The Role of Immunosuppression for Recurrent Cholangiocellular Carcinoma after Liver Transplantation.

Liver transplantation (LT) for cholangiocarcinoma (CCA), or biliary tract cancer (BTC), remains controversial regarding high recurrence rates and poor prognosis. Oncological follow-up may benefit from tumor-inhibiting properties of mTOR inhibitors (mTORI), shown with improved survival for recurrent hepatocellular carcinoma (HCC) patients after LT. The aim of this study was to investigate the recurrence and survival in relation to tumor type and type of immunosuppression (IS). LT patients with CCA or mixed HCC/CCA (mHCC/CCA) (n = 67) were retrospectively analyzed. Endpoints were the time from LT to recurrence (n = 44) and survival after recurrence. Statistically significant impairment in survival for recurrent CCA (rCCA) was shown in patients not eligible for surgical resection (HR 2.46 (CI: 1.2−5.1; p = 0.02). Histological proven grading >1 and N1 status at initial transplantation were associated with impaired survival (HR 0.13 (CI: 0.03−0.58); p < 0.01 and HR 3.4 (CI: 1.0−11.65); p = 0.05). Reduced IS after tumor recurrence improved survival (HR 4.2/CI: 1.3−13.6; p = 0.02). MTORI initiation before recurrence or after had no significant impact on survival. Our data thereby indicate, similar to findings in recurrent HCC after LT, that patients with rCCA after LT benefit from a reduction in IS upon recurrence.

Definitions of Computer-Assisted Surgery and Intervention, Image-Guided Surgery and Intervention, Hybrid Operating Room, and Guidance Systems: Strasbourg International Consensus Study.

OBJECTIVE: To develop consensus definitions of image-guided surgery, computer-assisted surgery, hybrid operating room, and surgical navigation systems. SUMMARY BACKGROUND DATA: The use of minimally invasive procedures has increased tremendously over the past 2 decades, but terminology related to image-guided minimally invasive procedures has not been standardized, which is a barrier to clear communication. METHODS: Experts in image-guided techniques and specialized engineers were invited to engage in a systematic process to develop consensus definitions of the key terms listed above. The process was designed following review of common consensus-development methodologies and included participation in 4 online surveys and a post-surveys face-to-face panel meeting held in Strasbourg, France. RESULTS: The experts settled on the terms computer-assisted surgery and intervention, image-guided surgery and intervention, hybrid operating room, and guidance systems and agreed-upon definitions of these terms, with rates of consensus of more than 80% for each term. The methodology used proved to be a compelling strategy to overcome the current difficulties related to data growth rates and technological convergence in this field. CONCLUSIONS: Our multidisciplinary collaborative approach resulted in consensus definitions that may improve communication, knowledge transfer, collaboration, and research in the rapidly changing field of image-guided minimally invasive techniques.

Protective effects of coffee consumption following liver transplantation for hepatocellular carcinoma in cirrhosis.

BACKGROUND: Increasing evidence suggests that coffee consumption might protect against hepatocellular carcinoma (HCC) and liver cirrhosis-associated death risk. Caffeine is a natural antagonist to extracellular adenosine and exhibits experimental tumoricidal activity. AIM: To evaluate if coffee consumption has beneficial effects on HCC recurrence after orthotopic liver transplantation (OLT). METHODS: Coffee consumption of patients before and after OLT for HCC was assessed and correlated with HCC recurrence. HepG2 cells were analysed for proliferation and metastasis potential after treatment with adenosine, in the presence or absence of adenosine receptor antagonists. Expression of adenosine receptors was determined, and known adenosine-mediated cancer pathways inclusive of MAPK and NF-kappa B were tested. RESULTS: Ninety patients underwent OLT for HCC. Sixteen (17.8%) patients experienced HCC recurrence after median time of 11.5 months (range 1-40.5). For overall survival postoperative coffee intake emerged as major factor of hazard reduction in a multivariate analysis (HR = 0.2936, 95% CI = 0.12-0.71, P = 0.006). Those with such postoperative coffee intake (≥3 cups per day) had a longer overall survival than those who consumed less or no coffee: M = 11.0 years, SD = 0.52 years vs. M = 7.48 years, SD = 0.76 years = 4.7, P = 0.029). CONCLUSIONS: Coffee consumption is associated with a decreased risk of HCC recurrence and provides for increased survival following OLT. We suggest that these results might be, at least in part, associated with the antagonist activity of caffeine on adenosine-A2AR mediated growth-promoting effects on HCC cells.

