[A Case of Intestinal Lymphoma with Two Perforation in a Short Period Time].

An 86 years old man was diagnosed with jejunum tumor by detail examination of anemia. Eight days after endoscopy he developed abdominal pain, an emergency surgery was performed by a diagnosis of gastrointestinal perforation. They detected perforation in jejunum and performed jejunum resection, small intestinal lymphoma was diagnosed by histopathological examination. We were talked about chemotherapy against lymphoma, he was transferred at our hospital. The first chemotherapy was provided, abdominal pain appeared at 2 days after chemotherapy. Computed tomography revealed air bubbles out of intestinal tract, we performed emergency operation. A perforation of jejunum in the part where is different from the last time was existed, we performed jejunum resection. Chemotherapy was performed postoperatively, resulted in successful progress. Lymphoma of gastrointestinal tract often causes intestinal perforations, but reports that perforations heterochrony in separate parts multiple tumors of intestine is rare. We report a case of intestinal lymphoma with 2 perforations in a short period time.

Nationwide retrospective observational study of idiopathic dendriform pulmonary ossification: clinical features with a progressive phenotype.

BACKGROUND: Diffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO. METHODS: We conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO. RESULTS: Twenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22-56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed. CONCLUSIONS: IDPO develops at a young age with gradually progressive phenotype. Further research and long-term (>20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO.

[Thymic Cancer Associated with Spontaneous Regression of Multilocular Thymic Cysts].

Thymic cancer associated with spontaneous regression of thymic cysts is a rare disease. A 47-yearold man was referred to our hospital for right chest pain and chest abnormal shadow. Chest computed tomography( CT) revealed a solid lesion 1.3 cm in diameter and a cystic lesion 1.0 cm in diameter at the right anterior mediastinum. A second CT study after six months showed a solid lesion increased to 1.7 cm in diameter and a cystic lesion reduced to 0.7 cm in diameter. A second magnetic resonance imaging (MRI) showed a cystic lesion reduced and high signal intensity region in the thymus enlarged on T2-weighted imaging. Under the diagnosis of thymoma associated with multilocular thymic cysts, total thymectomy was performed for these mediastinal lesions by video-assisted thoracic surgery. Histopathological finding was thymic squamous cell carcinoma (Masaoka stage II) associated with multilocular thymic cysts. Additional postoperative radiotherapy was performed, and there has been no recurrence after one postoperative year.

Clinical Outcome in Soft Tissue Sarcoma Patients with Lung Metastasis Who Received Metastasectomy and/or Radiofrequency Ablation: Tokai Musculoskeletal Oncology Consortium Study.

PURPOSE: Here, we investigated the oncological outcomes of lung metastasectomy and/or radiofrequency ablation (RFA) of 92 patients with soft tissue sarcoma (STS) at nine institutions. METHODS: The study cohort included 65 men and 27 women with a mean age of 59 years at the time of metastasis. The mean follow-up duration was 51 months. All patients underwent metastasectomy and/or RFA for lung metastasis. RESULTS: The mean maximum size of the initial lung metastasis was 14.6 mm. At the initial evaluation, 41 patients had a single metastasis, whereas 51 patients had multiple metastases. The mean number of metastasectomies and/or RFA was 2 per patient. A total of 70 patients underwent lung metastasectomy, whereas the other 13 underwent lung RFA. The remaining nine patients underwent both RFA and metastasectomy. The 5-year post-metastatic survival rate was 52%. The patients who underwent complete treatment for the initial metastasis had better post-metastatic survival rates than those who underwent incomplete treatment. A univariate analysis of all possible prognostic factors for complete treatment confirmed the predictive value of disease-free interval, metastasis at initial presentation, distribution, tumor size, and number of lung metastases. Of the 92 patients, 74 underwent complete treatment for initial metastasis; in these patients, univariate and multivariate analyses showed that a smaller tumor size and single-lung metastasis were prognostic factors for superior post-metastatic survival. The patients with a smaller (<11.5 mm) single metastasis had better post-metastasis survival. The 5-year post-metastatic survival rates were 89.9% for patients with a smaller (<11.5 mm) single metastasis versus 22.7% for patients with larger (>11.5 mm) and multiple metastases. DISCUSSION: We propose that complete treatment for lung metastasis in patients with STS may improve post-metastatic survival rates. Furthermore, tumor number and size are important variables for clinical decision-making.

