Undifferentiated Embryonal Sarcoma of the Liver with Epithelioid Features: A Case Report of an Exceptional Histological Heterogeneity among Rare Diseases.

INTRODUCTION: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive malignant tumor, with nonspecific clinical symptoms and radiological features. Less than 150 cases have been reported in adults across the world. PRESENTATION OF CASE: We report a case of an extremely rare subtype of UESL with epithelioid features in a 29-year-old woman, presenting as a cystic lesion of 27 × 17 cm, completely subverting the right hepatic lobe. She underwent a right hepatectomy with anterior approach, complete hilum lymphadenectomy and partial diaphragmatic resection for local infiltration, followed by systemic chemotherapy. She remains with no evidence of disease and liver mass has been restored after 6 months. DISCUSSION: The present case report represents the second case of UESL with epithelioid features described across the world. The immunohistochemical expression pattern, cytokeratin (CK)19 + and CK7 -, strongly suggests an origin of this epithelioid component from native biliary cells and not from a reshaped ductal plate. Due to the rarity of this form, to date it is impossible to define the prognostic impact of this subtype of UESL, and treatment remains challenging. CONCLUSION: UESL is associated with a poor prognosis, especially in adults, but a comprehensive and multidisciplinary treatment based on radical resection and adjuvant therapy may provide a survival benefit. Surgical excision with negative margins remains mandatory to diagnose and treat UESL.

The Role of Non-Peripancreatic Lymph Nodes in the Survival of Patients Suffering from Pancreatic Cancer of the Body and Tail: A Systematic Review and Meta-Analysis of High-Quality Studies.

Lymph nodes (LNs)' metastases have a well-known detrimental impact on the survival outcomes of patients suffering from pancreatic cancer of the body and tail. However, the extent of the lymphadenectomy for this tumor location is still debated. The aim of this study was to systematically review the current literature to explore the incidence and the prognostic impact of non-peripancreatic lymph nodes (PLNs) in patients suffering from pancreatic cancer of the body and tail. A systematic review was conducted according to PRISMA and MOOSE guidelines. The primary endpoint was to assess the impact of non-PLNs on overall survival (OS). As a secondary endpoint, the pooled frequencies of different non-PLN stations' metastatic patterns according to tumor location were explored. Eight studies were included in data synthesis. An increased risk of death for patients with positive non-PLNs was detected (HR: 2.97; 95% CI: 1.81-4.91; p < 0.0001). Meta-analysis of proportions pointed out a 7.1% pooled proportion of nodal infiltration in stations 8-9. The pooled frequency for station 12 metastasis was 4.8%. LN stations 14-15 were involved in 11.4% of cases, whereas station 16 represented a site of metastasis in 11.5% of cases. Despite its potential beneficial effect on survival outcome, a systematic extended lymphadenectomy could not be recommended yet for patients suffering from PDAC of the body/tail.

3D reconstruction in complex parenchymal sparing liver surgery.

Background: Prognosis of stage IV colorectal cancer is related to control of liver metastasis. As of now, surgery provides survival advantage for patients affected by resectable colorectal liver metastases (CRLM), with parenchymal sparing strategies representing the most accepted strategy {[1]. In this setting, 3D reconstruction programs represent the newest available technological leap to improve anatomical accuracy [2]. Despite being quite expensive, 3D models have proved themselves as helpful adjunctive tools to enhance pre-operative strategy [3] in complex liver procedures, even in the eyes of expert hepatobiliary surgeons [4]. Methods: We present a video describing the practical use of a custom-made 3D model, acquired following specific quality criteria [2], for a case of bilateral CLRM after neoadjuvant chemotherapy. Results: In our reported case and as described in the video, pre-operative visualization of 3D reconstructions altered significantly the pre-operative surgical plan. First, following the principles of parenchymal sparing surgery, challenging atypical resections of metastatic lesions close to main vessels (right posterior branch of the portal vein, inferior vena cava) were preferred to anatomic resections/major hepatectomies, allowing the highest projected future liver remnant volume possible (up to 65%) amongst different available strategies. Secondly, the order of hepatic resections was planned to follow a decreasing degree of difficulty, in order minimize the effect of blood redistribution after previous resections during parenchymal dissection (thus starting from atypical resections close to main vessels, followed by anatomical resections and atypical resections of superficial resections). In addition, the availability of the 3D model in the operating room was crucial in the surgical field to guide safe surgical pathways, especially during atypical resections of lesions close to the main vessels: detection and navigation were further enhanced thanks to tools of augmented reality that allowed the surgeon to manipulate the 3D model through a touchless sensor in a dedicated screen in the operating room and to replicate a mirroring snapshot of the surgical field, without compromising sterility nor the surgical set-up. In the setting of these complex liver procedures, the application of 3D printed models has been described [4]; when available, 3D printed models, particularly useful in the pre-operative phase when explaining the procedure to patients and relatives, have been reported to have comparable significant impact, with feedback from expert hepatobiliary surgeons that is very similar to the one we are reporting in our experience [4]. Conclusion: Routine use of 3D technology does not claim to revolutionize the world of traditional imaging but may be impactful in helping the surgeon visualize the anatomy of that specific individual in a dynamic and three-dimensional way that is similar to the surgical field, thus improving multidisciplinary preoperative planning and intraoperative navigation during complex liver surgery.

Kimura's vs Warshaw's technique for spleen preserving distal pancreatectomy: a systematic review and meta-analysis of high-quality studies.

