Predictive value of early postoperative lactate (<6†h) during normothermic machine perfusion and outcome after liver transplantation: results from a multicentre study.

BACKGROUND: Biomarkers with strong predictive capacity towards transplantation outcome for livers undergoing normothermic machine perfusion (NMP) are needed. We investigated lactate clearing capacity as a basic function of liver viability during the first 6 h of NMP. METHODS: A trial conducted in 6 high-volume transplant centres in Europe. All centres applied a back-to-base NMP approach with the OrganOx metra system. Perfusate lactate levels at start, 1, 2, 4 and 6 h of NMP were assessed individually and as area under the curve (AUC) and correlated with EAD (early allograft dysfunction), MEAF (model for early allograft function) and modified L-GrAFT (liver graft assessment following transplantation) scores. RESULTS: A total of 509 livers underwent ≥6 h of NMP before transplantation in 6 centres in the UK, Germany and Austria. The donor age was 53 (40-63) years (median, i.q.r.).The total NMP time was 10.8 (7.9-15.7) h. EAD occurred in 26%, MEAF was 4.72 (3.54-6.05) and L-GrAFT10 -0.96 (-1.52--0.32). Lactate at 1, 2 and 6 h correlated with increasing robustness with MEAF. Rather than a binary assessment with a cut-off value at 2 h, the actual 2 h lactate level correlated with the MEAF (P = 0.0306 versus P = 0.0002, Pearson r = 0.01087 versus r = 0.1734). The absolute lactate concentration at 6 h, the AUC of 0-6 h and 1-6 h (P < 0.0001, r = 0.3176) were the strongest predictors of MEAF. CONCLUSION: Lactate measured 1-6 h and lactate levels at 6 h correlate strongly with risk of liver allograft dysfunction upon transplantation. The robustness of predicting MEAF by lactate increases with perfusion duration. Monitoring lactate levels should be extended to at least 6 h of NMP routinely to improve clinical outcome.

Liver transplant outcomes after ex vivo machine perfusion: a meta-analysis.

BACKGROUND: The pressure on liver-transplant programmes has expanded the usage of extended-criteria allografts. Machine perfusion may be better than conventional static cold storage (SCS) in alleviating ischaemia-reperfusion injury in this setting. Recipient outcomes with hypothermic or normothermic machine perfusion were assessed against SCS here. METHODS: A search in MEDLINE, EMBASE and Scopus was conducted in February 2021. Primary studies investigating ex vivo machine perfusion were assessed for the following outcomes: morbidity, ICU and hospital stay, graft and patient survival rates and relative costs. Meta-analysis was performed to obtain pooled summary measures. RESULTS: Thirty-four articles involving 1742 patients were included, of which 20 were used for quantitative synthesis. Odds ratios favoured hypothermic machine perfusion (over SCS) with less early allograft dysfunction, ischaemic cholangiopathy, non-anastomotic strictures and graft loss. Hypothermic machine perfusion was associated with a shorter hospital stay and normothermic machine perfusion with reduced graft injury. Two randomized clinical trials found normothermic machine perfusion reduced major complication risks. CONCLUSION: Machine perfusion assists some outcomes with potential cost savings.

Outcomes of primary arteriovenous fistulas in patients older than 70 years.

BACKGROUND: The population of elderly hemodialysis patients is increasing, yet the most suitable approach for providing permanent hemodialysis access remains unclear. Here we report outcomes using an approach aimed predominantly at creating radiocephalic (RC) fistulas. METHODS: A single-center retrospective cohort study was performed in which access outcomes for primary arteriovenous fistulas created between January 1, 2005, and December 31, 2012, in patients aged 70 years or older were compared. RESULTS: During the study period, 204 RC, 1 brachiobasilic, and 9 brachiocephalic (BC) primary fistulas were created initially for patients requiring dialysis. Immediate failure rates for RC fistulas were lower than for BC fistulas but not significantly so (12% vs 22%; Fisher's exact text, P = .319). One-year primary and secondary patency for RC fistulas was 54% and 66%, respectively, and similar for those created in patients between 70 and 80 years old and in those older than 80 years. The secondary patency rate at 1 year for RC fistulas using cephalic vein of diameter <2.5 mm was lower than for fistulas created with cephalic vein >2.5 mm (49% vs 72%; log-rank test, P = .005). Creation of a BC fistula was associated with a significantly higher incidence of steal syndrome than with an RC fistula (10% vs 2%; Fisher's exact text, P = .009). CONCLUSIONS: RC fistulas formed in the elderly carry a lower risk of steal syndrome than BC fistulas and offer the potential for further revision surgery, such that acceptable secondary patency is achieved for RC fistulas formed using even small (<2.5 mm) cephalic veins.

