Combined Application of Nivolumab and Intravesical Bacillus Calmette-Guérin Led to Acute-Onset Type 1 Diabetes.

We report a case of acute-onset type 1 diabetes due to combined application of nivolumab and intravesical Bacillus Calmette-Guérin (BCG). An 84-year-old woman underwent lung resection for pulmonary squamous cell carcinoma. She had been treated for type 2 diabetes and later experienced lung cancer recurrence. She was started on nivolumab treatment, and complete response was achieved for one year. However, during this time, she was diagnosed with superficial bladder cancer and underwent surgery but experienced recurrence. After one month of intravesical BCG instillation, the patient developed acute-onset type 1 diabetes. Thus, we recommend that combined application of nivolumab and intravesical BCG be avoided.

Pirfenidone-induced Eosinophilic Pleurisy.

The patient was a 69-year-old man with idiopathic pulmonary fibrosis who was taking pirfenidone. After 7 weeks of treatment, he suffered from left-sided eosinophilic pleurisy. Medical thoracoscopy was performed and the histopathological examination of the parietal pleura revealed the massive infiltration of eosinophils and lymphoid follicles. After stopping pirfenidone therapy, the patient's pleural effusion disappeared without additional treatment, and never recurred. This is the first case report of pirfenidone-induced pleurisy.

Efficacy and tolerability of nanoparticle albumin-bound paclitaxel in combination with carboplatin as a late-phase chemotherapy for recurrent and advanced non-small-cell lung cancer: A multi-center study of the Fukushima lung cancer association group of surgeons.

The present retrospective multi-center study aimed to evaluate the efficacy and feasibility of nanoparticle albumin-bound (nab)-paclitaxel plus carboplatin as a second or late-phase chemotherapy in patients with non-small cell lung cancer (NSCLC). A total of 25 patients with recurrent or advanced NSCLC who had received previous chemotherapy were treated with nab-paclitaxel (70-100 mg/m2, intravenously) on days 1, 8 and 15 every 28 days with a carboplatin area under the concentration-time curve of 4-6 on day 1. The overall response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicities were statistically evaluated. Of the 25 patients, there were 9 cases of recurrent disease following surgery, 16 cases of advanced disease, 13 cases of adenocarcinoma, 11 cases of squamous cell carcinoma and 1 case of large cell carcinoma. A total of 13 patients received second-line chemotherapy and 12 received fourth-line or later chemotherapy. One patient exhibited a complete response, 7 had a partial response, 10 exhibited stable disease and 7 had progressive disease. The overall response rate was 32.0% and the disease control rate was 72.0%. The median PFS and median OS following nab-paclitaxel treatment were 4.0 and 14.0 months, respectively. Frequent treatment-associated adverse events were myelosuppression, peripheral neuropathy, gastrointestinal symptoms and baldness, the majority of which were grade 1-2. Grade 3-4 neutropenia, thrombocytopenia and anemia occurred in 7 (28.0%), 3 (12.0%) and 2 (8.0%) patients, respectively. No patients experienced grade 3-4 sensory neuropathy and no grade 5 adverse effects were observed. Nab-paclitaxel plus carboplatin as second-phase or later chemotherapy provided a small but significant survival benefit for patients with recurrent or advanced NSCLC, with tolerable adverse effects. To the best of our knowledge, the results of the present study demonstrated for the first time that nab-paclitaxel plus carboplatin is a promising and feasible late-phase chemotherapeutic agent for NSCLC.

Bronchoscopic Investigation of Atypical Drug-induced Hypersensitivity Syndrome Showing Viral Lung Involvement.

We herein report a case of atypical drug-induced hypersensitivity syndrome (DIHS) involving serological reactivation of cytomegalovirus induced by carbamazepine with pulmonary and skin manifestations. These lesions were not present on admission, but developed on virus reactivation as indicated by the presence of inclusion bodies and multinucleated giant cells in alveolar cells with CD8(+) T lymphocyte infiltration on a transbronchial lung biopsy. Although the precise mechanism of DIHS remains unknown, this case suggests the crucial role of viral reactivation in pulmonary lesions in DIHS.

Microscopic findings of sheet-type collagen applied to air leaks after pulmonary resection.