ABCG2 C421A polymorphisms affect exposure of the epidermal growth factor receptor inhibitor gefitinib.

ATP-binding castle protein G2 (ABCG2) is thought to inhibit the activities of certain gefitinib transporters, thereby affecting drug pharmacokinetics. The C421A polymorphism affects the function and expression of ABCG2 on the cell membrane. Previous studies have shown that proton-pump inhibitors (PPIs) inhibit gefitinib absorption, as well as the function of ABCG2. We evaluated the plasma concentrations of gefitinib in patients with and without the ABCG2 C421A polymorphism, who were or were not taking PPIs. In total, 61 patients with advanced epidermal-growth-factor-positive non-small-cell lung cancer were enrolled in this study. They were treated with gefitinib at a dose of 250 mg per day. Plasma gefitinib concentration and ABCG2 C421A status were determined after 2 weeks. The patients were divided into CC- and CA/AA genotype groups. We compared the trough and peak gefitinib levels and the area under the curve (AUC) values for 24-h gefitinib concentrations. We also compared these parameters among four groups distinguished according to the presence or absence of the polymorphism and PPI use. The mean trough gefitinib level and AUC value for 24-h gefitinib concentration were significantly lower in the CA/AA group compared to the CC group (mean trough level: 333.2 vs. 454.5 ng/mL, respectively, P = 0.021; AUC: 9949.9 vs. 13,085.4 ng・h/mL, respectively, P = 0.034). Among patients taking PPIs, the mean trough gefitinib level was significantly lower in the CA/AA group than the CC group (220.1 vs. 340.5 ng/mL, respectively, P = 0.033). The CA/AA-type of ABCG2 C421A polymorphism may be associated with lower gefitinib plasma concentrations.

An autopsy case of anaplastic lymphoma kinase-positive lung cancer exacerbated in a short period of time: a case report.

BACKGROUND: Anaplastic lymphoma kinase-positive lung cancer is a form of lung cancer that accounts for approximately 5% of non-small cell lung cancers. Recently, anaplastic lymphoma kinase inhibitors have been used for treatment of anaplastic lymphoma kinase-positive lung cancer, and their high clinical effect has also been demonstrated in cases of advanced stage lung cancer. Alectinib is an anaplastic lymphoma kinase inhibitor that it is recognized as a standard drug for primary therapy because of its superiority to crizotinib. CASE PRESENTATION: A 37-year-old Japanese man was admitted to our hospital due to multiple brain metastases. An autopsy report revealed that the cause of death was anaplastic lymphoma kinase-positive lung cancer, exacerbated in a short period despite treatment with alectinib. Necropsy revealed anaplastic lymphoma kinase-positive adenosquamous carcinoma of the lung, suggesting that it was involved in the prognosis of this patient. Based on the autopsy results, we reviewed the pathological tissue from transbronchial lung biopsy at the time of clinical diagnosis. The tissue specimen for clinical diagnosis in this case was a papillary adenocarcinoma. However, when this tissue was immunostained, thyroid transcription factor 1-negative and cytokeratin 5/6-positive parts were recognized. This result indicates that we could diagnose this patient as having had adenosquamous carcinoma of the lung. CONCLUSION: In cases of anaplastic lymphoma kinase-positive lung cancer poorly responsive to anaplastic lymphoma kinase inhibitors, re-examination of the tissue should be considered because there is a possibility of anaplastic lymphoma kinase-positive adenosquamous carcinoma.

Phase II trial of induction chemotherapy with carboplatin and paclitaxel plus bevacizumab in patients with stage IIIA to IV nonsquamous non-small cell lung cancer.

