Pulmonary Apical Opacities on Thin-Section Computed Tomography: Relationship to Primary Spontaneous Pneumothorax in Young Male Patients and Corresponding Histopathologic Findings.

OBJECTIVE: The purpose of this study was to test the hypothesis that apical opacities on computed tomography (CT) are related to occurrence of primary spontaneous pneumothorax (PSP) in young male patients. METHODS: We compared the frequency of apical opacities on thin-section CT between 70 male patients with PSP (PSP group) and 74 male patients without a history of PSP (non-PSP group). We also evaluated histopathologic findings of 39 specimens from 37 surgical cases in the PSP group. RESULTS: Apical opacities were significantly more frequent in the PSP group than in the non-PSP group (right side, P = 0.01; left side, P = 0.005). Histopathologically, subpleural band-like alveolar collapse was seen in 35 specimens (89.7%), which was always accompanied by fibroelastosis and fibroblastic foci. CONCLUSIONS: Apical opacities on CT were significantly associated with PSP in young male patients. These apical opacities histopathologically correspond to fibrotic pleural thickening with subpleural alveolar collapse.

Predictive biomarkers and effectiveness of MUC1-targeted dendritic-cell-based vaccine in patients with refractory non-small cell lung cancer.

BACKGROUND: The dendritic cell (DC)-based vaccine targeting the highly immunogenic tumor antigen, MUC1, has been promising for a cancer immunotherapy; however, predictive biomarkers for beneficial clinical responses of the vaccine remain to be determined. METHODS: DCs loaded with MUC1-derived peptide were subcutaneously administered to patients with MUC1-positive non-small cell lung cancer (NSCLC) that was refractory to standard anticancer therapies, every 2 weeks. The effectiveness and tolerability of the vaccine were evaluated, and predictive biomarkers of clinical responses were explored. RESULTS: Between August 2005 and May 2015, 40 patients received the vaccines. The median survival time (MST) after the initial vaccination was 7.4 months, and the 1-year survival rate was 25.0%. The MST for patients who received more than six vaccinations was 9.5 months, and the 1-year survival rate was 39.3%. In this cohort, patients who experienced immune-related adverse events, including skin reactions at the vaccination site and fever, had significantly longer survival times compared with patients without those immune-related adverse events (12.6 versus 6.7 months, p = 0.042). Longer survival times were also observed in patients whose peripheral white blood cells contained >20.0% lymphocytes (12.6 versus 4.5 months; p = 0.014). MUC1-specific cytotoxic immune responses were achieved in all of seven patients analyzed who received six vaccinations. CONCLUSION: The MUC1-targeted DC-based vaccine induced an antitumor immune response that promoted prolonged survival of patients with refractory NSCLC. The occurrence of immune-related adverse events and having a higher percentage of peripheral lymphocytes were predictive biomarkers of a beneficial clinical response during cancer immunotherapy for NSCLC.

[A Case of Successful Collective Treatment of Colon Cancer with Multiple Metachronous Pulmonary Metastases].

A case is a 46-year-old woman visited us with a chief complaint of bloody stools. A diagnosis of rectal cancer(Rs)was made, and laparoscopic resectomy plus D3 was performed. After progressing to pT4a(SE)N2, M0, pStage III b, postoperative adjuvant chemotherapy(6 courses of XELOX)was administered. Two months after initiating chemotherapy, since the CEA value increased, chest abdominal CT was performed. Five nodules were found in the bilateral lungs and diagnosed as lung metastases(PUL2). Systemic chemotherapy(IRIS plus BV)is administered to PUL2(Grade C)of rectal cancer metachronous metastases. After 3 courses, the effect judgment was SD. Based on the recurrence period from postoperative adjuvant chemotherapy and the findings during this time, it was judged that weight loss surgery was appropriate for the rectal cancer lung metastatic lesions in which chemotherapy was ineffective, and partial resection of both lungs under thoracoscopic assistance was performed. Systemic chemotherapy(TAS-102 plus BV)was initiated to prevent postoperative recurrence. The patient is currently alive without relapse after 12 months. We reported a case of metachronous metastasis of colon cancer in which multidisciplinary treatment was successful.