PURPOSE: It has been reported that Integran(®), a sheet-type absorbable topical collagen hemostat, is feasible for preventing pulmonary fistula after lung surgery. The most favorable aspect of Integran(®) is that it contains no blood products. However, the microscopic findings of post-surgery application of Integran(®) to the lung are not known. We identified 2 such cases of Integran(®) application, which were carried out a few years earlier, and described the microscopic findings. METHOD: In case 1, a 53-year-old man underwent video-assisted left upper lobectomy for primary lung cancer. Integran(®) was applied to the left lower lobe. Completion left pneumonectomy was performed after 2 years and 1 month due to recurrence. In case 2, a 77-year-old woman underwent video-assisted right middle lobectomy for primary lung cancer. Integran(®) was applied to the right upper lobe. Completion right upper lobectomy was performed after 1 year and 8 months due to recurrence. RESULTS: The repaired visceral pleura of the 2 patients were covered with proliferated collagen fibers. However, there was little infiltration of inflammatory cells and fibroblasts. CONCLUSION: The microscopic findings revealed that the ability of Integran(®) to generate inflammation or adhesion is weak, but it has the ability to repair damaged visceral pleura.

A case of choroidal metastasis of lung cancer successfully treated with erlotinib.

We present a case of choroidal metastasis of lung cancer in which choroidal metastasis, the first manifestation of recurrence, was successfully treated with erlotinib. A 49-year-old woman with a 2. 0 cm nodule in the right lung was diagnosed with adenocarcinoma, and a right upper lobectomy was performed. After 2 months, she presented with blurred vision of the right eye. Her right visual acuity had decreased to 0. 1, and there was a visual field defect temporal to the macula. Fundus examination of the right eye revealed an elevated mass with exudative retinal detachment temporal to the disc. Fluorescein angiography revealed hypofluorescence during the prearterial and arteriovenous phases, and fluorescein leakage surrounded by a circular hypofluorescence area during the venous phase. Spectral-domain optical coherence tomography showed exudative retinal detachment. The cancer cells had a mutation of the epidermal growth factor receptor gene in exon 19. She was treated with erlotinib at 100 mg per day, and after 4 days, her right visual acuity had improved to 1. 2.

A case of diaphragmatic clear cell carcinoma in a patient with a medical history of ovarian endometriosis.

We present a case of clear cell carcinoma located in the diaphragm in a patient with a medical history of ovarian endometriosis. Ultrasonography revealed the presence of a 2.5-cm nodule on the surface of the liver in a 65-year-old woman. She had undergone right salpingo-oophorectomy for treatment of an endometrial cyst of the right ovary at the age of 43 years and hysterectomy for treatment of a myoma of the uterus at the age of 51 years. We performed laparotomy and found that the tumor had originated from the diaphragm and invaded the liver. The diaphragm and liver were partially resected. Histopathological examination revealed the presence of clear cells and hobnail cells. The clear cells contained pale or eosinophilic cytoplasm and were arranged in a solid pattern. The hobnail cells lined the lumen and papillae. Immunohistochemical examination of the tumor cells showed positive staining for CK-7 and CA-125; negative staining for CK-20, TTF-1, and CA19-9; and weak positive staining for CEA. The findings were compatible with those of ovarian clear cell carcinoma. After 1 year, the patient had metastasis in the lung, and right lower lobectomy was performed.

Immunoglobulin G4-related inflammatory pseudotumor of the lung.

An 82-year-old man presented with a nodule in the right S(2)a of the lung as seen by chest computed tomography (CT). He had undergone treatment for chronic obstructive lung disease. He had a 53-year history of smoking 20 cigarettes a day. Subsequent to the appearance of the nodule in the right S(2)a, the CT images revealed consolidations in the right S(2)b, right S(3), and left S(5). The nodule in the right S(2)a was diagnosed as squamous cell carcinoma after performing video-assisted thoracoscopic wedge resection of the lung. After 4 months, the size of the consolidation in the right S(2)b increased. Recurrence of lung cancer was suspected. Using transbronchial lung biopsy, the consolidation in the left S(5) was diagnosed as organizing pneumonia; therefore, right upper lobectomy was performed. The consolidations in the right S(2)b and right S(3) were diagnosed as inflammatory pseudotumors with infiltrations of immunoglobulin G4-positive plasma cells.

Solitary fibrous tumors of the pleura presenting satellite tumors.

