Safe Conversion From Tacrolimus to Belatacept in High Immunologic Risk Kidney Transplant Recipients With Allograft Dysfunction.

There is no literature on the use of belatacept for sensitized patients or regrafts in kidney transplantation. We present our initial experience in high immunologic risk kidney transplant recipients who were converted from tacrolimus to belatacept for presumed acute calcineurin inhibitor (CNI) toxicity and/or interstitial fibrosis/tubular atrophy. Six (mean age = 40 years) patients were switched from tacrolimus to belatacept at a median of 4 months posttransplant. Renal function improved significantly from a peak mean estimated glomerular filtration rate (eGFR) of 23.8 ± 12.9 mL/min/1.73 m(2) prior to the switch to an eGFR of 42 ± 12.5 mL/min/1.73 m(2) (p = 0.03) at a mean follow-up of 16.5 months postconversion. No new rejection episodes were diagnosed despite a prior history of rejection in 2/6 (33%) patients. Surveillance biopsies performed in 5/6 patients did not show subclinical rejection. No development of donor-specific antibodies (DSA) was noted. In this preliminary investigation, we report improved kidney function without a concurrent increase in risk of rejection and DSA in six sensitized patients converted from tacrolimus to belatacept. Improvement in renal function was noted even in patients with chronic allograft fibrosis without evidence of acute CNI toxicity. Further studies with protocol biopsies are needed to ensure safety and wider applicability of this approach.

Cholangiocarcinoma complicating primary sclerosing cholangitis: a 24-year experience.

AIM: To report the prevalence and outcome of cholangiocarcinoma arising in primary sclerosing cholangitis for a British tertiary referral centre. METHODS: All patients diagnosed with primary sclerosing cholangitis and concurrent cholangiocarcinoma were identified from a prospectively maintained departmental database, and the mode of presentation, management and outcome were determined. RESULTS: Of 370 patients with primary sclerosing cholangitis, 48 patients (13%) were diagnosed with a cholangiocarcinoma within a median time of 0.51 months (range: 0-73.12) from presentation to the unit. Mode of presentation included: inoperable tumours (n = 14); incidental findings in transplant hepatectomy specimens (n = 13); primary sclerosing cholangitis follow-up (n = 9); transplant work-up (n = 5); transplant waiting list (n = 5); suspected tumour confirmed at transplant (n = 1), and incidental finding at cholecystectomy (n = 1). The diagnosis was confirmed by: radiology-guided biopsy (n = 27); MRI (n = 3); CT (n = 2); laparoscopy or laparotomy (n = 2), and frozen section at transplant (n = 1). Management consisted of: transplantation (n = 14, including 1 abandoned); hepatic resection (n = 8), and palliation through stenting (n = 26). The overall median survival of the cohort was 4.9 months (range: 0.09-104.5). Median survival ranged from 2.6 months (range: 0.09-35.3) for palliation to 7.6 months (range: 0.6-99.6) for transplantation and 52.8 months (range: 3.7-104.5) for resection. There was no difference in survival between the transplant and resection groups (p = 0.14). CONCLUSIONS: Cholangiocarcinoma is a common finding in primary sclerosing cholangitis and regular screening of this cohort of patients at referring centres is advocated to detect early tumours, as surgical treatment at an early stage offers significantly better outcomes for this cohort of patients.

The microbiological impact of pre-operative biliary drainage on patients undergoing hepato-biliary-pancreatic (HPB) surgery.

BACKGROUND: The merit of pre-operative biliary drainage in managing hepatic, biliary or pancreatic patients remains unclear with previous studies demonstrating significant increases in bacterobilia. AIMS: To establish if pre-operative biliary drainage was associated with (i) a change in bacterial flora, (ii) post-operative sepsis and (iii) to ascertain if a modification of antibiotic prophylaxis was warranted. METHODS: Data were collected on 331 patients undergoing hepatic, biliary or pancreatic surgery for malignant obstruction between August 2000 and June 2005. Microbiological data from intra-operative bile, post-operative wounds, blood cultures, urine and sputum were analysed. All episodes of pre-operative endoscopic retrograde cholangiopancreatography (ERCP), stenting and percutaneous drainage were documented. RESULTS: One hundred and sixty two patients had ERCP prior to surgery and 154 had surgery only. In comparison to patients who had surgery alone stented patients had significantly increased rates of bacterobilia (40 vs. 85%) and fungobilia (8 vs. 34%, both P < 0.001). Pre-operative biliary drainage significantly increased post-operative sepsis, wound infections and prolonged in-patient stay (P < 0.05). The most common organisms cultured were coliforms and enterococcus with percutaneous transhepatic cholangiography (PTC) highly significant for the development of MRSA sepsis. CONCLUSIONS: Pre-operative biliary drainage is associated with a high incidence of bacterobilia and fungal colonization. Pre-operative biliary drainage should be utilized selectively, with modification of antibiotic prophylaxis according to patient characteristics.

The role of splenectomy in the setting of refractory humoral rejection after kidney transplantation.

Living donor kidney transplantation remains the best option for presensitized recipients to avoid excessive time on the waiting list. However, the possibility for a positive crossmatch with a potential living donor is high. A desensitization protocol may be required to avoid antibody-mediated rejection (AMR). Current protocols are not always effective to prevent AMR and in some cases fail to convert subjects to a negative crossmatch before transplantation. From March 2006 to January 2011, the 11 presensitized patients who displayed AMR after living donor kidney transplantation underwent splenectomy as a rescue procedure due to failure of standard rejection treatments. Splenectomy was considered to be effective in six recipients who normalized their renal function without the need for other immunomodulating therapy. Our analysis suggested that splenectomy can be successfully performed alone or in association with other treatments like bortezomib or rituximab to overcome severe AMR.

