Philadelphia chromosome (Ph1)-negative chronic myelogenous leukemia (CML): a clonal disease with origin in a multipotent stem cell

It has been shown with glucose 6-phosphate dehydrogenase (G-6-PD) mosaicism that Ph1-positive chronic myelogenous leukemia (CML) is a clonal disease that involves multipotent hematopoietic stem cells. We now report G-6-PD studies of a 79-yr-old woman with Ph1-negative CML. Equal amounts of B and A-type activities were found in nonhematopoietic tissues, indicating that the patient was heterozygous for G-6-PD. In contrast, only A-type G-6-PD was found in marrow cells, blood erythrocytes, leukocytes, and platelets and in granulocyte-monocyte and eosinophil colonies grown from blood mononuclear cells. Unlike most cases of PH1-positive CML, colony growth in this patient increased during blastic transformation and the colonies contained only immature monocytic cells. The data indicate that in this patient, Ph1-negative CML is similar to the Ph1-positive form of the disease in involvement of multipotent stem cells and probable clonal origin, but the two disorders differ in the rapidity with which they enter blastic transformation and in the pattern of granulocyte-monocyte colony growth at that time.     

美国国家骨髓库20年回顾:捐献活动和非家族异体造血移植产品性能

异基因造血细胞移植已被广泛用于恶性血液疾病、非恶性血液疾病,以及其他疾病的治疗.自1987年来,NMDP实施了以下工作:捐献者身份确认、从匹配的捐献者采集干细胞、运输并输注给没有合适亲缘捐献者的患者.随着移植技术发展,良好的辅助医疗支持以及HLA配型的规范化,越来越多的NMDP产品应用于不同的患者.充足造血干细胞的捐献者是保证造血干细胞移植(HCT)成功的重要因素,然而,通过这些大量数据,可分析捐献者个体的捐献经验和HCT产品的特性.本文研究了NMDP捐献者的捐献活动,它包括多次BM捐献,PBSC捐献以及用于支持免疫重建、提供输血支持、治疗移植后并发症的辅助产品的捐献.本文还对影响HCT产品完整性的诸如采集袋破损、肉眼凝块的情况进行了总结.     

Ethics review: 'Living wills' and intensive care – an overview of the American experience

Withdrawal and limitation of life support in the intensive care unit is common, although how this decision is reached can be varied and arbitrary. Inevitably, the patient is unable to participate in this discussion because their capacity is limited by the nature of the illness and the effects of its treatment. Physicians often discuss these decisions with relatives in an attempt to respect the patient's wishes despite evidence suggesting that the relatives may not correctly reflect the patient's desires. Advance decisions, commonly known as 'living wills', have been proposed as a way of facilitating the maintenance of an individual's autonomy when they become incapacitated. Others have argued that legalising advance decisions is euthanasia by the back door. In October 2007 in England and Wales, advance decisions will become legally binding as part of the 2005 Mental Capacity Act. This has been the case in the USA for many years. The purpose of the present review is to examine the published literature regarding the effect of advance decisions in relation to the provision of adult critical care.     

A single centre evaluation of risk prediction models and imaging modalities in acute appendicitis

IntroductionPatients with suspected appendicitis remain a diagnostic challenge. The aim of this study was to validate risk prediction models, and to investigate diagnostic accuracy of ultrasonography and computed tomography (CT) in adults undergoing appendicectomy.MethodsA retrospective case review was performed of patients aged 16–45 years having an appendicectomy between January 2019 and January 2020 at a tertiary referral centre. Primary outcomes were the accuracy of a high risk appendicitis risk score and ultrasonography and CT imaging modalities compared with histological reports following appendicectomy.ResultsA total of 206 patients (52% female) were included in the study. Removal of a histologically normal appendix was equally likely in men and women (13.1% vs 11.2% respectively, relative risk: 1.17, 95% confidence interval: 0.56–2.44, p=0.674). A high risk appendicitis score correctly identified 84.0% (79/94) of cases in men and 85.9% (67/78) of cases in women. Ultrasonography was reported as equivocal in 85.7% (18/21) of low risk women and 59.0% (23/39) of high risk women. CT correctly detected or excluded appendicitis in 75.0% (6/8) of low risk women and 88.5% (23/26) of high risk women.ConclusionsThis study suggests that risk prediction models may be useful in both women and men to identify appendicitis. Ultrasonography gave high rates of equivocal results and should not be relied on for the diagnosis of appendicitis. CT is a highly accurate diagnostic tool and could be considered in those at low risk where clinical suspicion remains to reduce negative appendicectomy rates.     

Two-year follow-up after catheter-based radiotherapy to inhibit coronary restenosis

