.

AIMS: Podoplanin expression in cancer-associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early-stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expression in patients with pathological stage (p-stage) IA lung adenocarcinoma as categorised by the 8th edition of the tumour-node-metastasis classification for lung cancer. METHODS AND RESULTS: Immunohistochemical analyses using anti-podoplanin antibody were performed on resected specimens from 158 patients with p-stage IA lung adenocarcinoma. When more than 10% of cancer cells or CAFs showed immunoreactivity with podoplanin, the specimens were classified as podoplanin-positive. Podoplanin-positive status in cancer cells (n = 8) was not correlated with clinicopathological factors or with patient prognosis. Podoplanin-positive status in CAFs (n = 41) was correlated significantly with poorer tumour differentiation (P < 0.001), the presence of lymphatic invasion (P < 0.001) and high-grade (solid and/or micropapillary) components constituting ≥1% of the entire tumour (P < 0.001). The log-rank test showed that podoplanin-positive status in CAFs was associated significantly with shorter disease-free survival (DFS) (P < 0.001) and disease-specific survival (P = 0.015). In Cox's multivariate analysis, podoplanin-positive status in CAFs had the most significant effect on shorter DFS [hazard ratio (HR) = 4.411, P = 0.004], followed by the presence of high-grade components (HR = 3.581, P = 0.013). CONCLUSIONS: Podoplanin expression in CAFs could be an independent predictor of increased risk of recurrence in patients with p-stage IA lung adenocarcinoma.

Initial Results of Robotic Surgery for Primary Lung Cancer: Feasibility, Safety and Learning Curve.

BACKGROUND: At the end of 2016, robot-assisted thoracoscopic surgery (RATS) was still not covered by Japanese national health insurance. Therefore, few institutions in Japan perform RATS and even fewer have reported procedures as they occurred earlier. So, we decided to focus on the initial results of RATS for primary lung cancer. METHODS: We retrospectively reviewed 44 patients who underwent RATS for primary lung cancer from January 2011 to August 2016. After mastering the initial procedure, we introduced a completely portal robotic pulmonary resection procedure using a carbon dioxide insufflation system. Cases were divided into 2 groups: the early period (20 cases) and the later period (24 cases). RESULTS: There was no case of conversion to video-assisted thoracoscopic surgery or thoracotomy. In the 44 cases of primary lung cancer, median operating time was 239.5 min, console time was 179 min, blood loss was 10 mL, drainage period was 2 days, morbidity of Grade 2 or more (Clavien-Dindo classification) was 18.2%, morbidity of Grade 3 or more was only 4.6%, and there was no 30-day mortality. Median operating and console times were significantly shorter in the later period (215 min and 159.5 min, respectively) than in the initial period (300.5 min and 228 min, respectively). Median blood loss was significantly lower in the later period (5 mL) than in the initial period (50 mL). Five-year overall and disease-free survival rates were 100% and 88.9%, respectively. CONCLUSION: RATS for primary lung cancer is feasible and safe, has a faster learning curve, and provides satisfactory. Studies with longer follow-ups and larger numbers of cases are necessary.

Clinicopathological Characteristics of Lung Adenocarcinoma with Unexpected Lymph Node Metastasis.

PURPOSE: The objective is to demonstrate the clinicopathological characteristics of patients with unexpected node-positive lung adenocarcinoma and to analyze predictive factors of unexpected disease. METHODS: We reviewed 225 patients with lung adenocarcinoma who underwent curative-intent operation between January 2008 and December 2014. Unexpected node-positive diseases were defined as cases with hilar or mediastinal lymph nodes metastasis in spite of both negative significant enlargement of lymph nodes on preoperative chest computed tomography (CT) and negative fluorodeoxyglucose (FDG) uptake in lymph nodes on preoperative positron emission tomography (PET)/CT. We retrospectively analyzed clinical features of these patients and evaluated associated factors for unexpected diseases. RESULTS: There were 41 patients (18%) with unexpected node-positive disease, consisting of 16 (39%) unexpected pN1 and 25 (61%) unexpected pN2 diseases. The most common predominant subtype was papillary (22 patients; 54%), and 17 patients (41%) had micropapillary component in the tumors. Younger age (p <0.01), left side (p <0.01), larger tumor size (p <0.01), and having a micropapillary component (p <0.01) were significant associated factors of unexpected diseases in multivariate analysis. CONCLUSION: Histological findings of the primary tumor are often important because they can provide predictive information for lymph nodes status. Having a micropapillary component was one of the significant predictors of unexpected node-positive diseases.

