Ext-mutation analysis in Italian sporadic and hereditary osteochondromas.

Osteochondromas represent the largest group of benign tumors of bone. Multiple osteochondromatosis or hereditary multiple exostoses (EXT) is an autosomal dominant inherited disorder characterized by the presence of multiple benign cartilage-capped exostoses. EXT is genetically heterogeneous with at least 3 chromosomal loci: EXT1 (8q24.1), EXT2 (11p11-p13), and EXT3 (19p). In <5% of EXT patients, the inactivation of both copies of EXT alleles (LOH) is associated with malignant transformation. We have analyzed the EXT1 and EXT2 genes in 9 unrelated EXT families and in a patient with a sporadic osteochondroma, all originating from Italy. Four families show an EXT1 mutation, consisting of a small deletion in 3 of them and a small insertion in the 4th. All these mutations lead to premature termination of translation and thus a truncated EXT1 protein. Three families presented EXT2 mutations consisting of nucleotide substitutions leading to alterations of the third intron splice-site, to an amino acid substitution and to a nonsense mutation. All these mutations cosegregate with the disease phenotype. The sporadic osteochondroma patient carried a novel missense mutation in exon 11 of EXT2 gene, leading to an amino acid substitution. Seven of these mutations have never been described before. EXT2 missense mutations were also confirmed by amino acids conservation between human and mouse and by analysis of a healthy control population. In conclusion, our study provide further evidence that loss of function of the EXT1 or EXT2 gene is the main cause of EXT supporting the putative tumor-suppressor function of these genes.     

Prognostic markers in malignant lymphoma: an analysis of 1,198 patients treated at a single centre.

The prognostic significance of 20 putative markers has been assessed in a consecutive series of 1,198 patients with malignant lymphoma seen by the Sheffield Lymphoma Group over three decades. Univariate analysis disclosed that ten factors for both Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) Grade I, and twelve factors for NHL Grade II had prognostic significance. However, multivariate analysis selected only three (age, serum albumin and lymphocyte count) for HD, one (serum albumin) for NHL Grade I and five (age, stage, erythrocyte sedimentation rate, serum albumin and serum lactate dehydrogenase) for NHL Grade II as independent predictors for survival. Risk adjusted prognostic models were derived for Hodgkin's disease and NHL Grade II. For Hodgkin's disease the presence of 3 risk factors predicted for only 35% long-term survival for this group of patients. For NHL Grade II the group with 3-5 risk factors present had a median survival of less than 2 years compared to a 9-year median survival in patients with 1 risk factor present. Whilst these models are being validated on a larger series of patients and will also be tested prospectively, new markers are needed to facilitate decisions on treatment for individual patients.     

手术中发现胆囊癌41例分析

目的探讨手术中意外发现的胆囊癌的临床及病理特征,分析术前误诊原因及影响预后的因素。方法对41例经病理证实的手术意外发现的胆囊癌患者的临床及病理资料进行回顾性研究分析。结果41例患者术前影像学均误诊为胆石症。24例选择经腹腔镜胆囊切除术,其中有3例术中改为开腹只取活检而未手术切除;17例选择剖腹胆囊切除术,其中有1例术中改为胆囊切除及局部淋巴结清扫术,2例术中改为胆囊及肝楔形切除术。病理类型腺癌30例、粘液腺癌5例、腺鳞癌2例、鳞癌3例、未分化癌1例。病理学分期(PTNM)Ⅰ期3例、Ⅱ期5例,Ⅲ期22例,Ⅳ期11例。有39例胆囊癌患者(95%)合并胆囊结石。术后1年存活率为35·4%,5年存活率为6·1%。结论手术中意外发现的胆囊癌以中晚期患者居多,临床表现缺乏特异性,早期诊断困难,术前误诊率高,大多数患者合并胆囊结石及对该病认识不足是造成术前误诊的主要原因。疗效不佳、预后差与早期诊断困难、手术方式选择及肿瘤的临床病理分期有关。经腹腔镜胆囊切除术胆囊癌误诊率高,应慎重选择,手术中对疑为胆囊癌的病例应改行开腹手术。     

