Carcinoma and multiple lymphomas in one patient: establishing the diagnoses and analyzing risk factors

Multiple malignancies may occur in the same patient, and a few reports describe cases with multiple hematologic and non-hematologic neoplasms. We report the case of a patient who showed the sequential occurrence of four different lymphoid neoplasms together with a squamous cell carcinoma of the lung. A 62-year-old man with adenopathy was admitted to the hospital, and lymph node biopsy was positive for low-grade follicular lymphoma. He achieved a partial remission with chemotherapy. Two years later, a PET-CT scan showed a left hilar mass in the lung; biopsy showed a squamous cell carcinoma. Simultaneously, he was diagnosed with diffuse large B cell lymphoma in a neck lymph node; after chemo- and radiotherapy, he achieved a complete response. A restaging PET-CT scan 2 years later revealed a retroperitoneal nodule, and biopsy again showed a low-grade follicular lymphoma, while a biopsy of a cutaneous scalp lesion showed a CD30-positive peripheral T cell lymphoma. After some months, a liver biopsy and a right cervical lymph node biopsy showed a CD30-positive peripheral T cell lymphoma consistent with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. Flow cytometry and cytogenetic and molecular genetic analysis performed at diagnosis and during the patient’s follow-up confirmed the presence of two clonally distinct B cell lymphomas, while the two T cell neoplasms were confirmed to be clonally related. We discuss the relationship between multiple neoplasms occurring in the same patient and the various possible risk factors involved in their development.     

国产利妥昔单抗治疗弥漫大B细胞淋巴瘤的疗效及安全性

摘要 目的：探讨弥漫大B细胞淋巴瘤患者采用国产利妥昔单抗为基础的化疗方案的疗效及安全性。方法：回顾性分析2020年3月至2022年5月份在安徽省第二人民医院血液内科诊治的弥漫大B淋巴瘤患者31例,均接受国产利妥昔单抗为基础的联合方案化疗,其中非生发中心来源的弥漫大B细胞淋巴瘤患者25例,生发中心来源的弥漫大B细胞淋巴瘤患者6例。21~28 d为一个疗程,这些患者至少接受2~8个疗程的联合化疗,并且2个疗程以后进行疗效评估及不良反应监测。结果：①本研究31例弥漫大B细胞淋巴瘤患者接受利妥昔单抗为基础的联合化疗方案治疗后,疗效评估为完全缓解CR 16例（51.6%）,部分缓解PR 10例（32.3%）,疾病稳定SD 2例（6.5%）,疾病进展PD 3例（9.7%）,总体反应率ORR 83.9%。②31例弥漫大B细胞淋巴瘤患者接受国产利妥昔单抗治疗后,常见的不良反应发生率依次为：血液学毒性29.0%（9/31）,包括中性粒细胞减少、血小板减少等等。其次为感染19.4%（6/31）、消化道症状16.1%（5/31）,包括腹痛、腹泻、便秘等等。所有常见不良反应经过对症处理后均可好转。仅有1例患者发生过敏反应3.2%（1/31）,1例患者因病情严重而死亡。结论：国产利妥昔单抗在弥漫大B细胞淋巴瘤患者的治疗中具有良好的临床疗效及安全性,不良反应较少,值得进一步探讨和应用。     

NK cell lymphoma, nasal type, with massive lung involvement: a case report

Extranodal NK/T cell lymphoma, nasal type, is an Epstein–Barr virus-associated lymphoma that most commonly involves the nasal cavity and upper respiratory tract. Lung involvement by NK/T cell lymphoma is rare and seldom reported in the literature. We describe the unusual case of a 41-year-old male with NK cell lymphoma, nasal type, who presented with massive secondary lung involvement 2.5 years after the detection of a retroperitoneal mass. The diagnosis was made by open lung biopsy. Despite aggressive treatment, the patient died shortly after the initiation of therapy. Lung involvement by NK/T cell lymphoma occurs most commonly as part of widely disseminated disease and carries a poor prognosis for the patient. Novel agents and innovative therapies need to be developed for this aggressive lymphoma.     