PURPOSE: Surgery remains the best curative treatment option for non-small cell lung cancer (NSCLC), but is of benefit only to patients with localized disease. A meta-analysis showed a significant beneficial effect of induction chemotherapy on survival, but there is still no clear evidence. This phase II study was conducted to establish whether induction chemotherapy with carboplatin (CBDCA) and paclitaxel (PTX) plus bevacizumab prior to surgery reduces the risk of progression. METHODS: The subjects of this study were 29 patients with treatment-naive nonsquamous NSCLC (clinical stages IIIA to IV). Patients received PTX (200 mg/m2), CBDCA (area under the curve, 5), and bevacizumab (15 mg/kg) followed by surgery. Chemotherapy was repeated every 3 weeks for up to six cycles. RESULTS: The overall response rate was 72.4%. Of the 29 patients, ten underwent surgery after the induction chemotherapy and complete resection was achieved in 7 (70%). The median progression-free-survival (PFS) time and the 3-year PFS rate were 0.92 years and 16.2%, respectively. The median overall survival (OS) time and the 3-year OS rate were 1.96 years and 44.9%, respectively. CONCLUSION: Combined modality therapy with surgery after induction chemotherapy with CBDCA and PTX plus bevacizumab is clinically feasible and tolerable for patients with unknown or negative molecular profiles.

The relationship between the expression of thymidylate synthase, dihydropyrimidine dehydrogenase, orotate phosphoribosyltransferase, excision repair cross-complementation group 1 and class III ß-tubulin, and the therapeutic effect of S-1 or carboplatin plus paclitaxel in non-small-cell lung cancer.

Previous studies have reported that the expressions of specific proteins may predict the efficacy of chemotherapy agents for non-small cell lung cancer (NSCLC) patients. The present study evaluated the expression of proteins hypothesized to be associated with the effect of chemotherapeutic agents in 38 NSCLC patients with pathological stage II and IIIA. The subjects received carboplatin plus paclitaxel (CP) or S-1 as adjuvant chemotherapy following complete resection. The protein expressions evaluated were those of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phsphoribosyltransferase (OPRT), which were suspected to be associated with the effect of S-1 agents, excision repair cross-complementation group 1 (ERCC1), which was suspected to be associated with the effect of platinum-based agents, and class III ß-tubulin (TUBB3), which was suspected to be associated with the effect of taxane-based agents. The positive rate of TS was 55.3% (n=21/38), DPD was 57.9% (n=22/38), OPRT was 42.1% (n=16/38), ERCC1 was 47.4% (n=18/38) and TUBB3 was 44.7% (n=17/38). Among the patients who received S-1 adjuvant chemotherapy, TS-negative cases demonstrated a significantly better disease-free survival than positive cases. Thus, TS protein expression may have been a factor that predicted the effect of S-1 agent as adjuvant chemotherapy.

S-1 vs. paclitaxel plus carboplatin as adjuvant chemotherapy for completely resected stage II/IIIA non-small-cell lung cancer.

The majority of patients with completely resected stage II or IIIA non-small-cell lung cancer (NSCLC) require adjuvant chemotherapy to improve survival following surgery. In the present trial, the 2-year disease-free survival (DFS), and the feasibility and safety of S-1 as an adjuvant chemotherapy for advanced lung cancer were evaluated. A total of 40 patients with completely resected stage II or IIIA NSCLC were enrolled and randomized to receive postoperative chemotherapy with either up to 4 cycles of paclitaxel plus carboplatin (arm A) or with up to 1 year of S-1 (arm B). The primary endpoint was 2-year DFS. The secondary endpoints were feasibility and toxicity. A total of 40 patients were enrolled, but 3 were excluded in accordance with the exclusion criteria. The remaining 37 patients were analyzed. The 2-year DFS rate was 54.2% in arm A and 84.2% in arm B. Overall, 15/18 (83.3%) patients completed 4 cycles of paclitaxel plus carboplatin and 13/19 (68.4%) completed 1-year of S-1adjuvant chemotherapy. Of the 18 (16.7%) patients in arm A, 3 experienced grade 3 or 4 adverse events, while none in arm B experienced such events. Therefore, S-1 chemotherapy for patients with completely resected stage II or IIIA NSCLC was a feasible and safe regimen, and it may therefore be considered as a potential adjuvant chemotherapy option for advanced NSCLC.

Validity of Ultrasound Lung Comets for Assessment of the Severity of Interstitial Pneumonia.

