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Pancreatic carcinoma is one of the most lethal cancers and the absence of efficient therapeutic strategies results in poor prognosis. Transcriptional dysregulation due to alterations in KRAS and MYC impacts initiation, development, and survival of this tumor type. Using patient-derived xenografts of pancreatic carcinoma driven by KRAS and MYC oncogenic transcription, we show that co-inhibition of Topoisomerase 1 (TOP1) and bromodomain containing protein 4 (BRD4) synergistically induce tumor regression through targeting promoter pause-release, a rate-limiting step in transcription elongation. By comparing the nascent transcriptome with the recruitment of elongation and termination factors along genes, we found that co-inhibition of TOP1 and BRD4, while globally impairing RNA production, disturbs recruitment of proteins involved in termination. Thus, RNA polymerases continue transcribing downstream of genes for hundreds of kilobases leading to readthrough transcription. This pervasive transcription also occurs during replication, perturbing replisome progression and leading to DNA damage. The synergistic effect of TOP1 and BRD4 inhibition is specific for cancer cells leaving normal cells unharmed, highlighting the sensitivity of the tumor to these transcriptional defects. This preclinical study provides a mechanistic understanding of the benefit of combining TOP1 and BRD4 inhibitors to treat pancreatic carcinomas addicted to oncogenic drivers of high transcription and replication.One Sentence SummaryTOP1 and BRD4 inhibitors synergize to selectively kill pancreatic cancerin vivo viareadthrough transcription without emergence of drug resistance

Background: Pancreatic Ductal Adenocarcinoma (PDAC) lacks effective treatment options beyond chemotherapy. Although molecular subtypes such as classical and QM (quasi-mesenchymal)/basal-like with transcriptome-based distinct signatures have been identified, deduced therapeutic strategies and targets remain elusive. Gene expression data show enrichment of glycolytic genes in the more aggressive and therapy resistant QM subtype. However, whether the glycolytic transcripts are translated into functional glycolysis that could further be explored for metabolic targeting in QM subtype is still not known. Methods: We used different patient-derived PDAC model systems (conventional and primary patient derived cells, patient derived xenografts (PDX) and patient FFPE samples) and performed transcriptional and functional metabolic analysis. These included: RNAseq and Illumina HT12 bead array, in vitro Seahorse metabolic flux assays and metabolic drug targeting, and in vivo hyperpolarized [1-13C]pyruvate and [1-13C]lactate magnetic resonance spectroscopy (HP-MRS) in PDAC xenografts. Results: We found that glycolytic metabolic dependencies are not unambiguously functionally exposed in all QM PDACs. Metabolic analysis demonstrated functional metabolic heterogeneity in patient-derived primary cells and less so in conventional cell lines independent of molecular subtype. Importantly, we observed that the glycolytic product lactate is actively imported in the PDAC cells and used in mitochondrial oxidation in both classical and QM PDAC cells, although more actively in the QM cell lines. By using hyperpolarized 13C-magnetic resonance spectroscopy (HP-MRS), we were able to non-invasively identify highly glycolytic PDAC xenografts by detecting the last glycolytic enzymatic step and prominent intra-tumoral [1‑13C]pyruvate and [1-13C]lactate interconversion in vivo.Conclusion: Our study adds functional metabolic phenotyping to transcriptome-based analysis and proposes a functional approach to identify highly glycolytic PDACs as candidates for anti-metabolic therapeutic avenues.

The outcome after living kidney donation was assumed to be comparable to that of the general population. However, recent register studies reveal negative changes in kidney function, quality of life and fatigue. Avoiding methodological issues of previous studies, the Safety of the Living Kidney Donor (SoLKiD) cohort study analyzed the outcome of donors in a multicenter and interdisciplinary fashion. Donor data were collected pre-donation and two-, six- and 12-months post-donation in 20 German transplantation centers. Primary parameters were kidney function, quality of life, and fatigue. Secondary endpoints were blood pressure, hemoglobin, hemoglobin A1c, body mass index, depression and somatization. Parameters were analyzed with non-parametric statistical tests and a mixed model regression for changes in time, their clinical relevance and interaction encompassing 336 donors with mean age of 52 years. Most of the physical secondary parameters, depression, and quality of life showed little or no changes and regained their pre-donation level. Kidney function decreased significantly with a 37% loss of glomerular filtration rate and an increase of donors with chronic kidney disease stage 3 from 1.5% pre-donation to about 50%. Donors consistently showed increased fatigue and somatization. Mental fatigue increased from 10.6% to 28.1%. The main influencing factors for decreased kidney function and increased fatigue were their respective pre-donation levels, and donor age for kidney function and subject stress level in fatigue. Thus, our study showed that a significant number of donors developed clinically relevant changes in physical and mental health and emphasizes the urgent need to inform potential donors about these risks.