Gray zones around diffuse large B cell lymphoma. Conclusions based on the workshop of the XIV meeting of the European Association for Hematopathology and the Society of Hematopathology in Bordeaux, France

The term “gray-zone” lymphoma has been used to denote a group of lymphomas with overlapping histological, biological, and clinical features between various types of lymphomas. It has been used in the context of Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL), including classical HL (CHL), and primary mediastinal large B cell lymphoma, cases with overlapping features between nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B cell lymphoma, CHL, and Epstein–Barr-virus-positive lymphoproliferative disorders, and peripheral T cell lymphomas simulating CHL. A second group of gray-zone lymphomas includes B cell NHL with intermediate features between diffuse large B cell lymphoma and classical Burkitt lymphoma. In order to review controversial issues in gray-zone lymphomas, a joint Workshop of the European Association for Hematopathology and the Society for Hematopathology was held in Bordeaux, France, in September 2008. The panel members reviewed and discussed 145 submitted cases and reached consensus diagnoses. This Workshop summary is focused on the most controversial aspects of gray-zone lymphomas and describes the panel’s proposals regarding diagnostic criteria, terminology, and new prognostic and diagnostic parameters.     

Prognostic impact of C-REL expression in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) phenotype is believed to confer a better prognosis than DLBCL with an activated B-cell (ABC) phenotype. Previous studies have suggested that nuclear factor-κB (NF-κB) activation plays an important role in the ABC subtype of DLBCL, whereas c-REL amplification is associated with the GCB subtype. Using immunohistochemical techniques, we examined 68 newly diagnosed de novo DLBCL cases (median follow-up 44 months, range 1 to 142 months) for the expression of c-REL, BCL-6, CD10, and MUM1/IRF4. Forty-four (65%) cases demonstrated positive c-REL nuclear expression. In this cohort of patients, the GCB phenotype was associated with a better overall survival (OS) than the non-GCB phenotype (Kaplan–Meier survival (KMS) analysis, p = 0.016, Breslow–Gehan–Wilcoxon test). In general, c-REL nuclear expression did not correlate with GCB vs. non-GCB phenotype, International Prognostic Index score, or OS. However, cases with a GCB phenotype and negative nuclear c-REL demonstrated better OS than cases with a GCB phenotype and positive nuclear c-REL (KMS analysis, p = 0.045, Breslow–Gehan–Wilcoxon test), whereas in cases with non-GCB phenotype, the expression of c-REL did not significantly impact the prognosis. These results suggest that c-REL nuclear expression may be a prognostic factor in DLBCL and it may improve patient risk stratification in combination with GCB/non-GCB phenotyping.     

Prospective investigation of transfusion transmitted infection in recipients of over 20 000 units of blood. TTI Study Group

ObjectivesTo follow up recipients of 20 000 units of blood to identify any transmissions of infections through blood transfusion.DesignFollow up study of recipients of transfusion.Setting 22 hospitals in north London.ParticipantAdult patients who had recently been transfused.Results9220 patients were recruited, and 5579 recipients of 21 923 units of blood were followed up. No transfusion transmitted infections were identified. The incidence of transfusion transmitted infections was 0 in 21 043 units (95% confidence interval for risk 0 to 1 in 5706 recipients) for hepatitis B; 0 in 21 800 units (0 to 1 in 5911 recipients) for hepatitis C; 0 in 21 923 units (0 to 1 in 5944 recipients) for HIV; and 0 in 21 902 units (0 to 1 in 5939 recipients) for human T cell leukaemia/lymphoma virus. Three patients acquired hepatitis B during or after hospital admission but not through transfusion; 176 (3%) had pre-existing hepatitis B infection. Sixteen (0.29%) patients had hepatitis C, and five (0.09%) had human T cell leukaemia/lymphoma virus.ConclusionsThe current risk of transfusion transmitted infections in the United Kingdom is very small, though hospital acquired infections may arise from sources other than transfusion. A considerable proportion of patients have pre-existing infections.     

Lack of evidence for changing virulence of HIV-1 in North America

Background

Several long-term cohort studies and in-vitro fitness assays have resulted in inconsistent reports on changes in HIV-1 virulence, including reports of decreasing, stable, and increasing virulence over the course of the AIDS pandemic. We tested the hypothesis of changing HIV-1 virulence by examining trends in prognostic clinical markers of disease progression from 1984 to 2005 among nearly 400 antiretroviral-naïve participants in the United States Multicenter AIDS Cohort Study (MACS), a longitudinal study of HIV infection in men who have sex with men (MSM).

