胃癌癌前病变癌变机制及其逆转的研究进展

胃癌癌前病变与胃癌的发生关系,日益受到重视,近几年来特别强调幽门螺杆菌为引起慢性萎缩性胃炎与胃癌的重要危险因子.因此,许多学者进一步深入研究幽门螺杆菌感染对发生胃癌的危险性,胃癌癌前病变发生癌变的机制以及如何使其逆转,是预防和降低胃癌发病的重要课题.     

Reduced myocardial perfusion reserve and transmural perfusion gradient in heart transplant arteriopathy assessed by magnetic resonance imaging

OBJECTIVES: The goal of this study was to detect transplant arteriopathy (Tx-CHD) by a reduced myocardial perfusion reserve (MPR) and resting endomyocardial/epimyocardial perfusion ratio (Endo/Epi ratio). BACKGROUND: Transplant arteriopathy often lacks clinical symptoms and is the reason for frequent surveillance angiography in heart transplant (Tx) recipients. Magnetic resonance perfusion imaging (MRPI) allows noninvasive assessment of transmural and selective endomyocardial and epimyocardial perfusion. METHODS: Fifteen healthy volunteers (controls) and three groups (A, B, C) of Tx recipients were included. In controls and patients, MPR (hyperemic/resting perfusion) and Endo/Epi ratio were determined with MRPI after injection of gadolinium-diethylenetriamine pentaacetic acid at rest and during hyperemia (intravenous adenosine). Group A (n = 10) had no left ventricular (LV) hypertrophy and/or prior rejection, while patients in group B (n = 10) had at least one of these characteristics. Patients in group A and B had a normal coronary angiogram and a coronary flow reserve (CFR) of > or =2.5 (CFR = hyperemic/resting blood flow). Group C (n = 7) had Tx-CHD diagnosed by angiography and a reduced CFR (<2.5). RESULTS: In group C, MPR (1.7 +/- 0.5) and Endo/Epi ratio (1.1 +/- 0.2) were significantly reduced compared with controls (4.2 +/- 0.7 and 1.6 +/- 0.3; both p < 0.0001), group A (3.6 +/- 0.7 and 1.6 +/- 0.2; both p < 0.0001) and B (2.7 +/- 0.9, p < 0.01 and 1.4 +/- 0.1, p < 0.04). Transplant arteriopathy can be excluded by an MPR of >2.3 with sensitivity and specificity of 100% and 85%. If LV hypertrophy and prior rejection are excluded, Tx-CHD can be excluded by an Endo/Epi ratio of >1.3 with 100% and 80%. CONCLUSIONS: Magnetic resonance perfusion imaging detects Tx-CHD by a decreased MPR. After exclusion of LV hypertrophy and prior rejection, resting Endo/Epi ratio alone might be sufficient to indicate Tx-CHD.     

Anti-thymocyte globulin overcomes the negative impact of HLA mismatching in transplantation from unrelated donors

OBJECTIVE: About one third of patients requiring allogeneic hematopoetic stem cell transplantation (HSCT) would not find a matched sibling or alternative donor. Allogeneic HSCT from matched unrelated and mismatched donors carries an increased risk of graft-vs-host disease (GVHD) and transplant-related mortality (TRM). MATERIALS AND METHODS: We used anti-thymocyte globulin (ATG-Fresenius) at a median dose of 90 mg/kg body weight as part of a total body irradiation or busulfan-based conditioning regimen for prevention of serious GVHD. All patients received cyclosporine A and short-course methotrexate. We compared outcomes of 65 recipients of human leukocyte antigen (HLA)-mismatched unrelated grafts and 194 recipients of HLA-matched unrelated grafts. Mismatches involved one or two loci. Both groups were comparable in age, graft source, diagnosis, stage of disease, and conditioning regimen, and differed only in dose of ATG administered. RESULTS: For matched and mismatched transplants, respectively, there was no significant difference in graft failure (0.5% vs 3%; p = 0.16), in the cumulative incidence of grade II to IV acute GVHD (45% vs 35%; p = 0.14) and no difference in overall chronic GVHD (42% vs 40%; p = 0.68). Estimated overall survival (OS) and disease-free survival (DFS) at 5 years were 55% vs 50% (p = 0.99) and 47% vs 47% (p = 1.0), respectively. The cumulative incidence of relapse and TRM at 5 years were 24% vs 25% (p = 0.63), and 29% vs 27% (p = 0.59), respectively. CONCLUSION: Inclusion of ATG-Fresenius in the conditioning regimen permits HSCT from mismatched unrelated donors without excess TRM and GVHD, resulting in identical OS and DFS of recipients of HLA-matched and HLA-mismatched grafts.     

