Murat Barlan

Efficacy of liver transplantation for alcoholic cirrhosis with respect to recidivism and compliance.

Many transplant centers are reluctant to accept alcoholic patients for OLT because of their supposed potential for alcoholic recidivism and poor compliance with the required immunosuppressive regimen, both of which result in graft failure. Only inconclusive data related to these arguments are available. From May 1982 to January 1993, 58 patients received OLT at our institution for end-stage cirrhosis, where alcohol was the only toxic component. The indication for OLT in these patients was considered with particular attention to recidivism and compliance. Overall survival in this group was 71% and 63% at 1 and 5 years, respectively, with an average survival time of 78 months. Actuarial survival of patients transplanted since January 1989 (n = 37) was 86% and 83% at 1 and 2 years (average survival 42 months). Nonfatal clinical endpoints were analyzed in those patients surviving at least 3 months (n = 44). Return to alcohol abuse has been documented in 14 persons at routine short-term outpatient checkups. The estimated risk for alcoholic recidivism amounts to 31%, with a median follow-up of 33 months. Compliance with immunosuppressive regimen was expressed as a dependent value of acute rejection episodes (0.3 per patient, median follow-up 33 months), chronic rejection (occurred in none of the patients), and measurements of CsA HPLC blood trough level (92.2% within the target range). The preversus postoperative improvement of employment, marital, and social status after OLT showed a statistically significant difference. Unwillingness to offer OLT to individuals with alcoholic liver disease because of failure to demonstrate 100% long-term abstinence appears difficult to defend in the face of good results in survival, compliance, and social rehabilitation.

Surgical treatment for severe acute pancreatitis: extent and surgical control of necrosis determine outcome.

In patients operated on for severe acute pancreatitis (SAP), the factors determining outcome remain unclear. From 1986 to 1998 a total of 340 patients with a diagnosis of SAP and in need of operative treatment were admitted to the intensive care unit (ICU) of a university hospital and a secondary care hospital. The mean APACHE II score on the day of admission was 16.1 (range 8–35). All patients required operative therapy. Among the 340 patients, 270 (79.4%) had to be reoperated: 196 patients (72.6%) underwent operative revisions on demand, and 74 (27.4%) patients had preplanned reoperation. The overall mortality was 39.1% (133 patients). Septic organ failure in 126 patients (37.1%) and myocardial infarction or pulmonary embolism in 7 patients (2%) were the causes of death. The patient’s age (p <0.0002), APACHE II scores at admission (p <0.0001), presence or development of (single or multiple) organ failure (p <0.002), infection (p <0.02) and extent (p <0.04) of pancreatic necrosis, and surgical control of local necrosis (p <0.0001) significantly determined survival. SAP that requires surgical treatment is associated with high in-hospital mortality. Surgical control of local necrosis is the precondition for survival. Advanced age of the patient, high APACHE II score at admission, development of organ failure, and the extent and infection of pancreatic necrosis influence the outcome.

Candida infection of local necrosis in severe acute pancreatitis is associated with increased mortality.

The aim of this study was to evaluate the frequency of Candida infection of pancreatic necrosis in patients suffering from severe acute pancreatitis (SAP) and to analyze its impact on the outcome. Two-hundred and fifty consecutive patients with SAP from January 1986 to December 1998 were studied retrospectively. Their mean APACHE II score at the day of admission was in 16.1 (range 8-35). All patients were in need of operative therapy. Overall mortality was 38.8% (97 patients). One-hundred and eighty-two patients (72.8%) suffered from local infected necrosis. Among these patients, local Candida infection was observed in 31 patients, whereof 23 patients (74%) suffered from local fungal infection detected at first operation. During the course of disease, 12 patients (39%) also revealed fungemia. Local Candida infection as compared to no Candida infection was associated with an increased mortality rate (84% vs. 32%; P 0.0001). Multivariate logistic regression analysis identified APACHE II score (P < 0.0001), age of the patient (P < 0.003), extent of pancreatic necrosis (P < 0.002), and local bacterial (P < 0.04) and fungal infection (P < 0.004) as independent factors significantly contributing to mortality. SAP, requiring surgical treatment, is associated with high in-hospital mortality. Patients suffering from local Candida infection are at high risk of fatal outcome.

