Paul Tait

Preoperative portal vein embolization for major liver resection: a meta-analysis.

Introduction:Preoperative portal vein embolization (PVE) is used clinically to prevent postoperative liver insufficiency. The current study examined the impact of portal vein embolization on liver resection. Method:A comprehensive Medline search to identify all registered literature in the English language on portal vein embolization. Meta-analysis was performed to assess the result of PVE and its impact on major liver resection. Result:A total of 75 publications met the search criteria but only 37 provided data sufficiently enough for analysis involving 1088 patients. The overall morbidity rate for PVE was 2.2% without mortality. Four weeks following PVE, 85% patients underwent the planned hepatectomy (n = 930). Twenty-three patients had transient liver failure following resection after PVE (2.5%) but 7 patients developed acute liver failure and died (0.8%). The reason for nonresection following PVE (n = 158, 15%) included inadequate hypertrophy of remnant liver (n = 18), severe progression of liver metastasis (n = 43), extrahepatic spread (n = 35), refusal to surgery (n = 1), poor general condition (n = 1), altered treatment to transcatheter artery embolization or chemotherapy (n = 24), complete remission after treatment with 3 cycles of fluoracil and interferon α in a patient with hepatocellular carcinoma (n = 1), incomplete pre- or postembolization scanning (n = 8). Of those who underwent laparotomy without resection, (n = 27) reasons included intraoperative finding of peritoneal dissemination (n = 15), portal node metastasis (n = 2), severe invasion of the tumor to the hepatic artery and portal vein (n = 1), and gross tumoral extension precluding curative resection (n = 9). Two techniques were used for portal vein embolization: percutaneous transhepatic portal embolization, (PTPE) and transileocolic portal embolization, (TIPE). The increase in remnant liver volume was much greater in PTPE than TIPE group (11.9% vs. 9.7%; P = 0.00001). However, the proportion of patients who underwent resection following PVE was 97% in TIPE and 88% PTPE, respectively (P = <0.00001). Although there was no significant difference in patients who had major complications post-PVE, the rate for minor complications was significantly higher among patients who had PTPE (53.6% vs. 0%, P = <0.0001). Conclusion:PVE is a safe and effective procedure in inducing liver hypertrophy to prevent postresection liver failure due to insufficient liver remnant.

Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update.

The British Society of Gastroenterology guidelines on the management of cholangiocarcinoma were originally published in 2002. This is the first update since then and is based on a comprehensive review of the recent literature, including data from randomised controlled trials, systematic reviews, meta-analyses, cohort, prospective and retrospective studies.

Characterization and Clinical Application of Human CD34+ Stem/Progenitor Cell Populations Mobilized into the Blood by Granulocyte Colony‐Stimulating Factor

A phase I study was performed to determine the safety and tolerability of injecting autologous CD34+ cells into five patients with liver insufficiency. The study was based on the hypothesis that the CD34+ cell population in granulocyte colony‐stimulating factor (G‐CSF)‐mobilized blood contains a subpopulation of cells with the potential for regenerating damaged tissue. We separated a candidate CD34+ stem cell population from the majority of the CD34+ cells (99%) by adherence to tissue culture plastic. The adherent and nonadherent CD34+ cells were distinct in morphology, immunophenotype, and gene expression profile. Reverse transcription‐polymerase chain reaction‐based gene expression analysis indicated that the adherent CD34+ cells had the potential to express determinants consistent with liver, pancreas, heart, muscle, and nerve cell differentiation as well as hematopoiesis. Overall, the characteristics of the adherent CD34+ cells identify them as a separate putative stem/progenitor cell population. In culture, they produced a population of cells exhibiting diverse morphologies and expressing genes corresponding to multiple tissue types. Encouraged by this evidence that the CD34+ cell population contains cells with the potential to form hepatocyte‐like cells, we gave G‐CSF to five patients with liver insufficiency to mobilize their stem cells for collection by leukapheresis. Between 1 × 106 and 2 × 108 CD34+ cells were injected into the portal vein (three patients) or hepatic artery (two patients). No complications or specific side effects related to the procedure were observed. Three of the five patients showed improvement in serum bilirubin and four of five in serum albumin. These observations warrant further clinical trials.