Respiratory insufficiency in neuronopathic and neuropathic disorders

Twenty-nine patients with a neuronopathic or neuropathic disorder were referred for assessment of respiratory insufficiency between 1978 and 1994. Diagnoses included spinal muscular atrophy (6), chronic idiopathic demyelinating neuropathy (4), Vialetto-van Laere syndrome (3), hereditary motor and sensory neuropathy (3) and a miscellaneous group (5). We also describe seven patients with Guillain-Barre syndrome (GBS) who required long-term ventilatory support for over 6 months to 7 years after the initial illness. Respiratory insufficiency occurred as a consequence of respiratory muscle weakness, impaired bulbar function and restrictive lung defects. In some groups presentation was with progressive nocturnal hypoventilation culminating in acute respiratory failure. Five patients with GBS or chronic idiopathic demyelinating neuropathy were weaned from ventilatory support up to 18 months after the initial illness. The remaining 24 patients required continuous or nocturnal ventilatory support using intermittent positive-pressure ventilation (13), negative pressure ventilation (4), nasal-mask-delivered intermittent positive-pressure ventilation (4), nasal-mask-delivered continuous positive-pressure ventilation (3), mouthpiece-assisted ventilation by day (2) and rocking bed (1). None have been weaned from support after a period of ventilation ranging from one month to 10 years. Eight patients have subsequently died.      

SELECTIVE ENDOSCOPY IN MANAGEMENT OF INGESTED FOREIGN BODIES OF THE UPPER GASTROINTESTINAL TRACT: IS IT SAFE?

During a four-year period, 308 patients presented following ingestion of foreign bodies. Ingestion was accidental in 272 cases (88.3%) and deliberate in the remainder. Symptoms at presentation included dysphagia, odynophagia, nausea and vomiting, chest pain and pharyngeal discomfort. Sixty-eight patients were asymptomatic. A policy of expectant management and selective endoscopy was employed. Following initial assessment 202 patients (65.6%) were discharged without treatment, 30 (9.7%) of whom were later reviewed as outpatients and did not require admission. Forty-nine patients (16%) were admitted for treatment; 27 had oesophagoscopy, five bronchoscopy and two had foreign body extraction with direct laryngoscopy. In nine patients who were endoscoped, no foreign body was identified. Twenty-seven others were referred to the otorhinolaryngology service in another hospital. There were no deaths in the group and morbidity was 1.2%. We conclude that a policy of selective endoscopy is safe and effective in the management of patients following ingestion of foreign bodies.     

Persistent diarrhea associated with AIDS

Chronic diarrhea and wasting are very common manifestations of AIDS in adults in developing countries. Etiologic studies show that protozoa (including Cryptosporidium parvum, Isospora belli , and Enterocytozoon bieniusi ) and Mycobacterium avium-intracellulara are the most frequently identified pathogens. Limited data in children suggest that common enteric pathogens are equally as likely in HIV⁺ and HIV^- babies. Preliminary analysis of an ongoing longitudinal study of 469 babies born to mothers with known HIV serostatus in Kinshasa, Zaire, reveals progression of acute to persistent diarrhea is six times greater in HIV⁺ compared to HIV^- babies, and 3.5 times greater in HIV^- babies born of HIV⁺ mothers in comparison to HIV^- babies with HIV^- mothers. HIV⁺ babies were also at greater risk than HIV^- babies to have recurrent episodes of diarrhea (RR = 2.3). Fifty percent of the deaths were due to acute or persistent diarrhea, and were strongly associated with HIV infection. Efforts to improve child survival in AIDS infected populations will need to address HIV infections in both mothers and infants.     

Clinicopathological analysis of ATRX,DAXX and NOTCH receptor expression in angiosarcomas

Aims

Multiple genetic alterations, including alternative lengthening of telomeres (ALT) and NOTCH mutations, have been described in angiosarcoma. Loss of α‐thalassaemia/mental retardation syndrome X‐linked (ATRX) and death domain‐associated protein 6 (DAXX) expression is frequently associated with the ALT phenotype. Additionally, inhibition of NOTCH signalling induces the development of malignant vascular tumours in mice, indicating a tumour suppressive role of the NOTCH pathway in the pathogenesis of angiosarcoma. The aim of this study was to evaluate the immunohistochemical expression of ATRX, DAXX and NOTCH receptors (NOTCH1 and NOTCH2) in a large cohort of angiosarcomas, and study their clinicopathological and prognostic significance.

Methods and results

One hundred and forty cases of angiosarcoma were stained for ATRX, DAXX, NOTCH1 and NOTCH2. ATRX loss (<10% labelling) was seen in seven of 118 (6%) cases, and was more frequent in deep soft tissue tumours than in other body sites (P = 0.004). Angiosarcomas with ATRX loss were associated with worse event‐free survival than angiosarcomas with retained ATRX expression (P = 0.003). DAXX was retained in all specimens examined. Decreased NOTCH1 expression (≤1+ intensity) was seen in 29 of 123 (24%) cases, and was associated with a cutaneous site of origin (P = 0.013) and advanced disease (P = 0.026). NOTCH2 expression was decreased in 16 of 103 (16%) cases, was associated with visceral tumours (P = 0.001), and correlated with worse disease‐specific survival (P = 0.033).

Conclusions

ATRX, NOTCH1 and NOTCH2 expression varies in angiosarcomas and shows significant correlations with site of origin and poor clinical outcome, thus highlighting the biological heterogeneity within this tumour type.     

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