Serum Type IV Collagen Concentration Correlates with Indocyanine Green Retention Rate and is an Indicator Of Hepatotoxicity In Patients Receiving FOLFOX for Colorectal Cancer.

BACKGROUND: Assessment of oxaliplatin-associated hepatotoxicity in patients receiving oxaliplatin, fluorouracil and leucovorin chemotherapy (FOLFOX) for colorectal cancer remains controversial. The aims of this study were to clarify which variables are indicators of such hepatotoxicity. METHODOLOGY: Twenty-seven patients who were to receive FOLFOX for colorectal cancer were included in this study. A range of liver function tests, including serum hyaluronic acid (HA) and type IV collagen concentrations, indocyanine green (ICG) retention rate at 15 min (ICGR15) and splenic volume were assessed before commencement of chemotherapy and after four cycles of FOLFOX. RESULTS: No significant changes were found in conventional liver function tests or splenic volume. Significant changes pre- and post-FOLFOX were found in type IV collagen concentrations and ICGR15. Correlation analyses showed that the following two factors were associated with significant changes in ICGR15 after four cycles of FOLFOX: platelet count (p = 0.028, correlation coefficient 0.423), and type IV collagen concentration (p < 0.001, correlation coefficient 0.830). The regression line between type IV collagen concentration and ICGR15 was Y = 2.70 + 0.84 x X. CONCLUSION: Serum type IV collagen concentration is an indicator of oxaliplatin-associated hepatotoxicity and correlates with significant changes in ICGR15 in patients receiving FOLFOX.

Serum Type IV Collagen Concentration Correlates with Indocyanine Green Retention Rate.

BACKGROUND/AIMS: Assessment of oxaliplatin-associated hepatotoxicity in patients receiving oxaliplatin, fluorouracil and leucovorin chemotherapy (FOLFOX) for colorectal cancer remains controversial. The aims of this study were to clarify which variables are indicators of such hepatotoxicity. METHODOLOGY: Twenty-seven patients who were to receive FOLFOX for colorectal cancer were included in this study. A range of liver function tests, including serum hyaluronic acid (HA) and type IV collagen concentrations, indocyanine green (ICG) retention rate at 15 min (ICGR15) and splenic volume were assessed before commencement of chemotherapy and after four cycles of FOLFOX. RESULTS: No significant changes were found in conventional liver function tests or splenic volume. Significant changes pre- and post-FOLFOX were found in type IV collagen concentrations and ICGR15. Correlation analyses showed that the following two factors were associated with significant changes in ICGR15 after four cycles of FOLFOX: platelet count (p = 0.028, correlation coefficient 0.423), and type IV collagen concentration (p < 0.001, correlation coefficient 0.830). The regression line between type IV collagen concentration and ICGR15 was Y = 2.70 + 0.84 x X. CONCLUSION: Serum type IV collagen concentration is an indicator of oxaliplatin-associated hepatotoxicity and correlates with significant changes in ICGR15 in patients receiving FOLFOX.

Complications associated with endobronchial ultrasound-guided transbronchial needle aspiration: a nationwide survey by the Japan Society for Respiratory Endoscopy.

BACKGROUND: With the recent widespread use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), there have been occasional reports on complications associated with its use. Previous reviews on EBUS-TBNA have been limited to studies by skilled operators, thus the results may not always be applicable to recent clinical practice. To assess the safety of EBUS-TBNA for the staging and diagnosis of lung cancer in Japan, a nationwide survey on its current usage status and complications associated with its use was conducted by the Japan Society for Respiratory Endoscopy (JSRE). METHODS: A questionnaire about EBUS-TBNA performed between January 2011 and June 2012 was mailed to 520 JSRE-accredited facilities. RESULTS: Responses were obtained from 455 facilities (87.5%). During the study period, EBUS-TBNA was performed in 7,345 cases in 210 facilities (46.2%) using a convex probe ultrasound bronchoscope, for 6,836 mediastinal and hilar lesions and 275 lung parenchymal lesions. Ninety complications occurred in 32 facilities. The complication rate was 1.23% (95% confidence interval, 0.97%-1.48%), with hemorrhage being the most frequent complication (50 cases, 0.68%). Infectious complications developed in 14 cases (0.19%) (Mediastinitis, 7; pneumonia, 4; pericarditis, 1; cyst infection, 1; and sepsis, 1). Pneumothorax developed in 2 cases (0.03%), one of which required tube drainage. Regarding the outcome of the cases with complications, prolonged hospitalization was observed in 14 cases, life-threatening conditions in 4, and death in 1 (severe cerebral infarction) (mortality rate, 0.01%). Breakage of the ultrasound bronchoscope occurred in 98 cases (1.33%) in 67 facilities (31.9%), and that of the puncture needle in 15 cases (0.20%) in 8 facilities (3.8%). CONCLUSIONS: Although the complication rate associated with EBUS-TBNA was found to be low, severe complications, including infectious complications, were observed, and the incidence of device breakage was high. Since the use of EBUS-TBNA is rapidly expanding in Japan, an educational program for its safe performance should be immediately established.

