Irreversible Electroporation as a Valid Treatment Option for Hepatic Epithelioid Hemangioendothelioma: An International Multicenter Experience.

PURPOSE: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with currently no established standard of care. This international multicenter retrospective study assesses the use of percutaneous irreversible electroporation (IRE) as an ablative tool to treat HEHE and provides a clinical overview of the current management and role of IRE in HEHE treatment. MATERIAL AND METHODS: Between 2017 and 2023, 14 patients with 47 HEHE tumors were treated with percutaneous IRE using CT-scan guidance in 23 procedures. Baseline patient and tumor characteristics were evaluated. Primary outcome measures included safety and effectiveness, analyzed using Common Terminology Criteria for Adverse Events (CTCAE) and treatment response by mRECIST criteria. Secondary outcome measures included technical success, post-treatment tumor sizes and length of hospital stay. Technical success was defined as complete ablation with an adequate ablative margin (intentional tumor free ablation margin > 5 mm). RESULTS: IRE treatment resulted in technical success in all tumors. Following a median follow-up of 15 months, 30 tumors demonstrated a complete response according to mRECIST criteria. The average tumor size pre-treatment was 25.8 mm, accompanied by an average reduction in tumor size by 7.5 mm. In 38 out of 47 tumors, there was no evidence of local recurrence. In nine tumors, residual tumor was present. There were no cases of progressive disease. Median length of hospital stay was one day. Only one grade 3 CTCAE event occurred, a pneumothorax requiring chest tube placement. CONCLUSION: The current study provides evidence that IRE is a safe and efficacious minimally invasive treatment option for HEHE.

Treatment of unresectable locally advanced pancreatic cancer with percutaneous irreversible electroporation (IRE) following initial systemic chemotherapy (LAP-PIE) trial: study protocol for a feasibility randomised controlled trial.

BACKGROUND: Approximately 30% of patients with pancreas cancer have unresectable locally advanced disease, which is currently treated with systemic chemotherapy. A new treatment option of irreversible electroporation (IRE) has been investigated for these patients since 2005. Cohort studies suggest that IRE confers a survival advantage, but with associated, procedure-related complications. Selection bias may account for improved survival and there have been no prospective randomised trials evaluating the harms and benefits of therapy. The aim of this trial is to evaluate the feasibility of a randomised comparison of IRE therapy with chemotherapy versus chemotherapy alone in patients with locally advanced pancreatic cancer (LAPC). METHODS AND ANALYSIS: Eligible patients with LAPC who have undergone first-line 5-FluoroUracil, Leucovorin, Irinotecan and Oxaliplatin chemotherapy will be randomised to receive either a single session of IRE followed by (if indicated) further chemotherapy or to chemotherapy alone (standard of care). Fifty patients from up to seven specialist pancreas centres in the UK will be recruited over a period of 15 months. Trial follow-up will be 12 months. The primary outcome measure is ability to recruit. Secondary objectives include practicality and technical success of treatment, acceptability of treatment to patients and clinicians and safety of treatment. A qualitative study has been incorporated to evaluate the patient and clinician perspective of the locally advanced pancreatic cancer with percutaneous irreversible electroporation trial. It is likely that the data obtained will guide the structure, the primary outcome measure, the power and the duration of a subsequent multicentre randomised controlled trial aimed at establishing the clinical efficiency of pancreas IRE therapy. Indicative procedure-related costings will be collected in this feasibility trial, which will inform the cost evaluation in the subsequent study on efficiency. ETHICS AND DISSEMINATION: The protocol has received approval by London-Brent Research Ethics Committee reference number 21/LO/0077.Results will be analysed following completion of trial recruitment and follow-up. Results will be presented to international conferences with an interest in oncology, hepatopancreaticobiliary surgery and interventional radiology and be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN14986389.

Margin ACcentuation for resectable Pancreatic cancer using Irreversible Electroporation - Results from the MACPIE-I study.