A 29-year-old man presented with a mass in the left lower lung field on a chest radiograph obtained during a medical checkup. Computed tomography revealed a tumor adjacent to the diaphragm. A sessile tumor measuring 10.5 x 8.5 x 4.5 cm arising from the parietal pleura was resected. The tumor was accompanied by several little tumors on the nearby diaphragm. Pathologically, the major tumor consisted of typical spindle-shaped cells with myxoid degeneration. There was no increased cellularity, cellular pleomorphism, or a high mitotic count. In immunohistochemical studies, the spindle cells showed positive staining for CD34 and were negative for bcl-2. The smaller tumors also consisted of myxoid degeneration. We diagnosed benign solitary fibrous tumor of the pleura with satellite tumors. We must be aware of the possibility of satellite tumors when we treat patients with a benign solitary fibrous tumor.

[A case of non-Hodgkin's lymphoma after chemotherapy for cancer of unknown origin].

We present a case of non-Hodgkin's lymphoma after chemotherapy for a cancer of unknown origin. A 68-year-old man was hospitalized for hoarseness. Computed tomography(CT)scans showed a swelling of the superior mediastinal lymph node and a tumor of the right lobe of thyroid gland. Resection of the superior mediastinal lymph node and right hemithyroidectomy were performed. Pathological findings of the lymph node showed adenosquamous cell carcinoma, but no malignant lesion was found in the thyroid gland. Post-operative systemic survey failed to identify the origin of the adenosquamous cell carcinoma. Six courses of chemotherapy consisting of carboplatin and docetaxel were carried out. Seven months later, CT and positron emission tomography revealed swelling of the mediastinal lymph nodes and a tumor in the left abdominal tumor. An open biopsy of the abdominal tumor demonstrated non-Hodgkin's lymphoma, mature B cell type, follicular lymphoma, grade 1. Radiotherapy was done for the malignant lymphoma, and radiochemotherapy for the mediastinal lymph nodes. Seven months later, the patient died of systemic metastases of the adenosquamous cell carcinoma.

Carbohydrate status detecting by PNA is changeable through cancer prognosis from primary to metastatic nodal site: A possible prognostic factor in patient with node-positive lung adenocarcinoma.

Carbohydrates antigens in cancer cells are considered to be important molecules, which may play a critical role for metastasis. To elucidate the prognostic relevance of the expression of peanut agglutinin (PNA) binding carbohydrates in patients with lung adenocarcinoma, we investigated the PNA binding carbohydrates immunohistochemically in both of primary tumors and involving nodal lesions. A total of 62 patients with node-positive primary lung adenocarcinoma, who had undergone complete resection and regional nodes dissection were subjected to this study. There were no significant correlations between PNA staining rates and clinicopathological variables. The survival rate of patients who had positive PNA staining in both of primary tumor and nodal lesion was significantly higher than those of patients in the other groups. Furthermore, the loss of the staining rate of PNA was an independent prognostic factor beside the lymphatic vessel invasion using multivariate analysis. The expression of PNA binding carbohydrates in tumor tissue and nodal lesion would be a novel significant prognostic factor for patients with node-positive lung adenocarcinomas.

Identification of the decay-accelerating factor CD55 as a peanut agglutinin-binding protein and its alteration in non-small cell lung cancers.

PURPOSE: Peanut agglutinin (PNA) recognizes tumor-associated carbohydrates. In this study, we aimed to identify the core protein harboring PNA-binding sugars in the human lung and to explore the relationship with the pathology of primary non-small cell lung cancers (NSCLC). EXPERIMENTAL DESIGN: PNA lectin blotting was used to detect PNA-binding proteins in the microsomal fraction of lung tissue from 24 patients with NSCLC. The 55- to 65-kDa core peptide PNA-binding protein was characterized by enzymatic treatment and identified by immunoprecipitation and affinity chromatography. The expression level and increase in size of the 55- to 65-kDa PNA-binding protein/decay-accelerating factor (DAF) were compared between normal and tumor regions of the tumor tissue by Western blotting and quantitative PCR. RESULTS: The 55- to 65-kDa PNA-binding protein was observed in human lung. This was a glycosylphosphatidylinositol-anchored membrane protein carrying O-linked carbohydrates. This core protein was identified as DAF, one of the complementary regulatory proteins. DAF was enlarged to 65 to 75 kDa in NSCLC tumor lesions due to sialylation in the sugar moiety. At the transcription level, DAF levels were significantly lower in tumor regions, suggesting its down-regulation in NSCLC cells. CONCLUSIONS: DAF was identified as a new PNA-binding protein in the human lung. The down-regulation and heavy sialylation of DAF was associated with pathology in NSCLC, and these alterations make this protein a potential marker for NSCLC.