Defatting of donor transplant livers during normothermic perfusion-a randomised clinical trial: study protocol for the DeFat study.

BACKGROUND: Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. METHODS: In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). DISCUSSION: This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. TRIAL REGISTRATION: ISRCTN ISRCTN14957538. Registered in October 2022.

Bridging locoregional treatment prior to liver transplantation for cirrhotic patients with hepatocellular carcinoma within the Milan criteria: a systematic review and meta-analysis.

Background: We performed a meta-analysis to assess the benefit of bridging locoregional treatment (LRT) before liver transplantation for cirrhotic patients with hepatocellular carcinoma (HCC) already within the Milan criteria at diagnosis. Methods: We included original studies with HCC cases within the Milan criteria at diagnosis, comparing patients with and without bridging LRT before liver transplantation. Results: Twenty-six retrospective original studies were included. Out of the 9068 patients within the Milan criteria, 6435 (71%) received bridging LRT and 2633 (29%) did not. The most frequent LRTs were transarterial chemoembolization, radiofrequency ablation, and microwave ablation. Most of the patient and tumor characteristics were similar between the 2 groups. Maximum tumor diameter on scans was slightly larger in the LRT arm (mean difference: 0.36 cm, 95% confidence interval [CI] 0.11-0.61; I2=79%). The LRT group also had multifocal disease slightly more frequently (risk ratio [RR] 1.21, 95%CI 1.04-1.41; I2=0%) and disease extent outside the Milan criteria (RR 1.3, 95%CI 1.03-1.66; I2=0%) on pathological examination of explanted livers. There was no difference between the 2 arms in the waiting time for transplant, dropout rates, disease-free survival at 1, 3, 5 years after transplant, or overall survival at 3 and 5 years after transplant. However, cases with LRT had better overall survival at 1 year after transplant (hazard ratio 0.54, 95%CI 0.35-0.86; I2=0%). Conclusions: The precise benefit of bridging LRT for cirrhotic patients with HCC within the Milan criteria at diagnosis is unclear. There may be an advantage regarding short-term overall survival after liver transplantation.

The British transplantation society guidelines on organ donation from deceased donors after circulatory death.

Recipient outcomes after transplantation with organs from donation after circulatory death (DCD) donors can compare favourably and even match recipient outcomes after transplantation with organs from donation after brain death donors. Success is dependent upon establishing common practices and accepted protocols that allow the safe sharing of DCD organs and maximise the use of the DCD donor pool. The British Transplantation Society 'Guideline on transplantation from deceased donors after circulatory death' has recently been updated. This manuscript summarises the relevant recommendations from chapters specifically related to organ donation.

Donor-Recipient Body Surface Area Mismatch and the Outcome of Liver Transplantation in the UK.