Myeloma during a decade: Clinical experience in a single centre

One hundred and fifty-six patients with multiple myeloma weretreated over a period of 12 years at St. Bartholomew's Hospital.The progress of the disease was affected in 96/156 patients(61%). Response was defined as achieving a plateau of M component.A partial or complete response was seen in 68/120 patients treatedconventionally (56.5%), and in 28/36 patients treated with high-dosetherapy (77.7%). The median survival of the group as a wholewas 20 months, with a 2-year survival of just over 40%. In the36 patients treated with high-dose therapy, median survivalwas 6 years, and in a small group who have had maintenance Interferontherapy, the median has not yet been reached. In a univariateanalysis, age, intensity of therapy, haemoglobin and creatininelevels were significant, but multivariate analysis showed thatonly age and intensity of therapy were independent predictorsfor survival. The outlook for relapsed patients who showed progressionof disease remains poor, but palliation was best achieved bysteroid and Interferon in combination. Patients who achievecomplete responses and are maintained on Interferon appear tobe doing better both in terms of freedom from symptoms and insurvival, and methods to enable an elderly population to toleratethis form of therapy need to be explored. intensive chemotherapy, maintenance and relapse therapy, myeloma, survival     

妊娠合并急性白血病39例临床特征及预后分析

目的 探讨妊娠合并急性白血病(AL)患者的临床特征及预后情况.方法 收集2010年1月至2017年4月在郑州大学第一附属医院血液科就诊的39例单胎妊娠合并AL患者临床资料,回顾性分析其临床特征及预后情况.结果 除孕前发病1例外,妊娠早、中、晚期AL患者所占比例分别为23.7％(9/38)、52.6％(20/38)、23.7％(9/38).共31例患者接受化疗,妊娠早、中、晚期患者化疗完全缓解(CR)率分别为71.4％(5/7)、94.1％(16/17)、100.0％(7/7).31例流产或引产,8例剖宫产产下活婴.22例存在染色体核型异常,主要为与分型相关的特异性染色体重排;AML患者高表达CD117、CD13、CD33、CD38,ALL患者高表达CD19、CD38、CD22、cCD79a、CD58.诱导治疗后微小残留病(MRD)阳性的10例患者CR7例,CR后复发4例,死亡7例,而MRD阴性患者19例均获CR,CR后复发5例,死亡9例.所有患者中,29例为AML,10例为ALL,CR率分别为95.7％(22/23)、75.0％(6/8).所有患者1年生存率53.1％,2年生存率26.4％,其中AML患者生存率高于ALL患者.结论 妊娠合并AL患者临床特征复杂,需全面综合处理;MRD是预后判断的重要指征;ALL患者预后较AML差.     

胃肠道间质瘤92例临床病理观察

目的:探讨胃肠道间质瘤(gastroin testinal stromal tumors,GIST)临床病理特征.方法:收集116例手术切除的胃肠道间叶性肿瘤标本,通过常规HE制片,单抗CD117等免疫组化标记确诊GIST 92例,分析和观察患者的临床和病理资料,并复习文献.结果:GIST高峰年龄55～75岁,占胃肠道间叶性肿瘤的79.31%,约15.22%伴发消化道癌.好发部位是胃(54.35%)和小肠(18.48%),其次是肠系膜、结直肠及食管.瘤体大小为0.2～22 cm,单发或多发性结节(9.78%).显微镜下,瘤细胞梭形和上皮样呈束状交叉或弥漫性排列为主,细胞异形性在同一瘤体内的不同区域可存在明显差异,可伴有骨软骨化生(4.35%).免疫组化,瘤细胞表达CD117(96.74%)或CD34(89.23%),灶性表达DES、SMA、S-100及NSE.结论:GIST是具独特的临床表现和组织学上高度异质性、免疫表型上表达c-kit蛋白(CD117)的胃肠道最常见的间叶源性肿瘤;掌握其临床病理特点有助于治疗方案的拟定.     

Studies on ectopic ACTH-producing tumors. II. Clinical and biochemical features of 30 cases.

This report describes the clinical and biochemical features of 30 cases of ectopic ACTH-producing tumors diagnosed by the detection of ACTH in the tumor tissues. Several uncommon tumors, such as tumors of the esophagus, stomach, and larynx, were included in this series. None of the patients with bronchogenic carcinoma showed signs of classical Cushing's syndrome, whereas 7 of the remaining 13 patients with other tumors were Cushingoid in appearance. Adrenocortical hyperfunction was present in 61 percent at the first examination and developed during the course of the disease in 18 percent more. In the remaining patients (21 percent), adrenocortical function remained within normal limits. These results indicate that there exist ectopic ACTH-producing tumors without clinical and biochemical sequelae of excess hormone. In some of the tumor extracts studied, MSH and CRF-like activities and serotonin were detected. This suggests that multiple hormone production is not uncommon in ectopic ACTH-producing tumors.     

