Early adoption of laparoscopic liver surgery in Poland: a national retrospective cohort study.

BACKGROUND: The need for safe and efficient dissemination of minimally invasive approach in liver surgery is among the current challenges for hepatobiliary surgeons. After the stage of innovators and pioneers, the following countries should adopt a laparoscopic approach. The aim of this study was to assess the national experience and trend in implementing laparoscopic liver resection (LLR) in Poland. MATERIALS AND METHODS: A national registry of LLR performed in Poland was established in June 2020. All LLR cases performed before were included retrospectively, followed by prospectively collected new cases. Baseline characteristics, preoperative and intraoperative data, short-term results and long-term follow-up were recorded. RESULTS: Since 2010 up to the end of 2022 there were 718 LLRs performed in Poland. The national rate of laparoscopic approach has gradually increased since 2017 ( P <0.001), reaching the rate of 11.7% in 2022. There were 443 (61.7%), 107 (14.9%), and 168 (23.4%) LLRs performed in accordance to increasing grades of difficulty. The move towards more demanding cases had an increasing trend over the years ( P <0.001). Total intraoperative adverse event and postoperative severe complications rates were estimated for 13.5% ( n =97) and 6.7% ( n =48), respectively. 30-day reoperation, readmission and postoperative mortality rates were 3.6% ( n =26), 2.8% ( n =20), and 0.8% ( n =6), respectively. While the R0 resection margin was assessed in 643 (89.6%) cases, the total textbook outcomes (TO) were achieved in 525 (74.5%) cases. Overcoming the learning curve of 60 LLRs, resulted in an increasing TO rate from 72.3 to 80.6% ( P =0.024). CONCLUSIONS: It is the first national analysis of a laparoscopic approach in liver surgery in Poland. An increasing trend of minimizing invasiveness in liver resection has been observed. Responsible selection of cases in accordance with difficulty may provide results within global benchmark values and textbook outcomes already during the learning curve.

Pharmacogenetic Variation in Neanderthals and Denisovans and Implications for Human Health and Response to Medications.

Modern humans carry both Neanderthal and Denisovan (archaic) genome elements that are part of the human gene pool and affect the life and health of living individuals. The impact of archaic DNA may be particularly evident in pharmacogenes-genes responsible for the processing of exogenous substances such as food, pollutants, and medications-as these can relate to changing environmental effects, and beneficial variants may have been retained as modern humans encountered new environments. However, the health implications and contribution of archaic ancestry in pharmacogenes of modern humans remain understudied. Here, we explore 11 key cytochrome P450 genes (CYP450) involved in 75% of all drug metabolizing reactions in three Neanderthal and one Denisovan individuals and examine archaic introgression in modern human populations. We infer the metabolizing efficiency of these 11 CYP450 genes in archaic individuals and find important predicted phenotypic differences relative to modern human variants. We identify several single nucleotide variants shared between archaic and modern humans in each gene, including some potentially function-altering mutations in archaic CYP450 genes, which may result in altered metabolism in living people carrying these variants. We also identified several variants in the archaic CYP450 genes that are novel and unique to archaic humans as well as one gene, CYP2B6, that shows evidence for a gene duplication found only in Neanderthals and modern Africans. Finally, we highlight CYP2A6, CYP2C9, and CYP2J2, genes which show evidence for archaic introgression into modern humans and posit evolutionary hypotheses that explain their allele frequencies in modern populations.

High-Throughput Screening of Epigenetic Inhibitors in Meningiomas Identifies HDAC, G9a, and Jumonji-Domain Inhibition as Potential Therapies.

