Neoadjuvant therapy and biliary decompression lower biliary and pancreatic juice vascular endothelial growth factor levels in patients with periampullary adenocarcinoma

Increased expression of vascular endothelial growth factor (VEGF) by pancreatic cancer correlates with poor survival. The significance of VEGF in biliary and pancreatic secretions in periampullary cancers is unknown. Bile and pancreatic juice samples were collected from patients undergoing pancreaticoduodenectomy (PD). All samples were frozen at -70 degrees C until subsequent analysis for VEGF concentration using enzyme-linked immunoabsorbent assay (ELISA). Plasma VEGF levels in pancreatic cancer patients were <10 pg/mL. The biliary VEGF concentration for patients with malignancy was significantly elevated compared to benign disease (P = 0.05). There was no difference in pancreatic VEGF concentrations between benign and malignant disease. Cancer patients undergoing preoperative chemoradiation (CRT) had lower biliary and pancreatic VEGF concentrations than those who did not. Preoperative biliary drainage (BD) was associated with decreased VEGF concentrations in bile (3500 pg/mL vs 7740 pg/mL, P = 0.027). Patients undergoing both CRT and BD had diminished biliary and pancreatic VEGF concentrations compared to those who had neither. This was statistically significant for pancreatic VEGF concentrations (917 pg/mL vs 4723 pg/mL, P = 0.044). VEGF is highly concentrated in bile and pancreatic juice compared to plasma. Preoperative CRT and BD significantly reduce these levels in patients with periampullary cancers. Antiangiogenic therapy aimed at interrupting the VEGF pathway appears to be a logical target in periampullary cancer.     

Apoptosis of peripheral CD4(+) T-lymphocytes in end-stage renal disease patients under hemodialysis and rhEPO therapies

End-stage renal disease (ESRD) under hemodialyses (HD) is related with a higher propensity to infections, essentially due to T-cell lymphopenia. We postulated that HD procedure affects CD4(+) T cells, especially by inducing apoptotic death and that recombinant human erythropoietin (rhEPO) therapy may also play an important role in the modulation of the immune system in these patients. T-cell phenotype and apoptosis of HD patients and healthy controls were evaluated by flow cytometry using anticoagulated whole-blood samples. In 12 HD patients, these parameters were also analyzed before and immediately after HD procedure. HD patients showed a decrease in total circulating CD3(+) lymphocytes, especially in CD4(+) T cells (0.747 ± 0.410 vs. 0.941 ± 0.216 × 10(9)/L, p < 0.05), which could be a consequence of the higher proportion of CD3(+) and CD4(+) lymphocytes in the latest stage of apoptosis (or death) and of the higher proportion of apoptotic CD4(+) T cells observed in the patients immediately after HD procedure (2.91 ± 0.780 vs. 3.90 ± 1.96, p < 0.05). A positive and statistically significant correlation between CD3(+) and CD4(+) lymphocytes in latest stage of apoptosis (or death) with HD time was found (CD3(+): r = 0.592, p < 0.01; CD4(+): r = 0.501, p < 0.01). We also found a negative and significant correlation between weekly rhEPO doses and the number of CD4(+) T cells (r = -0.358, p < 0.05). In conclusion, HD procedure still contributes to the development of T-cell lymphopenia, at least in part, by apoptosis induction. It was also shown that rhEPO therapy is associated with the CD4(+) T-cell decline, possibly by immune modulation, eliminating atypical cells and helping to restore the CD4(+) T-cell subset.     

Omentopexy with Glubran®2 for reducing complications after laparoscopic sleeve gastrectomy: results of a randomized controlled study

Background

Gastric fistulas, bleeding, and strictures are commonly reported after laparoscopic sleeve gastrectomy (LSG), that increase morbidity and hospital stay and may put the patient’s life at risk. We report our prospective evaluation of application of synthetic sealant, a modified cyanoacrylate (Glubran®2), on suture rime, associated with omentopexy, to identify results on LSG-related complications.

Methods

Patients were enrolled for LSG by two Bariatric Centers, with high-level activity volume. Intraoperative recorded parameters were: operative time, estimated intraoperative bleeding, conversion rate. We prospectively evaluated the presence of early complications after LSG during the follow up period. Overall complications were analyzed. Perioperative data and weight loss were also evaluated. A control group was identified for the study.

Results

Group A (treated with omentopexy with Glubran®2) included 96 cases. Control group included 90 consecutive patients. There were no differences among group in terms of age, sex and Body Mass Index (BMI). No patient was lost to follow-up for both groups. Overall complication rate was significantly reduced in Group A. Mean operative time and estimated bleeding did not differ from control group. We observed three postoperative leaks in Group B, while no case in Group A (not statistical significancy). We did not observe any mortality, neither reoperation. Weight loss of the cohort was similar among groups. In our series, no leaks occurred applying omentopexy with Glubran®2.

Conclusion

Our experience of omentopexy with a modified cyanoacrylate sealant may lead to a standardized and reproducible approach that can be safeguard for long LSG-suture rime.

Trial registration

Retrospective registration on clinicaltrials.gov PRS, with TRN NCT03833232 (14/02/2019).

     

The clinical pharmacology of integrase inhibitors

Introduction: Treatment of HIV infection has consistently evolved in the last three decades. A steady improvement in efficacy tolerability, safety, and practical aspects of treatment intake has made HIV infection much easier to manage over the long term, and in optimal treatment conditions the life expectancy of persons living with HIV infection now approaches the values of the general population. The last category of antiretrovirals to be fully developed for clinical use is the one of strand-transfer integrase inhibitors (INSTIs).

Areas covered: In this review, the evolution of the knowledge on INSTIs use in the clinical setting is reviewed, analyzed, and interpreted. Emphasis is placed on the properties possibly accounting for several superiority results achieved by INSTIs in non-inferiority designed comparative clinical trials, which led to their inclusion as first line options in all versions of HIV therapeutic guidelines.

Expert commentary: Some unprecedented clinical-pharmacological properties of INSTIs, such as their rapid and sustained action against HIV replication, the optimal tolerability and safety profile and a clinically proven robust genetic barrier are the main factors justifying the successful clinical use of INSTIs. Based on these unique features, novel INSTIs-based treatment modalities are being developed, including the reduction of antiretroviral regimens to two drugs only.     

The Dysphagia Handicap Index: Development and Validation

Quality-of-life indicators for dysphagia provide invaluable information to the treating clinician regarding the success or failure of swallowing therapy. The purpose of this study was to develop a clinically efficient, statistically robust patient-reported outcomes tool that measures the handicapping effect of dysphagia on emotional, functional, and physical aspects of individual’s lives. 60 statements describing the handicapping effect of dysphagia were collected from patient reports and divided into subscales of physical, emotional, and functional problems. The statements were presented to 77 individuals with dysphagia. Respondents replied never, sometimes, or always to each statement and rated their self-perceived dysphagia severity on a 7-point equal-appearing interval scale. Cronbach’s α was performed to assess the internal consistency validation of the items within the questionnaire. The final questionnaire was reduced to 25 items and administered to 214 individuals with dysphagia and 74 controls. Test–retest was performed on 63 individuals with dysphagia. Cronbach’s α for the initial and final versions was strong at r = 0.96 and r = 0.94, respectively. Significant differences occurred between the dysphagia and control groups. Test–retest reliability was strong. We present a new, easy-to-complete, statistically robust, patient-reported outcomes measure for assessing the handicapping effect of dysphagia.