Intention to Treat Laparoscopic Versus Open Hemi-Hepatectomy: A Paired Case-Matched Comparison Study.

BACKGROUND: The benefits of laparoscopic hemi-hepatectomy compared to open hemi-hepatectomy are not clear. OBJECTIVE: This study aims to share our experience with the laparoscopic hemi-hepatectomy compared to an open approach. METHODS: A total of 40 consecutive laparoscopically started hemi-hepatectomy (intention-to-treat analysis) cases between August 2012 and October 2015 were matched against open cases using the following criteria: laterality of surgery and pathology (essential criteria); American Society of Anesthesiologists score, body mass index, pre-operative bilirubin, neo-adjuvant chemotherapy, additional procedures, portal vein embolization, and presence of cirrhosis/fibrosis on histology (secondary criteria); age and gender (tertiary criteria). Hand-assisted and extended hemi-hepatectomy cases were excluded from the study. The two groups were compared for blood loss, operative time, hospital stay, morbidity, mortality, and oncological outcomes. All complications were quantified using the Clavien-Dindo classification. RESULTS: Two groups were well matched (p = 1.00). In the two groups, 10 patients had left and 30 had right hemi-hepatectomy. Overall conversion rate was 15%. Median length of hospital and high dependency unit stay was less in the intention to treat laparoscopic hemi-hepatectomy group: 6 versus 8 days, p = 0.025 and 1 versus 2 days, p = 0.07. Median operative time was longer in the intention to treat laparoscopic hemi-hepatectomy group: 420 min (range: 389.5-480) versus 305 min (range: 238.8-348.8; p = 0.001). Intra-operative blood loss was equivalent, but the overall blood transfusions were higher in the intention to treat laparoscopic hemi-hepatectomy (50 vs 29 units, p = 0.36). The overall morbidity (18 vs 20 patients, p = 0.65), mortality (2.5%), and the positive resection margin status were similar (18% vs 21%, p = 0.76). The 1- (87.5% vs 92.5%, p = 0.71) and 3-year survival (70% vs 72.5%, p = 1.00) was also similar. CONCLUSIONS: We observed lower hospital and high dependency unit stay in the laparoscopic group. However, the laparoscopic approach was associated with longer operating time and a non-significant increase in blood transfusion requirements. There was no difference in morbidity, mortality, re-admission rate, and oncological outcomes.

Comparison of risk-scoring systems in the prediction of outcome after liver resection.

BACKGROUND: Risk prediction techniques commonly used in liver surgery include the American Society of Anesthesiologists (ASA) grading, Charlson Comorbidity Index (CCI) and cardiopulmonary exercise tests (CPET). This study compares the utility of these techniques along with the number of segments resected as predictive tools in liver surgery. METHODS: A review of a unit database of patients undergoing liver resection between February 2008 and January 2015 was undertaken. Patient demographics, ASA, CCI and CPET variables were recorded along with resection size. Clavien-Dindo grade III-V complications were used as a composite outcome in analyses. Association between predictive variables and outcome was assessed by univariate and multivariate techniques. RESULTS: One hundred and seventy-two resections in 168 patients were identified. Grade III-V complications occurred after 42 (24.4%) liver resections. In univariate analysis of CPET variables, ventilatory equivalents for CO2 (VEqCO2) was associated with outcome. CCI score, but not ASA grade, was also associated with outcome. In multivariate analysis, the odds ratio of developing grade III-V complications for incremental increases in VEqCO2, CCI and number of liver segments resected were 1.09, 1.49 and 2.94, respectively. CONCLUSIONS: Of the techniques evaluated, resection size provides the simplest and most discriminating predictor of significant complications following liver surgery.

The pre-operative rate of growth of colorectal metastases in patients selected for liver resection does not influence post-operative disease-free survival.

