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A man in his 40s with no medical history presented with right-sided abdominal and chest pain. A CT scan of the abdomen demonstrated a 7.7 cm heterogeneous mass arising from the second part of the duodenum. Oesophagogastroduodenoscopy confirmed a malignant-appearing duodenal lesion, with biopsy showing features consistent with small cell carcinoma. The patient underwent three cycles of neoadjuvant chemotherapy, followed by elective Kausch-Whipple pancreaticoduodenectomy. A combination of immunohistochemistry and molecular studies confirmed the diagnosis of a rare Ewing's sarcoma tumour originating from the duodenum with invasion into the duodenal lumen. The patient recovered well from surgery and remains disease-free 18 months following resection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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 CO 2 (VEqCO 2 ) 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 VEqCO 2 , 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.

Background: Centralisation of specialist surgical services requires that patients are referred to a regional centre for surgery. This process may disadvantage patients who live far from the regional centre or are referred from other hospitals by making referral less likely and by delaying treatment, thereby allowing tumour progression. The aim of this study is to explore the outcome of surgery for peri-ampullary cancer (PC) with respect to referring hospital and travel distance for treatment within a network served by five hospitals., Methods: Review of a unit database was undertaken of patients undergoing surgery for PC between January 2006 and May 2014., Results: 394 patients were studied. Although both the median travel distance for patients from the five hospitals (10.8, 86, 78.8, 54.7 and 89.2 km) (p < 0.05), and the annual operation rate for PC (2.99, 3.29, 2.13, 3.32 and 3.07 per 100,000) (p = 0.044) were significantly different, no correlation was noted between patient travel distance and population operation rate at each hospital. No difference was noted between patients from each hospital in terms of resection completion rate or pathological stage of the resected tumours. The median survival after diagnosis for patients referred from different hospitals ranged from 1.2 to 1.7 years and regression analysis revealed that increased travel distance to the regional centre was associated with a small survival advantage., Conclusion: Although variation in the provision and outcome of surgery for PC between regional hospitals is noted, this is not adversely affected by geographical isolation from the regional centre., Trial Registration: This study is part of post-graduate research degree project. The study is registered with ClinicalTrials.gov (unique identifier NCT02296736 ) November 18, 2014.

