Status quo of operative training in emergency surgery in Germany - results of a survey.

BACKGROUND: Emergencies and emergency surgeries are a central part of everyday surgical care in Germany. However, it is unclear how emergency surgery is practically trained in clinics on a daily basis and what training concept is underlying. Therefore, the aim of this survey study was to capture the status quo of emergency surgical training of German general and visceral surgeons. METHODS: The members of the German Society for General and Visceral Surgery were surveyed online (n = 5281). The questionnaire included demographic data and expertise in surgery and assistance in emergency surgery regarding common emergency surgical operations. In addition, further training measures in emergency surgery and their support by employers were queried. RESULTS: Only complete questionnaires (n = 184, response rate 3.5%) were included in the analysis. Most participants were in training (n = 69; 38%), followed by senior physicians (n = 52; 29%), specialists (n = 31; 17%) and chief physicians (n = 30; 17%). 64% of the participants were employed at university hospitals or maximum care hospitals. Regarding further training opportunities, in-clinic shock room training was most frequently used. Outside of their own clinic, the ATLS course was most frequently mentioned. Operations for cholecystitis and appendicitis as well as emergency stoma procedures are the most common emergency procedures. There was a strong difference in the frequency of operated cases depending on the level of training. For operations to treat acute abdominal traumas (hemostasis of liver and spleen, packing) as well as outside of visceral surgery, only low competence was reported. Over 90% of survey participants consider emergency surgery to be an indispensable core competence. Neither in the old (76%) nor in the new training regulations (47%) is emergency surgery adequately represented according to the participants' assessment. There was a significantly lower prevalence of the "sub-steps concept" in emergency surgery at 38% compared to elective surgery (44%). Important elements of imparting skills in emergency surgery are simulation and courses as well as operative sub-steps, according to the majority of survey participants. CONCLUSION: The results show that general and visceral surgeons in Germany are introduced to emergency surgery too little structured during further training and at specialist level. The survey participants had, as expected, hardly any experience in emergency surgery outside of visceral surgery but surprisingly also little experience in visceral surgical trauma care. There is a need to discuss the future organization of emergency surgical training. Adequate simulation structures and extracurricular courses could contribute to an improvement in this respect.

Hybrid-ALPPS followed by Ante Situm with Cardiopulmonary Bypass: Rapid Liver Augmentation and Complex Surgery.

BACKGROUND: Tumors invading the inferior vena cava (IVC) and hepatic veins pose a challenge for surgeons. Hannoun et al.1 were able to show that the resection of these tumors can be done under hypothermia in the Ante-Situm position. Additionally, not only the localization of the tumor but the remaining volume of the remnant liver (FLR) needs to be considered. Schnitzbauer et al.2 were able to induce massive liver hypertrophy in a short period, combining an in-situ split with a portal vein ligation (ALPPS). As this controversial technique has evolved, a safe ALPPS can be performed nowadays.3 To our knowledge, this is the first case that combines a laparoscopic partial ALPPS with an extended resection requiring cardiopulmonary bypass (CPB). METHODS: A 58-year-old female presented with a known chronic hepatitis C suffered from a pulmonary embolism, caused by a large, central hepatocellular carcinoma (HCC) with invasion of the suprahepatic IVC and continuous growth into the right atrium (RA). Due to the small FLR, we performed a laparoscopic hybrid-partial-ALPPS with an embolization of the right portal vein. We were able to remove the mass with an Ante-Situm position and resection of the RA under CPB. RESULTS: The postoperative course was complicated by posthepatic liver failure and bleeding. However, after 28 days the patient was discharged in a good medical condition. CONCLUSIONS: Although tumors invading the suprahepatic IVC and RA pose a surgical challenge, patients can be treated adequately with multidisciplinary management. Advanced HCCs have high recurrence rates; however, a R0 resection might improve overall survival. Wakayma et al. showed in their retrospective study with 13 patients a median survival of 30.8 months when a complete resection was performed.4 Our patient had a disease-free survival of 11 months and is still alive after 24 months. Taking the complexity of the operation and the oncological prospect with a probable recurrence into account, indication for surgery needs to be considered on an individual basis.

