Evaluation of quality and quantity of randomized controlled trials in hepatobiliary surgery: A scoping/mapping review.

AIM: To evaluate the quantity and quality of randomized controlled trials (RCTs) in hepatobiliary surgery and for identifying gaps in current evidences. METHODS: A systematic search was conducted in MEDLINE (via PubMed), Web of Science, and Cochrane Controlled Register of Trials (CENTRAL) for RCTs of hepatobiliary surgery published from inception until the end of 2023. The quality of each study was assessed using the Cochrane risk-of-bias (RoB) tool. The associations between risk of bias and the region and publication date were also assessed. Evidence mapping was performed to identify research gaps in the field. RESULTS: The study included 1187 records. The number and proportion of published randomized controlled trials (RCTs) in hepatobiliary surgery increased over time, from 13 RCTs (.0005% of publications) in 1970-1979 to 201 RCTs (.003% of publications) in 2020-2023. There was a significant increase in the number of studies with a low risk of bias in RoB domains (p < .01). The proportion of RCTs with low risk of bias improved significantly after the introduction of CONSORT guidelines (p < .001). The evidence mapping revealed a significant research focus on major and minor hepatectomy and cholecystectomy. However, gaps were identified in liver cyst surgery and hepatobiliary vascular surgery. Additionally, there are gaps in the field of perioperative management and nutrition intervention. CONCLUSION: The quantity and quality of RCTs in hepatobiliary surgery have increased over time, but there is still room for improvement. We have identified gaps in current research that can be addressed in future studies.

Surgical management of primary liver cancers during the COVID-19 pandemic: overcoming the dilemma with standardization.

BACKGROUND: The present study evaluates the impact of the pandemic on outcomes after surgical treatment for primary liver cancer in a high-volume hepatopancreatobiliary surgery center. METHODS: Patients, who underwent liver resection for primary liver resection between January 2019 and February 2020, comprised pre-pandemic control group. The pandemic period was divided into two timeframes: early pandemic (March 2020-January 2021) and late pandemic (February 2021-December 2021). Liver resections during 2022 were considered as the post-pandemic period. Peri-, and postoperative patient data were gathered from a prospectively maintained database. RESULTS: Two-hundred-eighty-one patients underwent liver resection for primary liver cancer. The number of procedures decreased by 37.1% during early phase of pandemic, but then increased by 66.7% during late phase, which was comparable to post-pandemic phase. Postoperative outcomes were similar between four phases. The duration of hospital stay was longer during the late phase, but not significantly different compared to other groups. CONCLUSION: Despite an initial reduction in number of surgeries, COVID-19 pandemic had no negative effect on outcomes of surgical treatment for primary liver cancer. The structured standard operating protocol in a high-volume and highly specialized surgical center can withstand negative effects, a pandemic may have on treatment of patients.

Repeat liver resection for recurrent intrahepatic cholangiocarcinoma: meta-analysis.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a relatively rare malignancy. The aim of this meta-analysis was to evaluate outcomes of repeat liver resection and non-surgical approaches for treatment of recurrent ICC. METHODS: PubMed, Embase, and Web of Science databases were searched from their inception until March 2021 for studies of patients with recurrent ICC. Studies not published in English were excluded. Two meta-analyses were performed: a single-arm meta-analysis of studies reporting pooled short- and long-term outcomes after repeat liver resection for recurrent ICC (meta-analysis A), and a meta-analysis of studies comparing 1-, 3-, and 5-year overall survival (OS) rates after repeat liver resection and non-surgical approaches for recurrent ICC (meta-analysis B). RESULTS: Of 543 articles retrieved in the search, 28 were eligible for inclusion. Twenty-four studies (390 patients) were included in meta-analysis A and nine studies (591 patients) in meta-analysis B. After repeat liver resection, 1-, 3-, and 5-year OS rates were 87 (95 per cent c.i. 81 to 91), 58 (48 to 68), and 39 (29 to 50) per cent respectively. The 1-, 3-, and 5-year OS rates were higher after repeat liver resection than without surgery: odds ratio 2.70 (95 per cent c.i. 1.28 to 5.68), 2.89 (1.15 to 7.27), and 5.91 (1.59, 21.90) respectively. CONCLUSION: Repeat liver resection is a suitable strategy for recurrent ICC in selected patients. It improves short- and long-term outcomes compared with non-surgical treatments.