Background: A period of recovery is commonly allowed between completion of chemotherapy for colorectal liver metastases (CRLM) and resection, during which tumour progression may occur. The study-aim is to assess the growth of CRLM in this interval and association with outcome., Method: Data on 146 patients were analysed. Change in tumour size was assessed by comparing size determined by imaging performed on completion of chemotherapy with that determined by examination of the resected specimen, categorised by RECIST criteria., Results: In the interval before surgery sixteen patients (11%) fulfilled criteria for partial response (PR), 48 (33%) had stable disease (SD) and 82 (56%) had progressive disease (PD). Among patients with PD following chemotherapy the median disease-free survival of patients who initially responded (26 months) was longer than in those who initially had stable disease (7 months) (P = 0.002). No association was noted between rate of tumour growth after completion of chemotherapy and disease-free survival., Conclusion: Change in tumour size after completion of chemotherapy is variable and can be rapid, especially in patients who initially respond to treatment. However, disease-free survival is determined by tumour behaviour during treatment and not by change in size after completion of chemotherapy., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Delay between diagnosis of peri-ampullary cancer (PC) and surgery may allow tumour progression and affect outcome. The aim of this study was to explore associations of interval to surgery (IS) with pathological outcomes and survival in patients with PC., Method: A database review of all patients undergoing surgery between 2006 and 2014 was undertaken. IS was measured from diagnosis by imaging. Potential association between IS and survival was measured using Cox regression analysis, and between IS and pathological outcome with multivariate logistic analysis., Results: 388 patients underwent surgery. The median IS was 49 days (1-551 days), and was not associated with any of the evaluated outcomes in patients with pancreatic (149) or distal bile duct (46) cancer. For patients with ampullary cancer (71) longer IS was associated with improved survival, with median survival of 27.5 months for patients waiting ≤ median IS (35) and 38.3 months for patients waiting > median IS (36) for surgery (p = 0.041). A higher rate of margin positivity (31.4%) was also noted among patients who waited less than the median IS compared to those waiting longer than this interval (11.4%) (p = 0.032)., Conclusion: For patients with ampullary cancer there is a paradoxical improvement in outcome among those with a longer IS, which may be explained by progression to inoperability of more aggressive lesions., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Liver resection is associated with significant morbidity, and assessment of risk is an important part of preoperative consultations. Objective methods exist to assess operative risk, including cardiopulmonary exercise testing (CPX). Subjective assessment is also made in clinic, and patients perceived to be high-risk are referred for CPX at our institution. This article addresses clinicians' ability to identify patients with a higher risk of surgical complications after hepatectomy, using selection for CPX as a surrogate marker for increased operative risk., Materials and Methods: Prospectively collected data on patients undergoing hepatectomy between February 2008 and November 2013 were retrieved and the cohort divided according to CPX referral. Complications were classified using the Clavien-Dindo system., Results: CPX testing was carried out before 101 of 405 liver resections during the study period. The median age was 72 and 64 in CPX and non-CPX groups, respectively (P < 0.001). The resection size was similar between the groups. No difference was noted for grade III complications between CPX and non-CPX tested-groups; however, 19 (18.8%) and 28 (9.2%) patients suffered grade IV-V complications, respectively (P = 0.009). There was no difference in long-term survival between groups (P = 0.63)., Conclusions: This study attempts to assess clinicians' ability to identify patients at greater risk of complications after hepatectomy. The confirmation that patients identified in this way are at greater risk of grade IV-V complications demonstrates the value of preoperative counseling. High-risk patients do not have worse long-term outcomes suggesting survival is determined by other factors, particularly disease recurrence., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to compare the socioeconomic profile of patients undergoing liver resection for colorectal liver metastasis (CLM) in a regional hepatopancreatobiliary unit with that of the local population. A further aim was to determine if degree of deprivation is associated with tumour recurrence after resection., Methods: A retrospective analysis of patients undergoing liver resection for CLM was performed. Geodemographic segmentation was used to divide the population into five categories of socioeconomic status (SES)., Results: During a 7-year period, 303 patients underwent resection for CLM. The proportion of these patients in the two least deprived categories of SES was greater than that of the local population (50.2% versus 40.2%) and the proportion in the two most deprived categories was lower (18.3% versus 30.1%) (P < 0.001). There was no difference in recurrence rate (P = 0.867) or disease-free survival among categories of SES (P = 0.913). Multivariate analysis demonstrated no association between SES and tumour recurrence (P = 0.700)., Conclusions: Liver resection for CLM is performed more commonly among the least socioeconomically deprived population than among the most deprived. However, degree of deprivation was not associated with tumour recurrence after resection., (© 2014 International Hepato-Pancreato-Biliary Association.)

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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.

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.

Background: The aim of this study was to determine if the post-operative serum arterial lactate concentration is associated with mortality, length of hospital stay or complications following hepatic resection., Methods: Serum lactate concentration was recorded at the end of liver resection in a consecutive series of 488 patients over a seven-year period. Liver function, coagulation and electrolyte tests were performed post-operatively. Renal dysfunction was defined as a creatinine rise of >1.5x the pre-operative value., Results: The median lactate was 2.8 mmol/L (0.6 to 16 mmol/L) and was elevated (≥2 mmol/L) in 72% of patients. The lactate concentration was associated with peak post-operative bilirubin, prothrombin time, renal dysfunction, length of hospital stay and 90-day mortality (P < 0.001). The 90-day mortality in patients with a post-operative lactate ≥6 mmol/L was 28% compared to 0.7% in those with lactate ≤2 mmol/L. Pre-operative diabetes, number of segments resected, the surgeon's assessment of liver parenchyma, blood loss and transfusion were independently associated with lactate concentration., Conclusions: Initial post-operative lactate concentration is a useful predictor of outcome following hepatic resection. Patients with normal post-operative lactate are unlikely to suffer significant hepatic or renal dysfunction and may not require intensive monitoring or critical care.

