Safety and efficacy of irreversible electroporation treatment in hepatobiliary and pancreatic tumours: a single-centre experience.

AIM: To report initial experience with irreversible electroporation (IRE) in a single tertiary oncology centre and to describe its role in the management of liver and pancreatic tumours. MATERIALS AND METHODS: The present study was a retrospective review of the technical success rate, complications, and treatment efficacy of patients who had undergone IRE treatment for hepatobiliary and pancreatic tumours between February 2014 to January 2020. The patients were divided into two cohorts: first 30 patients (cohort A) and subsequent 70 patients (cohort B) after a change in protocol. RESULTS: One hundred IRE procedures (n=69 liver lesions; n=28 pancreatic lesions, n=3 nodal disease) were reviewed. The overall technical success rate was 99%. Early and immediate complications were 4% and 3%, respectively. In cohort A, the complete tumour ablation rate was 65% (13/20) for hepatic tumours, 20% (1/5) for locally advanced pancreatic adenocarcinoma, 50% (2/4) for pancreatic neuroendocrine tumours, and 0% (0/1) for nodal metastasis. For cohort B, the rate improved to 87.76% (43/49) for hepatic tumours, 28.57% (4/14) for locally advanced pancreatic adenocarcinoma, 80% (4/5) for pancreatic neuroendocrine, and 50% (1/2) for nodal metastasis. After the initial cohort A, cohort B showed a significant increase in the initial complete ablation rate in hepatic tumours (p=0.028). CONCLUSION: IRE is a complex technique with a steep learning curve. It is safe, effective, and is valuable in the treatment of liver tumours that are unsuitable or considered high risk for conventional thermal ablation. Its role in the management of pancreatic tumours is less clear and requires larger studies.

Transplantation crisis at the time of economic recession in Greece.

OBJECTIVES: Aim of the study was to assess the effect of economic recession on organ donation and transplantation in Greece. METHODS: Retrospective data (2002-2016) provided by the Hellenic Transplant Organization (HTO), International Registry in Organ Donation and Transplantation, Eurotransplant, Scandiatransplant, National Health Service Blood and Transplant (NHSBT), and United Network of Organ Sharing (UNOS) databases were analyzed. HTO database was divided into the precrisis (2002-2008) and crisis (2009-2016) era. Donation and transplantation rates between the two periods were compared. Trend estimation analysis was applied on the latter period. RESULTS: Since 2009, organ donation significantly declined without significant change in the reported brain deaths. Overall solid organ transplantations decreased (319.63 ± 70.4 from 460 ± 55.25 transplants/year, P = 0.001). Kidney transplantation rates declined (139.38 ± 29.7 from 209.43 ± 20.9 transplants/year, P = 0.000), with dramatic reduction in both deceased (99 ± 27.5 from 136.43 ± 131.4 transplants/year, P = 0.030) and living donor kidney transplantations (40.38 ± 6.1 from 73 ± 12.5 transplants/year, P = 0.000). Liver, heart, and lung transplant rates were not significantly affected; however, they have been low throughout both periods. Convertion to donation has not been affected by the crisis. Time series logistic regression of the crisis period demonstrated declining trends in organ donation, total solid organ transplantation, and deceased donor kidney, liver, and lung transplantation. In 2015, Greek organ donation rates were inferior to Eurotransplant, Scandiatransplant, NHSBT, UNOS, and Italy. CONCLUSIONS: There has been a temporal correlation between the economic recession and organ donation and transplantation crisis in Greece. Irrespective of the cause, measures should be taken to reverse this in order to avert the increased morbidity and mortality on the transplant waiting list.

Evaluation of treatment delays in hepatopancreatico-biliary surgery during the first COVID-19 wave.

