霉酚酸酯治疗35例Ⅳ型狼疮性肾炎的长期随访

目的回顾性总结霉酚酸酯(MMF)治疗Ⅳ型狼疮性肾炎(LN)的临床疗效,探讨MMF的剂量,了解复发情况.方法35例活动性LN患者(其中10例为初治,25例已经使用大剂量激素或联合间断环磷酰胺静脉冲击疗法),采用MMF联合激素治疗6个月以上.所有患者治疗前尿蛋白＞2.0g/24h,有明显血尿或管型尿,肾活检显示活动性Ⅳ型LN.MMF起始剂量1.0～1.5g/d,初治患者同时给予足量激素诱导治疗,对已经使用大剂量激素者继续口服中、小剂量强的松.疗效标准分为缓解、部分缓解及无效.在患者病情明显好转后MMF逐步减至0.5～0.75g/d维持.结果①MMF治疗时间6～36个月(平均12.7±6.8月).在治疗期间共有27例(占77.1%)获得缓解(尿蛋白＜1.0g/d,无活动性尿沉渣、肾功能稳定、血清A-dsDNA阴性,无肾外活动),6例获部分缓解,2例无效.获得缓解的时间为3～15个月(平均6.5±4.7月).随着MMF治疗时间延长,缓解率逐步增高MMF治疗3、6、12、24个月的缓解率分别为25.7%、60%、72.7%及83.3%.18例患者减量或停药前行重复肾活检,肾组织活动性指数显著下降.②30例患者在治疗3～6个月,临床获得缓解或部分缓解后开始减量.在MMF维持治疗3～9个月间12.5%患者复发,7例患者停用MMF3～9个月后3例复发.③治疗过程中各有2例患者并发肺炎及疱疹病毒感染,未见肝功能异常及白细胞减少.结论MMF1.0～1.5g/d剂量联合激素治疗能有效控制狼疮性肾炎活动,诱导治疗时间应6个月以上.在获得缓解或部分缓解后MMF可逐步减量,但维持剂量不宜太小.停止MMF治疗后复发率高,因此必须有替代药物治疗以降低MMF停药后的高复发率.     

弥漫增生型狼疮性肾炎的远期预后

目的:回顾性分析弥漫增生型狼疮性肾炎(DPLN)的远期预后及影响预后的因素。方法:临床符合SLE,经肾活检存在弥漫增生性病变的狼疮性肾炎(Ⅳ/Ⅳ V,ISN/RPS2003肾脏病理分型标准)患者441例[女性377例,男性64例,平均年龄(29.6±9.85)岁]。通过Kaplan-Meier法估算人肾存活率,并建立COX风险模型,分析影响预后的危险因素。结果:(1)人、肾存活率:441例平均随访(60.8±43.3)个月(中位时间61个月)。共15例(3.4%)死亡(感染11例,脑血管意外2例,肺出血1例,猝死1例),5年、10年人存活率分别为96.5%和92%;共28例(6%)在随访期间进展至终末期肾病(endstageranaldisease,ESRD),5年、10年肾存活率分别为94.5%和86.4%。随访初SCr≥132.6μmol/L(HR6.54)、慢性化指数(CI)≥3(HR3.52)、伴有血管病变(HR10.37)及V型病变(HR2.80)、治疗未获缓解(HR10.22)及复发(HR6.13)是肾脏进入ESRD的独立危险因素。(2)1999至2003年DPLN患者5年人、肾存活率均高于1993至1998年(分别为96.3%vs93.6%;95.7%vs90%,P>0.05),但未达统计学差异;(3)复发及转型:323例(73.2%)在随访(7.6±8.5)月(中位时间5月)时达缓解,139例(31.5%)平均随访(35.4±28.2)月(中位时间26月)时复发,5年累积复发率达34.7%。71例因治疗未缓解或复发行重复肾活检,其中17例(23.9%)发生转型(Ⅳ型转为Ⅳ V型)。(4)并发症:共发生并发症270例次(61.2%),主要包括感染(21.3%),月经紊乱(20.2%),股骨头坏死(5.4%),肝酶升高(4.5%)等,5年累积无并发症发生率56.7%。结论:本组DPLN5年人肾存活率可达90%,但复发率及并发症发生率高。随访初合并血管病变、肾功能不全、肾组织慢性化损伤严重、治疗未缓解及复发进入ESRD风险增大。感染仍为主要死因。提高缓解率、降低复发率及减少并发症仍是重型LN临床研究重点。     