Severe acute pancreatitis causes alterations in HLA-DR and CD14 expression on peripheral blood monocytes independently of surgical treatment

OBJECTIVE To find out if the severity of acute pancreatitis or the surgical treatment of severe acute pancreatitis influences HLA-DR and CD14 expression on peripheral blood monocytes. DESIGN Prospective open study. SETTING University hospital, Austria. SUBJECTS 9 consecutive patients with severe acute pancreatitis in need of operative treatment, 5 patients with mild acute pancreatitis, and 7 healthy volunteers. INTERVENTIONS Samples of 5 ml blood were taken daily into endotoxin free tubes at same time points. Surgical treatment for severe acute pancreatitis consisted of blunt necrosectomy, operative lavage, laparostomy, and open drainage. MAIN OUTCOME MEASURES Correlation between HLA-DR and CD14 expression on peripheral blood monocytes on the one hand and the severity of acute pancreatitis and operative treatment of severe acute pancreatitis, on the other. RESULTS In patients with severe acute pancreatitis expression of HLA-DR and CD14 was significantly downregulated both before and after operation (p < 0.0001; ANOVA), compared with patients with mild acute pancreatitis or healthy controls. However the expression of the two cell surface markers was not affected either by the first operation, or by the reoperations. CONCLUSION These findings suggest that in acute pancreatitis the expression of cell surface markers on peripheral blood monocytes is related to the severity of disease but is not influenced by operative treatment.

The surgical concepts of planned and on-demand reoperation in the treatment of diffuse intra-abdominal infection

SummaryBackground: Planned and “on-demand” reoperations are well established concepts in the management of severe diffuse peritonitis. Both concepts being applied at our surgical department, were reviewed regarding specific complications and lethality. Methods: During a five year study period 62 patients with the diagnosis of diffuse peritonitis underwent operative treatment at the department of surgery, University of Vienna. The mean age of 29 female and 33 male patients was 58.2 years (range 17–93 years). The origin of peritonitis was the stomach in 8.1 %, duodenum in 16.1 %, small intestine in 12.9 %, large intestine in 41.9 % and the pancreas in 16.1 %. Results: Among these 62 patients 15 patients were reoperated according to plan and 47 were reoperated on demand. The intraoperatively gained Mannheim peritonitis index as well as the Apache II Score were similar in both groups. The average number of reoperations was 5 in the group of planned revisions and 3 in the group of on-demand revisions. In both groups mortality was similar. Regarding mortality only the age of the patient (p<0.03) and the preoperatively assessed Apache II Score (p<0.01) reached statistical significance. As expected the eradication of the infectious source was precondition of survival regardeless the type of reoperation. Conclusions: Planned or on-demand reoperations lead to similar results in the surgical treatment of diffuse peritonitis. The crucial point of success is an early as possible and consequent elimination of the infectious source.ZusammenfassungGrundlagen: Die geplante Revision und die „On-demand“-Relaparotomie sind etablierte Konzepte in der chirurgischen Therapie der schweren diffusen Peritonitis. Diese beiden Konzepte, parallel an unserer Klinik eingesetzt, wurden in einer retrospektiven Analyse bezüglich spezifischer Komplikationen und Letalität verglichen. Methodik: An der Chirurgischen Universitätsklinik Wien wurden in einem fünfjährigen Studienzeitraum 62 Patienten mit diffuser Peritonitis in ein Relaparotomieprogramm aufgenommen. Das Durchschnittsalter der 29 weiblichen und 33 männlichen Patienten betrug 58,2 Jahre (17–93 Jahre). Ausgangspunkt der Peritonitis war bei 5 Patienten (8,1 %) der Magen, bei 10 Patienten (16,1 %) das Duodenum, bei 8 Patienten (12,9 %) der Dünndarm, bei 26 Patienten (41,9 %) der Dickdarm, bei 3 Patienten (4,9 %) sowohl Dünn- als auch Dickdarm, bei 10 Patienten (16,1 %) eine Pankreatitis. Ergebnisse: Diese 62 Patienten mußten nach dem Primäreingriff ein oder mehrere Male revidiert werden, wovon 15 Patienten geplant und 47 Patienten „on-demand“ revidiert wurden. Die Entscheidung über die chirurgische Taktik blieb der subjektiven Einschätzung des Operateurs vorbehalten. Sowohl der intraoperativ erhobene Mannheim-Peritonitis-Index als auch der Apache-II-Score waren in beiden Revisionsgruppen gleich. Die durchschnittliche Revisionsanzahl betrug in der Gruppe der geplanten Revisionen 5 und in der Gruppe der „On-demand“-Revisionen 3. Die Letalität war in beiden Gruppen gleich groß („Ondemand“-Revision: 48,1 %, geplante Revision: 43 %; p<0,4). Prognostisch relevant hinsichtlich der Letalität waren das Alter (p<0,03) und der Apache-II-Score (p<0,01). Unabhängig vom Revisionstyp war jedoch die rasche Sanierung der Sepsisquelle Grundvoraussetzung für das Überleben. Bei allen überlebenden Patienten konnte die Peritonitisquelle nach durchschnittlich 1,2 Revisionen saniert werden. Schlußfolgerungen: Die geplante und die „On-demand“-Revision erzielen im chirurgischen Therapiekonzept der diffusen Peritonitis vergleichbare Ergebnisse. Entscheidend für den Erfolg ist nicht die Anwendung eines dieser Konzepte, sondern die möglichst rasche und konsequente Sanierung der Peritonitisquelle.