Autologous Infusion of Expanded Mobilized Adult Bone Marrow-Derived CD34+ Cells Into Patients With Alcoholic Liver Cirrhosis

OBJECTIVES: Recent advances in regenerative medicine, including hematopoietic stem cell (HSC) transplantation, have brought hope for patients with severe alcoholic liver cirrhosis (ALC). The aim of this study was to assess the safety and efficacy of administering autologous expanded mobilized adult progenitor CD34+ cells into the hepatic artery of ALC patients and the potential improvement in the liver function.METHODS: Nine patients with biopsy-proven ALC, who had abstained from alcohol for at least 6 months, were recruited into the study. Following granulocyte colony-stimulating factor (G-CSF) mobilization and leukapheresis, the autologous CD34+ cells were expanded in vitro and injected into the hepatic artery. All patients were monitored for side effects, toxicities, and changes in the clinical, hematological, and biochemical parameters.RESULTS: On average, a five-fold expansion in cell number was achieved in vitro, with a mean total nucleated cell count (TNCC) of 2.3 × 108 pre infusion. All patients tolerated the procedure well, and there were no treatment-related side effects or toxicities observed. There were significant decreases in serum bilirubin (P < 0.05) 4, 8, and 12 wk post infusion. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) showed improvement through the study period and were significant (P < 0.05) 1 wk post infusion. The Child-Pugh score improved in 7 out of 9 patients, while 5 patients had improvement in ascites on imaging.CONCLUSION: It is safe to mobilize, expand, and reinfuse autologous CD34+ cells in patients with ALC. The clinical and biochemical improvement in the study group is encouraging and warrants further clinical trials.

Long-term clinical results of autologous infusion of mobilized adult bone marrow derived CD34+ cells in patients with chronic liver disease

Abstract.  Evidence is growing in support of the role of stem cells as an attractive alternative in treatment of liver diseases. Recently, we have demonstrated the feasibility and safety of infusing CD34+ adult stem cells; this was performed on five patients with chronic liver disease. Here, we present the results of long‐term follow‐up of these patients. Between 1 × 106 and 2 × 108 CD34+ cells were isolated and injected into the portal vein or hepatic artery. The patients were monitored for side effects, toxicity and changes in clinical, haematological and biochemical parameters; they were followed up for 12–18 months. All patients tolerated the treatment protocol well without any complications or side effects related to the procedure, also there were no side effects noted on long‐term follow‐up. Four patients showed an initial improvement in serum bilirubin level, which was maintained for up to 6 months. There was marginal increase in serum bilirubin in three of the patients at 12 months, while the fourth patients serum bilirubin increased only at 18 months post‐infusion. Computed tomography scan and serum α‐foetoprotein monitoring showed absence of focal lesions. The study indicated that the stem cell product used was safe in the short and over long term, by absence of tumour formation. The investigation also illustrated that the beneficial effect seemed to last for around 12 months. This trial shows that stem cell therapy may have potential as a possible future therapeutic protocol in liver regeneration.

Management of Delayed Postoperative Hemorrhage After Pancreaticoduodenectomy : A Meta-analysis

OBJECTIVE To determine whether interventional radiology (IR) or laparotomy (LAP) is the best management of delayed postoperative hemorrhage (DPH) after pancreaticoduodenectomy. Data Source We undertook an electronic search of MEDLINE and selected for analysis only original articles published between January 1, 1990, and December 31, 2007. STUDY SELECTION Two of us independently selected studies reporting on clinical presentation and incidence of postoperative DPH and the following outcomes: complete hemostasis, morbidity, and mortality. DATA EXTRACTION Two of us independently performed data extraction. Data were entered and analyzed by means of dedicated software from The Cochrane Collaboration. A random-effects meta-analytical technique was used for analysis. DATA SYNTHESIS One hundred sixty-three cases of DPH after pancreaticoduodenectomy were identified from the literature. The incidence of DPH after pancreaticoduodenectomy was 3.9%. Seventy-seven patients (47.2%) underwent LAP; 73 (44.8%), IR; and 13 (8%), conservative treatment. On meta-analysis comparing LAP vs IR for DPH, no significant difference was found between the 2 treatment options for complete hemostasis (73% vs 76%; P = .23), mortality (43% vs 20%; P = .14), or morbidity (77% vs 35%; P = .06). CONCLUSIONS This meta-analysis, although based on data from small case series, is unable to demonstrate any significant difference between LAP and IR in the management of DPH after pancreaticoduodenectomy. The management of this life-threatening complication is difficult, and the appropriate treatment pathway ultimately will be decided by the clinical status of the patient and the institution preference.