Assessment of survival advantage in ampullary carcinoma in relation to tumour biology and morphology.

INTRODUCTION: Carcinoma of the ampulla of Vater is said to carry a significantly better prognosis than pancreatic ductal adenocarcinomas arising in the pancreatic head. However, it is uncertain as to whether this is due to the fact that they have differing oncological characteristics or simply an earlier presentation as a result of the exophytic morphology of ampullary lesions causing obstruction of the bile ducts. METHODS: All patients undergoing pancreaticoduodenectomy between January 1998 and December 2004 were identified from a prospectively maintained database. Patients with a pathologically confirmed ampullary (AMP) tumour were compared to those with a carcinoma of the head of the pancreas (HOP). Tumour characteristics including size, stage and degree of differentiation were analysed as were survival data. RESULTS: 71 AMP and 144 HOP tumours were resected during the period studied and had full histology reports available for assessment. The median diameter of the AMP tumours was significantly less than those of the HOP (2 cm vs. 3 cm; p = 0.04). The T stage distribution differed significantly between the AMP and HOP tumours in favour of the former (Stages I--10 vs. 0 (p = 0.03); II--29 vs. 13 (p = 0.04); III--25 vs. 121 (p = 0.01); IV--7 vs. 10). The number of resection specimens with positive lymph nodes was lower in the AMP group (31 vs. 121; p = 0.03) as was the prevalence of vascular invasion (33 vs. 114; p = 0.006) and neural invasion (23 vs. 134; p = 0.009). There was no difference in the degree of differentiation of the AMP and HOP tumours. The 5-year survival rates were significantly better in the AMP group at 60% vs. 20% (p = 0.008). Subdivision of AMP carcinoma into polypoid (60%) and ulcerating (40%) lesions revealed a non-significant survival advantage in favour of polypoid tumours at (64% vs. 60%; p = 0.07) at 5 years. CONCLUSIONS: The outcome of resection for AMP is significantly better than for pancreatic ductal adenocarcinomas arising in the periampullary region. Although the anatomical position of AMP tumours may contribute to this survival advantage, the HOP tumours exhibit more adverse histological features suggesting that they are different diseases and hence the difference in survival.

Use of bioelectrical impedance analysis to assess liver steatosis.

BACKGROUND: The shortage of donor livers has led to increased utilization of steatotic marginal livers. Bioelectrical impedance analysis (BIA) uses the principles of electric current flows through tissue, with less resistance offered if the water content is high and the opposite in the presence of fat. Our hypothesis was that liver steatosis would result in an increased resistance to current flow, and correlate with the degree of liver steatosis. METHODS: Before studying cadaveric donor livers for transplantation, this study was performed in patients undergoing liver resection. A total of 37 patients undergoing liver resection for cancer were analysed with BIA, using a handheld, specially calibrated Maltron BIA analyser (BioScan 915) with modified tertrapolar electrodes. These electrodes were applied to the liver surface and resistance was recorded. To validate the results of BIA, a liver biopsy was performed. Histopathology was graded quantitatively as no steatosis, mild, moderate, or severe steatosis according the percentage of fat as well as qualitatively by type of fat (micro and macrovesicular). RESULTS: Bioelectric resistance showed a correlation with macroveiscular steatosis (P = .03). CONCLUSION: BIA is a simple, noninvasive technique and its use should be explored in donor livers to assess steatosis.

A tale of three spilled gall stones: one liver mass and two abscesses.

Spilled gall stone has been one of the most common complications of laparoscopic cholecystectomy. Spillage occurs in up to 40% of cases; complications related to spillage are rare and can present within weeks to years. We report 3 cases referred to a tertiary centre for management of such complications. The first patient presented with clinical and radiological findings of cyst 1 week after laparoscopic cholecystectomy. She was initially thought to have a hydatid cyst. At laparotomy it turned out to be a liver abscess with stones at the centre of the cavity. The second patient presented with recurrent episodes of fever and on investigation was found to have a sub-hepatic abscess. The third patient had similar clinical symptoms to the second patient but presented 7 years after surgery. We recommend that every attempt should be made to avoid gall-bladder perforation during dissection; if this happens every effort should be made to remove the spilled stones.

Role of completion pancreatectomy as a damage control option for post-pancreatic surgical complications.

INTRODUCTION: Management of pancreatic leak and haemorrhage is complex with high mortality rates. In this study, the results of completion pancreatectomy which was performed as a last resort option were analysed. PATIENTS AND METHODS: 25 patients who had completion pancreatectomy from among 677 patients who had pancreatoduodenectomy or distal pancreatectomy over a period of 18 years were analysed in terms of the indications for completion pancreatectomy, outcome and survival data. RESULTS: Indications for completion pancreatectomy include pancreatic leak in 12 patients (48%), both bleeding and pancreatic leak in 8 (32%), and haemorrhage alone in 5 (20%) patients. 18 (72%) patients also had splenectomy. Median ITU stay was 4 and 8 days for those who survived and died post-completion pancreatectomy, respectively. 36% patients had septicaemia and 32% patients had multiple organ failure. 12 patients survived the operation with a median survival of 52 months. CONCLUSION: 25 (3.6%) patients required surgical intervention for pancreatic complications. The incidence of splenectomy was 84.6% in those who died after completion pancreatectomy compared to 58.3% of those who survived (Fisher's exact test two-sided 0.20). Despite significant morbidity and mortality, completion pancreatectomy has a role in the management of post-pancreatic surgical complications.