Mortality after liver surgery in Germany.

BACKGROUND: Mortality rates after liver surgery are not well documented in Germany. More than 1000 hospitals offer liver resection, but there is no central regulation of infrastructure requirements or outcome quality. METHODS: Hospital mortality rates after liver resection were analysed using the standardized hospital discharge data (Diagnosis-Related Groups, ICD-10 and German operations and procedure key codes) provided by the Research Data Centre of the Federal Statistical Office and Statistical Offices of the Länder in Wiesbaden, Germany. RESULTS: A total of 110 332 liver procedures carried out between 2010 and 2015 were identified. The overall hospital mortality rate for all resections was 5·8 per cent. The mortality rate among 17 574 major hepatic procedures was 10·4 per cent. Patients who had surgery for colorectal liver metastases (CRLMs) had the lowest mortality rate among those with malignancy (5·5 per cent), followed by patients with gallbladder cancer (7·1 per cent), hepatocellular carcinoma (9·3 per cent) and intrahepatic cholangiocarcinoma (11·0 per cent). Patients with extrahepatic cholangiocarcinoma had the highest mortality rate (14·6 per cent). The mortality rate for extended hepatectomy was 16·2 per cent and the need for a biliodigestive anastomosis increased this to 25·5 per cent. Failure to rescue after complications led to mortality rates of more than 30 per cent in some subgroups. There was a significant volume-outcome relationship for CRLM surgery in very high-volume centres (mean 26-60 major resections for CRLMs per year). The mortality rate was 4·6 per cent in very high-volume centres compared with 7·5 per cent in very low-volume hospitals (odds ratio 0·60, 95 per cent c.i. 0·42 to 0·77; P < 0·001). CONCLUSION: This analysis of outcome data after liver resection in Germany suggests that hospital mortality remains high. There should be more focused research to understand, improve or justify factors leading to this result, and consideration of centralization of liver surgery.

ANTECEDENTES: En Alemania, los datos de mortalidad después de la cirugía no están bien documentados. En más de 1.000 hospitales se realizan resecciones hepáticas, pero no existe una regulación central de los prerrequisitos estructurales necesarios y de la calidad de los resultados. MÉTODOS: Las tasas de mortalidad hospitalaria relacionadas con las resecciones hepáticas se analizaron utilizando los datos estandarizados del alta hospitalaria (Diagnóstico de grupos relacionados, DRG), la clasificación internacional de enfermedades 10 (ICD10) y la clave de procedimientos y operaciones (códigos OPS) proporcionados por el RDC de la Oficina Federal de Estadística y Oficinas de Estadística de Länder en Wiesbaden, Alemania. RESULTADOS: Se identificaron un total de 110.332 procedimientos hepáticos (de 2010 a 2015). La tasa global de mortalidad hospitalaria para todas las resecciones fue del 5,8%. Las resecciones hepáticas mayores (n = 15.333) presentaron una mortalidad del 10,4%. Los pacientes con metástasis hepáticas colorrectales (colorectal liver metastases, CRLM) tuvieron la mortalidad más baja de entre los pacientes con neoplasias malignas (5,5%), seguidos de los pacientes con cáncer de vesícula biliar (7,1%), colangiocarcinoma intrahepático (intrahepatic colangiocarcinoma, iCC) (11,0%) y carcinoma hepatocelular (hepatocellular carcinoma, HCC) (9,3%). Los pacientes con colangiocarcinoma extrahepático (extrahepatic cholangiocarcinoma, eCC) presentaron la mortalidad más alta (14,6%). Las hepatectomías extendidas (16,2%) y la necesidad de una anastomosis biliodigestiva (biliodigestive anastomosis, BDA) aumentaron la mortalidad a un 25,5%. La falta de solución de algunas complicaciones llevó a tasas de mortalidad de más del 30% en algunos subgrupos. Hubo una relación significativa volumen-resultado para las CRLM en centros de alto volumen (25,3 a 59,7 resecciones mayores/año; razón de oportunidades, odds ratio, OR 0,60, i.c. del 95%: 0,42-0,77; P < 0,001), lo que resultó en una disminución en las tasas de mortalidad de 7,5/6,4/7,5/6,5% a 4,6%. CONCLUSIÓN: El análisis de los resultados después de la resección hepática en Alemania muestra una alta mortalidad hospitalaria inesperada. Este análisis indica la necesidad de efectuar una investigación más específica para comprender, mejorar o justificar los factores que determinan estos hallazgos.