Hilar en bloc resection for hilar cholangiocarcinoma in patients with limited liver capacities-preserving parts of liver segment 4.

BACKGROUND: A right trisectionectomy with portal vein resection represents the conventional approach for hilar cholangiocarcinoma. Here, we present a technical modification of hilar en bloc resection in order to increase the remnant volume by partially preserving liver segment 4. METHODS: The caudal parenchymal dissection line starts centrally between the left lateral and left medial segments. Cranially, the resection line switches to the right towards Cantlie's line and turns again upwards perpendicularly. Hence, segment 4a and subtotal segment 4b are partially preserved by this novel technique. The left hepatic duct is dissected at the segmental ramification and reconstruction is performed as a single hepaticojejunostomy. The feasibility of the novel parenchyma-sparing approach for hilar cholangiocarcinoma was proven in a case series and medical records were reviewed retrospectively. RESULTS: Ten patients (6 male, 4 female) underwent segment 4 partially preserving right trisectionectomy for hilar cholangiocarcinoma. Estimated future liver remnant volume was significantly increased (FLRV 38.3%), when compared to standard right trisectionectomy (FLRV 23.9%; p < 0.01). Three of 10 liver resections were associated with major surgical complications (≥IIIb; n = 3); categorized according to the Dindo-Clavien classification. No patient died due to complications associated with postoperatively impaired liver function. Tumor-free margins could be achieved in 8 patients while median overall survival and disease-free survival were 547 and 367 days, respectively. CONCLUSION: This novel parenchyma-sparing modification of hilar en bloc resection by partially preserving segment 4 allows to safely increase the remnant liver volume without neglecting principles of local radicality.

Angiogenic miRNAs, the angiopoietin axis and related TIE2-expressing monocytes affect outcomes in cholangiocarcinoma.

BACKGROUND: Tumour angiogenesis is modulated on both an epigenetic and protein level and has potential implications for immune cell responses. However, the importance of related angiogenic biomarkers in cholangiocarcinoma (CCA) is unknown. This study assessed human CCA samples for the expression of angiogenesis-associated microRNAs, angiopoietins (Angs) and monocytes expressing the Ang-receptor, TIE2, with regards to prognostic significance after liver resection. METHODS: Angiogenic miRNAs were analysed in frozen samples of intrahepatic CCA (iCC; n = 43) and hilar CCA (HC; n = 45). Ang-1 and Ang-2, as well as TIE2-expressing monocytes (TEMs), were detected in paraffin-embedded iCC sections (n = 88). MiRNA expression and the abundance of TEMs and Angs were correlated with clinicopathological characteristics and survival. RESULTS: MiR-126 was downregulated in 76.7% of all CCA samples, with high relative expression associated with smaller tumours and reduced lymph node metastasis. High Ang-1 expression was associated with less lymphangiosis carcinomatosa and better histological grading (all p < 0.05). The absence of TEMs in iCC correlated with elevated CA19-9 levels. High relative miR-126 and low miR-128 levels were associated with improved survival in iCC and HC, respectively (all p < 0.05). High miR-126, low miR-128 and TEMs were independent prognostic factors for recurrence-free and overall survival (all p < 0.05). CONCLUSIONS: These results suggest that angiogenic miRNAs, Angs and TEMs are of prognostic value in CCA. In addition to the possible functional links between angiogenic miRNA expression profiles, Angs and immune-cell responses by TEMs, these data have clinical implications as novel diagnostic tools.

Correction to: Hilar en bloc resection for hilar cholangiocarcinoma in patients with limited liver capacities-preserving parts of liver segment 4.

[This corrects the article DOI: 10.1007/s10353-017-0507-8.].

Tumor necrosis and infiltrating macrophages predict survival after curative resection for cholangiocarcinoma.

