After the development of EGFR tyrosine kinase inhibitors (TKIs), genetic testing of EGFR became required for effective treatment of lung cancer. Initially, the testing was conducted separately for each mutated region. However, many EGFR mutations have since been identified that determine the efficacy of EGFR-TKIs. Therefore, genetic testing of EGFR by next generation sequencing (NGS) may be a suitable strategy for lung cancer. Here we examined the applicability of the NGS method in regard to sensitivity, time and cost. A total of 939 specimens were obtained from 686 lung cancer patients at our hospital. DNA and RNA were simultaneously extracted from specimens derived from surgery, bronchoscopy, and fluid aspiration. Specimens included cerebrospinal fluid, pleural effusion, abdominal fluid, and pericardial effusion. From RNA, target regions (EGFR, KRAS, ALK fusion and RET fusion) were enriched by RT-PCR and sequenced with MiSeq. From DNA, PCR or PCR-RFLP conventional methods were performed. NGS and conventional methods were carried out routinely per week. Among the total 939 specimens, 38 specimens could not be examined with NGS. Among these, 34 specimens were analyzed by conventional testing with simultaneously extracted DNA. The remaining four specimens could not be tested with either method. Compared with the conventional method, the concordance rate of mutations was 99% (892/901), excluding specimens with NGS failure. The time period required from processing of specimens to results was 4 days, and the cost per sample was sufficiently low. In conclusion, the genetic testing with NGS method was useful for lung cancer treatment. The cost, sensitivity and time were able to tolerate routine examinations.

Concurrent chemoradiation therapy (CRT) is standard for stage III non-small cell lung cancer (NSCLC). In our institute, patients undergo surgery after CRT if possible. We aimed to assess the efficacy and adverse event of CRT in patients with stage III NSCLC and investigate the risk of radiation pneumonitis (RP). Two hundred fifty seven patients received CRT for newly diagnosed stage III NSCLC from 2003 to 2013. Patient characteristics were as follows: 87.2% male; median age, 67 years; 55.6% stage IIIA; and 44.4% IIIB. CRT was prescribed, with 40Gy to the primary tumor and mediastinum and a boost of 20Gy to all gross disease. All patients also received platinum based doublet regimen concurrently. After CRT, the patients were re-evaluated in the resectability and underwent surgery. We analyzed tumor volume reduction ratio near the end of radiation therapy. All patients were classified by their lung condition about emphysematous and interstitial changes with CT images before treatment into three degree (slight / moderate / severe). Patients with grade 2 or worse RP were ebaluated with their Dose-Volume Histofram(DVH) parameteres of both lungs. The median follow up time was 73.9 months. The 3-year and 5-year overall survival rates were 44.8% and 33.0% in all patients, and 74.7% and 64.7% in patients with CRT followed by surgery. The 3-year and 5-year local control rates were 68.8% and 49.0%, respectively, in all patients. More than 50 % volume reduction was observed in 73.2 % of patients surviving over 2-years, but 32.3% of these good responder had local failure. Grade 2 or worse RP were observed in 70 patients (27%), grade3 in 11 patients (4%), grade 5 in 3 patients (1%). The median of V5Gy, V10Gy, V20Gy, V40Gy, and mean dose of group with grade 2 or worse RP were 32.1, 27.5, 22.5, 16.5 %, and 13.5Gy, respectively, and with grade 3 to 5 RP were 31.5, 27.9, 23.9, 19.0 %, and 12.8Gy, respectively. In patients with grade 3 to 5 RP, 8 of 14 patients had severe emphysematous lung and moderate or severe interstitial change, or had over 30 % lung V20Gy. CRT for stage III NSCLC was effective with acceptable toxicities. Even though patients had good early response to CRT, local control was not sufficient. Grade 3 or worse RP may relate not only to DVH parameters, but also pulmonary complication before CRT.