Micropapillary components in a lung adenocarcinoma predict stump recurrence 8 years after resection: a case report.

We report a rare case of lung adenocarcinoma in which micropapillary components were considered to cause stump recurrence. A woman in her fifties was diagnosed with lung cancer in the right middle lobe with invasion to the upper lobe, which was treated by a right middle lobectomy together with upper lobe partial resection. The cancer was pathologically diagnosed as adenocarcinoma and had a free surgical margin. There was no recurrence during the following 5 years and 8 months, and thus periodical surveillance, including computed tomography, was stopped. However, 2 years and 7 months after this, she was discovered to have an abnormal shadow on chest radiography, and a thorough examination revealed a 3-cm-sized tumor involving the previous surgical margin. Therefore, she underwent right upper lobectomy. We pathologically re-evaluated the first tumor and found that it was an adenocarcinoma with a micropapillary component in the periphery, 6mm away from the surgical margin. In addition, a few tiny clusters of tumor cells were found to be floating within the alveolar spaces near the margin. The first and second tumors showed almost the same histological mixture of components of adenocarcinoma and the same EGFR mutation. From these results, we concluded the second tumor was a stump recurrence originating from the first tumor resection. This case illustrates the importance of careful pathological investigation when an autosuture instrument is used for a partial resection in a case of lung adenocarcinoma with micropapillary components. In such cases, it is particularly important to clarify if micropapillary components are floating near a stump.

Pulmonary focal fibrosis associated with microscopic arterio-venous fistula manifesting as focal ground-glass opacity on thin-section CT.

BACKGROUND: Focal ground-glass opacity (GGO) on thin-section computed tomography (CT) may be seen in atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ that has recently been renamed from bronchioloalveolar carcinoma (BAC) and various benign conditions. CASE PRESENTATION: We report a case of pulmonary focal fibrosis associated with microscopic arterio-venous fistula (AVF), which showed a focal area of GGO on thin-section CT. The patient was a 58-year-old woman with a GGO on thin-section CT which had increased in size over the period of 2 years. Slightly dilated vessels and thickened interlobular septa were also noted around the GGO. It was diagnosed preoperatively as adenocarcinoma in situ and a partial lung resection by video-assisted thoracic surgery (VATS) was performed. Pathological examination yielded a diagnosis of focal fibrosis associated with microscopic AVF. CONCLUSION: We speculate that the focal fibrosis was produced by a prolonged congestion due to the AVF and that the dilated vessels and thickening of interlobular septa on thin-section CT related to the AVF. Microscopic AVF may be one of the etiologies of focal fibrosis showing focal GGO on thins-section CT. Dilated vessels and thickened interlobular septa around the GGO might offer a clue to the diagnosis of this disease entity. In addition, it should be noted that focal fibrosis may increase in size.

Bronchoscopic practice in Japan: a survey by the Japan Society for Respiratory Endoscopy in 2010.