Background Epigenetics may predict treatment sensitivity and clinical course for patients with meningiomas more accurately than histopathology. Nonetheless, targeting epigenetic mechanisms is understudied for pharmacotherapeutic development for these tumors. The bio-molecular insights and potential therapeutic development of meningioma epigenetics led us to investigate epigenetic inhibition in meningiomas. Methods We screened a 43-tumor cohort using a 139-compound epigenetic inhibitor library to assess sensitivity of relevant meningioma subgroups to epigenetic inhibition. The cohort was composed of 5 cell lines and 38 tumors cultured directly from surgery; mean patient age was 56.6 years ± 13.9 standard deviation. Tumor categories: 38 primary tumors, 5 recurrent; 33 from females, 10 from males; 32 = grade 1; 10 = grade 2; 1 = grade 3. Results Consistent with our previous results, histone deacetylase inhibitors (HDACi) were the most efficacious class. Panobinostat significantly reduced cell viability in 36 of 43 tumors; 41 tumors had significant sensitivity to some HDACi. G9a inhibition and Jumonji-domain inhibition also significantly reduced cell viability across the cohort; tumors that lost sensitivity to panobinostat maintained sensitivity to either G9a or Jumonji-domain inhibition. Sensitivity to G9a and HDAC inhibition increased with tumor grade; tumor responses did not separate by gender. Few differences were found between recurrent and primary tumors, or between those with prior radiation versus those without. Conclusions Few efforts have investigated the efficacy of targeting epigenetic mechanisms to treat meningiomas, making the clinical utility of epigenetic inhibition largely unknown. Our results suggest that epigenetic inhibition is a targetable area for meningioma pharmacotherapy.

Alpha-Fetoprotein Response after First Transarterial Chemoembolization (TACE) and Complete Pathologic Response in Patients with Hepatocellular Cancer.

Transarterial chemoembolization (TACE) is used as a bridging treatment in liver transplant candidates with hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the main tumor marker used for HCC surveillance. The aim of this study was to assess the potential of using the AFP change after the first TACE in the prediction of complete tumor necrosis. The study comprised 101 patients with HCC who underwent liver transplantation (LT) after TACE in the period between January 2011 and December 2020. The ΔAFP was defined as the difference between the AFP value before the first TACE and AFP either before the second TACE or the LT. The receiver operator characteristics (ROC) curves were used to identify an optimal cut-off value. Complete tumor necrosis was found in 26.1% (18 of 69) and 6.3% (2 of 32) of patients with an initial AFP level under and over 100 ng/mL, respectively (p = 0.020). The optimal cut-off value of ΔAFP for the prediction of complete necrosis was a decline of ≥10.2 ng/mL and ≥340.5 ng/mL in the corresponding subgroups. Complete tumor necrosis rates were: 62.5% (5 of 8) in patients with an initial AFP < 100 ng/mL and decline of ≥10.2 ng/mL; 21.3% (13 of 61) in patients with an initial AFP < 100 ng/mL and decline of <10.2 ng/mL; 16.7% (2 of 12) in patients with an initial AFP > 100 ng/mL and decline of ≥340.5 ng/mL; and null in 20 patients with an initial AFP > 100 ng/mL and decline of <340.5 ng/mL, respectively (p = 0.003). The simple scoring system, based on the initial AFP and AFP decline after the first treatment, distinguished between a high, intermediate and low probability of complete necrosis, with an area under the ROC curve of 0.699 (95% confidence intervals 0.577 to 0.821, p = 0.001). Combining the initial AFP with its change after the first treatment enables early identification of the efficacy of TACE.

Targeting DNA Methyl Transferases with Decitabine in Cultured Meningiomas.

OBJECTIVE: Meningiomas are a common primary central nervous system tumor that lack a U.S. Food and Drug Administration-approved pharmacotherapy. Approximately 20%-35% of meningiomas are classified as higher grade with poor outcome, whereas patients with lower-grade meningiomas are known to have long-term neurologic deficits and reduced overall survival. Recent efforts to understand the epigenetic landscape of meningiomas have highlighted the importance of DNA methylation for predicting tumor outcomes and prognosis; therefore, inhibition of these pathways may present a viable therapy for these tumors. METHODS: In this study, we perform dose-response curves of decitabine, a DNA methyltransferase inhibitor, on patient-cultured tumors and meningioma cell lines. RESULTS: Thirty total samples were evaluated, including 24 patient-cultured tumors and 6 established meningioma cell lines. Meningiomas were found to have a significant reduction in cell viability after decitabine treatment in a dose dependent manner. The effect was primarily driven by 11 of the 30 tumors in our cohort, or 36.7%. Decitabine significantly reduced cell viability across all grades, tumors from different sexes, recurrent and primary tumors, as well as tumors without a history of previous radiation. Surprisingly, our single radiation-induced tumor did demonstrate greater viability after decitabine treatment. CONCLUSIONS: Our work has identified a potential drug candidate in decitabine for the treatment of meningiomas regardless of clinical subgroup. These data require further evaluation in preclinical models, and the conclusions based on clinical subgroups need to be evaluated in a larger cohort to achieve appropriate statistical power.