INTRODUCTION: Margin accentuation (MA) using Irreversible electroporation (IRE) offers an unique opportunity to reduce the R1 resections in resectable pancreatic cancer (RPC). This study aims to assess the rate of margin positivity using IRE for MA during pancreaticoduodenectomy (PD) for resectable pancreatic head tumours. MATERIALS AND METHODS: Following ethical approval, MA using IRE was carried out in 20 consecutive patients to posterior and superior mesenteric vein (SMV) margin, and the pancreatic neck, prior to the PD resection. The control group (non-IRE; n = 91) underwent PD without MA over the study period, March 2018 to March 2020. RESULTS: There was no difference between the two groups in terms of patients' age, gender, pre-op biliary drainage, site of malignancy or pre-operative TNM stage. The overall margin positive rate for IRE group was lesser (35.0%) when compared to non-IRE group (51.6%; p = 0.177), with significantly less posterior pancreatic margin positivity (5.0% vs. 25.3%; p = 0.046). When only treated margins (SMA margin excluded) were compared, the IRE group had significantly lower margin positive rates (20.0% vs. 51.6%; p = 0.013). There was no difference between the two groups in terms of intra- or post-operative complications. With a median follow-up of 15.6 months, the median DFS and OS for IRE and non-IRE groups were 17 and 18 months (p = 0.306) and 19 and 22 months (p = 0.227) respectively. CONCLUSION: Our pilot study confirms the safety of MA using IRE for RPC, with reduction in margin positivity. These results as a proof of concept are promising and need further validation with a randomised controlled trial.

Complications from percutaneous microwave ablation of liver tumours: a pictorial review.

Percutaneous microwave ablation of liver tumours is a well-established technique that has been proven to be effective in the curative and palliative treatment of small volume primary and secondary liver tumours. Microwave ablation is designed to achieve larger areas of necrosis compared to radiofrequency ablation and has a good safety profile among liver tumour treatments. Mortality is unreported and major complications are rare. Knowledge of potential complications is essential for interventional radiologists performing liver ablation in order to reduce patient morbidity. The aim of this review is to illustrate major complications post microwave ablation in a pictorial format as well as a discussion on how best to avoid these complications.

Irreversible electroporation in borderline resectable pancreatic adenocarcinoma for margin accentuation.

Achieving clear microscopic resection margins following pancreaticoduodenectomy (PD) is challenging particularly in borderline resectable pancreatic carcinoma (BRPC). Positive resection margins has been identified as a major independent prognostic factor. Irreversible electroporation (IRE) has emerged as a promising non-thermal ablative method that could be used in the treatment of pancreatic cancer as an adjunct to chemotherapy and surgery. This case report describes the successful simultaneous intraoperative IRE and PD in a patient with BRPC, achieving clear microscopic resection margins. Technical aspects and histology showing the effect of IRE are presented. The role of IRE in the treatment of pancreatic adenocarcinoma should be further evaluated in prospective studies.

Clinical and prognostic associations of liver volume determined by computed tomography in acute liver failure.

BACKGROUND: Liver volume (LV) can be non-invasively determined from the analysis of computed tomography (CT) images, and in patients with acute liver injury (ALI) or failure (ALF), it can reflect the balance of structural collapse with hepatic regeneration. We examined its relation to cause of liver injury, measures of liver function and histopathological findings, and utility in prediction of complications and mortality. METHODS: Two hundred and seventy-three patients with ALF/ALI admitted to a specialist intensive care unit were studied. One hundred and ninety-nine patients (73%) had non-acetaminophen (NA) aetiologies and 74 (27%) had acetaminophen-induced disease. LV and proportion of predicted LV (PLV%) were determined from admission CT imaging. RESULTS: LV and PLV% showed marked variation when aetiologic groups were compared (P < .0001), including loss in cases with indeterminate cause (LV 939 cm3 [IQR 680-1259], PLV% 56% [42-84]) and increase in Budd-Chiari syndrome (1891 cm3 [1601-2094], 121% [111-131]). Progression to high-grade encephalopathy was more common with smaller LV and PLV. A < 1000 cm3 threshold identified NA patients who later developed it with 93% (95%CI 83-98) specificity and odds ratio 10.6 (3.3-34.5) at median 5 days prior to onset, and risk of death in those with NA-drug-induced (DILI) or indeterminate disease with 91% (71-99) specificity and 63% (50-75) sensitivity. CONCLUSION: In patients with ALF/ALI, LV shows marked variation by the cause of disease, and in prognostic importance. In indeterminate and DILI cases, loss of volume to <1000 cm3 may indicate irreversible liver injury and regenerative failure and serve as an early clinical predictor for the development of high-grade encephalopathy and death.