Colorectal cancer is one of the leading malignancies and still accounts for almost 25 000 deaths in Germany each year. Although there is accumulating data on the molecular basis, treatment and clinical outcome of patients within clinical trials evidence from the real-world setting is mostly lacking. We started the molecular registry trial Colopredict Plus in 2013 to collect clinical and molecular data from a real-world cohort of patients with early colon cancer stage II and III in 70 German colon cancer centers focusing on the prognostic impact of high microsatellite instability. In this interim report, we characterize a clinical cohort of 2615 patients, of whom 1787 tissue probes were analyzed. Microsatellite status was assessed using immunhistochemistry and fragment length analysis, with a concordance of 91.4 %. These established histopathological methods are sensitive and cost-effective. The median age was 72 years, significantly higher compared to clinical trial populations, with a median Charlson Comorbidity Index of 3. The stage-dependent incidence of microsatellite instability was 23.7 % and was associated with female gender, BRAF-mutation, UICC stage II and localization in the right colon. Survival calculated in disease free, relapse free and overall survival significantly differed between MSI-H and MSS, in favor of MSI-H patients. Multivariate age-adjusted analyses of relapse-free survival, disease-free survival, and overall survival highlighted microsatellite instability as a robust and positive prognostic marker for early colon cancer independent of age.Das kolorektale Karzinom ist weiterhin eine der häufigsten Tumorerkrankungen mit einer Mortalität von fast 25 000 pro Jahr in Deutschland. Obwohl wir mehr und mehr Daten zur molekularen Basis, zu neuen Behandlungsmethoden und Verläufen von Patienten im Rahmen klinischer Studien generieren, gibt es nur wenige Informationen aus der klinischen Versorgungsrealität. Wir starteten die molekulare Registerstudie Colopredict Plus im Jahre 2013, um klinische sowie molekulare Daten von einer „Real-World“-Kohorte von Patienten mit Kolonkarzinomen im UICC-Stadium II und III aus 70 deutschen Darmkrebszentren zu dokumentieren. Der Fokus liegt hier auf dem prognostischen Wert einer hochgradigen Mikrosatelliteninstabilität. In dieser Interimsanalyse charakterisieren wir das klinische Kollektiv von 2615 Patienten, von denen 1787 Tumorproben analysiert wurden. Der Mikrosatellitenstatus wurde via Immunhistochemie und Fragmentlängenanalyse mit einer Konkordanz von 91,4 % durchgeführt, was eine kosteneffektive histopathologische Nachweismethodik darstellt. Das mediane Alter lag bei 72 Jahren und damit deutlich höher als üblicherweise in klinischen Studien, der mediane Charlson Comorbidity Index lag bei 3. Die stadienabhängige Mikrosatelliteninstabilität-Inzidenz lag bei 23,7 % und war assoziiert mit dem weiblichen Geschlecht, BRAF-Mutationen, UICC-Stadium II und der Primärtumorlokalisation im rechten Kolon. Das Überleben berechnet in krankheitsfreiem, rezidivfreiem sowie Gesamtüberleben unterschied sich signifikant zugunsten der MSI-H-Patienten. Multivariate altersadjustierte Analysen des rezidivfreien und krankheitsfreien Überlebens sowie des Gesamtüberlebens bestätigten eine hochgradige Mikrosatelliteninstabilität als robusten und positiven prognostischer Marker für frühe Kolonkarzinome unabhängig vom Alter.

BACKGROUND Passenger lymphocyte syndrome (PLS), a subtype of graft-versus-host disease, is a rare disorder encountered mainly in ABO-mismatched hematopoietic stem cell transplantation and infrequently in all types of ABO-mismatched solid organ transplantation. We here report the fifth case of PLS in small bowel transplantation (SBTx) and the first one describing the successful management of PLS in a cadaveric, isolated SBTx. CASE REPORT A 60-year-old Caucasian female with blood group A D+ suffering from short bowel syndrome received a small bowel transplant from a 32-year-old Caucasian female with blood group O D+ (HLA mismatch 2/6). After onset of massive hemolysis on Postoperative Day 9 the positive direct and indirect antiglobulin tests showing antibodies against A1 and A2 red blood cells (RBCs) led to the diagnosis of PLS. This complication was successfully treated by transfusion of blood group O RBC transfusions, increased immunosuppression, and plasmapheresis. CONCLUSION In the event of severe hemolysis and anemia after ABO-mismatched SBTx, PLS should be considered. In our case successful treatment consisted of transfusion of donor-specific RBCs, increased immunosuppression, and plasmapheresis.

An accurate blood-based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti-EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood-based RAS mutation testing is a viable alternative to standard-of-care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin-fixed paraffin-embedded) tumor samples. Discordant tissue RAS results were re-examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood-based RAS mutation testing is a viable alternative to tissue-based RAS testing.

Aberrations within the PI3K/AKT signaling axis are frequently observed in numerous cancer types, highlighting the relevance of these pathways in cancer physiology and pathology. However, therapeutic interventions employing AKT inhibitors often suffer from limitations associated with target selectivity, efficacy, or dose-limiting effects. Here we present the first crystal structure of autoinhibited AKT1 in complex with the covalent-allosteric inhibitor borussertib, providing critical insights into the structural basis of AKT1 inhibition by this unique class of compounds. Comprehensive biological and preclinical evaluation of borussertib in cancer-related model systems demonstrated a strong antiproliferative activity in cancer cell lines harboring genetic alterations within the PTEN, PI3K, and RAS signaling pathways. Furthermore, borussertib displayed antitumor activity in combination with the MEK inhibitor trametinib in patient-derived xenograft models of mutant KRAS pancreatic and colon cancer. Significance: Borussertib, a first-in-class covalent-allosteric AKT inhibitor, displays antitumor activity in combination with the MEK inhibitor trametinib in patient-derived xenograft models and provides a starting point for further pharmacokinetic/dynamic optimization.

Aberrations within the PI3K/AKT signaling axis are frequently observed in numerous cancer types, highlighting the relevance of these pathways in cancer physiology and pathology. However, therapeutic interventions employing AKT inhibitors often suffer from limitations associated with target selectivity, efficacy, or dose-limiting effects. Here we present the first crystal structure of autoinhibited AKT1 in complex with the covalent-allosteric inhibitor borussertib, providing critical insights into the structural basis of AKT1 inhibition by this unique class of compounds. Comprehensive biological and preclinical evaluation of borussertib in cancer-related model systems demonstrated a strong antiproliferative activity in cancer cell lines harboring genetic alterations within the PTEN, PI3K, and RAS signaling pathways. Furthermore, borussertib displayed antitumor activity in combination with the MEK inhibitor trametinib in patient-derived xenograft models of mutant