狼疮性肾炎患者肾脏远期生存率及影响因素

目的:分析狼疮性肾炎(LN)患者的临床特征和肾脏远期预后,并对影响肾脏预后的危险因素进行评估. 方法:收集本中心经肾活检明确诊断为LN,随访时间≥1年汉族患者的资料,观察终点为进入终末期肾病(ESRD). 结果:本研究共纳入患者1 814例,其中男性253例(13.9％),女性1 561例(86.1％);肾脏病理改变为Ⅱ型患者127例(7.0％)、Ⅲ型244例(13.5％)、Ⅲ+Ⅴ型202例(11.1％)、Ⅳ型711例(39.2％)、Ⅳ+Ⅴ型284例(15.7％)和Ⅴ型246例(13.6％);LN患者5年、10年、15年、20年和25年肾脏生存率分别为93.1％、87.9％、81.0％、68.3％和58.7％;患者的性别、LN病程、平均动脉压、尿蛋白定量、血清肌酐、血红蛋白、血清补体水平及病理类型是ESRD的独立危险因素.随访指标时间平均尿蛋白和时间平均平均动脉压均为ESRD的独立危险因素,且其预测价值分别高于基线尿蛋白和平均动脉压. 结论:结果显示中国汉族LN患者远期预后良好.肾脏预后和病理类型相关,Ⅳ型和Ⅳ+Ⅴ型LN患者肾脏预后最差.病程中应积极控制尿蛋白和血压以减少ESRD的发生.     

The new World Health Organization classification of lung tumours.

Tumour classification systems provide the foundation for tumour diagnosis and patient therapy and a critical basis for epidemiological and clinical studies. This updated classification was developed with the aim to adhere to the principles of reproducibility, clinical significance, and simplicity in order to minimize the number of unclassifiable lesions. Major changes in the revised classification as compared to the previous one (WHO 1981) include the addition of two pre-invasive lesions to squamous dysplasia and carcinoma in situ; atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Another change is the subclassification of adenocarcinoma: the definition of bronchioalveolar carcinoma has been restricted to noninvasive tumours. There has been substantial evolution of concepts in neuroendocrine lung tumour classification. Large cell neuroendocrine carcinoma (LCNEC) is now recognized as a histologically high grade non small cell carcinoma showing histopathological features of neuroendocrine differentiation as well as immunohistochemical neuroendocrine markers. The large cell carcinoma class has been enriched with several variants, including the LCNEC and the basaloid carcinoma, both with a dismal prognosis. Finally, a new class was defined called carcinoma with pleomorphic, sarcomatoid, or sarcomatous elements, which brings together a number of proliferations characterized by a spectrum of epithelial to mesenchymal differentiation. Immunohistochemistry and electron microscopy are invaluable techniques for diagnosis and subclassification, but our intention was to render the classification simple and practical to every surgical laboratory, so that most lung tumours could be classified by light microscopic criteria.     

Long-term outcomes for unselected patients with acute myeloid leukemia categorized according to the World Health Organization classification: a single-center experience

The actual utility of a new classification system of acute myeloid leukemia (AML) recently introduced by the World Health Organization (WHO) has not been thoroughly investigated yet. In this study, we evaluated long-term outcomes of unselected AML patients categorized according to the new WHO classification. Between 1990 and 2002, 109 adult AML cases were referred to our hospital. For the entire population, the median survival duration was 1.2 yr with a 5-yr survival rate of 31%. AML with recurrent genetic abnormalities accounted for 26%, AML with multilineage dysplasia for 29%, therapy-related AML for 13%, and AML not otherwise categorized for 32% of classifiable cases. Among the four groups, a significant difference was observed in terms of overall survival (P < 0.0001). Univariate analysis showed that six variables affected survival: cytogenetic risk, age, multilineage dysplasia, prior chemo/radiotherapy, type of treatment (intensive or palliative), and transplantation. However, in multivariate analysis no adverse prognostic impact of multilineage dysplasia and prior chemo/radiotherapy was detected (P = 0.4979 and 0.8702), whereas cytogenetic risk and patient age maintained their prognostic value (P = 0.0005 and 0.0100). These results indicate that outcomes for AML patients appear to be distinguished on the basis of the WHO classification, but the prognostic significance of multilineage dysplasia and prior therapy is lost after adjusting for cytogenetic risk and age. Our findings suggest that the WHO classification may be strengthened by greater emphasis on genetic/cytogenetic information.     