Introduction: The aim of this study was to analyse the influence of factors reported in the minimum histopathology dataset for colorectal liver metastases (CRLM) and other pre-operative factors compared with additional data relating to the presence of tumour pseudocapsules and necrosis on recurrence 1 year after a resection., Methods: For a period of 14 months, extended histological reporting of CRLM specimens was performed, including the presence of pseudocapsules and necrosis in each tumour. The details of recurrence were obtained from surveillance imaging., Results: In 66 patients there were 27 recurrences within 1 year. The rates were lower for patients with tumour pseudocapsules (8/27) than for patients without (19/36) (P = 0.030). Pseudocapsules were associated with a younger age (P = 0.005), nodal stage of the primary colorectal tumour (P = 0.025) and metachronous tumours (P = 0.004). In patients with synchronous disease and pseudocapsules, the recurrence rate was 2/12 compared with 13/23 patients without pseudocapsules (P = 0.026)., Discussion: These findings demonstrate that histological examination of resection specimens can provide significant additional prognostic information for patients after resection of CRLM, compared with clinical and radiological data. The present finding that the absence of a pseudocapsule in patients with synchronous CRLM is associated with a dramatically worse outcome may help direct patient-specific adjuvant treatment and care., (© 2012 International Hepato-Pancreato-Biliary Association.)

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.

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.

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.

Background: Current assumptions rely on intra-abdominal pressure (IAP) being uniform across the abdominal cavity. The abdominal contents are, however, a heterogeneous mix of solid, liquid and gas, and pressure transmission may not be uniform. The current study examines the upper and lower IAP following liver transplantation., Methods: IAP was measured directly via intra-peritoneal catheters placed at the liver and outside the bladder. Compartmental pressure data were recorded at 10-min intervals for up to 72 h following surgery, and the effect of intermittent posture change on compartmental pressures was also studied. Pelvic intra-peritoneal pressure was compared to intra-bladder pressure measured via a FoleyManometer., Results: A significant variation in upper and lower IAP of 18% was observed with a range of differences of 0 to 16 mmHg. A sustained difference in inter-compartmental pressure of 4 mmHg or more was present for 23% of the study time. Head-up positioning at 30° provided a protective effect on upper intra-abdominal pressure, resulting in a significant reduction in all patients. There was excellent agreement between intra-bladder and pelvic pressure., Conclusions: A clinically significant variation in inter-compartmental pressure exists following liver transplantation, which can be manipulated by changes to body position. The existence of regional pressure differences suggests that IAP monitoring at the bladder alone may under-diagnose intra-abdominal hypertension and abdominal compartment syndrome in these patients. The upper and lower abdomen may need to be considered as separate entities in certain conditions.

We offer this case for publication as we believe that this is the first report of widespread aortic thrombosis secondary to acute severe pancreatitis.

Dieulafoy lesions are a rather uncommon cause of gastrointestinal bleeding that can be torrential and life-threatening. Extragastric location and pediatric cases are very rare. We report the first case of synchronous Dieulafoy lesions in the stomach and jejunum. This case is discussed in the light of the reported literature on this condition.

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.

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.

Background: Adult orthotopic liver transplantation is associated with significant use of allogenic blood products, which places considerable demands on finite resources. This could be reduced by autologous red cell salvage use, and we evaluated its cost effectiveness in this prospective study., Methods: Intraoperative autotransfusion was used in 660 adult liver transplant patients between January 1997 and July 2002. These included 134 with acute liver failure, 62 retransplants, 90 alcohol-related, 183 viral, 98 cholestatic chronic liver diseases, and 93 with other etiologies., Results: The total volume of red blood cells transfused was 3641+/-315 ml, 2805+/-234 ml, 2603+/-443 ml, and 2785+/-337 ml for alcohol-related, viral, cholestatic, and others, respectively. Low preoperative hemoglobin was significantly associated with higher intraoperative transfusion requirements. Blood volumes transfused at retransplantation were significantly higher (7077+/-1110 ml vs. 2864+/-138 ml; P<0.001) than for acute liver failure and chronic liver disease. Autologous blood volumes transfused were similar in all diagnostic groups, but were significantly greater in retransplantation (2754+/-541 ml vs. 1524+/-77 ml; P<0.01). Venovenous bypass was significantly associated with higher transfusion requirements. Total savings per case were similar for all diagnostic groups but were greater in cases of retransplantation (864+/-222 pounds (1235+/-317 US dollars) vs. 238+/-24 pounds (340+/-34 US dollars; P<0.001). With the use of autologous transfusion over the study period, a cost saving of 131,901 pounds (188,618 US dollars) was achieved., Conclusions: Intraoperative red blood cell salvage and autologous transfusion is cost effective in adult liver transplantation. Currently, where optimum resource utilization and fiscal constraint are paramount in healthcare delivery, autologous transfusion is an important adjunct in 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.

