Intérêt d'une polychimiothérapie dans le lymphome B intravasculaire

We describe three cases of intravascular lymphoma B with different clinical presentation: one case of a cutaneous variant and two cases with surrenal and cutaneous localisation. All patients are in complete remission after chemotherapy alone or after chemotherapy and autologous stem cells transplantation. The review of the literature as well as our cases specify the interest of an aggressive chemotherapy with autologous of peripheral stem cells if it was possible.     

Diabetes is associated with high risk of severe adverse events during chemotherapy for cancer patients: A single-center study

Diabetes mellitus (DM) is a common comorbidity among cancer patients, but its impact on chemotherapy tolerance has not been widely studied. We aimed to compare the occurrence of severe grade 3/4 adverse events (G3/4 AEs) within 90 days of starting chemotherapy between patients with and without diabetes. We conducted a retrospective single-center study in Lille University Hospital Oncology Department, France. Patients who received the first cycle of chemotherapy for gastrointestinal, gynecological or cancer of unknown primary source between 1 May 2013 and 1 May 2016, were included. Overall, 609 patients were enrolled: 490 patients without diabetes (80.5%) and 119 patients with diabetes (19.5%). Within 90 days of starting chemotherapy, patients with diabetes had a significantly higher occurrence of AEs G3/4 compared to those with no diabetes (multivariate odds ratio [OR]: 1.57 [1.02-2.42], P = .04). More frequent G3/4 AEs in patients with diabetes were infection (26%), hematological disorders (13%), endocrine disorders (13%) and deterioration of the general condition (13%). In the year following the beginning of chemotherapy, patients with diabetes were twice as likely to be hospitalized as those without diabetes (univariate OR: 2.1 [1.40-3.15], P = .0003). After multivariate adjustment, diabetes was no longer significantly associated with the risk of hospitalization (P = .051). There were no differences between patients with and without diabetes regarding dose reduction and chemotherapy treatment delays (P = .61 and P = .30, respectively). Our study suggests the need for better consideration of DM in the personalized care plan to improve chemotherapy tolerance and quality of life of patients with DM.     

COX-2 as a determinant of lower disease-free survival for patients affected by ameloblastoma

Ameloblastoma is a locally aggressive neoplasm with a poorly understood pathogenesis. Therefore, the aim of this study is to investigate whether COX-2 expression is associated with ameloblastoma microvascular density (MVD) and with tumor aggressiveness. Sixty-three cases of primary ameloblastomas arranged in tissue microarray were submitted to immunohistochemistry against cyclooxigenase-2 (COX-2) and CD34. Clinicopathological parameters regarding sex, age, tumour size, tumour duration, tumour location, treatment, recurrences, radiographic features, vestibular/lingual and basal cortical disruption and follow-up data were obtained from patients’ medical records and correlated with the proteins expression. The results on BRAF-V600E expression were obtained from our previous study and correlated with COX-2 and CD34 expressions. Log-rank univariate analysis and multivariate Cox regression model were done to investigate the prognostic potential of the molecular markers. Twenty-eight cases (44.4%) exhibited cytoplasmic positivity for COX-2, predominantly in the columnar peripheral cells, with a mean MVD of 2.2 vessels/mm². COX-2 was significantly associated with recurrences (p?<?0.001) and BRAF-V600E expression (p?<?0.001), whereas lower MVD was associated with the use of conservative therapy (p?=?0.004). Using univariate and multivariate analyses, COX-2 was significantly associated with a lower 5-year disease-free survival (DFS) rate (p?<?0.001 and p?=?0.012, respectively), but not with a higher MVD (p?=?0.68). In conclusion, COX-2 expression in ameloblastomas is not associated with MVD, but it is significantly associated with recurrences and with a lower DFS.     

Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing

The human epidermis serves 2 crucial barrier functions: it protects against water loss and prevents penetration of infectious agents and allergens. The physiology of the epidermis is maintained by a balance of protease and antiprotease activities, as illustrated by the rare genetic skin disease Netherton syndrome (NS), in which impaired inhibition of serine proteases causes severe skin erythema and scaling. Here, utilizing mass spectrometry, we have identified elastase 2 (ELA2), which we believe to be a new epidermal protease that is specifically expressed in the most differentiated layer of living human and mouse epidermis. ELA2 localized to keratohyalin granules, where it was found to directly participate in (pro-)filaggrin processing. Consistent with the observation that ELA2 was hyperactive in skin from NS patients, transgenic mice overexpressing ELA2 in the granular layer of the epidermis displayed abnormal (pro-)filaggrin processing and impaired lipid lamellae structure, which are both observed in NS patients. These anomalies led to dehydration, implicating ELA2 in the skin barrier defect seen in NS patients. Thus, our work identifies ELA2 as a major new epidermal protease involved in essential pathways for skin barrier function. These results highlight the importance of the control of epidermal protease activity in skin homeostasis and designate ELA2 as a major protease driving the pathogenesis of NS.     

Quantitative study of digestive enzyme secretion and gastrointestinal lipolysis in chronic pancreatitis.

BACKGROUND & AIMS: The contribution of human gastric lipase (HGL) to the overall lipolysis process in chronic pancreatitis (CP), as well as the relative pancreatic enzyme levels, rarely are addressed. This study was designed to quantify pancreatic and extrapancreatic enzyme output, activity, and stability in CP patients vs. healthy volunteers. METHODS: Healthy volunteers (n = 6), mild CP patients (n = 5), and severe (n = 7) CP patients were intubated with gastric and duodenal tubes before the administration of a test meal. HGL, human pancreatic lipase (HPL), chymotrypsin, and amylase concentrations were assessed in gastric and duodenal samples by measuring the respective enzymatic activities. Intragastric and overall lipolysis levels at the angle of Treitz were estimated based on quantitative analysis of lipolysis products. Similar analyses were performed on duodenal contents incubated ex vivo for studying enzyme stability and evolution of lipolysis. RESULTS: Although HPL, chymotrypsin, and amylase outputs all were extremely low, HGL outputs in patients with severe CP (46.8 +/- 31.0 mg) were 3-4-fold higher than in healthy controls (13.3 +/- 13.8 mg). Intragastric lipolysis did not increase, however, in patients with severe CP, probably because of the rapid decrease in the pH level of the gastric contents caused by a higher gastric acid secretion. HGL remains active and highly stable in the acidic duodenal contents of CP patients, and, overall, can achieve a significant lipolysis of the dietary triglycerides (30% of the control values) in the absence of HPL. CONCLUSIONS: Although all pancreatic enzyme secretions are simultaneously reduced in severe CP, gastric lipase can compensate partly for the loss of pancreatic lipase but not normalize overall lipolytic activity.