Focal proliferative lupus nephritis: A clinicopathologic study using the W.H.O. classification

Focal proliferative lupus glomerulonephritis has traditionally been considered to be more benign than the diffuse form. A recent study of lupus nephritis using the W.H.O. classification demonstrated no difference in 4-year survival between those with focal and those with diffuse disease. Because of this development, a comparative Clinicopathologic study of 15 patients with focal proliferative lupus glomerulonephritis and 15 with diffuse proliferative lupus glomerulonephritis was done using the W.H.O. classification. Generally, patients with focal proliferative lupus glomerulonephritis presented with milder renal disease with respect to proteinuria and renal insufficiency. Involvement of the central nervous system was more prominent in focal proliferative lupus glomerulonephritis. Therapy for both types of disease was similar. Mean duration of renal disease was 48 months for focal and 50.7 months for diffuse disease. Three patients with focal proliferative lupus glomerulonephritis and two with diffuse proliferative lupus glomerulonephritis were dead at the end of the follow-up period. Established renal failure was present in one patient with focal disease and two with diffuse disease. Deterioration of renal function was noted in two patients with focal proliferative lupus glomerulonephritis and five with diffuse proliferative lupus glomerulonephritis at the end of the follow-up period. No statistically significant differences in cumulative five-year survival rates (focal = 0.751; diffuse = 0.858), cumulative five-year renal survival rates (focal = 1.00; diffuse = 0.846), deterioration of renal function and quantitative proteinuria at the end of the follow-up period were noted. Although qualitatively milder, the focal form of renal disease followed a course similar to that of the diffuse type.     

Long-term followup of patients treated with total lymphoid irradiation for lupus nephritis

OBJECTIVE: To describe the long-term survival, renal condition, and morbidity outcomes in patients who received total lymphoid irradiation (TLI) for the treatment of lupus nephritis. METHODS: Twenty-one patients with biopsy-proven, diffuse membranoproliferative glomerulonephritis and significant proteinuria of >2.5 grams/day received TLI from 1980 to 1987 at Stanford University Medical Center. All patients had previously failed to respond to treatment with high-dose corticosteroids or therapy with corticosteroids plus immunosuppressive agents (azathioprine, cyclophosphamide, or chlorambucil). RESULTS: The mean duration of followup since TLI was 10.7 years. Fifteen of 21 patients (71%) remained alive at the time of this assessment. Nine of the 21 patients (43%) survived without developing end-stage renal disease (ESRD). The probability of long-term survival without ESRD and without need for additional immunosuppressive agents after TLI was 19% (4 of 21). Factors predicting renal failure at the time of TLI included elevated creatinine levels, increased interstitial fibrosis on renal biopsy, and increased fractional excretion of immunoglobulin and albumin. Malignancies were found in 4 patients, and opportunistic infections occurred in 7 patients. CONCLUSION: Overall, patients with lupus nephritis treated with TLI do not appear to have better 10-year survival with lower incidence of ESRD compared with patients in published series treated with conventional immunosuppressive therapies. However, in this series of patients, treatment with conventional immunosuppressive therapies had been unsuccessful and given the limited number of adverse events and the efficacy seen in some patients, TLI appears to be a reasonable therapeutic option for the treatment of severe lupus nephritis among patients who fail to respond under standard cytotoxic regimens.     

Prospective study of low-dose cyclosporine A in patients with refractory lupus nephritis

We evaluated the efficacy and safety of low-dose cyclosporine A (CsA) in patients with refractory lupus nephritis. Nine patients with systemic lupus erythematosus who had lupus nephritis resistant to previous treatment with glucocorticoids and immunosuppressants other than CsA were enrolled in a prospective, open-label study. All patients initially received 2.5 mg/kg per day of CsA; the dosage was adjusted to reach a blood trough level of 80–150 ng/ml. The urinary protein concentration decreased significantly 2 weeks after the initiation of treatment. After 30 weeks of CsA treatment, the mean urinary protein concentration was more than 50% lower than the baseline value, and urinary casts had decreased significantly. There were no significant changes in the levels of serum creatinine, serum anti-double-stranded DNA antibodies, or CH50 during any part of the study. The dose of glucocorticoids was significantly tapered by approximately 50%, without any disease flare. Hypertension developed in one patient, but was controlled with antihypertensive agents. Our results suggest that low-dose CsA therapy is an effective and less toxic alternative to conventional cyclophosphamide therapy for the management of refractory lupus nephritis.     

World Health Organization classification of the acute leukemias and myelodysplastic syndrome

Under the auspices of the European Association of Hematopathologists and the Society for Hematopathology, 100 hematopathologists and clinicians have met together and in subcommittees over a 5-year period. The model used was that developed by the International Lymphoma Study Group, which used morphologic, immunologic, and genetic features. It resulted in the revised European-American Lymphoma classification. The newly proposed leukemia classification uses a similar format and eliminates purely morphologic subtypes that have no current clinical relevance. As with all consensus proposals, these classifications must withstand criticism and debate by potential users.     