[Chylous ascites and acute appendicitis - more than an accidental finding?]. / Chylöser Aszites bei akuter Appendizitis - Zufallsbefund oder ätiologischer Zusammenhang?

INTRODUCTION: Chylous ascites with a simultaneously presenting acute appendicitis is a uncommon finding which has been rarely reported in present literature. CASE REPORT: We present the case of a 36 years old patient showing the clinical signs of an acute appendicitis with an intraoperative finding of chylous ascites. DISCUSSION: The causing factors for chylous ascites are numerous, the clinical manifestations nonspecific. Thus the adequate diagnostic measures vary. The therapy is mainly based on medicational and dietary treatment but also benefits from a surgical approach.

Single center experience of endoscopic submucosal dissection (ESD) in early Barrett's adenocarcinoma.

BACKGROUND: Endoscopic mucosal resection (EMR) or radical surgical resection are the standard treatment options for patients with early Barrett's adenocarcinoma (EBAC). Endoscopic submucosal dissection (ESD) is a new endoscopic technique, which allows--in contrast to EMR--endoscopic en-bloc resection of neoplastic lesions greater than 2 cm with complete histological evaluation of the resected specimen. In contrast to Western countries, Barrett's esophagus is less common in Asia indicating the low volume of published data of ESD in EBAC in Japanese series. Therefore, the aim of the present study is to describe the results of ESD in patients with EBAC performed in a German tertiary referral center. METHODS: Between November 2009 and April 2014 ESDs were performed in 22 patients with histologically proven EBAC. Data were given for the en-bloc, the R0, the R0 en-bloc, and the curative resection rate as well as for the complication and the local recurrence rate. RESULTS: ESD was technically possible in all of the 22 patients. 20 of the resected EBAC were mucosal carcinomas, whereas in two patients the tumor showed submucosal invasion. The en-bloc, R0, R0 en-bloc, and curative resection rates were 95.5, 81.8, 81.8 %, and 77.3 %, resp. Complication rate was 27.3 % (perforation n = 1, bleeding n = 2, stenosis n = 3). In case of curative tumor resection, only one local tumor recurrence (5.9 %) occurred after a medium follow-up of 1.6 years. CONCLUSIONS: Despite the small number of patients and a relatively short follow-up, the present data underline the value of ESD, especially in case of curative resections in the definite and less invasive therapy of EBAC. Attention should be drawn toward subsquamous extension of EBAC requiring a sufficient safety margin as an obligate condition for curative R0 resections. Due to the required learning curve and the management of potential complications, ESD should be restricted to greater endoscopic centers.

[Single centre experience of endoscopic submucosal dissection (ESD) in premalignant and malignant gastrointestinal neoplasia]. / Single-Center-Erfahrung mit der Endoskopischen Submukosa-Dissektion (ESD) bei prämalignen und malignen gastrointestinalen Neoplasien.

