Drug-induced hypertension: an unappreciated cause of secondary hypertension

A myriad variety of therapeutic agents or chemical substances can induce either a transient or persistent increase in blood pressure, or interfere with the blood pressure-lowering effects of antihypertensive drugs. Some agents cause either sodium retention or extracellular volume expansion, or activate directly or indirectly the sympathetic nervous system. Other substances act directly on arteriolar smooth muscle or do not have a defined mechanism of action. Some medications that usually lower blood pressure may paradoxically increase blood pressure, or an increase in pressure may be encountered after their discontinuation. In general, drug-induced pressure increases are small and transient: however, severe hypertension involving encephalopathy, stroke, and irreversible renal failure have been reported. The deleterious effect of therapeutic agents is more pronounced in patients with preexisting hypertension, in those with renal failure, and in the elderly. Careful evaluation of a patient's drug regimen may identify chemically induced hypertension and obviate unnecessary evaluation and facilitate antihypertensive therapy. Once chemical-induced hypertension has been identified, discontinuation of the causative agent is recommended, although hypertension can often be managed by specific therapy and dose adjustment if continued use of the offending agent is mandatory. The present review summarizes the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action.     

Cell lineage analysis of acute leukemia relapse uncovers the role of replication-rate heterogeneity and microsatellite instability

Human cancers display substantial intratumoral genetic heterogeneity, which facilitates tumor survival under changing microenvironmental conditions. Tumor substructure and its effect on disease progression and relapse are incompletely understood. In the present study, a high-throughput method that uses neutral somatic mutations accumulated in individual cells to reconstruct cell lineage trees was applied to hundreds of cells of human acute leukemia harvested from multiple patients at diagnosis and at relapse. The reconstructed cell lineage trees of patients with acute myeloid leukemia showed that leukemia cells at relapse were shallow (divide rarely) compared with cells at diagnosis and were closely related to their stem cell subpopulation, implying that in these instances relapse might have originated from rarely dividing stem cells. In contrast, among patients with acute lymphoid leukemia, no differences in cell depth were observed between diagnosis and relapse. In one case of chronic myeloid leukemia, at blast crisis, most of the cells at relapse were mismatch-repair deficient. In almost all leukemia cases, > 1 lineage was observed at relapse, indicating that diverse mechanisms can promote relapse in the same patient. In conclusion, diverse relapse mechanisms can be observed by systematic reconstruction of cell lineage trees of patients with leukemia.     

Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia

We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10(-16)). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.     

Role of endoscopy in patients with diverticular disease

Acute diverticulitis occurs in 10-25% of patients with diverticulosis. Colonoscopy is advised 6 weeks after an attack of acute diverticulitis in order to completely evaluate the colonic lumen and exclude a potential malignancy. We conducted several studies aimed to evaluate the feasibility and safety of early colonoscopy in patients with acute diverticulitis. Consecutive patients hospitalized for acute diverticulitis were included. In the first phase of the study, patients with adjacent peri-diverticular air/fluid on CT were excluded. In the second phase of the study, we included patients with peri-diverticular air/fluid on CT as well. During the first phase of the study, 39 patients underwent uneventful colonoscopy. During the second phase of the study, 40 patients underwent colonoscopy and 1 of 6 patients with peri-diverticular air had perforation of her sigmoid colon. Two patients had a more protracted course and were clearly those who benefited most from the early colonoscopy. Based on our study, we concluded that early colonoscopy in acute diverticulitis is feasible. It should be reserved either for all patients with no air adjacent to diverticuli on CT or just for those with a more protracted course. In the third phase, a prospective randomized study was conducted on patients with acute diverticulitis with no peri-diverticular air. Such patients were randomized into those who underwent early colonoscopy and those who underwent colonoscopy 6 weeks later. Eighty-three patients were included in both groups and in none has a significant lesion been identified (except polyps). It seems therefore that the current abdominal CT with its excellent resolution is enough to exclude colonic cancer. Colonoscopy should be reserved only for patients with a protracted unresolved course of acute diverticulitis.     

Single-incision transumbilical levels 1 and 2 axillary lymph node dissection using a flexible endoscope in human cadaveric models

Background

The use of the flexible endoscope as a surgical platform potentially exposes a range of new surgical approaches and benefits yet to be fully defined. A new method using the flexible endoscope to undertake axillary dissection for breast cancer treatment is explored together with an investigation into its acceptability to the general public.

Methods

Endoscopic axillary dissection via a transumbilical approach using the flexible endoscope passed subcutaneously from the umbilicus is described for four human cadaveric axillas. A questionnaire, validated by clinicians, explored the general public’s reaction to the approach and how it might be influenced by potentially serious morbidity such as an increased rate of cancer recurrence.

Results

All axillas were accessed successfully via the transumbilical approach. Levels 1 and 2 axillary dissection was attempted on four axillas. Scarring from previous axillary surgery prevented dissection in one case. In the remaining three cases, respectively 12, 11, and 14 lymph nodes were harvested. The operative times improved with each case, from 1080 to 390 min. A total of 127 people responded to the questionnaire, with 73 % preferring the described approach over the open and periareolar alternatives when morbidities were considered equivalent. When a hypothetical elevated risk of cancer recurrence was included with the transumbilical approach, one-fifth of the public still accepted the approach due to the likelihood of a superior cosmesis.

Conclusion

The use of the flexible endoscope for oncologically safe levels 1 and 2 axillary dissection is possible and would be acceptable to the general public if it were clinically approved. However, significant challenges with the current endoscopic equipment and relevant instrumentation limit the potential of the technique. Technical innovation in terms of new instrument design with improved ergonomics will reduce long operating times and fatigue, thus ensuring surgical acceptance of the flexible endoscope.