Background: Retransplantation of the liver is the only means of prolonging survival in children whose initial graft has failed. Patient and graft survival rates after retransplantation in most series have been inferior to rates after first transplantation., Patients and Methods: Of 450 pediatric liver transplantations performed between January 1990 and March 2001, 50 were first retransplantations, 9 were second retransplantations, and 1 was a third retransplantation. The overall retransplantation rate was 13.3% (median age at retransplantation 4 years and median weight 15 kg). The median post-retransplantation follow-up was 73 (range, 6-139) months., Results: Kaplan-Meier patient survival rates for the group (n=50) were 71.7%, 64.7%, and 64.7% at 1, 3, and 5 years, respectively. Graft survival rates were 65.6%, 56.7%, and 56.7% at 1, 3, and 5 years, respectively. This is significantly worse than rates for children undergoing first liver transplantation. There were 17 deaths, of which 9 occurred in the first month. Biliary complications occurred in 5 (10%) patients and vascular complications in 6 (12%). Improved patient and graft survival rates were observed in the later phase of the program, although the difference was not significant. Higher preoperative serum creatinine (P=0.001) and serum bilirubin (P=0.02) levels were associated with a higher postoperative mortality., Conclusion: Results of retransplantation in children remain inferior to those after first transplantation. There is a trend toward improving results. Liver retransplantation makes an important contribution to overall survival in children.

Objective: To analyze the outcome of 80 consecutive pediatric split liver transplants performed at the authors' center between 1994 and 2000., Summary Background Data: Split liver transplantation has become an accepted method of increasing the number of available grafts for pediatric liver transplant recipients., Methods: The age of the patients at the time of transplantation ranged from 5 days to 16 years (median 3 years). Sixteen transplants were performed for acute liver failure and 64 for chronic liver failure. The ex situ splitting technique was used for all but four grafts. Fourteen livers were split for two pediatric recipients. Posttransplant follow-up ranged from 6 to 84 months (median 42 months)., Results: Overall patient survival at 6 months follow-up was 96.2%. Graft survival at six months was 93.7%. The Kaplan-Meier patient survival rates at 1 and 3 years were 93.5% and 88.1%, and the graft survival rates were 89.7% and 86.1%, respectively. Four patients required retransplantation. In the acute group (n = 16), the patient survival rates were 93.7% at 1 year and 76.4% at 3 years; there were three deaths due to posttransplant lymphoproliferative disease (PTLD), sepsis, and chronic rejection. In the chronic group (n = 64), the 1- and 3-year patient survival rates were 93.6% and 90.9%, respectively. There were six deaths in this group. Four patients died in the first year after the transplant due to intracranial bleeding, cerebral tumor recurrence, PTLD, and chronic rejection. There were two deaths at 3 years, one due to progressive renal failure secondary to cyclosporin toxicity and the other due to sepsis, portal hypertension, and recurrent bleeding. Vascular complications occurred in six (7.5%) patients and biliary complications in seven (8.7%)., Conclusions: These results, which represent the experience of a single institution over the last 6 years, indicate that ex situ split liver transplantation can be performed in children with good overall outcome and acceptable morbidity.

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.

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.

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.

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.

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.

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.

