Chronic lymphocytic leukaemia is the most prevalent leukaemia in Western countries. It is an incurable disease characterized by a highly variable clinical course. Chronic lymphocytic leukaemia is an ...ideal model for studying clonal heterogeneity and dynamics during cancer progression, response to therapy and/or relapse because the disease usually develops over several years. Here we report an analysis by deep sequencing of sequential samples taken at different times from the affected organs of two patients with 12- and 7-year disease courses, respectively. One of the patients followed a linear pattern of clonal evolution, acquiring and selecting new mutations in response to salvage therapy and/or allogeneic transplantation, while the other suffered loss of cellular tumoral clones during progression and histological transformation.
Neuroendocrine tumors (NETs) or carcinoids represent a small percentage of gastrointestinal neoplasms (2%). The ileum (41.8%), rectum (27.4%) and stomach (8.7%) are the most common locations. We ...present an unusual case of NET due to its origin in the ampulla of Vater, as an extremely rare cause of biliary obstruction. A bibliographic review of the current recommendations of management and treatment for this case, different from other locations of the gastrointestinal tract is carried out. The curative treatment of choice for early-stage Vater ampulla NETs is Whipple surgery with lymphadenectomy due to Its high rate of lymphatic and metastatic dissemination, regardless of size and histological grade, although there are no updated official guidelines.
OBJECTIVEChoroidal thickness (CT) has been evaluated as a marker of systemic inflammation in ankylosing spondylitis (AS). This study evaluates the CT of AS patients before and after 6 months of ...biological treatment.
METHODSThis longitudinal multicenter study evaluated CT in 44 AS patients. The correlations between CT and C-reactive protein (CRP) with disease activity indices were calculated. The concordance between CT and CRP was determined. We assessed factors associated with response to treatment. Clinically important improvement was defined as a decrease in Ankylosing Spondylitis Disease Activity Score of 1.1 points or greater.
RESULTSForty-four eyes in patients aged 18 to 65 years were included. Mean CT values were significantly higher at baseline than after 6 months of treatment (baseline355.28 ± 80.46 μm; 6 months341.26 ± 81.06 μm; p < 0.001). There was a 95% concordance between CT and CRP at baseline and 6 months. Clinically important improvement was associated with lower baseline CT and age as independent factors (odds ratios, 0.97 95% confidence interval, 0.91–0.93; p = 0.009 and 0.81 95% confidence interval, 0.7–0.95; p = 0.005), with baseline CT of less than 374 μm (sensitivity 78%, specificity 78%, area under the curve 0.70, likelihood ratio 3.6).
CONCLUSIONSChoroidal thickness decreased significantly after 6 months of biological treatment in all treatment groups. Choroidal thickness and CRP had a 95% concordance. A high CT was associated with a risk of biological treatment failure. Choroidal thickness can be considered a useful biomarker of inflammation and a factor associated with response to treatment in AS.
BACKGROUND AND OBJECTIVEAnkylosing spondylitis (AS) is an inflammatory disease, and choroidal thickness (CT) has been proposed and evaluated as a potential marker of systemic inflammation associated ...with AS and other inflammatory diseases. This study compared CT measurements taken from patients with severe AS disease activity without eye inflammation with those taken from healthy subjects.
METHODSThis cross-sectional, multicenter study compared CT in 44 patients with high AS disease activity, and no history of eye inflammation with CT in 44 matched healthy subjects aged between 18 and 65 years. In the AS group, the correlation between CT and C-reactive protein, human leukocyte antigen (HLA) B27 positivity, disease duration, and disease activity was calculated.
RESULTSMean CT values of patients with AS were significantly higher in the right eye, the left eye, and the thickest choroid eye. The right eye mean CT was 338.3 ± 82.8 μm among patients with AS and 290.5 ± 71.2 μm among healthy subjects (p = 0.005). The left eye mean CT was 339.5 ± 84.7 μm for patients with AS and 298.4 ± 68.9 μm for healthy subjects (P = 0.015). The thickest choroid eye CT was 358.4 ± 82.1 μm among patients with AS and 314.1 ± 65.2 μm among healthy subjects (P = 0.006). We did not find a significant correlation between CT and disease activity, C-reactive protein, human leukocyte antigen B27 positivity, or disease duration.
