Does pre-operative embolization of a replaced right hepatic artery before pancreaticoduodenectomy for pancreatic adenocarcinoma affect postoperative morbidity and R0 resection? A bi-centric French cohort study

BackgroundSacrificing a replaced right hepatic artery (rRHA) from the superior mesenteric artery is occasionally necessary to obtain an R0 resection after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA). Preoperative embolization (PEA) of the rRHA has been proposed to avoid the onset of postoperative biliary and ischemic liver complications.MethodsEighteen patients with cephalic PA with an rRHA underwent PEA of the rRHA from 2013 to 2019. The monitoring after embolization and PD was systematic and included a clinical-biological evaluation and a computed tomography scan. This study aimed to determine the feasibility of PEA of the rRHA, postoperative morbidity at 90 days, and quality of oncologic resection after PD.ResultsFeasibility of PEA was 100% without complications. A PD was performed in 16/18 patients. Mortality was 2/16 with one death after septic shock with hepatic ischemia without an arterial obstruction. Overall morbidity was 44% including one hepatic abscess after hepatic ischemia (6%). Two resections were R1 (<1 mm) in contact with the origin of the rRHA (2/4 R1).ConclusionPEA of the rRHA before PD was safe and reproducible. PEA of the rRHA followed by en bloc PD resection seems to limit the risk of bilio-hepatic ischemia and could facilitate oncologic resection.     

Exploring a 7-gene prognostic model based on ferroptosis for efficiently guiding immunotherapy in melanoma patients

PurposeAlthough skin cutaneous melanoma (SKCM) is a relatively immunotherapy-sensitive tumor type, there is still a certain fraction that benefits less from treatment. Ferroptosis has been demonstrated to modulate tumor progression in many cancer types. This study focused on ferroptosis-related genes to construct a prognostic model for SKCM patients.Materials and methodsGene expression profiles of SKCM samples were obtained from public databases. Unsupervised consensus clustering was used to determine molecular subtypes related to ferroptosis. Least absolute shrinkage and selection operator (LASSO) and stepwise Akaike information criterion (stepAIC) were applied to construct a prognostic model based on differentially expressed genes between two molecular subtypes.ResultsC1 and C2 subtypes were identified with differential prognosis and immune infiltration. A 7-gene prognostic model was constructed to classify samples into high-FPRS and low-FPRS groups. Low-FPRS group with favorable prognosis had higher immune infiltration and more enriched immune-related pathways than the high-FPRS group. The two groups showed distinct sensitivity to immunotherapy, with the low-FPRS group predicted to have more positive response to immunotherapy than the high-FPRS group. A nomogram based on the FPRS score and clinical features was built for more convenient use.ConclusionsThe critical role of ferroptosis involved in SKCM development was further validated in this study. The prognostic model was efficient and stable to be applied in clinical conditions to support clinicians in determining personalized therapy for SKCM patients especially those with metastasis.     

High-Intensity Training for 6 Months Safely,but Only Temporarily,Improves Exercise Capacity in Selected Solid Organ Transplant Recipients

BackgroundOrgan transplantation is a life-saving intervention that improves quality of life of patients with irreversible organ failure. Although exercise training immediately after transplantation has been suggested to be beneficial, such interventions remain rare in stable transplant recipients, whereas effects of high-intensity training (HIT) are even less frequently investigated. Moreover, sustainability of such interventions has not yet been reported. We investigated the effects of a 6-month, cycling-based HIT program on physical performance in long-term stable solid organ transplant (SOT) recipients, with follow-up evaluation after 6 months.MethodsForty-two adult, stable, and selected SOT recipients participated in a 6-month individualized home- and group-based HIT program. Exercise capacity (VO₂max), maximal power (Wmax), and body mass index were measured before, at the end, and 6 months after completion of the intervention.ResultsThe study comprised 12 heart, 7 lung, 8 liver, and 15 kidney recipients (mean age, 41.4 ± 11.1 years; median time posttransplant, 3.4 [1.7-8.0] years). For 6 months, VO₂max increased in the heart, lung, and kidney groups, Wmax increased in the heart group, and body mass index decreased in the liver group. Six months after the HIT program, the achieved gain in exercise capacity had disappeared in all groups.ConclusionDespite voluntary participation selection bias, our observations indicate that HIT is safe and may result in a beneficial effect on physical performance in selected, stable SOT recipients. However, there was no sustained beneficial effect once training stopped. Larger scale and longer term studies are still required to investigate longevity of improvement and overall beneficial effects on clinical outcomes.     

