Jens Brockmann

Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial.

Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor–free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor–free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ⩽60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.

Liver Transplantation for Hilar Cholangiocarcinoma: A German Survey

BACKGROUND The present study reports a German survey addressing outcomes in nonselected historical series of liver transplantation (OLT) for hilar cholangiocarcinoma (HL). PATIENTS AND METHODS We sent to all 25 German transplant centers performing OLT a survey that addressed (1) the number of OLTs for HL and the period during which they were performed; (2) the incidence of HL diagnosed prior to OLT/rate of incidental HL (for example, in primary sclerosing cholangitis); (3) tumor stages according to Union Internationale Centre le Cancer; (4) patient survival; and (5) tumor recurrence rate. RESULTS Eighty percent of centers responded, reporting 47 patients who were transplanted for HL. Tumors were classified as pT2 (25%), pT3 (73%), or pT4 (2%). HL was diagnosed incidentally in 10% of cases. A primary diagnosis of PSC was observed in 16% of patients. Overall median survival was 35.5 months. When in-hospital mortality (n = 12) was excluded, the median survival was 45.4 months, corresponding to 3- and 5-year survival rates of 42% and 31%, versus 31% and 22% when in-hospital mortality was included. HL recurred in 34% of cases. Three- and 5-year survivals for the 15 patients transplanted since 1998 was 57% and 48%, respectively. Median survival ranged from 20 to 42 months based on the time period (P = .014). CONCLUSIONS The acceptable overall survival, the improved results after careful patient selection since 1998, and the encouraging outcomes from recent studies all suggest that OLT may be a potential treatment for selected cases of HL. Prospective multicenter randomized studies with strict selection criteria and multimodal treatments seem necessary.

Screening for clostridiae and treatment of clostridiae contamination to prevent fatal infections after liver transplantation.

CLOSTRIDIAE ARE anaerobic, gram-positive, sporeforming rods, which inhabit the gastrointestinal tract of healthy subjects. With a 5.9% incidence, contamination of the bilary tract with C. perfringens is not a rare finding in patients undergoing bilary surgery. In a report of 286 isolates obtained from bile specimens 27 were identified as C. perfringens, which can cause severe infections with gas gangrene, sepsis, and hemolysis. The outcome is fatal in most cases despite surgical and antbiotic treatment, particularly for liver transplant recipients receiving immunosuppressive therapy. Survival is possible when the focus can be eliminated by early retransplantation.

Therapeutical options in ureteral necrosis following kidney transplantation.

The necrosis of the ureter is a seldom but serious problem following kidney transplantation (KTX). Presenting a graft with primary good function, an ureteral necrosis can contribute to an impairment of the function and lead to a graft loss. Regardless of the reason for necrosis consequent therapy is necessary to safe kidney function. First-line therapy still is the re-ureterocystostomie or uretero-ureterostomie using the recipients ipsilateral ureter. If these alternatives do not work an ileum-interponate may be an option to safe graft function in those infrequent cases. We report our experience with an ileum interponate used for ureteral reconstruction. A 58-year-old patient was grafted using the left kidney of a 59-year-old donor with a cold ischaemic time of 9.5 h. The graft had normal vascular and ureteral anatomy, there was no evidence of a missed upper or lower polar artery. Vascular anastomoses were performed end-to-side to the external iliac vein and artery. The uretero-neocystostomy was performed by the modified LichGregoire technique after shortening the ureter. Early postoperative course showed delayed graft function with necessity of dialysis treatment for six times due to preexisting severe nephrosclerosis of the graft. Serum creatinine measured 2.3 mg/dl at the time of discharge. After 4 months, patient showed a pararenal urinoma in ultrasound and computerized tomography (CT) scan. A cystoscopy revealed necrosis of the distal ureter. Operative revision showed a leakage of urine running from the renal pelvis through an urinom into the bladder. Re-ureterocystostomie was not possible with necrotic ureter and patient’s own ureter was missing after nephrectomy. Consequently, an ileum interponate was carried out. The pyelo-ileostomie was done using a continuous suture line, the distal ileum was sutured using an interrupted suture line; an external ureteral splint (7 French) was inserted. The postoperative course was uneventful. Kidney function showed to be stable with a minimum creatinine of 2.0 mg/dl. Early postoperative pyelo-cystografy ruled out any leakage from pyelo-ileostomie and ileo-cystostomie. Eighteen months post-transplantation, 14 months postileum interposition kidney function is excellent with creatinine of 2.0 mg/dl. Ureteral obstruction of different origins may cause the need for a reconstructive procedure to prevent damage from the graft. In the nontransplanted patients, ureteral obstruction is mostly based on idiopathic or secondary retroperitoneal fibrosis due to radiotherapy or surgery for malignant tumours [1]. Ileal-ureteral substitution in these patients was done mostly in cases where other possibilities (ureteral re-anastmosis, boari flap, psoas-hitch with ureteral re-implantation) were not feasible and led to an improved technique over the years [1,2]. Long-term follow-up in the nontransplanted patients showed satisfactory results so that this technique was transferred to the grafted patients [3,4] (Figs 1 and 2). The incidence of ureteral problems vary in different transplant centres from 2% to 20% [5,6,7]. The main reasons are poor graft harvesting techniques or surgical problems at the time of implantation. High-dose steroid therapy [7] and chronic rejection [8] are further risk factors. Diagnosis usually can be matched by ultrasound, cystografy and cystoscopy as well as nuclear isotope scanning or MR urografy. Ureteral complications may on the one hand be splitted into leakage and stenosis problems, on the other hand into problems of the proximal and distal ureter. However, as blood supply of the distal