Typical and atypical benign liver lesions: A review.

Focal liver lesions are routinely encountered by clinical radiologists and represent a wide spectrum of pathology. Majority of these lesions are likely to be benign in nature, especially in the absence of chronic liver disease or primary cancer. A radiologist must be aware of common and uncommon imaging features of benign lesions across the various imaging modalities. This review discusses pathognomonic imaging features of common benign focal liver lesions seen on ultrasound, computed tomography and magnetic resonance, and adds to existing knowledge with the recent updates to have emerged in this area.

Irreversible electroporation for the treatment of pancreatic neuroendocrine tumors.

BACKGROUNDS/AIMS: Resection or enucleation is currently the treatment of choice for small pancreatic neuroendocrine tumors (NETs). Irreversible electroporation is a novel ablative method that is used for locally advanced pancreatic adenocarcinoma, but little data exists for its use for pancreatic NETs. We report an early experience of IRE for early pancreatic NETs. METHODS: Between April 2014 and March 2015, 3 patients with small (<2 cm) pancreatic NETs were treated with percutaneous IRE. RESULTS: There were no adverse effects during the procedure. Mean hospital stay was 2.6 days. All patients remained disease free on 12-19 months follow up. One patient developed recurrent pancreatitis with pseudocyst formation. CONCLUSIONS: IRE for small tumors of the pancreas is practical and may offer advantages over other thermal ablative techniques, since it preserves vital structures such as blood vessels, bile and pancreatic ducts. Further data regarding the long term disease free interval is required to establish efficacy.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure for hepatocellular carcinoma with chronic liver disease: a case report and review of literature.

The incidence of complications after liver resection is closely related to functional future liver remnant (FLR). The standard approach to augment FLR is surgical or radiological occlusion of the artery or portal vein on the tumor side. Associated liver partition and portal vein ligation for staged hepatectomy (ALLPS) has been introduced as an alternative method to augment FLR. It offers rapid and effective hypertrophy for resecting liver metastases. However, data regarding its application in patients with hepatocellular carcinoma (HCC) with a background of chronic liver disease are limited. Here we describe the use of ALPPS procedure to manage a large solitary HCC with a background of chronic liver disease. The rising incidence of HCC has increased the number of surgical resections in patients with advanced stage liver disease not considered for liver transplantation. We reviewed reported experience of ALPPS in established chronic liver disease and current therapeutic modalities for HCC on a background of chronic liver disease in patients with potential liver insufficiency where tumor burden is beyond liver transplant criteria.

Multiple ß-catenin mutations in hepatocellular lesions arising in Abernethy malformation.

An 18-year-old man underwent liver transplantation due to an Abernethy malformation associated with multiple hepatocellular nodules including one which was rapidly enlarging and was suspicious for malignant transformation. Analysis of the explanted liver showed a spectrum of multiple hepatocellular nodules ranging in appearance from focal nodular hyperplasia, hepatocellular adenoma and to a well-differentiated hepatocellular neoplasm borderline for hepatocellular carcinoma. Mutational analysis revealed wild-type ß-catenin expression in the background liver and some nodules, whilst different variants were present in other lesions irrespective of their morphological appearance. No telomerase reverse transcriptase (TERT) promoter mutation was identified. Abernethy malformations can lead to independent genetic events which can result in ß-catenin mutations associated with malignant transformation of hepatocellular nodules. When following up such patients, one must therefore have a high index of suspicion, particularly if radiological surveillance reveals a change in the nature of hepatic lesions.

