The Role of Donor Gamma-Glutamyl Transferase as a Risk Factor for Early Graft Function after Liver Transplantation.

BACKGROUND: Growing interest has been recently reported in the potential detrimental role of donor gamma-glutamyl transferase (GGT) peak at the time of organ procurement regarding the risk of poor outcomes after liver transplantation (LT). However, the literature on this topic is scarce and controversial data exist on the mechanisms justifying such a correlation. This study aims to demonstrate the adverse effect of donor GGT in a large European LT cohort regarding 90-day post-transplant graft loss. METHODS: This is a retrospective international study investigating 1335 adult patients receiving a first LT from January 2004 to September 2018 in four collaborative European centers. RESULTS: Two different multivariable logistic regression models were constructed to evaluate the risk factors for 90-day post-transplant graft loss, introducing donor GGT as a continuous or dichotomous variable. In both models, donor GGT showed an independent role as a predictor of graft loss. In detail, the log-transformed continuous donor GGT value showed an odds ratio of 1.46 (95% CI = 1.03-2.07; p = 0.03). When the donor GGT peak value was dichotomized using a cut-off of 160 IU/L, the odds ratio was 1.90 (95% CI = 1.20-3.02; p = 0.006). When the graft-loss rates were investigated, significantly higher rates were reported in LT cases with donor GGT ≥160 IU/L. In detail, 90-day graft-loss rates were 23.2% vs. 13.9% in patients with high vs. low donor GGT, respectively (log-rank p = 0.004). Donor GGT was also added to scores conventionally used to predict outcomes (i.e., MELD, D-MELD, DRI, and BAR scores). In all cases, when the score was combined with the donor GGT, an improvement in the model accuracy was observed. CONCLUSIONS: Donor GGT could represent a valuable marker for evaluating graft quality at transplantation. Donor GGT should be implemented in scores aimed at predicting post-transplant clinical outcomes. The exact mechanisms correlating GGT and poor LT outcomes should be better clarified and need prospective studies focused on this topic.

The challenging surgical management of hepatic epithelioid hemangioendothelioma: a narrative review.

BACKGROUND AND OBJECTIVE: Hepatic epithelioid hemangioendothelioma (HEHE) is an uncommon vascular endothelial cell cancer involving the hepatic tissue with full malignant potential. HEHE diagnosis is challenging because blood tests and radiological findings are often non-pathognomonic. Therapeutic possibilities are manifold, ranging from a simple "wait and see" to surgical approaches, up to systemic therapies with vascular endothelial growth factor (VEGF) and mechanistic target of rapamycin (mTOR) inhibitors. The standardized adoption of the surgical approaches, namely resection or transplantation, still remains unclear. Aim of this review is to clarify the role of the surgical strategies for the management of HEHE. METHODS: A review of the literature was done with the intent to focus on the relevant studies exploring the role of the different surgical therapies. A search of these studies was done using the electronic database MEDLINE-PubMed. KEY CONTENT AND FINDINGS: The surgical approaches, namely resection or transplantation, represent the best option in treating well-selected patients with HEHE. Resection is indicated in the case of single lesion or oligonodular monolobar disease. Liver transplantation is indicated in the case of multifocal bilobar disease, even in the presence of resectable extrahepatic disease. The potential role of a minimally invasive approach should represent a relevant field to explore. CONCLUSIONS: The impact of surgery for the treatment of HEHE requires further studies to further clarify its relevant role. Standardized approaches are required.

Obstructive Uropathy Due to an Unusual Inguinal Hernia 35 Years After Kidney Transplant.

In a kidney transplant recipient, bladder and graft ureter displacement into a groin hernia is a highly unusual cause of obstructive uropathy that may lead to graft dysfunction or graft loss. We report the case of a White man, 56 years old, who had previously, at the age of 19 years, undergone a kidney transplant from a deceased donor, to mitigate chronic glomerulonephritis. The patient presented to us with a reducible left inguinal hernia with worsening kidney function, and we used the Lichtenstein hernioplasty technique to surgically repair the hernia, which was followed by an uneventful postoperative course. Existing literature has identified few cases of kidney graft dysfunction due to inguinal hernias. Groin hernia repair of this type in this specific circumstance remains a subject of debate. However, in our opinion, with attention to appropriate reductions of immunosuppressive therapy, the Lichtenstein technique is safe for transplant recipients and the use of mesh greatly reduces the risk of hernia recurrence.

Minimally Invasive Approach in the Setting of ALPPS Procedure: a Systematic Review of the Literature.

BACKGROUND: Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) represents a new surgical technique for the resection of advanced hepatic malignancies with predicted insufficient future liver remnant. In some patients, ALPPS can be associated with an increased risk of poor outcomes. Minimally invasive surgery (MIS) has been proposed in combination with ALPPS with the intent to minimize this risk. We systematically evaluated the outcomes of MIS-ALPPS cases to compare the relative outcomes of open ALPPS versus MIS-ALPPS. METHODS: A systematic review was done in accordance with the PRISMA guidelines. Search terms utilized included the following: ("ALPPS"[Title/Abstract] OR "associating liver partition and portal vein ligation for staged hepatectomy"[Title/Abstract] OR "in situ split"[Title/Abstract]) AND ("minimally invasive"[Title/Abstract] OR "laparoscopic"[Title/Abstract] OR "robotic"[Title/Abstract]). RESULTS: Fifteen articles were identified, with a total of 27 patients reported. Colorectal metastatic disease was the most commonly observed indication for MIS-ALPPS (66.7%), followed by hepatocellular carcinoma (25.9%). Time passed from the first to the second stage ranged 7-30 days. MIS-ALPPS patients did not experience procedure failures between the first and second stages. Only four (15.4%) subjects had a grade IIIb complication. No perioperative mortality after the first or second stage was reported. Compared with open ALPPS, MIS-ALPPS demonstrated better results. Hospital stay duration ranged 8-33 days with a follow-up ranging 1-20 months. CONCLUSIONS: MIS-ALPPS appears to be safe, with potentially lower morbidities and mortalities relative to open patients. The present results should be considered with caution. A limited number of articles exist on this topic. Furthermore, selection biases exist when comparing open versus MIS-ALPPS data. Registry studies are needed to better define the outcomes of patients undergoing MIS-ALPPS.