INTRODUCTION: Worldwide endoscopic submucosal dissection (ESD) of early GI cancers or premalignant neoplasia is becoming increasingly important. In Germany ESD is restricted to larger endoscopic institutions and only a few literature reports are available. The aim of the present study is to describe the results of 46 ESDs conducted in a German endoscopic centre. MATERIAL AND METHODS: Between June 2007 and May 2012 46 ESDs in 45 patients (33 men, 12 women, mean age 66.1 years) were performed in the oesophagus (n = 17), stomach (n = 23) and rectum (n = 6). Data were collected for the en-bloc, R0 and R0 en-bloc resection rates as well as for complications, the curative resection and the local recurrence rates. In order to demonstrate a learning curve, results were evaluated for two periods (June 2007 to November 2010 vs. December 2010 to May 2012). RESULTS: ESD was technically possible in 93.5%. En-bloc, R0, R0 en-bloc and curative resection rates were 90.7%, 74.4%, 67.4% and 65.1%, respectively. The complication rate was 13%. In the second period en-bloc and R0 en-bloc resection rates increased from 81% to 100% and, respectively, from 52.4% to 81.8%. After a medium follow-up of 11.4 months, local tumour recurrence occurred in 10%. In cases of curative R0 en bloc resection of malignant tumours no tumour recurrence occurred. DISCUSSION: Despite the small number of patients, the present data underline the value of ESD, especially in cases of R0 en-bloc resections in the therapy for premalignant and early malignant GI tumours. Due to the required learning curve, ESD should be restricted to larger endoscopic centres in Germany.

[EHEC-associated colon stenosis after ulcerous-chronic haemorrhagic colitis and consecutive resulting ileus]. / EHEC-assoziierte Kolonstenose nach ulzerös-chronisch hämorrhagischer Kolitis mit konsekutivem Ileus.

We report on the case of a segmentally emphasised, ulcerous chronic haemorrhagic colitis with the development of granulation tissue und scarred fibrosis with consecutive resulting stenosis of the colon. A 49-year-old male patient was infected with enterohaemorrhagic Escherichia coli bacteria during the EHEC-epidemic in northern Germany in early summer 2011. In the course of the infection the patient suffered from haemolytic uraemic syndrome (HUS) with acute renal failure and neurological symptoms. Haemodialysis and plasmapheresis had become mandatory. A simultaneous ileus was estimated to be of paralytic origin. One month after treatment of the acute phase of the infection a CT scan of the abdomen was performed and discovered a symptomatic stenosis of the proximal colon transversum. This obstruction needed to be treated by performing a right hemicolectomy with an ileo-transverso anastomosis. After surgery the patient recovered continuously. The histopathological examination verified an ulcerous-chronic haemorrhagic colitis on the background of an EHEC infection.

[Importance of displacement ventilation for operations and small surgical procedures from the infection preventive point of view]. / Infektiologische Bedeutung von Raumlufttechnischen Anlagen (RLTA) in Operations- und Eingriffsräumen.

Surgical teams need to breathe air that is conducive to their health. An adequate exchange of air ensures oxygen supply, the ventilation of humidity, smells, toxic substances, especially narcotic gases and surgical smoke, pathogens and particles. With regard to the infection risk, DIN 1946 / 4 -differentiates between operation theaters with the highest demand for clean air (operation room class I a), operation theatres with a high demand (operation room class I b) and rooms within the operation theatres without special requirements, meaning that the microbial load in the air is close to or equal to that of normal in-room air quality (room class II). For an operation room class I a, ventilation that displaces the used air is necessary, while a regular ventilation is sufficient for operation room class I b. Because of ambiguous -results in previous studies, the necessity to define a -class I a for operation rooms is being questioned. Therefore, this review focuses on the analysis of the existing publications with respect to this -question. The result of this analysis indicates that so far there is only one surgical procedure, the -implantation of hip endoprosthetics, for which a preventive effect on SSI of a class I a ventilation (displacement of the used air) is documented. One recent study, reviewed critically here, -showed opposite results, but lacks methodological clarity. Thus, it is concluded that evidence for the requirement of operation room classes can only be derived from risk assessment (infection risk by surgical intervention, extent of possible damages), but not from epidemiological studies. Risk assessment must be based on the following criteria: size and depth of the operation field, -duration of the procedure, vascular perfusion of the wound, implantation of alloplastic material and general risk of the patient for an infection. From an infection preventive point of view, no class I a "displacement ventilation" is necessary for small surgical procedures for which the RKI recommends only a procedure room, and for surgical procedures for which a risk evaluation indicates that the air in the operation theater can be equal to normal air.