Frequency of Epidermal Growth Factor Receptor Mutation in Smokers with Lung Cancer Without Pulmonary Emphysema.

BACKGROUND: Chronic obstructive pulmonary disease is a smoking-related disease, and is categorized into the emphysema and airway dominant phenotypes. We examined the relationship between emphysematous changes and epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma. PATIENTS AND METHODS: The medical records for 250 patients with lung adenocarcinoma were retrospectively reviewed. All patients were categorized into the emphysema or non-emphysema group. RESULTS: Wild-type EGFR was detected in 136 (54%) and mutant EGFR in 48 (19%). Emphysematous changes were observed in 87 (36%) patients. EGFR mutation was highly frequent in the non-emphysema group (p=0.0014). Multivariate logistic regression analysis showed that emphysema was an independent risk factor for reduced frequency of EGFR mutation (Odds Ratio=3.47, p=0.005). CONCLUSION: Our data showed a relationship between emphysematous changes and EGFR mutation status. There might be mutually exclusive genetic risk factors for carcinogenesis and development of emphysematous changes.

[Two Surgical Cases of Müllerian Cyst Arising From the Posterior Mediastinum].

We experienced 2 cases of Müllerian cyst. Case 1 was a 48-year-old woman with a paravertebral cystic tumor. The tumor grew from 23 to 31 mm in diameter for the 3 years. She underwent video-assisted thoracic surgery(VATS) for the excision of the tumor. Case 2 was a 40-year-old woman with a paravertebral cystic tumor, who underwent VATS. The Histological finding showed that the tumors of both cases were the cysts lined by non-stratified cuboidal to columnar epithelium and epithelial cells were positive in the nucleus with estrogen receptor immunohistochemically. The resected cysts were finally diagnosed as Müllerian cyst. Twenty four published cases of Müllerian cyst were reported before, including symptomatic and growing cases. There were some reports of malignant transformation in cases of pelvic origin.

Podoplanin Expression in Cancer-associated Fibroblasts Predicts Poor Prognosis in Patients with Squamous Cell Carcinoma of the Lung.

BACKGROUND/AIM: Podoplanin is a candidate cancer stem cell marker in squamous cell carcinoma (SCC). Several studies have reported the prognostic value of podoplanin expression in tumor cells in lung SCC but few have focused on its expression in cancer-associated fibroblasts (CAFs). The aim of this study was to analyze the prognostic significance of podoplanin expression, with special reference to the expression pattern in both tumor cells and CAFs. PATIENTS AND METHODS: Immunohistochemical analyses using anti-podoplanin antibody were performed on 126 resected specimens of lung SCC. When more than 10% of tumor cells or CAFs showed immunoreactivity with podoplanin levels as strong as those of the positive controls, the specimens were classified as a podoplanin-positive. RESULTS: Podoplanin-positive status in tumor cells (n=54) was correlated with a lower incidence of lymphatic invasion (p=0.031) but there were no significant differences in disease-free survival (DFS) and disease-specific survival (DSS) by the log-rank test. Podoplanin-positive status in CAFs (n=41) was correlated with more advanced stage (p=0.008), higher frequency of pleural invasion (p=0.002) and both shorter DFS (p=0.006) and DSS (p=0.006). In Cox's multivariate analysis, podoplanin-positive status in CAFs was an independent negative prognostic factor for DFS (p=0.027) and DSS (p=0.027). CONCLUSION: Podoplanin expression in CAFs might be an independent unfavorable prognostic indicator in patients with lung SCC, irrespective of the expression status of tumor cells.

Simplified comorbidity score for elderly patients undergoing thoracoscopic surgery for lung cancer.