Concordant F-18 FDG PET and Y-90 Bremsstrahlung scans depict selective delivery of Y-90-microspheres to liver tumors: confirmation with histopathology.

Selective Internal Radiation Therapy using yttrium-90 (Y-90) microspheres is a novel method for the treatment of advanced liver cancer. The procedure involves intrahepatic arterial delivery of the Y-90 microspheres. Since hepatic tumors derive their blood supply mainly from the hepatic arteries, it is assumed that the microspheres will be preferentially delivered to tumor cells. However, this has not been confirmed at histology. We report a case of hepatic metastasis from an unknown primary, where treatment with Y-90 microspheres was the only available option due to inoperability and low tolerance to chemotherapy. Pretherapy F-18 FDG-PET scan defined the distribution of the active tumor within the liver. Following the injection of Y-90 microspheres, Bremsstrahlung imaging showed uptake only in the F-18 FDG-PET-defined tumor area. Post therapy debulking surgery was performed and histopathology of tumor samples confirmed the preferential distribution of the injected microspheres in the hepatic tumor circulation with very little in the healthy liver tissue. The case confirms the preferential blood flow to hepatic tumors as depicted by the distribution of Y-90 microspheres injected directly in the hepatic arteries. It also demonstrates that concordance between F-18 FDG-PET and Y-90 Bremsstrahlung scans can be a useful clue to the in vivo distribution of microspheres.

Selective Internal Radiation Therapy with Yttrium-90 for Unresectable Liver Tumours

Primary and secondary liver tumours are common malignancies that are being treated more aggressively nowadays than decades ago. Surgery is the most effective method of treatment but is only suitable for a minority of patients with well-defined and easily accessible tumours. Surgical resection is contraindicated in patients with massive involvement of the liver or in cases where the disease involves the confluence of vessels at the porta hepatis. These patients may benefit from a variety of ablative and embolic therapies including selective internal radiation therapy (SIRT) with Yttrium-90 microspheres. SIRT has been introduced in the 1980s but the technology has been refined and made more available only recently. The microspheres are injected directly into the hepatic arteries, through a trans-femoral angiographic approach, and are delivered selectively to tumours due to their preferential blood supply by hepatic arteries. SIRT can therefore target small volumes disease with a higher dose of radiation compared with external-beam radiation and is associated the relatively low toxicity and a good response irrespective of tumor origin. Assessment of response to therapy is best performed with metabolic imaging using (18)F-FDG PET scanning. Although it is not considered as a cure, it has been shown to improve quality of life and prolong survival, with the main cause of death being extra-hepatic spread. The technical and clinical demands of patient selection, treatment planning, administration, and clinical follow-up require an interdisciplinary team willing to work cooperatively to achieve the best result for the patient.

Successful Removal of Malpositioned Chest Drain Within the Liver by Embolization of the Transhepatic Track

The insertion of a chest drain catheter for the management of a pneumothorax in an 82-year-old woman resulted in the unusual complication of liver penetration. The position of the drain was assessed by contrast-enhanced computed tomographic scan. Because the patient was hemodynamically stable and no damage to major vessels was seen on computed tomographic scan, the patient was treated in a nonoperative manner. A procedure was performed under controlled conditions using techniques used during transhepatic liver biopsies but with the addition of a balloon catheter. Embolization of the liver track was performed during chest drain removal. The drain was successfully removed without the complication of bleeding in a patient unsuitable for a general anesthetic.

90Y Radioembolization: Embolization of the Gastroduodenal Artery is not Always Appropriate

Sir, Radioembolization of primary or secondary liver tumours with yttrium-labeled (yttrium-90 [Y]) microspheres represents an innovative approach that has gained increasing awareness and clinical use during the past 5 to 10 years. To minimize side effects, special consideration in the angiographic evaluation before particle embolization should be given to the presence of flow to the gastrointestinal tract [1–3]. When resin microspheres (SIR-Spheres; Sirtex Medical, Lane Cove, Australia) are used there is a not inconsiderable particle load, and there is a consensus in the literature that the gastroduodenal artery (GDA) and right gastric artery (RGA) should be identified and prophylactically embolized. In this article, we present a case in which the GDA was not embolized due to reversed flow. The patient developed coeliac axis thrombosis, and the patent GDA was the only route available to deliver the Y particles into the liver circulation. Ethical Committee approval is not required at this institution for a study such as this. Case History