狼疮性肾炎患者并发感染的临床分析

目的:分析狼疮性肾炎(LN)治疗过程中感染的临床特点和流行病学特征. 方法:回顾性分析699例Ⅱ、Ⅲ、Ⅳ、Ⅴ、Ⅳ+Ⅴ及Ⅴ+Ⅲ型LN患者在治疗过程中感染的发生率、发生时期、部位及病原体种类特点.结果:(1)699例LN患者,其中男92例,女607例,平均年龄28.4±11.1岁,平均随访46月.191例(27.3％)患者共发生225例次感染,其中30例2次感染,2例3次感染.(2)225例次感染中,124例次(55.1％)发生在诱导期,发生时间2.6±1.6月;101例次(44.9％)发生在维持期,发生时间24.3±16.6月.(3)感染部位以皮肤软组织、肺、泌尿系统为主(89.3％);感染病原体以细菌最常见(54.2％),其次为病毒(39.6％)和深部真菌(4％)感染.(4)诱导期感染部位主要为皮肤软组织(50.8％)、肺(32.3％)和泌尿系统(11.3％);维持期感染部位主要为泌尿系统(35.6％)、皮肤软组织(30.7％)和肺(16.8％).(5)诱导期病毒(50.8％ vs 25.7％,P＜0.01)和真菌(6.5％vs 1％,P＜0.01)感染比例高于维持期,而细菌感染比例低于维持期(42.7％ vs 68.3％,P ＜0.01). 结论:LN并发感染的总体发生率为27.3％,感染最常发生于诱导治疗3月内,诱导期与维持期感染部位及病原体种类均存在差异.     

Long-term follow-up study of three patients with the long QT syndrome.

We studied three women with the long QT syndrome. They were aged 42, 52 and 25 years and had experienced recurrent syncopal attacks. We followed case 1 for 17, case 2 for 18, and case 3 for over 6 y. The attacks tended to occur during the premenstrual stage in case 1 and case 2; case 3 often experienced attacks after exercise. The QT(U)c intervals on admission were 0.68, 0.62, and 0.50 in case 1, 2, and 3, respectively. Torsade de pointes followed by ventricular fibrillation was documented in case 1 and case 2. Although each was treated with a beta-blocker, none was fully compliant with the regimen. In case 1, estrogen therapy administered to maintain the hormonal balance premenstrually effectively prevented attacks. Despite the inconsistent use of beta-blockers, the attacks in case 1 and case 2 tended to decrease with age. Case 2 experienced no attacks after menopause. Cause 3 took medication consistently and remained free of attacks for over 6 y. Although she discontinued beta-blocker therapy because of pregnancy, she has experienced no attacks to date. These case studies suggest that hormonal status may be important in the development of syncopal attacks in female patients with the long QT syndrome.     

Long-term renal outcomes of mesangial proliferative lupus nephritis in Chinese patients

Clinical Rheumatology - This study aimed to explore the long-term outcomes of mesangial proliferative lupus nephritis (LN class II) and the factors associated with its relapse and histological...     

The World Health Organization (WHO) classification of the myeloid neoplasms

A World Health Organization (WHO) classification of hematopoietic and lymphoid neoplasms has recently been published. This classification was developed through the collaborative efforts of the Society for Hematopathology, the European Association of Hematopathologists, and more than 100 clinical hematologists and scientists who are internationally recognized for their expertise in hematopoietic neoplasms. For the lymphoid neoplasms, this classification provides a refinement of the entities described in the Revised European-American Lymphoma (REAL) Classification-a system that is now used worldwide. To date, however, there has been no published explanation or rationale given for the WHO classification of the myeloid neoplasms. The purpose of this communication is to outline briefly the WHO classification of malignant myeloid diseases, to draw attention to major differences between it and antecedent classification schemes, and to provide the rationale for those differences.     

Controlled studies of oral immunosuppressive drugs in lupus nephritis. A long-term follow-up

From 1969 to 1975, 53 patients with lupus nephritis took part in randomized trials comparing prednisone, oral azathioprine plus low-dose prednisone, and oral cyclophosphamide plus low-dose prednisone. After a mean follow-up of 85 months, cyclophosphamide appears marginally superior to prednisone for maintaining renal function (p = 0.03) and preventing end-stage renal failure (p = 0.07). Chronic change shown by renal biopsy assessed by a chronicity index was found useful in predicting renal function outcomes and response to immunosuppressive therapy. Three of 21 patients with a low chronicity index and 9 of 10 patients with a high chronicity index doubled their serum creatinine (p less than 0.00003). The probability of renal functional deterioration was not different among the treatments studied. However, in 14 patients with an intermediate chronicity index, 1 of 11 patients treated with azathioprine or cyclophosphamide doubled the serum creatinine level whereas all 3 patients treated with prednisone have progressed to end-stage renal failure (p = 0.005). The study suggests that single-drug oral immunosuppressive treatment combined with prednisone is most beneficial in lupus patients with intermediate chronic change shown by renal biopsy.     

