Portal vein thrombosis and liver transplantation: management, matching, and outcomes. A retrospective multicenter cohort study.

BACKGROUND AND AIMS: Besides the increased risk of perioperative morbidity, graft failure, and mortality, the majority of PVT are diagnosed at liver transplantation (LT). Improving preoperative management and patient selection may lead to better short-term and long-term outcomes and reduce the risk of a futile LT. The authors aimed to identify predictors of adverse outcomes after LT in patients with nonmalignant portal vein thrombosis (PVT) and improve donor to recipient matching by analyzing the results of the Italian cohort of LT recipients. METHODS: Adult patients who underwent LT in Italy between January 2000 and February 2020 diagnosed with PVT pre-LT or at time of LT were considered eligible for inclusion. Based on a survey encompassing all 26 surgeons participating in the study, a binary composite outcome was defined. Patients were classified as having the composite event if at least one of these conditions occurred: operative time more than 600 min, estimated blood loss greater than 5000 ml, more than 20 ICU days, 90 days mortality, 90 days retransplant. RESULTS: Seven hundred fourteen patients were screened and 698 met the inclusion criteria. The analysis reports the results of 568 patients that fulfilled the criteria to enter the composite outcome analysis.Overall, 156 patients (27.5%) developed the composite outcome. PVT stage 3/4 at transplant and need for any surgical correction of PVT are independent predictors of the composite outcome occurrence. When stratified by PVT grade, overall survival at 1-year ranges from 89.0% with PVT grade 0/1 to 67.4% in patients with PVT grade 3/4 at LT ( P <0.001). Nevertheless, patients with severe PVT can improve their survival when identified risk factors are not present. CONCLUSIONS: Potential LT candidates affected by PVT have a benefit from LT that should be adequately balanced on liver function and type of inflow reconstruction needed to mitigate the incidence of adverse events. Nonetheless, the absence of specific risk factors may improve the outcomes even in patients with PVT grades 3-4.

Changes in chromatin accessibility and transcriptional landscape induced by HDAC inhibitors in TP53 mutated patient-derived colon cancer organoids.

Here we present the generation and characterization of patient-derived organoids (PDOs) from colorectal cancer patients. PDOs derived from two patients with TP53 mutations were tested with two different HDAC inhibitors (SAHA and NKL54). Cell death induction, transcriptome, and chromatin accessibility changes were analyzed. HDACIs promote the upregulation of low expressed genes and the downregulation of highly expressed genes. A similar differential effect is observed at the level of chromatin accessibility. Only SAHA is a potent inducer of cell death, which is characterized by the upregulation of BH3-only genes BIK and BMF. Up-regulation of BIK is associated with increased accessibility in an intronic region that has enhancer properties. SAHA, but not NKL54, also causes downregulation of BCL2L1 and decreases chromatin accessibility in three distinct regions of the BCL2L1 locus. Both inhibitors upregulate the expression of innate immunity genes and members of the MHC family. In summary, our exploratory study indicates a mechanism of action for SAHA and demonstrate the low efficacy of NKL54 as a single agent for apoptosis induction, using two PDOs. These observations need to be validated in a larger cohort of PDOs.

Preventing iatrogenic ureteral injury in colorectal surgery: a comprehensive and systematic review of the last 2 decades of literature and future perspectives.