Objective: We studied the relation between hematologic toxicity and demographic characteristics in patients who received Amrubicin (AMR). Methods: From 2008 through 2014, we retrospectively studied clinical characteristics, treatment course, hematologic toxicity, and other factors in 108 patients who received AMR for the treatment of recurrent small-cell lung cancer. Results: The study group comprised 88 men and 20 women, with a median age of 69 years. The performance status at the start of treatment with AMR was 0 in 18 patients, 1 in 58, 2 in 21, and 3 in 11. Previous treatment was received once in 68 patients, twice in 34, and 3 times in 6. At the time of starting treatment with AMR, 29 patients had bone metastasis, 5 had grade 2 liver disease, and 23 had a history of chest irradiation. The starting dose of AMR was 25 mg/m2 in 7 patients, 30 mg/m2 in 20, 35 mg/m2 in 60, 40 mg/m2 in 19, and 45 mg/m2 in 2. The median number of treatment cycles was 3, the response rate was 27%, and PFS was 103 days. The incidence of grade 3 or 4 hematologic toxicity was 48% for neutropenia, 8% for decreased hemoglobin concentrations, 6% for thrombocytopenia, and 26% for febrile neutropenia. Four patients died of treatment-related infections. All deaths were associated with a poor performance status or liver dysfunction at the start of treatment. The incidences of hematologic toxicity and febrile neutropenia increased in a dose-dependent manner. Conclusions: AMR has relatively mild nonhematologic toxicity and is a key drug for the management of recurrent small-cell lung cancer. However, caution is required because hematologic toxicity and febrile neutropenia increase in a dose-dependent manner. Particular caution should be exercised in patients with a poor performance status or severe liver dysfunction, and the starting dose of AMR should be reduced depending on background characteristics.

Aim: The aim of this trial was to evaluate the safety and efficacy of oral hydration as a substitute for intravenous (IV) hydration after CDDP administration.

Background: Pemetrexed is a key drug for the management of advanced non-squamous non-small-cell lung cancer (NSCLC) in first-line, second-line, and maintenance settings. Maintenance therapy is given until the development of progressive disease or unacceptable toxic effects, with the specific goal of improving progression-free survival and overall survival with minimal side effects. However, the long-term toxic effects of continued therapy with pemetrexed remain unclear. Methods: We evaluated safety, the incidence of grade 3/4 toxicity, and progression-free survival in 29 patients who received 10 or more cycles of pemetrexed (defined as long-term treatment). Results: The study group comprised 18 men and 11 women with a median age of 66 years (range: 49-75). Pemetrexed was used for maintenance therapy in 9 patients and for second- to sixth-line treatment in 20. All patients had adenocarcinoma. The median number of treatment cycles was 13 (range: 10-44, mean: 15.2). No patient had grade 3/4 hematologic toxicity after 10 cycles. The only grade 3/4 nonhematologic toxicity that developed after 10 cycles was empyema in 1 patient. Median progression-free survival was 11.1 months in patients who received second- to sixth-line treatment. Treatment was discontinued because of possibly drug-related adverse events in 2 patients, disease progression in 16, and other reasons in 2. The other 9 patients are still receiving treatment. Of the 20 patients who discontinued pemetrexed, 17 could receive subsequent treatment. Conclusions: In 29 patients who received long-term treatment with pemetrexed, there was no unexpected or irreversible toxicity.

Recent studies have demonstrated that epidermal growth factor receptor (EGFR) mutations are a predictive molecular marker of tumor response to gefitinib treatment in non-small-cell lung cancer (NSCLC). Early studies of EGFR mutations have been analyzed by direct sequencing with surgically resected specimens. However, it is often difficult to obtain sufficient and tumor-enriched tissue specimens from inoperative NSCLC patients for mutation analysis. Therefore, we set out to develop a simple, sensitive and reliable method based on polymerase chain reaction (PCR) and restriction endonuclease treatment to detect important EGFR mutations for gefitinib treatment, including G719S, deletion or insertion in exons 19 and 20, T790M, L858R and L861Q using bronchoscopic specimens. Two hundred and eleven bronchoscopic samples cytologically diagnosed as malignant were analyzed and mutations detected from 60 patients (28.4%). The present assay could detect deletion in exon 19 and L858R mutations in the presence of at least 1% and 5% mutant cells, respectively, from a background of normal cells. Comparison of mutation detection between bronchoscopic and surgical specimens from 42 patients indicated that the sensitivity of this assay using bronchoscopic specimens was 95% (18/19) with a specificity of 100% (23/23). Furthermore, deletion variants in exon 19 could be distinguished by native polyacrylamide gel electrophoresis. Consequently, this simple, sensitive and reliable assay can provide important information pertaining to optimal therapeutic strategies.

