Clinical Findings on Fibroblast Activation Protein in Patients with Gastric Cancer

Human fibroblast activation protein (FAP) is a 97-kDa surface glycoprotein expressed in tumor-associated fibroblasts. In this study, we immunohistochemically examined FAP levels in surgically resected gastric carcinomas and explored their association with clini-copathological findings and prognosis. Sections of paraffin-embedded specimens were obtained from 100 patients with advanced gastric cancer between 1989 and 2001 at our institution, and they were stained with an anti-FAP antibody. Expression of FAP was detected in 64 patients (64%). Lymphatic vessel invasion was observed in 90% of FAP-positive patients (P = 0.015). Blood vessel invasion was observed in 98% of FAP-positive patients (P < 0.001). The disease-specific 5-year survival rate of in the 64 patients with FAP-positive tumors (22%) was significantly lower than in the 36 patients with FAP-negative tumors (34%, P = 0.036). This indicates that vessel invasion is connected with the expression of FAP and that a positive finding of FAP confer a worse prognosis in the patients with gastric cancer

Laparoscopy-Assisted Pylorus-Preserving Gastrectomy for Treating Early Gastric Cancer

Laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG) with lymphadenectomy has been used for treating early gastric cancer located in the middle-third of the stomach. However, firm evidence supporting its safety and usefulness is scant. This study examined 24 and 10 gastric adenocarcinoma patients who had undergone conventional pylorus-preserving gastrectomy (CPPG) and LAPPG, respectively, at our institution. Operation time for LAPPG (362.8 ± 49.6 min) was significantly longer than that for CPPG (221.9 ± 50.0 min; P = 0.04). Estimated blood loss with LAPPG (127.5 ± 91.2 mL) was not significantly different from that with CPPG (167.9 ± 149.9 mL; P = 0.44). Total number of resected lymph nodes was 26.3 ± 9.5 and 21.3 ± 10.8 with LAPPG and CPPG, respectively, with no statistically significant difference. C-reactive protein in serum on postoperative day 1 was significantly lower in the LAPPG than in the CPPG group (5.3 ± 1.7 mg/dL versus 7.8 ± 3.6 mg/dL; P = 0.049). The requirement for analgesia after surgery was more frequent in the CPPG than in the LAPPG group (3.7 ± 2.0 versus 2.2 ± 1.7; P = 0.04). Time to first flatus was shorter in the LAPPG than in the CPPG group (1.9 ± 0.9 days versus 3.1 ± 0.9 days; P = 0.0006). Postoperative hospital stay was significantly shorter in the LAPPG than in the CPPG group (12.0 ± 4.0 days versus 23.0 ± 10.7days; P = 0.0036). With regard to postoperative complications, stasis was observed more frequently in the CPPG (33.3%) than in the LAPPG (10%) group. In conclusion, patients treated by LAPPG showed a comparable quality of surgical operation compared with those treated by CPPG

Superoxide anion production by neutrophils in myelodysplastic syndromes (preleukemia).

Superoxide anion (O2-) production by neutrophils from 14 untreated patients with acute nonlymphocytic leukemia (ANLL) was significantly less than that of healthy controls (4.93 +/- 1.99 vx 6.20 +/- 1.53 nmol/min/10(6) neutrophils, p less than 0.05). In 10 patients with myelodysplastic syndrome (MDS), however, it was not significantly different from the control level although 6 of the 10 patients had low levels, when individual patients were compared with the lower limit of the control range. An inverse correlation between the O2- production of neutrophils and the percentage of leukemic cells in the marrow existed in ANLL (r = -0.55, p less than 0.01), but not in MDS. Three of 4 MDS patients who died of pneumonia prior to leukemic conversion showed a low level of O2- production. The impaired O2- production by neutrophils from some MDS patients, probably due to the faulty differentiation from leukemic clones, may be one of the causes of enhanced susceptibility to infection.</p

Rearrangement of the breakpoint cluster region in Philadelphia chromosome positive acute leukemia.

The rearrangement of breakpoint cluster region (ber) was examined in leukemic cells obtained from 3 patients initially diagnosed as having Ph+ acute leukemia, 2 with acute lymphocytic leukemia (ALL) and one with acute mixed leukemia. DNA was digested with Bgl II and BamH I. The ber rearrangement was present in the case of acute mixed leukemia (Case 1), but was absent in the 2 cases of ALL (Cases 2 and 3). These results suggest that Case 1 represented a type of blast crisis of chronic myelocytic leukemia which was unusual in the sense of the occurrence of a myeloid-lymphoid conversion and lack of an apparent chronic phase. Cases 2 and 3 appeared to be de novo Ph+ ALL.</p

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Hypoplastic leukemia : Chemotherapy for bone marrow dyslasia

The effect of chemotherapy on dysplasia of bone marrow cells was studied in 10 patients with hypoplastic leukemia. Patients were all previously untreated, and ages ranged from 40 to 81 years old (median : 70). Male to female ratio was 1 : 1. Morphologic features studied were pseudo-Pelger neutrophils, absence or decreased Azur granules in the neutrophilis, multinu-cleated erythroblasts, megaloblastoid changes in erythroblasts, micromegakaryocytes, mononuclear megakaryoctes and megekaryocytes with multiple small separated nulei. Although 8 patients with chemotherapeutic effect showed little evidence of dysplasia, 2 patients without chemotherapeutic effect showed severe dysplasia in two or three blood cell lineages. These findings sre thought to indicate that a part of hypoplastic leukemia develops from myelodysplasia with hypoplastic marrow. The establishment of an optimal treatment for hypoplastic leukemia should be sytudied by stratification of bone marrow dysplasia

ヒト脳血管内皮細胞における一酸化窒素合成酵素の微細局在およびその細胞内移動に関する研究

京都大学0048新制・課程博士博士(医学)甲第7987号医博第2146号新制||医||721(附属図書館)UT51-99-S277京都大学大学院医学研究科外科系専攻(主査)教授 成宮 周, 教授 北 徹, 教授 橋本 信夫学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA