Impact of HER2 expression on EGFR-TKI treatment outcomes in lung tumors harboring EGFR mutations: A HER2-CS study subset analysis.

OBJECTIVES: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatment for EGFR-mutated non-small-cell lung carcinoma (NSCLC); however, a biomarker to predict their efficacy has not been established. Although human epidermal growth factor receptor-2 (HER2) aberrations constitute a potential mechanism for acquired resistance to EGFR-TKIs, the impact of HER2 on EGFR-TKI treatment outcomes has not been systematically evaluated. In this post-hoc subgroup study, we examined the impact of HER2 on the effect of EGFR-TKIs in patients with NSCLC harboring EGFR mutations. MATERIALS AND METHODS: Of 1126 patients with NSCLC enrolled into a prospective cohort study (HER2-CS study), we analyzed data of 356 (32 %) patients with EGFR-mutant tumors. HER2 protein expression levels were determined by immunohistochemistry (IHC) with the gastric cancer criteria. Patients were divided either to an HER2-P group (HER2-IHC2+/3+) or an HER2-N group (HER2-IHC0/1+). We primarily assessed differences in the time-to-treatment failure (TTF) of EGFR-TKI between the groups. RESULTS: The HER2 scoring was as follows: IHC0 (n = 76, 21 %), IHC1+ (n = 199, 56 %), IHC2+ (n = 72, 20 %), and IHC3+ (n = 9, 3 %). The patients' demographics were similar in the HER2-P and HER2-N groups. The HER2-P group showed a significantly shorter EGFR-TKI TTF than the HER2-N group (hazard ratio [HR]: 1.657, 95 % confidence interval [CI]: 1.076-2.552; median: 13.3 vs. 19.1 months). The magnitude of the negative impact of TTF was especially dependent on performance status (PS). HER2 expression significantly deteriorated the TTF in the subgroup with PS 2 (HR: 5.497, 95 % CI: 1.510-20.02), but not in that with better PS (HR: 1.437, 95 % CI: 0.899-2.298) (pinteraction = 0.015). CONCLUSION: In the current cohort, HER2 protein expression in EGFR-mutant NSCLC may have a negative impact on the effect of EGFR-TKIs, the effect of which was PS dependent.

Pulmonary Hyalinizing Granuloma Mimicking Primary Lung Cancer.

We herein report a case of pulmonary hyalinizing granuloma (PHG), which is a rare pulmonary mass. A 69-year-old man with no symptoms presented to our hospital because of the appearance of an abnormal shadow on chest X-ray. Computed tomography revealed a right middle-lobe mass with spicula and infiltration into the upper lobe. Since a bronchofiberscopic examination showed no malignant cells in the specimen, the patient underwent thoracoscopic surgery, which revealed PHG. Spiculation and interlobar infiltration, which comprise the characteristic features of primary lung cancer, are uncommon presentations of this rare entity.

Septic pulmonary embolism induced by dental infection.

Dental infection can be an important source for septic pulmonary embolism (SPE), but only a few cases of SPE accompanying dental infection have been reported. The aim of this study was to characterize the clinical features of SPE induced by dental infection. Patients who fulfilled the diagnostic criteria described in the text were recruited in a retrospective fashion. All 9 patients were men, with a median age of 59 years (range:47 to 74 years). Eight patients had chest pain (88.9%), 5 had a preceding toothache (55.6%) and 3 had preceding gingival swelling (33.3%). Blood cultures obtained from 7 patients were negative. Periodontitis was found in all of the cases, periapical periodontitis in 5 cases, and gingival abscess in 3 cases. The median duration of hospitalization was 15 days, and symptoms were mild in some cases. In addition to antimicrobial therapy, tooth extraction was performed in 3 cases, tooth scaling in 6. SPE induced by dental infection has prominent clinical characteristics such as male preponderance, chest pain, preceding toothache, and mild clinical course.

Clinical outcome in patients with leptomeningeal metastasis from non-small cell lung cancer: Okayama Lung Cancer Study Group.