Portal vein arterialization as a salvage procedure in hepatopancreatobiliary surgery: a systematic review.

Background: Portal vein arterialization (PVA) is a possible option when hepatic artery reconstruction is impossible during liver resection. The aim of this study was to review the literature on the clinical application of PVA in hepatopancreatobiliary (HPB) surgery. Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched the PubMed, Embase and Web of Science databases until December 2019. Experimental (animal) studies, review articles and letters were excluded. Results: Twenty studies involving 57 patients were included. Cholangiocarcinoma was the most common indication for surgery (40 patients [74%]). An end-to-side anastomosis between a celiac trunk branch and the portal vein was the main PVA technique (35 patients [59%]). Portal hypertension was the most common longterm complication (12 patients [21%] after a mean of 4.1 mo). The median followup period was 12 (range 1-87) months. The 1-, 3- and 5-year survival rates were 64%, 27% and 20%, respectively. Conclusion: Portal vein arterialization can be considered as a rescue option to improve the outcome in patients with acute liver de-arterialization when arterial reconstruction is not possible. To prevent portal hypertension and liver injuries due to thrombosis or overarterialization, vessel calibre adjustment and timely closure of the anastomosis should be considered. Further prospective experimental and clinical studies are needed to investigate the potential of this procedure in patients whose liver is suddenly de-arterialized during HPB procedures.

Contexte: L'artérialisation de la veine porte (AVP) est une option envisageable lorsqu'il est impossible de reconstruire l'artère hépatique au moment d'une résection du foie. Le but de cette étude était de faire le point sur la littérature concernant l'application clinique de l'AVP en cours de chirurgie hépatopancréatobiliaire (HPB). Méthodes: Nous avons procédé à une revue systématique selon les directives PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Nous avons interrogé systématiquement les bases de données PubMed, Embase et Web of Science jusqu'à décembre 2019. Les études expérimentales (chez l'animal), les articles de synthèse et les lettres ont été exclus. Résultats: Vingt études regroupant 57 patients ont été incluses. Le cholangiocarcinome était la plus fréquente indication de la chirurgie (40 patients [74 %]). L'anastomose terminolatérale d'une branche du tronc cæliaque avec la veine porte a été la principale technique d'AVP (35 patients [59 %]). L'hypertension portale a été la plus fréquente complication (12 patients [21 %] après une moyenne de 4,1 mois). Le suivi médian a été de 12 mois (éventail, 1­87 mois). Les taux de survie moyens à 1, 3 et 5 ans ont été de 64 %, 27 % et 20 %, respectivement. Conclusion: L'artérialisation de la veine porte peut être considérée comme une option de dernier ressort pour améliorer l'état des patients victimes d'une désartérialisation hépatique aiguë lorsque la reconstruction artérielle est impossible. Pour prévenir l'hypertension portale et les lésions au foie dues à la thrombose ou à l'hyperartérialisation, il faut veiller à ajuster le calibre vasculaire et fermer rapidement l'anastomose. D'autres études expérimentales et cliniques prospectives s'imposent afin d'analyser le potentiel de cette intervention chez les patients dont le foie se trouve subitement désartérialisé durant une chirurgie HPB.

The optimal intestinal segment length for experimental size-mismatched intestinal transplantation: Defining the maximum length with the lowest blood flow needs in a porcine model.

Transplanted Intestinal Segments (IS) must match the perfusion capacities of the recipient. This can be challenging during a size-mismatched SBTX. In this study, we defined the maximum IS length with lowest blood flow needs in a porcine model by evaluating the physiological perfusion rates of different IS lengths. Blood flow in the SMA, aorta segment four, and general circulatory parameters were monitored before and after sequential intestinal resection. IS lengths of 30 cm, 60 cm, 120 cm, and 300 cm (n = 8 each) were compared. The IS blood flow requirements increased with IS length (30 cm: 19.5 ± 3.4 mL/min; 60 cm: 16.9 ± 6.7 mL/min; 120 cm: 34.9 ± 8.5 mL/min; 300 cm: 62.9 ± 11.6 mL/min). Absolute IS blood flow (P = .004), percentage IS blood flow uptake from the SMA (P = .001), and percentage IS blood flow uptake from the aorta (P = .005) increased significantly between 60 cm and 120 cm. We concluded that 60 cm was the maximum IS length before blood flow demands significantly increased in a porcine model.