Iatrogenic ureteral injury (IUI) during colorectal surgery is a rare complication but related to a serious burden of morbidity. This comprehensive and systematic review aims to provide a critical overview of the most recent literature about IUI prevention techniques in colorectal surgery. We performed a comprehensive and systematic review of studies published from 2000 to 2022 and assessed the use of techniques for ureteral injury prevention and intraoperative localization. 26 publications were included, divided into stent-based (prophylactic/lighted ureteral stent and near-infrared fluorescent ureteral catheter [PUS/LUS/NIRFUC]) and fluorescent dye (FD) groups. Costs, the percentage and number of IUIs detected, reported limitations, complication rates and other outcome points were compared. The IUI incidence rate ranged from 0 to 1.9% (mean 0.5%) and 0 to 1.2% (mean 0.3%) in the PUS/LUS/NIRFUC and FD groups, respectively. The acute kidney injury (AKI) and urinary tact infection (UTI) incidence rate ranged from 0.4 to 32.6% and 0 to 17.3%, respectively, in the PUS/LUS/NIRFUC group and 0-15% and 0-6.3%, respectively, in the FD group. Many other complications were also compared and descriptively analyzed (length-of-stay, mortality, etc.). These techniques appear to be feasible and safe in select patients with a high risk of IUI, but the delineation of reliable guidelines for preventing IUI will require more randomized controlled trials.

Association between artificial nutrition in brain dead donors and early allograft function in liver transplant recipients: an observational study.

BACKGROUND: The role of nutrition in donor after brain deaths (DBDs) has yet to be adequately discussed. The primary aim of this study was to investigate whether the nutritional intake in the 48 h before organ retrieval may play a role on the graft functional recovery assessed with Model for Early Allograft Function (MEAF) Score. METHODS: Single-center retrospective study evaluating all liver transplants performed at the University Hospital of Udine from January 2010 to August 2020. Patients receiving grafts from DBD donors fed with artificial enteral nutrition in the 48 h prior to organ procurement (EN-group) or who did not (No-EN-group). Caloric debt was calculated using the difference between the calculated caloric needs and the effective calories delivered through enteral nutrition. RESULTS: Livers from EN-group presented a lower mean MEAF score compared to the no-EN-group: 3.39 ± 1.46 versus 4.15 ± 1.51, respectively (p = .04). A positive correlation between caloric debt and the MEAF score was found within the overall population (r = .227, p = .043) as well as in EN-group (r = .306, p = .049). CONCLUSIONS: Donor's nutritional intake in the final 48 h before organ procurement correlates with MEAF score, and nutrition probably plays a positive role on the functional recovery of the graft. Large future randomized controlled trials are needed to confirm this preliminary results.

Internal hernia after an open gastrectomy: an unusual treatment approach and a systematic review of the literature.

Internal hernia (IH) is a serious complication that can occur after both laparoscopic and open surgery for the treatment of gastric cancer; the transverse colon and mesocolon, act as a natural partition between stomach and the small intestine and, once any type of gastrojejunal anastomosis is constructed, a potential space for internal hernia is created. We present the case of a 68-year-old patient diagnosed with intestinal ischemia due to an IH in the site of the jejunojejunostomy after an open gastrectomy for gastric cancer, treated with negative wound pressure therapy (NWPT) on open abdomen (ABTHERATM dressing).

A rare case of duplication of the descending colon in a pregnant woman: case report and literature review.

INTRODUCTION: Gastrointestinal duplications are uncommon congenital abnormalities that can occur anywhere throughout the intestinal tract. The small bowel is more interested than the large one. Duplications are schematically classified as spherical and tubular, respectively representing 80% and 20% of cases, with different relationships and communications with the native intestinal wall. Although typically diagnosed during infancy and early childhood, tubular colonic sub-type stays frequently hidden for several years until a complication occurs. CASE PRESENTATION: we report the case of a T-shaped tubular duplication in a 20-year-old woman at the 30th week of gestation, who underwent an urgent exploratory laparotomy for intestinal occlusion, treated with the resection of the aberrant large bowel. The patient was notable for a long history of constipation and chronic pain. Diagnostic possibilities were limited by the on-going pregnancy. CONCLUSION: Intestinal duplications are uncommon malformations, and, of these, the T-shaped subtype of the colon is among the rarest ones. In the adulthood, diagnosis is usually established in the operating room during urgent or even emergency surgery performed for abdominal complications. A duplication of the descending colon is extremely rare, and this is, to our knowledge, the only article describing a case found in advanced state of pregnancy.

Is the indocyanine green clearance test useful in viral acute liver failure? Maybe!