AIMS: To assess the potential association between the change in diameter of colorectal liver metastases between pre-operative imaging and liver resection and disease-free survival in patients who do not receive pre-operative liver-directed chemotherapy. MATERIALS AND METHODS: Analysis of a prospectively maintained database of patients undergoing liver resection for colorectal liver metastases between 2005 and 2012 was undertaken. Change in tumour size was assessed by comparing the maximum tumour diameter at radiological diagnosis determined by imaging and the maximum tumour diameter measured at examination of the resected specimen in 157 patients. RESULTS: The median interval from first scan to surgery was 99 days and the median increase in tumour diameter in this interval was 38%, equivalent to a tumour doubling time (DT) of 47 days. Tumour DT prior to liver resection was longer in patients with T1 primary tumours (119 days) than T2-4 tumours (44 days) and shorter in patients undergoing repeat surgery for intra-hepatic recurrence (33 days) than before primary resection (49 days). The median disease-free survival of the whole cohort was 1.57 years (0.2-7.3) and multivariate analysis revealed no association between tumour DT prior to surgery and disease-free survival. CONCLUSIONS: The rate of growth of colorectal liver metastases prior to surgery should not be used as a prognostic factor when considering the role of resection.

The Interaction between Diabetes, Body Mass Index, Hepatic Steatosis, and Risk of Liver Resection: Insulin Dependent Diabetes Is the Greatest Risk for Major Complications.

Background. This study aimed to assess the relationship between diabetes, obesity, and hepatic steatosis in patients undergoing liver resection and to determine if these factors are independent predictors of major complications. Materials and Methods. Analysis of a prospectively maintained database of patients undergoing liver resection between 2005 and 2012 was undertaken. Background liver was assessed for steatosis and classified as <33% and ≥33%. Major complications were defined as Grade III-V complications using the Dindo-Clavien classification. Results. 504 patients underwent liver resection, of whom 56 had diabetes and 61 had steatosis ≥33%. Median BMI was 26 kg/m(2) (16-54 kg/m(2)). 94 patients developed a major complication (18.7%). BMI ≥ 25 kg/m(2) (P = 0.001) and diabetes (P = 0.018) were associated with steatosis ≥33%. Only insulin dependent diabetes was a risk factor for major complications (P = 0.028). Age, male gender, hypoalbuminaemia, synchronous bowel procedures, extent of resection, and blood transfusion were also independent risk factors. Conclusions. Liver surgery in the presence of steatosis, elevated BMI, and non-insulin dependent diabetes is not associated with major complications. Although diabetes requiring insulin therapy was a significant risk factor, the major risk factors relate to technical aspects of surgery, particularly synchronous bowel procedures.

Anti-inflammatory effects of ischemic preconditioning on rat small bowel allografts.

INTRODUCTION: Minimizing the inflammatory events that follow intestinal transplantation may influence immediate graft function and improve outcome. Ischemic preconditioning (IPc) has been shown to ameliorate early inflammatory responses, and it may also attenuate the potentially damaging inflammation after intestinal transplantation. Herein, we examine the influence of intestinal IPc on inflammatory indices (tissue expression of ICAM-1, CD11a, and CD44 and serum levels of the soluble ICAM-1, sICAM-1) after heterotopic intestinal transplantation. METHODS: Lewis rats received full-length preconditioned or non-preconditioned Brown Norway intestinal allografts in the absence of immunosuppression. Preconditioned grafts were subjected to 1 cycle of 10 minutes of ischemia-reperfusion. Preconditioned and non-preconditioned isografts acted as controls. Blood was collected on alternate days post-transplant, and graft tissue harvested on sacrifice. ICAM-1, CD44, and CD11a expression was determined by immunohistochemistry, and the area of staining was quantified using image analysis. Serum soluble ICAM-1 levels were determined using an R&D Systems Quantikine enzyme immunoassay. RESULTS: (1) IPc ameliorated serum levels of sICAM-1 until severe rejection (day 7) overcame this down-regulation when compared to non-preconditioned allografts (day 3: 34,304 vs 40,479 pg/mL; day 5: 52,441 vs 61,593 pg/mL; day 7: 75,114 vs 73,309 pg/mL; day 9: 72,872 vs 76,314 pg/mL, respectively). (2) ICAM-1 expression was significantly lower in preconditioned allografts (1.02 vs 2.01 mm(2)). (3) CD44 tissue levels were also found to be lower in preconditioned allografts (0.86 vs 1.13 mm(2)). (4) There was a significant relationship between tissue ICAM-1 expression and serum levels of soluble ICAM-1 (P < .02). CONCLUSIONS: IPc improves inflammatory indices in the early stages following intestinal transplantation, and this might lead to a preserved cellular, architectural, and functional graft status. Furthermore, our results support the use of soluble ICAM-1 as a marker of endothelial activation, and thence of inflammation and developing rejection.

