T. Chapelle

Fibrous intimal thickening at implantation as a risk factor for the outcome of cadaveric renal allografts.

BACKGROUND During the past decade, the donor age of cadaveric renal allografts steadily increased. Because cerebrovascular injury is the main cause of death in this donor population, an increased prevalence of atherosclerotic lesions in the retrieved grafts could be anticipated. In a prospective study, we investigated the predictive value of morphologic lesions at implantation for the functional and morphologic outcome of cadaveric renal allografts at 1 1/2 years. METHODS In 50 consecutive adult recipients of a cadaveric renal allograft, under cyclosporine-based regimen, implantation biopsies and subsequent protocol biopsies at 18 months were performed, and morphometrically analyzed for the extent of glomerulosclerosis, interstitial fibrosis, and atherosclerosis. Risk factors were assessed at implantation and during the subsequent observation period of 18 months. Endpoints for this study were: the 24-hr creatinine clearance (normalized for body surface area) and the fractional interstitial volume at 1 1/2 years. RESULTS In multivariate analysis, fibrous intimal thickening at implantation (FIT) was the main determinant of the functional and morphologic outcome at 1 1/2 years. FIT represented a relative risk of 4.55 for interstitial fibrosis (95% CI=1.855-11.138), and 1.89 for impaired renal function (95% CI=1.185-3.007) at 1 1/2 years. FIT adversely affected fractional interstitial volume at 1 1/2 years (34.3 vs. 27.7%, P=0.004), as well as renal function (54 vs. 68 ml/min/1.73 m2, P=0.028). CONCLUSIONS Fibrous intimal thickening at implantation is a determinant risk factor for the functional and morphologic outcome of cadaveric renal allografts at 1 1/2 years.

Tacrolimus-related polyneuropathy: Case report and review of the literature

Patients, in particular recipients of orthotopic liver transplants, receiving the immunosuppressant tacrolimus (FK-506), are at risk for developing central neurotoxic adverse events. We report the occurrence of a tacrolimus-induced peripheral neurotoxic event, i.e. pure motor axonal polyneuropathy of the lower limbs in a 44-year-old woman, 9 days after combined orthotopic liver and pancreas transplantation. She was treated for 5 days with intravenous immunoglobulins. Partial recovery followed over months to years. An overview of all 11 reported FK506-associated polyneuropathies is given.

Perforated Duodenal Ulcer After Laparoscopic Gastric Bypass

A patient with a history of a laparoscopic gastric bypass presented with a perforated duodenal ulcer. The ulcer was laparoscopically oversewn, and an omentoplasty was performed. Postoperatively, a broad spectrum antibiotic and a proton pump inhibitor were administrated. Several questions arise regarding the diagnosis and treatment of duodenal ulcers after gastric bypass. What are the diagnostic tools to detect a duodenal ulcer, and how should Helicobacter pylori be diagnosed after gastric bypass? The key question is whether the bypassed stomach should be resected as a definitive treatment for complicated duodenal ulcers.

Future remnant liver function estimated by combining liver volumetry on magnetic resonance imaging with total liver function on 99mTc-mebrofenin hepatobiliary scintigraphy: can this tool predict post-hepatectomy liver failure?

INTRODUCTION Posthepatectomy liver failure (PHLF) is a major complication after hepatectomy with a high mortality rate and is likely to happen in insufficient liver remnant. We hypothesize that assessment of the estimated future liver remnant function (eFLRF), combining future remnant liver volume (FLRV) with total liver function (TLF), is an accurate formula for prediction of PHLF. METHODS 88 patients undergoing hepatectomy were included. The ratio of the future liver remnant volume (FLRV%) was measured on MRI. TLF was estimated by liver clearance of (99m)Technetium (Tc)-mebrofenin on hepatobiliary scintigraphy (HBS). eFLRF was calculated by multiplying FLRV% by TLF. Cut-off values of FLRV% and eFLRF predicting PHLF, were defined by receiver-operating-characteristic (ROC) analysis. RESULTS PHLF occurred in 12 patients (13%). Perioperative mortality was 5/12 (41%). Multivariate analysis showed that FLRV% cut off at 40% was not an independent predictive factor. eFLRF cut off at 2.3%/min/m(2) was the only independent predictive factor for PHLF. For FLRV% vs. eFLRF, positive predictive value was 41% vs. 92% and Odds Ratio 26 vs. 836. CONCLUSION FRLF measured by combining FLRV% and TLF is a more valuable tool to predict PHLF than FLRV% alone. The cutoff of eFLRF can be used in clinical decision making.