Introduction: Too small or too big liver grafts for recipient's size has detrimental effects on transplant outcomes. Research Questions: The purpose was to correlate donor-recipient body surface area ratio or body surface area index with recipient survival, graft survival, hepatic artery or portal vein, or vena cava thrombosis. High and low body surface area index cut-off points were determined. Design: There were 11,245 adult recipients of first deceased donor whole liver-only grafts performed in the UK from January 2000 until June 2020. The transplants were grouped according to the body surface area index and compared to complications, graft and recipient survival. Results: The body surface area index ranged from 0.491 to 1.691 with a median of 0.988. The body surface area index > 1.3 was associated with a higher rate of portal vein thrombosis within the first 3 months (5.5%). This risk was higher than size-matched transplants (OR: 2.878, 95% CI: 1.292-6.409, P = 0.01). Overall graft survival was worse in transplants with body surface area index ≤ 0.85 (HR: 1.254, 95% CI: 1.051-1.497, P = 0.012) or body surface area index > 1.4 (HR: 3.704, 95% CI: 2.029-6.762, P < 0.001) than those with intermediate values. The graft survival rates were reduced by 2% for cases with body surface area index ≤ 0.85 but were decreased by 20% for cases with body surface area index > 1.4. These findings were confirmed by bootstrap internal validation. No statistically significant differences were detected for hepatic artery thrombosis, occlusion of hepatic veins/inferior vena cava or recipient survival. Conclusions: Donor-recipient size mismatch affects the rates of portal vein thrombosis within the first 3 months and overall graft survival in deceased-donor liver transplants.

Phlebotonics for haemorrhoids.

BACKGROUND: Haemorrhoids are variceal dilatations of the anal and perianal venous plexus and often develop secondary to the persistently elevated venous pressure within the haemorrhoidal plexus (Kumar 2005). Phlebotonics are a heterogenous class of drugs consisting of plant extracts (i.e. flavonoids) and synthetic compounds (i.e. calcium dobesilate). Although their precise mechanism of action has not been fully established, they are known to improve venous tone, stabilize capillary permeability and increase lymphatic drainage. They have been used to treat a variety of conditions including chronic venous insufficiency, lymphoedema and haemorrhoids.Numerous trials assessing the effect of phlebotonics in treating the symptoms and signs of haemorrhoidal disease suggest that there is a potential benefit. OBJECTIVES: The aim of this review was to investigate the efficacy of phlebotonics in alleviating the signs, symptoms and severity of haemorrhoidal disease and verify their effect post-haemorrhoidectomy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library 2011 issue 9 , MEDLINE (1950 to September 2011) and EMBASE (1974 to September 2011). SELECTION CRITERIA: Only randomised controlled trials evaluating the use of phlebotonics in treating haemorrhoidal disease were used. No cross-over or cluster-randomized trials were included for analysis and any trial which had a quasi-random method of allocation was excluded. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data and analysed the eligibility of the data for inclusion. Disagreements were resolved by meaningful discussion. MAIN RESULTS: We considered twenty-four studies for inclusion in the final analysis. Twenty of these studies (enrolling a total of 2344 participants) evaluated the use of phlebotonics versus a control intervention. One of these twenty studies evaluated the use of phlebotonics with a medical intervention and another study with rubber band ligation.The remaining four studies included two which compared different forms of phlebotonics with each other, one study which evaluated phlebotonics with a medical intervention and one study which compared the use of phlebotonics with infrared photocoagulation. Eight studies were excluded for various reasons including poor methodological quality.Phlebotonics demonstrated a statistically significant beneficial effect for the outcomes of  pruritus (OR 0.23; 95% CI 0.07 to 0.79) (P=0.02), bleeding (OR 0.12; 95% CI 0.04 to 0.37) (P=0.0002), bleeding post-haemorrhoidectomy (OR 0.18; 95% 0.06 to 0.58)(P=0.004), discharge and leakage (OR 0.12; 95% CI 0.04 to 0.42) (P=0.0008) and overall symptom improvement (OR 15.99 95% CI 5.97 to 42.84) (P< 0.00001), in comparison with a control intervention. Although beneficial they did not show a statistically significant effect compared with a control intervention for pain (OR 0.11; 95% CI 0.01 to 1.11) (P=0.06), pain scores post-haemorrhoidectomy (SMD -1.04; 95% CI -3.21 to 1.12 ) (P= 0.35) or post-operative analgesic consumption (OR 0.54; 95% CI 0.30 to 0.99)(P=0.05). AUTHORS' CONCLUSIONS: The evidence suggests that there is a potential benefit in using phlebotonics in treating haemorrhoidal disease as well as a benefit in alleviating post-haemorrhoidectomy symptoms. Outcomes such as bleeding and overall symptom improvement show a statistically significant beneficial effect and there were few concerns regarding their overall safety from the evidence presented in the clinical trials.However methodological limitations were encountered. In order to enhance our conclusion further, more robust clinical trials which take into account these limitations will need to be performed in the future.