Circulating RNA Profiling in Postreperfusion Plasma From Kidney Transplant Recipients

BackgroundIschemia/reperfusion injury (IRI) is inevitable in kidney transplantation (KT) and may lead to impaired tubular epithelial cell function and reduce graft function and survival. Renal IRI is a complex cellular and molecular event; therefore, investigating the genetic or molecular pathways associated with the early phase of KT would improve our understanding of IRI in KT. MicroRNAs (miRNAs) play a critical role in various pathologic events associated with IRI.MethodsWe compared the expression profile of miRNAs extracted from 2 blood plasma samples, 1 from periphery and the other form gonadal veins immediately after reperfusion, in a total 5 cases of KT.ResultsWe observed that the total RNA yield was higher in postreperfusion plasma and that a subset of miRNAs was upregulated (miR-let-7a-3p, miR-143-3p, and miR-214-3p) or downregulated (let-7d-3p, let-7d-3p, miR-1246, miR-1260b, miR-1290, and miR-130b-3p) in postreperfusion plasma. Gene ontology analyses revealed that these subsets target different biological functions. Twenty-four predicted genes were commonly targeted by the upregulated miRNAs, and gene ontology enrichment and pathway analyses revealed that these were associated with various cellular activities such as signal transduction or with components such as exosomes and membranous organelles.ConclusionWe present 2 subsets of miRNAs that were differentially upregulated or downregulated in postreperfusion plasma. Our findings may enhance our understanding of miRNA-mediated early molecular events related to IRI in KT.     

Insulin Sensitivity After Living Donor Nephrectomy

BackgroundThe kidney is essential for glucose and insulin metabolism. Living kidney donors (LKDs) experience a reduction in glomerular filtration rate of 25 to 30 mL/min after donor nephrectomy. Little is known about the effect of glomerular filtration rate decline on insulin sensitivity in LKDs.MethodsWe conducted a prospective pilot study on 9 LKDs (N = 9) who underwent dynamic metabolic testing (mixed meal tolerance test) to measure proxies of insulin sensitivity (homeostatic model assessment of insulin resistance, the area under curve [AUC] for insulin/glucose ratio, and Matsuda insulin sensitivity index) before and 3 months after donor nephrectomy. The primary outcome was the change in insulin sensitivity indices (delta [post-nephrectomy – pre-nephrectomy]).ResultsFour of the donors had a body mass index (BMI) between 32.0 and 36.7 predonation. Post–donor nephrectomy, compared with prenephrectomy values, median insulin AUC increased from 60.7 to 101.7 hr*mU/mL (delta median 33.3, P = .04) without significant change in median glucose AUC levels from 228.9 to 209.3 hr*mg/dL (delta median 3.2, P = .77). There was an increase in the median homeostatic model assessment of insulin resistance from 2 to 2.9 (delta median 0.8, P = .03) and the AUC insulin/glucose ratio from 30.9 to 62.1 pmol/mmol (delta median 17.5, P = .001), whereas the median Matsuda insulin sensitivity index decreased from 5.9 to 2.9 (delta median −2, P = .05). The changes were more pronounced in obese (BMI >32) donors.ConclusionLKDs appear to have a trend toward a decline in insulin sensitivity post–donor nephrectomy in the short term, especially in obese donors (BMI >32). Further investigation with a larger sample size and longer follow-up is needed.     

