Nodular regenerative hyperplasia: a deleterious consequence of chemotherapy for colorectal liver metastases?

AIMS: This report describes three patients suffering from nodular regenerative hyperplasia (NRH). METHODS: These patients have received six, 16 and 20 cycles of neoadjuvant 5-fluorouracil and oxaliplatin-based chemotherapy before planned extended hepatectomy. Two patients underwent uneventful portal vein embolization to hypertrophy the future remnant liver. RESULTS: At the end of chemotherapy, liver function tests deteriorated and portal hypertension appeared in two patients, including ascites, splenomegaly and oesophageal varices. Liver biopsy was performed through a percutaneous (two patients) or a transjugular approach (one patient) and allowed the diagnosis of NRH, which was considered to be a contraindication for major liver resection in all three patients, associated with extrahepatic disease progression in one patient. All patients died from neoplastic disease progression despite further chemotherapy at 6, 17 and 31 months following the diagnosis of NRH. One patient developed liver failure and ascites at the time of death. CONCLUSIONS: Physicians should be aware of the potential occurrence and therapeutic impact of NRH in patients suffering from CRLM and treated by neoadjuvant 5FU-oxaliplatin-based chemotherapy before major liver surgery.     

Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma

The pathogenesis of AIDS-related non-Hodgkin lymphomas (AIDS-NHLs) is associated with chromosomal translocations that deregulate the expression of various oncogenes. Recently, a novel mechanism of genetic lesion, termed aberrant hypermutation, has been identified in diffuse large B-cell lymphoma (DLBCL) of immunocompetent hosts. In these tumors, the somatic hypermutation (SHM) process that normally targets immunoglobulin V (IgV) genes in B cells appears to misfire and causes mutations in the 5' sequences of multiple proto-oncogenes, including PIM-1, PAX-5, RhoH/TTF, and c-MYC. To investigate whether aberrant hypermutation occurs also in AIDS-NHL, we studied the mutation profile of these 4 genes in various histologic subtypes. Mutations in 1 gene or more were detected in 19 of 39 (48.7%) AIDS-NHL cases (10 of 18 AIDS-diffuse large B-cell lymphoma; 4 of 11 AIDS-Burkitt lymphoma; 4 of 6 AIDS-primary effusion lymphoma; 1 of 4 AIDS-primary central nervous system lymphoma), with 9 of 39 (23.1%) cases carrying mutations in 2 or more genes. Overall, PIM-1 was mutated in 5 of 39 (12.8%), PAX-5 in 8 of 39 (20.5%), RhoH/TTF in 9 of 39 (23.1%), and c-MYC in 7 of 27 (25.9%) AIDS-NHL cases. Mutations were represented mainly by single base pair substitutions (n = 63) with rare deletions/insertions (n = 5) and displayed features typical of the IgV-associated SHM process. In addition, a number of mutations in PIM-1 and c-MYC were found to affect coding exons, leading to amino acid substitutions with likely functional consequences. Analysis of intraclonal heterogeneity documented that the aberrant hypermutation activity may be ongoing in at least some cases. These data indicate that aberrant hypermutation is associated with various subtypes of AIDS-NHL and may represent a major contributor to their pathogenesis.     

Centrosome amplification drives chromosomal instability in breast tumor development

Earlier studies of invasive breast tumors have shown that 60-80% are aneuploid and approximately 80% exhibit amplified centrosomes. In this study, we investigated the relationship of centrosome amplification with aneuploidy, chromosomal instability, p53 mutation, and loss of differentiation in human breast tumors. Twenty invasive breast tumors and seven normal breast tissues were analyzed by fluorescence in situ hybridization with centromeric probes to chromosomes 3, 7, and 17. We analyzed these tumors for both aneuploidy and unstable karyotypes as determined by chromosomal instability. The results were then tested for correlation with three measures of centrosome amplification: centrosome size, centrosome number, and centrosome microtubule nucleation capacity. Centrosome size and centrosome number both showed a positive, significant, linear correlation with aneuploidy and chromosomal instability. Microtubule nucleation capacity showed no such correlation, but did correlate significantly with loss of tissue differentiation. Centrosome amplification was detected in in situ ductal carcinomas, suggesting that centrosome amplification is an early event in these lesions. Centrosome amplification and chromosomal instability occurred independently of p53 mutation, whereas p53 mutation was associated with a significant increase in centrosome microtubule nucleation capacity. Together, these results demonstrate that independent aspects of centrosome amplification correlate with chromosomal instability and loss of tissue differentiation and may be involved in tumor development and progression. These results further suggest that aspects of centrosome amplification may have clinical diagnostic and/or prognostic value and that the centrosome may be a potential target for cancer therapy.     

Carotid artery stenting in the presence of contralateral carotid occlusion: mind the hyperperfusion syndrome!

Stroke is the third cause of death in western countries and its complications lead to significant socio-economic problems related to the prolonged hospitalization and rehabilitation of patients with neurological lesions. Severe atherosclerotic lesions of the carotid artery are the main cause of stroke and transient ischemic attacks. Their incidence may reach 5-7% per year in patients with carotid artery stenosis > 70% with or without symptoms. Time-honored carotid endarterectomy is still regarded as the gold standard therapy for primary and secondary prevention of stroke. However, surgery is not free of complications and the rate of perioperative stroke ranges from 5.1 to 14.3%. A group of patients at a particularly high risk of stroke during surgical endarterectomy is represented by patients with significant carotid stenosis in the presence of an occluded contralateral artery. Indeed, carotid cross-clamping during operative surgery in the absence of an adequate collateral flow may result in a critical flow reduction during the operation and therefore increases the risk of periprocedural strokes. In the North American Symptomatic Carotid Endarterectomy (NASCET) trial, the overall risk of stroke was 5.1%, whereas it increased up to 14.3% in patients with an occluded contralateral carotid artery. Recently, carotid stenting has been increasingly used as an endovascular technique for carotid revascularization, especially after the introduction of neuroprotection devices which improved the safety of the procedure. Therefore, it may be an attractive alternative to carotid endarterectomy, especially when the surgical risk is too high. We describe the immediate and late outcomes of 3 patients treated with carotid artery stenting in the presence of contralateral carotid occlusion.     

IgG Against Dengue Virus in Healthy Blood Donors,Zanzibar, Tanzania

We conducted a seroprevalence survey among 500 healthy adult donors at Zanzibar National Blood Transfusion Services. Dengue virus IgG seroprevalence was 50.6% and independently associated with age and urban residence. These data will aid in building a surveillance, preparedness, and response plan for dengue virus infections in the Zanzibar Archipelago.Key words: dengue, seroprevalence, Zanzibar, viruses, vector-borne infections     

Autoimmune cytopenias in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary autoimmune cytopenias (AIC) represented by autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia, and autoimmune granulocytopenia. The distinction of immune cytopenias from cytopenias due to bone marrow infiltration, usually associated with a worse outcome and often requiring a different treatment, is mandatory. AIHA and ITP are more frequently found in patients with unfavorable biological risk factors for CLL. AIC secondary to CLL respond less favorably to standard treatments than their primary forms, and treating the underlying CLL with chemotherapy or monoclonal antibodies may ultimately be necessary. Am. J. Hematol. 89:1055–1062, 2014. © 2014 Wiley Periodicals, Inc.