Methodology/Principal Findings

Because clinical AIDS endpoints could not be used (due to antiretroviral therapies and prophylaxis), three prognostic markers of disease progression were used as proxies for HIV-1 virulence: plasma viral RNA load and CD4+ T cell count at “set point” (between ∼9 and ∼15 months after seroconversion), and rate of CD4 cell decline within three years after seroconversion. We performed multivariate analyses of the association between these markers and seroconversion year, with covariates including MACS site, race/ethnic group, seroconversion age, and CCR5Δ32 status. No statistically significant association was found between year of seroconversion and “set point” plasma viral load (at ∼9 months after seroconversion: slope = −0.004 log₁₀ copies/mL/year, p = 0.76; at ∼15 months: slope = −0.005 log₁₀ copies/mL/year, p = 0.71), CD4 cell count after seroconversion (at ∼9 months: slope = −0.112 cells/µL/year, p = 0.22; at ∼15 months: slope = −0.047 cells/µL/year, p = 0.64), or rate of CD4 cell decline over the first three years after seroconversion (slope = −0.010 cells/ul/yr², p = 0.88).

Conclusions/Significance

The lack of significant trends from 1984 to 2005 in these prognostic markers of HIV disease progression suggests no major change in HIV-1 virulence over the AIDS pandemic in MSM in the US.     

Implementation of guidelines for implantable cardioverter-defibrillator therapy in clinical practice: Which patients do benefit?

Purpose

Based on multiple large clinical trials conducted over the last decades guidelines for implantable cardioverter-defibrillator (ICD) implantations have been evolving. The increase in primary prophylactic ICD implantations challenges us to be critical towards the indications in certain patient populations.

Methods

We retrospectively collected patient characteristics and rates of appropriate and inappropriate ICD therapy, appropriate and inappropriate ICD shock and mortality of all patients who received an ICD in the University Medical Center Utrecht (UMCU) over the years 2006–2011.

Results

A total of 1075 patients were included in this analysis (74 % male, mean age 61 ± 13 years, left ventricular ejection fraction 30 ± 13 %); 61 % had a primary indication and 58 % had ischaemic heart disease. During a mean follow-up period of 31 ± 17 months, 227 of the patients (21 %) received appropriate ICD therapy (149 (14 %) patients received an appropriate ICD shock). Females, patients with a primary prophylactic indication and patients with non-ischaemic heart disease experienced significantly less ICD therapy. Only a few patients (54, 5 %) received inappropriate ICD therapy; 33 (3 %) patients received an inappropriate ICD shock. Fifty-five patients died within one year after ICD implantation and were therefore, in retrospect, not eligible for ICD implantation.

Conclusion

Our study confirms the benefit of ICD implantation in clinical practice. Nevertheless, certain patients experience less benefit than others. A more patient-tailored risk stratification based on electrophysiological parameters would be lucrative to improve clinical benefit and cost-effectiveness.     

Follow-up of implantable cardioverter-defibrillator therapy: comparison of coronary artery disease and dilated cardiomyopathy

Purpose

Since several large trials have proven the effectiveness of implantable cardioverter-defibrillators (ICDs) in patients with left ventricular dysfunction, disadvantages have become more apparent. As the prognosis of patients with cardiovascular diseases is improving, assessment of ICD patients and re-evaluation of the current guidelines is mandatory. We aimed to evaluate differences in mortality and occurrence of (in)appropriate shocks in ICD patients with coronary artery disease (CAD) or dilated cardiomyopathy (DCM).

Methods

In a large teaching hospital, all consecutive patients with systolic dysfunction due to CAD or DCM who received an ICD with and without resynchronisation therapy, were collected in a database.

Results

A total of 320 consecutive patients (age 67 ± 10 years) were classified as CAD patients and 178 (63 ± 11 years) as DCM patients. Median follow-up was 40 months (interquartile range [IQR] 23─57 months). All–cause mortality was 14 % (CAD 15 % vs DCM 13 %). Appropriate shocks occurred in 13 % of all patients (CAD 15 % vs DCM 11 %, p = 0.12) and inappropriate shocks occurred in 10 % (CAD 8 % vs DCM 12 %, p = 0.27). Multivariate analysis demonstrated impaired left ventricular ejection fraction, QRS >120, age ≥75 years and low estimated glomerular filtration rate as predictors for all-cause mortality. Predictors for inappropriate shocks were permanent and paroxysmal atrial fibrillation.