Novel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas,but an absence of somatic SDHB mutations in sporadic phaeochromocytomas

Phaeochromocytomas arising in adrenal or extra-adrenal sites and paragangliomas of the head and neck, in particular of the carotid bodies, occur sporadically and also in a familial setting. In addition to mutations in RET and VHL in familial disease, germline mutations in SDHD and SDHB genes that encode subunits of mitochondrial complex II have also been associated with the development of familial phaeochromocytomas. To further investigate the role of SDHD and SDHB in the development of these tumours we determined the occurrence of germline SDHD and SDHB mutations in four patients with a family history of phaeochromocytoma with associated head and neck paraganglioma, one patient with a family history of phaeochromocytoma only and two patients with apparently sporadic extra-adrenal phaeochromocytoma, one of whom had early onset disease. Secondly, we investigated whether somatic SDHB mutations correlated with loss of heterozygosity at 1p36 in a subgroup of 11 sporadic and three MEN 2-associated RET-mutation-positive phaeochromocytomas. Novel SDHB mutations were identified in the probands from four families and two apparently sporadic cases (six of seven probands studied), including two missense mutations, a single nonsense and frameshift mutation, as well as two splice site mutations, one of which was shown to have partial penetrance resulting in 'leaky' splicing. Further, five intronic polymorphisms in SDHB were found. No SDHD mutations were identified. In addition, no somatic SDHB mutations were found in the remaining allele of the 11 sporadic adrenal phaeochromocytomas with allelic loss at 1p36 or the three MEN 2-associated RET-mutation-positive phaeochromocytomas. Therefore, we conclude that SDHB has a major role in the pathogenesis of familial phaeochromocytomas, but the possible role of SDHB in sporadic tumours showing allelic loss at 1p36 has yet to be ascertained.     

41例青少年甲状腺癌临床分析

目的探讨青少年甲状腺癌的临床病理特点、外科手术方式及预后。方法41例患者均采用手术治疗,辅以内分泌治疗,4例术后~(131)Ⅰ内照射治疗。结果术后病理:乳头状腺癌33例(80.5%),滤泡状腺癌8例(19.5%)。颈部淋巴结阳性者28例(68.3%),肺转移4例。40例获5年以上随访,1例失访,5年生存率95.1%(39/41),20例获10年以上随访,10年生存率90.0%(18/ 20)。结论青少年甲状腺癌颈部肿块临床表现大多数无特异性,难以与其他颈部肿块鉴别,易误诊。治疗手段以手术为主,预后良好。具体治疗方案应根据病理类型、肿瘤范围及转移情况决定。     

41例肝脏原发性恶性血管肿瘤的临床病理特点

目的 探讨肝脏原发性恶性血管肿瘤（PHMVT）的临床病理学及预后的特点。方法 回顾性分析1982年1月至2012年12月在我院手术切除并经病理组织学证实的41例PHMVT,对其临床表现、病理学特点及预后进行分析。结果 41例患者中,肝上皮样血管内皮瘤（EHE） 19例（46.3％）,平均瘤体直径为49cm（1.2～6.3cm）;肝血管肉瘤（PHA）14例（34.1％）,平均瘤体直径为8.3cm（3.0～14.0cm）;肝婴儿型血管内皮瘤（IHE）5例（12.2％）,平均瘤体直径为3.8cm（1.2～6.3cm）;肝恶性血管外皮瘤（MHP）3例（7.3％）,平均瘤体直径为7.8cm（2.1～13.0cm）。免疫组化显示41例肿瘤细胞均表达Vimentin、CD34或因子Ⅷ。EHE患者术后中位生存期为87个月,优于PHA的12个月（P＜0.05）;2例有完整随访资料的MHP患者分别于术后43个月死亡和术后84个月复发;IHE患者术后均无复发,预后良好。结论 PHMVT的病理类型与预后有关,PHMVT的恶性程度由高到低依次为PHA＞MHP＞EHE＞IHE。     