Background. Tumor necrosis as well as tumor-associated macrophages (TAMs) in the tumor invasive front (TIF) have been suggested to have a prognostic value in selected solid tumors, inclusive hilar cholangiocarcinoma. However, little is known regarding their influence on tumor progression and prognosis in intrahepatic cholangiocarcinoma (iCC). Methods. We analyzed surgically resected tumor specimens of human iCC (n = 88) for distribution and localization of TAMs, as defined by expression of CD68, formation of necrosis and extent of peritumoral fibrosis. Abundance of TAMs, tumor necrosis and grade of fibrosis were assessed immunohistochemically and histologically and correlated with clinicopathological characteristics, tumor recurrence and patients' survival. Statistical analysis was performed using SPSS software. Results. Patients with tumors characterized by low levels of TAMs in TIF or necrosis showed a significantly decreased 1-, 3- and 5-y recurrence-free survival and a significantly decreased overall survival, when compared with patients with tumors showing high levels of TAMs in TIF or no necrosis. Patients with high density of TAMs in TIF showed significantly lower incidence of tumor recurrence, as well (p < 0.05). Absence of tumor necrosis and TAMs in TIF were confirmed as independent prognostic variables in the multivariate survival analysis (all p < 0.05). Conclusions. High levels of TAMs in TIF or absence of histologic tumor necrosis are associated with a significantly improved recurrence-free and overall survival of patients with iCC. These results suggest TAMs and necrosis as valuable prognostic markers in routine histopathologic evaluation, and might indicate more individualized therapeutic strategies.

Prognostic Significance of Tumor Necrosis in Hilar Cholangiocarcinoma.

BACKGROUND: Tumor necrosis and peritumoral fibrosis have both been suggested to have a prognostic value in selected solid tumors. However, little is known regarding their influence on tumor progression and prognosis in hilar cholangiocarcinoma (HC). METHODS: Surgically resected tumor specimens of HC (n = 47) were analyzed for formation of necrosis and extent of peritumoral fibrosis. Tumor necrosis and grade of fibrosis were assessed histologically and correlated with clinicopathological characteristics, tumor recurrence, and patients' survival. Univariate Kaplan-Meier analysis and a stepwise multivariable Cox regression model were applied. RESULTS: Mild peritumoral fibrosis was evident in 12 tumor samples, moderate peritumoral fibrosis in 20, and high-grade fibrosis in 15. Necrosis was evident in 19 of 47 tumor samples. Patients with tumors characterized by necrosis showed a significantly decreased 5-year recurrence-free survival (37.9 vs. 25.7 %; p < .05) and a significantly decreased 5-year overall survival (42.6 vs. 12.4 %; p < .05), when compared with patients with tumors showing no necrosis. R status, tumor recurrence, and tumor necrosis were of prognostic value in the univariate analysis (all p < .05). Multivariate survival analysis confirmed tumor necrosis (p = .038) as the only independent prognostic variable. CONCLUSIONS: The assessment of tumor necrosis appears as a valuable additional prognostic tool in routine histopathological evaluation of HC. These observations might have implications for monitoring and more individualized multimodal therapeutic strategies.

Prognostic significance of TIE2-expressing monocytes in hilar cholangiocarcinoma.

BACKGROUND AND OBJECTIVES: Angiopoietins (Angs) play a pivotal role in angiogenesis and inflammation, and are associated with prognosis in malignancies. Monocyte express Ang-receptor TIE2 and correlate with prognosis in cancer. We aimed to investigate the prognostic value of Angs and TIE2-expressing monocytes (TEMs) in cholangiocarcinoma. METHODS: We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution of Angs (Ang 1/Ang 2) and TEMs, as defined by co-expression of CD14 and Ang receptor TIE2. Ang expression and abundance of TEMs were correlated with clinicopathologic characteristics, tumor recurrence and patients' survival. RESULTS: High Ang 1 expression correlated with reduced metastasis (P < 0.05). Patients characterized by invading Ang-receptor bearing TEMs in tumor showed lower tumor recurrence (P < 0.05). Furthermore, TEMs in tumor and tumor invasive front correlated with increased survival (P < 0.05). TEMs in tumor invasive front were confirmed as independent prognosticator in multivariate survival analysis (P < 0.05). CONCLUSIONS: High Ang 1 expression in hilar cholangiocarcinoma and infiltration of TEMs defines a subgroup of patients with beneficial tumor characteristics and prolonged survival. Besides suggested functional links between Ang expression and recruitment of TEMs, our data have possible clinical implications as novel diagnostic tools. J. Surg. Oncol. 2016;114:91-98. © 2016 Wiley Periodicals, Inc.

microRNA signatures in peripheral blood fail to detect acute cellular rejection after liver transplantation.