Background: This study investigated the relationships between cyclosporin A (CsA) blood levels and episodes of renal allograft rejection and nephrotoxicity following renal transplantation, with the aim of establishing whether CsA profiles provided more useful information than single CsA blood levels in respect of these relationships., Methods: One hundred and sixty-two profiles were performed over 16 months in 40 patients and analysed retrospectively. Blood samples were taken at 0, 2, 4, 6 and 8 h after the morning CsA dose. Rejection episodes were diagnosed by renal biopsy and CsA nephrotoxicity by a fall in serum creatinine 1 week after a cut in CsA dose., Results: The mean area under the curve (AUC) was lower for profiles performed at the time of rejection (3821 h.ng/ml) than that of a matched group of non-rejecting profiles (5479 h.ng/ml; P < 0.02). An AUC above 6400 h.ng/ml significantly discriminated rejection from non-rejection, whereas pre-dose and peak CsA concentrations did not have such discriminating cut-off values. A comparison of CsA-toxic and non-toxic profiles showed that there were no significant differences between mean CsA concentrations nor between the mean AUCs of these groups., Conclusion: We conclude that basing CsA dosing on CsA profiles could help to avoid some early episodes of rejection without increasing the risk of nephrotoxicity.

Soluble MHC class I antigens can be detected in the serum of humans and various animals and appear in the circulation shortly after liver transplantation. The precise role of these antigens is currently uncertain, but soluble MHC class I may be involved in immunomodulation. We have developed an enzyme linked immunosorbent assay for soluble rat MHC class I (RT1a) molecules and monitored the kinetics of antigen release following in vitro stimulation of splenic mononuclear cells. A 4 day DA splenocyte Con A supernatant provided a source of soluble class I antigens and was arbitrarily assigned a concentration of 1000 units/ml. Ninety six well plates were coated with a rat RT1a-specific mAb (MN4-91-6) and soluble class I binding was detected using a biotinylated mAb reactive with a monomorphic region of the rat MHC class I molecule (OX18) followed by a streptavidin-alkaline phosphatase conjugate and substrate. The intra- and interassay variations were typically less than 5% and 10% respectively, to give a working range for the assay of between 62.5 and 1000 units/ml. Mitogenic stimulation led to a progressive increase in soluble class I levels in culture supernatants. This assay will be valuable in differentiating recipient and graft responses following experimental organ transplantation.

This investigation used flow cytometry to monitor peripheral blood lymphocyte morphology after rat small bowel transplantation. Preliminary studies demonstrated that in vitro activated peripheral blood lymphocytes exhibited increased cell size and granularity as measured by flow cytometric analysis of forward (FSc) and side (SSc) light scatter characteristics. The formation of distinct 'activated' light scatter regions by such lymphoblastoid transformation occurred concomitantly with up-regulated p55IL-2R expression. Heterotopic small bowel transplantation was performed between PVG donor and DA recipient rats without immunosuppression. Animals receiving isografts served as controls. Peripheral blood lymphocyte subsets were identified using appropriate MoAbs, and the light scatter characteristics of each cell subset were determined by backgating strategies. Increased proportions of activated alpha/beta T cell receptor (TCR)-positive cells could be detected in allografted animals as early as day 2 post-transplantation. B cells showed peak activation by day 4, at which time the proportion of activated cells was over two-fold greater than that seen in untransplanted animals--few activated B cells were detected in isografted animals. Resting natural killer (NK) cell light scatter regions only partially overlap with those of resting T and B lymphocytes, but in allografted animals almost the entire NK population fell outside the resting lymphocyte gate by day 2 post-transplantation, an activation state which was maintained until day 4. These findings associate peripheral blood cell subset lymphoblastoid transformation with developing small bowel allograft rejection. Importantly, changes were detected early and prior to the onset of overt rejection. These data suggest that analysis of peripheral blood lymphocyte light scatter properties may provide an insight into in vivo immune status after small bowel transplantation.

This study describes the development of a sandwich enzyme immunoassay (ELISA) for rat soluble IL-2 receptors (sIL-2R) using a combination of monoclonal antibodies reactive with different epitopes on the rat IL-2R. Coating plates with NDS61 and NDS64 monoclonal antibodies produced similar dose-response curves when incubated with a standard sIL-2R preparation followed by biotinylated OX39, streptavidin-alkaline phosphatase and the substrate. Although normal rat serum inhibited the assay, the effects were more profound when NDS64 was used as the capture antibody and subsequent development of the assay was performed using NDS61. The intra- and interassay variations were typically less than 5%. This assay will be valuable for monitoring immune activation status in a variety of experimental models.