BACKGROUND: Spleen preserving distal pancreatectomy (SPDP) represents a widely adopted procedure in the presence of benign or low-grade malignant tumors. Splenic vessels preservation and resection (Kimura and Warshaw techniques respectively) represent the two main surgical modalities to avoid splenic resection. Each one is characterized by strengths and drawbacks. The aim of the present study is to systematically review the current high-quality evidence regarding these two techniques and analyze their short-term outcomes. METHODS: A systematic review was conducted according to PRISMA, AMSTAR II and MOOSE guidelines. The primary endpoint was to assess the incidence of splenic infarction and splenic infarction leading to splenectomy. As secondary endpoints, specific intraoperative variables and postoperative complications were explored. Metaregression analysis was conducted to evaluate the effect of general variables on specific outcomes. RESULTS: Seventeen high-quality studies were included in quantitative analysis. A significantly lower risk of splenic infarction for patients undergoing Kimura SPDP (OR = 0.14; p < 0.0001). Similarly, splenic vessel preservation was associated with a reduced risk of gastric varices (OR = 0.1; 95% p < 0.0001). Regarding all secondary outcome variables, no differences between the two techniques were noticed. Metaregression analysis failed to identify independent predictors of splenic infarction, blood loss, and operative time among general variables. CONCLUSIONS: Although Kimura and Warshaw SPDP have been demonstrated comparable for most of postoperative outcomes, the former resulted superior compared to the latter in reducing the risk of splenic infarction and gastric varices. For benign pancreatic tumors and low-grade malignancies Kimura SPDP may be preferred.

Preoperative indocyanine green (ICG) clearance test: Can we really trust it to predict post hepatectomy liver failure? A systematic review of the literature and meta-analysis of diagnostic test accuracy.

INTRODUCTION: Post hepatectomy liver failure (PHFL) still represents a potentially fatal complication after major liver resection. Indocyanine green (ICG) clearance test represents one of the most widely adopted examinations in the preoperative workup. Despite a copious body of evidence which has been published on this topic, the role of ICG in predicting PHLF is still a matter of debate. METHODS: A systematic review of the literature was conducted according to PRISMA-DTA guidelines. The primary outcome was the assessment of diagnostic performance of ICG in predicting PHLF. The secondary outcome was the mean ICGR15 and ICGPDR in patients experiencing PHLF. RESULTS: Seventeen studies, for a total of 4852 patients, were deemed eligible. Sensitivity ranged from 25% to 83%; Specificity ranged from 66.1% to 93.8%. ICG clearance test pooled AUC was 0.673 (95% CI: 0.632-0.713). The weighted mean ICGR15 was 11 (95%CI: 8.3-13.7). The weighted mean ICGPDR was 16.5 (95%CI: 13.3-19.8). High risk of bias was detected in all examined domains. CONCLUSIONS: Preoperative ICG clearance test alone may not represent a reliable method to predict post hepatectomy liver failure. Its diagnostic significance should be framed within multiparametric models involving clinical and imaging features.

Sequential Use of Normothermic Regional and Ex Situ Machine Perfusion in Donation After Circulatory Death Liver Transplant.

In Italy, 20 minutes of a continuous flat line on an electrocardiogram are required for declaration of death. In the setting of donation after circulatory death (DCD), prolonged warm ischemia time prompted the introduction of abdominal normothermic regional perfusion (NRP) followed by postprocurement ex situ machine perfusion (MP). This is a retrospective review of DCD liver transplantations (LTs) performed at 2 centers using sequential NRP and ex situ MP. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, and 11 (32.4%) were discarded based on NRP parameters (n = 1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n = 9, 26.5%), or severe macroangiopathy at back-table evaluation (n = 1, 3.0%). A total of 20 grafts (58.8%; 11 uncontrolled DCDs, 9 controlled DCDs) were considered eligible for LT, procured and perfused ex situ (9 normothermic and 11 dual hypothermic MPs). In total, 18 (52.9%; 11 uncontrolled) livers were eventually transplanted. Median (interquartile range) no-flow time was 32.5 (30-39) minutes, whereas median functional warm ischemia time was 52.5 (47-74) minutes (controlled DCD), and median low-flow time was 112 minutes (105-129 minutes; uncontrolled DCD). There was no primary nonfunction, while postreperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury occurred in 5 (28%). After a median follow-up of 15.1 (9.5-22.3) months, 1 case of ischemic-type biliary lesions and 1 patient death were reported. DCD LT is feasible even with the 20-minute no-touch rule. Strict NRP and ex situ MP selection criteria are needed to optimize postoperative results.

Procurement and ex-situ perfusion of isolated slaughterhouse-derived livers as a model of donors after circulatory death.

Ex-situ machine perfusion (MP) techniques are increasingly used in clinical settings, especially on grafts derived from donors after cardiac death (DCD). However, comprehension of biological effects elicited during MP are largely unknown and a substantial number of animal studies are presently focused on this topic. The aim of the present study was to describe a model of DCD based on ex-situ perfusion of liver grafts derived from animals dedicated to food production. Procurement took place within a slaughterhouse facility. A clinically fashioned closed circuit normothermic MP (NMP) was built up. Autologous blood-enriched perfusion fluid was adopted. Perfusate and tissue samples were collected to asses NMP functionality. Grafts were classified as transplantable (LT-G) or not (n-LT) according to clinical criteria, while histopathological analysis was used to confirm graft viability. After cold storage, the liver grafts were connected to the NMP. During the rewarming phase, temperature and flows were progressively increased to reach target values. At the end of NMP, 4 grafts were classified as LT-G and 3 nLT-G. Histology confirmed absence of major damage in LT-G, while diffuse necrosis appeared in nLT-G. Interestingly, in nLT-G an early impairment of hepatocyte respiratory chain, leading to cell necrosis and graft non-viability, was documented for the first time. These parameters, together with indocyanine-green dye and citrate clearance could contribute to graft evaluation in clinical settings. In conclusion, this model provides a promising and reproducible method to replace dedicated experimental animals in DCD and MP research, in line with the 3Rs principles.