OBJECTIVES: Ultrasound (US) lung comets are often observed in patients with interstitial lung disease or congestive heart failure, but few studies have explored the clinical importance of US lung comets in patients with the former condition. We explored whether the US lung comet number could be used to assess the severity of interstitial pneumonia. METHODS: Forty stable patients with interstitial pneumonia were examined. Lung comets evident on transthoracic US imaging in 12 selected regions of the posterior chest wall were analyzed. We defined lung comets accompanied by thickened and irregular pleural lines as interstitial US lung comets; these predominated in patients with interstitial pneumonia. The total number of interstitial US lung comets was correlated with the data from chest high-resolution computed tomography, pulmonary function tests, serologic tests, and the 6-minute walk test. RESULTS: The 40 patients included 16 with idiopathic pulmonary fibrosis and 24 with nonspecific interstitial pneumonia. Thirty-four patients had interstitial US lung comets, which were more common in the lower than the upper lung area. Good correlations were evident between the lung comet number and the extent of the reticular pattern on chest high-resolution computed tomography (r = 0.710; P < .01), predicted forced vital capacity (r = -0.614; P < .01), and lung diffusion capacity for carbon monoxide (r = -0.577; P < .01). Notably, the lung comet number had a strong negative correlation with the percutaneous oxygen saturation level after the 6-minute walk test (r = -0.751; P < .01). CONCLUSIONS: The number of interstitial US lung comets evident on transthoracic US imaging may be a valuable marker of disease severity in patients with interstitial pneumonia.

Association Between Endothelial Progenitor Cells and Treatment Response in Non-Squamous Non-small Cell Lung Cancer Treated with Bevacizumab.

BACKGROUND/AIM: To investigate the association between the number of circulating endothelial progenitor cells (EPCs) in non-squamous non-small cell lung cancer (NSCLC) and disease outcome, in combination chemotherapy with and without bevacizumab. MATERIALS AND METHODS: We retrospectively identified 25 non-squamous NSCLC cases, and divided them into high-EPC and low-EPC groups. Within each group, we compared disease outcomes, with or without the administration of bevacizumab. RESULTS: In the high-EPC group, chemotherapy with bevacizumab produced a significantly higher tumor reduction rate and objective response rate, with significantly longer progression-free survival, compared to chemotherapy without bevacizumab (p<0.001, p=0.010, and p<0.001, respectively). However, in the low-EPC group, there were no significant differences in disease outcomes in groups with versus those without bevacizumab. CONCLUSION: The number of EPCs may be a useful biomarker to guide decision-making in the use of bevacizumab in non-squamous NSCLC.

Low plasma concentration of gefitinib in patients with EGFR exon 21 L858R point mutations shortens progression-free survival.

PURPOSE: The relationship between the pharmacokinetics and effects of gefitinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) is unknown. In this study, we examined the correlation between gefitinib plasma concentration and progression-free survival (PFS) in patients with two common types of EGFR mutations: a deletion in exon 19 and point mutations in exon 21 L858R. METHODS: The retrospective analysis examined 40 patients who were administered 250 mg of gefitinib daily. All patients were diagnosed with and treated for advanced non-small cell lung carcinoma with sensitive EGFR mutations between January 2011 and November 2013 at Akita University Hospital, Akita, Japan. The 40 patients were divided into four groups by trough plasma concentration (high or low) and mutation type (exon 19 deletions or exon 21 L858R point mutations). PFS, response rate, and toxic effects were analyzed in all four groups. RESULTS: After excluding 5 patients, the remaining 35 were successfully analyzed. For the patients with exon 19 deletions, there was no significant difference in PFS between the high and low plasma concentration groups (median survival: 12.0 vs. 17.0 months, P = 0.9548). In contrast, the PFS was significantly shorter for patients with exon 21 point mutations and low vs. high concentrations of gefitinib (median survival: 8.0 vs. 16.0 months, P < 0.05). CONCLUSIONS: The results suggest that low gefitinib plasma concentrations in patients with exon 21 L858R point mutations may be associated with shorter PFS in NSCLC patients.

[Suggesting the Significance of Pericardial Fat Pad in Bronchial Stump Fistula].