Does acid-base equilibrium correlate with remnant liver volume during stepwise liver resection?

Small for size and flow syndrome (SFSF) is one of the most challenging complications following extended hepatectomy (EH). After EH, hepatic artery flow decreases and portal vein flow increases per 100 g of remnant liver volume (RLV). This causes hypoxia followed by metabolic acidosis. A correlation between acidosis and posthepatectomy liver failure has been postulated but not studied systematically in a large animal model or clinical setting. In our study, we performed stepwise liver resections on nine pigs to defined SFSF limits as follows: step 1: segment II/III resection, step 2: segment IV resection, step 3: segment V/VIII resection (RLV: 75, 50, and 25%, respectively). Blood gas values were measured before and after each step using four catheters inserted into the carotid artery, internal jugular vein, hepatic artery, and portal vein. The pH, [Formula: see text], and base excess (BE) decreased, but [Formula: see text] values increased after 75% resection in the portal and jugular veins. EH correlated with reduced BE in the hepatic artery. Pco2 values increased after 75% resection in the jugular vein. In contrast, arterial Po2 increased after every resection, whereas the venous Po2 decreased slightly. There were differences in venous [Formula: see text], BE in the hepatic artery, and Pco2 in the jugular vein after 75% liver resection. Because 75% resection is the limit for SFSF, these noninvasive blood evaluations may be used to predict SFSF. Further studies with long-term follow-up are required to validate this correlation.NEW & NOTEWORTHY This is the first study to evaluate acid-base parameters in major central and hepatic vessels during stepwise liver resection. The pH, [Formula: see text], and base excess (BE) decreased, but [Formula: see text] values increased after 75% resection in the portal and jugular veins. Extended hepatectomy correlated with reduced BE in the hepatic artery. Because 75% resection is the limit for small for size and flow syndrome (SFSF), postresection blood gas evaluations may be used to predict SFSF.

Analysis of the hemostatic potential of modern topical sealants on arterial and venous anastomoses: an experimental porcine study.

One of the widely accepted adjunctive agents in the variety of surgical modalities are sealants. Our study aim was to compare four commonly used modern sealants in a standardized experimental setting to assess their feasibility, and hemostatic efficacy in vascular anastomosis. Forty landrace pigs (weight: 24.7 ± 3.8 kg) were randomized into the control (n = 8) and four sealant groups; TachoSil® (n = 8), Tissucol Duo® (n = 8), Coseal® (n = 8), and FloSeal® (n = 8). After doing a portal vein end-to-end anastomosis as well as stitches of aortic incision, the sealants were applied on anastomotic site. The control group was left intact. In portal vein anastomosis, the sealants led to a complete hemostasis significantly better than control group. The mean of blood loss was also significantly reduced. In successful subgroups, there was a difference in the mean-time to reach complete hemostasis ranging from 15 s in Coseal® to 76 s in FloSeal® group (p < 0.05). In aortotomy experiments, except Tissucol Due®, which had insufficient hemostasis, other sealants led to a complete hemostasis. The mean blood loss was significantly reduced in sealants groups as well. The four sealants are effective in reducing the suture-hole bleeding in portal vein anastomosis. However, the hemostatic potential is heterogeneous among sealants. This means that "one-size-fits-all" approach is not appropriate for application of sealants in diversity of vascular surgery and it should be based on the type and the severity of injury and the structure of tissue. Comparison of hemostasis efficacy of four modern sealants (TachoSil®, Tissucol Duo®, Coseal®, and FloSeal®) in vascular anastomosis in porcine model. The figures below show the total blood loss (g) in the control and sealant groups after aortotomy (left) and portal vein anastomosis (right). The mean of blood loss decreased significantly by the usage of sealants in both experiment groups as compared to control group (*: p < 0.05; sealant groups vs. control group). 1. The right column shows the mean of blood loss (g) in all experiments in each group. 2. The middle column presents the subgroup with unsuccessful hemostasis at the end of observation time (Tmax = 20 sec. for aortotmy and 300 sec. for portal vein anastomosis). 3. The left column shows mean of total blood loss in subgroups with successful hemostasis during observation time (20 sec for aortotomy and 300 sec for portal vein).