Molecular cloning and characterization of novel splicing variants of human decay-accelerating factor.

Decay-accelerating factor (DAF) is one of the complement regulatory proteins. Two isoforms of DAF have been identified in humans. In this study, we isolated novel cDNAs encoding five isoforms of DAF from the human lung, which were generated by insertion of new exonic sequences. RT-PCR revealed that all isoforms were expressed in almost all tissues tested, although the expression patterns and levels differed among the tissues. Transfection of isoform vDAF1, 2, and 3 cDNAs into CHO cells showed that these molecules are soluble forms secreted after glycosylation. Isoform vDAF4 and vDAF5 cDNAs included a part of and the entire intron 7 sequence, respectively, and the transfection of vDAF4 cDNA produced a large, glycosylated, membrane-bound form. These results suggest that more than seven isoforms of human DAF are involved in the regulation of complement activation under physiological conditions through their specific structures and localization.

Prognostic impact of p53 protein overexpression in patients with node-negative lung adenocarcinoma.

Prognostic value of p53 protein expression in node-negative lung adenocarcinoma is still controversy. The expression of p53 protein was examined immunohistochemically in lung adenocarcinoma using monoclonal antibody BP53-12. A total 131 cases of primary lung adenocarcinoma were examined. Relationship between expression of p53 protein and clinicopathologic factors were studied. Overexpression of p53 protein was found in 19 patients (14.5%). Univariate and multivariate analysis showed that overexpression of p53 protein was an independent prognostic factor in node-negative lung adenocarcinoma. p53 alteration could be a valuable predictor for prognosis in node-negative lung adenocarcinoma.

[Tissue array analysis of the aberrant expression of HLA class I molecules in human non small cell lung cancer].

A clinical significance of the aberrant expression of HLA class I molecules including HLA class I and HLA-G was analyzed using tissue array analysis. Our institute has established a two millimeter spot sized tissue array set of 105 clinical cases of resected human non small cell lung cancer tissues. A loss of HLA class I was observed in the 58.3% of cancer tissues. The aberrant expression of HLA G was also observed in the 55.2% of cancer tissues. Statistically significant correlations were observed among HLA class I expression and tumor size, nodal involvement and pathological stage. Survival analyses were shown that the HLA class I loss was correlated to a recurrence free survival time. The HLA-G expression did not correlate with any clinico-pathological parameters. A loss of HLA class I was probably involved due to a cancer progression in human non-small cell lung cancer through the mechanism of immune escape from the host immune system.

Extent of mediastinal lymph node dissection for clinical T1 non-small cell lung cancer.

The present study was designed to determine the extent of lymph node dissection for clinical T1 non-small cell lung cancer without negatively influencing curability. The study included 192 cases with clinical T1 non-small cell lung cancers who underwent lobectomy with mediastinal lymphadenectomy. Among 69 cases with right upper lobe tumors, metastasis was found in subcarinal lymph node in one case only. No metastasis was found in subcarinal node in cases free of metastasis in hilar and/or superior mediastinal nodes. Among 33 cases with right lower lobe tumors, metastasis was detected in the superior mediastinal node only in cases with metastasis in hilar and/or subcarinal nodes. Among 51 cases with left upper lobe tumors, no metastasis was found in the subcarinal node. Among 22 cases with left lower lobe tumors, metastasis was found in the superior mediastinal nodes only in cases with metastasis in hilar and/or subcarinal nodes. We propose the following scheme for the extent of mediastinal node dissection. Dissection of mediastinal node for clinical T1 non-small cell lung cancer cannot be omitted. But, 1) for upper lobe tumors, subcarinal lymphadenectomy could be omitted if no metastasis is found in hilar and superior mediastinal nodes based on gross and microscopic examination of frozen sections. 2) Similarly, for lower lobe tumors, superior mediastinal lymphadenectomy could be omitted if no metastasis is detected in the hilar and subcarinal nodes.

Triad of thymoma, myasthenia gravis and pure red cell aplasia combined with Sjögren's syndrome.