PURPOSE: We investigated the efficiency of the Simplified Comorbidity Score (SCS) for predicting postoperative complications and prognosis in elderly patients undergoing video-assisted thoracoscopic surgery (VATS) for lung cancer. METHODS: We reviewed 216 patients aged 75 years or older, who underwent pulmonary resection by VATS for lung cancer between January, 2005 and December, 2012. The SCS assigns different scores to patients' comorbidities; namely, smoking (n = 7); diabetes mellitus (n = 5); renal insufficiency (n = 4); and respiratory, neoplastic, and cardiovascular comorbidities or alcoholism (n = 1 each). Patients were divided into a high SCS group (SCS ≥ 9; n = 154) and a low SCS group (<9; n = 62), for a comparative analysis of differences in perioperative factors and prognoses. RESULTS: Limited resection was more frequent in the high SCS group (58 %) than in the low SCS group (40 %; P = 0.02). Postoperative complications were more frequent in the high SCS group (45 %) than in the low SCS group (15 %; P < 0.01). A logistic regression analysis revealed that a high SCS was significantly predictive of postoperative complications (odds ratio 2.7; P = 0.02). The 5-year overall survival rate was 79 % for the low SCS group and 52 % for the high SCS group (P < 0.01). CONCLUSIONS: The SCS can predict the likelihood of postoperative complications and prognosis of elderly patients with VATS-treated lung cancers.

Prognostic Significance of Solid and Micropapillary Components in Invasive Lung Adenocarcinomas Measuring ≤3 cm.

BACKGROUND/AIM: We aimed to analyze the clinical impact of solid and micropapillary components in a series of Japanese patients resected for ≤3 cm lung adenocarcinoma. PATIENTS AND METHODS: A total of 115 patients with ≤3 cm lung adenocarcinomas were reviewed and classified according to the American Thoracic Society and the European Respiratory Society classification. The presence of solid (S+) or micropapillary component (MP+) was defined when the component constituted ≥1% of the entire tumor. The impact of these components on disease-free (DFS) and disease-specific (DSS) survival was analyzed. RESULTS: Thirty (26.1%) cases with S+ and 27 (23.5%) with MP+ were identified, and multivariate analysis indicated that S+ status significantly reduced the duration of DFS and DSS. In 86 patients of acinar- and papillary-predominant subgroups, S+ and/or MP+ had the most significant effect on DFS and DSS by multivariate analysis. CONCLUSION: S+ and/or MP+ status predict worse prognosis in patients with acinar- and papillary-predominant lung adenocarcinoma.

Cytoplasmic expression of maspin predicts unfavourable prognosis in patients with squamous cell carcinoma of the lung.

AIMS: Maspin is known to be a tumour suppressor protein, and its prognostic significance in patients with several types of cancer, including lung squamous cell carcinoma (SCC), has been reported. However, its prognostic impact on lung SCC has been controversial. We explored the prognostic value of maspin expression with particular reference to its subcellular localization in patients with lung SCC. METHODS AND RESULTS: Paraffin-embedded tissue samples from 101 curatively resected patients with lung SCC were analysed immunohistochemically using an antibody for maspin. Maspin positivity was defined as strong expression in only the cytoplasm and observed in 25 patients (24.6%). It correlated significantly with the presence of lymph node metastasis (P = 0.006) and higher pathological stage (P = 0.003). The patients were followed-up for 2-119 months (median: 50 months), and the maspin-positive group had shorter disease-free survival (DFS) and disease-specific survival (DSS) by log-rank test (P = 0.002, P = 0.016, respectively). Multivariate analysis revealed that the status of maspin was the only independent prognostic factor for DFS and DSS (P = 0.017, P = 0.047, respectively). CONCLUSIONS: Cytoplasmic expression of maspin could be an independent unfavourable prognostic indicator in patients with lung SCC.

Distribution and Prevalence of Locoregional Recurrence after Video-Assisted Thoracoscopic Surgery for Primary Lung Cancer.

Background The aim of this study is to evaluate cases with locoregional recurrence after video-assisted thoracoscopic surgery (VATS) for primary lung cancer. Methods We reviewed 248 patients with primary lung cancer who underwent lobectomy or segmentectomy with mediastinal lymph node dissection by VATS between January 2005 and December 2011. Locoregional recurrence is defined as per its occurrence in (1) bronchial stump or lung parenchymal cut end, (2) ipsilateral pleura, and (3) ipsilateral hilar and mediastinal lymph nodes, and we analyzed recurrence rate and significant associated factors for locoregional recurrence by logistic regression analysis. Results There were 47 cases of postoperative recurrence, which consisted of 26 distant, 6 locoregional and distant, and 15 locoregional recurrences. The locoregional recurrence rate was 6.0%. Of the 15 locoregional recurrence cases, there were two cases of bronchial stump and lung parenchyma cut end (0.4%), five cases of ipsilateral pleura (2.0%), and eight cases of ipsilateral hilar and mediastinal lymph nodes (3.2%). Pleural and lymphovascular invasion and advanced stages were significant associated factors in univariate analysis. Multivariate analysis revealed that advanced stages were only a significant associated factor for locoregional recurrence (p < 0.01, odds ratio: 3.3). Conclusion Although locoregional recurrence rates of our surgical treatments for primary lung cancer by VATS might be acceptable, we should explore more effective modalities against pathologically proven local advanced lung cancer for preventing not only distant but also locoregional recurrences.