A simplified technique of pancreas transplantation in a porcine model.

BACKGROUND: The incidence of diabetes has been steadily increasing. The only curative option for diabetes is pancreas transplantation (PTx). Porcine models are valuable because of their anatomical and physiological similarities to human beings. Our aim is to introduce a simplified technique of PTx in a porcine model. METHODS: In Landrace pigs (n = 32), after median laparotomy, the pancreas was mobilized, and the portal and splenic veins were divided. The proper hepatic and splenic arteries and the bile duct were also prepared, and the duodenal bulb was prepared and stapled. The third portion of the duodenum was freed up to the ligament of Treitz and stapled, and the renal arteries were ligated. After systemic heparinization, the pancreas was perfused through the abdominal aorta with histidine-tryptophan-ketoglutarate solution. The portal and splenic veins were cut for evaluating the sufficiency of perfusion. Whole pancreaticoduodenal graft was procured along with an aortic jump graft containing mesenteric and celiac trunks. In recipients, after total pancreatectomy, the suprarenal inferior vena cava and infrarenal aorta were prepared for vascular anastomosis in an end-to-side manner. After pancreas reperfusion, duodenoduodenostomy was performed in an end-to-side manner. RESULTS: Median cold and warm ischemia times were 10 h (range, 9-14 h) and 50 min (range, 35-80 min), respectively. The hemodynamic status was stable throughout the operation. The median follow-up period was 7 days (range, 4-10). There were no major intra- and postoperative complications. CONCLUSION: By using an aortic jump graft, there was no need to perform additional arterial reconstruction resulting in a short warm ischemic and operation time. End-to-side portocaval and duodenoduodenal anastomoses make this model of PTx a very feasible method for experimental evaluations.

Robot-assisted versus laparoscopic living donor nephrectomy: superior outcomes after completion of the learning curve.

The use of robots in donor nephrectomy has increased in recent years. However, whether robot-assisted methods have better outcomes than traditional laparoscopic methods and how surgical experience influences these outcomes remains unclear. This meta-analysis compares the outcomes of robot-assisted donor nephrectomy (RADN) with those of laparoscopic donor nephrectomy (LDN) and to investigate the effects of surgical experience on these outcomes. A systematic literature search was conducted in Medline (through PubMed) and Web of Science databases. Perioperative data were extracted for meta-analysis. To assess the impact of the learning curve, a subgroup analysis was performed to compare outcomes between inexperienced and experienced surgeons. Seventeen studies with 6970 donors were included. Blood loss was lower (mean difference [MD] = - 13.28, p < 0.01) and the warm ischemia time was shorter (MD = - 0.13, p < 0.05) in the LDN group than the RADN group. There were no significant differences in terms of conversion to open surgery, operation time, surgical complications, hospital stay, costs, and delayed graft function between the groups. Subgroup analysis revealed that operation time (MD = - 1.09, p < 0.01) and length of hospital stay (MD = - 1.54, p < 0.05) were shorter and the rate of conversion to open surgery (odds ratios [OR] = 0.14, p < 0.0001) and overall surgical complications (OR = 0.23, p < 0.05) were lower in experienced RADN surgeons than in experienced LDN surgeons. Surgical experience enhances the perioperative outcomes following RADN more than it does following LDN. This suggests that RADN could be the method of choice for living donor nephrectomy as soon as surgeons gain sufficient experience in robotic surgery.

The role of HBIg as hepatitis B reinfection prophylaxis following liver transplantation.

