Phase I Clinical Study of the Dietary Supplement, Agaricus blazei Murill, in Cancer Patients in Remission

Although many cancer patients use complementary and alternative medicine, including Agaricus blazei Murill (ABM), safety is not yet well understood. Cancer survivors took 1.8, 3.6, or 5.4 g ABM granulated powder (Kyowa Wellness Co., Ltd., Tokyo, Japan) per day orally for 6 months. Adverse events were defined by subjective/objective symptoms and laboratory data according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v3.0). Seventy-eight patients were assessed for safety of ABM (30/24/24 subjects at 1/2/3 packs per day, resp.). Adverse events were observed in 9 patients (12%). Most were digestive in nature such as nausea and diarrhea, and one patient developed a liver dysfunction-related food allergy, drug lymphocyte product. However, none of these adverse events occurred in a dose-dependent manner. This study shows that ABM does not cause problems in most patients within laboratory parameters at the dosages tested over 6 months. This trial supports previous evidence that the ABM product is generally safe, excluding possible allergic reaction

Video-Assisted Thoracoscopic Surgery Using Extracorporeal Membrane Oxygenation for Intractable Pneumothorax

Intractable pneumothorax with poor lung function that has received multiple conservative treatments may occur. Case 1 was a 70-year-old woman with aspergilloma who was admitted for pneumothorax. Case 2 was a 68-year-old man with acute exacerbation of interstitial pneumonia who developed pneumothorax. In both cases, multiple conservative therapies were administered, but the leak continued; thus, operations using veno-venous extracorporeal membrane oxygenation (ECMO) were planned. By video-assisted thoracoscopic surgery (VATS), we obtained the optimal surgical field by lung collapse. We removed many blood clots that were used for pleurodesis, ligated the bulla in case 1, and covered the leak point with strengthening agents in case 2. For cases of intractable pneumothorax, lung collapse by ECMO is advantageous because we can check details and leak points even in blood clots or in poor condition of the lung, and we can maneuver the lung in poor condition with a clear surgical field

Prognostic Factors for Post Recurrence Survival in Resected Pathological Stage I Non-small Cell Lung Cancer

[Background]Recurrence of lung cancer after surgical resection is a major obstacle in the cure and long-term survival of patients and has become the most common cause of death. However, prognostic factors and efficacy of therapy after recurrence remain controversial. We evaluated the prognostic factors of post recurrence survival (PRS) in patients of resected stage I non-small cell lung cancer (NSCLC). [Methods]Of the 551 patients who underwent surgery　for stage I NSCLC between 2005 and 2013, we reviewed 89 (16.2%) patients who had recurrence. We examined PRS using the Kaplan?Meier method and multivariate　Cox regression analyses. [Results]The median follow-up period after recurrence was 21.0 months. The median recurrence free interval (RFI) was 16.8 months. The 1-year PRS and 3-year PRS were 65.6% and 44.7%, respectively. Multivariate analysis revealed that size of primary lesion > 25 mm (P = 0.048), RFI ? 17 months (P = 0.048) and no treatment for recurrence (P < 0.001) were independent poor-prognosis factors of PRS. We further examined PRS in 66 patients who underwent any post recurrence therapy. For the patients who underwent treatment after recurrence, bone metastasis (P = 0.025) and treatment without epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) (P = 0.049) were independent poor prognostic factors. [Conclusion]PRS may be associated with characteristics of a recurrent lesion, including the biology of the recurrent tumor, RFI, recurrent site, the treatment for recurrence, rather than characteristics of primary lesion. Although further validation is needed, this information is important for the design of clinical trials for post-recurrence therapy

Initial Results of Robotic Surgery for Primary Lung Cancer: Feasibility, Safety and Learning Curve

[Background] At the end of 2016, robot-assisted thoracoscopic surgery (RATS) was still not covered by Japanese national health insurance. Therefore, few institutions in Japan perform RATS and even fewer have reported procedures as they occurred earlier. So, we decided to focus on the initial results of RATS for primary lung cancer. [Methods] We retrospectively reviewed 44 patients who underwent RATS for primary lung cancer from January 2011 to August 2016. After mastering the initial procedure, we introduced a completely portal robotic pulmonary resection procedure using a carbon dioxide insufflation system. Cases were divided into 2 groups: the early period (20 cases) and the later period (24 cases). [Results] There was no case of conversion to video-assisted thoracoscopic surgery or thoracotomy. In the 44 cases of primary lung cancer, median operating time was 239.5 min, console time was 179 min, blood loss was 10 mL, drainage period was 2 days, morbidity of Grade 2 or more (Clavien-Dindo classification) was 18.2%, morbidity of Grade 3 or more was only 4.6%, and there was no 30-day mortality. Median operating and console times were significantly shorter in the later period (215 min and 159.5 min, respectively) than in the initial period (300.5 min and 228 min, respectively). Median blood loss was significantly lower in the later period (5 mL) than in the initial period (50 mL). Fiveyear overall and disease-free survival rates were 100% and 88.9%, respectively. [Conclusion] RATS for primary lung cancer is feasible and safe, has a faster learning curve, and provides satisfactory. Studies with longer follow-ups and larger numbers of cases are necessary

The Blimp1–Bcl6 axis is critical to regulate osteoclast differentiation and bone homeostasis

Controlling osteoclastogenesis is critical to maintain physiological bone homeostasis and prevent skeletal disorders. Although signaling activating nuclear factor of activated T cells 1 (NFATc1), a transcription factor essential for osteoclastogenesis, has been intensively investigated, factors antagonistic to NFATc1 in osteoclasts have not been characterized. Here, we describe a novel pathway that maintains bone homeostasis via two transcriptional repressors, B cell lymphoma 6 (Bcl6) and B lymphocyte–induced maturation protein-1 (Blimp1). We show that Bcl6 directly targets ‘osteoclastic’ molecules such as NFATc1, cathepsin K, and dendritic cell-specific transmembrane protein (DC-STAMP), all of which are targets of NFATc1. Bcl6-overexpression inhibited osteoclastogenesis in vitro, whereas Bcl6-deficient mice showed accelerated osteoclast differentiation and severe osteoporosis. We report that Bcl6 is a direct target of Blimp1 and that mice lacking Blimp1 in osteoclasts exhibit osteopetrosis caused by impaired osteoclastogenesis resulting from Bcl6 up-regulation. Indeed, mice doubly mutant in Blimp1 and Bcl6 in osteoclasts exhibited decreased bone mass with increased osteoclastogenesis relative to osteoclast-specific Blimp1-deficient mice. These results reveal a Blimp1–Bcl6–osteoclastic molecule axis, which critically regulates bone homeostasis by controlling osteoclastogenesis and may provide a molecular basis for novel therapeutic strategies