Building a bioresource for esophageal research: lessons from the early experience of an academic medical center

The establishment of biorepositories, linked to clinical and epidemiologic data, are central to the goals of personalized medicine and individualized cancer therapy. Repositories of DNA, RNA, and serum samples are valuable resources for cancer research, enabling the investigation of the underlying causes of cancer development, progression, and prognosis, as well as providing a resource for the investigation of biomarkers for early detection and prediction of response. With a greater reliance on sample‐derived data for molecular‐based research and clinical care, improved standards and informatics for sample procurement, storage, and analysis are necessary to maximize the value of tissue collection for research participants, investigators, and academic medical centers. We present herein the experience of an academic medical center in establishing a repository for esophageal research, with discussion of elements to be considered when establishing such a resource, from the quality assurance of samples to the organized collection and storage of associated clinical data. The development of this biorepository required significant planning to identify and consent participants by dedicated clinical and research personnel. Ensuring the quality of any biobank is of utmost importance, and one must understand the sample variability that exists during the acquisition of biospecimens. The time and type of fixative have been optimized in our unit by standard operating protocols. Methods for biomolecule extraction were tested by examining both the quality and the quantity of recovered sample. These procedures were overseen by a designated biobank manager, responsible for the acquisition of the sample from surgery, which limits variability in sample collection. Our unit also has a dedicated database manager for the maintenance of quality clinical data linked to the bioresource. The development and expansion of such repositories, at local and national levels, is required to enable leading academic medical centers and their investigators to provide optimal and molecularly guided care to their patients.     

结核病与恶性肿瘤的关系探讨

目的探讨结核病与恶性肿瘤的关系。方法采用聚合酶链反应(PCR)技术检测恶性肿瘤组织中结核杆菌DNA(TB-DNA)。结果23例恶性肿瘤组织中检出TB-DNA阳性患者5例,占总数的21.7%,且TB-DNA阳性患者肿瘤发病部位与结核病的好发部位基本一致。结论结核杆菌感染与一些恶性肿瘤之间可能存在着相关性。     

Principles and present status of a prospective multicenter study on the clinical relevance of the kiel classification

Summary On the basis of the retrospective analysis of 405 patients, suggesting the clinical relevance of the Kiel classification of non-Hodgkin lymphomas (NHL), a prospective multicenter study was started on October 1st, 1975, by the Kiel Lymphoma Study Group in order to further clarify the clinical and prognostic features of the different lymphoma entities defined by this histopathologic scheme. Diagnostic protocol provides initial staging evaluation according to a modification of the Ann Arbor classification. Therapeutic approach is based on the hypothesis that, like Hodgkin's disease, NHL originate, at least in part, as localized lymphatic or extralymphatic tumors. Thus, extended field irradiation is performed in stages I and II (except for lymphoblastic lymphoma in children and young adults) whereas in the more advanced stages III and IV (except for stage III of centroblastic-centrocytic lymphoma) chemotherapy with additional radiotherapy is applied. Until June 1979, 815 patients entered the study (69.7% with NHL of low-grade malignancy). For the interim evaluation underlying the present and the other papers of this series data of 511 patients were available. Survival of patients with NHL of low-grade malignancy significantly exceeds that of patients with NHL of high-grade malignancy. NHL with good prognosis such as chronic lymphocytic leukaemia and centroblastic-centrocytic lymphoma can be differentiated from NHL with a poor course such as lymphoblastic and immunoblastic lymphomas. In addition, the existence of a third group with an intermediate prognosis comprising centrocytic and centroblastic lymphomas and, possibly, also LP immunocytoma is suggested. However, different initial slope of survival curves shows that this latter group of NHL is not homogeneous with regard to prognosis.Supported by the Deutsche Krebshilfe e. V., Bonn, and the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg (Sonderforschungsbereich No 102: Experimentelle und klinische Leukämie- und Tumorforschung, Essen)Presented in part at the 5th Meeting of the International Society of Haematology, Europe-an and African Division, Hamburg, August 26–31, 1979     

Particle-bound DNA polymerase activity in haematological disorders and normal controls