CONCLUSIONSPatients with active AS but without a history of eye inflammation had a thicker choroid than healthy subjects. This finding suggests that CT is a marker of systemic inflammation in patients with inflammatory disease, regardless of known eye symptoms.
CLL remains an incurable disease, making it crucial to continue searching for new therapies efficient in all CLL cases. We have studied the effect of combining arsenic trioxide (ATO) with ...fludarabine, a frontline drug in CLL. We have found a synergistic interaction between 1 μM ATO and 5 μM fludarabine that significantly enhanced the cytotoxic effect of the individual drugs. Importantly, ATO sensitized fludarabine-resistant cells to the action of this drug. The mechanism behind this effect included the downregulation of phospho-Akt, phospho-ERK, and the Mcl-1/Bim and Bcl-2/Bax ratios. The combination of ATO and fludarabine partially overcame the survival effect induced by co-culturing CLL cells with stromal cells. Therefore, low concentrations of ATO combined with fludarabine may be an efficient therapeutic strategy in CLL patients.
•We have identified a synergistic interaction between ATO and fludarabine.•ATO sensitize to fludarabine the CLL cases with poor response to this drug.•The combination ATO/fludarabine downregulates crucial survival pathways in CLL.•The combination of ATO/fludarabine partially overcomes the survival effect of stroma.•ATO may be efficient for CLL treatment in combined therapies with fludarabine.
The prognostic impact of biallelic ATM abnormalities (ATM mutation and concurrent 11q deletion) remains unknown. We studied ATM, BIRC3, SF3B1, and NOTCH1 genes in 118 treatment-naïve CLL patients at ...diagnosis. Patients with biallelic ATM alteration had a similar time to first treatment (TTFT) and shorter overall survival (OS) compared with patients with isolated 11q deletion and shorter TTFT and OS when compared to patients with wild-type ATM. Furthermore, biallelic ATM alteration (HR: 6.4; p ≤ 0.007) was significantly associated with an increased risk of death similar to p53 deletion (HR: 6.1; p ≤ 0.004), superior to 11q deletion alone (HR: 2.8; p ≤ 0.022) and independent of other significant parameters such as age, advanced clinical stage, and complex karyotype. Our results suggest the identification of ATM mutations in CLL patients with 11q deletion at diagnosis is clinically relevant and predicts disease progression, poor response to the treatment, and reduced OS independent of other molecular prognostic factors.
Defects of the urachus obliteration may lead to urachal abnormalities such an urachal cyst, which
tend to rest asymptomatic. We report a case of a four-old-year boy who referred a three-week history
...of abdominal pain, dysuria and fever. A hypogastric mass was observed at the exploration. The
ultrasonography and the computed tomography were compatible with an infected urachal cyst.
Intravenous antibiotic therapy was started, with an optimal response. Four months later, a chirurgical
complete excision of the urachal cyst was performed. Among different congenital disorders of the
urachus, urachal cysts and patent urachi are the most frequent. Urachal cysts may become infected,
causing suprapubic pain, dysuria, fever and abdominal mass, as well as signs of peritonism. The main
tool for diagnose these lesions is ultrasonography. They could potentially degenerate into
adenocarcinoma in adults, which is rare but associated to bad prognosis. Urachal remnants have been
classically managed surgically. However, an active surveillance of these lesions with a conservative
treatment could be an alternative, since spontaneous resolution is more common than previously
thought.