OBJECTIVE: We investigated whether microRNA signatures in whole blood samples are associated with acute cellular rejection (ACR) after liver transplantation. MATERIALS AND METHODS: Blood samples were collected using Paxgene technology and analyzed by microarrays and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: microRNA signatures failed to distinguish between 19 patients with ACR and 16 controls. Let-7b-5p and let-7c were upregulated in a subgroup of patients with ACR during the 6th and 7th postoperative days but failed in an independent validation of 20 patients. CONCLUSION: microRNA signatures in whole blood processed by Paxgene technology are not suited for the detection of ACR after liver transplantation.

Prognostic Accuracy of the Seventh Edition of the TNM Classification Compared with the Fifth and Sixth Edition for Distal Cholangiocarcinoma.

BACKGROUND: The TNM classification for distal cholangiocarcinoma was first introduced in the 7th edition, which was published in 2009; however, prognostic accuracy compared with the 5th and 6th editions has not yet been evaluated and requires validation. METHODS: A prospective histological database of patients with distal bile duct cancer was analyzed, and histological parameters and stage of the distal cholangiocarcinoma were assessed according to the 5th, 6th, and 7th editions of the TNM classification. RESULTS: Between 1994 and 2012, a total of 516 patients underwent pancreatic head resection, of whom 59 patients (11.4 %) experienced histologically confirmed distal cholangiocarcinoma. The median overall survival time was 22.2 months (13.1-31.4). Tumor recurrence occurred in 23 patients after a median disease-free survival time of 14.1 months. The 7th edition showed a monotonicity of all gradients, with a stepwise increase of mortality related to a stepwise increase of tumor stage (log-rank test; p < 0.05) demonstrating best discrimination of all tested editions [area under the receiver operating characteristic curve (AUC) 0.82; 95 % CI 0.70-0.95; p = 0.012]. The discrimination rate was low for the 5th (AUC 0.67; 95 % CI 0.42-0.91; p = 0.18) and 6th editions (AUC 0.70; 95 % CI 0.47-0.93; p = 0.11), while the log-rank test did not reach statistical significance. On multivariate analysis, lymph node involvement and positive resection margins were positive and independent predictors of inferior survival (p < 0.05). CONCLUSIONS: The 7th edition of the TNM classification was favorable in terms of predicting outcome, and generated a monotonicity of all grades. Strikingly, the 7th edition, but not the 5th and 6th editions, was of prognostic significance to predict outcome.

Prognostic significance of macrophage invasion in hilar cholangiocarcinoma.

BACKGROUND: Tumor-associated macrophages (TAMs) promote tumor progression and have an effect on survival in human cancer. However, little is known regarding their influence on tumor progression and prognosis in human hilar cholangiocarcinoma. METHODS: We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution and localization of TAMs, as defined by expression of CD68. Abundance of TAMs was correlated with clinicopathologic characteristics, tumor recurrence and patients' survival. Statistical analysis was performed using SPSS software. RESULTS: Patients with high density of TAMs in tumor invasive front (TIF) showed significantly higher local and overall tumor recurrence (both ρ < 0.05). Furthermore, high density of TAMs was associated with decreased overall (one-year 83.6% vs. 75.1%; three-year 61.3% vs. 42.4%; both ρ < 0.05) and recurrence-free survival (one-year 93.9% vs. 57.4%; three-year 59.8% vs. 26.2%; both ρ < 0.05). TAMs in TIF and tumor recurrence, were confirmed as the only independent prognostic variables in the multivariate survival analysis (all ρ < 0.05). CONCLUSIONS: Overall survival and recurrence free survival of patients with hilar cholangiocarcinoma significantly improved in patients with low levels of TAMs in the area of TIF, when compared to those with a high density of TAMs. These observations suggest their utilization as valuable prognostic markers in routine histopathologic evaluation, and might indicate future therapeutic approaches by targeting TAMs.