Conclusion

Mortality rates were similar in patients with CAD and DCM who received an ICD. Furthermore, no differences were found in the occurrence of appropriate and inappropriate ICD interventions between these patient groups.     

Diffuse large B cell lymphoma presenting as Horner's syndrome in a patient diagnosed with neurofibromatosis type 1: a case report and review of the literature

Introduction

Horner's syndrome has a variety of etiologies ranging from benign to serious life-threatening conditions and has been infrequently reported as a presenting symptom of patients with lymphoid neoplasms. Only one case of Burkitt's lymphoma presenting with toothache, paresthesia, and Horner's syndrome has been described and no case reports of diffuse large B-cell lymphoma as the etiology of Horner's syndrome currently exist in the literature. In addition, lymphoid neoplasms have rarely been reported to occur in patients with neurofibromatosis type 1 despite an increased risk of many types of cancer in such cases.

Case presentation

A 28-year-old Thai man presented with a progressively enlarged left supraclavicular mass together with a significant weight loss and night sweating for four months. He also noticed hoarseness and ptosis of his left eye associated with double vision for two months. Physical examination revealed large supraclavicular lymphadenopathy and Horner's syndrome (ptosis, miosis, and anhydrosis) on the left side of his face. A large mediastinal mass was clearly detected by chest X-ray and computed tomography and subsequent lymph node biopsy provided a diagnosis of diffuse large B-cell lymphoma. Interestingly, the patient was also definitely diagnosed with neurofibromatosis type 1 from multiple café au lait macules, axillary freckles, three neurofibromas, multiple Lisch nodules, and a history of affected family members. He subsequently received chemotherapy with a good response. Twenty-seven cases of various types of lymphoid neoplasms previously reported to occur in neurofibromatosis type 1 patients were also extracted from the literature. All cases were non-Hodgkin lymphoma and the major subtype was T-cell. Only nine cases were B-cell lymphoma. The majority of cases were young with a median age at lymphoma diagnosis of 9.4 years (range 1.1 to 77 years). Two-thirds of the cases were boys or men. Other concomitant malignancies were brain tumor, colorectal cancer, pheochromocytoma, and acute lymphoblastic leukemia.

Conclusions

We describe for the first time a case of diffuse large B-cell lymphoma that occurred in a neurofibromatosis type 1 patient with Horner's syndrome. Horner's syndrome can be an initial manifestation of diffuse large B-cell lymphoma. Patients who present with a classical triad of Horner's syndrome should always be fully investigated for lymphomatous involvement, especially in the thorax. The exact molecular mechanism for diffuse large B-cell lymphoma development in neurofibromatosis type 1 cases remains to be elucidated.     

Primary gastric T cell lymphoma mimicking marginal zone B cell lymphoma of mucosa-associated lymphoid tissue

Primary gastric T cell lymphoma is rare and mostly of large cell type. In this paper, we present a case of gastric T cell lymphoma morphologically similar to the gastric marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT). Morphologically, the cells are small with abundant clear cytoplasm. Lymphoepithelial lesions are readily identified with diffuse destruction of gastric glands. Immunohistochemically, the neoplastic cells are CD3+/CD4+/CD8−/Granzyme B−. Molecular studies revealed monoclonal T cell receptor γ gene rearrangement. Clinically, the patient responded initially to four cycles of R-CHOP, but then progressed. Because peripheral T cell lymphoma is usually associated with a poor prognosis, whereas marginal zone B cell lymphoma is an indolent lymphoproliferative disorder, this morphologic mimicry should be recognized and completely investigated when atypical small lymphoid infiltrates with lymphoepithelial lesions are encountered in the stomach.     