INTRODUCTION: The COVID-19 pandemic has caused oncological services worldwide to face unprecedented challenges resulting in treatment disruption for surgical patients. Hepatopancreatico-biliary (HPB) cancers are characterised by rapid disease progression. This study aims to assess delays in receiving surgery for this patient cohort during the first COVID-19 wave. METHODS: Patients undergoing surgery between April and July 2020 (COVID-19 period) were compared with a control group from the preceding year. Delay in receiving surgery was defined as more than 50 days between referral and surgery date. Statistical analysis was carried out to evaluate predictors of delay and short-term outcomes. RESULTS: During the COVID-19 and pre-COVID-19 periods, 94 and 115 patients underwent surgery, respectively. No patients contracted COVID-19 postoperatively. Some 118 patients waited more than 50 days for surgery versus 91 who received surgery within 50 days from referral. Independent predictors for surgical delay were undergoing surgery in the COVID-19 era (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.2-4.1; p=0.015), referral pathway (OR 35.1, 95% CI 4.2-296; p=0.001) and presenting pathology (OR 8.3, 95% CI 1.2-56.1; p=0.03). Short-term outcomes were comparable between groups. CONCLUSIONS: Patient referral pathway and presenting pathology may contribute to delays in undergoing HPB cancer surgery during COVID-19 outbreaks. It is hoped that a better understanding of these factors will aid in designing shifts in healthcare policy during future pandemic outbreaks.

Predictors of recurrence following laparoscopic minor hepatectomy for hepatocellular carcinoma in the UK.

AIMS: Minor hepatectomy, which is increasingly carried out laparoscopically (LLR), is a cornerstone of curative treatment for hepatocellular carcinoma (HCC). The majority of relevant publications however originate from regions with endemic viral hepatitis. Although the incidence of HCC in the UK is increasing, little is known about outcomes following LLR. METHODS: Consecutive patients undergoing minor (involving ≤2 segments) LLR or open resection (OLR) at our institute between 2014 and 2021 were compared. Selection from a plethora of factors potentially impacting on overall (OS) and disease free survival (DFS) was optimised with Lasso regression. To enable analysis of patients having repeat resection, multivariate frailty modelling was utilised to calculate hazard ratios (HR). RESULTS: The analysis of 111 liver resections included 55 LLR and 56 OLR. LLR was associated with a shorter hospital stay (5 ± 2 vs. 7 ± 2 days; p < 0.001) and a lower comprehensive complication index (4.43 vs. 9.96; p = 0.006). Mean OS (52.3 ± 2.3 vs. 49.9 ± 3.0 months) and DFS (33.9 ± 3.4 vs. 36.5 ± 3.6 months; p = 0.59) were comparable between LLR and OLR, respectively (median not reached). Presence of mixed cholangiocarcinoma/HCC, satellite lesions and AFP level predicted OS and DFS. In addition tumour size was predictive of DFS. CONCLUSIONS: In the studied population minor LLR was associated with shorter hospital stay and fewer complications while offering non-inferior long-term outcomes. A number of predictors for disease free survival have been elucidated that may aid in identifying patients with a high risk of disease recurrence and need for further treatment.

Prediction models of donor arrest and graft utilization in liver transplantation from maastricht-3 donors after circulatory death.

Shortage of organs for transplantation has led to the renewed interest in donation after circulatory-determination of death (DCDD). We conducted a retrospective analysis (2001-2009) and a subsequent prospective validation (2010) of liver Maastricht-Category-3-DCDD and donation-after-brain-death (DBD) offers to our program. Accepted and declined offers were compared. Accepted DCDD offers were divided into donors who went on to cardiac arrest and those who did not. Donors who arrested were divided into those producing grafts that were transplanted or remained unused. Descriptive comparisons and regression analyses were performed to assess predictor models of donor cardiac arrest and graft utilization. Variables from the multivariate analysis were prospectively validated. Of 1579 DCDD offers, 621 were accepted, and of these, 400 experienced cardiac arrest after withdrawal of support. Of these, 173 livers were transplanted. In the DCDD group, donor age < 40 years, use of inotropes and absence of gag/cough reflexes were predictors of cardiac arrest. Donor age >50 years, BMI >30, warm ischemia time >25 minutes, ITU stay >7 days and ALT ≥ 4× normal rates were risk factors for not using the graft. These variables had excellent sensitivity and specificity for the prediction of cardiac arrest (AUROC = 0.835) and graft use (AUROC = 0.748) in the 2010 prospective validation. These models can feasibly predict cardiac arrest in potential DCDDs and graft usability, helping to avoid unnecessary recoveries and healthcare expenditure.

Clinical outcomes for patients with liver-limited metastatic colorectal cancer: Arguing the case for specialist hepatobiliary multidisciplinary assessment.