Prediction of graft dysfunction by analysis of liver biopsies after cold storage

Abstract  Failure of the hepatic al‐lograft continues to be a serious life‐threatening risk for the recipient. Because no effective method of ex‐tracorporeal support is available for these patients, early retransplanta‐tion is the only alternative that offers the potential for survival. The aim of this prospective analysis was to search for a predictor of primary non‐function of hepatic allografts before reperfusion. From March to June 1993 we investigated 19 liver biopsies which were obtained during the preparation of the donor liver in the back table bath immediately before the implantation of the organ. All organs were preserved by UW solution. Biopsies were stored at ‐80°C, the working‐up process was started by dividing the biopsy into several portions for the determination of fat (petrol‐ether extraction), water (weighing before thawing and after drying) and free amino acids (OPA‐HPLC method). Graft function was categorized into three groups: (1) good function; (2) fair function; (3) primary non‐function (PNF). In addition to known risk factors for delayed graft function such as a long stay of the donor in intensive care and a prolonged an‐hepatic period of the recipient, we were able to demonstrate that organs with malfunction had a higher fat and water content. Donor livers developing PNF showed a trend towards higher total and subdivided amino acids, which could be explained by the incapacity of the liver to utilize available substrates for gluconeogenesis.

Reasons for 50% reduction in the number of organ donors within 2 years--opinion poll amongst all ICUs of a transplant centre.

Abstract To detect the reasons for a massive decrease in the annual number of organ donors and as a means of evaluating the effectiveness of our information programme, a questionnaire was designed and sent to all intensive care units (ICUs) in our catchment area. We wished to obtain information about medical, organizational and capacity problems and negative occurrences that had happend during past retrievals. Although 60% of the answers we reiceved (87% feedback rate) mentioned the additional workload involved in treating an organ donor (and 88% had serious problems because of the shortage of nurses), less than 16% remembered a “lost” donor because of capacity problems. Eighty‐ix percent recognized our efforts to support them in any respect and were satisfied with the amount of “service” provided by the transplantation (TX) centre. About 45% remembered negative occurrences. More than 85% of all replies asked for more and continuing information related to organ donation and transplantation. We think that the key to a successful TX programme is a system of active care for the ICU staff in all peripheral hospitals; repeated mailing of updated information brochures, annual lectures about new developments, letters of thanks after each reported donor (including information on the fate of the organs), visiting donor ICUs accompanied by successfully transplanted recipients, etc. The downwards trend of donor rates in our area clearly shows that it takes more than a stable legal situation to ensure the necessary amount of donor organs, even a very successful TX centre has to work hard to maintain a certain standard of knowledge, information and motivation amongst the staff of the peripheral hospitals. Moreover, the high turnover rate of ICU personnel requires a steady “flow of information” and cooperation between the “transplant people” and their coworkers outside to guarantee a permanent state of awareness concerning organ donation and transplantation. In fact, awareness seems to be the key issue: the activity of sending out the questionnaires was enough to raise the number of reported donors from 72 (estimated in July) to 96 (31 December 1992).

Immunological risk factors are solely responsible for primary non‐funetion of renal allografts

Abstract Primary non‐function (PNF) of renal allografts has been attributed to various risk factors, among them immunological ones, as well as unfavourable preservation conditions. To investigate the impact of these risk factory on the occurrence of PNF, 1335 consecutive kidney transplants performed at a single centre over a 10‐year period were analysed. All patients received immunosuppression based on cyclosporine. As the method of analysis a conditional stepwise logistic regression model was chosen, comparing each graft suffering PNF with its partner kidney retrieved from the same donor. Thus, all donor‐related variables could be omitted from the analysis, as they are the same in every pair of grafts. Risk factors analysed included panel‐reactive antibodies, number of pretransplant transfusions, pregnancies, number of prior transplants, cold and second warm ischaemia time, mismatches on HLA loci A, B and DR and recipient age. The overall incidence of PNF was 87 grafts (6.5%). One patient suffered immediate rejection due to transplantation of an ABO incompatible graft. This case was excluded from further analysis. PNF occurred three times in recipients of living related grafts, twice in recipients of en‐bloc grafts and four times in grafts, in which the paired kidney was either not transplanted or shipped outside the Eurotransplant region, so that no paired graft was available for matched case‐control analysis. Of the remaining 77 pairs, twice both organs of one donor failed immediately. The remaining 73 complete pairs were analysed. Two of the investigated risk factors have independently a significant impact on the occurrence of PNF. Increasing the number of pretransplant transfusions raises the relative risk of graft failure up to six fold (P=0.02), while a history of prior transplants bears a felative risk of 0.21E05 (P=0.005). Ischaemia has no significant impact on the occurrence of PNF. Our data strongly suggest that immunological rather than donor risk factors are responsible for the non‐function of kidney grafts.