CD44 and CXCL9 serum protein levels predict the risk of clinically significant allograft rejection after liver transplantation.

The diagnosis of acute cellular rejection (ACR) after liver transplantation is based on histological analysis of biopsies because noninvasive biomarkers for allograft rejection are not yet established for clinical routines. CD31, CD44, and chemokine (C-X-C motif) ligand (CXCL) 9 have previously been described as biomarkers for cross-organ allograft rejection. Here, we assessed the predictive and diagnostic value of these proteins as serum biomarkers for clinically significant ACR in the first 6 months after liver transplantation in a prospective study. The protein levels were measured in 94 patients immediately before transplantation, at postoperative days (PODs) 1, 3, 7, and 14 and when biopsies were performed during episodes of biochemical graft dysfunction. The CD44 serum protein levels were significantly lower at POD 1 in patients who experienced histologically proven ACR in the follow-up compared with patients without ACR (P < 0.001). CXCL9 was significantly higher before transplantation (P = 0.049) and at POD 1 (P < 0.001) in these patients. Low CD44 values (cutoff, <200.5 ng/mL) or high CXCL9 values (cutoff, >2.7 ng/mL) at POD 1 differentiated between rejection and no rejection with a sensitivity of 88% or 60% and a specificity of 61% or 79%, respectively. The combination of both biomarker cutoffs at POD 1 had a positive predictive value of 91% and a negative predictive value of 67% for clinically significant ACR. Moreover, CD44 was significantly lower at the time of ACR (P < 0.001) and differentiated the rejection group from patients with graft dysfunction due to other reasons. Our results suggest that CD44 and CXCL9 may serve as predictive biomarkers to identify liver allograft recipients at risk for clinically significant ACR.

Alternative treatment of symptomatic pancreatic fistula.

BACKGROUND: The management of symptomatic pancreatic fistula after pancreaticoduodenectomy is complex and associated with increased morbidity and mortality. We here report continuous irrigation and drainage of the pancreatic remnant to be a feasible and safe alternative to total pancreatectomy. MATERIALS AND METHODS: Between 2005 and 2011, patients were analyzed, in which pancreaticojejunal anastomosis was disconnected because of grade C fistula, and catheters for continuous irrigation and drainage were placed close to the pancreatic remnant. Clinical data were monitored and quality of life was evaluated. RESULTS: A total of 13 of 202 patients undergoing pancreaticoduodenectomy required reoperation due to symptomatic pancreatic fistula. Ninety-day mortality of these patients was 15.3%. Median length of stay on the intensive care unit and total length of stay was 18 d (range 3-45) and 46 d (range 33-96), respectively. Patients with early reoperation (<10 d) had significantly decreased length of stay on the intensive care unit and operation time (P < 0.05). Global health status after a median time of 22 mo (range 6-66) was nearly identical, when compared with that of a healthy control group. Mean follow-up was 44.4 mo (±27.2). Four patients (36.6 %) died during the follow-up period; two patients from tumor recurrence, one patient from pneumonia, and one patient for unknown reasons. CONCLUSIONS: Treatment of pancreatic fistula by continuous irrigation and drainage of the preserved pancreatic remnant is a simple and feasible alternative to total pancreatectomy. This technique maintains a sufficient endocrine function and is associated with low mortality and reasonable quality of life.

Early prediction of survival after open surgical repair of ruptured abdominal aortic aneurysms.