BACKGROUND AND OBJECTIVE: To ensure the safety of bronchoscopic practice, the Japan Society for Respiratory Endoscopy conducted a national survey to investigate the current state of procedure for this technique. METHODS: A questionnaire survey about procedures carried out during the whole of the year 2010 was mailed to 538 facilities accredited by the society. RESULTS: Responses were obtained from 511 facilities (95.0%). Rigid bronchoscopes were used in only 18.5% of the facilities, while mobile/thin bronchoscopes were used in ≥ 50%, and fluoroscopy systems were used in 99.8%. Biopsies were performed after discontinuation of therapy in patients receiving antiplatelet drugs and anticoagulants in 96.7% and 97.4% of the facilities, respectively. Atropine was administered for premedication in 67.5% of the facilities, a decrease from previous surveys. Intravenous sedation was given in 36.1% of the facilities. In 21.9% of these, the procedure was conducted in the outpatient clinic for ≥ 70% of patients. A bronchoscope was orally inserted in ≥ 70% of patients in 95.7% of the facilities. Intravenous access was maintained during the examination in 92.5% of the facilities, oxygen saturation was monitored during examinations in 99.0%, oxygen was administered in 97.6% and resuscitation equipment was available in 96%. In 98.6% of the facilities, bronchoscopes were disinfected using an automatic washing machine, with glutaraldehyde used in 42.2%. CONCLUSIONS: Japan-specific characteristics of bronchoscopic practice were identified. Whether procedures used in Japan meet international guidelines with respect to safety should be monitored continuously. In addition, a Japanese evidence-based consensus is needed.

Well differentiated fetal adenocarcinoma of the lung in a 38-year-old woman: dynamic computed tomography findings.

We report a case of well-differentiated fetal adenocarcinoma (WDFA) of the lung, with emphasis on dynamic CT (computed tomography) findings. The patient was a 38-year-old woman who was found to have a mass in the left upper lung field in chest radiograph screening. Chest radiograph showed a 5.5 cm well-defined mass in the left upper lung field. CT revealed a well-circumscribed mass measuring 5.5 × 5.5 × 5.0 cm with a lobulated margin in the left upper lobe. Intratumoral enhancing vasculature was noted in the early phase of dynamic CT. In the delayed phase, persistent and plateau enhancement was seen. The tumor also had consistently unenhanced areas, suggesting the presence of necrosis. Left upper lobectomy with mediastinal lymph node dissection was performed. The pathology specimen contained tubular glands consisting of non-ciliated columnar cells with areas of solid nests of epithelial cells with weakly eosinophilic cytoplasm (morule) mimicking fetal lung tissue. The tumor was moderately vascularized with areas of comedo necrosis; the stroma was relatively scanty. Final pathological diagnosis was WDFA with left hilar lymph node metastasis (stage T2bN1M0). This is the first report of dynamic CT findings of WDFA, a rare lung tumor. Although these findings are non-specific, they well reflected the pathological characteristics of this tumor.

A phase II study of docetaxel plus nedaplatin in patients with metastatic non-small-cell lung cancer.

PURPOSE: Nedaplatin is a cisplatin derivative, which has similar activity to cisplatin in non-small-cell lung cancer (NSCLC) when combined with vindesine, and causes less nausea/vomiting and nephrotoxicity compared with cisplatin. The aim of this study was to evaluate the efficacy and safety of combination chemotherapy with docetaxel plus nedaplatin in patients with metastatic NSCLC. METHODS: Patients with metastatic stage IIIB excluding locally advanced diseases or stage IV NSCLC were enrolled between March 2004 and March 2006. They were treated with docetaxel (60 mg/m(2)) and nedaplatin (80 mg/m(2)) on day 1 every 3-4 weeks until progression or intolerable toxicity for up to 4 cycles. RESULTS: Forty-four patients (mean age, 65 years; range, 40-79 years) received a total of 140 treatment cycles. Responses could be assessed in all patients (complete response, 0; partial response, 22; stable disease, 11; and progressive disease, 11). Response rate was 50.0 % (95 % confidence interval [CI], 35.2-64.8 %) with a disease control rate of 75.0 % (95 % CI, 62.2-87.8 %). A high response rate was achieved in patients with squamous cell carcinoma (66.7 %) compared with that in patients with adenocarcinoma (41.4 %). Median survival time from the start of the combination chemotherapy was 13.0 months, and the progression-free survival time was 7.4 months. Grade 3 or 4 hematologic toxicities included leukopenia (28.6 %) and neutropenia (61.4 %). Nonhematologic toxicities were mild. CONCLUSION: The combination of docetaxel plus nedaplatin was well tolerated and demonstrated potent activity in patients with metastatic NSCLC, particularly squamous cell carcinoma of the lung.