Cytokine-Laden Extracellular Vesicles Predict Patient Prognosis after Cerebrovascular Accident.

BACKGROUND: A major contributor to disability after hemorrhagic stroke is secondary brain damage induced by the inflammatory response. Following stroke, global increases in numerous cytokines-many associated with worse outcomes-occur within the brain, cerebrospinal fluid, and peripheral blood. Extracellular vesicles (EVs) may traffic inflammatory cytokines from damaged tissue within the brain, as well as peripheral sources, across the blood-brain barrier, and they may be a critical component of post-stroke neuroinflammatory signaling. METHODS: We performed a comprehensive analysis of cytokine concentrations bound to plasma EV surfaces and/or sequestered within the vesicles themselves. These concentrations were correlated to patient acute neurological condition by the Glasgow Coma Scale (GCS) and to chronic, long-term outcome via the Glasgow Outcome Scale-Extended (GOS-E). RESULTS: Pro-inflammatory cytokines detected from plasma EVs were correlated to worse outcomes in hemorrhagic stroke patients. Anti-inflammatory cytokines detected within EVs were still correlated to poor outcomes despite their putative neuroprotective properties. Inflammatory cytokines macrophage-derived chemokine (MDC/CCL2), colony stimulating factor 1 (CSF1), interleukin 7 (IL7), and monokine induced by gamma interferon (MIG/CXCL9) were significantly correlated to both negative GCS and GOS-E when bound to plasma EV membranes. CONCLUSIONS: These findings correlate plasma-derived EV cytokine content with detrimental outcomes after stroke, highlighting the potential for EVs to provide cytokines with a means of long-range delivery of inflammatory signals that perpetuate neuroinflammation after stroke, thus hindering recovery.

Incisional Surgical Site Infections After Mass and Layered Closure of Upper Abdominal Transverse Incisions: First Results of a Randomized Controlled Trial.

OBJECTIVE: To compare the early results of mass and layered closure of upper abdominal transverse incisions. SUMMARY OF BACKGROUND DATA: Contrary to midline incisions, data on closure of transverse abdominal incisions are lacking. METHODS: This is the first analysis of a randomized controlled trial primarily designed to compare mass with layered closure of transverse incisions with respect to incisional hernias. Patients undergoing laparotomy through upper abdominal transverse incisions were randomized to either mass or layered closure with continuous sutures. Incisional surgical site infection (incisional-SSI) was the primary end-point. Secondary end-points comprised suture-to-wound length ratio (SWLR), closure duration, and fascial dehiscence (clinicatrials.gov NCT03561727). RESULTS: A total of 268 patients were randomized to either mass (n=134) or layered (n=134) closure. Incisional-SSIs occurred in 24 (17.9%) and 8 (6.0%) patients after mass and layered closure, respectively (P =0.004), with crude odds ratio (OR) of 0.29 [95% confidence interval (95% CI) 0.13-0.67; P =0.004]. Layered technique was independently associated with fewer incisional-SSIs (OR: 0.29; 95% CI 0.12-0.69; P =0.005). The number needed to treat, absolute, and relative risk reduction for layered technique in reducing incisional-SSIs were 8.4 patients, 11.9%, and 66.5%, respectively. Dehiscence occurred in one (0.8%) patient after layered closure and in two (1.5%) patients after mass closure (P >0.999). Median SWLR were 8.1 and 5.6 (P <0.001) with median closure times of 27.5 and 25.0 minutes (P =0.044) for layered and mass closures, respectively. CONCLUSIONS: Layered closure of upper abdominal transverse incisions should be preferred due to lower risk of incisional-SSIs and higher SWLR, despite clinically irrelevant longer duration.