Summary A DNA polymerase present in particles with a density greater than 1.20 g/cm³ and capable of using a synthetic RNA template has been sought in human malignancies. This report deals with a study of a great number of peripheral-blood samples from normal controls and patients with malignant and non-neoplastic haematological disorders. For screening purposes a simplified detection test was used. In 63 controls low levels of enzyme activity were found. The enzyme activities showed a biphasic distribution pattern. Three out of 53 patients with non-neoplastic, miscellaneous haematological disorders had an elevated enzyme level associated with active viral infections (hepatitis, mononucleosis infectiosa). In 128 patients suffering from haematological malignancies 18 out of 21 cases of elevated enzyme level were associated with the presence of more than 10% pathological cells in the white blood cell fraction.Supported by the Queen Wilhelmina Foundation, Netherlands Organization for the Fight against Cancer     

Hepatocellular cancer in liver transplantation

Hepatocellular carcinoma (HCC) is a malignant epithelial tumor that accounts for over 80% of primary liver tumors. It affects males more than females, and is responsible for over 1 million yearly deaths worldwide. HCC tends to be relentless in nature and of rapid evolution. Most cases of HCC are associated with cirrhosis, usually caused by chronic viral hepatitis or alcohol ingestion. In cases of established cirrhosis, HCC develops with an annual incidence of 3–10%. Hepatocellular carcinoma may present in a generalized way with overall clinical deterioration and malaise, as a palpable liver mass, or as an asymptomatic lesion that is discovered incidentally. Alpha‐fetoprotein (AFP) measurements allow for the differentiation of HCC in cirrhotics, and can act as predictive markers. Patients with cirrhosis and small tumors (up to 3 cm, or 5 cm if solitary), no more than three nodules, and no portal vein involvement were found to benefit more from orthotopic liver transplantation (OLTx) than from resection. Tumors under 3 cm in size were unlikely to recur, while those over 5 cm posed the greatest risk. An incidental HCC in a transplant patient should be treated as seriously and aggressively as if the transplant had been undertaken for HCC.     

Myocardial Metastasis in Patient with Cholangiocarcinoma

Myocardium is a rare site for metastasis. We present here the case of myocardial metastasis from cholangiocarcinoma.     

Self-expandable metallic stents for malignant biliary obstruction： Efficacy on proximal and distal tumors

AIM:To compare the efficacy of self-expandable metallicstents (EMS) in the treatment of distal and proximalstricture of malignant biliary tumors.METHODS:From March 1995 to June 2004,61 patients(40 males,21 females) with malignant biliary obstructionwho received self-expandable metallic stent implantationwere reviewed retrospectively.The stents were insertedby an endoscopic or percutaneous transhepatic method.We tried to place two stents in the biliary system in Tor Y configuration in cases of hilar tumors with bilateralhepatic duct obstruction.The end points of the studywere stent occlusion or patient death.RESULTS:The mean time of stent patency was 421±67d in the group of proximal stricture( group Ⅰ) and 168±18 d in the group of distal stricture (group Ⅱ).Thedifference was significant in borderline between thetwo groups (P=0.0567).The mean survival time was574±76 d in group Ⅰ and 182 25 d in group Ⅱ.Therewas a significant difference between the two groups(P=0.0005).CONCLUSION:EMS implantation is a feasible,palliativemethod for unresectable malignant biliary obstruction.The clinical efficacy of EMS in patients with proximal hilartumors is better than that in patients with distal tumors.     

皮肌炎和多发性肌炎伴发肿瘤临床特点及文献回顾

目的比较皮肌炎(DM)、多发性肌炎(PM)合并肿瘤与未合并肿瘤患者的临床特点,寻找可能的危险因素。方法对北京协和医院2007至2012年诊断DM或PM合并肿瘤患者的临床资料进行回顾性分析,对DM或PM合并肿瘤与同期未合并肿瘤患者的临床表现、实验室检查、转归进行比较。检索近10年的炎性肌病合并肿瘤的中文文献,并进行回顾性分析。将文献资料结合本文病例进行描述性分析。结果北京协和医院2007年至2012年DM或PM合并肿瘤患者30例;2007年至2008年DM或PM患者105例,其中5例伴发恶性肿瘤,均为女性,DM4例、重叠综合征1例(DM合并SLE)。DM或PM合并恶性肿瘤患者的肺间质病变发生率低于未合并恶性肿瘤组(P=0.022)。中文文献及本文病例694例患者中,合并鼻咽癌的DM或PM患者最多(30.26%)。结论对于年龄偏大的炎性肌病患者,尤其不伴有肺间质病变及典型抗体的患者,应积极筛查肿瘤。鼻咽癌是DM或PM患者最常见的肿瘤类型,推荐对DM或PM患者行鼻咽部内镜检查提高肿瘤检出率。     

Current issues in the biology of AIDS-related lymphoma

Three important issues have been the focus of much recent attention in the biology of AIDS-related lymphomas. The altered epidemiology in the era of highly active antiretroviral therapy, the role of herpesviruses including human herpesvirus 8 and the molecular genetics of HIV-associated T-cell lymphomas. These topics are covered in this article and their potential application to the clinical management of AIDS-related lymphomas are discussed.     