N/A.

PO2 21% oxygenated hypothermic machine perfusion in kidney transplantation: Any clinical benefit?

BACKGROUND: In deceased donor kidney transplantation (KT), the use of hypothermic machine perfusion (HMP) has been acquiring the status of best practice in the pre-transplant management of kidney grafts. Two types of HMP are currently available, oxygenated HMP and non-oxygenated HMP. However, data on the real clinical impact of oxygenation on KT outcome are still heterogeneous. METHODS: Retrospective study on a cohort of 103 patients transplanted with a single kidney graft that was managed either with end-ischemic oxygenated (O2 group, Waves Machine, n = 51, 49.5%) or non-oxygenated HMP (no-O2 group, Life Port Kidney Transporter Machine, n = 52, 50.5%), during the period January 2016-December 2020. Oxygenation was performed at pO2 21%. RESULTS: The median cold ischemia time was 29 h:40 min [IQR 26 h:55 min-31 h:10 min] and the prevalence of grafts from extended criteria donors (ECD) was 46.7%, with a median kidney donor profile index (KDPI) of 72 [41-94]. The study groups were homogeneous in terms of recipient characteristics, ischemia times and donor characteristics. O2 and no-O2 groups showed comparable outcomes in terms of delayed graft function (O2 vs no-O2, 21.5% vs 25%, p = 0.58), vascular (0.2% vs 0.2%, p > 0.99) and urologic (13.7% vs 11.5%, p = 0.77) complications, and episodes of graft rejection (11.7% vs 7.7%, p = 0.52). At 1 year follow up, even creatinine serum levels were comparable between the groups (1.27 mg/dL [1.09 and 1.67] vs 1.4 mg/dL [1.9-1.78], p = 0.319), with similar post-transplant trend (p = 0.870). No significant benefit was either observed in ECD or KDPI > 60 subgroups, respectively. CONCLUSIONS: Oxygenation at pO2 21% during HMP seems not to significantly enhance the KT outcomes in terms of postoperative complications or graft function.

Re-thinking of T-tube use in whole liver transplantation: an analysis on the risk of delayed graft function.

The liver-gut axis has been identified as crucial mediator of liver regeneration. Thus, the use of a T-tube in liver transplantation (LT), which interrupts the enterohepatic bile circulation, may potentially have a detrimental effect on the early allograft functional recovery. We retrospectively analyzed a cohort of 261 patients transplanted with a whole liver graft, with a duct-to-duct biliary anastomosis, who did not develop any surgical complication within postoperative day 14. Early allograft dysfunction (EAD) was defined according to the criteria of Olthoff et al. (EAD-O), and graded according to the Model for Early Allograft Function (MEAF) score. EAD-O developed in 24.7% of recipients and the median MEAF score was 4.0 [interquartile range 2.9-5.5]. Both MEAF and EAD predicted 90-day post-LT mortality. A T-tube was used in 49.4% of cases (n = 129). After a propensity score matching for donor age, cold and warm ischemia time, donor risk index, balance of risk score, Child-Pugh class C, and MELD score, the T-tube group showed a significantly higher prevalence of EAD-O and value of MEAF than the no-T-tube group (EAD-O: 29 [34.1%] vs 16 [19.0%], p = 0.027; MEAF 4.5 [3.5-5.7] vs 3.7 [2.9-5.0], p = 0.014). In conclusion, T-tube use in LT may be a risk factor for EAD and higher MEAF, irrespective of graft quality and severity of pre-LT liver disease.

Current practice with grafts with multiple renal arteries in kidney transplantation: role of the methylene blue in the lower pole.