Combining Donor and Recipient Age With Preoperative MELD and UKELD Scores for Predicting Survival After Liver Transplantation.

OBJECTIVES: The end-stage liver disease scoring systems MELD, UKELD, and D-MELD (donor age × MELD) have had mediocre results for survival assessment after orthotopic liver transplant. Here, we introduced new indices based on preoperative MELD and UKELDscores and assessed their predictive ability on survival posttransplant. MATERIALS AND METHODS: We included 1017 deceased donor orthotopic liver transplants that were performed between 2008 (the year UKELD was introduced) and 2019. Donor and recipient characteristics, liver disease scores, transplant characteristics, and outcomes were collected for analyses. D-MELD, D-UKELD (donor age × UKELD),DR-MELD[(donor age + recipient age) × MELD], and DR-UKELD [(donor age + recipient age) × UKELD] were calculated. RESULTS: No score had predictive value for graft survival. For patient survival,DR-MELD and DR-UKELD provided the best results but with low accuracy. The highest accuracy was observed at 1 year posttransplant (areas under the curve of 0.598 [95% CI, 0.529-0.667] and 0.609 [95% CI, 0.549-0.67]forDR-MELDandDR-UKELD). Addition of donor and recipient age significantly improved the predictive abilities of MELD and UKELD for patient survival, but addition of donor age alone did not. For 1-year mortality (using receiver operating characteristic curves), optimal cut-off points were DR-MELD>2345 and DR-UKELD>5908. Recipients with DR-MELD >2345 (P < .001) and DR-UKELD >5908 (P = .002) had worse patient survival within the first year, but only DR-MELD >2345 remained significant after multivariable analysis (P = .007). CONCLUSIONS: DR-MELD and DR-UKELD scores provided the best, albeit mediocre, predictive ability among the 6 tested models, especially at 1 year after posttransplant, although only for patient but not for graft survival. A DR-MELD >2345 was considered to be an additional independent risk factor for worse recipient survival within the first postoperative year.

Longevity and replenishment of human liver-resident memory T cells and mononuclear phagocytes.

The human liver contains specialized subsets of mononuclear phagocytes (MNPs) and T cells, but whether these have definitive features of tissue residence (long-term retention, lack of egress) and/or can be replenished from the circulation remains unclear. Here we addressed these questions using HLA-mismatched liver allografts to discriminate the liver-resident (donor) from the infiltrating (recipient) immune composition. Allografts were rapidly infiltrated by recipient leukocytes, which recapitulated the liver myeloid and lymphoid composition, and underwent partial reprogramming with acquisition of CD68/CD206 on MNPs and CD69/CD103 on T cells. The small residual pool of donor cells persisting in allografts for over a decade contained CX3CR1hi/CD163hi/CD206hi Kupffer cells (KCs) and CXCR3hi tissue-resident memory T cells (TRM). CD8+ TRM were found in the local lymph nodes but were not detected egressing into the hepatic vein. Our findings inform organ transplantation and hepatic immunotherapy, revealing remarkably long-lived populations of KCs and TRM in human liver, which can be additionally supplemented by their circulating counterparts.

Cigarette smoking as a risk factor for the development of and mortality from hepatocellular carcinoma: An updated systematic review of 81 epidemiological studies.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and its incidence has increased during the past decade. While hepatitis B and C virus infections and alcohol were established risk factors, the impact of smoking on the incidence and mortality of HCC was needed to be confirmed. METHODS: We reviewed cohort and case-control studies evaluating the association between cigarette smoking and incidence and mortality of HCC from MEDLINE and Google Scholar. We also checked reference lists of original studies and review articles manually for cross-references up to February 2016. We extracted the relevant information on participant characteristics and study outcomes, as well as information on the methodology of the studies. We also assessed the quality of the included trials using critical appraisal skills program checklists. Meta-analysis was performed by using RevMan 5.3 software. RESULTS: A total of 81 studies were included in the systematic review. Pooled OR for HCC development with current smokers was 1.55 (95% CI: 1.46 to 1.65; P < 0.00001). Pooled OR for HCC development with former smokers was 1.39 (95% CI: 1.26 to 1.52; P < 0.00001) and pooled OR for HCC development with heavy smokers was 1.90 (95% CI: 1.68 to 2.14; P < 0.00001). Pooled OR for the mortality of current smokers with HCC was 1.29 (95% CI: 1.23 to 1.34; P < 0.00001); and for former smokers with HCC, it was 1.20 (95% CI: 1.00 to 1.42; P = 0.04). CONCLUSIONS: Cigarette smoking increases the incidence and mortality of HCC. Further studies are needed to evaluate possible impact of quitting smoking on decreasing this risk.