BACKGROUND: Although early trials indicate the treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The possibility of late untoward consequences, such as aneurysm formation, perforation, and accelerated vascular disease, is of significant concern. Furthermore, it is not known whether the beneficial effects of radiation therapy will be durable or whether radiation will only delay restenosis. METHODS AND RESULTS: A double-blind, randomized trial was undertaken to compare 192Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Patients were randomly assigned to receive a 0.76-mm (0. 03-in) ribbon containing sealed sources of either 192Ir or placebo. All patients underwent repeat coronary angiography at 6 months. All living patients were contacted 24 months after their index study procedure. Patients were assessed with respect to the need for target-lesion revascularization or nontarget-lesion revascularization, occurrence of myocardial infarction, or death. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192Ir and 29 to placebo. Follow-up was obtained in 100% of living patients at a minimum of 24 months. Target-lesion revascularization was significantly lower in the 192Ir group (15.4% versus 44.8%; P<0. 01). Nontarget-lesion revascularization was similar in 192Ir and placebo patients (19.2% versus 20.7%; P=NS). There were 2 deaths in each group. The composite end point of death, myocardial infarction, or target-lesion revascularization was significantly lower in 192Ir-treated versus placebo-treated patients (23.1% versus 51.7%; P=0.03). No patient in the 192Ir group sustained a target-lesion revascularization later than 10 months. CONCLUSIONS: At 2-year clinical follow-up, treatment with 192Ir demonstrates significant clinical benefit. Although further follow-up (including late angiography) will be necessary, no clinical events have occurred to date in the 192Ir group to suggest major untoward effects of vascular radiotherapy. At the intermediate follow-up time point, vascular radiotherapy continues to be a promising new treatment for restenosis.     

Hematopoietic regulatory factors produced in long-term murine bone marrow cultures and the effect of in vitro irradiation

The nature of hematopoietic regulatory factors elaborated by the adherent (stromal) cells of long-term murine bone marrow cultures and the effect of in vitro stromal irradiation (XRT) on the production of these factors was investigated. Using an in situ stromal assay employing a double layer of semisolid agar, it was possible to demonstrate stromal elaboration of at least two colony-stimulating activities, ie, granulocyte/macrophage colony-stimulating activity (G/M- CSA) and megakaryocyte colony-stimulating activity (Meg-CSA). Exposure of the stroma to XRT resulted in dose-dependent elevations of both activities that correlated inversely with total myeloid cell mass as determined by concurrent reductions in total supernatant cell recoveries from irradiated cultures. Mixture experiments that combined control and irradiated stroma revealed that the hematopoietically active control stroma could block detection of XRT-related G/M-CSA elevations. These data implicate a local negative feedback mechanism in the regulation of hematopoiesis. Antiserum directed against purified L cell colony-stimulating factor (CSF) reduced granulocyte/macrophage colony formation in the target layer but did not effect the increased Meg-CSA. While a radioimmunoassay for L-cell type CSF was unable to detect significant differences in concentrated media from control and irradiated cultures, bioassays of these media revealed XRT-related G/M- CSA elevations. These results indicate that the G/M-CSA elaborated in these cultures is immunologically distinct from the Meg-CSA produced, and although distinct from L cell CSF, the G/M-CSA is crossreactive with the L cell CSF antiserum. Morphologic, histochemical, and factor VII antigen immunofluorescent studies were performed on the stromal cell population responsible for production of these stimulatory activities. In addition to "fat" cells, the stromal cells remaining after XRT were composed of two predominant cell populations. These included a major population of acid phosphatase and nonspecific esterase-positive macrophage-like cells and a minor population of factor VII antigen negative epithelioid cells.     

The Current Role of Staging Laparoscopy in Oesophagogastric Cancer

Introduction

Oesophagogastric cancers are known to spread rapidly to locoregional lymph nodes and by transcoelomic spread to the peritoneal cavity. Staging laparoscopy combined with peritoneal cytology can detect advanced disease that may not be apparent on other staging investigations. The aim of this study was to determine the current value of staging laparoscopy and peritoneal cytology in light of the ubiquitous use of computed tomography in all oesophagogastric cancers and the addition of positron emission tomography in oesophageal cancer.

Methods

All patients undergoing staging laparoscopy for distal oesophageal or gastric cancer between March 2007 and August 2013 were identified from a prospectively maintained database. Demographic details, preoperative staging, staging laparoscopy findings, cytology and histopathology results were analysed.

Results

A total of 317 patients were identified: 159 (50.1%) had gastric adenocarcinoma, 136 (43.0%) oesophageal adenocarcinoma and 22 (6.9%) oesophageal squamous carcinoma. Staging laparoscopy revealed macroscopic metastases in 36 patients (22.6%) with gastric adenocarcinoma and 16 patients (11.8%) with oesophageal adenocarcinoma. Positive peritoneal cytology in the absence of macroscopic peritoneal metastases was identified in a further five patients with gastric adenocarcinoma and six patients with oesophageal adenocarcinoma. There was no significant difference in survival between patients with macroscopic peritoneal disease and those with positive peritoneal cytology (p=0.219).

Conclusions

Staging laparoscopy and peritoneal cytology should be performed routinely in the staging of distal oesophageal and gastric cancers where other investigations indicate resectability. Currently, in our opinion, patients with positive peritoneal cytology should not be treated with curative intent.     

Drainage of pelvic abscesses through the greater sciatic foramen

A computed tomographic (CT) guided transgluteal approach through the greater sciatic foramen was used to drain pelvic abscesses and fluid collections in 21 patients. Ideal catheter placement should traverse the lower portion of the greater sciatic foramen at the level of the sacrospinous ligament. This avoids the vascular and neural elements that are located slightly cephalad at the level of the piriformis muscle. Percutaneous drainage through this approach was successful in avoiding surgery in 17 patients (81%). Pain was the most common complication and was generally associated with a more cephalad approach, transgressing the piriformis and the sacral plexus. CT-guided percutaneous drainage of pelvic abscesses through the greater sciatic foramen should be used when the more standard transperitoneal approach is not possible.