Background Liver transplantation (LTx) is a potentially curative treatment option for hepatocellular carcinoma (HCC) in cirrhosis. However, patients, where HCC is already a systemic disease, LTx may be individually harmful and has a negative impact on donor organ usage. Thus, there is a need for improved selection criteria beyond nodule morphology to select patients with a favorable outcome for LTx in multifocal HCC. Evolutionary distance measured from genome-wide single-nucleotide polymorphism data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after LTx for multifocal HCC. Methods In a retrospective multicenter study, clinical data and formalin-fixed paraffin-embedded specimens of the liver and 2 tumor nodules were obtained from explants of 30 patients in the discovery and 180 patients in the replication cohort. DNA was extracted from formalin-fixed paraffin-embedded specimens followed by genome wide single-nucleotide polymorphism genotyping. Results Genotype quality criteria allowed for analysis of 8 patients in the discovery and 17 patients in the replication set. DNA concentrations of a total of 25 patients fulfilled the quality criteria and were included in the analysis. Both, in the discovery (P = 0.04) and in the replication data sets (P = 0.01), evolutionary distance was associated with the risk of recurrence of HCC after transplantation (combined P = 0.0002). In a univariate analysis, evolutionary distance (P = 7.4 × 10−6) and microvascular invasion (P = 1.31 × 10−5) were significantly associated with survival in a Cox regression analysis. Conclusions Evolutionary distance allows for the determination of a high-risk group of recurrence if preoperative liver biopsy is considered., The authors of this multicenter retrospective study assess whether the evolutionary distance measured from genome-wide single nucleotide polymorphism (SNP) data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after liver transplantation for multifocal hepatocellular carcinoma. Supplemental digital content is available in the text.

The VIPP study compared valganciclovir prophylaxis with preemptive treatment regarding efficacy, safety, and long-term graft outcome in cytomegalovirus (CMV)-positive (R+) renal transplant recipients.Multicenter, open-label, randomized clinical study with a 12-month study phase and a follow-up of up to 84 months. Patients in the prophylaxis group received 2 × 450 mg/d oral valganciclovir for 100 days adjusted to renal function. Preemptive treatment with 2 × 900 mg/d valganciclovir was initiated at a viral load of 400 CMV copies/mL or greater (polymerase chain reaction) and maintained over ≥14 days, followed by secondary prophylaxis. Patients were stratified by donor CMV IgG serostatus (donor CMV IgG positive [D+]/R+, donor CMV IgG negative [D-]/R+).The 12-month results were reported previously (Witzke et al Transplantation 2012). The intent-to-treat/safety population comprised 148 patients in the prophylaxis (61.5% D+/R+) and 151 patients in the preemptive group (52.3% D+/R+). Overall, 47% patients completed the follow-up. Significantly fewer patients in the prophylaxis compared with preemptive group experienced a CMV infection or disease up to month 84 (11.5%; 95% confidence interval [95% CI], 6.8-17.8%] vs 39.7%; 95% CI, 31.9-48.0%; P0.0001 and 4.7%; 95% CI, 1.9-9.5% vs 15.9%; 95% CI, 10.5-22.7%; P = 0.002). Incidences of graft loss (7.4% vs 8.6%), death (9.5% vs 11.3%), rejection (29.1% vs 28.5%), and renal function (estimated glomerular filtration rate [mean ± SD]: 58.2 ± 26.3 vs 59.9 ± 25.7 mL/min per 1.73 m) were not significantly different between prophylaxis and preemptive treatment. Tolerability was comparable between groups.Prophylaxis was more effective than the preemptive approach, applying a low-intense surveillance protocol in preventing CMV infection and disease in intermediate-risk patients. Both strategies were similarly effective in preventing graft loss and death under the conditions of this long-term trial with a threshold of 400 copies/mL for initiation of anti-CMV treatment.

Perihilar cholangiocarcinomas are often considered incurable. Late diagnosis is common. Advanced disease therefore frequently causes questioning of curative surgical outcome.This study aimed to develop a prediction model of curative surgery in patients suffering from perihilar cholangiocarcinomas based on preoperative endosonography and computer tomography.A cohort of 81 patients (median age 67 (54-75) years, 62% male) with perihilar cholangiocarcinoma was retrospectively analyzed. Multivariate logistic regression analysis of staging variables taken from the European Staging System was performed and applied to ROC analysis.The correlation of predicted rates of eligibility for surgery with actual rates reached AUC values between 0.652 and 0.758 for endosonography and computer tomography (Our predictive web-based model pSurg with inclusion of T, N, M, B, PV, HA and V stage of the recently published European Staging System for perihilar cholangiocarcinoma results in highly significant predictability for curative surgery when combining preoperative endosonography and computer tomography, thus allowing for better patient selection in terms of possibility of curative surgery.

Background Hepatocellular carcinoma (HCC) represents the main cause of death among patients with cirrhotic liver disease, but little is known about mechanisms of cirrhosis associated carcinogenesis. We investigated the diagnostic impact of microRNA-200 (miR-200) family members as important epigenetic regulators of epithelial–mesenchymal transition (EMT) to differentiate between patients with HCC and liver cirrhosis. Methods Expression of the miR-200 family was investigated by qRT-PCR in specimens of HCC patients with and without cirrhosis. Benign specimens with and without cirrhosis served as controls. Expression of the EMT markers ZEB-1, E-cadherin and vimentin was examined using immunohistochemistry. Results MiR-200a and miR-200b were significantly downregulated in HCC (miR-200a: −40.1% (P = 0.0002); miR-200b: −52.3% (P = 0.0002)), and in HCC cirrhotic tissue (miR-200a: −40.2% (P = 0.004); miR-200b: −51.1% (P = 0.007)) compared to liver cirrhosis. Spearman's Rho analysis revealed a significant negative correlation of miR-200a and miR-200b to the expression of the mesenchymal markers Vimentin (P

We report on a small bowel transplant patient, donor/recipient seropositive (D+/R+) for cytomegalovirus (CMV), with a clinical course complicated by CMV disease. Anti-CMV prophylaxis was given for 100 days. Immunosuppression consisted of alemtuzumab, tacrolimus, mycophenolate mofetil and prednisolone. Five months posttransplant, CMV tissue invasive disease of the upper gastrointestinal tract was evident without the presence of viremia, tested by quantitative polymerase chain reaction (PCR). Complete viral load suppression was achieved with intravenous ganciclovir, followed by valganciclovir for secondary prophylaxis. Mycophenolate mofetil and prednisolone were discontinued. Shortly thereafter the patient presented with recurrent CMV and candida esophagitis. While on ganciclovir and caspofungin, the patient developed CMV tissue invasive disease of the ileal graft, with persistent absence of viremia. Foscarnet and CMV immunoglobulin were added. Viral load declined to undetectable levels; however, clinical improvement did not occur due to occurrence of graft rejection. Despite infliximab and high dose prednisolone, graft rejection was progressive, requiring surgical explantation of the graft. This case highlights the importance of additional diagnostic tools such as endoscopy including PCR analysis of tissue samples. Extension of primary antiviral prophylaxis interval up to 6 months and prolonged retreatment for recurrent CMV disease may be useful to avoid severe CMV-related complications.