Kidneys with multiple renal arteries (MRAs) from different patches, may provide to the surgeon additional technical difficulties that make kidney transplants very challenging. MRAs have been largely debated over the years whether to be anastomosed or not due to the disappointing outcomes when it comes to inappropriate ligation or anastomosis.  Some authors empirically reassure that smaller branches can be safely ligated and dissected without intraoperative and postoperative complications or compromising the functional recovery of the graft. Literature is poor about the possible differences in the management of superior and inferior polar arteries. Inferior polar arteries represent a topic of great interest as they may also supply the proximal ureter. The aim of this article is to merge the current knowledge about the management of inferior polar arteries and to highlight if there is any role of the methylene blue dye (MB) in the study of the ureteral vascularization in kidney transplantation. MB can be considered a safe and simple tool of vascular perfusion assessment in kidney transplantation. By injecting the dye-solution into the inferior MRA hidden ureteral branches can be unmasked and guide the surgeon to preserve important vessels. In view of their fundamental role in the vascularization of the ureter, the lower polar arteries of the graft, should be invariably studied by MB. It provides an objective, simple and fast tool for the evaluation of the ureteral vascularization when injected through the inferior MRA of the graft.

Association between preoperative diastolic dysfunction and early allograft dysfunction after orthotopic liver transplantation: An observational study.

OBJECTIVES: To investigate the association between the grade of diastolic dysfunction (DD) and the occurrence of early allograft dysfunction (EAD) in liver transplant patients following the new 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) guidelines. METHODS: From January 2015 to December 2019, we retrospectively analyzed 83 patients who underwent orthotopic liver transplantation (OLTx) and their susceptibility to develop EAD according to the grade of preoperative DD. EAD was defined according to the criteria proposed by Olfhoff et al.; DD was defined with four parameters: E/A, e/e', Left Atrium volume, and Tricuspid Regurgitation velocity. RESULTS: According to the ASE/EACVI guidelines grade II DD was detected in 20 patients (24.1%) undergoing OLTx. A statistically significant association was found between grade II DD and the occurrence of EAD (p-value < 0.003). The Kaplan-Meier analysis failed to find any significant difference between the survival probability, nevertheless at the end of a 90-day follow-up period, mortality showed a different trend in classes with more severe diastolic dysfunction. CONCLUSION: According to the ASE/EACVI guidelines from 2016, patients with grade II DD seem to have a higher propensity to develop early allograft dysfunction EAD after OLTx. Our study advises a need for an urgent prospective multicenter study to elucidate the long-term outcomes of liver transplants patients with diastolic dysfunction.

Assessment of hepatic steatosis based on needle biopsy images from deceased donor livers.

BACKGROUND: Assessment of hepatic steatosis (HS) before transplantation requires the pathologist to read a graft biopsy. A simple method based on the evaluation of images from tissue samples with a smartphone could expedite and facilitate the liver selection. This study aims to assess the degree of HS by analysing photographic images from liver needle biopsy samples. METHODS: Thirty-three biopsy-images were acquired with a smartphone. Image processing was carried out using ImageJ: background subtraction, conversion to HSB colour space, segmentation of the biopsy area, and evaluation of statistical features of Hue, Saturation, Brightness, Red, Green, and Blue channels on the biopsy area. After feature extraction, correlations were made with gold standard HS percentage assessed at two levels (frozen-section vs glass-slide). Sensitivity, specificity, and accuracy were calculated for each feature. RESULTS: Correlations were found for H, S, R. The sensitivity, specificity, and accuracy of the final classifier based on the K* algorithm were 94%, 92%, 94%. LIMITATIONS: Accuracy assessment was performed considering macrovesicular steatosis on specimens with mostly < 30% HS. CONCLUSIONS: The steatosis assessment based on needle biopsy images, proved to be an effective and promising method. Deep learning approaches could also be experimented with a larger set of images.

The Challenging Management of an Intracardiac Thrombus in a Liver Transplant Patient at the Reperfusion Phase: A Case Report and Brief Literature Review.