BACKGROUND: Scoring models are widely established in the intensive care unit (ICU). However, the importance in patients with ruptured abdominal aortic aneurysm (RAAA) remains unclear. Our aim was to analyze scoring systems as predictors of survival in patients undergoing open surgical repair (OSR) for RAAA. METHODS: This is a retrospective study in critically ill patients in a surgical ICU at a university hospital. Sixty-eight patients with RAAA were treated between February 2005 and June 2013. Serial measurements of Sequential Organ Failure Assessment score (SOFA), Simplified Acute Physiology Score II (SAPS II) and Simplified Therapeutic Intervention Scoring System-28 (TISS-28) were evaluated with respect to in-hospital mortality. Eleven patients had to be excluded from this study because 6 underwent endovascular repair and 5 died before they could be admitted to the ICU. RESULTS: All patients underwent OSR. The initial, highest, and mean of SOFA and SAPS II scores correlated significant with in-hospital mortality. In contrast, TISS-28 was inferior and showed a smaller area under the receiver operating curve. The cut-off point for SOFA showed the best performance in terms of sensitivity and specificity. An initial SOFA score below 9 predicted an in-hospital mortality of 16.2% (95% CI, 4.3-28.1) and a score above 9 predicted an in-hospital mortality of 73.7% (95% CI, 53.8-93.5, p < 0.01). Trend analysis showed the largest effect on SAPS II. When the score increased or was unchanged within the first 48 h (score >45), the in-hospital mortality rate was 85.7% (95% CI, 67.4-100, p < 0.01) versus 31.6% (95% CI, 10.7-52.5, p = 0.01) when it decreased. On multiple regression analysis, only the mean of the SOFA score showed a significant predictive capacity with regards to mortality (odds ratio 1.77; 95% CI, 1.19-2.64; p < 0.01). CONCLUSION: SOFA and SAPS II scores were able to predict in-hospital mortality in RAAA within 48 h after OSR. According to cut-off points, an increase or decrease in SOFA and SAPS II scores improved sensitivity and specificity.

Independent effects of sham laparotomy and anesthesia on hepatic microRNA expression in rats.

BACKGROUND: Studies on liver regeneration following partial hepatectomy (PH) have identified several microRNAs (miRNAs) that show a regulated expression pattern. These studies involve major surgery to access the liver, which is known to have intrinsic effects on hepatic gene expression and may also affect miRNA screening results. We performed two-third PH or sham laparotomy (SL) in Wistar rats to investigate the effect of both procedures on miRNA expression in liver tissue and corresponding plasma samples by microarray and qRT-PCR analyses. As control groups, non-treated rats and rats undergoing anesthesia only were used. RESULTS: We found that 49 out of 323 miRNAs (15%) were significantly deregulated after PH in liver tissue 12 to 48 hours postoperatively (>20% change), while 45 miRNAs (14%) were deregulated following SL. Out of these miRNAs, 10 miRNAs were similarly deregulated after PH and SL, while one miRNA showed opposite regulation. In plasma, miRNA upregulation was observed for miR-133a and miR-133b following PH and SL, whereas miR-100 and miR-466c were similarly downregulated following anesthesia and surgery. CONCLUSIONS: We show that miRNAs are indeed regulated by sham laparotomy and anesthesia in rats. These findings illustrate the critical need for finding appropriate control groups in experimental surgery.

Selective hypertrophy of the lobus caudatus as a novel approach enabling extended right hepatectomy in the presence of a non-perfused left lateral liver lobe.

INTRODUCTION: Portal vein embolization (PVE) is a well-established technique to enhance functional hepatic reserves of segments II and III before curative extended right hepatectomy for tumors of the right liver lobe. However, an adequate hepatopetal flow of the left lateral portal vein branches is required for a sufficient PVE-associated hypertrophy. CASE REPORT: Here, we report a 65-year old patient suffering from a locally advanced intrahepatic cholangiocarcinoma in the right liver lobe and segment IV. A curative extended right hepatectomy after preoperative PVE of liver segments IV-VIII was initially impossible because of partial thrombosis of the left lateral portal vein branches resulting in an ischemic-type atrophy of segments II and III. However, due to a massive hypertrophy of the caudate lobe following PVE of liver segments IV-VIII, subsequent extended right hepatectomy with intraoperative thrombectomy of segments II and III was made possible. CONCLUSIONS: To our knowledge this is the first case in which an extended right hepatectomy for a liver malignancy, in the presence of atrophic left lateral section, was made possible by a massive PVE-associated hypertrophy of the caudate lobe.

Single-center experience using organs after rescue allocation for pancreas transplant in the eurotransplant region.