Sexual Activity After Bariatric Surgery: A Prospective Monocentric Study Using the PISQ-IR Questionnaire

IntroductionObesity can lead to pelvic floor disorders, interfering with women’s sexual life; Prolapse/Incontinence Sexual Questionnaire-International Urogynecology Association–Revised (PISQ-IR) is a new instrument to measure sexual life in women with pelvic floor disorders.AimsTo assess the utility of using PISQ-IR in morbidly obese women undergoing bariatric surgery and to show the improvement of bariatric surgery on sexuality.MethodsThis prospective monocentric study included all women who underwent bariatric surgery from June 2016–May 2017. Sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) was performed by 1 surgeon, and data were collected by 1 researcher. Demographics, medical history, number of deliveries, and type of bariatric surgery (SG or RYGB) were collected at baseline. At the 1-year follow-up consultation, postoperative complications, percentage of total body weight loss (TWL) and percentage excess weight loss were assessed. Questionnaires were given at baseline and at 1-year follow-up.Main Outcome MeasuresPostoperative complications and total weight loss were measured at the 1-year follow-up. Sexual activity, using the PISQ-IR, and pelvic organ prolapse, urinary incontinence, and anal incontinence, using the urinary symptom profile and PFDI (Pelvic Floor Distress Inventory) 20, were compared before surgery and at 1-year follow-up.Results72 patients were included at baseline, 54 (75%) were considered for final analysis (30 RYGB and 24 SG), and 51 patients were considered for PISQ-IR. The mean preoperative body mass index was 41 ± 5.4 kg/m², and mean age was 43 ± 11.8 years. Both procedures induced an important weight loss (mean TWL of 33%) and had a similar percentage of TWL for each procedure: 31 (15–46) for SG vs 34 (9–51) for RYGB. 9 patients (17 [6%]) became sexually active 1 year after surgery. For the sexually inactive population after 1 year, there was no differences in the PISQ-IR in the follow-up. When body mass index loss was >13 kg/m², a higher percentage of the sexually active population improved their different scores, and there were significant results for both global quality of life and desire (P = .026 and .046). The other questionnaires showed a significant decrease in urinary incontinence symptoms (P < .001) associated with weight loss, whereas there was no difference in terms of pelvic organ prolapse or anal incontinence.ConclusionPISQ-IR is a useful instrument to measure sexual function regarding pelvic floor disorders. Bariatric surgery improves sexual activity in obese women 1 year after surgery.Treacy PJ, Mazoyer C, Falagario U, et al. Sexual Activity After Bariatric Surgery: A Prospective Monocentric Study Using the PISQ-IR Questionnaire. J Sex Med 2019;16:1930–1937.     

Measurement of oxidant and antioxidant levels in liver tissue obtained from patients with liver transplantation: A case-control study

ObjectiveThis study aimed to compare oxidant and antioxidant substance accumulation in the liver tissues of patients with chronic liver disease (recipients) who underwent liver transplantation (LT) with living liver donors (LLDs) who underwent living donor hepatectomy (LDH).MethodsThis prospective study included 160 recipients (LT group) and 40 LLDs (LLD group). During surgery, a piece of liver tissue measuring a minimum of 10 × 10 mm was obtained from the edge of the right lobe of the liver of recipients and LLDs, incubated for 10 min in saline to remove blood, and stored at −70 °C until biochemical analysis was performed. Catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), myeloperoxidase (MPO), prolidase, reduced glutathione (GSH), malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), total thiol, native thiol, and disulfide levels were measured in stored liver tissues.ResultsThere was a statistically significant difference between LT and LLD groups in terms of age (p < 0.001), body mass index (p = 0.019), GSH-Px (p < 0.001), SOD (p = 0.001), MPO (p < 0.001), prolidase (p < 0.001), GSH (p < 0.001), and MDA (p = 0.003) values in favor of the LT group. Furthermore, there was a statistically significant difference between LT and LLD groups in terms of CAT (p < 0.001), TAS (p < 0.001), TOS (p < 0.001), OSI (p < 0.001), total thiol (p < 0.001), native thiol (p < 0.001), and disulfide (p < 0.001) values in favor of the LLD group. There were no differences between the groups in terms of sex.ConclusionThis study demonstrated that it is possible to assess the extent of oxidative stress in liver tissues by measuring the levels of antioxidant enzymes, oxidants, or the end-products of oxidative stress. With the use of optimum and minimally invasive methods, quantifying these molecules will potentially help evaluate the extent of liver disease and prognostication of liver cirrhosis.