Deaths and complications associated with respiratory endoscopy: a survey by the Japan Society for Respiratory Endoscopy in 2010.

BACKGROUND AND OBJECTIVE: In order to survey the current status of the use and complications associated with respiratory endoscopy, the Japan Society for Respiratory Endoscopy conducted a nationwide postal questionnaire survey. METHODS: The survey was mailed to all 538 facilities certified by the society. The subjects were patients who underwent respiratory endoscopy in 2010. The numbers of procedures, and associated complications and deaths were investigated according to lesion and procedure using a specific inventory. RESULTS: The inventory was completed by 483 facilities (89.8%). The total number of diagnostic flexible bronchoscopy procedures performed was 103 978, and four patients died (0.004%). The complication rate according to lesion ranged from 0.51% to 2.06%, with the highest rate being observed in patients with diffuse lesions. The complication rate according to procedure ranged from 0.17% to 1.93%, with the highest rate being observed in patients who underwent forceps biopsy. The complication rate after forceps biopsy of solitary peripheral pulmonary lesions was 1.79% (haemorrhage: 0.73%, pneumothorax: 0.63%), and that after endobronchial ultrasound-guided transbronchial needle aspiration of hilar and/or mediastinal lymph node lesions was 0.46%. Therapeutic bronchoscopy was performed in 3020 patients; one patient (0.03%) died due to haemorrhage induced by insertion of an expandable metallic stent. The complication rate according to procedure was highest for foreign body removal (2.2%). Medical pleuroscopy was performed in 1563 patients. The highest complication rate was for biopsy without electrocautery (1.86%). A total of 228 facilities (47.2%) experienced breakage of bronchoscopes and/or devices. CONCLUSIONS: Respiratory endoscopy was performed safely, but education regarding complications caused by new techniques is necessary.

Podoplanin expression in cancerous stroma induces lymphangiogenesis and predicts lymphatic spread and patient survival.

CONTEXT: Podoplanin is a mucin-type glycoprotein and a lymphatic endothelial marker. Immunohistochemical staining for podoplanin is currently used as a routine pathologic diagnosis tool in Japan to identify lymphatic invasion of cancer cells. Recent reports suggest that podoplanin and other proangiogenic molecules are expressed in stromal fibroblasts and myofibroblasts. OBJECTIVE: To analyze the distribution of podoplanin expression in tumor stroma and its clinical and biologic significance. DESIGN: We performed immunohistochemistry for podoplanin on tissue microarrays from 1350 cases of 14 common cancer types. RESULTS: Two hundred eighty-seven of 662 cases (43%) showed podoplanin expression in the stromal cells within cancer nests. Stromal podoplanin expression in 14 common cancer types was significantly associated with tumor stage (P < .001), lymph node metastases (P < .001), lymphatic invasion (P  =  .02), and venous invasion (P < .001). The stromal cells positive for podoplanin were also positive for α-smooth muscle actin but negative for desmin, confirming a myofibroblasts phenotype. In contrast, myofibroblasts in inflammatory fibrotic lung diseases were podoplanin negative. Lymphatic vessel density was greater in the stromas with podoplanin expression than in the stroma lacking podoplanin-expressing stromal cells (P  =  .01). Survival data were available for non-small cell lung cancer. Stromal podoplanin expression was associated with poorer prognosis in adenocarcinoma (P < .001) and remains statistically significant after adjustment for sex, age, and stage (P  =  .01). CONCLUSION: Our data indicate that podoplanin expression in stromal myofibroblasts may function as a proangiogenic biomarker and may serve as a predictive marker of lymphatic/vascular spread of cancer cells and a prognostic marker of patient survival.

Inhibition of transforming growth factor-beta-mediated immunosuppression in tumor-draining lymph nodes augments antitumor responses by various immunologic cell types.