Microcalcification of Tumor is a Predictor of Response to Neoadjuvant Chemotherapy for Invasive Breast Carcinoma.

BACKGROUND: In recent years, neoadjuvant chemotherapy (NAC) is often performed for patients with unresectable breast carcinoma or without indication of breast conserving therapy. However, it is currently difficult to predict response to NAC with diagnostic imaging of breast carcinoma. In this study, we investigated imaging findings that could serve as a predictor of the response to NAC for patients with invasive breast carcinoma. METHODS: Twenty-six patients with invasive breast carcinoma who received NAC at the Division of Breast and Endocrine Surgery of Tottori University Hospital between January 2010 and May 2014 were retrospectively investigated. Their imaging findings from mammograms and ultrasonograms were reviewed. The association between findings on mammograms and ultrasonograms captured before NAC and response to treatment after NAC was examined. RESULTS: Of the 26 patients with invasive breast carcinoma, 19 (73%) responded well to treatment and 7 (27%) did not. Most notably, all 10 patients who had microcalcifications on mammogram responded well to treatment (53% of responders), and all patients who did not respond to treatment had no microcalcifications (P < 0.05). Of these 10 patients, 9 (90%) had microcalcifications of comedo type and one (10%) had non comedo type. As a distribution, 8 of the 10 (80%) had a clustered type of microcalcifications and the remaining 2 (20%) had a segmental type of them. CONCLUSION: Microcalcifications of tumor observed in mammogram (particularly comedo type) could be a predictor of response to NAC for patients with invasive breast carcinoma.

Cytoplasmic maspin expression is a predictor of poor prognosis in patients with lung adenocarcinoma measuring <3 cm.

AIMS: Maspin is known to be a tumour suppressor protein, and few studies focused upon its prognostic significance in patients with small-size lung adenocarcinoma have been reported; however, its clinical significance remains controversial. We explored the prognostic value of maspin with particular reference to its subcellular localization in patients with resected lung adenocarcinoma measuring <3 cm. METHODS AND RESULTS: Immunohistochemical analyses were performed on resected 110 specimens of lung adenocarcinoma measuring <3 cm. Maspin positivity was defined as strong expression in only the cytoplasm and was observed in 27 patients (24.5%). It correlated significantly with the presence of lymph node metastasis (P = 0.009) and micropapillary component (P < 0.001). The patients were followed-up for 6-88 months (median: 71 months), and the maspin-positive group had shorter disease-free survival (DFS) and overall survival (OS) by log-rank test (P < 0.001, P < 0.001, respectively). Using Cox's multivariate analysis, the status of maspin was an independent prognostic factor for DFS and OS (P = 0.004, P = 0.022, respectively), as well as lymph node metastasis. CONCLUSIONS: Cytoplasmic maspin expression could be an independent poor prognostic indicator of patients with lung adenocarcinoma measuring <3 cm.

Excellent prognosis of lepidic-predominant lung adenocarcinoma: low incidence of lymphatic vessel invasion as a key factor.

AIM: To clarify the prognostic value of predominant histological subtypes for small-sized lung adenocarcinoma. MATERIALS AND METHODS: Sixty-four specimens of resected invasive lung adenocarcinoma less than 20 mm in diameter with no lymph node metastasis were studied. These specimens were microscopically classified into predominant histological subtypes (21 lepidic, 16 acinar, 24 papillary, and three solid) according to the International association for the study of lung cancer/American thoracic society/European respiratory society adenocarcinoma classification. The relationships between tumor relapse and predominant histological subtypes were statistically analyzed. In addition the relationships between several pathological factors and predominant histological subtypes were statistically assessed. RESULTS: Kaplan-Meier relapse-free curves showed a five-year relapse-free rate of 100% in 64 patients with lepidic-predominant adenocarcinoma, compared with a rate of 73.7% (p=0.035 by log rank test) in patients with non-lepidic-predominant adenocarcinoma (papillary, acinar, and solid). The only statistically significant pathological factor between lepidic-predominant and non-lepidic-predominant histological subtypes was lymphatic vessel invasion as assessed by logistic regression analysis. CONCLUSION: In small-sized lung adenocarcinoma, lepidic-predominant histological subtype is the best prognostic factor, and a low incidence of lymphatic vessel invasion in the histological subtype is a key factor for an excellent prognosis.