遗传性乳腺癌卵巢癌91例临床分析

目的探讨遗传性乳腺癌卵巢癌(HBOC)患者所患卵巢癌的临床特点。方法对91例HBOC患者的发病年龄、两癌发病间隔、病理类型、分期、家族史和生存期等进行分析。观察患者2,5年生存率,分析影响预后的因素。结果91例HBOC患者的中位生存期为47个月,2,5年生存率分别为71．2％和33．5％。卵巢癌的中位发病年龄为52岁,55岁前发病者占60．4％。在39例双原发癌中．两癌发病间隔≥60个月的患者20例,占51．3％。在91例卵巢癌中,浆液性腺癌最常见,有54例(59．3％)：Ⅲ、Ⅳ期患者70例(76．9％);低分化者54例(59．3％)。结论HBOC患者的卵巢癌发病年龄比散发者早,多数为晚期低分化,病理类型以浆液性腺癌为主,肿瘤分期和分化程度是影响患者预后的因素。对于乳腺卵巢双原发癌患者,卵巢癌的临床特点是影响其预后的主要因素。HBOC患者患卵巢癌后的中位生存期与散发性卵巢癌相似。     

Allelic loss on chromosome 11 in hereditary and sporadic tumors related to familial multiple endocrine neoplasia type 1.

Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant disorder characterized by tumors of the parathyroid glands, pancreatic islets, and anterior pituitary. The gene for this disease maps to chromosome 11q12-11q13, and allelic loss in this region has been shown in both sporadic and FMEN1-related parathyroid tumors. FMEN1-related pancreatic islet tumors, and rarely in sporadic anterior pituitary tumors. We tested for allelic loss at 7 loci on chromosome 11 in 17 tumors outside the parathyroid. We found loss of heterozygosity in 2 of 2 FMEN1-related benign pancreatic islet tumors but in none of 8 informative sporadic islet tumors (P = 0.02) including 5 malignant gastrinomas. Of 3 islet tumors from patients who had some but not all features of FMEN1, one showed allelic loss for 5 of 5 informative restriction fragment length polymorphisms, and the other 2 retained heterozygosity for all informative markers. A bronchial carcinoid from an FMEN1 patient and 3 sporadic anterior pituitary tumors showed no allelic loss. These data provide new evidence that many sporadic pancreatic islet neoplasms, even when malignant, do not develop through homozygous inactivation of the MEN1 gene.     

Prognostic factors in pancreatic endocrine neoplasms: an analysis of 136 cases with a proposal for low-grade and intermediate-grade groups.

PURPOSE: In some organs (eg, the lung), endocrine tumors are classified on the basis of mitotic rate and necrosis. The purpose of this study was to evaluate prognostic factors in pancreatic endocrine neoplasms recently treated at a single institution. PATIENTS AND METHODS: In 136 patients undergoing surgery from 1979 to 1998, the influence on disease-free survival (DFS) and disease-specific survival (DSS) of tumor size, mitotic rate, vascular invasion, necrosis, metastases, and nuclear grade was determined. Cases were further grouped according to an existing proposed classification system and then regrouped on the basis of mitotic rate (< 2 mitoses per 50 high-power fields v higher) and necrosis (present or absent) into low- and intermediate-grade groups. RESULTS: Correlations with DFS and DSS in univariate analysis included < or = 2 mitoses per 50 high-power fields (P =.001, P =.002), vascular invasion (P =.02, P =.04), size < or = 2 cm (P =.01, P =.05), metastases (P =.0002, P =.07), necrosis (P =.002, P =.16), and nuclear grade (P =.04, P =.33), respectively. By multivariate analysis, for DFS, tumor necrosis and presence of metastases retained significance (P =.01, P =.04, respectively). For DSS, only mitotic rate was a prognostic factor (P =.02). Among the 18 macroadenomas, eight borderline tumors, and 48 low-grade carcinomas, there was no significant difference in DSS between any groups (P =.3). However, in evaluating our newly proposed groups, the differences in DFS and DSS between low- and intermediate-grade groups were highly significant (P =.0007, P =.006, respectively). CONCLUSION: Pancreatic endocrine neoplasms exhibit a spectrum of biologic behavior, and the proposed benign (macroadenoma) and borderline groups contain potentially aggressive tumors. An alternative system based on mitotic rate and necrosis correlates strongly with survival without specifically designating any group as benign.     

Genetic analysis of the RNASEL gene in hereditary, familial, and sporadic prostate cancer.

