A 4-week versus a 3-week schedule of gemcitabine monotherapy for advanced pancreatic cancer: a randomized phase II study to evaluate toxicity and dose intensity

Background

This randomized phase II study compared the efficacy and toxicity between 4-week and 3-week schedules of gemcitabine monotherapy in advanced pancreatic cancer.

Methods

Patients with advanced pancreatic cancer were randomly assigned to either a 4-week schedule (gemcitabine at 1000?mg/m2 as a 30-min infusion weekly for 3 consecutive weeks every 4?weeks) or a 3-week schedule (gemcitabine at 1000?mg/m2 as a 30-min infusion weekly for 2 consecutive weeks every 3?weeks). The primary endpoint was the compliance rate during the first 8?weeks between the two groups.

Results

A total of 90 patients were enrolled. The compliance rate during the first 8?weeks was the same (53.3%). For the 4- and 3-week schedules, the tumor response rates were 14.2 and 17.1% (p?=?0.92), median progression free survival was 112 and 114?days (p?=?0.82), and median overall survival was 206 and 250?days (p?=?0.84), respectively. Grade 3?? neutropenia was the major adverse event in both schedules: 37.7 and 35.5% (p?=?0.82). In contrast, thrombocytopenia (platelet count <70000/mm3) was significantly higher for the 4-week schedule: 26.6 and 4.4% (p?=?0.008). The mean received dose intensity was equal: 588 and 550?mg/m2/week (p?=?0.14).

Conclusions

The 3-week schedule of gemcitabine did not improve the compliance rate during 8?weeks compared with the 4-week schedule, but it attained a comparable efficacy with lower toxicity. Further investigation will be needed to introduce it into daily practice. Clinical trial registration number: UMIN ID 974.     

Recruitment of CCR6-expressing Th17 cells by CCL 20 secreted from IL-1 beta-, TNF-alpha-, and IL-17A-stimulated endometriotic stromal cells

In a novel paradigm of T cell differentiation, type 17 T helper (Th17) cells may play a significant role in endometriosis, a chronic inflammatory disease. However, the mechanism regulating the accumulation of Th17 cells in endometriotic tissues remains unknown. We hypothesized that Th17 cells migrate to endometriotic tissues through an interaction of the chemokine CC chemokine ligand (CCL)20 and its receptor CCR6. Using endometriotic tissues from women with endometriosis, we demonstrated, by flow cytometry, that Th17 cells in endometriotic tissues express CC chemokine receptor (CCR)6. Immunohistochemistry also revealed that CCL20 was expressed in the epithelial cells and stromal cells beneath the epithelium of endometriotic tissues. CCR6+ cells were small and round and scattered in the stroma in which abundant CCL20+ cells were detected. CCL20 caused selective migration of Th17 cells in the peripheral blood in a migration assay. IL-1β, TNF-α, and IL-17A increased the secretion of CCL20 in cultured endometriotic stromal cells. Inhibitors of p38- and p42/44-MAPKs, and stress-activated protein kinase/c-Jun kinase suppressed the secretion of CCL20 increased by IL-1β, TNF-α, and IL-17A. This suggests that the CCL20/CCR6 system is involved in the migration of Th17 cells to endometriotic tissues and that proinflammatory cytokines contribute to the development of endometriosis via up-regulation of CCL20 secretion from endometriotic stromal cells.     

Serum vitamin C concentration and hs-CRP level in middle-aged Japanese men and women

ObjectiveTo examine the association between concentrations of serum vitamin C, a contributive factor to prevention of cardiovascular disease and levels of hs-CRP, a risk factor for cardiovascular disease, in population-based samples of middle-aged men and women.DesignA cross-sectional study.Methods and resultsThe subjects were 778 men and 1404 women, aged 40–69 years, who participated in a cardiovascular risk survey in Kyowa, Ibaraki prefecture in 2002 as part of the Circulatory Risk in Communities Study (CIRCS). Inverse associations between serum vitamin C concentrations and hs-CRP levels were established for both men and women. Multivariable-adjusted mean values of hs-CRP for the lowest to highest quintiles of vitamin C levels were 0.75, 0.65, 0.61, 0.61 and 0.47 mg/L (P for trend <0.001) for men, and 0.56, 0.51, 0.49, 0.41 and 0.41 mg/L (P for trend <0.001) for women. The inverse association between vitamin C and hs-CRP was stronger for non-smoking men and women, non-overweight women and postmenopausal women.ConclusionsSerum vitamin C concentrations were found to be inversely associated with hs-CRP levels in both men and women, primarily among non-smokers, non-overweight women and postmenopausal women. The respective roles of serum vitamin C and hs-CRP levels in the development of cardiovascular disease thus warrant further investigation.     