A 36-year-old woman complained of cough and high fever. Computed tomographic scans demonstrated a mediastinal mass. A couple of months later, she developed dryness in her eyes and mouth. Biopsy of the lip confirmed the diagnosis of Sjögren's syndrome. She underwent thymo-thymomectomy. Pathological findings of the mass revealed thymoma. At two months after surgery, she developed ptosis and dysphagia that were compatible with myasthenia gravis. The clinical symptoms were adequately controlled with prednisolone. At eleven months after surgery, she presented with severe anemia, which led to the diagnosis of pure red cell aplasia. The following treatment with cyclosporin caused hemoglobin concentration to rise. However, she continues to suffer from dryness of her eyes and mouth. The case is the first to be reported with Sjögren's syndrome and the triad of thymoma, myasthenia gravis and pure red cell aplasia, and is compared with previously reported cases of the three conditions.

Hemopneumothorax associated with Marfan syndrome and congenital afibrinogenemia.

In patients with afibrinogenemia who require operation, prophylaxis against bleeding is important. We report the case of a 14-year-old boy with Marfan syndrome and congenital afibrinogenemia in whom hemopneumothorax developed. Video-assisted thoracoscopic surgery was performed successfully under intravenous administration of fibrinogen and with careful monitoring of plasma fibrinogen level.

Preoperative pulmonary function as a predictor of respiratory complications and mortality in patients undergoing lung cancer resection.

OBJECTIVE: We evaluated preoperative pulmonary function as a predictor of respiratory complications and mortality in patients undergoing lung cancer resection to confirm the guideline of the British Thoracic Society: lung cancer surgery in patients with predictive postoperative FEV(1.0) (%FEV(1.0)ppo) > 40% and predictive postoperative diffusion capacity for carbon monoxide (%DL(co)ppo) > 40% can be carried out with average risk. METHODS: We retrospectively studied 356 consecutive patients who underwent pulmonary resection at our Department from January 1992 to December 2001. Preoperative pulmonary function tests included vital capacity (VC), %VC, forced expiratory volume in one second (FEV(1.0)), FEV(1.0)%, diffusion capacity for carbon monoxide (DL(co)), predictive postoperative FEV(1.0) (FEV(1.0)ppo), postoperative respiratory function expressed as a percentage of the predicted normal value (%FEV(1.0) ppo, %DL(co)ppo). Postoperative complications were divided into 2 groups: respiratory complications (pneumonia, atelectasis, etc) and other complications (bronchopleural fistula, prolonged air leak, arrhythmia, etc). RESULTS: Postoperative deaths occurred in 14 (3.9%) patients. Postoperative respiratory complications developed in 27 (7.6%) patients. Pneumonectomy (p < 0.001), preoperative chemotherapy (p < 0.01) and advanced stage (p < 0.05) were identified as risk factors of postoperative deaths. Patients undergoing lobectomy with FEV(1.0) > or = 1,500 ml did not die of respiratory complications. Patients undergoing pneumonectomy with FEV(1.0)ppo > or = 800ml/m2 did not die of respiratory complications. Patients undergoing pneumonectomy with %FEV(1.0)ppo < 40% and %DL(co)ppo < 40% did not survive. Five of the 7 patients who died of respiratory complications were treated with preoperative chemotherapy. The values of their %DL(co)ppo were all less than 40%. By multivariate analysis, %FEV(1.0)ppo was significant independent factor associated postoperative death. CONCLUSIONS: We conclude that the guideline is useful for the selection for surgery of lung cancer patients. If preoperative chemotherapy is performed, the measurement of %DL(co) is recommended before surgery.

Expression of peanut agglutinin-binding carbohydrates correlates with nodal involvement in human lung adenocarcinoma.

The expression of 15 kinds of lectin-binding carbohydrates was examined histochemically in lung adenocarcinoma. The relation between expression of lectin binding carbohydrates and clinicopathologic factors was studied. The expression of peanut agglutinin (PNA) binding carbohydrates showed a high lymph node metastatic rate. Relation between PNA-binding carbohydrate expression and lymphatic vessel invasion was also recognized. Multivariate analysis showed that PNA-binding carbohydrate expression was an independent predictive factor of lymph node metastasis (odds ratio: 2.8) and of lymphatic vessel invasion (odds ratio: 5.2). The expression of PNA-binding carbohydrates would be a significant predictive factor for lymph node metastasis of lung adenocarcinomas.