Hereditary antithrombin (AT) deficiency increases the risk of venous thromboembolism (VTE) in pregnant woman. We report the first case of administration of recombinant human antithrombin (rhAT) to a pregnant Japanese woman with AT deficiency. A 30-year-old woman, gravida 2 para 0, was referred to our hospital because of AT deficiency. Unfractionated heparin was administered from 13 weeks of gestation and rhAT was administered from labor onset. A cesarean section was performed and the patient and her baby were healthy, with no sequelae. We concluded that rhAT was effective for preventing VTE during delivery, with no potential infection risks.
e19054 Background: The addition of BV to cytotoxic agent(s) prolonged survival for non-Sq NSCLC patients (pts). However, there is no definitive evidence for the cytotoxic agent(s) plus BV is superior to the cytotoxic agent(s) alone for elderly non-Sq NSCLC. We conducted the feasibility study of PEM plus BV as the first-line treatment for elderly advanced or recurrent non-Sq NSCLC. Methods: Major eligibility and exclusion criteria were followings; chemotherapy-naïve; unfit for bolus combination chemotherapy; stage III/IV or relapsed non-Sq NSCLC; age≥70; PS 0-1; no evidence of brain metastasis; no history of hemoptysis and irradiation for thorax. PEM (500 mg/m 2 ) and BV (15 mg/kg) were administrated intravenously on day 1 every 3 weeks. The primary endpoint was toxicity and the secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the percentage of pts who completed more than 3 cycles. Results: From November 2010 to April 2012, total 12 pts were enrolled. Patients characteristics were following; male/female=6/6; Median age (range) 78 (72-81); histology was all adenocarcinoma; activating EGFR mutation no/yes/unknown=9/2/1; stage IIIB/IV/recurrence=2/8/2; ECOG PS 0/1=6/6; smoking history yes/no=6/6. Severe toxicities (Grade 3≥) were leukopenia (25%), neutropenia (25%), anemia (8%), thrombocytopenia (8%), febrile neutropenia (8%), anorexia (8%), hypertension (8%), fatigue (8%), nausea (8%), and perforation (colon) (8%). No dose-limiting toxicity and treatment-related death was occurred. Three patients achieved PR and the ORR was 25%. The median PFS and OS were 5.6 months (mo) (95% C.I. 1.1-7.9 mo) and 10.3 mo (95% C.I. 6.9-15.6 mo) in 11 evaluated pts, respectively. The 1-year survival rate was 49% (95% C.I. 12-79%). Seven of 12 pts (58%) received more than 3 cycles. Conclusions: PEM plus BV as first-line treatment for elderly non-Sq NSCLC was well tolerable and promising. Clinical trial information: UMIN000004263.
The purpose of this study is to examine effedts of hyperoxic gas mixtures on changes of blood indices during bicycle exercise of human. Oxygen-enriched gases (30%O2) were inspired druing the ramp load exercise of 25 watt/min. Changes of blood indices were analyzed with Sequential Multiple Analyzer with the computer (SMAC).
A pylorous-preserving pancreatoduodenectomy (PPPD) was performed in patients with an invasive ductal adenocarcinoma of the pancreatic head, but with no direct invasion to the duodenal bulb or pyloric ring and no perigastric lymph node metastasis. This study compares the results achieved by the Whipple procedure in patients with invasive ductal adenocarcinoma of the pancreatic head.Over the past 14 years, we have treated 109 patients with an invasive ductal adenocarcinoma of the head of the pancreas, this number excluding low-grade malignancies such as intraductal papillary mucinous carcinoma or cystadenocarcinoma. The postoperative survival rate, level of postoperative social activity and changes in body weight were studied in 48 resected patients and compared with the results of those who underwent the Whipple procedure.In the resected patients, the 3-year survival rate was 20.8%, and the 5-year survival rate was 16.7%. All patients who underwent the bypass operation, however, had a survival rate of less than 2 years, hence the prognosis for resected patients was better (p < 0.01). Among the resected patients, the postoperative survival rate was better in those who underwent a curative resection than in those who underwent a non-curative resection (p < 0.01). No difference was observed in the postoperative survival rate of PPPD vs Whipple procedure patients. The level of postoperative resumption of social activity and changes in body weight were significantly better after the PPPD than after the Whipple operation.For patients with cancer of the pancreatic head, but with no direct invasion of the duodenal bulb or pyloric ring and no perigastric lymph node metastasis, a PPPD proved more effective than the Whipple operation. Further, as the prognosis was also better after curative resection, an extended lymphadenectomy in conjunction with the PPPD was also considered necessary to ensure a cancer-free state following resection.