OBJECTIVES: Because of the shortage of available organs for transplants, graft allocation polices have been modified recently. This report deals with the effect of using organs after rescue allocation for pancreas transplant in a single center in the Eurotransplant Region to possibly expand the donor pool. MATERIALS AND METHODS: A retrospective analysis was performed. Between 2007 and 2010, thirty-one pancreas transplants were performed at the University Hospital of Leipzig, in Leipzig, Germany. Among these, 7 cases used rescue organs. These organs had been officially offered to, but rejected by, at least 3 consecutive transplant centers. Donor/recipient and clinical/laboratory transplant/posttransplant outcomes from patients receiving rescue organs were collected and were compared with organs from conventional donors. RESULTS: Mean donor age was greater in the rescue organ group than in the conventional donor group (28.3 ± 10.7 y vs 23.0 ± 12.5 y). During follow-up (2.3 ± 0.6 y rescue organ group vs 3.9 ± 1.2 y conventional donor group), patient, kidney, and pancreas graft survival rates were 85% in all 3 categories in the rescue organ group, whereas outcomes for conventional donors were 88%, 85%, and 83%. Incidences of pancreatic graft thrombosis, delayed graft function, acute and late rejection episodes (eg, perioperative complications) were comparable between groups. No differences existed between mean serum urea levels and mean HbA1c levels between groups 2 years after transplant. Whereas 2 years after surgery, mean serum creatinine levels (rescue organ group, 78.8 ± 21.0 µmol/L vs 114.3 ± 28.4 µmol/L in the conventional donor group) showed significant differences between groups. CONCLUSIONS: Results are promising. Further pro-spective studies are warranted to evaluate routine transplant of organs after rescue allocation.

The collateral caval shunt as an alternative to classical shunt procedures in patients with recurrent duodenal varices and extrahepatic portal vein thrombosis.

Upper gastrointestinal bleeding episodes from variceal structures are severe complications in patients with portal hypertension. Endoscopic sclerotherapy and variceal ligation are the treatment options preferred for upper variceal bleeding owing to extrahepatic portal hypertension due to portal vein thrombosis (PVT). Recurrent duodenal variceal bleeding in non-cirrhotic patients with diffuse porto-splenic vein thrombosis and subsequent portal cavernous transformation represent a clinical challenge if classic shunt surgery is not possible or suitable.In this study, we represent a case of recurrent bleeding of duodenal varices in a non-cirrhotic patient with cavernous transformation of the portal vein that was successfully treated with a collateral caval shunt operation.

Immunosuppressive protocol with delayed use of low-dose tacrolimus after aortic transplantation suppresses donor-specific anti-MHC class I and class II antibody production in rats.

BACKGROUND: Arterial allografts are used as vascular conduits in the treatment of prosthetic graft infection. Immunosuppression decreases their rupture risk rate. However, immunosuppression can be unprofitable in florid infection. Previously, we confirmed inhibition of cell-mediated destruction of rat aortic grafts by delayed use of tacrolimus. In this work, we studied the influence of this protocol on the antibody-mediated rejection. MATERIAL AND METHODS: Flow cytometry was used for the retrospective analysis of day 0, 14, and 30 sera obtained from Lewis rat recipients of isogeneic fresh infrarenal aortic grafts (group A) or Brown-Norway rat aortic grafts (group B,C,D) for the presence of donor-specific anti-MHC class I and II antibodies. Tacrolimus in daily dose of 0.2 mg/kg was administered from day 1 to day 30 (group C) or from day 7 to day 30 (group D). RESULTS: Inhibition of fluorescence-labeled anti-BN MHC class I and MHC class II antibodies binding to BN-splenocytes was observed only by day 14 and day 30 sera of allogeneic non-immunosuppressed Lewis rats (group B). The day 30 sera significantly decreased anti-MHC I (42±3%) and anti-MHC II antibody binding (56±3%) compared to day 0 (76±9%, p=0.005 and 79±5%, p=0.003, respectively). Deposition of immunoglobulins G into the tunica media was observed only in non-immunosuppressed aortic allografts on day 30. CONCLUSIONS: Fresh aortic allografts induce donor-specific anti-MHC class I and anti-MHC class II antibody production. Delayed administration of tacrolimus completely suppressed antibody production and antibody-mediated destruction of aortic allografts.