Of the 1548 patients with primary lung cancer who were admitted to our hospital from January 2001 through March 2005, 37 in whom meningeal carciomatosis was diagnosed on cytologic examination of cerebrospinal fluid or magnetic resonance imaging of the brain and spinal cord were studied retrospectively. The most common histologic type was adenocarcinoma, diagnosed in 70% of those patients. The results of cytologic examination of cerebrospinal fluid were positive in 71%. The time from the date of diagnosis of lung cancer to the date of diagnosis of meningeal carcinomatosis ranged from -2 days to 8 years (median, 407 days). Survival from the date of diagnosis of meningeal carcinomatosis ranged from 10 to 392 days (median, 106 days). Treatment for meningeal carcinomatosis was decided on the basis of the patient's general condition and the contorol status of the primary lesion. Radiotherapy, systemic chemotherapy, and palliative therapy were combined. Gefitinib was most often used for chemotherapy after the onset of meningeal carcinomatosis, and 60% of the patients given gefitinib had stable disease. One of these patients (adenocarcinoma) survived for longer than 1 year. Further investigatons are needed to establish standard treatments, including the use of gefitinib, that can improve the quality of life and prolong the survival of patients with meningeal carcinomatosis.

Journal Article Proliferated Bile Ductules Observed by Scanning Electron Microscopy Using the Chemical Digestion Method after Liver Capsule Mechanical Stripping Get access Kazushi KOBAYASHI, Kazushi KOBAYASHI Department of Internal Medicine, Kawasaki Hospital, Kawasaki Medical College2-1-80, Nakasange, Okayama City, Okayama, 700 Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Yoshiki NOSAKA, Yoshiki NOSAKA Department of Internal Medicine, Kawasaki Hospital, Kawasaki Medical College2-1-80, Nakasange, Okayama City, Okayama, 700 Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Junichi SUDO, Junichi SUDO Department of Internal Medicine, Kawasaki Hospital, Kawasaki Medical College2-1-80, Nakasange, Okayama City, Okayama, 700 Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Yasukage ASAKURA, Yasukage ASAKURA Department of Internal Medicine, Kawasaki Hospital, Kawasaki Medical College2-1-80, Nakasange, Okayama City, Okayama, 700 Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Toshinari KOBAYASHI Toshinari KOBAYASHI Department of Internal Medicine, Kawasaki Hospital, Kawasaki Medical College2-1-80, Nakasange, Okayama City, Okayama, 700 Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Electron Microscopy, Volume 33, Issue 4, 1984, Pages 375–377, https://doi.org/10.1093/oxfordjournals.jmicro.a050478 Published: 01 January 1984 Article history Published: 01 January 1984 Received: 29 July 1984 Accepted: 13 December 1984

子宮原発悪性リンパ腫に伴つた寒冷凝集素症の1例を報告した.症例は78才の女性で,第12胸椎圧迫骨折のために入院した際に,貧血および下腹部腫瘤を指摘された.検査所見では,正色素性貧血,網状赤血球数の増加,間接型ビリルビン血症,ハプトグロビンの低値および骨髄の赤芽球過形成など溶血性貧血の所見がみられた.寒冷凝集反応は高値(×102400)を示し,寒冷凝集素は抗I特異性をもち, IgM (κ)であつた.以上により寒冷凝集素症と診断し,溶血のためステロイド投与を行なつたが,入院第21病日に消化管出血および溶血クリーゼのため死亡した.剖検では下腹部腫瘤は子宮体部原発の悪性リンパ腫であり, LSG分類による組織型はびまん性リンパ腫混合型であつた.腫瘍細胞は光顕および電顕所見では,未分化なリンパ芽球様細胞が主体をなしていた.免疫組織学的な検索では, PAP法では腫瘍細胞細胞質内にlgMおよびκ鎖の陽性像を認め,電顕酵素抗体法でも腫瘍細胞の核膜周囲,ポリゾームおよび粗面小胞体にlgMの局在が認められた.以上により,本症例は形態的に未公化な腫瘍細胞が,自己の赤血球に対する抗体を産生していたと考えられ興味深い.