Multisciplinary management of patients with liver metastasis from colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Surgery, radiotherapy and chemotherapy have been till now the main therapeutic strategies for disease control and improvement of the overall survival. Twenty-five per cent (25%) of CRC patients have clinically detectable liver metastases at the initial diagnosis and approximately 50% develop liver metastases during their disease course. Twenty-thirty per cent (20%-30%) are CRC patients with metastases confined to the liver. Some years ago various studies showed a curative potential for liver metastases resection. For this reason some authors proposed the conversion of unresectable liver metastases to resectable to achieve cure. Since those results were published, a lot of regimens have been studied for resectability potential. Better results could be obtained by the combination of chemotherapy with targeted drugs, such as anti-VEGF and anti-EGFR monoclonal antibodies. However an accurate selection for patients to treat with these regimens and to operate for liver metastases is mandatory to reduce the risk of complications. A multidisciplinary team approach represents the best way for a proper patient management. The team needs to include surgeons, oncologists, diagnostic and interventional radiologists with expertise in hepatobiliary disease, molecular pathologists, and clinical nurse specialists. This review summarizes the most important findings on surgery and systemic treatment of CRC-related liver metastases.

Simultaneous Kidney-Parathyroid Allotransplantation From a Single Donor After 20 Years of Tetany: A Case Report

Persistent hypocalcemia after total parathyroidectomy and autotransplantation is rare and occasionally has been treated using allotransplantation of parathyroid tissue. We present the case of a 32-year-old woman with terminal renal failure who at age 5 years underwent a first renal transplantation from a brain-dead donor. The graft was lost as a result of acute rejection. Tertiary hypoparathyroidism developed, which was treated with total parathyroidectomy and implantation in the forearm of a standardized amount of parathyroid tissue. The graft failed, and hypoparathyroidism developed. Despite a second implantation of cryopreserved autologous tissue, severe hypocalcemia persisted with a tendency for tetany. Although the patient was highly dependent on high-dose vitamin D(3) (tacalcitol) and calcium supplements, regular paresthesias and tetany developed. At age 9 years, the patient underwent a second renal transplant from a living related donor (her mother). After 18 years, the graft was lost as a result of chronic cyclosporine toxicity and angiosclerosis. Four years later, the patient underwent combined kidney and parathyroid transplantation from a local brain-dead donor. Preservation of the parathyroid glands was in University of Wisconsin solution, with cold ischemia time of 14 hours. Directly after the renal transplantation, parathyroid transplantation was performed, with implantation in the forearm of the total amount of donor parathyroid tissue. Postoperatively, there was recovery of parathyroid function, and the patient was able to discontinue vitamin D and calcium supplements after more than 20 years.

Effect of immunosuppression on damage, leukocyte infiltration, and regeneration after servere warm ischemia/reperfusion renal injury

BACKGROUND Post-ischemia/reperfusion (I/R) damage, accompanied by leukocyte infiltration, is unavoidable in renal transplantation, as is the need for immunosuppressive treatment. Influence of immunosuppressive treatment on post-I/R renal damage, nonalloimmune cellular infiltration, and regeneration is not well studied. METHODS Uninephrectomized inbred LEW rats were submitted to warm renal ischemia of 45 minutes/60 minutes, and received different immunosuppressive regimens: cyclosporine (CsA) 10 mg/kg/day subcutaneously in the neck daily, or mycophenolate mofetil (MMF) 20 mg/kg/day by daily oral gavage. Control animals underwent sham operation (unilateral nephrectomy) with immunosuppressive treatment or ischemia with vehicle administration. In addition the effect of MMF/mycophenolic acid (MPA) on renal tubule cell proliferation in culture was studied with bromodeoxyuridine incorporation. RESULTS The post-I/R interstitial cellular infiltration/proliferation consisted mainly of mononuclear leukocytes [first monocytes/macrophages (Mo/MPhi) followed by CD4+ cells]. This mononuclear cell infiltration became apparent 24 hours after injury at the time of acute tubular necrosis, and was most prominent during the phase of regeneration. Severe I/R combined with CsA aggravated morphologic damage and dysfunction, without effect on tubular cell proliferation and tubular regeneration. Early leukocyte infiltration was qualitatively and quantitatively comparable to control animals, yet decreased moderately later in time. In contrast, MMF in combination with severe I/R did not influence initial morphologic damage and dysfunction. Although the initial leukocyte infiltration was comparable to control animals, the subsequent mononuclear cell accumulation, especially CD4 T cells decreased dramatically during MMF treatment. This was concomitant with a decrease of tubular cell proliferation and hence tubular regeneration. Increasing MPA concentrations in renal tubular cell culture caused a significant decrease in total cell number, and an almost arrest of bromodeoxyuridine incorporation, as measurement of cell proliferation. CONCLUSION Immunosuppressive treatment with CsA or MMF affected significantly and in a different manner post-I/R renal morphologic damage, interstitial leukocyte, accumulation and regeneration.