The exact origin of intracardiac thrombi formation during orthotopic liver transplant remains unknown. The altered balance between hypercoagulability, hypocoagulation, and endothelial dysfunction associated with end-stage liver disease is thought to play a pivotal role. Venous stasis, vascular clamping, and reperfusion could also contribute to clot formation. The incidence of intracardiac thrombi formation stands at 4.2%, associated with a mortality rate of 45.5%, and to date, no consensus exists regarding the best way to treat this complication. Intraoperative transesophageal echocardiography is the only effective method for diagnosing intracardiac thrombi formation early, while point-of-care coagulation testing could guide the coagulation management potentially improving patient outcomes.

Association between the donor to recipient ICG-PDR variation rate and the functional recovery of the graft after orthotopic liver transplantation: A case series.

BACKGROUND: Despite current advances in liver transplant surgery, post-operative early allograft dysfunction still complicates the patient prognosis and graft survival. The transition from the donor has not been yet fully understood, and no study quantifies if and how the liver function changes through its transfer to the recipient. The indocyanine green dye plasma disappearance rate (ICG-PDR) is a simple validated tool of liver function assessment. The variation rate between the donor and recipient ICG-PDR still needs to be investigated. MATERIALS AND METHODS: Single-center retrospective study. ICG-PDR determinations were performed before graft retrieval (T1) and 24 hours after transplant (T2). The ICG-PDR relative variation rate between T1 and T2 was calculated to assess the graft function and suffering/recovering. Matched data were compared with the MEAF model of graft dysfunction. OBJECTIVE: To investigate whether the variation rate between the donor ICG-PDR value and the recipient ICG-PDR measurement on first postoperative day (POD1) can be associated with the MEAF score. RESULTS: 36 ICG-PDR measurements between 18 donors and 18 graft recipients were performed. The mean donor ICG-PDR was 22.64 (SD 6.35), and the mean receiver's ICG-PDR on 1st POD was 17.68 (SD 6.60), with a mean MEAF value of 4.51 (SD 1.23). Pearson's test stressed a good, linear inverse correlation between the ICG-PDR relative variation and the MEAF values, correlation coefficient -0.580 (p = 0.012). CONCLUSION: The direct correlation between the donor to recipient ICG-PDR variation rate and MEAF was found. Measurements at T1 and T2 showed an up- or downtrend of the graft performance that reflect the MEAF values.

Association between indocyanine green clearance test and ischemic type biliary lesions within one year after orthotopic liver transplantation.

BACKGROUND: Ischemic type biliary lesions (ITBLs), a particular subset of non-anastomotic biliary strictures (NAS), are characterized by intra and extrahepatic strictures that occur in the absence of either hepatic artery thrombosis or stenosis. When they occur within the first year after liver transplantation their development is mostly related to ischemia-reperfusion injury (IRI). The indocyanine green plasma disappearance rate (ICG-PDR) might be able to predict the probability of IRI-induced graft damage after liver transplantation. OBJECTIVE: Our aim was to evaluate the association between ICG-PDR and the occurrence of ITBLs. Secondly, we searched for evidence of IRI in patients presenting ITBLs. METHODS: This retrospective single-center observational study assessed a cohort of 60 liver transplant patients. Each patient underwent ICG-PDR on the 1st postoperative day. ITBLs were identified by means of either cholangiography or magnetic resonance imaging evidence of a deformity and narrowing of the biliary tree in the absence of hepatic artery thrombosis/stenosis. RESULTS: ITBLs were discovered in 10 patients out of 60 liver recipients (16.67%) within one year after transplantation. A low ICG-PDR value was found to be a significant predictive factor for ITBL development, with an OR of 0.87 and a 95% CI of 0.77-0.97. Liver biopsies were performed in 56 patients presenting unexplained abnormal liver function test results. A statistically significant association was found between the development of ITBLs and anatomopathological evidence of IRI. LIMITATIONS: Retrospective, single-center study. CONCLUSIONS: The findings from this study show a relationship between low ICG-PDR values on first post-operative-day and the occurrence of ITBLs within 1 year after transplantation.

Early Graft Dysfunction Following Kidney Transplantation: Can Thermographic Imaging Play a Predictive Role?