OBJECTIVE: We examined the prognosis of patients with leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC) and that stratified by epidermal growth factor receptor (EGFR) mutation status in LM patients receiving EGFR-tyrosine kinase inhibitors (TKIs). METHODS: We retrospectively analyzed a series of 91 consecutive NSCLC patients with LM between 2001 and 2010. RESULTS: Most of the LM patients had adenocarcinoma histology and a poor performance status (PS). The median survival time (MST) for all patients was 3.6 months. Adenocarcinoma and TKI treatment were associated with a better prognosis. Among the patients, 51 received EGFR-TKIs. Of these, the EGFR mutation status was assessed in 30 patients; 7 (23%) showed no mutation (group 1), 10 (33%) had a mutation in exon 21 (group 2), and 13 (43%) had deletions in exon 19 (group 3). Interestingly, PS was significantly improved in groups 2 and 3 but not in group 1. The MST in these subgroups was 1.4, 7.1, and 11.0 months in groups 1, 2, and 3, respectively (p<0.001). The median time to progression or symptom deterioration was 0.9, 2.0, and 7.8 months for groups 1, 2, and 3, respectively (p<0.001). A multivariate analysis showed that EGFR-mutant tumors were associated with a better prognosis in patients receiving EGFR-TKIs. CONCLUSIONS: The prognosis for patients with LM from NSCLC was still poor. Survival after the initiation of EGFR-TKI treatment differed according to the type of EGFR mutation, suggesting the potential benefit of TKIs for patients with EGFR mutations, even though they suffered from LM.

A case of mediastinal lymph node carcinoma of unknown primary site treated with docetaxel and cisplatin with concurrent thoracic radiation therapy.

Mediastinal lymph node carcinoma of unknown primary site is rare and may have a better prognosis if extensive treatment is performed. Case, A 69-year-old-male presented with a persistent cough. Chest computed tomography (CT) demonstrated a large tumor 9.5 × 8.2 cm, in the mediastinum, compressing the right main bronchus, the right pulmonary artery, and the superior vena cava. Because fiberoptic bronchoscopy was insufficient for diagnosis, mediastinoscopic tumor biopsy under general anesthesia was undertaken. Histological examination revealed adenocarcinoma. Extensive examinations revealed no other neoplastic lesion except in the mediastinum. Mediastinal lymph node carcinoma of unknown primary site was diagnosed. The patient was treated with docetaxel and cisplatin with concurrent thoracic radiation therapy. A month after the start of chemoradiotherapy, the mediastinal tumor regressed markedly. The patient remained free of symptoms without regrowth of the primary site. Exploration of the body showed no further abnormalities 20 months after disease onset.

Benefits and adverse events among elderly patients receiving concurrent chemoradiotherapy for locally advanced non-small cell lung cancer: analysis of the Okayama Lung Cancer Study Group trial 0007.

INTRODUCTION: Thoracic radiotherapy (RT) with concurrent chemotherapy may be offered to selected elderly patients with locally advanced non-small cell lung cancer. The Okayama Lung Cancer Study Group (OLCSG) 0007 trial with patients up to 75 years showed that with concurrent RT, docetaxel and cisplatin (DP) chemotherapy was an alternative to mitomycin C, vindesine, and cisplatin (MVP) chemotherapy. METHODS: Of the 99 patients in the DP arm, 73 were younger than 70 years and 26 were 70 years or older. Of the 101 patients in the MVP arm, 75 were younger than 70 years and 26 were 70 years or older. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method and were compared using an early period weighted log-rank test. Toxicities and treatment intensities were compared by χ(2) and t tests, respectively. RESULTS: OS and PFS tended to be longer in the DP arm versus MVP arm: median OS (months), 27.5 versus 22.9 (p = 0.109) and 25.6 versus 23.4 (p = 0.064) in the ≥70-year and <70-year groups, respectively; median PFS (months), 19.0 versus 11.5 (p = 0.175) and 12.0 versus 9.3 (p = 0.132) in the ≥70-year and less than 70-year groups, respectively. Severe toxicity (neutropenia, esophagitis, and pneumonitis) rates did not differ between age groups. Nevertheless, the absence of statistically significant differences in this retrospective analysis might be due to the small number of patients. Radiation intensity was similar between the groups, but chemotherapy intensity was lower in the ≥70-year group. CONCLUSION: Chemotherapy with concurrent RT may be effective and tolerable in elderly patients with locally advanced non-small cell lung cancer.