Assessment of the value of MRI scan in addition to CT in the pre-operative staging of colorectal liver metastases.

PURPOSE: The aims of this study were to measure the accuracy of computerised tomography (CT) and magnetic resonance imaging (MRI) scans in detecting colorectal liver metastases (CRLM) and to determine if patients who are staged with MRI in addition to CT have longer liver recurrence-free survival compared to those having CT alone in a unit performing routine intra-operative ultrasound. METHODS: A retrospective analysis of patients undergoing liver resection for CRLM was performed. Patients staged pre-operatively with CT or with additional MRI were included and those with additional PET imaging were excluded from survival analysis. Timing and site of tumour recurrence were recorded. RESULTS: During a 7-year period, 303 patients underwent resection for CRLM of whom 47 (15.5 %) were staged with CT alone and 36 (11.9 %) with additional MRI. The overall accuracy of CT (63 %) and MRI (61.9 %) was similar in the detection of tumour nodules (P = 0.905). There was no difference in the rate of intra-hepatic recurrence between groups with 13/47 and 8/36 cases, respectively (P = 0.737). There was no difference in the disease-free survival curves between the groups (P = 0.487). CONCLUSIONS: Our recommendation is that MRI should not be a mandatory imaging modality in referral guidelines for patients with hepatic CRLM, as the cost and delay associated with the scan outweigh any potential benefit in terms of improved sensitivity compared to CT.

Renal dysfunction is an independent risk factor for mortality after liver resection and the main determinant of outcome in posthepatectomy liver failure.

Introduction. The aim of this study was to assess the interaction of liver and renal dysfunction as risk factors for mortality after liver resection. Materials and Methods. A retrospective analysis of 501 patients undergoing liver resection in a single unit was undertaken. Posthepatectomy liver failure (PHLF) was defined according to the International Study Group of Liver Surgery (ISGLS) definition (assessed on day 5) and renal dysfunction according to RIFLE criteria. 90-day mortality was recorded. Results. Twenty-three patients died within 90 days of surgery (4.6%). The lowest mortality occurred in patients without evidence of PHLF or renal dysfunction (2.7%). The mortality rate in patients with isolated PHLF or renal dysfunction was 20% compared to 45% in patients with both. Diabetes (P = 0.028), renal dysfunction (P = 0.030), and PHLF on day 5 (P = 0.011) were independent predictors of 90-day mortality. Discussion. PHLF and postoperative renal dysfunction are independent predictors of 90-day mortality following liver resection but the predictive value for mortality is significantly higher when failure of both organ systems occurs simultaneously.

The Preoperative Assessment of Hepatic Tumours: Evaluation of UK Regional Multidisciplinary Team Performance.

Introduction. In the UK, patients where liver resection is contemplated are discussed at hepatobiliary multidisciplinary team (MDT) meetings. The aim was to assess MDT performance by identification of patients where radiological and pathological diagnoses differed. Materials and Methods. A retrospective review of a prospectively maintained database of all cases undergoing liver resection from March 2006 to January 2012 was performed. The presumed diagnosis as a result of radiological investigation and MDT discussion is recorded at the time of surgery. Imaging was reviewed by specialist gastrointestinal radiologists, and resultswereagreedonby consensus. Results. Four hundred and thirty-eight patients were studied. There was a significant increase in the use of preoperative imaging modalities (P ≤ 0.01) but no change in the rate of discrepant diagnosis over time. Forty-two individuals were identified whose final histological diagnosis was different to that following MDT discussion (9.6%). These included 30% of patients diagnosed preoperatively with hepatocellular carcinoma and 25% with cholangiocarcinoma of a major duct. Discussion. MDT assessment of patients preoperatively is accurate in terms of diagnosis. The highest rate of discrepancies occurred in patients with focal lesions without chronic liver disease or primary cancer, where hepatocellular carcinoma was overdiagnosed and peripheral cholangiocarcinoma underdiagnosed, where particular care should be taken. Additional care should be taken in these groups and preoperative multimodality imaging considered.