Congenital extrahepatic portosystemic shunt complicated by the development of hepatocellular carcinoma.

Congenital extrahepatic portosystemic shunt, also known as Abernethy malformation, is a rare congenital malformation. It causes shunting of blood through a communication between the portal and systemic veins such as a patent ductus venous. We report 3 cases of Abernethy malformation complicated by the development of hepatocellular carcinoma. Additionally, we comprehensively reviewed all previously reported cases and highlighted common features that may help in early diagnosis and appropriate management. Patients with Abernethy malformation may have an increased propensity to develop hepatocellular carcinoma. All 5 previously reported cases, plus the three of our patients, have a type 1 (complete) shunt suggesting a role for absent portal blood flow in the pathogenesis of hepatocellular carcinoma. Congenital extrahepatic portosystemic shunt should be sought for in cases with raised serum ammonia, hepatic encephalopathy or hepatocellular carcinoma in the absence of cirrhosis.

Benign histology after pancreaticoduodenectomy for suspected malignancy. Lessons to be learned--a single centre experience.

UNLABELLED: The aim of the study was to perform a comprehensive analysis of patients with a benign final histology after pancreaticoduodenectomies (PD) for suspected pancreatic and periampullary cancer. MATERIAL AND METHODS: We searched the pathology database at the King's College Hospital for negative PD specimens submitted between January 2004-December 2010. Clinical, diagnostic, surgical,histopathological and outcome data were collected retrospectively. Pathology specimens and imaging results have been re-evaluated. A literature review was performed to identify factors affecting the incidence across centres. RESULTS: 469 PD were performed for presumed cancer. The incidence of benign disease encountered in this group was 7.25% (34/469). Autoimmune pancreatitis (AIP) was a finding in 26.47% (9/34) of cases. 17.65% of PD were complicated by a pancreatic leak and the overall mortality rate was 8.82%(3/34). Radiologists revised over 75% of pre-operative diagnoses. The incidence of benign disease was correlated with the overall centre experience and utilisation of CT imaging, but not ERCP or EUS. CONCLUSIONS: It is impossible with current diagnostics to entirely avoid cases of benign disease inpatients undergoing PD for suspected cancer. The mortality rate is higher in this group, but it is possible to avoid unnecessary procedures in experienced centres. AIP represents an important diagnostic entity, which should be actively pursued pre-operatively.

Demonstration of an occult biliary-arterial fistula using percutaneous contrast-enhanced ultrasound cholangiography in a transplanted liver.

We present a case of a biliary-arterial communication as a consequence of the placement of an internal-external biliary drainage catheter in a liver transplant patient diagnosed on contrast-enhanced ultrasound using a novel application by injecting microbubble contrast into the catheter tube. We postulate that this method may be sensitive in identifying occult communications between the biliary tree and the vascular compartment when a catheter drain is positioned, and there is hemobilia or unexplained sepsis.

Selective embolization for bleeding visceral artery pseudoaneurysms in patients with pancreatitis.