Interstitial lung disease during trimethoprim/sulfamethoxazole administration.

We studied clinical and radiographic features of interstitial lung disease (ILD) during trimethoprim/sulfamethoxazole (TMP/SMX) administration. Ten patients who had received prednisolone treatment for underlying diffuse pulmonary disease showed various ILDs after introduction of TMP/SMX. The radiographic features of the ILDs were not consistent with infectious disease or exacerbation of the underlying disease, and these diagnoses were excluded radiographically and on clinical grounds during the differential diagnosis of the ILDs. These ILDs emerged relatively early after introduction of TMP/SMX, which is consistent with the former case report of drug-induced ILD (DI-ILD) caused by TMP/SMX. Therefore DI-ILDs caused by TMP/SMX were suspected in these cases. In most of these cases, the ILDs were clinically mild and disappeared immediately although administration of TMP/SMX was continued.

Transthoracic Collis-Nissen repair for massive type IV paraesophageal hernia.

An 80-year-old woman presented with type IV massive hiatal hernia with intrathoracic upside-down stomach and transverse colon. She was dyspneic and vomited upon consuming food or water. Consequently, she developed aspiration pneumonia. Both esophagoscopy and upper gastrointestinal series demonstrated significant cephalad displacement of the gastroesophageal junction. A Collis-Nissen hernial repair by muscle-sparing mini-thoracotomy was performed successfully. To date, 3 years after surgery, the patient is enjoying normal oral intake, has an excellent activities of daily living level, and there is no hernia recurrence. Cases of massive paraesophageal hernia are frequently associated with esophageal shortening that causes tension on the repairs and late failure. Advantages of the transthoracic approach in such cases include feasibility of direct esophageal mobilization, accurate assessment of esophageal tension, and facilitation of Collis gastroplasty. The true indication for transthoracic Collis-Nissen repair among cases of paraesophageal hiatal hernia with a short esophagus should be acknowledged more in the era of laparoscopy.

Primary pulmonary hypertension treated with short-term epoprostenol infusion.

We describe the use of short-term epoprostenol in a 61-year-old man with primary pulmonary hypertension. The patient was on a ventilator because of respiratory distress. Continuous infusion of epoprostenol was started and it initially reduced the pulmonary artery pressure by 32%. Epoprostenol was tapered, and even after discontinuation, the pulmonary artery pressure was controlled. The ventilator was removed, and the patient remained well on home oxygen therapy 3 months after discharge.

[Bowel perforation due to metastatic lung cancer: a case report].

We report a case of small bowel perforation secondary to metastasis from a lung squamous cell carcinoma that occurred in a 72-year-old man. He was admitted to the hospital because of remittant hemoptysis after undergoing a right upper lobectomy. Fiberoptic bronchoscopy revealed bleeding from the right upper lobe bronchial stump that was due to recurrence of the tumor. He developed abdominal pain, nausea and vomiting four months after resection of the primary tumor. An abdominal radiograph demonstrated free air in the abdominal cavity. He was diagnosed as having intestinal perforation and was operated on. The operative findings indicated adherence and perforation of the jejunum and ileum. The pathological diagnosis of the removed tumor was poorly differentiated squamous cell carcinoma. The patient died 32 days after the second operation. Although abdominal metastasis from lung cancer is not an unusual postmortem finding, it is rare in clinical situations. If a patient with lung cancer complains of abdominal pain, it is important to consider the possibility of abdominal metastasis.

[A case of benign asbestos pleural effusion suspected on thoracoscopic examination under local anesthesia].