Allogeneic administration of fetal membrane-derived mesenchymal stem cells attenuates acute myocarditis in rats

We reported previously that the autologous administration of bone marrow-derived mesenchymal stem cells (BM-MSC) significantly attenuated myocardial dysfunction and injury in a rat model of acute myocarditis by stimulating angiogenesis and reducing inflammation. Because BM aspiration procedures are invasive and can yield low numbers of MSC after processing, we focused on fetal membranes (FMs) as an alternative source of MSC to provide a large number of cells. We investigated whether the allogeneic administration of FM-derived MSC (FM-MSC) attenuates myocardial injury and dysfunction in a rat myocarditis model. Experimental autoimmune myocarditis (EAM) was induced in male Lewis rats by injecting porcine cardiac myosin. Allogeneic FM-MSC obtained from major histocompatibility complex-mismatched ACI rats (5 × 10⁵ cells/animal) were injected intravenously into Lewis rats one week after myosin administration. At day 21, severe cardiac inflammation and deterioration of cardiac function were observed. The allogeneic administration of FM-MSC significantly attenuated inflammatory cell infiltration and monocyte chemoattractant protein 1 expression in the myocardium and improved cardiac function. In a T-lymphocyte proliferation assay, the proliferative response of splenic T lymphocytes was significantly lower in cells obtained from FM-MSC-treated EAM rats that reacted to myosin than in cells obtained from vehicle-treated rats with EAM. T-lymphocyte activation was significantly reduced by coculture with FM-MSC. The allogeneic administration of FM-MSC attenuated myocardial dysfunction and inflammation, and the host cell-mediated immune response was attenuated in a rat model of acute myocarditis. These results suggest that allogeneic administration of FM-MSC might provide a new therapeutic strategy for the treatment of acute myocarditis.     

Living donor liver transplantation in a patient with giant hepatic hemangioma complicated by Kasabach-Merritt syndrome: Report of a case

We herein present a case of unresectable giant hepatic hemangiomas with Kasabach-Merritt syndrome which was successfully treated by living donor liver transplantation using a left lobe graft. The patient was a 45-year-old woman who complained of abdominal distension. Two sessions of transarterial embolization were performed, but failed to reduce the size of the tumor. The hepatic tumors were thus judged untreatable and the only option for a cure was to offer living donor liver transplantation, because of the tumor size, its location, and the association with Kasabach-Merritt syndrome. A left lobe graft with the middle hepatic vein donated by her 47-year-old brother was transplanted under venovenous bypass. The postoperative course of the recipient was complicated by small-for-size graft syndrome, which developed after episodes of acute cellular rejection on postoperative day 8 and sepsis on day 31. The patient successfully recovered from the complications and was discharged on day 72, and she remains well at 10 months after transplantation. In conclusion, living donor liver transplantation was found to be an effective option for the treatment of a patient with unresectable giant hepatic hemangiomas complicated by Kasabach-Merritt syndrome.     

Left ventricular-free wall rupture after successful coronary intervention: Report of a case

We experienced the case of a left ventricular-free wall rupture (LVFWR) following successful coronary intervention for acute myocardial infarction (AMI). A 73-year-old woman was hospitalized because of chest oppression that had been continuing for 8 days. She was diagnosed to have AMI, and percutaneous coronary intervention (PCI) was performed. PCI was successful. However, immediately following PCI, she developed electromechanical dissociation secondary to tamponade because of blow-out-type LVFWR. The perforation tear was initially closed by a direct suture, followed by reinforcement using bovine pericardium patches sealed with GRF glue. The patient died of irreversible brain damage on postoperative day 3, but no re-bleeding or aneurysmal dilatation was detected at autopsy.     

Preoperative evaluation of a tracheal bronchus by three-dimensional 64-row multidetector-row computed tomography (MDCT) bronchography and angiography: Report of a case

We performed successful surgery for lung cancer after confirming the anatomical abnormality of a tracheal bronchus by three-dimensional multidetector-row computed tomography (3D-MDCT) bronchography and angiography. Tracheal bronchus is unusual, and right upper lobectomy for lung cancer would rarely be performed in a patient with a tracheal bronchus. Most clinicians are unfamiliar with the anatomy of a right upper lobe that includes a tracheal bronchus. Preoperative 3D imaging of the tracheal bronchus and its related vessels familiarized us with the anatomy of this patient before the operation. Thus, we recommend preoperative 3DMDCT bronchography and angiography, especially for patients with a possible bronchial anomaly.     

Pneumopericardium caused by a permanent endocardial pacing lead

A 59-year-old woman with a history of bronchiectasis was admitted due to a two-day history of fever and hemosputum. A permanent pacemaker (DDD mode, screw-in lead) had been implanted three months previously to treat complete atrioventricular block. On computed tomography, pneumopericardium was seen, and the right atrium pacing lead was stuck into the right lung. A semi-emergency operation to remove the pacing lead and part of the right middle lobe was performed through a right thoracotomy. Although pneumopericardium caused by pacing lead perforation is rare, the possibility of perforation by the pacing lead should always be considered.