Patient-related factors associated with depressive state in caregivers of patients with dementia at home.

OBJECTVES: To identify patient-related factors associated with depressive state in caregivers of patients with dementia, we investigated the caregivers' and patients' characteristics in relation to the depressive state in their caregivers. DESIGN: Prospective hospital-based cohort study. SETTING: Two memory clinics in Japan. PARTICIPANTS: Outpatients with dementia (n = 135) and their caregivers at home. MEASUREMENTS: The outpatients and their caregivers were divided into 2 groups according to the Center for Epidemiologic Studies Depression Scale for caregivers. To identify the patient-related factors that cause depressive state in caregivers, Mini-Mental State Examination (MMSE), the Physical Self-Maintenance Scale for fundamental activities of daily living (ADL), and the instrumental ADL scale (IADL) scores for instrumental ADL and the neuropsychiatric inventory (NPI) subscale score for behavioral and psychological symptoms of dementia were compared between the 2 groups. We used logistic regression to determine the independent predictors of caregiver depressive state. RESULTS: There was no significant difference in MMSE score between the 2 groups. Logistic regression analysis revealed that the depressive state in caregivers was related with IADL score and delusion in NPI subscale of patients. CONCLUSIONS: Depressive state in caregivers was independent of the decline in cognitive function in patients with dementia but was associated with decline in instrumental ADL and severity of delusion.

Desmoid tumor requiring differentiation from port-site relapse after surgery for lung cancer.

Thoracoscopic left lower lobectomy with lymph node dissection for lung cancer was performed in a 76-year-old man. The diagnosis was pT2aN2M0 adenocarcinoma. Sixteen months after surgery, CT revealed a pleural tumor measuring 38 mm at the surgical port wound. CT-guided biopsy revealed fibroma. However, the tumor size increased 4 months after biopsy, and surgery was performed. An intraoperative diagnosis revealed benign fibroma. Thoracoscopic tumorectomy was conducted. The pathological diagnosis was desmoid tumor. As the margins of the resected specimen were positive, radiotherapy was performed. During the 16-month follow-up period, there has been no relapse. Pleural desmoid tumors must be differentiated from port-site relapse.

Sarcoid-like reaction in Cryptococcus neoformans infection.

We report a patient with Cryptococcus (C.) neoformans infection, who developed a case of sarcoid-like reaction (SLR). There have been reports of SLRs associated with malignancies. Although differentiating sarcoidosis from SLR is difficult, the patient was diagnosed as SLR because propionibacterium acnes bacterial (PAB) antibody staining of biopsy specimens was negative and the chest radiological findings improved after antifungal treatment. To our knowledge, this is the first report of SLR occurring during cryptococcal infection, and we believe that cryptococcal infection should be considered as a potential cause of SLR.

A case of sinobronchial syndrome complicated with myeloperoxidase antineutrophil cytoplasmic antibody associated vasculitis: review of the literature.

We report a case of long-standing sinobronchial syndrome complicated by microscopic polyangiitis (MPA) during the clinical course. The patient showed a mild elevation of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) 17 months prior to the diagnosis of MPA. Subsequently, her MPO-ANCA level gradually became more elevated, and finally her MPO-ANCA level peaked when purpura appeared. Histologic examination of the skin biopsy was consistent with leukocytoclastic vasculitis. Based on the pathological and clinical findings, a diagnosis of MPA was made. Corticosteroid therapy finally led to a remission of MPA with normalized MPO-ANCA titers.

[Adenocarcinoma of the lung in a young adult].

We report a case of 24-year-old young man with lung adenocarcinoma. The patient had been treated malignant lymphoma when he was 5 years old. The patient was pointed out a tumor shadow of the right lung at his 2008 health check, but he did not receive further examination. He was again pointed out a same tumor at his 2009 health check. Plain chest computed tomography (CT) revealed a nodule in S8 of right lung. A diagnosis of lung adenocarcinoma was established by the cytology specimens obtained with bronchoscopic examination. The patient underwent right lower lobectomy with systematic lymph node dissection. Pathological stage was pT2N2M0 stage IIIA. Lung cancer patients aged under 30 years old are rare. Lung cancer should be considered even in young patients with abnormal chest shadows.