BACKGROUND The shortage of organ donors has led to the introduction of the Eurotransplant Senior Program (ESP) to optimize the allocation of kidneys from elderly donors by age-matching. In the face of a rapidly aging population, identification of prognostic factors for kidney allograft survival within the ESP population will be of enormous significance. MATERIAL AND METHODS Donor and recipient data from 89 patients transplanted under the ESP protocol between 1999 and 2007 were retrospectively analyzed. Data were correlated with initial graft function, graft survival, acute rejection episodes, serum creatinine levels, glomerular filtration rates, and patient survival using univariate and multivariate analysis. Maximum follow-up was 5 years. RESULTS Cold ischemia time (CIT) >16 hours, body mass index (BMI) ≥25 kg/m(2), and kidney re-transplantation were significant risk factors for delayed graft function (DGF). Odds ratio for primary non-function was significantly increased with prolonged CIT, BMI ≥25 kg/m(2), and duration of renal replacement therapy >69 months. CIT >15 h, DGF, and kidney re-transplantation were associated with poor graft survival (P

Background Urinary tract infections (UTI) are common nosocomial infections in kidney transplant recipients, with limited evidence to guide antibiotic prophylaxis at urinary catheter removal. The aim of our study was to evaluate the effect of short-term antibiotic therapy at the moment of catheter removal after kidney transplantation. Methods Twenty kidney transplant recipients received 250 mg of ciprofloxacin orally twice daily 1 day before and at the day of the removal of the urinary catheter and were compared with 20 kidney transplant recipients without prophylaxis. UTI was diagnosed by use of urine culture and clinical signs. Results All patients were comparable in sex, age, etiology of end-stage renal failure, immunosuppression, donor type, and initial function. After catheter removal at the 6th postoperative day, a rapid rise of UTI in kidney transplant recipients without prophylaxis (n = 12, 60%) was observed, whereas in patients with antibiotic prophylaxis the rate of UTI could be significantly reduced to 20%. Escherichia coli was the most isolated pathogen in the patients with UTI and was detected at the catheter tip in more than 50% of cases. In 2 patients (10%) after antibiotic prophylaxis, a ciprofloxacin-resistant E coli strain was detected. Conclusions The use of antibiotic prophylaxis during urinary catheter removal is recommended to prevent UTI in kidney transplant recipients.

Endoscopic ultrasound (EUS) is considered a gold standard in the initial staging of esophageal cancer. There is an ongoing debate whether EUS is useful for tumor staging after neoadjuvant chemotherapy (NAC). Ninety-five patients with esophageal cancer were retrospectively analyzed. In 45 patients, EUS was performed prior to and after NAC, while 50 patients had no induction therapy. Histological correlation through surgery was available. uT/uN classifications were compared to pT/pN stages. Statistical analysis included calculation of sensitivity, specificity, and accuracy rates. Agreement between endosonography and T staging was assessed with Cohen's kappa statistics. For those patients with prior NAC, overall accuracy of yuT and yuN classification was 29 and 62%, respectively. Sensitivity, specificity, and accuracy rates for local tumor extension after NAC were as follows (%): T1: –/97/84, T2: 13/76/53, T3:86/29/46, T4:20/100/91, T1/2: 27/83/56, T3/4: 89/31/56. Cohen's kappa indicated poor agreement (kappa = 0.129) between yuT classification and ypT stage. Relative to positive lymph node detection, sensitivity and specificity were 100 and 6%, respectively (kappa = 0.06). T stage was overstaged in 23 (51%) and understaged in seven (16%) patients. EUS is an unreliable tool for staging esophageal cancer after NAC. Overstaging of the T stage is common after NAC.

Poor arterial inflow during orthotopic liver transplantation (OLT) may necessitate arterial revascularisation using aorto-hepatic bypasses with supraceliac (SC) or infrarenal (IR) allografts. This study compared both techniques focusing on the patients’ preoperative conditions, postoperative graft/organ function, complications and survival. Fifteen out of 114 OLT patients underwent revascularisation (7 IR/8 SC) between 2005 and 2008 and were included in the study. The patients’ records were reviewed retrospectively. IR patients presented with a higher BMI, received more male donor organs and their reperfusion sequence was predominately portal venous (SC: primary arterial). SC patients presented a significantly worse preoperative creatinine clearance and a trend towards a higher MELD score. The postoperative graft/organ function, morbidity and mortality did not differ between the groups despite a trend towards a worse survival in the SC group. A deteriorated preoperative creatinine clearance and higher MELD score negatively impacted the survival. Postoperative bleeding episodes and major re-interventions also affected the outcome. We found no evidence for superiority of either bypass technique in our OLT patients. The trend toward a worse survival in SC patients was most likely caused by the worse preoperative conditions of these patients and highlights the importance of the impact of the MELD score on the outcome after OLT.