High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas.

BACKGROUND: Meningiomas are the most common primary central nervous system tumors. 20-30% of these tumors are considered high-grade and associated with poor prognosis and high recurrence rates. Despite the high occurrence of meningiomas, there are no FDA-approved compounds for the treatment of these tumors. METHODS: In this study, we screened patient-cultured meningiomas with an epigenetic compound library to identify targetable mechanisms for the potential treatment of these tumors. Meningioma cell cultures were generated directly from surgically resected patient tumors and were cultured on a neural matrix. Cells were treated with a library of compounds meant to target epigenetic functions. RESULTS: Although each tumor displayed a unique compound sensitivity profile, Panobinostat, LAQ824, and HC toxin were broadly effective across most tumors. These three compounds are broad-spectrum Histone Deacetylase (HDAC) inhibitors which target class I, IIa, and IIb HDACs. Panobinostat was identified as the most broadly effective compound, capable of significantly decreasing the average cell viability of the sample cohort, regardless of tumor grade, recurrence, radiation, and patient gender. CONCLUSIONS: These findings strongly suggest an important role of HDACs in meningioma biology and as a targetable mechanism. Additional validation studies are necessary to confirm these promising findings, as well to identify an ideal HDAC inhibitor candidate to develop for clinical use.

PEComa-A Rare Liver Tumor.

PEComa (perivascular epithelioid cell tumor) is a rare liver tumor. Decisions regarding patient management are currently based on a few small case series. The aim of this study was to report the clinicopathological features of PEComa in order to provide guidance for management, complemented by our own experience. This retrospective observational study included all patients with PEComa who underwent surgical treatment in two departments between 2002 and 2020. A total of 20 patients were diagnosed with PEComa following histopathological examination. The age of the patients ranged from 21 to 73 years. The majority of patients were women (85%). In most patients, the tumors were incidental. In diagnostic studies, PEComas with high arterial vascularization have been described. Liver resection was the treatment of choice. There was only one postoperative complication. During histopathological evaluation, tumors were composed mostly of epithelioid cells, rarely with spindle cell components, thick-walled vessels, and adipocytes in different proportions. Melanocytic markers (HMB45, MelanA) and at least one smooth muscle marker were expressed in all tumors. Features suggestive of malignancy were found in three cases. In conclusion, PEComa is a rare liver tumor that is usually diagnosed incidentally. In radiological studies, tumors with high arterial vascularization are observed. Liver resection is the treatment of choice.

Performance of initial LI-RADS 2018 treatment response in predicting survival of patients with hepatocellular carcinoma following TACE: a retrospective, single-center cohort study.

PURPOSE: Treatment response following transarterial chemoembolization (TACE) is frequently evaluated with Liver Imaging Reporting and Data System Treatment Response (LR-TR) algorithm, but its association with patients' outcomes is not supported in the literature. The purpose of this study was to provide such data. METHODS: A retrospective analysis of 99 TACE patients with stage A/B hepatocellular carcinoma according to Barcelona-Clinic Liver Cancer staging system was performed. Two radiologists assessed LR-TR, while a third radiologist re-assessed divergent results. Overall survival (OS) and time to disease progression (TTP) were the primary endpoints of the study, while the Cox proportional hazard model was used for outcome analyses. RESULTS: Interobserver agreement was substantial between the two readers with κ = 0.69 (95% CI 0.58-0.81). The median OS in viable, equivocal, and non-viable groups were 27, 27, and 73 months, respectively (p < 0.001). However, after adjustment for confounding factors, there was no significant association between initial viable response and OS (HR 0.98 [95% CI 0.37-2.63], p = 0.97), while equivocal response remained statistically significant (HR 3.52. [95% CI 1.27-9.71], p = 0.015). No significant association was noted when viable and equivocal groups were analyzed in aggregate (HR 1.03 [95% CI 0.4-2.4], p = 0.96). The median TTP did not differ between non-viable and viable groups (23 vs 18 months, respectively; p = 0.98). None of the analyzed predictors was associated with TTP. CONCLUSION: Initial LR-TR response was not an independent predictor for OS nor TTP. The preliminary results suggest the necessity for more aggressive management of equivocal patients.

