David M. Lloyd

Efficacy and safety of microwave ablation for primary and secondary liver malignancies: A systematic review

This article reviews the therapeutic efficacy and complications of microwave ablation (MWA) in the treatment of primary and secondary liver malignancies. A PubMed search using keywords ‘microwave’, ‘liver’, ‘malignancy’, ‘cancer’ and ‘tumour’ was performed to identify articles related to MWA of liver malignancies published in English from 1975 to February 2008. MWA is an effective treatment options for both primary and secondary liver malignancies with survivals comparable with those of liver resections. Local recurrences can be managed with further ablation. Small tumour size, well-differentiated tumour and a reduced number of lesions are factors associated with good prognosis. Temporary occlusion of the portal venous and hepatic arterial flow may increase the size of ablation but the safety aspect requires further validation. MWA is a minimally invasive technique that has broadened the therapeutic option for patients with conventionally unresectable liver tumours with promising survival data. Future advances in the applicator design and treatment monitoring may further improve its efficacy and widen the indications.

Immunoregulatory effects of liver ablation therapies for the treatment of primary and metastatic liver malignancies

Ablation of liver tissue produces in situ tumoural antigens and elicits specific immune responses. The aim of this review is to examine the available data about the local and systemic responses produced and to compare differences between the methods available. A literature search was undertaken for all papers focusing on immune responses following ablative therapy of the liver, including experimental and clinical studies. Following ablative procedures, the cellular response is elicited by the presentation of antigens by dendritic cells to specific CD4+ T cells, which in turn stimulate natural killer or CD8+ cytotoxic cells. The local release of intracellular debris activates Kupffer cells to produce cytokines, which, in the immediate vicinity, activate monocytes/macrophages or specific T cells that respond and produce systemic reactions such as fever, thrombocytopaenia or shock. The immune responses elicited by cryotherapy, both cellular and cytokine, seem far greater than those produced by radiofrequency or microwave ablation, probably as a consequence of the peculiar mechanism of cell death of the former (disruptive necrosis). This mechanism is considered central to the pathogenesis of cryoshock. Ablative techniques stimulate the immune system and provide an easy way to achieve in vivo vaccination against tumoural antigens. Immunomodulatory approaches have the potential to augment the initial immune stimulation and this combined approach could pave the way to a more selective and specific method of treating liver tumours.

Liver ablation techniques: a review

BackgroundAblation techniques for unresectable liver carcinomas have evolved immensely since their introduction. Results of studies involving these techniques are restricted to reports of patient case series, which are often not presented in a standardised manner. This review aims to summarise the major studies in ablation technologies and present them in a way that may make comparison between the major modalities easier.MethodsAll major databases (Medline, Cochrane, Embase and Pubmed) were searched for studies using microwave, radiofrequency or cryoablation to treat unresectable liver tumours. Only studies with at least 30 patients and 3-year follow-up were included. Complication, recurrence and survival rates of all studies are summarised and presented.Results and conclusionIt is difficult to compare ablation modalities, as probe design and energy sources have evolved rapidly over the last decade. Ablation offers an invaluable palliative option and in some cases it may offer rates of cure approaching that of surgical resection with lower morbidity and mortality. Perhaps the time has come, therefore, for prospective large-scale randomised control trials to take place comparing ablation modalities to each other and surgical resection.

Microwave ablation for unresectable hepatic tumours: clinical results using a novel microwave probe and generator.

BACKGROUNDnMicrowave ablation is an in situ method of tumour destruction used to treat patients with unresectable liver tumours. A new microwave generator and probe, designed to deliver high energy into solid tumours quickly has been developed at our institution. We report the results of its use in patients with unresectable liver tumours treated by a single surgeon in a single institution.nnnMETHODSnThirty-one patients with 89 unresectable liver tumours were recruited into the study and underwent microwave ablation in a single procedure.nnnRESULTSnThere were no post-operative complications. At a median of 24 months post ablation, 15 patients were alive with 7 patients disease free. At a median of 26 months, 8 patients were alive with tumour recurrence but only 1 with local recurrence. The remaining 7 patients with recurrence were found to have new disease at locations remote from the ablation site. Fourteen patients died of disease progression at a median survival of 15 months, with only 1 patient with local and remote tumour recurrence. Of the total numbers of tumours treated (n=89), a local tumour recurrence rate of 2% was observed. Overall median survival was 29 months with 3 year survival of 40%.nnnDISCUSSIONnMicrowave tissue ablation using this novel generator and probe has a low local recurrence and complication rate. Overall survival is comparable to alternative ablation modalities and its ability to treat, even large tumours, with a single insertion of the probe makes it an extremely attractive treatment option.