Unresectable Hepatic Metastasis of Uveal Melanoma: Hepatic Chemosaturation with High-Dose Melphalan-Long-Term Overall Survival Negatively Correlates with Tumor Burden.

INTRODUCTION: Percutaneous hepatic perfusion with melphalan (PHP-M) for hepatic metastasis of uveal melanoma (LMUM) achieves high local response rates, but the individual clinical benefit is poorly defined. We aimed to determine cofactors of response and clinical outcomes including the probability of long-term (5-years) overall survival (OS) in PHP-M-treated patients with LMUM. Patients and Methods. We retrospectively reviewed clinicopathological, radiological, and outcome data of 19 patients with unresectable LMUM treated with 43 PHP-M (median 2 PHP-M) between 2014 and 2019. Tumor response and adverse events were evaluated using RECIST 1.1 and the Clavien-Dindo classification. Kaplan-Meier methods and Cox regression hazard proportional models were used. RESULTS: Of 19 patients, 10 (53%) achieved a partial response (PR) and 9 (47%) had stable disease (SD). There was no progressive disease (PD) and no adverse events exceeding Clavien-Dindo grade IV. Median OS was 16.7 months after the first PHP-M treatment and 26.4 months after initial diagnosis. Low hepatic tumor volume (median of 10 mL vs. 150 mL) was an independent predictor of favorable OS (hazard ratio (95% confidence interval): 0.190 (0.041, 0.893); p < 0.05), and female patients were at a lower risk compared with males (0.146 (0.017, 1.240)). Estimates of the overall survival were 0.213 (0.0449, 1) from first imaging (95% confidence interval) to 5 years and 0.793 (0.609, 1) and 0.604 (0.380, 0.960) for 1 and 2 years after chemosaturation, respectively. Discussion. PHP-M for nonresectable LMUV provides a safe and locally efficient liver-directed procedure that offers patients a chance for long-term OS, especially for patients with a low hepatic tumor burden.

Metachronous hepatic resection for liver only pancreatic metastases.

BACKGROUND: The value of liver resection (LR) for metachronous pancreatic ductal adenocarcinoma (PDAC) metastases remains controversial. However, in light of increasing safety of liver resections, surgery might be a valuable option for metastasized PDAC in selected patients. METHODS: We performed a retrospective, multicenter study including patients undergoing hepatectomy for metachronous PDAC liver metastases between 2004 and 2015 to analyze postoperative outcome and overall survival. All patients were operated with curative intent. Patients with oligometastatic metachronous liver metastasis with definitive chemotherapy (n = 8) served as controls. RESULTS: Overall 25 patients in seven centers were included in this study. The median age at the time of LR was 63.8 years (56.9-69.9) and the median number of metastases in the liver was 1 (IQR 1-2). There were eight non-anatomical resections (32%), 15 anatomical minor (60%) and 2 major LR (8%). Postoperative complications occurred in eleven patients (eight Clavien-Dindo grade I complications (32%) and three grade IIIa complications (12%), respectively). The 30-day mortality was 0%. The median length of stay was 8.6 days (IQR 5-11). Median overall survival following LR was 36.8 months compared to 9.2 months in patients with metachronous liver metastasis with chemotherapy (p = 0007). DISCUSSION: Liver resection for metachronous PDAC metastasis is safe and feasible in selected patients. To address general applicability and to find factors for patient selection, larger trials are urgently warranted.

[Navigated liver surgery : Current state and importance in the future]. / Navigierte Leberchirurgie : Aktueller Stand und Bedeutung in der Zukunft.