Introduction: Cigarette smoke (CS)-induced mitochondrial damage has been implicated in COPD pathogenesis. We have reported that PARK2-mediated mitophagy plays a key regulatory role in CS extract-induced oxidative stress and cellular senescence through the degradation of damaged mitochondria in airway epithelial cells (AEC). Additionally, decreased PARK2 protein levels in COPD lungs were demonstrated. To further elucidate the physiological implication of PARK2-mediated mitophagy in COPD pathogenesis, PARK2-deficient mouse models were used. Methods: C57BL/6 WT and PARK2-deficient mice were exposed to CS for 6 months. Lung and airway morphometry was assessed using lung sections stained with Pico Sirius Red. Senescence associated beta-galactosidase (SA-β-gal) staining, and immunostaining for p-histone H2A. X and p21 were performed to evaluate cellular senescence. Western blotting of lung homogenates was performed to assess cellular senescence and autophagy. Mitochondrial structural integrity was examined by electron microscopy (EM). Results: Compared with WT mice, PARK2-deficient mice demonstrated severe emphysema and fibrous thickening of the airway wall. Advanced cellular senescence in AEC was elucidated in PARK2-deficient mice by detecting enhanced staining for SA-β-gal, p-Histone H2A.X, and p21. Increased protein levels of ubiquitin and p62, reflecting insufficient autophagic degradation were observed in lung homogenates from PARK2-deficient mice. EM examination in PARK2-deficient mice showed increased number of damaged mitochondria with crista disruption in AEC. Conclusion: These findings suggest that PARK2-mediated mitophagy plays a pivotal role in COPD pathogenesis via regulating cellular senescence.
e19583 Background: PF is commonly concomitant disorder with lung cancer. Because PF sometimes deteriorates and results unfavorable clinical course, patients with PF are excluded from most cancer clinical trials. S-1 is a novel active oral fluoropyrimidine anticancer agent consisting of tegafur, gimeracil and oteracil potassium. Although most anti-cancer agent have pulmonary toxicity, post marketing surveillance reported S-1 has lower pulmonary toxicity incidence. We have conducted feasibility study of S-1 and carboplatin combination for patients with advanced or ineligible for other treatment modality of NSCLC patients. Methods: Patients with histologically or cytologically confirmed NSCLC, clinically diagnosed pulmonary fibrosis, aged 80 years old or younger, performance status 0-2 and chemo naive were eligible for the study. Carboplatin (AUC 5) was administered on day 1 and S-1 (80mg/m 2 /day) on day 1 to 14 for four to six cycles. Endpoints were response rate, common safety profiles and effect to PF. Results: From March 2009 to December 2011, 21 pts (19 males/ 2 females, median age 67 years old, ranged 55 to 77, 10 adenocarcinoma, 10 squamous, 1 adenosquamous, stage IIA: 1, IIIA: 3, IIIB: 9, IV: 4, recurrence: 4) were enrolled. All patients had moderate or severe PF. Treatment delivery; 1 cycle: 3pts, 2: 3pts, 3: 3pts, 4: 10pts, 5; 1pts, 6: 1pts. Partial responses were observed in 7 patients (RR; 33%). The median progression free survival duration was 4.0 months and the median overall survival duration in 10.4 months. During the treatment, 2 patient experienced moderate deterioration of pulmonary fibrosis, 1 experienced infectious pneumonia, all three patients recovered from the event. There was no treatment related death. Besides pulmonary toxicity, most common adverse events were myelotoxicities. Conclusions: This is the first trial of S-1 and carboplatin combination for patients with PF and NSCLC. The study revealed S-1 and carboplatin combination was feasible and active even in patients with PF and NSCLC who are usually excluded from cancer clinical trials.