Intraductal papillary neoplasm of the bile duct - A comprehensive review.

BACKGROUND: Intraductal papillary neoplasm of the bile ducts is a rare tumor type. Management decisions are currently based upon a small case series. The authors have large own experience with IPNB. OBJECTIVE: The review aims at reporting on clinicopathological features of IPNB in order to provide guidance for management. METHODS: We searched PubMed, Medline, Microsoft Academic and Embase databases to identify studies of relevance. The analysis of own experience was also included. RESULTS: We analyzed 59 retrospective series and 25 cases from authors' clinical experience. The main sign was jaundice and cholangitis, 33% and 48%, respectively. CT's were performed in 63-76% and MR in 40-56%. Intraductal mass was found in 31-32% and duct dilatation in 27-30%. Endoscopic Retrograde Cholangio-Pancreatography (ERCP) was performed in 48-62%. IPNB with invasive carcinoma was found in 35.7-60% and IPNB with intraepithelial neoplasia in 36-60%. Histopathological confirmation before surgery was rare. The main treatment of IPNB is resection, in our material, both, hepatectomy and hepatectomy plus bile duct resections were performed in 40% of patients. The percentage of postoperative complications was 20%. The 5-year survival rate of all IPNB's patients was 53.6%; in patients with associated invasive carcinoma - 22.2% and without invasive carcinoma - 100% (p â€‹= â€‹0.001). CONCLUSIONS: Early surgery is advisable for radiologically suspected IPNB. The results of treatment depend on histopathology. They are worse at intraductal invasive carcinoma than at neoplasm with neoplasia.

G-Quadruplexes act as sequence-dependent protein chaperones.

Maintaining proteome health is important for cell survival. Nucleic acids possess the ability to prevent protein aggregation more efficiently than traditional chaperone proteins. In this study, we explore the sequence specificity of the chaperone activity of nucleic acids. Evaluating over 500 nucleic acid sequences' effects on protein aggregation, we show that the holdase chaperone effect of nucleic acids is sequence-dependent. G-Quadruplexes prevent protein aggregation via quadruplex:protein oligomerization. They also increase the folded protein level of a biosensor in E. coli. These observations contextualize recent reports of quadruplexes playing important roles in aggregation-related diseases, such as fragile X and amyotrophic lateral sclerosis (ALS), and provide evidence that nucleic acids have the ability to modulate the folding environment of E. coli.

Totally extraperitoneal inguinal hernia repair with or without fixation leads to similar results. Outcome of randomized prospective trial.

INTRODUCTION: The use of implants in inguinal hernia repair has reduced its recurrence rate. However, postoperative groin pain still remains an unresolved problem. There are suggestions that in totally extraperitoneal inguinal hernia repair (TEP-IHR) two of the likely factors responsible for pain are use of fixation and the type of fixation used. AIM: To evaluate the impact of mesh fixation on the incidence of postoperative pain, restriction of physical activities, hernia recurrence risk, return to normal activities and demand for analgesics in patients after unilateral TEP-IHR. MATERIAL AND METHODS: Unilateral TEP-IHR was performed in 139 male patients randomized to three groups: self-gripping mesh (SG), lightweight mesh (L) and lightweight mesh with fixation (LF). Full study-inclusion criteria were met by 110 patients; 43, 18 and 49 in groups SG, L and LF respectively. Follow-up occurred on the 1st, 2nd, and 7th day and 3, 6, 12 months postoperatively. The numeric rating scale (NRS) was used to assess pain and the EuraHS-QoL (European Registry for Abdominal Wall Hernias Quality of Life Score) questionnaire to compare quality of life (QoL) prior to surgery and one year later. RESULTS: No statistically significant differences were observed between study groups with regard to the incidence rate and intensity of acute post-operative pain, chronic pain, analgesic demand, return to normal activity, hernia recurrence rate and post-operative QoL. CONCLUSIONS: Lack of fixation in TEP-IHR does not increase the risk of hernia recurrence, and its presence does not significantly worsen the treatment results; especially it does not increase the incidence of chronic pain.