BACKGROUND This study evaluated the effect of liver transplantation (LTX) and STACE on overall survival in palliative patients with HCC exceeding Milan criteria. MATERIAL AND METHODS At a single center 63 HCC patients exceeding Milan criteria were retrospectively analyzed. Forty patients underwent STACE as palliative therapy modality and 23 palliative patients were scheduled for LTX. The primary endpoint was overall patient survival. Statistical analysis included Kaplan-Meier method, log rank, chi squared tests and Cox regression model for the identification of prognostic factors. RESULTS There was no significant difference when comparing the 2 groups (LTX vs. no LTX) in terms of Child classification, co-morbidities, underlying disease, and sex. Overall survival was significantly prolonged after LTX was performed (p=0.012). In the Cox regression model, LTX (p=0.021), LTX

Einleitung: Perihilare Cholangiozellulare Karzinome (pCC) sind haufig mit einer schlechten Prognose vergesellschaftet. Haufig wird ein fortgeschrittenes Tumorstadium erst im Rahmen einer operativen Exploration festgestellt mit der Konsequenz einer Inkurabilitat. Ziel: Mit unserer Studie verfolgen wir das Ziel, ein Vorhersagemodell fur die Moglichkeit einer potentiell kurativen operative Resektion basierend auf den diagnostischen Verfahren EUS, IDUS und CT anhand des 2011 publizierten neuen Europaischen Staging Systems (ESS) fur pCC zu etablieren. Methodik: In unsere Studie konnten bisher 67 Patienten (medianes Alter 67 [57 – 72] Jahre, 62% mannlich) eingeschlossen werden, die die Einschlusskriterien erfullten. Eine multivariate logistische Regressionsanalyse basierend auf den Staging-Variablen des ESS wurde durchgefuhrt und mittels ROC Analyse abgebildet (Abbildung 1). Ergebnisse: Die Korrelation der vorausgesagten Moglichkeit einer kurativen Operation mittels Kombination von EUS, IDUS und CT als haufig eingesetzte diagnostische bildgebende Verfahren mit der tatsachlichen Operabilitatsrate erreichte einen AUC-Wert von0.933 (95%CI 0.871 – 0.994, p < 0.0001). Schlussfolgerung: Das von uns entwickelte Pradiktionsmodell (psurg) basierend auf der diagnostischen Erfassung der im ESS genannten Variablen mittels EUS, IDUS und CT resultiert in einer hoch signifikanten Vorhersagewahrscheinlichkeit fur die Moglichkeit einer kurativen operativen Resektion von pCC. Es besteht somit die Moglichkeit, anhand praoperativ erhobener Parameter eine statistisch signifikante Aussage bezuglich der Moglichkeit einer Resektion zu treffen und ggf. unnotige operative Eingriffe zu vermeiden.

Cytomegalovirus infections cause the most frequent infection after solid-organ transplant. While Cytomegalovirus prophylaxis is established in high-risk patients (donor+/ recipient-), data on Cytomegalovirus prophylaxis in other serostatus constellation are rare. The aim of this study was to evaluate the influence of Cytomegalovirus treatment strategy after a liver transplant (preemptive therapy vs general prophylaxis) in the largest group of patients: Cytomegalovirus seropositive donor and recipient.Forty-seven seropositive recipients of seropositive donor liver transplants (D+/R+, 2005-2012) were included in this retrospective study. Twenty-one patients received oral valganciclovir as Cytomegalovirus prophylaxis 100 days after transplant. Cytomegalovirus infection and Cytomegalovirus disease were monitored during the first 6 months.A Cytomegalovirus infection could be detected in 4 out of 47 patients (8.5%), including Cytomegalovirus disease in 2 patients (Cytomegalovirus pneumonia and Cytomegalovirus-CNS disease). Three of these patients received no Cytomegalovirus prophylaxis (P = .408). Eight patients developed a graft failure; this occurred more frequently among patients without Cytomegalovirus prophylaxis (P = .044). Patients receiving Cytomegalovirus prophylaxis more often developed leukopenia. No difference was seen regarding the number of platelets, hemoglobin, and creatinine.Cytomegalovirus prophylaxis can minimize the risk of Cytomegalovirus reactivation and graft failure. However, disadvantages of the prophylaxis as leukopenia should be considered.

Background The ascertainment of brain death (the irreversible, total loss of brain function) gives the physician the opportunity to limit or stop further treatment. Alternatively, if the brain-dead individual is an organ donor, the mode of treatment can be changed from patient-centered to donationcentered. Consensus-derived recommendations for the organ-protective treatment of brain-dead organ donors are not yet available in Germany. Methods This review is based on pertinent publications retrieved by a selective search in PubMed, and on the authors' clinical experience. Results Brain death causes major pathophysiological changes, including an increase in catecholamine levels and a sudden drop in the concentration of multiple hormones, among them antidiuretic hormone, cortisol, insulin, and triand tetraiodothyronine. These changes affect the function of all organ systems, as well as the hemodynamic state and the regulation of body temperature. The use of standardized donor management protocols might well increase the rate of transplanted organs per donor and improve the quality of the transplanted organs. In addition, the administration of methylprednisolone, desmopressin, and vasopressin could be a useful supplement to treatment in some cases. Randomized controlled trials have not yet demonstrated either improved organ function or prolonged survival of the transplant recipients. Conclusion The evidence base for organ-protective intensive care is weak; most of the available evidence is on the level of expert opinion. There is good reason to believe, however, that the continuation of intensive care, in the sense of early donor management, can make organ transplantation more successful both by increasing the number of transplantable organs and by improving organ quality.

Immunosuppression is the major risk factor for BK virus nephropathy (BKVN) after renal transplantation (RTx). As the individual tacrolimus (Tac) metabolism rate correlates with Tac side effects, we hypothesized that Tac metabolism might also influence the BKV infection risk. In this case-control study RTx patients with BK viremia within 4 years after RTx (BKV group) were compared with a BKV negative control group. The Tac metabolism rate expressed as the blood concentration normalized by the daily dose (C/D ratio) was applied to assess the Tac metabolism rate. BK viremia was detected in 86 patients after a median time of 6 (0–36) months after RTx. BKV positive patients showed lower Tac C/D ratios at 1, 3 and 6 months after RTx and were classified as fast Tac metabolizers. 8 of 86 patients with BK viremia had histologically proven BKN and a higher median maximum viral load than BKV patients without BKN (441,000 vs. 18,572 copies/mL). We conclude from our data that fast Tac metabolism (C/D ratio

Passenger lymphocyte syndrome (PLS), a subtype of graft-versus-host disease, is a rare disorder encountered mainly in ABO-mismatched hematopoietic stem cell transplantation and infrequently in all types of ABO-mismatched solid organ transplantation. We here report the fifth case of PLS in small bowel transplantation (SBTx) and the first one describing the successful management of PLS in a cadaveric, isolated SBTx.A 60-year-old Caucasian female with blood group A D+ suffering from short bowel syndrome received a small bowel transplant from a 32-year-old Caucasian female with blood group O D+ (HLA mismatch 2/6). After onset of massive hemolysis on Postoperative Day 9 the positive direct and indirect antiglobulin tests showing antibodies against A1 and A2 red blood cells (RBCs) led to the diagnosis of PLS. This complication was successfully treated by transfusion of blood group O RBC transfusions, increased immunosuppression, and plasmapheresis.In the event of severe hemolysis and anemia after ABO-mismatched SBTx, PLS should be considered. In our case successful treatment consisted of transfusion of donor-specific RBCs, increased immunosuppression, and plasmapheresis.