In patients with liver-limited metastatic colorectal cancer, hepatic resection can offer a significant survival benefit over systemic therapy alone. Specialist hepatobiliary multidisciplinary meetings are currently believed to provide the best forum to discuss the management for these patients. A retrospective analysis was undertaken of patients diagnosed with liver-limited metastatic colorectal cancer over 6 months within a cancer network in the United Kingdom. In addition, patients who were diagnosed but not referred to the hepatobiliary meeting were discussed within a virtual multi-disciplinary setting. Contributors were blinded and proposed management recorded. 159 newly diagnosed patients with liver-limited metastatic colorectal cancer were identified. 68 (43%) were referred at initial diagnosis and 38 (24%) referred following systemic treatment. 35 (51%) who were discussed at baseline underwent a subsequent hepatectomy or radiofrequency ablation, as did 18 (47%) patients referred after chemotherapy. Of the remaining 53 (33%) patients not referred, imaging was available for 31 (58%). Decisions regarding potential liver-directed therapy were discussed within a multi-disciplinary setting. 13 (42%) were identified as resectable or potentially resectable and 11 (36%) may have been suitable for a clinical trial. In reality, none of these 31 patients (100%) underwent surgery or ablation. Whilst the majority of patients with liver-limited metastatic colorectal cancer were referred appropriately, this study demonstrates that a significant number with potentially resectable disease are not being discussed at specialist meetings. A review of all diagnosed cases would ensure that an increased number of patients are offered hepatic resection or ablation.

Liver transplantation in adults coinfected with HIV.

OBJECTIVE: To report our experience of prospectively identifying and transplanting livers into HIV-positive patients. DESIGN: Liver transplantation in HIV-positive patients remains controversial. The finding of HIV is usually considered a contraindication to any form of transplantation. Previously reported cases are few and refer to patients who tested HIV positive after they had their liver transplantations or who seroconverted in the posttransplantation period. This is, to our knowledge, the only report of patients who were known to be HIV positive at the time of decision for listing for transplantation. METHODS: The medical records of five HIV-positive patients who received liver transplants in King's College Hospital, London, during a 5-year period (January 1995-December 1999) were reviewed. All five were known to be HIV positive at the time of listing for liver replacement. Three of them had end-stage liver disease due to hepatitis C (two of them had underlying Hemophilia A) while the other two had acute liver failure, one due to hepatitis B infection and one due to nonA-nonB-nonC hepatitis. In all but one patient the HIV infection had been asymptomatic. RESULTS: All patients survived the immediate posttransplantation period, but the three patients with hepatitis C died of complications of recurrent hepatitis C between 6 and 25 months posttransplantation. The other two patients are currently alive 4 and 34 months posttransplantation with good graft function and without complications from their HIV infection. CONCLUSION: The early outcome of liver transplantation in HIV seropositive patients can be good, and patients should not be excluded from transplantation if their liver disease determines their prognosis. More effective antiviral therapy for hepatitis C given posttransplantation, and for hepatitis B reinfection, should improve the longer-term outcome of HIV patients with end-stage liver disease due to hepatitis.

Liver transplantation with monosegments.

BACKGROUND: Shortage of size-matched pediatric donors led to the development of surgical techniques to reduce or split livers and thus increase the potential pool of donors. Despite this, neonatal transplantation remains a problem because of the small size of the recipients. Further reduction of the left lateral segment is possible to provide a single segment graft (segment III). We report our experience of transplanting 6 babies using this technique. METHODS: Of 310 children transplanted in our center between October 1989 and March 1998, 6 patients, 2 male and 4 female, median age 37.5 days (range 5 to 92 days), median weight 3.45 kg (range 2.45 to 5.46 kg) were transplanted with a monosegment. The cause of liver failure was neonatal hemochromatosis in 4, retransplantation for hepatic artery thrombosis in 1, and hepatitis B in one. The donor liver was reduced or split to a left lateral segment. Segment II was then resected and discarded before transplantation. RESULTS: Overall, graft and patient survival is 83.3%. Five patients are alive with good graft function at a mean follow-up of 30.4 months (range 8 to 82 months). One child who was transplanted for hepatic artery thrombosis died from sepsis and multiorgan failure 48 hrs after transplant. None of the survivors had vascular or biliary complications. CONCLUSIONS: Monosegment liver transplantation with segment III appears to be a satisfactory option for treating small babies with liver failure.

Surgery in Greece.