The shortage of organs and the growing need for them over recent years have led to the adoption of less stringent donor acceptance criteria, resulting in the approval of marginal organs for transplant, especially from elderly donors. This implies a higher risk of graft dysfunction, a higher frequency of immunological and vascular complications, and shorter graft survival. Several strategies have been implemented in clinical practice to assess graft quality and suitability for transplantation. We have started to test the prospective intraoperative use of thermo-vision cameras during graft reperfusion. Images were acquired using the FLIR One Pro thermo-vision camera for android devices. We hypothesized that thermal images would give a better perspective about the quality of arterial perfusion and graft revascularization of the renal cortex. Thermo-vision cameras provide an easy-to-use, noninvasive, cost-effective tool for the global assessment of kidney graft cortical microcirculation in the immediate post-reperfusion period, providing additional data on the immediate viability and function of a graft.

Immunonutrition in elective colorectal surgery and early inflammatory response.

BACKGROUND: Immunonutrition has gained increasing interest over years, enough to be recommended in several international guidelines and to be included in the ERAS protocol for colorectal surgery. Although clinical advantages have been proved for malnourished cancer-affected patients, its role is more controversial in other settings. We evaluated the impact of immunonutrition in major colorectal elective surgery for benign and malignant diseases, regardless of the preoperative nutritional status. METHODS: We conducted a single center retrospective analysis of a database of patients who underwent elective major colon-rectal surgery for benign and malignant diseases between January 2018 and February 2020. In January 2019 we started a protocol to define which patients should receive preoperative immunonutrition, regardless of their nutritional status. We compared early postoperative outcomes and laboratory data of this group (IMN) to those of patients who met all the characteristics to be included in the protocol, but who did not receive immunonutrition (CTRL). RESULTS: The IMN group showed significantly lower total leukocytes and neutrophils values and a lower pathological leukocytosis rate on 1st postoperative day compared to the CTRL group (P=0.004). Although differences in early postoperative clinical outcomes were not significant, patients belonging to the IMN group needed less postoperative antibiotic treatment (P=0.047). CONCLUSIONS: Immunonutrition could affect granulocytopoiesis and neutrophils recruitment in damaged tissues. This could lead to better and faster tissue healing and, consequently, to a reduction in postoperative complications even in normo-nourished patients. The lower need for antibiotic treatment could reflect a reduced susceptibility to postoperative infections.

Postoperative Trends and Prognostic Values of Inflammatory and Nutritional Biomarkers after Liver Transplantation for Hepatocellular Carcinoma.

Preoperative inflammatory biomarkers such as the Platelet-to-Lymphocyte Ratio (PLR) and the Neutrophil-to-Lymphocyte Ratio (NLR) strongly predict the outcome in surgically treated patients with hepatocellular carcinoma (HCC), while nutritional biomarkers such as the Controlling Nutritional Status (CONUT) and the Prognostic Nutritional Index (PNI) show an analogue prognostic value in hepatic resection (HR) but not in liver transplant (LT) cases. Data on the impact of LT on the inflammatory and nutritional/metabolic function are heterogeneous. Therefore, we investigated the post-LT trend of these biomarkers up to postoperative month (POM) 12 in 324 HCC patients treated with LT. Inflammatory biomarkers peaked in the early post-LT period but at POM 3 leveled off at values similar (NLR) or higher (PLR) than pre-LT ones. CONUT and PNI worsened in the early post-LT period, but at POM 3 they stabilized at significantly better values than pre-LT. In LT recipients with an overall survival >1 year and no evidence of early HCC recurrence, 1 year post-LT NLR and PNI independently predicted patient overall survival, while 1 year post-LT PLR independently predicted late tumor recurrence. In conclusion, at 1 year post-LT, the nutritional status of liver-transplanted HCC patients significantly improved while their inflammatory state tended to persist. Consequently, post-LT PLR and NLR maintained a prognostic value for LT outcome while post-LT CONUT and PNI acquired it.