BACKGROUND AND INTRODUCTION: Without adequate prophylaxis, liver transplantation (LTx) is frequently followed by hepatitis B virus (HBV) reinfection, which results in rapidly progressing liver disease and significantly decreased overall survival. In the last two decades, significant progress has been made in the prophylaxis and treatment of HBV. DISCUSSION: We present an overview of different protocols and regimens used for prophylaxis of HBV reinfection after LTx and describe the protocol implemented at our center. Following LTx, HBV reinfection can be effectively prevented by administration of anti-hepatitis B immunoglobulin (HBIg) alone or more recently in combination with antiviral nucleoside/nucleotide analogs (NUCs). Several studies reported good results with the use of HBIg alone, but combination treatment with HBIg and NUCs has proven to be a superior prophylactic regimen for HBV recurrence. At present, combination therapy (HBIg and a nucleoside or nucleotide analog) is the gold standard used in many transplantation centers. This preventive regimen reduces the risk of a recurrence of HBV infection and thereby the need for re-transplantation. Future and ongoing studies will show how long HBIg must be given after transplantation, especially when used in combination with potent antivirals, such as entecavir or tenofovir.

Portocaval shunt can optimize transhepatic flow following extended hepatectomy: a short-term study in a porcine model.

The aim of this study was to evaluate whether the portocaval shunt (PCS) corrects these unwanted changes in transhepatic flow after extended hepatectomy (EH). Forty female Landrace pigs were divided into two main groups: (A) EH (75%) and (B) no EH. Group A was divided into 3 subgroups: (A1) EH without PCS; (A2) EH with side-to-side PCS; and (A3) EH with end-to-side PCS. Group B was divided into 2 subgroups: (B1) side-to-side PCS and (B2) end-to-side PCS. HAF, PVF, and PVP were measured in each animal before and after the surgical procedure. EH increased the PVF/100 g (173%, p < 0.001) and PVP (68%, p < 0.001) but reduced the HAF/100 g (22%, p = 0.819). Following EH, side-to-side PCS reduced the increased PVF (78%, p < 0.001) and PVP (38%, p = 0.001). Without EH, side-to-side PCS reduced the PVF/100 g (68%, p < 0.001) and PVP (12%, p = 0.237). PVP was reduced by end-to-side PCS following EH by 48% (p < 0.001) and without EH by 21% (p = 0.075). PCS can decrease and correct the elevated PVP and PVF/100 g after EH to close to the normal values prior to resection. The decreased HAF/100 g in the remnant liver following EH is increased and corrected through PCS.

Case Report: Successful DaVinci-Assisted Major Liver Resection for Alveolar Echinococcosis.

We report a case of successful robot-assisted major liver resection in a patient with liver alveolar echinococcosis (AE). A 62-year-old male patient was incidentally diagnosed with a large infiltrative lesion in the right liver lobe suspicious for AE. A radical surgical resection as a right-sided hemihepatectomy was indicated. The operation was carried out via a robotic-assisted procedure using the DaVinci Xi Surgical System. The tumor measured 12.4 × 8.8 cm and was successfully resected through a suprapubic incision of 13 cm. The patient was free of pain after the second post-operative day. A fluid collection near the resection plate was easily drained without bile leakage. The patient had no surgical complications. Radical resection is inevitable for adequate curative therapy of AE and provides clear margins. Robotic surgery is a relatively new and safe option for curative resection of AE lesions, with remarkable advantages for patients and surgeons.

A fast and easy-to-learn technique for liver resection in a porcine model.

OBJECTIVE: Despite the recent advances in surgical techniques and perioperative care, liver resection (especially extended hepatectomy) is still a high-risk procedure with considerable morbidity and mortality. Experimental large animal models are the best option for studies in this regard. The present study was performed to present an easy-to-learn, fast, and multipurpose model of liver resection in a porcine model. METHOD: Stepwise liver resections (resection of segments II/III, IVa/IVb, and VIII/IV) were performed in eight pigs with intraoperative monitoring of hemodynamic parameters. The technical aspects, tips, and tricks of this method are explained in detail. RESULTS: Based on the specific anatomical characteristics of the porcine liver, all resection types including segmental resection, hemihepatectomy, and extended hepatectomy could be performed in one animal in an easy-to-learn and fast technique. All animals were hemodynamically stable following stepwise liver resection. CONCLUSION: Stepwise liver resection using stapler in a porcine model is a fast and easy-to-learn method with which junior staff and research fellows can perform liver resection up to extended hepatectomy under stable conditions.