The expenditure on health care reached 7.8% of the gross domestic product in Greece in 1991. Almost 9000 specialized surgeons in 11 recognized specialties provide services to more than 10 million people living in Greece and 2 million visitors annually. Medical studies comprise a 6-year course of 5000 to 5500 teaching hours in 7 medical schools and are free. Organizational reform of the health care system in vital and long overdue to move the system into the 21st century. The quality of surgical services provided is high by international standards; cardiac surgery, organ transplantation, surgical oncology, and anesthesiology are some areas of excellence. In addition, Greece has a good record in medical technology and instrumentation. Research activities cover a range of subjects, and the number of clinical medicine articles from Greece that appear in peer-reviewed journals compares favorably with other larger countries. Reforms in the postgraduate training system and ongoing education are necessary.

Use of mycophenolate mofetil in the experimental allo-transplantation of hepatocytes in rats with fulminant hepatic failure.

AIM: The aim of the study was to evaluate the beneficial effect of mycophenolate mofetil (MMF) as an immunosuppressive agent for experimental transplantation of hepatocytes in rats with fulminant hepatic failure (FHF). MATERIALS AND METHODS: Six Wistar rats were used as donors and 40 Lewis rats at recipients, including four groups of 10 animals each. Group A received no treatment; Group B, cyclosporine (20 mg/kg days 0-5 and 10 mg/kg days 6-15); Group C, MMF (12 mg/kg per os every day); and Group D, MMF (23 mg/kg per os every day). Hepatocytes were transplanted intrasplenically. Animals were followed for 15 days. RESULTS: The survival rates for Group A were maximum 72 h, whereas Groups B, C, and D showed 50%, 70%, and 80%, respectively. Biochemical evaluation and histology showed satisfactory function and engraftment, respectively. CONCLUSION: The use of MMF in this experimental model yielded safe, satisfactory immunosuppression especially at the dose of 23 mg/kg.

Review article: the investigation and management of gastric neuroendocrine tumours.

BACKGROUND: Gastric carcinoids (GCs) or neuroendocrine tumours (NETs) are increasingly identified at endoscopy, and account for 0.6-2% of all gastric polyps identified. The SEER database in the US has demonstrated a rising incidence of gastric NETs amongst all NETs; from 2.2% between 1950 and 1969 to 6.0% between 2000 and 2007. AIM: To review the literature and assist clinicians in managing patients with GCs. METHODS: A literature search was conducted through MEDLINE using search terms: gastric, carcinoid, neuroendocrine tumour, therapy, endoscopy, mucosal resection, submucosal dissection. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles. RESULTS: There are three types of GCs with important epidemiological, pathophysiological, histological and endoscopic differences that affect prognosis and management. Type 1 and 2 GCs develop in the context of hypergastrinaemia that originates from achlorhydria in atrophic gastritis and a gastrinoma, respectively. Type 3 GCs occur sporadically and independent of gastrin. The histological type, grade and Ki67 index are used to determine prognosis and direct clinical management. Type 1 GCs >1 cm in size and type 2 GCs should be assessed for invasion beyond the submucosa with EUS prior to endoscopic resection with EMR or ESD. Type 3 GCs should be managed as per recommendations for gastric adenocarcinoma. The treatment of advanced disease is multimodal. CONCLUSIONS: Patients with gastric carcinoids should be discussed in a specialist neuroendocrine tumour multidisciplinary meeting to ensure all treatment options are explored in localised and advanced disease. Areas of controversy exist that need further research.

Differentiation between infection in kidney and liver cysts in autosomal dominant polycystic kidney disease: use of PET-CT in diagnosis and to guide management.

Positron emission tomography-computed tomography (PET-CT) is a useful imaging method for localizing infective lesions. We report a case of autosomal dominant polycystic kidney disease in which PET-CT was used to differentiate between infection in the kidney and liver cysts. Localization of infection to the liver rather than to kidney cysts altered patient management. We briefly review the role of PET-CT in localization of an occult focus of infection.

Ex vivo liver surgery for extraadrenal pheochromocytoma.

A case of a 15-year-old girl with a malignant extraadrenal pheochromocytoma situated between the inferior vena cava and the portal triad is described. Using ex vivo technique, the tumour was successfully resected on the bench, as a previous attempt to remove the tumour in situ had been abandoned. The surgical aspects and implications of ex vivo surgery are discussed, highlighting the increased operative risk, perioperative mortality, and poor long-term results in patients with malignant tumours.