利妥昔单抗联合化疗治疗弥漫型大B细胞淋巴瘤患者的临床研究

目的:探讨利妥昔单抗与化疗相结合治疗弥漫型大B细胞淋巴瘤(diffuse large Bcelllymphoma,DLBCL)患者的可行性。方法:选取2002年1月至2011年5月我院收治的84例CD20阳性的DLBCL患者,采用利利妥昔单抗与化疗相结合的方法治疗,对其疗效及安全性进行评价,并对其影响因素进行分析。结果:有56例患者治疗艹6个周期,占66.67%;有28例患者治疗6个周期,占33.33%。84例患者治疗的总有效率为83.33%。其中,初治组的总有效率为91.67%,明显高于复治组的62.5%,差异有统计学意义(P0.05)。红细胞沉降率、国际预后指数评分、是否为初治、是否存在B症状以及利妥昔单抗的治疗周期等变量成为影响治疗效果的独立危险因素(P0.05)。随访5年,治疗后第l年、2年、3年和5年患者的生存率分别为88.1%(74/84)、72.62%(61/84)、60.71%(51/84)、60.71%(51/84)。国际预后指数评分、利妥昔单抗的治疗周期以及治疗效果等变量是影响患者生存的独立危险因素(P0.05)。结论:对于弥漫型大B细胞淋巴瘤患者尤其是对初治患者而言,利妥昔单抗联合化疗治疗具有更好的治疗效果,临床应用时不会加重患者的不良反应。     

Survival outcomes and effect of early vs. deferred cART among HIV-infected patients diagnosed at the time of an AIDS-defining event: a cohort analysis

Objectives

We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART).

Methods

Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997–2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (<30 days after AIDS event) or deferred (30–270 days after AIDS event) cART.

Results

The median (interquartile range) CD4 count and viral load (VL) at diagnosis of the 584 patients were 42 (16, 119) cells/µL and 5.2 (4.5, 5.7) log₁₀ copies/mL. Clinical progression was observed in 165 (28.3%) patients. Older age, a higher VL at diagnosis, and a diagnosis of non-Hodgkin lymphoma (NHL) (vs. other AIDS events) were independently associated with disease progression. Of 366 patients with an opportunistic infection, 178 (48.6%) received early cART. There was no significant difference in clinical progression between those initiating cART early and those deferring treatment (adjusted hazard ratio 1.32 [95% confidence interval 0.87, 2.00], p = 0.20).

Conclusions

Older patients and patients with high VL or NHL at diagnosis had a worse outcome. Our data suggest that earlier initiation of cART may be beneficial among HIV-infected patients diagnosed with clinical AIDS in our setting.     

A Pilot Study of Diffusion-Weighted MRI in Patients Undergoing Neoadjuvant Chemoradiation for Pancreatic Cancer

PURPOSE: In the current study we examined the ability of diffusion MRI (dMRI) to predict pathologic response in pancreatic cancer patients receiving neoadjuvant chemoradiation. METHODS: We performed a prospective pilot study of dMRI in patients with resectable pancreatic cancer. Patients underwent dMRI prior to neoadjuvant chemoradiation. Surgical specimens were graded according to the percent tumor cell destruction. Apparent diffusion coefficient (ADC) maps were used to generate whole-tumor derived ADC histogram distributions and mean ADC values. The primary objective of the study was to correlate ADC parameters with pathologic and CT response. RESULTS: Ten of the 12 patients enrolled on the study completed chemoradiation and had surgery. Three were found to be unresectable at the time of surgery and no specimen was obtained. Out of the 7 patients who underwent pancreaticoduodenectomy, 3 had a grade III histopathologic response (> 90% tumor cell destruction), 2 had a grade IIB response (51% to 90% tumor cell destruction), 1 had a grade IIA response (11% to 50% tumor cell destruction), and 1 had a grade I response (> 90% viable tumor). Median survival for patients with a grade III response, grade I-II response, and unresectable disease were 25.6, 18.7, and 6.1 months, respectively. There was a significant correlation between pre-treatment mean tumor ADC values and the amount of tumor cell destruction after chemoradiation with a Pearson correlation coefficient of 0.94 (P = .001). Mean pre-treatment ADC was 161 × 10^− 5 mm²/s (n = 3) in responding patients (> 90% tumor cell destruction) compared to 125 × 10^− 5 mm²/s (n = 4) in non-responding patients (> 10% viable tumor). CT imaging showed no significant change in tumor size in responders or non-responders. CONCLUSIONS: dMRI may be useful to predict response to chemoradiation in pancreatic cancer. In our study, tumors with a low ADC mean value at baseline responded poorly to standard chemoradiation and would be candidates for intensified therapy.     