Partial Preservation of Segment IV Confers No Benefit When Performing Extended Right Hepatectomy for Colorectal Liver Metastases.

Introduction. Reducing the volume of resected liver parenchyma may lead to lower morbidity and mortality. The aim of this study was to determine whether partial preservation of segment IV leads to improved outcomes when undertaking extended right hepatectomy for colorectal liver metastases (CRLM). Materials and Methods. A retrospective analysis of patients undergoing right-sided hepatectomy for CRLM was performed. Rates of 90-day mortality and organ dysfunction were compared in 117 patients undergoing right hepatectomy (n = 85), partially extended right hepatectomy with preservation of part of segment IV (n = 20), and fully extended right hepatectomy (n = 12). Results. The 90-day mortality rate of those undergoing right hepatectomy (3/85) was similar to that of those undergoing extended right hepatectomy (0/12) (P = 1.000) but lower than that of those undergoing partially extended right hepatectomy (4/20) (P = 0.024). The rates of hepatic and renal dysfunction were similar between patients undergoing right hepatectomy, partially extended or extended hepatectomy. Discussion. Preservation of part of segment IV confers little clinical benefit when performing extended right hepatectomy for CRLM.

An experimental technique to assess the immunologic consequences of segmental small bowel transplantation.

BACKGROUND: The amount of native small bowel required for adequate nutrition is variable, but lies between 10% and 20% of full length. Currently, for patients requiring small bowel transplantation (SBT), standard practice is to transplant the entire small bowel if space permits. Few experimental studies have addressed the effect of the length of small bowel transplanted on immune responses and in those that have, the amount of mesenteric lymph node (MLN) transplanted has always been a potential confounding factor, as have differences between jejunum and ileum. METHODS: Full-length and segmental heterotopic rat SBT was performed between PVG donor and DA recipients. To transplant reduced length small bowel grafts but to exclude immunologic differences between jejunum and ileum, equal lengths of bowel were resected from proximal and distal ends in the donor. A proportional amount of MLN was carefully dissected using a microvascular technique and then excised. Serial serum samples from the transplant recipients were tested for anti-PVG (rejection) and anti-DA (graft-versus-host) antibodies using a two-color flow cytometric technique, described previously, with the aim of looking for differences in immunologic responses to full and segmental grafts. RESULTS: We have established a model of segmental SBT that includes a proportional amount of MLN and is free from differences between jejunum and ileum. Preliminary data have demonstrated the development of circulating anti-host and anti-graft antibodies with time for both full-length and segmental SBT.

Perioperative analgesia in experimental small bowel transplantation.

BACKGROUND: Despite numerous studies in experimental rat small bowel transplantation (SBT), few authors make reference to perioperative analgesia. Recent changes to the Animals (Scientific Procedures) Act 1986 in the United Kingdom have made the use of analgesia in laboratory animals compulsory because pain is unnecessary in the majority of scientific procedures. METHODS: Heterotopic SBT (PVG-->DA) was performed on male rat recipients weighing 220 to 250 mg under isoflurane with a mean anesthetic time of 100 minutes. Recovery from anesthesia was usually within 15 minutes. Analgesia regimens were based on those in common use for other procedures. All drugs were administered in the 30 minutes prior to recovery from anesthesia. Group A received carprofen (2 mg/kg IM or SC). Group B was given buprenorphine (0.05 mg/kg either IM or SC). Group C received paracetamol (10- 30 mg) rectally. An early postoperative scoring system of four criteria was used, giving a maximum (least desirable) score of 16. Sixty transplants were performed, divided between the three groups. RESULTS: In group A animals scored a median of 1 of 16 but all except three recipients died within 3 hours. Those in group B scored a median of 8 of 16, but all animals except one died between 4 to 16 hours after surgery. Group C had a median score of 11 of 16, but there was no early mortality. Postmortem examination excluded technical failures in all but three animals. CONCLUSION: We recommend the use of paracetamol for perioperative analgesia in SBT because of the high mortality associated with other drugs when used in this procedure.

Anti-interleukin 2 receptor antibodies and mycophenolate mofetil for treatment of steroid-resistant rejection in adult liver transplantation.