Tumor-draining lymph nodes (DLN) are the most important priming sites for generation of antitumor immune responses. They are also the location where an immunosuppressive cytokine, transforming growth factor-beta (TGF-beta), plays a critical role in suppressing these antitumor immune responses. We focused on TGF-beta-mediated immunosuppression in DLNs and examined whether local inhibition of TGF-beta augmented antitumor immune responses systemically in tumor-bearing mice models. For inhibition of TGF-beta-mediated immunosuppression in DLNs, C57BL/6 mice subcutaneously bearing E.G7 tumors were administered plasmid DNA encoding the extracellular domain of TGF-beta type II receptor fused to the human IgG heavy chain (TGFR DNA) i.m. near the established tumor. In DLNs, inhibition of TGF-beta suppressed the proliferation of regulatory T cells and increased the number of tumor antigen-specific CD4(+) or CD8(+) cells producing IFN-gamma. Enhancement of antitumor immune responses in DLNs were associated with augmented tumor antigen-specific cytotoxic and natural killer activity in spleen as well as elevated levels of tumor-specific antibody in sera. The growth of the established metastatic as well as primary tumors was effectively suppressed via augmented antitumor immune responses. Inhibition of TGF-beta-mediated immunosuppression in DLNs is significantly associated with augmented antitumor responses by various immunocompetent cell types. This animal model provides a novel rationale for molecular cancer therapeutics targeting TGF-beta.

Bronchoscopy in Japan: a survey by the Japan Society for Respiratory Endoscopy in 2006.

BACKGROUND AND OBJECTIVE: In order to obtain information on the clinical application of bronchoscopy in Japan, the Japan Society for Respiratory Endoscopy (JSRE) conducted a postal survey. METHODS: A questionnaire was sent to 526 authorized institutes of the JSRE. The subject was bronchoscopy procedures performed during 2006. RESULTS: The response rate was 71.3%. The total number of bronchoscopies performed was 74,770. Of these, 74,412 were flexible bronchoscopies and 358 were rigid bronchoscopies. At least one JSRE-authorized specialist had worked with 97% of respondents. Eighty-five per cent of respondents performed bronchoscopy under topical anaesthesia for almost all patients. Seventy-five per cent of respondents routinely used the oral route. The reported numbers of diagnostic bronchoscopies was 12,509 for simple bronchoscopy, 25,971 for forceps biopsy, 26,289 for brush biopsy, 25,659 for bronchial washing, 1387 for transbronchial needle aspiration and 6716 for BAL. Three deaths were caused by forceps biopsy (0.012%). The morbidity rates for these diagnostic procedures ranged from 0.14% to 2.5%. The reported numbers of therapeutic bronchoscopies was 476 for tracheobronchial stent, 164 for neodymium (Nd): yttrium-aluminium garnet (YAG) laser photoresection (LPR), 40 for photodynamic therapy, 81 for balloon dilatation, 145 for endobronchial electrocautery, 120 for argon plasma coagulation, 109 for microwave coagulation (MWC), 116 for ethanol injection, 110 for foreign body removal and 89 for bronchial occlusion. Deaths occurred only as a consequence of Nd : YAG LPR (0.61%). The morbidity rates for these therapeutic procedures ranged from 0% to 5%. CONCLUSIONS: The preparation for, and practice of, bronchoscopy varied greatly between respondents. Diagnostic bronchoscopy was well tolerated and safe. Therapeutic procedures did not appear to be practised widely or frequently.

Pulmonary infarction associated with bronchogenic carcinoma.

Computed tomography findings of pathologically proven pulmonary infarction associated with bronchogenic carcinoma are reported for two patients. In one case, the infarction was demonstrated as a well-defined pleura-based large nodule in the peripheral portion of the same lobe of the tumor. The nodule had a smooth, convex border and a linear strand from the apex of the lesion toward the hilum. The obstruction of the subsegmental pulmonary artery due to tumor invasion was considered the cause of pulmonary infarction. In the second case, the infarction was demonstrated as a rapidly appeared, pleura-based consolidation in the same lobe of the tumor with a blurred border. Obstruction of the pulmonary vein by a tumor might have played an important role in the development of the pulmonary infarction in association with a large pulmonary artery obstruction. We conclude that pulmonary infarction should be considered as a differential diagnosis when peripheral pulmonary nodules or masses are located in the same lobe as the primary cancer.

HER1-4 expression status correlates with the efficacy of gefitinib treatment and tumor cell proliferative activity in non-small cell lung cancer.