Experimental Rat Model for Brain Death Induction and Kidney Transplantation.

Background: Experimental animal research has been pivotal in developing clinical kidney transplantation (KTx). One donor-associated risk factor with negative affect of transplantation outcome is brain death (BD). Many rat models for BD and KTx have been developed in the last decade, but no surgical guidelines have been developed for these models. Here, we describe a surgical technique for BD induction and the cuff technique for experimental KTx in rats.Methods: After intubation and mechanically ventilation of sixteen healthy adult male Sprague-Dawley rats were induction of BD performed. Animals were kept hemodynamically stable for eight hours. Then, the kidney was prepared and perfused with standard histidine-tryptophan-ketoglutarate solution. After explantation, grafts were immediately implanted in recipients using the cuff technique and reperfused. After 2 h of observation, animals were sacrificed by intravenous administration of potassium chloride.Results: In the early phase of BD, heart rate increased and mean arterial pressure decreased. Partial variations were observed in O2 partial pressure, O2 saturation, and HCO3. During the 2-h observation phase, all transplanted kidneys were sufficiently perfused macroscopically. There was no hyperacute rejection.Conclusions: It is feasible to observe BD for 8 h with maintained circulation in small experimental settings. The cuff technique for KTx is simple, the complication rate is low, and the warm ischemia time is short, therefore, this could be a suitable technique for KTx in the rat model.

Oral Preconditioning of Donors After Brain Death With Calcineurin Inhibitors vs. Inhibitors of Mammalian Target for Rapamycin in Pig Kidney Transplantation.

Background: The systemic inflammatory cascade triggered in donors after brain death enhances the ischemia-reperfusion injury after organ transplantation. Intravenous steroids are routinely used in the intensive care units for the donor preconditioning. Immunosuppressive medications could be potentially used for this purpose as well. Data regarding donor preconditioning with calcineurin inhibitors or inhibitors of mammalian target for Rapamycin is limited. The aim of this project is to investigate the effects of (oral) donor preconditioning with a calcineurin inhibitor (Cyclosporine) vs. an inhibitor of mammalian target for Rapamycin (Everolimus) compared to the conventional administration of steroid in the setting of donation after brain death in porcine renal transplantation. Methods: Six hours after the induction of brain death, German landrace donor pigs (33.2 ± 3.9 kg) were randomly preconditioned with either Cyclosporine (n = 9) or Everolimus (n = 9) administered via nasogastric tube with a repeated dose just before organ procurement. Control donors received intravenous Methylprednisolone (n = 8). Kidneys were procured, cold-stored in Histidine-Tryptophane-Ketoglutarate solution at 4°C and transplanted in nephrectomized recipients after a mean cold ischemia time of 18 h. No post-transplant immunosuppression was given to avoid confounding bias. Blood samples were obtained at 4 h post reperfusion and daily until postoperative day 5 for complete blood count, blood urea nitrogen, creatinine, and electrolytes. Graft protocol biopsies were performed 4 h after reperfusion to assess early histological and immunohistochemical changes. Results: There was no difference in the hemodynamic parameters, hemoglobin/hematocrit and electrolytes between the groups. Serum blood urea nitrogen and creatinine peaked on postoperative day 1 in all groups and went back to the preoperative levels at the conclusion of the study on postoperative day 5. Histological assessment of the kidney grafts revealed no significant differences between the groups. TNF-α expression was significantly lower in the study groups compared with Methylprednisolone group (p = 0.01) Immunohistochemistry staining for cytochrome c showed no difference between the groups. Conclusion: Oral preconditioning with Cyclosporine or Everolimus is feasible in donation after brain death pig kidney transplantation and reduces the expression of TNF-α. Future studies are needed to further delineate the role of oral donor preconditioning against ischemia-reperfusion injury.

Evaluation of the impact of Tacrolimus-based immunosuppression on Heidelberg liver transplant cohort (HDTACRO): Study protocol for an investigator initiated, non-interventional prospective study.