A Fuller Understanding of Pancreatic Neuroendocrine Tumours Combined with Aggressive Management Improves Outcome

Background: Neuroendocrine tumours of the pancreas (PNETs) represent 1–2% of all pancreatic tumours. The terms ‘islet cell tumours’ and ‘carcinoids’ of the pancreas should be avoided. The aim of this review is to offer an overview of the history and diagnosis of PNETs followed by a discussion of the available treatment options. Methods: A search on PubMed using the keywords ‘neuroendocrine’, ‘pancreas’ and ‘carcinoid’ was performed to identify relevant literature over the last 30 years. Results: The introduction of a revised classification of neuroendocrine tumours by the World Health Organisation (WHO) in 2000 significantly changed our understanding of and approach to the management of these tumours. Advances in laboratory and radiological techniques have also led to an increased detection of PNETs. Surgery remains the only treatment that offers a chance of cure with increasing number of non-surgical options serving as beneficial adjuncts. The better understanding of the behaviours of PNETs together with improvements in tumour localisation has resulted in a more aggressive management strategy with a concomitant improvement in symptom palliation and a prolongation of survival. Conclusion: Due to their complex nature and the wide range of therapeutic options, the involvement of specialists from all necessary disciplines in a multidisciplinary team setting is vital to provide optimal treatment of this disease.

International multicentre prospective study on microwave ablation of liver tumours: preliminary results

BACKGROUNDnMicrowave ablation (MWA) is increasingly utilized in the treatment of hepatic tumours. Promising single-centre reports have demonstrated its safety and efficacy, but this modality has not been studied in a prospective, multicentre study.nnnMETHODSnEighteen international centres recorded operative and perioperative data for patients undergoing MWA for tumours of any origin in a voluntary Internet-based database. All patients underwent operative MWA using a 2.45-GHz generator with a 5-mm antenna.nnnRESULTSnOf the 140 patients, 114 (81.4%) were treated with MWA alone and 26 (18.6%) were treated with MWA combined with resection. Multiple tumours were treated with MWA in 40.0% of patients. A total of 299 tumours were treated in these 140 patients. The median size of ablated lesions was 2.5 cm (range: 0.5-9.5 cm). Tumours were treated with a median of one application (range: 1-6 applications) for a median of 4 min (range: 0.5-30.0 min). A power setting of 100 W was used in 78.9% of cases. Major morbidity was 8.3% and in-hospital mortality was 1.9%.nnnCONCLUSIONSnThese multi-institution data demonstrate rapid ablation time and low morbidity and mortality rates in patients undergoing operative MWA with a high rate of multiple ablations and concomitant hepatic resection. Longterm follow-up will be required to determine the efficacy of MWA relative to other forms of ablative therapy.

An Algorithm for the Management of Bile Leak Following Laparoscopic Cholecystectomy

INTRODUCTIONnThe management of bile leaks following laparoscopic cholecystectomy has evolved with increased experience of ERCP and laparoscopy. The purpose of this study was to determine the impact of a minimally invasive management protocol.nnnPATIENTS AND METHODSnTwenty-four patients with a bile leak following laparoscopic cholecystectomy were recorded consecutively between 1993 and 2003. Between 1993-1998, 10 patients were managed on a case-by-case basis. Between 1998-2003, 14 patients were managed according to a minimally invasive protocol utilising ERC/biliary stenting and re-laparoscopy if indicated.nnnRESULTSnBile leaks presented as bile in a drain left in situ post laparoscopic cholecystectomy (8/10 versus 10/14) or biliary peritonitis (2/10 versus 4/14). Prior to 1998, neither ERC nor laparoscopy were utilised routinely. During this period, 4/10 patients recovered with conservative management and 6/10 (60%) underwent laparotomy. There was one postoperative death and median hospital stay post laparoscopic cholecystectomy was 10 days (range, 5-30 days). In the protocol era, ERC +/- stenting was performed in 11/14 (P = 0.01 versus pre-protocol) with the main indication being a persistent bile leak. Re-laparoscopy was necessary in 5/14 (P = 0.05 versus preprotocol). No laparotomies were performed (P < 0.01 versus pre-protocol) and there were no postoperative deaths. Median hospital stay was 11 days (range, 5-55 days).nnnCONCLUSIONSnThe introduction of a minimally invasive protocol utilising ERC and re-laparoscopy offers an effective modern algorithm for the management of bile leaks after laparoscopic cholecystectomy.