Aims: To assess 5-year efficacy, renal, and safety outcomes following early conversion from cyclosporine to everolimus vs. a standard cyclosporine-based regimen in living-donor kidney transplant (LDKT) recipients. Materials and methods: The ZEUS study was a randomized, open-label, 1-year, multicenter study in which 300 de novo kidney transplant recipients continued to receive cyclosporine or converted to everolimus at 4.5 months post-transplant, with annual follow-up visits to 5 years post-transplant. Results: Of the 80 LDKT patients who were randomized, 75 completed the 1-year core study and 60 attended the 5-year follow-up visit. At year 5, 15/31 (48.4%) everolimus patients and 20/29 (69.0%) cyclosporine patients remained on the study drug. Mean adjusted estimated glomerular filtration rate (GFR) at year 5 in LDKT recipients was 67.2 vs. 60.8 mL/min/1.73m(2) for everolimus vs. cyclosporine (mean difference 6.4 mL/min/1.73m(2);p = 0.031). For patients who remained on study drug, the mean difference was 13.2 mL/min/1.73m(2) (p = 0.003), but no significant difference was seen in patients who switched from study drug (mean -2.6 mL/min/1.73m(2), p = 0.701). Patient and graft survival rates were similar with everolimus and cyclosporine. Biopsy-proven acute rejection occurred in 22.0% vs. 7.5% of LDKT patients randomized to everolimus vs. cyclosporine (p = 0.116). Only 1 LDKT patient discontinued everolimus due to adverse events during years 1 - 5. Conclusions: Early initiation of everolimus with calcineurin-inhibitor (CNI) withdrawal after LDKT improved graft function to 5 years post-transplant compared to standard CNI-based therapy. The renal benefit was concentrated in patients who remained on everolimus. An increase in mild acute rejection was not associated with long-term graft loss.

International audience; 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.TRIAL REGISTRATION:ClinicalTrials.gov NCT00355862.

BACKGROUND Anastomotic insufficiency after pancreatoduodenectomy (PD) represents a major complication in pancreatic surgery. Early detection and treatment of pancreatic fistulas (PF) are essential for the outcome of affected patients. Procalcitonin (PCT) is a biochemical marker which allows detection of bacterial infections. The aim of this study was to evaluate if PCT is suitable for early detection of PF after PD. METHODS In this prospective study patients undergoing PD from 08/2010 to 09/2012 were included into three groups: (1) patients without complications (n = 19), (2) patients with postoperative infections (n = 14) and (3) PF (n = 7). Using a defined study protocol, clinical (e.g., vital signs, drain fluid, etc.) and laboratory parameters (full blood count, inflammatory markers) were assessed daily for the first ten postoperative days. RESULTS 76 patients were assessed. 40 (52.6%) patients underwent PD and were included. CRP and PCT demonstrated an initial peak at the 1st to 3rd postoperative day with subsequent normalization. Patients with postoperative infections and PF showed a significant increase of PCT and CRP (p < 0.05) compared to patients without complications. Leucocyte counts demonstrated a variance in all three groups and clinical use for detection of complications was not evident. CONCLUSIONS Patients with a postoperative complication revealed significantly increased levels of PCT and CRP without the expected normalization. PCT and/or CRP did not enable a distinction between patients with PF or postoperative infections. Thus, PCT does not seem to be suitable for detecting PF after PD and its use in the postoperative course after PD cannot be recommended.

Item does not contain fulltext BACKGROUND: In the Eurotransplant Kidney Allocation System (ETKAS), transplant candidates can be considered for high-urgency (HU) status in case of life-threatening inability to undergo renal replacement therapy. Data on the outcomes of HU transplantation are sparse and the benefit is controversial. METHODS: We systematically analysed data from 898 ET HU kidney transplant recipients from 61 transplant centres between 1996 and 2010 and investigated the 5-year patient and graft outcomes and differences between relevant subgroups. RESULTS: Kidney recipients with an HU status were younger (median 43 versus 55 years) and spent less time on the waiting list compared with non-HU recipients (34 versus 54 months). They received grafts with significantly more mismatches (mean 3.79 versus 2.42; P < 0.001) and the percentage of retransplantations was remarkably higher (37.5 versus 16.7%). Patient survival (P = 0.0053) and death with a functioning graft (DwFG; P < 0.0001) after HU transplantation were significantly worse than in non-HU recipients, whereas graft outcome was comparable (P = 0.094). Analysis according to the different HU indications revealed that recipients listed HU because of an imminent lack of access for dialysis had a significantly worse patient survival (P = 0.0053) and DwFG (P = 0.0462) compared with recipients with psychological problems and suicidality because of dialysis. In addition, retransplantation had a negative impact on patient and graft outcome. CONCLUSIONS: Facing organ shortages, increasing wait times and considerable mortality on dialysis, we question the current policy of HU allocation and propose more restrictive criteria with regard to individuals with vascular complications or repeated retransplantations in order to support patients on the non-HU waiting list with a much better long-term prognosis.