BACKGROUND: Steroid-resistant rejection (SRR) results in significant morbidity and mortality from the adverse effects of rescue therapy and in graft loss from chronic rejection. In our knowledge, the efficacy and safety of anti-interleukin (IL) 2r antibodies (daclizumab and basiliximab) for the treatment of SRR in adult liver transplantation has not previously been evaluated. METHODS: Twenty-five patients received either daclizumab or basiliximab as rescue therapy for SRR. Outcome and biochemical parameters were recorded before and after treatment with an anti-IL-2r antibody. RESULTS: The median time from transplantation to SRR was 25 days. Secondary immunosuppression included mycophenolate mofetil in 18 patients. Twelve patients (48%) had complete resolution of SRR. Aspartate transaminase levels normalized at a median of 37 days (range, 1-168 days). In 13 patients (52%) progressive hepatic dysfunction developed. Four of these patients received another transplant, and 6 patients had chronic rejection. Three patients died with graft failure. Of 16 patients with acute cellular rejection, 12 (75%) had resolution, 2 had chronic rejection, 1 required a repeat transplantation, and 1 died with graft failure. In contrast, all 9 patients with established chronic rejection in their pretreatment biopsy continued to have significant graft dysfunction, with 4 having persistent chronic graft dysfunction, 3 requiring repeat transplantation, and 2 dying with graft failure. CONCLUSION: Twelve (48%) of 25 patients who received an anti-IL-2r antibody because of SRR were successfully treated. All successfully treated patients had ongoing acute cellular rejection at liver biopsy (75%), whereas patients with histologic evidence of chronic rejection responded poorly.

Antimurine immunoglobulin antibody responses after the administration of murine monoclonal antibodies to rats are altered by small bowel allograft rejection.

BACKGROUND: This study monitored the induction of antimurine immunoglobulin antibody responses after the administration of anti-CD4 (OX38) and anti-LFA-1 (WT.1) monoclonal antibodies to DA rats. METHODS: Monoclonal antibody was administered i.v. on 3 consecutive days to untransplanted DA rats, and DA recipients of PVG small bowel allografts. Control animals received no monoclonal antibody. Antimurine immunoglobulin antibody levels in serum samples were determined by enzyme immunoassay. RESULTS: No antimurine immunoglobulin antibody was detected in untransplanted animals receiving OX38 alone. Reactivity was apparent in WT.1-treated animals, but this response was totally abrogated by the co-administration of OX38. A combination of OX38 and WT.1 had no effect on allograft recipient survival and antimurine immunoglobulin antibody responses were detected in all allograft recipients, irrespective of the treatment regimen. CONCLUSIONS: Although OX38 inhibited the antibody response both to itself and to WT.1 in untransplanted animals, the immune reaction induced by small bowel allograft rejection overcame this inhibitory capacity.

Localized, benign, nontraumatic strictures of the extrahepatic biliary tree in children.

BACKGROUND: Benign, nontraumatic, inflammatory strictures of the extrahepatic biliary tree are rare in children and have been reported infrequently in the literature. We describe 7 children with this type of stricture and describe the results of their surgical treatment. METHODS: There were 6 girls and 1 boy, aged 2(1/2) to 15 years. The majority, who had no significant medical or surgical history, were first seen with obstructive jaundice. Investigations revealed isolated strictures of the extrahepatic biliary tree and varying degrees of secondary biliary change within the liver. All 7 patients underwent biliary-enteric anastomosis; 5 also had resection of the stricture. RESULTS: No child experienced significant early complications from the operation, although 2 patients with unresectable lesions required further surgical treatment since their initial bypass. All patients are currently well at 1 to 17 years from initial referral without evidence of recurrent biliary disease after resection. CONCLUSIONS: Children who present with benign strictures of the extrahepatic biliary tree can be treated very satisfactorily with resection and hepaticojejunostomy. This rare condition should be considered as part of the differential diagnosis in children who present with obstructive jaundice. The etiology remains unknown.

Living related liver transplantation in biliary atresia with absent inferior vena cava.

The success of the triangulation technique for hepatic venous anastomosis in left lateral segment liver transplantation has led to standardization of this procedure. We report a case of syndromic biliary atresia with absent inferior vena cava in which we constructed a neo cava to implant a living related left lateral segment graft by using the triangulation technique.