Development of a Prognostic Model That Predicts Survival After Pancreaticoduodenectomy for Ampullary Cancer.

OBJECTIVES: The aims of this study were to (i) identify independent predictors of survival after pancreaticoduodenectomy for ampullary cancer and (ii) develop a prognostic model of survival. METHODS: Data were analyzed retrospectively on 110 consecutive patients who underwent pancreaticoduodenectomy between 2002 and 2013. Subjects were categorized into 3 nodal subgroups as per the recently proposed nodal subclassification: N0 (node negative), N1 (1-2 metastatic nodes), or N2 (≥3 metastatic nodes). Clinicopathological features and overall survival were compared by Kaplan-Meier and Cox regression analyses. RESULTS: The overall 1-, 3-, and 5-year survival rates were 79.8%, 42.2%, and 34.9%, respectively. The overall 1-, 3-, and 5-year survival rates for the N0 group were 85.2%, 71.9%, and 67.4%, respectively. The 1-, 3-, 5-year survival rates for the N1 and N2 subgroups were 81.5%, 49.4%, and 49.4% and 75%, 19.2%, and 6.4%, respectively (log rank, P < 0.0001). After performing a multivariate Cox regression analysis, vascular invasion and lymph node ratio were the only independent predictors of survival. Hence, a prediction model of survival was constructed based on those 2 variables. CONCLUSIONS: Using data from a carefully selected cohort of patients, we created a pilot prognostic model of postresectional survival. The proposed model may help clinicians to guide treatments in the adjuvant setting.

Incidental non-benign gallbladder histopathology after cholecystectomy in an United Kingdom population: Need for routine histological analysis?

AIM: To analyse the range of histopathology detected in the largest published United Kingdom series of cholecystectomy specimens and to evaluate the rational for selective histopathological analysis. METHODS: Incidental gallbladder malignancy is rare in the United Kingdom with recent literature supporting selective histological assessment of gallbladders after routine cholecystectomy. All cholecystectomy gallbladder specimens examined by the histopathology department at our hospital during a five year period between March 2008 and March 2013 were retrospectively analysed. Further data was collected on all specimens demonstrating carcinoma, dysplasia and polypoid growths. RESULTS: The study included 4027 patients. The majority (97%) of specimens exhibited gallstone or cholecystitis related disease. Polyps were demonstrated in 44 (1.09%), the majority of which were cholesterol based (41/44). Dysplasia, ranging from low to multifocal high-grade was demonstrated in 55 (1.37%). Incidental primary gallbladder adenocarcinoma was detected in 6 specimens (0.15%, 5 female and 1 male), and a single gallbladder revealed carcinoma in situ (0.02%). This large single centre study demonstrated a full range of gallbladder disease from cholecystectomy specimens, including more than 1% neoplastic histology and two cases of macroscopically occult gallbladder malignancies. CONCLUSION: Routine histological evaluation of all elective and emergency cholecystectomies is justified in a United Kingdom population as selective analysis has potential to miss potentially curable life threatening pathology.

Delayed dynamic abdominal wall closure following multi-visceral transplantation.