PURPOSE: The RNASEL gene has been proposed as a candidate gene for the HPC1 locus through a positional cloning and candidate gene approach. Cosegregation between the truncating mutation E265X and disease in a hereditary prostate cancer (HPC) family and association between prostate cancer risk and the common missense variant R462Q has been reported. To additionally evaluate the possible role of RNASEL in susceptibility to prostate cancer risk, we performed a comprehensive genetic analysis of sequence variants in RNASEL in the Swedish population. EXPERIMENTAL DESIGN: Using 1624 prostate cancer cases and 801 unaffected controls, the truncating mutation E265X and five common sequence variants, including the two missense mutations R462Q and D541E, were evaluated for association between genotypes/haplotypes and prostate cancer risk. RESULTS: The prevalence of E265X carriers among unaffected controls and prostate cancer patients was almost identical (1.9 and 1.8% in controls and cases, respectively), and evidence for segregation of E265X with disease was not observed within any HPC family. Overall, the analyses of common sequence variants provided limited evidence for association with prostate cancer risk. We found a marginally significant inverse association between the missense mutation D541E and sporadic prostate cancer risk (odds ratio, 0.77; 95% confidence interval, 0.59-1.00) and reduced risk of prostate cancer in carriers of two different haplotypes being completely discordant. CONCLUSIONS: Considering the high quality in genotyping and the size of this study, these results provide solid evidence against a major role of RNASEL in prostate cancer etiology in Sweden.     

慢性淋巴细胞白血病503例临床及实验室特征回顾性分析

目的 探讨慢性淋巴细胞白血病(CLL)患者的临床及主要实验室特征.方法 回顾性分析1998年10月至2015年2月收治的503例CLL患者的临床及实验室检查资料,应用χ2检验进行差异性检验,并利用Log-rank法检验各组患者生存率的差异.结果 503例CLL患者中位年龄58岁(26~86岁),男性335例,女性168例.初诊时临床分期以Binet A期为主,为204例(40.5%),其次为Binet B期和C期,分别为148例(30.1%)和151例(29.3%).初诊时108例(21.1%)患者存在贫血(血红蛋白<100 g/L);427例进行血清乳酸脱氢酶检测的患者中,有113例(26.5%)升高;344例进行CD38检测的患者中有100例(29.1%)表达阳性.330例具有完整荧光原位杂交(FISH)资料的患者中,156例(47.3%)伴13q缺失(13q-),为检出率最高的细胞遗传学异常;其次为IgH易位(22.4%),12号染色体三体(+12,21.2%)和17p缺失(17p-,14.5%).在230例进行免疫球蛋白重链可变区(IGHV)突变状态检测的患者中,165例(71.7%)IGHV为突变状态,表达V4-34基因的患者比例最高,占12.4%(28例).中位无进展生存(PFS)时间为89.0个月(95%CI 75.0~103.0个月),中位总生存(OS)时间为129.0个月(95%CI 106.9~151.1个月).结论与欧美国家的CLL患者相比,本组CLL患者发病年龄偏低,总体生存期较长,一定程度上反映了我国CLL患者的特点.     

Clinical outcomes of surgical resections for primary liver sarcoma in adults: results from a single centre.

BACKGROUND: Primary hepatic sarcoma is a rare tumour with a poor prognosis. METHODS: From 1997 to 2002 eight patients had liver resection for primary sarcoma of the liver at our institution. The clinical characteristics, imaging findings, surgical procedures, adjuvant therapy and outcome were retrospectively reviewed. There were two patients each with angiosarcoma (AS), leiomyosarcoma (LMS), and undifferentiated embryonal sarcoma (UES), one patient with epithelioid hemangioendothelioma (EHE) and one patient with malignant peripheral nerve sheath sarcoma (PNSS). RESULTS: The most common presenting symptoms were right upper quadrant pain and fever. Typical imaging findings were a heterogenous mass with poorly defined margins, pseudocapsule and aberrant vasculature. Preoperative diagnosis of a primary liver sarcoma was made in 7/8 cases, either by fine needle aspiration (n = 5) or angiography (n = 2). Five right hepatectomies and three trisegmentectomies were performed. An R (0) resection was possible in three cases. Two patients developed complications and there was one death. Adjuvant chemoradiotherapy was administered to 5/7 patients. Systemic chemotherapy led to tumour regression in both patients with UES which enabled a second hepatic resection. CONCLUSIONS: The majority of patients with primary liver sarcoma present with right upper quadrant pain, fever and a liver mass. Differentiating the rare primary liver sarcoma from the much more common hepatocellular carcinoma (HCC) may aid in planning therapy. Patients with resectable tumours should be referred for surgery. Liver resection combined with adjuvant chemotherapy are the mainstays of treatment for UES in the adult.