Induction of antigraft and antirecipient antibody responses after fully allogeneic and semiallogeneic rat small bowel transplantation.

BACKGROUND: Given the potential influence of alloantibodies on organ graft outcome, this study investigated the induction of antigraft and antirecipient antibodies after allogeneic and semiallogeneic rat small bowel transplantation. METHODS: Fully allogeneic, unidirectional rejection and unidirectional graft-versus-host disease (GvHD) heterotopic small bowel transplantation was performed using DA, PVG, and (PVGxDA)F1 donor-recipient combinations. Serum was obtained before and at time points after transplantation and incubated with blood from untransplanted DA and PVG rats. Antibody binding to T cells was detected by whole blood flow cytometry using FITC-conjugated anti-rat IgM murine monoclonal antibody. Antibody levels were determined by reference to a standard curve of fluorescent intensity generated using a serum sample with known anti-target cell IgM activity. Data are presented as arbitrary units/ml (AU/ml). RESULTS: In the PVG-->DA combination, five of six DA recipients had detectable anti-graft (PVG) antibodies by day 4 after transplantation (mean 72 AU/ml) and all animals were positive by day 6 (976 AU/ml). Antirecipient (DA) antibodies were also induced, however, they were only apparent after 6 days in five of eight animals (90 AU/ml). Antigraft (DA) antibody responses were also induced in the DA-->PVG combination (day 6-218 AU/ml), however no antirecipient (PVG) response was apparent. Transplantation induced antirecipient (DA) antibodies in the unidirectional GvHD model (day 6-90 AU/ml) and an anti-graft (PVG) response in the unidirectional rejection model (day 6-60 AU/ml). However, the latter was quantitatively lower than that generated in the PVG-->DA combination (day 6-976 AU/ml). CONCLUSIONS: Antigraft and antirecipient antibody responses are simultaneously induced after fully allogeneic small bowel transplantation, despite rejection being the predominant clinical feature. Further studies are required to elucidate their influence on graft outcome.

Effect of anti-CD4 monoclonal antibody administration on rat small bowel allograft survival and circulating leukocyte populations.

This study assessed the effect of an anti-rat CD4 monoclonal antibody (OX38) on heterotopic small bowel allograft rejection. Fully allogeneic small bowel transplants were performed in the PVG-to-DA-rat strain combination. Animals received either i) short course (days -1, 0 and 1) of 1 mg/kg per day OX38, ii) short course of 5 mg/kg per day or iii) extended course (days -2, -1, 0, 1, 2 and twice weekly thereafter) of 1 mg/kg per day. Both the high dose (13 days) and extended low-dose (12 days) courses prolonged graft survival compared to untreated control animals (7 days). The low-dose, short-course treatment had no effect. Similar regimens were given to animals that did not receive transplants and in which peripheral blood CD4+ cell counts fell to between 20 and 55 % of pretreatment levels and 20-30% of binding sites were blocked. In summary, anti-CD4 monoclonal antibody therapy delayed rejection of rat small bowel allografts; however, long-term survival was not achieved.

Effect of anti-LFA-1 monoclonal antibody on rat small bowel allograft survival and circulating leukocyte populations.

Anti-LFA-1 monoclonal antibodies (mAb) prolong graft survival in several animal models. This study assessed the effect of an anti-LFA-1 mAb (WT.1) on small bowel allograft rejection, circulating leukocyte subsets and in vivo target cell antigen blockade. Heterotopic small bowel transplantation was performed between PVG donor and DA recipient rats. Transplanted animals received 1 mg/kg per day WT.1 on days -1, 0 (day of transplantation) and 1. Three doses of WT.1 were also administered to a group of untransplanted animals to monitor circulating leukocyte populations and in vivo binding. WT.1 prolonged recipient survival from 7 to 14 days. Peripheral leukocyte counts increased more than twofold, primarily due to marked increases in both CD4+ and CD8+ lymphocytes. Approximately 85% of WT.1 binding sites on lymphocytes and monocytes were blocked/modulated after the course of therapy. WT.1 has marked effects on circulating leukocytes and target cell binding capacities and can affect the survival of rat small bowel transplant recipients.