Bronchial stump fistula is a post-operative complication with poor outcome after pulmonary lobectomy. In order to prevent this complication, the bronchial stump is covered with pericardial fat tissue in our hospital. The case was 58 year old male who received adjuvant chemotherapy after sigmoidectomy for sigmoid colon cancer. As he developed multiple pulmonary metastases, 48 courses of chemotherapy were performed. The lesions had been localized at the right lower lobe, and neither increase in the size of these lesions nor development of other lesions were observed. Hence, an operation was performed. After right lower lobectomy, the bronchial stump was covered with the pericardial fat tissue. Three months after the operation, he developed pneumothorax, and bubbles were detected inside the fat. The pneumothorax was cured conservatively, and the bubbles disappeared spontaneously after 10 months. It is rare that the patient with bubbles in the covering tissue observed for a long time is cured conservatively, suggesting the significance of the stump pad.

[Post Fenestrated Thoracic Empyema with Broncopleural Fistula, Healed Successfully without Plombage].

A 60-year-old man was performed right middle and lower bilobectomy. High fever was observed on the 17th postoperative day and the patient was diagnosed as having empyema with bronchopleural fistula(BPF). Chest tube drainage and antibiotics were started followed by open window thoracotomy on the 61st postoperative day. The repetition of closing package procedure was done daily or every other day. BPF was successfully covered by good granulation and was healed 6 months after open thoracotomy. The empyema cavity gradually decreased in size, and was completely epithelized 1 year after fenestration. Usually, the treatment of empyema with BPF is surgical treatment such as muscle flap plombage, following open window thoracotomy. But if the fistula is small and the infection is controlled effectively non-surgical treatment following open window thoracotomy is potentially useful way to cure the empyema with BPF.

Adverse events of stapling in thoracic surgery: relations between an incidence of adverse events and a stapling volume.

PURPOSE: The use of staplers for thoracic surgery has been widely accepted and regarded as a safe procedure. However, sometimes adverse events (AEs) of stapling are experienced. The aim of the present study was to retrospectively analyze AEs of stapling in thoracic surgery. METHODS: A retrospective multi-institutional review was conducted by the 27 institutions of the Central Japan Lung Cancer Surgery Study Group. Between January 2009 and December 2010, 4495 patients underwent thoracic surgery using mechanical stapling. RESULTS: Stapling of various tissues was performed 16403 times. Total number of AEs related to stapling was 126 (0.77%). One hundred and nine events occurred intraoperative and 17 events occurred postoperative. The AE rates ranged from 0% to 1.8%. No relationship was seen between the incidence of AE and a stapling volume of thoracic surgery. CONCLUSION: We have investigated intraoperative and postoperative AEs of stapling. Generally, stapling in thoracic surgery was safe. An AE rate of stapling in thoracic surgery is not influenced by the numbers of stapling in institutions.

Questionnaire survey on the continuity of home oxygen therapy after a disaster with power outages.

BACKGROUND: After the Great East Japan Earthquake, oxygen-dependent patients in areas experiencing power outages could not continue home oxygen therapy (HOT) without oxygen cylinders. The purpose of this study was to examine use of oxygen cylinders in areas experiencing power outages and the effects of HOT interruption on patients' health. METHODS: Questionnaires were mailed to 1106 oxygen-dependent patients and HOT-prescribing physicians in Akita, near the disaster-stricken area. We investigated patients' actions when unable to use an oxygen concentrator and classified the patients based on oxygen cylinder use. Patients who experienced an interruption of or reduction in oxygen flow rate by their own judgment were assigned to the "interruption" and "reduction" groups, respectively; those who maintained their usual flow rate were assigned to the "continuation" group. Differences were tested using analysis of variance and the χ2 tests. RESULTS: In total, 599 patients responded to the questionnaire. Oxygen cylinders were supplied to 574 patients (95.8%) before their oxygen cylinders were depleted. Comparison of the continuation (n=356), reduction (n=64), and interruption (n=154) groups showed significant differences in family structure (p=0.004), underlying disease (p=0.014), oxygen flow rate (p<0.001), situation regarding use (p<0.001), knowledge of HOT (p<0.001), and anxiety about oxygen supply (p<0.001). There were no differences in changes in physical condition. CONCLUSIONS: Most patients could receive oxygen cylinders after the disaster. Some patients discontinued their usual oxygen therapy, but their overall health status was not affected.