Background: The bullet tuna (Auxis rochei) is an epipelagic fish with a worldwide distribution that is highly targeted by fisheries. Genetic diversity and population genetics are good indicators of ...population structure and thus, essential tools for fisheries management. Knowing which factors (biotic and abiotic) might be shaping such structure is crucial for management plans. In the present study, we assessed the population structure of the bullet tuna in the western and central Mediterranean Sea. Methods: We used two types of genetic data: the mitochondrial DNA control region and seven microsatellite loci. The analysis of 431 sequences with a length of 386 bp from the mtDNA CR and the results from 276 individuals were genotyped by seven microsatellite loci. Results: Both types of markers coincided in showing significant genetic differences between an Iberian Peninsula–Strait of Gibraltar stock in comparison with a North African stock. Conclusions: We argue that this differentiation pattern is likely caused by reproductive strategies such as coastal spawning, larval retention, and natal homing behavior. These results should endorse the implementation of management plans for a resource that currently is not being managed. Thus, to ensure sustainability, these new policies should consider the presence of at least two genetically identified stocks.
Intrahepatic pancreatic pseudocyst: a case report Martínez-Sanz, Nuria; González-Valverde, F Miguel; Vicente-Ruiz, María ...
Revista española de enfermedades digestivas
107, Issue:
4
Journal Article
Chronic Lymphocytic Lymphoma (CLL) is a heterogeneous disease in which many important factors for its prognosis have been identified. The normal functioning of p53 is one of the most critical ...barriers against cancer; therefore, if it has a deletion and/or mutation, it is a robust biomarker for the therapeutic response in CLL. The possibility was raised that some germline single - nucleotide polymorphisms of TP53 in healthy populations may also affect p53 function. One of the most studied polymorphisms of the TP53 gene is codon 72 in exon 4, a CGC to CCC transition (R72P), due to its potential effect on cancer risk. As with many types of cancer, its association with a worse prognosis in CLL is unclear. We analyzed the relationship of the genotypes of the TP53 codon 72 polymorphism in a large cohort of patients with CLL, to demonstrate the association of codon 72 with the evolution of the disease.
Using the IDIPHIM patient database, 558 patients with a diagnosis of CLL were included, with clinical data, immunophenotype studies, FISH, IgHV, and karyotype, at the time of diagnosis and during follow-up. The TP53 codon 72 Arg/Arg, Arg/Pro, and Pro/Pro genotypes were analyzed using RT-PCR and Sanger sequencing techniques.
After analyzing the sample of patients, 321 patients with the Arg/Arg genotype, 202 with the Arg/Pro genotype, and 35 with the Pro/Pro genotype were found. In the comparative analysis of the three groups, the patients with the Pro/Pro genotype had a higher number of patients in advanced stages B and C. The latter had a significant association with Binet staging (p = 0.002) compared to the other groups. Likewise, patients with the Pro/Pro genotype had a higher incidence of Richter transformation, whose association was significant (p = 0.013). Also, the patients who were within the Pro/Pro genotype group showed a significant association (p = 0.030) with the Time to the first treatment (TFT), also observing that the group of patients with the Arg/Pro genotype had a more considerable time until your first treatment. 19.7% (110/558) had a second neoplasm, having a significantly higher association with the homozygous groups (Arg/Arg and Pro/Pro) than with the Arg/Pro group, which on the contrary, had fewer second neoplasms (p = 0.016) (see Table 1). Regarding the type of tumors, we found 14.5% of the bladder, 14.5% of the skin, 14.5% of the colon, 13.6% of the prostate, and 12.7% of the lung. No associations were found between Codon 72 and CD38+, ZAP70+, complex karyotype, IgHV, NOTCH-1, del 11q, 12+, p53, del 13q, TP53 mutation. Still, when forming a group between the p53 deletion and TP53 mutation, if significant differences were found (p = 0.023), Pro / Pro group had the highest percentage. The overall survival was 156.32 months (139.92 - 172.72), showing that patients with the Arg/Pro genotype live 40 months more significantly than the other groups (p = 0.028) (see Figure 1). Finally, in the multivariate analysis, age, complex karyotype, 11q deletion, p53 deletion, unmutated IgHV, and Pro/Pro genotype at codon 72 were identified as independent variables associated with an increased risk of death (see Table 2).
In conclusion, the Pro/Pro genotype of TP53 Codon 72 has a potential role in the progression and the higher mortality of patients with CLL. Conversely, the Arg / Pro genotype was associated with a lower incidence of second malignancies and higher overall survival.
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No relevant conflicts of interest to declare.
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