The expression of human epidermal growth factor receptor (HER) family proteins was examined in specimens of 52 non-small cell lung cancers to evaluate their significance in tumor cell proliferation and their response to gefitinib. Epidermal growth factor receptor (EGFR; HER1) protein was expressed most frequently (43/52 cases). HER2 and HER3 were detected in 13 and 18 cases, respectively. HER4 was detected in only one case of squamous cell carcinoma. HER3 was expressed preferentially in adenocarcinomas of the papillary type. In most HER3-positive cases with or without other HER family proteins, the Ki-67 labelling index (18.2%) was significantly lower than in HER3-negative cases (30.6%) (P<0.05). Adenocarcinomas co-expressing EGFR, HER2 and HER3 frequently showed both a good response to gefitinib (6/7 cases) and a mutation of EGFR (4/6 cases). However, cases with a favourable response to gefitinib did not always express EGFR. Gefitinib appears to suppress growth signal pathways other than EGFR-tyrosine kinase activation in non-small cell lung cancers.

Assessment of diaphragmatic motion after lung resection using magnetic resonance imaging.

PURPOSE: The aim of this study was to assess quantitatively the impairment of diaphragmatic motion after lung resection, with special reference to the location of the resected lobe, duration of the postoperative period, and patient posture. We used magnetic resonance imaging to make the assessments. MATERIALS AND METHODS: In 44 patients (29 men, 15 women; mean age 62.2 years) with lung cancer, diaphragmatic motion was measured during maximum deep, slow breathing using a spoiled gradient-recalled echo sequence before and after lung resection. The study group consisted of 34 patients who were examined using a 1.5-T unit in the supine position and 10 patients using a vertically open 0.5-T unit in both the sitting and supine positions. The influence of surgery site and patient posture on diaphragmatic motion after lung resection was investigated. RESULTS: In all cases after lung resection, diaphragmatic motion on the operated side was significantly decreased (P < 0.001), and that on the nonoperated side was significantly increased (P = 0.045). After left upper lobectomy and right bilobectomy, the diaphragmatic motion on the operated side was significantly decreased (P < 0.001), and that of the other side was significantly increased (P < 0.001). The diaphragmatic motion was not significantly changed after right middle lobectomy. The diaphragmatic motion on the operated side was impaired significantly more (P = 0.035) in the supine position than in the sitting position. CONCLUSION: After lobe resection, diaphragmatic motion was impaired more significantly in the supine than in the sitting position; and it differed according to the location of the resected lobe. The improvement in diaphragmatic function after lobectomy was observed over a period of 3-24 months.

Preparation of fully activated dendritic cells capable of priming tumor-specific cytotoxic T lymphocytes in patients with metastatic cancer using penicillin-killed streptococcus pyogenes (OK432) and anti-CD40 antibody.

In order to achieve sufficient therapeutic potency, it has been proposed that vaccine therapy with dendritic cells needs to be combined with manipulation of immunological checkpoints, such as inhibition of regulatory T cells and blockade of negative signals, and enhancement of T cell trafficking to tumor sites. In the combinatorial cancer immunotherapy, use of matured/activated dendritic cells (DCs) with more potent antigen presenting capacity seems to be essential for eliciting anti-tumor immune responses. We herein established an ex vivo induction strategy for activated DCs capable of eliciting efficient tumor antigen-specific cytotoxic T lymphocytes (CTLs) from patients with metastatic cancer as well as healthy donors. Immature DCs were matured by 48-h culture in the presence of anti-CD40 antibody and penicillin-killed streptococcus pyogenes (OK432). Supplementation with both anti-CD40 and OK432 resulted in induction of activated DCs with higher surface expression of CD80, CD83, CD86 and major histocompatibility complex class II antigens, compared with other mature DCs that were induced by the combination of anti-CD40 with tumor necrosis factor-alpha or lipopolysaccharide. In analysis of the produced cytokine profiles, the activated DCs produced the highest T-helper 1-type cytokines for at least 72 h. Furthermore, the activated DCs, pulsed with tumor-associated antigen peptide, elicited in vitro tumor-specific CTLs, but DCs activated with other combinations did not in cancer patients. Therefore, we suggest that the activated DCs studied here might be used as a basic element for the combinatorial cancer immunotherapy.