Serum bilirubin concentration as a marker of severity of acute appendicitis.

INTRODUCTION: Acute appendicitis (AA) is one of the most common causes of urgent admission to the hospital. Clinically applicable classification distinguishes simple and complex inflammation. Among commonly used inflammation markers of AA, bilirubin concentration is not well studied and thus is rarely applied. AIM: To examine the association between increased serum total bilirubin concentration and the severity of AA. MATERIAL AND METHODS: This retrospective study included 169 patients with a presumptive diagnosis of AA who were operated upon between 2015 and 2017. The determined study endpoints were simple complex inflammation and a different diagnosis after surgery. The Mann-Whitney U, Kruskal-Wallis, Fisher's exact, Spearman correlation coefficient and logistic regression tests and receiver-operating characteristics (ROC) were used in analyses. The area under the curve (AUC) was presented with 95% confidence intervals (95% CIs). Statistical significance was set at 0.05. RESULTS: In total, 84 (49.7%) patients underwent laparotomy and 85 (50.3%) laparoscopy. After surgery, 45 (26.6%) patients had a diagnosis other than AA. Furthermore, 83 (49.1%) and 41 (24.3%) patients had simple and complex AA, respectively. The median bilirubin concentration was 0.56, 0.69, and 1.08 mg/dl in patients without AA, with simple, and complex AA, respectively (p < 0.01). The optimal cut-off for serum bilirubin concentration to predict AA severity was ≥ 0.94 mg/dl (AUC = 0.652; 95% CI: 0.543-0.761) with a 44.9% positive and 83.9% negative predictive value (p = 0.006). CONCLUSIONS: The serum bilirubin concentration should be considered as one of the possible markers of AA. Moreover, it can be used to predict the severity of AA.

Genome-wide functional analyses of plant coiled-coil NLR-type pathogen receptors reveal essential roles of their N-terminal domain in oligomerization, networking, and immunity.

The ability to induce a defense response after pathogen attack is a critical feature of the immune system of any organism. Nucleotide-binding leucine-rich repeat receptors (NLRs) are key players in this process and perceive the occurrence of nonself-activities or foreign molecules. In plants, coevolution with a variety of pests and pathogens has resulted in repertoires of several hundred diverse NLRs in single individuals and many more in populations as a whole. However, the mechanism by which defense signaling is triggered by these NLRs in plants is poorly understood. Here, we show that upon pathogen perception, NLRs use their N-terminal domains to transactivate other receptors. Their N-terminal domains homo- and heterodimerize, suggesting that plant NLRs oligomerize upon activation, similar to the vertebrate NLRs; however, consistent with their large number in plants, the complexes are highly heterometric. Also, in contrast to metazoan NLRs, the N-terminus, rather than their centrally located nucleotide-binding (NB) domain, can mediate initial partner selection. The highly redundant network of NLR interactions in plants is proposed to provide resilience to perturbation by pathogens.

Transjugular Intrahepatic Portosystemic Shunt in patients after orthotopic liver transplantation (OLTx) due to life threatening gastrointestinal hemorrhage. A single-center experience based on three cases and literature review.