Donor-to-recipient gender match in liver transplantation: A systematic review and meta-analysis.

AIM: To perform a systematic review and meta-analysis on donor-to-recipient gender mismatch as a risk factor for post-transplant graft loss. METHODS: A systematic literature search was performed using PubMed, Cochrane Library database and EMBASE. The primary outcome was graft loss after liver transplantation. Odds ratios and 95% confidence intervals were calculated to compare the pooled data between groups with different donor-to-recipient gender matches. Three analyses were done considering (1) gender mismatches (F-M and M-F) vs matches (M-M and F-F); (2) Female-to-Male mismatch vs other matches; and (3) Male-to-Female mismatch vs other matches. RESULTS: A total of 7 articles were analysed. Gender mismatch (M-F and F-M) was associated with a significant increase of graft loss respect to match (M-M and F-F) (OR: 1.30; 95%CI: 1.13-1.50; P < 0.001). When F-M mismatch was specifically investigated, it confirmed its detrimental role in terms of graft survival (OR: 1.83; 95%CI: 1.20-2.80; P = 0.005). M-F mismatch failed to present a significant role (OR: 1.09; 95%CI: 0.73-1.62; P = 0.68). CONCLUSION: Gender mismatch is a risk factor for poor graft survival after liver transplantation. Female-to-male mismatch represents the worst combination. More studies are needed with the intent to better clarify the reasons for these results.

Collaterals management during pancreatoduodenectomy in patients with celiac axis stenosis: A systematic review of the literature.

BACKGROUND/OBJECTIVES: Celiac axis stenosis (CAS) represents an uncommon and typically innocuous condition. However, when a pancreatic resection is required, a high risk for upper abdominal organs ischemia is observed. In presence of collaterals, such a risk is minimized if their preservation is realized. The aim of the present study is to systematically review the literature with the intent to address the routine management of collateral arteries in the case of CAS patients requiring pancreatoduodenectomy. METHODS: A systematic search was done in accordance with the PRISMA guidelines, using "celiac axis stenosis" AND "pancreatoduodenectomy" as MeSH terms. Seventy-four articles were initially screened: eventually, 30 articles were identified (n = 87). RESULTS: The main cause of CAS was median arcuate ligament (MAL) (n = 31; 35.6%), followed by atherosclerosis (n = 20; 23.0%). CAS was occasionally discovered during the Whipple procedure in 15 (17.2%) cases. Typically, MAL was divided during surgery (n = 24/31; 77.4%). In the great majority of cases (n = 83; 95.4%), vascular abnormalities involved the pancreatoduodenal arteries (i.e., dilatation, arcade, channels, aneurysms). Collateral arteries were typically preserved, being divided or reconstructed in only 14 (16.1%) cases, respectively. Severe ischemic complications were reported in six (6.9%) patients, 20.0% of whom were reported in patients with preoperatively unknown CAS (p-value 0.06). CONCLUSIONS: A correct pre-operative evaluation of anatomical conditions as well as a correct surgical planning represent the paramount targets in CAS patients with arterial collaterals. Vascular flow must be always safeguarded preserving/reconstructing the collaterals or resolving the CAS, with the final intent to avoid dreadful intra- and post-operative complications.

Platelet-to-lymphocyte ratio in the setting of liver transplantation for hepatocellular cancer: A systematic review and meta-analysis.

AIM: To perform a systematic review and meta-analysis on platelet-to-lymphocyte ratio (PLR) as a risk factor for post-transplant hepatocellular cancer (HCC) recurrence. METHODS: A systematic literature search was performed using PubMed. Participants of any age and sex, who underwent liver transplantation for HCC were considered following these criteria: (1) studies comparing pre-transplant low vs high PLR values; (2) studies reporting post-transplant recurrence rates; and (3) if more than one study was reported by the same institute, only the most recent was included. The primary outcome measure was set for HCC recurrence after transplantation. RESULTS: A total of 5 articles, published between 2014 and 2017, fulfilled the selection criteria. As for the quality of the reported studies, all the investigated articles presented an overall high quality. A total of 899 cases were investigated: 718 cases (80.0%) were males. Three studies coming from European countries and one from Japan presented HCV as the main cause of cirrhosis. On the opposite, one Chinese study presented a greater incidence of HBV-related cirrhotic cases. In all the studies apart one, the PLR cut-off value of 150 was reported. At meta-analysis, high PLR value was associated with a significant increase in recurrence after transplantation (OR = 3.33; 95%CI: 1.78-6.25; P < 0.001). A moderate heterogeneity was observed among the identified studies according to the Higgins I2 statistic value. CONCLUSION: Pre-transplant high PLR values are connected with an increased risk of post-operative recurrence of hepatocellular cancer. More studies are needed for better clarify the biological mechanisms of this results.