BACKGROUND: Pancreatitis is associated with arterial complications in 4%-10% of patients, with untreated mortality approaching 90%. Timely intervention at a specialist center can reduce the mortality to 15%. We present a single institution experience of selective embolization as first line management of bleeding pseudoaneurysms in pancreatitis. METHODS: Sixteen patients with pancreatitis and visceral artery pseudoaneurysms were identified from searches of the records of interventional angiography from January 2000 to June 2007. True visceral artery aneurysms and pseudoaneurysms arising as a result of post-operative pancreatic or biliary leak were excluded from the study. RESULTS: In 50% of the patients, bleeding complicated the initial presentation of pancreatitis. Alcohol was the offending agent in 10 patients, gallstones in 3, trauma, drug-induced and idiopathic pancreatitis in one each. All 16 patients had a contrast CT scan and 15 underwent coeliac axis angiography. The pseudoaneurysms ranging from 0.9 to 9.0 cm affected the splenic artery in 7 patients: hepatic in 3, gastroduodenal and right gastric in 2 each, and left gastric and pancreaticoduodenal in 1 each. One patient developed spontaneous thrombosis of the pseudoaneurysm. Fourteen patients had effective coil embolization of the pseudoaneurysm. One patient needed surgical exclusion of the pseudoaneurysm following difficulty in accessing the coeliac axis radiologically. There were no episodes of re-bleeding and no in-hospital mortality. CONCLUSIONS: Pseudoaneurysms are unrelated to the severity of pancreatitis and major hemorrhage can occur irrespective of their size. Co-existent portal hypertension and sepsis increase the risk of surgery. Angiography and selective coil embolization is a safe and effective way to arrest the hemorrhage.

Selective use of endoscopic retrograde cholangiopancreatography in the diagnosis of biliary atresia in infants younger than 100 days.

OBJECTIVES: We investigated the role and safety of endoscopic retrograde cholangiopancreatography (ERCP) in diagnosing biliary atresia (BA) in prolonged neonatal cholestasis, when standard workup was inconclusive. PATIENTS AND METHODS: We reviewed notes of 48 cholestatic infants younger than 100 days undergoing ERCP from 1997 to 2007. RESULTS: Amongst approximately 3300 infants evaluated for liver disease during the study, 224 (6.8%) were diagnosed with BA. Forty-eight children underwent ERCP. Findings at liver biopsy (n=47) included nonspecific cholestasis (n=19, 40%), giant-cell hepatitis (n=12, 26%), "large bile duct obstruction" (n=9, 19%) in the presence of pigmented stools, and mixed cholestatic/hepatitic features (n=7, 15%). ERCP demonstrated a patent biliary tree in 20 infants (42%). BA was confirmed at exploratory laparotomy in all 3 infants (6%) in whom cannulation failed. The remaining 25 infants (52%) also proceeded to exploratory laparotomy, in which BA was confirmed in 22 (46%). Amongst the 20 children in whom ERCP ruled out BA, 8 (17%) had normal biliary anatomy, whilst 12 (25%) had an abnormal biliary tree, including 6 (12.5%) with neonatal sclerosing cholangitis. After ERCP none developed clinical pancreatitis or peritonitis. CONCLUSIONS: ERCP is a safe procedure for diagnosing BA even in the smallest infants with high positive and negative predictive values.

Small bowel haemorrhage associated with partial midgut malrotation in a middle-aged man.

We describe a case of life-threatening small bowel haemorrhage in a 56 year old man, who was found to have partial midgut malrotation at laparotomy. An association between congenital malrotation and gastrointestinal haemorrhage has not previously been reported in this age group. We discuss the association between gut malrotation and small intestinal pathology and describe the principles of management in these patients.

Localized pigmented villonodular synovitis: arthroscopic treatment of a lesion arising from the quadriceps tendon sheath.

Pigmented villonodular synovitis (PVNS) is a rare benign proliferative growth of synovium of obscure etiology with a wide spectrum of clinical presentation. Localized PVNS, also known as giant cell tumor of the tendon sheath, is even more uncommon. Localized PVNS of the knee is a rare, idiopathic condition presenting with symptoms that can mimic other intra-articular pathologies. The condition is usually monoarticular, the knee being the most commonly affected joint. We report a rare case of PVNS arising from the quadriceps tendon sheath. It was successfully treated with arthroscopic intralesional excision. At 18 months' follow-up, there has been no recurrence.