Cytomegalovirus (CMV) prevention can be achieved by prophylaxis or preemptive therapy. We performed a prospective randomized trial to determine whether renal transplant recipients with a positive CMV serostatus (R+) had a higher rate of CMV infection and disease after transplantation when treated preemptively for CMV infection, compared with primary valganciclovir prophylaxis.Prophylaxis was 2 × 450 mg oral valganciclovir/day for 100 days; preemptive patients were monitored by CMV-polymerase chain reaction (PCR), and after a positive PCR test received 2 × 900 mg valganciclovir/day for at least 14 days followed by secondary prophylaxis. Valganciclovir dosage was adjusted according to renal function. Patients are followed up for 5 years and initial 12-month data are presented. Two hundred and ninety-six recipients were analyzed (168 donor/recipient seropositive [D+/R+], 128 donor seronegative/recipient seropositive [D-/R+]; 146 receiving prophylaxis and 150 preemptive therapy).Overall, CMV infection (asymptomatic CMV viral load ≥ 400 CMV DNA copies/mL proven by CMV-PCR) was significantly higher in recipients under preemptive therapy (38.7% vs. 11.0%, P0.0001), with the highest incidence in D+/R+ preemptive patients (53.8% vs. 15.6%, P0.0001). D+/R+ recipients with preemptive therapy also had the highest rate of CMV disease (CMV syndrome and tissue-invasive disease that was clinically diagnosed and biopsy proven) (19.2% vs. 4.4%, P=0.003). Renal function assessed by creatinine clearance was similar for both groups. Graft loss occurred in 7 vs. 4 patients on preemptive versus prophylactic therapy (P0.05). Tolerability was similar for both treatment groups.Oral valganciclovir prophylaxis significantly reduces CMV infection and disease, particularly for D+/R+ patients. Hence, our study supports routine prophylaxis for all D+/R+ recipients.

Background Renal allograft outcome in heart–kidney transplantation (HKTx) might be affected by hemodynamic instability and high levels of calcineurin inhibitor-dependent immunosuppression. Methods From November 1999 to March 2008, 13 patients who received HKTx were compared with a matched control group of 13 kidney transplantation (KTx) recipients with similar cardiovascular risk factors. Graft function, rejection periods, and patient survival were analyzed. Results Renal allograft rejection was noted in three patients (23%) after HKTx and in four patients (31%) after KTx. Serum creatinine levels were comparable at 1 week, 1 month, 1, 2, and 3 years after transplantation. Patient survival rates at 1, 2, and 3 years were 100% for HKTx recipients and 100, 92, and 92% for isolated KTx patients. Graft survival was 92% at 1, 2, and 3 years after HKTx and 100% at 1 year and 92% at 2 and 3 years after isolated KTx. Conclusions Our results with excellent long-term graft function and survival after combined HKTx indicate that this procedure is a valuable option for a growing number of patients suffering from coexistent cardiac and renal failure.

Posttransplant immunosuppression with calcineurin inhibitors (CNIs) is associated with impaired renal function, while mTor inhibitors such as everolimus may provide a renal-sparing alternative. In this randomized 1-year study in patients with liver transplantation (LTx), we sought to assess the effects of everolimus on glomerular filtration rate (GFR) after conversion from CNIs compared to continued CNI treatment. Eligible study patients received basiliximab induction, CNI with/without corticosteroids for 4 weeks post-LTx, and were then randomized (if GFR > 50 mL/min) to continued CNIs (N = 102) or subsequent conversion to EVR (N = 101). Mean calculated GFR 11 months postrandomization (ITT population) revealed no significant difference between treatments using the Cockcroft-Gault formula (-2.9 mL/min in favor of EVR, 95%-CI: [-10.659; 4.814], p = 0.46), whereas use of the MDRD formula showed superiority for EVR (-7.8 mL/min, 95%-CI: [-14.366; -1.191], p = 0.021). Rates of mortality (EVR: 4.2% vs. CNI: 4.1%), biopsy-proven acute rejection (17.7% vs. 15.3%), and efficacy failure (20.8% vs. 20.4%) were similar. Infections, leukocytopenia, hyperlipidemia and treatment discontinuations occurred more frequently in the EVR group. No hepatic artery thrombosis and no excess of wound healing impairment were noted. Conversion from CNI-based to EVR-based immunosuppression proved to be a safe alternative post-LTx that deserves further investigation in terms of nephroprotection.

The increasing demand for transplantation has led to consideration of liver grafts from donors exposed to hepatitis B virus (HBV). Six transplantations of liver grafts from hepatitis B surface antigen (HBsAg) positive donors have been reported; two recipients suffered from HBV/HDV (hepatitis Delta virus) coinfection and were followed up for 10-12 months. Here, we report a 56 months follow-up of a HBV/HDV-coinfected recipient of a HBsAg positive liver graft. Posttransplant combination prophylaxis consisted of hepatitis immunoglobulin, lamivudine and adefovir dipivoxil. HBsAg remained positive during stable posttransplant follow-up and subclinical HDV reinfection with low replication rate was detected at 1 month. Pegylated interferon therapy was introduced after documentation of histological evidence of mild chronic hepatitis, but without virological response after 48 weeks. Finally, antiviral treatment was switched to tenofovir disoproxil fumarate. More than 50 months posttransplant the recipient revealed clinical symptoms of decompensated liver cirrhosis and has been relisted for liver transplantation. In conclusion HBsAg positive liver grafts in HBsAg positive recipients with HDV coinfection may result in virological recurrence and rapid development of liver cirrhosis.

Hereditary systemic amyloidosis is a genetically and clinically heterogeneous group of diseases caused by deposits of insoluble proteins within tissues. The majority of cases are due to a mutation ...

The management of an asymptomatic failed renal graft remains controversial. The aim of our study was to explore the effect of failed allograft nephrectomy on kidney retransplantation by comparing the outcome of recipients who underwent graft nephrectomy prior to retransplantation with those who did not. Retrospective comparison of patients undergoing kidney retransplantation with (group A, n = 121) and without (group B, n = 45) preliminary nephrectomy was performed, including subgroup analysis with reference to patients with multiple (≥2) retransplantations and patients of the European Senior Program (ESP). Nephrectomy leads to increased panel reactive antibody (PRA) levels prior to retransplantation and is associated with significantly increased rates of primary nonfunction (PNF; P = 0.05) and acute rejection (P = 0.04). Overall graft survival after retransplantation was significantly worse in group A compared with group B (P = 0.03). Among the subgroups especially ESP patients showed a shorter graft survival after previous allograft nephrectomy. On the multivariate analysis, pretransplant graft nephrectomy and PRA >70% were independent and significant risk factors associated with graft loss after kidney retransplantation. Nephrectomy of the failed allograft was not beneficial for retransplant outcome in our series. Patients with failed graft nephrectomy tended to have a higher risk of PNF and acute rejection after retransplantation. The possibility that the graft nephrectomy has a negative impact on graft function and survival after retransplantation is worth studying further.