BACKGROUND: Transjugular intrahepatic portosystemic shunt system (TIPS) is a well-recognized method of treatment of symptomatic portal hypertension in patients awaiting liver transplantation. The effectiveness of TIPS treatment in patients after liver transplantation is still not fully established. Indications for both groups of patients, with and without liver graft, are similar and include bleeding from gastrointestinal varices, ascites, pleural effusion, and Budd-Chiari syndrome. Feasibility of TIPS in emergency treatment in patients after OLTx due to life-threatening hemorrhage is not well described. MATERIALS AND METHODS: Patients, after OLTx performed using classical, non-piggyback technique had severe hemorrhages from gastrointestinal varices due to lost graft function. Patients were in an unstable condition, required blood transfusions on admittance and monitoring in Intensive Care Unit. TIPS were implanted urgently, after unsuccessful endoscopic treatment, as a life-saving procedure. RESULTS: In all cases, the procedure was successfully completed. The bleeding did not reoccur during the postoperative course. CONCLUSION: TIPS procedure appears to be justified as a bridge to a planned retransplantation, or as a treatment of choice in patients disqualified from retransplantation. Emergency performance of the TIPS procedure as a treatment for acute variceal bleeding should still be considered individually for each patient and only as a procedure leading to further treatment.

Individual Surgeon Experience Yields Bimodal Effects on Patient Outcomes After Deceased-Donor Liver Transplant: Results of a Quantile Regression for Survival Data.

OBJECTIVES: Data on the relevance of surgeon experience in liver transplant procedures are scarce. In this study, we evaluated the effects of individual surgeon experience on survival outcomes after deceased-donor liver transplant. MATERIALS AND METHODS: In this retrospective analysis of 1193 liver transplant procedures, quantile regression for survival data was performed to assess the effects of surgeon experience. Conditional quantiles of mortality and graft loss were set as primary and secondary outcome measures, respectively, which were categorized as early, midterm, and late. RESULTS: Greater experience of a surgeon performing hepatectomy increased the risk of early mortality (P = .005) and graft loss (P = .025) when the recipient Model for End-Stage Liver Disease was ≤ 25 and the donor Model for End-Stage Liver Disease was ≤ 1600. In conventional transplant procedures, greater experience of surgeon performing hepatectomy additionally increased the risk of midterm mortality (P = .027) and graft loss (P = .046). Conversely, a graft implant procedure performed by a more experienced surgeon was associated with better early, midterm, and late outcomes after conventional transplants (all P < .037) and reduced the risk of early graft loss when the donor Model for End-Stage Liver Disease score was > 1600 (P = .027). CONCLUSIONS: Unexpectedly, individual surgeon experience yields bimodal effects on posttransplant outcomes, dependent on the stage of operation, operative technique, severity of recipient status, and transplant risk profile.

Liver Function in Patients With Nonalcoholic Fatty Liver Disease Randomized to Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy: A Secondary Analysis of a Randomized Clinical Trial.

OBJECTIVES: The aim of the study was to compare the influence of sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB) on liver function in bariatric patients with non-alcoholic fatty liver disease (NAFLD) in a randomized clinical trial (NCT01806506). BACKGROUND: Rapid weight loss and malabsorption after bariatric surgery in patients with NAFLD or steatohepatitis (NASH) may impair liver function. METHODS: Sixty-six morbidly obese patients randomized to SG or RYGB were included in a secondary outcome analysis. Intraoperative liver biopsies were categorized with NAFLD Activity Score (NAS) and liver function tests were done before surgery and after 1, 6 and 12 months. RESULTS: NASH was present in 54.5% RYGB and 51.5% SG patients (P > 0.05). At 12 months excess weight loss was 68.7 ±â€Š19.7% after SG and 62.8 ±â€Š18.5% after RYGB (P > 0.05). At 1 month international normalized ratio (INR) increased after RYGB (0.98 ±â€Š0.05 vs 1.14 ±â€Š0.11; P < 0.05) and SG (0.99 ±â€Š0.06 vs 1.04 ±â€Š0.06; P < 0.05), RYGB induced significantly greater increase in INR in the whole group and NASH patients than SG. After RYGB albumin decreased at 1 month (41.2 ±â€Š2.7 vs 39.0 ±â€Š3.2 g/L; P < 0.05). At 12 months, INR and albumin returned to baseline. At 12 months in NASH group, SG induced significant improvement in aspartate aminotransferase (32.4 ±â€Š17.4 vs 21.5 ±â€Š6.9U/L), alanine aminotransferase (39.9 ±â€Š28.6U/L vs 23.8 ±â€Š14.1U/L), gamma-glutamyl transpeptidase (34.3 ±â€Š16.6 vs 24.5 ±â€Š16.8U/L), and lactate dehydrogenase (510.8 ±â€Š33 vs 292.4 ±â€Š29). Variables predictive of INR change after 1 month included operation type, NAS ≥ 5, bilirubin, body mass index, hemoglobin A1C, and dyslipidemia. CONCLUSIONS: Patients with NASH undergoing RYGB are more susceptible to early transient deterioration of liver function than after SG.