This study used flow cytometric analyses to monitor activation antigen expression (MHC class II; interleukin-2 receptor, p55IL-2R and 3.2.3/NKR-P1 antigen) on peripheral blood neutrophils following rat small bowel transplantation. The rat 3.2.3 antigen is a member of the NKR-P1 family of natural killer (NK) cell-associated molecules, which are expressed at high levels on NK cells and lymphokine-activated killer cells, and low levels on at least one T cell subset. Peripheral blood neutrophils in normal animals express very low or undetectable levels of NKR-P1. Detectable levels of NKR-P1 were induced as early as day 1 following small bowel transplantation in all allografted animals, whereas expression was only rarely detected in isografted animals. In addition, NKR-P1 density was significantly higher in allografted animals and was maintained as rejection developed. MHC class II and p55IL-2R expression was also induced following transplantation. The mechanisms of induction and functional relevance of NKR-P1 expression on neutrophils remain to be defined. However, the concomitant increased expression of MHC class II and p55IL-2R suggest NKR-P1 to be a neutrophil activation marker and implicate a potential role for NKR-P1+ neutrophils in small bowel allograft rejection. This hypothesis is further supported by the loss of detectable peripheral blood neutrophils only with developing rejection. Flow cytometric analysis of neutrophil activation antigen expression may be useful for monitoring human small bowel transplant recipients.

Tumour-associated HMFG2 monoclonal antibody (MAb) was labelled with indium-111 and administered intravesically to 20 patients with known or suspected superficial bladder carcinoma. The antibody solution was kept in the bladder for 1 hr and was then washed out. Cystoscopy was performed at 2 and 24 hr after instillation. Radioactivity of tumour and normal tissue obtained from the bladder during cystoscopy and cells recovered from urine after the instillation were counted in a gamma-counter. Conventional histology, immunocytochemistry and autoradiography were also performed. Mean uptake at 2 and at 24 hr was higher in tumours than in normal samples. Autoradiography showed selective accumulation of radioactivity in cells which expressed the antigen detected by the HMFG2 MAb. There was no correlation of tumour uptake with the grade of tumour. No radioactivity was found in the blood of patients after the instillation. Based on dosimetric calculations, however, the radiation dose that can be delivered to the tumours is not sufficient to be cytotoxic, possibly due to inadequate penetration and retention by tumour tissue. Nevertheless, the significant difference between antibody uptake by the tumours and that by normal urothelium, observed in our study, allow for the possibility of using this approach therapeutically.

Eighteen male patients (aged 40-66 years) with confirmed ischaemic heart disease and a minimum of four angina attacks per week were included in a double-blind comparison of dilevalol 200 mg, dilevalol 400 mg and atenolol 100 mg. Following a one-week placebo run-in period patients were randomly allocated to one of the three treatments, after which they crossed to the remaining two treatments according to a balanced Latin square design. Each treatment was given once-daily over four weeks. Symptom-limited treadmill exercise testing using a modified Bruce protocol was performed at the end of placebo, and after each treatment around 24 hours post-dosing. The mean exercise time on placebo was 7.0 (+/- 0.91) minutes which changed to 7.8 (+/- 0.93) minutes on dilevalol 200 mg, 7.3 (+/- 0.88) minutes on dilevalol 400 mg and 8.2 minutes (+/- 1.06) on atenolol 100 mg. Nine patients had a greater exercise tolerance on dilevalol (200 or 400 mg), and nine a greater exercise tolerance on atenolol. Maximum exercise heart rate on placebo was 113 (+/- 5.0) beats per minute (bpm) which was reduced to 101 (+/- 3.6), 96 (+/- 2.7) and 98 (+/- 4.9) bpm. on dilevalol 200 mg, dilevalol 400 mg and atenolol 100 mg, respectively. Correspondingly, the rate-pressure product was reduced from 18.1 (x 10(3)) units on placebo to 14.8, 13.4 and 14.4 (x 10(3)) units on each treatment. Pairwise comparisons by the least square mean procedure showed no significant differences between treatments for any of the measured parameters. All treatments caused a reduction in both angina attack rates and trinitrate consumption.(ABSTRACT TRUNCATED AT 250 WORDS)