TREATMENT OF MALIGNANCY-ASSOCIATED HYPERCALCEMIA WITH NORETHISTERONE: A CASE REPORT

Hypercalcemia is a common cause of morbidity in cancer patients. The mechanism of malignancy-associated hypercalcemia includes increased bone resorption and decreased renal calcium clearance which also occur in primary hyperparathyroidism. Norethisterone can inhibit bone resorption and has recently been shown to be effective treatment for mild hyperparathyroidism in post menopausal women. We report the successful use for the first time of norethisterone (5 mg daily) in a case of malignancy-associated hypercalcemia after other standard agents failed. (Aust NZ J Med 1989; 19: 51–54.)     

Clodronate Treatment in Patients with Malignancy-associated Hypercalcemia

ABSTRACT. Rastad J, Benson L, Johansson H, Knuutila M, Pettersson B, Wallfelt C, Åkerström G, Ljunghall S (Departments of Surgery and Internal Medicine, University Hospital, Uppsala, Sweden). Clodronate treatment in patients with malignancy-associated hypercalcemia. Acta Med Scand 1987; 221:489–94. The possibility of reducing symptomatic hypercalcemia and of maintaining total serum calcium concentrations <2.8 mmol/1 with clodronate (dichloromethylene bisphosphonate) was evaluated in 28 patients with various types of malignant tumors. Four episodes of hypercal-cemic crisis with mean serum calcium concentrations of 4.43 mmol/1 were controlled within 4–6 days of intravenous clodronate (4 mg/kg BW/day). This was accompanied by a moderate increase in serum creatinine values which, however, returned to pretreatment levels after therapy withdrawal in all but one case. Oral clodronate successfully reduced a mean serum calcium concentration of 3.16 mmol/1 in 22 out of 25 patients after 3–12 days (800–3 200 mg/ day). After reversal of the hypercalcemias oral clodronate controlled the serum calcium concentration for up to 42 weeks in six out of 15 patients After discontinuation of initial therapy five of seven recurrent hypercalcemias were successfully treated with oral or intravenous clodronate. Hypocalcemia and subjective side-effects were uncommon. It is concluded that clodronate is a valuable clinical tool in the management of patients with malignancy-associated hypercalcemia.     

Primary malignancies mistaken for pseudotumours in haemophilic patients

Pseudotumours are a rare complication of haemophilia. Surgery undertaken for pseudotumour on a lesion that is subsequently found to be malignant can be expected to adversely affect patient outcome. We present six case reports found from a literature search of patients with haemophilia who underwent surgery on what was a primary malignancy misdiagnosed as a pseudotumour and give a subsequent discussion.     

糖皮质激素受体水平与造血系统恶性肿瘤疗效关系的探讨

研究７６例造血系统恶性肿瘤的ＧＣＲ水平，其中淋巴瘤２５例，急淋１１例，急粒１８例，慢粒１３例，多发性骨髓瘤９例。结果显示：急淋病人ＧＣＲ水平与化疗疗效密切相关，急粒、慢粒、多发性骨髓瘤、淋巴瘤病人ＧＣＲ水平与化疗疗效无相关性。     

New leukemia in the course of therapy of acute lymphoblastic leukemia.

We have recently observed the development of second leukemia of a morphologically different type in three patients with acute lymphoblastic leukemia (ALL) while on therapy. The "second" leukemia occurred while on therapy at 23, 27, and 32 months of initial remission. All three were receiving systemic chemotherapy (CT) and prophylactic fractional irradiation to the central nervous system (CNS). The second leukemias in these three cases were one case of juvenile chronic myelogenous leukemia (JCML) and two cases of acute leukemia of the myeloblastic type by the usual morphologic criteria including the presence of Auer rods in one. In two cases a cytogenetically new clone was detected in the remission marrow 10 and 12 months preceding the overt change in clinical status. These three cases demonstrate that second leukemia occurs in patients with ALL and that some late "relapses" fall into this categpry. The possible etiologic role of modern intensive treatment regimens in the development of second leukemia is discussed.