Ghrelin, leptin, and glycemic control after sleeve gastrectomy versus Roux-en-Y gastric bypass-results of a randomized clinical trial.

BACKGROUND: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) cause weight loss and metabolic improvement, but results of published studies are contradictory. OBJECTIVES: The aim of this study was to compare the effects of SG and RYGB on ghrelin, leptin, and glucose homeostasis in a randomized controlled trial. SETTING: University hospital, Poland. METHODS: Seventy-two morbidly obese patients were randomly selected to undergo either SG (n = 36) or RYGB (n = 36). Fasting ghrelin, leptin, glucose, insulin, C-peptide, glucagon, glycated hemoglobin, and homeostasis model assessment of insulin resistance were assessed preoperatively and at 1, 6, and 12 months postoperatively. No differences were found in anthropometric and biochemical parameters between the study groups at baseline. RESULTS: Sixty-nine (95.8%) patients completed the study. Percentage of excess weight loss at 12 months was 67.6±19.3% after SG and 64.2±18.5% after RYGB (P>.05). Fasting ghrelin levels decreased 1 month after SG (from 76.8 pmol/L to 35.3 pmol/L; P<.05) and remained reduced until 12 months (41.6 pmol/L; P<.05) but increased 12 months after RYGB from 74.6 pmol/L to 130.2 pmol/L (P<.05). Leptin, glucose, insulin, and C-peptide concentrations and glycated hemoglobin and homeostasis model assessment of insulin resistance values decreased significantly in both groups during 12 months. CONCLUSIONS: RYGB and SG induce comparable weight loss and improvement in metabolism of glucose. Ghrelin levels decrease after SG and increase after RYGB, but this difference does not affect similar outcomes of these procedures during 1-year follow-up. The contribution of ghrelin to weight loss or metabolic benefits after bariatric surgery is not straightforward, but rather influenced by multiple factors.

Expression of resistin in the liver of patients with non-alcoholic fatty liver disease.

Adipokines are cytokines that presumably connect the pathologies of metabolic syndrome. One of the adipokines is resistin, the role of which in insulin resistance, obesity, and non-alcoholic fatty liver disease (NAFLD) needs to be determined. Liver biopsy specimens were obtained intraoperatively from 214 obese patients. Histological assessment was based on NAFLD activity score according to Kleiner. Statistical analysis involved semi-quantitive immunohistochemistry assessment of resistin staining and: NAFLD status in obese patients compared with a non-obese control group, selected clinical data (age, sex, body mass index - BMI), selected biochemical data, comorbidities (hypertension, type 2 diabetes mellitus, dyslipidaemia), and metformin treatment in patients with type 2 diabetes mellitus. Resistin expression was observed in the histiocytes of inflammatory infiltrate, Kupffer cells, and histiocytes surrounding the hepatocytes with steatosis. There was a positive correlation between the total expression of resistin and: (1) NAFLD advancement (NAFLD Activity Score- NAS), (2) AST, ALT, BMI, glucose, insulin, Homeostasis Model Assessment (HOMA), LDH, GGT, triglycerides (TG), and glycated haemoglobin (HbA1c). Resistin expression was more intense in patients with type 2 diabetes mellitus and dyslipidaemia and less intense in the control group. Resistin probably plays a role in the pathogenesis of hepatic insulin resistance and aggravates pathologic changes in the liver of patients with NAFLD.