Molecular analysis of primary central nervous system and primary intraocular lymphomas

Primary central nervous system lymphoma (PCNSL) is usually a large B-cell, high grade non-Hodgkin's lymphoma (NHL) classified as a diffuse large cell lymphoma (DLCL). In rare cases, however, T cell lymphomas have been described. Although a relatively rare tumor, the incidence of PCNSL has increased dramatically over the past 15 years in both immuno-competent and immunocompromised patients. The disease is aggressive with a 5-year survival rate of less than 25 %. The cause of death is progressive and recurrent disease in the CNS, despite aggressive treatment. Approximately 20-25% of patients with PCNSL also have primary intra-ocular lymphoma (PIOL). PCNSL and PIOL are closely related and inter-connected pathologies involving two immune privileged sites. The study of PCNSL and PIOL has been limited due to the fact that viable malignant cells are rare and difficult to recognize. Moreover, the cells are difficult to culture and to date there is no good animal model for the disease. Here, we will present the current literature on the disease. In particular, we will present data suggesting that PCNSL in immuno-compromised and AIDS patients may correspond to two different pathologies. Furthermore, we will discuss how the study of these lymphomas can benefit from new advanced molecular biology techniques including single cell PCR and laser capture microdissection (LCM). PCNSL and PIOL are aggressive tumors, therefore, early diagnosis and prompt, aggressive treatment may improve prognosis. Advanced molecular biology will help delineate the oncogenesis of PCNSL and PIOL.     

利妥昔单抗维持治疗弥漫大B 细胞淋巴瘤的初步研究

目的:对弥漫大B细胞淋巴瘤患者进行利妥昔单抗维持治疗(Maintenance Rituximab,MR)的安全性及疗效的研究和探讨.方法:38例患者诱导治疗结束后根据患者及家属意见和经济条件分为MR组和观察组.每组19例.诱导治疗阶段两组患者均接受6～8个疗程R-CHOP(每3周)或R-EPOCH方案治疗.维持阶段,利妥昔单抗在诱导治疗完成后4-8周开始,375mg/m2,每3个月1次共2年(8次)或直至疾病复发、进展、死亡.维持前均经影像学检查证实无复发.结果与结论:MR对R-EPOCH或R-CHOP的诱导治疗后达到CRu/CR初治DLBCL病人,有很好的近期疗效,能提高其DFS率,但OS率无改善,而且其毒副反应小,可以耐受.     

Overexpression of microRNAs from the miR-17-92 paralog clusters in AIDS-related non-Hodgkin's lymphomas

Background

Individuals infected by HIV are at an increased risk for developing non-Hodgkin''s lymphomas (AIDS-NHL). In the highly active antiretroviral therapy (HAART) era, there has been a significant decline in the incidence of AIDS-associated primary central nervous system lymphoma (PCNSL). However, only a modest decrease in incidence has been reported for other AIDS-NHL subtypes. Thus, AIDS-NHLs remain a significant cause of morbidity and mortality in HIV infected individuals. Recently, much attention has been directed toward the role of miRNAs in cancer, including NHL. Several miRNAs, including those encoded by the miR-17-92 polycistron, have been shown to play significant roles in B cell tumorigenesis. However, the role of miRNAs in NHL in the setting of HIV infection has not been defined.

Methodology/Principal Findings

We used quantitative realtime PCR to assess the expression of miRNAs from three different paralog clusters, miR-17-92, miR-106a-363, and miR-106b-25 in 24 cases of AIDS-NHLs representing four tumor types, Burkitt''s lymphoma (BL, n = 6), diffuse large B-cell lymphoma (DLBCL, n = 8), primary central nervous system lymphoma (PCNSL, n = 5), and primary effusion lymphoma (PEL, n = 5). We also used microarray analysis to identify a differentiation specific miRNA signature of naïve, germinal center, and memory B cell subsets from tonsils (n = 4). miRNAs from the miR-17-92 paralog clusters were upregulated by B cells, specifically during the GC differentiation stage. We also found overexpression of these miRNA clusters in all four AIDS-NHL subtypes. Finally, we also show that select miRNAs from these clusters (miR-17, miR-106a, and miR-106b) inhibited p21 in AIDS-BL and DLBCL cases, thus providing a mechanistic role for these miRNAs in AIDS-NHL pathogenesis.

Conclusion

Dysregulation of miR-17-92 paralog clusters is a common feature of AIDS-associated NHLs.     