We report the case of a 92-year-old man with a 13-year history of occupational asbestos exposure who presented with a complaint of dyspnea. In September 2001, bilateral pleural effusions were revealed on chest radiography, and continued to progress despite treatment for heart failure. Chest CT revealed calcification of the pleura but no abnormal findings in the lung fields. Both pleural effusions were exudative and lymphocytes were the predominant cells contained in them. Antituberculous chemotherapy had no effect on the exudates. In March 2002, thoracoscopy was performed under local anesthesia (medical thoracoscopy). Plaque was recognized on the parietal pleura; however, the serosal surfaces of the parietal and visceral pleura were smooth, and no evidence of malignancy, especially malignant mesothelioma, was noted. The patient's condition was diagnosed as benign asbestos pleural effusions. Prednisolone was administered, and these effusions gradually decreased. Cases of benign asbestos pleural effusion occurring simultaneously with massive bilateral effusions are rare. Thoracoscopy aided in the differential diagnosis of this case.

Pulmonary sequestration associated by Mycobacterium intracellulare infection.

A case of a 29-year-old woman with intralobar pulmonary sequestration infected with Mycobacterium intracellulare is presented. A chest CT scan revealed a density in the posterior segment of the left lower lobe, and an acid-fast bacillus sputum culture yielded Mycobacterium intracellulare. After 3 months of treatment with clarithromycin, streptomycin, rifampicin and ethambutol, the patient underwent partial resection of the left lower lobe. At the 6-month follow-up the patient's clinical status is excellent. A review of the literature revealed only three case reports of pulmonary sequestration associated with Mycobacterium avium-intracellulare complex infection.

Septic pulmonary embolism associated with periodontal disease: reports of two cases and review of the literature.

We report two cases of septic pulmonary embolism associated with periodontitis. Chest CT revealed multiple nodular shadows with features characteristic of septic pulmonary embolism in both patients. Both patients had toothache, fever, and chest pain, and showed findings of periodontitis at initial presentation. Antimicrobial agents combined with dental surgery were successful in treatment. While septic pulmonary embolism from the lesions of periodontitis appears to be rare, periodontitis remains important in the differential diagnosis of septic pulmonary embolism.

Intracellular IL-5 and T-lymphocyte subsets in atopic and nonatopic bronchial asthma.

BACKGROUND: Allergen-stimulated IL-5 production by CD4+ T cells is the key issue in atopic asthma. On the other hand, virus-specific CD8+ T cells produce IL-5 and might play an important role in the pathogenesis of nonatopic asthma. OBJECTIVES: We sought to compare the IL-5-producing T-lymphocyte subsets in the peripheral blood of atopic and nonatopic asthmatic subjects, especially the contribution of IL-5-producing CD8(+) T cells in nonatopic asthma. METHODS: Heparinized blood samples were obtained from subjects with atopic asthma (n = 10), subjects with nonatopic asthma (n = 10), and healthy subjects (n = 10) and stimulated with ionomycin and phorbol myristate acetate in the presence of brefeldin A. Two-color flow cytometric analysis with mAbs to cell-surface antigens and intracellular IL-5 was used to detect the IL-5-producing T-cell subsets. RESULTS: A higher percentage of IL-5-producing CD3(+) T cells was detected in subjects with atopic and nonatopic asthma than that seen in the healthy subjects. The percentage of IL-5-producing CD4(+) T cells was significantly higher in subjects with atopic asthma than in the healthy subjects. The percentage of IL-5-producing CD8(+) T cells was significantly higher in subjects with nonatopic asthma than in the healthy subjects. The percentage of IL-5-producing CD8(+) T cells was higher in subjects with nonatopic asthma than in those with atopic asthma, but the difference was not statistically significant. CONCLUSIONS: CD4(+) T cells are the major source of IL-5 among CD3(+) lymphocytes in subjects with atopic asthma. On the other hand, increased IL-5 production by CD8(+) T cells, as well as by CD4(+) T cells, is a characteristic feature of nonatopic asthma.