INTRODUCTION: Primary closure of the abdominal wall following intestinal transplantation or multivisceral transplantation could become a challenging problem in a significant number of patients. PRESENTATION OF CASE: A 38-year-old woman with familial adenomatous polyposis (FAP) underwent a multi-visceral transplantation for short gut syndrome. She subsequently developed acute graft rejection that proved resistant to conventional treatment. She was relisted and underwent re-transplantation along with kidney transplantation. Abdominal wall closure could not be achieved because of the large size of the graft and bowel oedema. The wound was initially managed with laparostomy followed by insertion of the delayed dynamic abdominal closure (DDAC) device (Abdominal Retraction Anchor - ABRA(®) system). Continuous dynamic traction to the wound edges resulted in gradual approximation and complete closure of the abdominal wound was achieved within 3 weeks. DISCUSSION: Successful abdominal closure after multivisceral transplantation or isolated intestinal transplantation often requires biological mesh, vascularised flaps or abdominal wall transplantation. DDAC eliminated the need for a prosthetic mesh or skin graft and provided an excellent cosmetic result. Adjustment of the dynamic traction at the bedside minimised the need for multiple returns to the operating theatre. It resulted in a well-healed linear scar without a hernia. CONCLUSION: Dynamic traction allows delayed closure of laparotomy resulting in strong and cosmetically sound wound healing with native tissue.

Treatment of dialysis access-associated steal syndrome with the "revision using distal inflow" technique.

PURPOSE: Dialysis access-associated steal syndrome (DASS) is a common, serious complication of antecubital fossa (ACF) arteriovenous fistulas (AVFs). We describe our experience of the "revision using distal inflow" (RUDI) technique for the treatment of DASS and review the literature. METHODS: Patients underwent fistula ligation at the anastomosis with re-establishment of inflow via the proximal radial or ulnar arteries using a venous interposition graft or venous collateral. A retrospective analysis of outcomes of all patients undergoing this procedure at our center was carried out. RESULTS: Seven patients with autogenous ACF AVFs underwent the RUDI procedure, four under local anesthesia. Interposition vein grafts were used in five patients, and inflow was achieved through the proximal radial artery in four cases. The median post-operative rise in digital systolic blood pressure was 65.5 mmHg. Follow-up at 7-36 months found that three fistulas had failed (one at 8 months, two within days), two patients had died with patent fistulas, one patient was transplanted with a functional AVF, and the remaining patient continues to dialyze through the fistula. No patients developed DASS post-operatively and no further interventions were required to maintain patency. CONCLUSIONS: Although RUDI was successful at treating DASS, a high rate of AVF failure was seen. With technical modifications and further experience, RUDI may become a valuable tool in the surgical armamentarium.

Phlebotonics for haemorrhoids

BACKGROUND Haemorrhoids are variceal dilatations of the anal and perianal venous plexus and often develop secondary to the persistently elevated venous pressure within the haemorrhoidal plexus. Phlebotonics are a heterogenous class of drugs consisting of plant extracts (i.e. flavonoids) and synthetic compounds (i.e. calcium dobesilate). Although their precise mechanism of action has not been fully established, they are known to improve venous tone, stabilize capillary permeability and increase lymphatic drainage. They have been used to treat a variety of conditions including chronic venous insufficiency, lymphoedema and haemorrhoids. OBJECTIVE The aim of this review was to investigate the efficacy of phlebotonics in alleviating the signs, symptoms and severity of haemorrhoidal disease and verify their effect post-haemorrhoidectomy. METHODS Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library 2011 issue 9, MEDLINE (1950 to September 2011) and EMBASE (1974 to September 2011). Selection criteria: Only randomized controlled trials evaluating the use of phlebotonics in treating haemorrhoidal disease were used. No cross-over or cluster-randomized trials were included for analysis and any trial which had a quasi-random method of allocation was excluded. Data collection and analysis: Two authors independently extracted the data and analyzed the eligibility of the data for inclusion. Disagreements were resolved by meaningful discussion. MAIN RESULTS We considered twenty-four studies for inclusion in the final analysis. Twenty of these studies (enrolling a total of 2344 participants) evaluated the use of phlebotonics versus a control intervention. One of these twenty studies evaluated the use of phlebotonics with a medical intervention and another study with rubber band ligation. AUTHORS' CONCLUSIONS The evidence suggests that there is a potential benefit in using phlebotonics ...