Diabetes mellitus and pre-diabetes are frequently undiagnosed and underreported in patients referred for pancreatic surgery. A prospective observational study

OBJECTIVE Previous reports on the prevalence of diabetes in pancreatic cancer and chronic pancreatitis patients are based on inconsistent and equivocal criteria. The objective of this study is to prospectively assess with conclusive methods the preoperative glycaemic status of patients undergoing pancreatic surgery. We hypothesise that most of those patients are unaware of these disturbances in glycaemic status and that the prevalence is underestimated. METHODS During the last 2 years, patients referred for pancreatic surgery and without history of diabetes underwent a prospective preoperative screening with an oral glucose tolerance test (OGTT) and determination of the glycated haemoglobin level (HbA1c). The American Diabetes Associations criteria for diabetes and pre-diabetes were used. Beta-cell function and insulin sensitivity were calculated using HOMA2 indices. Impact on surgical policy has been scored. RESULTS 99 patients were screened, 25 had a history of diabetes. The other 74 underwent an OGTT and HbA1c determination. Only 29.7% (22/74) had a normal glucose metabolism, while 8.1% (6/74) had impaired fasting glucose, 21.6% (16/74) had impaired glucose tolerance, 6.7% (5/74) had a combination of both, and 33.8% (25/74) had undiagnosed diabetes. In 15.2% (15/99) of the patients, this preoperative assessment had an impact on surgical policy. CONCLUSIONS 77.7% of patients referred for pancreatic surgery had some degree of (pre-)diabetes. In 70.3% of patients without a history of diabetes, these disturbances in glucose metabolism are a new finding. Physicians involved in pancreatic surgery should be aware of the frequently undiagnosed (pre-)diabetes and actively check for it. This prevalence is underestimated.

Does Kidney Donor Risk Index implementation lead to the transplantation of more and higher-quality donor kidneys?

Abstract Background The Kidney Donor Risk Index (KDRI) is a quantitative evaluation of the quality of donor organs and is implemented in the US allocation system. This single-centre study investigates whether the implementation of the KDRI in our decision-making process to accept or decline an offered deceased donor kidney, increases our acceptance rate. Methods From April 2015 until December 2016, we prospectively calculated the KDRI for all deceased donor kidney offers allocated by Eurotransplant to our centre. The number of the transplanted versus declined kidney offers during the study period were compared to a historical set of donor kidney offers. Results After implementation of the KDRI, 26.1% (75/288) of all offered donor kidneys were transplanted, compared with 20.7% (136/657) in the previous period (P < 0.001). The median KDRI of all transplanted donor kidneys during the second period was 0.97 [Kidney Donor Profile Index (KDPI) 47%], a value significantly higher than the median KDRI of 0.85 (KDPI 34%) during the first period (P = 0.047). A total of 68% of patients for whom a first-offered donor kidney was declined during this period were transplanted after a median waiting time of 386 days, mostly with a lower KDRI donor kidney. Conclusions Implementing the KDRI in our decision-making process increased the transplantation rate by 26%. The KDRI can be a supportive tool when considering whether to accept or decline a deceased donor kidney offer. More data are needed to validate this score in other European centres.

Prediction of delayed graft function using different scoring algorithms: A single-center experience

AIM To compare the performance of 3 published delayed graft function (DGF) calculators that compute the theoretical risk of DGF for each patient. METHODS This single-center, retrospective study included 247 consecutive kidney transplants from a deceased donor. These kidney transplantations were performed at our institution between January 2003 and December 2012. We compared the occurrence of observed DGF in our cohort with the predicted DGF according to three different published calculators. The accuracy of the calculators was evaluated by means of the c-index (receiver operating characteristic curve). RESULTS DGF occurred in 15.3% of the transplants under study. The c index of the Irish calculator provided an area under the curve (AUC) of 0.69 indicating an acceptable level of prediction, in contrast to the poor performance of the Jeldres nomogram (AUC = 0.54) and the Chapal nomogram (AUC = 0.51). With the Irish algorithm the predicted DGF risk and the observed DGF probabilities were close. The mean calculated DGF risk was significantly different between DGF-positive and DGF-negative subjects (P < 0.0001). However, at the level of the individual patient the calculated risk of DGF overlapped very widely with ranges from 10% to 51% for recipients with DGF and from 4% to 56% for those without DGF. The sensitivity, specificity and positive predictive value of a calculated DGF risk ≥ 30% with the Irish nomogram were 32%, 91% and 38%. CONCLUSION Predictive models for DGF after kidney transplantation are performant in the population in which they were derived, but less so in external validations.