Hepatocellular carcinoma (HCC) is the most common tumor in cirrhotic patients with a median survival of only 8-10 months if untreated. Supraselective transarterial chemoembolization (STACE) is supposed to be a well-established method for treating HCC patients. In the present study, we evaluated the effect of STACE on post-transplant survival in patients with HCC.The charts of 53 HCC patients were retrospectively analyzed. Twenty-seven patients had STACE as a bridging therapy while 26 patients were scheduled for liver transplantation (LTX) without prior STACE therapy. A total of 53% of the patients who underwent LTX preoperatively fulfilled the Milan criteria, while 70.6% fulfilled the expanded University of California, San Francisco (UCSF) transplant criteria. Primary endpoint was the post-transplant survival. Statistical analysis included Kaplan-Meier-method, log rank, and chi square tests.Between the LTX groups (STACE vs. non-STACE), there was no significant difference in terms of age, Child classification, Okuda stage, co-morbidities, underlying disease, and post-transplant survival (p0.05). Independent of prior STACE, however, disease-free survival after LTX was highly significantly prolonged if LTX was performed within 3 months after initial diagnosis of HCC (p0.01) or if patients met the expanded transplant UCSF criteria (p = 0.02). Post-transplant survival did not depend on tumor size.We conclude that STACE performed prior to LTX does not secure any post-transplant survival benefit, while early LTX, i.e. within 3 months after HCC diagnosis, does improve survival regardless of whether STACE was performed or not. Additionally, fulfillment of the expanded transplant UCSF criteria leads to a prolonged post-transplant survival.

Ureteral defect lesions are severe complications caused by iatrogenic lesions or trauma. For ureteral defect lesions elaborate surgical intervention is needed, such as autotransplantation or ureteral replacement with small bowel. Thus, we developed a new technique for ureteral defect reconstruction in a pig model using an autologous vein graft splinted by an endoluminal biodegradable poly-L-lactic acid stent (Institute of Textile Technology and Process Engineering, Denkendorf, Germany).In 42 pigs we removed the external jugular vein and used it as an autologous vein graft. After median laparotomy a 3 cm segment was resected from the proximal ureter and replaced by the vein with or without an endoluminal biodegradable poly-L-lactic acid stent. As controls, we used 14 pigs. We observed survival, kidney function, and neoureteral and kidney morphological changes for 7 days and for 6 months.After 6 months the stent material was completely broken down and the vein graft was relined with urothelium. It resembled native ureter with cytokeratin-7 positive columnar epithelium and newly formed capillaries in the ureteral wall. All animals had normal kidney function without renal pelvis congestion.This new technique for ureteral defect reconstruction using an autologous vein graft and a biodegradable endoluminal stent is feasible. It is an interesting alternative in the clinic due to the preservation of physiological urine passage and the antireflux mechanism.

Background De novo sirolimus in calcineurin inhibitor-free regimens, although potentially useful to improve early renal function, are complicated by various drug-related side effects. Methods We report a prospective open-label, multicenter, randomized trial to evaluate early conversion from a CsA-based to a sirolimus (SRL)-based regimen 10 to 24 days after renal transplantation. Of the 196 patients, 141 patients with a low-to-moderate immunological risk were eligible to be converted to SRL or to continue CsA. All patients received antithymocyte globulin-F single-bolus induction, mycophenolate mofetil, and steroids. Results The primary endpoint, renal function determined by S-creatinine and estimated glomerular filtration rate calculated by Nankivell formula at 12 months was significantly better in the SRL group (1.51+/-0.59 vs. 1.87+/-0.98 mg/dL or 64.5+/-25.2 vs. 53.4+/-18.0 mL/min/1.73 m). Patient survival, graft survival, and incidence of biopsy-proven acute rejection after conversion were not statistically different. Drug discontinuations were significantly higher in the SRL group (36.2% vs. 19.7%). Significantly, more patients in the SRL group reported acne, aphtous, and temporary hyperlipidemia, whereas cytomegalovirus viremia was significantly decreased (7.3% vs. 28.2%). Conclusions Early conversion to a calcineurin inhibitor-free regimen with SRL in combination with mycophenolate mofetil may be a useful strategy to improve renal function. The identification of appropriate candidates and safe management of SRL-related adverse events will be a key to avoid the high rate of dropouts, which currently limit the broad applicability of this protocol.

The objective of this study was to identify genomic alterations in resectable pancreatic cancer (PCA). Chromosomal imbalances were correlated with histopathological and clinical data to verify their prognostic significance.Specimens of 33 PCA were investigated by comparative genomic hybridization. Microdissection was used for separation of PCA from the normal cells before isolation of DNA; nick-end labeling and hybridization were performed according to standard protocols. Aberrations were correlated with staging and grading using log-rank test and Cox regression. Survival rates were plotted using the Kaplan-Meier method.Twenty-eight (85%) PCA showed aberrations. Gains of chromosomal material were most frequently identified on 8q (42%), 13q (30%), 18p (21%), and 3q (18%). Genetic losses were frequently detected on 1p (45%), 22 (42%), 19 (36%), 17p (27%), 18q and 8p (15% each), and 3p (12%). Losses of 8p (n = 5) and 3p (n = 4) were only detected in stages III and IV (P0.05). Median survival time of all patients was 13 months. Median survival time of patients with aberration of 8q (n = 14) was 8.5 months compared to 16 months in patients without gain of 8q (n = 19; P = 0.029).The chromosomal regions containing genetic alterations represent potential loci for new target genes in PCA. The significant correlation of gain of chromosome 8q with short survival time suggests that 8q may be a new marker to assess prognosis and malignant potential of resected PCA in the individual patient, thereby helping to identify patients at risk for recurrence that might profit from adjuvant therapy.