Changes in interleukin-1β and 6 after hepatic microwave tissue ablation compared with radiofrequency, cryotherapy and surgical resections.

BACKGROUNDnCytokine changes after microwave tissue ablation (MTA) were compared with hepatic resection, cryotherapy (CRYO), and radiofrequency ablation (RFA). Cytokine production was measured at various ablation volumes for each modality and correlated with the transitional inflammatory zone produced by the ablation techniques.nnnMETHODSnLive rats underwent MTA, surgical resection, CRYO or RFA of 15%, 33%, or 66% of the total hepatic volume. Serum samples were collected preoperatively and at 1, 3, 6, 24, and 48 hours after surgery and analyzed for pro-inflammatory cytokines interleukin (IL)-1β and IL-6.nnnRESULTSnSignificantly higher levels of both cytokines were present after CRYO and RFA compared with MTA, hepatic resection, or controls (P < .001). All animals survived except those undergoing RFA or CRYO of 66% of the hepatic volume, which died within 6 hours. Transitional zones produced after RFA were larger than those after CRYO or MTA, but no correlation was present with the amount of cytokines.nnnCONCLUSIONSnLarge-volume MTA is associated with a significant decreased cytokine response and is well tolerated compared with RFA and CRYO.

The inguinal release procedure for groin pain: initial experience in 73 sportsmen/women

Objective: To assess the impact of the laparoscopic inguinal release procedure with mesh reinforcement on athletes with groin pain. Design: Prospective cohort study. Setting: Private sector. Patients: Professional and amateur sportsmen/women undergoing the inguinal release for groin pain. Main outcome measurements: Change in patient’s symptoms, functional limitation and time to resuming sporting activity following surgery. Results: 73 sportsmen/women underwent laparoscopic inguinal release in the study period, 37 (51%) of whom were professionals. 95% were male with a median age of 30 years. Following operation, patients returned to light training at a median of 1 week, full training at 3 weeks (professionals—2 weeks) and playing competitively at 4 weeks (professionals—3 weeks). 74% considered themselves match-fit by 4 weeks (84% of professionals). Following surgery, there was a highly significant improvement in frequency of pain, severity of pain and functional limitation in both the whole cohort and professional group. 88% reported a return to full fitness at follow-up, with 73% reporting complete absence of symptoms. 97% of the cohort thought the operation had improved their symptoms. Conclusions: This study shows that the laparoscopic inguinal release procedure may be effective in the treatment of a subgroup of athletes with groin pain.

Expression of Thrombospondin-1 in Resected Colorectal Liver Metastases Predicts Poor Prognosis

Purpose: The aim of this study was to examine the expression and prognostic relevance of thrombospondin-1 (TSP-1) in tumor biopsies taken from a consecutive series of liver resections done at the University Hospitals of Leicester and the Royal Liverpool Hospital. Experimental Design: Patients having undergone a liver resection for colorectal liver metastases at our institutions between 1993 and 1999 inclusive were eligible. Inclusion criteria were curative intent, sufficient tumor biopsy, and patient follow-up data. One hundred eighty-two patients were considered in this study. Standard immunohistochemical techniques were used to study the expression of TSP-1 in 5-μm tumor sections from paraffin-embedded tissue blocks. TSP-1 was correlated with survival using the Kaplan-Meier method and log-rank test for univariate analysis and the Cox proportional hazard model for multivariate analysis. Results: One hundred eighty-two patients (male, n = 122 and female, n = 60) ages between 25 and 81 years (mean, 61 years) were included. TSP-1 was expressed around blood vessels (n = 45, 25%) or in the stroma (n = 59, 33%). No expression was detected in the remaining tumors. TSP-1 significantly correlated with poor survival on univariate (P = 0.01 for perivascular expression and P = 0.03 for stromal expression) and multivariate analysis (P = 0.01 for perivascular expression). Conclusion: TSP-1 is a negatively prognostic factor for survival in resected colorectal liver metastases.