BACKGROUND: Tacrolimus-based immunosuppression has resulted in enormous improvements on liver transplantation (LTx) outcomes. However, dose adjustment and medication adherence play a key role in post-transplant treatment success. The aim of the present study is to assess the trough levels and the need for adaptation of therapeutic doses in de novo LTx patients treated with Tacrolimus in the clinical routine, without any intervention to the treatment regimen. METHODS AND ANALYSIS: This is a pilot, prospective, exploratory, monocentric, non-interventional and non-randomized investigator-initiated study. Prospectively maintained data of 100 patients treated with various oral Tacrolimus-based immunosuppressants (Prograf or Envarsus) will be analyzed. The number of required dose adjustments of Tacrolimus formulations used in clinical routine for achieving the target trough level, Tacrolimus trough level, Tacrolimus dosing, concentration/dose ratio, routine laboratory tests, efficacy data (incl. survival, acute rejection, re-transplantation), patients therapy adherence, and infections requiring the need to reduce individual immunosuppressant dosing will be evaluated for each patient. RESULT: This study will evaluate the trough levels and the need for adaptation of therapeutic doses in de novo LTx patients treated with Tacrolimus in the clinical routine, without any intervention to the treatment regimen. CONCLUSION: The HDTACRO study will be the first study to systematically and prospectively evaluate various oral Tacrolimus-based immunosuppressants in de novo liver transplanted patients. If a difference between the therapy-subgroups is evident at the end of the trial, a randomized control trial will eventually be designed. Registration number: ClinicalTrials.gov: NCT04444817.

Histopathological effects of modern topical sealants on the liver surface after hepatectomy: an experimental swine study.

The present study aimed to determine the impact of different sealant materials on histopathological changes to the liver surface after liver resection. Thirty-six landrace pigs underwent left anatomical hemihepatectomy and were assigned to a histopathological control group (HPC, n = 9) with no bleeding control, a clinically simulated control group (CSC, n = 9) with no sealant but bipolar cauterization and oversewing of the liver surface, and two treatment groups (n = 9 each) with a collagen-based sealant (CBS) or a fibrinogen-based sealant (FBS) on resection surface. After postoperative day 6, tissue samples were histologically examined. There were no significant differences in preoperative parameters between the groups. Fibrin production was higher in sealant groups compared with the HPC and CSC groups (both p < 0.001). Hepatocellular regeneration in sealant groups was higher than in both control groups. A significantly higher regeneration was seen in the FBS group. Use of sealants increased the degree of fibrin exudation at the resection plane. Increased hepatocellular necrosis was seen in the CBS group compared with the FBS group. The posthepatectomy hepatocellular regeneration rate was higher in the FBS group compared with the CBS group. Randomized studies are needed to assess the impact of sealants on posthepatectomy liver regeneration in the clinical setting.

Simultaneous Serial Transverse Enteroplasty (STEP) in Size Mismatch Small Bowel Transplantations.

BACKGROUND: Small bowel transplantation (SBTX) in children receiving larger grafts from adults can be challenging because of size mismatch. The aim of the present study was to assess whether a simultaneous serial transverse enteroplasty (STEP) can address the problem of size mismatch. METHODS: Three different size ratio groups between donors and recipients were compared in a porcine model with a 14-day follow-up. The groups were size matched, size mismatched (1:3.8 weight ratio), and size mismatched + STEP (each n = 8). RESULTS: It was technically feasible to simultaneously perform a STEP and SBTX of a mismatched intestinal segment. The postoperative clinical course was uneventful. No signs of bleeding, leakage, stenosis, or ileus were observed and the intestinal segment was well perfused at relaparotomy. Body weight decreased in all groups, but the percentage decrease was lowest in the mismatched + STEP group. Vital enterocyte masses were similar in all the groups (citrulline levels) and the nutritional status was best in the STEP group (transferrin levels, p = 0.04). CONCLUSIONS: We have demonstrated that a simultaneous STEP and SBTX procedure is technically feasible and clinically useful in overcoming the challenges associated with size mismatched SBTX. Our short-term findings justify further investigation in a larger series to elucidate the long-term outcomes of this procedure.