Long-term follow-up study of patients with adrenal incidentalomas

BACKGROUND: The incidence of adrenal incidentalomas has sharply increased in recent decades and concurrent subtle endocrine abnormalities, or even subclinical conditions, have been identified. Nonetheless, data concerning possible changes in adrenal size and/or hormonal pattern during follow-up are still inadequate. OBJECTIVE: To evaluate long-term morphological and functional evolution of adrenal incidentalomas after initial diagnosis and to identify possible risk factors for hormonal hyperactivity and mass enlargement. PATIENTS: Sixty-four patients (34-79 years) were followed-up for 12-120 months (median 25.5 months). Initial computerized tomography scan showed a unilateral mass in 51 patients and bilateral lesions in 13 patients. Average mass diameter at diagnosis was 2.5+/-0.1 cm (range 1.0-4.0). Twelve patients had subclinical Cushing's syndrome, 41 had mild hormonal alterations, and 11 had normal adrenal function at baseline. All patients were investigated by morphological and functional evaluation 6 and 12 months after diagnosis, and then at 1-year intervals. RESULTS: During follow-up, a mass size increase >/=1 cm was observed in 13 patients, and 18 developed further subtle endocrine alterations. Cumulative risk of developing endocrine abnormalities was 17% at 1 year, 29% at 2 years, and 47% at 5 years. The risk was higher in the first 2 years of follow-up if the initial tumor diameter was >or=3 cm. Overall, cumulative risk of mass enlargement was 6% at 1 year, 14% at 2 years, and 29% at 5 years, and it was greater in patients with normal adrenal function than in those with subtle hormonal abnormalities (P<0.05). One female subject showed a mass enlargement after 6 months of follow-up and was eventually diagnosed with non-Hodgkin's lymphoma. CONCLUSIONS: Patients with an adrenal incidentaloma are at risk for tumor growth and development of hormonal alterations. The risk of adrenal malignancy, although not elevated, also indicates the need for long-term follow-up.     

Neuroendocrine neoplasms of liver-A 5-year retrospective clinico-pathological study applying World Health Organization 2010 classification

AIM To study the clinicopathological characteristics of neuroendocrine neoplasms(NEN) on liver samples and apply World Health Organization(WHO) 2010 grading of gastroenteropancreatic(GEP) NEN.METHODS Clinicopathological features of 79 cases of NEN of the liver diagnosed between January 2011 to December 2015 were analyzed. WHO 2010 classification of GEP NEN was applied and the tumors were graded as G1, G2 or G3. Two more categories, D1/2(discordant 1/2) and D2/3(discordant 2/3) were also applied. The D1/2 grade tumors had a mitotic count of G1 and Ki-67 index of G2. The D2/3 tumors had a mitotic count of G2 and Ki-67 index of G3. The follow up details which were available till the end of the study period(December 2015) were collected.RESULTS Of the 79 tumors, 16 each were G1 and G2, and 18 were G3 tumors. Of the remaining 29 tumors, 13 were assigned to D1/2 and 16 were D2/3 grade. Male preponderance was noted in all tumors except for G2 neoplasms, which showed a slight female predilection. The median age at presentation was 47 years(range 10-82 years). The most common presentation was abdominal pain(81%). Pancreas(49%) was the most common site of primary followed by gastrointestinal tract(24.4%) and lungs(18%). Radiologically, 87% of the patients had multiple liver lesions. Histopathologically, necrosis was seen in only D2/3 and G3 tumors. Microvascular invasion was seen in all grades. Metastasis occurred in all grades of primary NEN and the grades of the metastatic tumors and their corresponding primary tumors were similar in 67% of the cases. Of the 79 patients, 36 had at least one follow up visit with a median duration of follow up of 8.5 mo(range: 1-50 mo). This study did not show any impact of the grade of tumor on the short term clinical outcome of these patients.CONCLUSION Liver biopsy is an important tool for clinicopathological characterization and grading of NEN, especially when the primary is not identified. Eighty-seven percent of the patients had multifocal liver lesions irrespective of the WHO grade, indicating a higher stage of disease at presentation. Follow up duration was inadequate to derive any meaningful conclusion on long term outcome in our study patients.