Ki-67 as a prognostic marker in mantle cell lymphoma��consensus guidelines of the pathology panel of the European MCL Network

Mantle cell lymphoma (MCL) has a heterogeneous clinical course and is mainly an aggressive B cell non-Hodgkin lymphoma; however, there are some indolent cases The Ki-67 index, defined by the percentage of Ki-67-positive lymphoma cells on histopathological slides, has been shown to be a very powerful prognostic biomarker. The pathology panel of the European MCL Network evaluated methods to assess the Ki-67 index including stringent counting, digital image analysis, and estimation by eyeballing. Counting of 2 × 500 lymphoma cells is the gold standard to assess the Ki-67 index since this value has been shown to predict survival in prospective randomized trials of the European MCL Network. Estimation by eyeballing and digital image analysis showed a poor concordance with the gold standard (concordance correlation coefficients [CCC] between 0.29 and 0.61 for eyeballing and CCC of 0.24 and 0.37 for two methods of digital image analysis, respectively). Counting a reduced number of lymphoma cells (2 × 100 cells) showed high interobserver agreement (CCC = 0.74). Pitfalls of the Ki-67 index are discussed and guidelines and recommendations for assessing the Ki-67 index in MCL are given.     

Antithrombotic therapy in patients undergoing TAVI: an overview of Dutch hospitals

Purpose

To assess current antithrombotic treatment strategies in the Netherlands in patients undergoing transcatheter aortic valve implantation (TAVI).

Methods

For every Dutch hospital performing TAVI (n = 14) an interventional cardiologist experienced in performing TAVI was interviewed concerning heparin, aspirin, thienopyridine and oral anticoagulation treatment in patients undergoing TAVI.

Results

The response rate was 100 %. In every centre, a protocol for antithrombotic treatment after TAVI was available. Aspirin was prescribed in all centres, concomitant clopidogrel was prescribed 13 of the 14 centres. Duration of concomitant clopidogrel was 3 months in over two-thirds of cases. In 2 centres, duration of concomitant clopidogrel was based upon type of prosthesis: 6 months versus 3 months for supra-annular and intra-annular prostheses, respectively.

Conclusions

Leaning on a small basis of evidence and recommendations, the antithrombotic policy for patients undergoing TAVI is highly variable in the Netherlands. As a standardised regimen might further reduce haemorrhagic complications, large randomised clinical trials may help to establish the most appropriate approach.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-013-0496-6) contains supplementary material, which is available to authorized users.     

Development and Clinical Evaluation of Clotrimazole–β-Cyclodextrin Eyedrops for the Treatment of Fungal Keratitis

Fungal keratitis is a serious corneal disease that may result in loss of vision. There are limited treatment options available in Iraqi eye hospitals which might be the main reason behind the poor prognosis of many cases. The purpose of this study was to prepare and pharmaceutically evaluate clotrimazole–β-cyclodextrin (CTZ–β-CD) eyedrops then clinically assess its therapeutic efficacy on fungal keratitis compared with extemporaneous amphotericin B eyedrops (0.5% w/v). A CTZ–β-CD ophthalmic solution was prepared and evaluated by various physicochemical, microbiological, and biological tests. The prepared formula was stable in 0.05 M phosphate buffer pH 7.0 at 40 ± 2°C and 75 ± 5% RH for a period of 6 months. Light has no significant effect on the formula’s stability. The CTZ–β-CD eyedrops efficiently complied with the isotonicity, sterility, and antimicrobiological preservative effectiveness tests. Results of the clinical study revealed that 20 (80%) patients showed a favorable response to the CTZ–β-CD eyedrops, while 16 patients (64%) exhibited a favorable response to amphotericin B (P > 0.05). The mean course of treatment was significantly (P < 0.05) less in the CTZ treatment group than in the amphotericin group (21.5 ± 5.2 vs. 28.3 ± 6.4 days, respectively). The CTZ formulation was significantly (P < 0.05) more effective in the management of severe cases and also against Candida sp. than amphotericin B. There was no significant difference (P < 0.05) between both therapies against filamentous fungi. The CTZ–β-CD formulation can be used alternatively to other ophthalmic antimycotic treatment options in developing countries where stability, cost, or efficacy is a limiting factor.Key words: clotrimazole, β-cyclodextrin, eyedrops, fungal keratitis, Iraq