Haemodynamic changes in ischaemic vs. anhepatic pig experimental model of acute liver failure.

BACKGROUND AND OBJECTIVE: The removal of the non-functioning liver in cases of fulminant liver failure has been advocated by some authors as a means of improving haemodynamic instability and acid-base disturbances associated with acute liver failure. METHODS: The aim of the present experimental study was to investigate whether maintaining a non-functioning liver is preferable over removing it in terms of haemodynamic variables, after acute hepatic failure has been surgically induced. Twenty Landrace pigs were used in the study. All of them underwent portocaval anastomosis and ligation of the hepatic artery. After an 18-h period and with biochemical indices of fulminant hepatic failure clearly demonstrated, the animals were randomly assigned to one of two groups: in 10 pigs (Group A) the ischaemic liver was left in situ and no further surgical intervention was undertaken. The other 10 (Group B) underwent total hepatectomy. Haemodynamic monitoring was the same in both groups. No inotropes were administered throughout the whole period of observation. RESULTS: Haemodynamic deterioration was observed in the hepatectomized pigs (Group B) whereas the group with the ischaemic liver in situ (Group A) remained stable in terms of the haemodynamic variables evaluated until the end of the experiment. (Cardiac index in Group A 7.59 +/- 1.25 L min(-1) m(-2) vs. 2.92 +/- 0.68 L min(-1) m(-2) in Group B, P < 0.05.) CONCLUSIONS: The concept of salvage hepatectomy in cases of acute liver failure should be redefined since there seems to be some experimental evidence that it may not be as beneficial as originally thought.

Retroperitoneal tumors: do the satellite tumors mean something?

BACKGROUND AND OBJECTIVES: Primary retroperitoneal tumors constitute a rather uncommon disease with an incidence of 2 in 100,000. Local recurrence after surgical resection is reported between 60% and 90% at 10 yr. The aim of this study was to present the problem of satellite tumors around the main tumor mass and their possible relation to local recurrence. METHODS: Twenty-nine patients with retroperitoneal tumors underwent surgical resection in our department during an 8-yr period. We reviewed their records including their preoperative computed tomography (CT) scans. RESULTS: Twenty patients had "complete" resections requiring seven nephrectomies, four colectomies, two splenectomies, and one appendectomy. In nine cases the resection was incomplete because of tumor invasion to vital structures. Histopathology revealed that the resected tumors were: liposarcomas (12), leiomyosarcomas (4), paragangliomas (5), malignant fibrous histiocytomas (3), other sarcomas (3), schwannoma (1), myelolipoma (1), and the malignancy grade was I in 6, grade II in 11, and grade III in 12 cases. Two patients died within 30 d of the operation. The I year recurrence rate was 41.4% (12/29) and the total recurrence rate 55.2% (16/29). Survival at 5 yr was 31% (9/29), whereas the disease-free survival was 20.7% (6/29). Four patients required reoperations. In seven cases (24,1%) preoperative CT scans revealed small nodular lesions around the main tumor that were removed en bloc and were of the same histopathological type as the main tumor. We called these "satellite" tumors. All seven patients had local recurrence within 1 yr. CONCLUSIONS: There seems to be a close relationship between the finding of satellite tumors and the recurrence of the disease. The existence of satellite tumors on the preoperative CT scan may be used as a guide for the extent of the resection, and further investigations are necessary before they are used as a prognostic sign.

Liver transplantation for alpha-1-antitrypsin deficiency in children.

Alpha-1-antitrypsin (a1-AT) deficiency is an inborn error of metabolism, which can cause liver disease. The condition is one of the most common genetic disorders in the Caucasian population. Here we review our experience with 21 children suffering from end-stage liver disease due to a1-AT deficiency. All children are PIZZ homozygotes. Nineteen of them initially presented with neonatal jaundice and two with hepatosplenomegaly in childhood. Twenty-five liver transplantations were performed. All children are currently alive at a median followup of 40 months. Liver replacement provides the only definite treatment for children with end-stage liver disease associated with a1-AT deficiency. Excellent results can be achieved by reducing waiting time for transplantation and by early referral to a liver transplant centre.