The preoperative computer-assisted resection planning is the basis for every navigation. Thanks to modern algorithms, the prerequisites have been created to carry out a virtual resection planning and a risk analysis. Thus, individual segment resections can be precisely planned in any conceivable combination. The transfer of planning information and resection suggestions to the operating theater is still problematic. The so-called stereotactic liver navigation supports the exact intraoperative implementation of the planned resection strategy and provides the surgeon with real-time three-dimensional information on resection margins and critical structures during the resection. This is made possible by a surgical navigation system that measures the position of surgical instruments and then presents them together with the preoperative surgical planning data. Although surgical navigation systems have been indispensable in neurosurgery and spinal surgery for many years, these procedures have not yet become established as standard in liver surgery. This is mainly due to the technical challenge of navigating a moving organ. As the liver is constantly moving and deforming during surgery due to respiration and surgical manipulation, the surgical navigation system must be able to measure these alterations in order to adapt the preoperative navigation data to the current situation. Despite these advances, further developments are required until navigated liver resection enters clinical routine; however, it is already clear that laparoscopic liver surgery and robotic surgery will benefit most from navigation technology.

[Approach to liver, spleen and pancreatic injuries including damage control surgery of terrorist attacks]. / Vorgehen bei Leber­, Milz­ und Pankreasverletzungen inklusive "damage control surgery" bei Terroranschlägen.

BACKGROUND: Terrorist attacks have outreached to Europe with more and more attacks on civilians. Derived from war surgery experience and from lessons learned from major incidents, it seems mandatory for every surgeon to improve understanding of the special circumstances of trauma following a terrorist attack and its' management. METHOD: A short literature review is followed by outlining the damage control surgery (DCS) principle for each organ system with practical comments from the perspective of a specialized hepatobiliary (HPB) surgery unit. CONCLUSION: Every surgeon has to become familiar with the new entities of blast injuries and terrorist attack trauma. This concerns not only the medical treatment but also tailoring surgical treatment with a view to a lack of critical resources under these circumstances. For liver and pancreatic trauma, simple treatment strategies are a key to success.

A safe and feasible "clock-face" duct-to-mucosa pancreaticojejunostomy with a very low incidence of anastomotic failure: A single center experience of 248 patients.

INTRODUCTION: Postoperative pancreatic fistula (POPF) is one of the most frequent and serious postoperative complications of pancreatoduodenectomy (PD). We sought to assess the impact of a novel pancreaticojejunostomy (PJ) on the rates of POPF and overall postoperative complications. METHODS: Between 01/2010 and 12/2013, a total of 248 consecutive patients who underwent PD with a modified PJ were identified from our database and retrospectively analyzed. POPF cases were divided into three categories (ISGPF-international study group-guidelines): biochemical fistula without clinical sequelae (grade A), fistula requiring any therapeutic intervention (grade B), and fistula with severe clinical sequelae (grade C). Perioperative outcomes were recorded and analyzed. RESULTS: The overwhelming majority of patients had no evidence of fistula. Grade A POPF was observed in 9 (3.62%), grade B in 1 (0.40%), and grade C in 0 patients. There were no postoperative deaths. Overall complications occurred in 61 patients (24.59%) of patients after PD. CONCLUSIONS: This modified pancreaticojejunostomy is widely applicable and is associated with very low rates of POPF, low postoperative morbidity and mortality. Overall, it is a feasible and safe novel approach with excellent short-term outcomes.

Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation.

PURPOSE: Tumor recurrence is the major limitation of long-term survival after liver transplantation for hepatocellular carcinoma (HCC) or fibrolamellar carcinoma (FLC). Understanding tumor-biologic characteristics is important for selection of patients and for development of adjuvant therapeutic strategies. PATIENTS AND METHODS: The study included 69 patients who underwent potentially curative liver transplantation for HCC/FLC and survived for more than 150 days; minimum follow-up was 33 months. Frequency, localization, and timing of recurrence were analyzed and compared with primary tumor and patient characteristics. RESULTS: Tumor recurrence was observed in 39 patients at 67 locations. Hematogenous spread was the major route of tumor recurrence (87%), and the most frequent sites were the liver (62%), lung (56%), and bone (18%). Parameters associated with recurrence were absence of cirrhosis, tumor size greater than 5 cm, more than five nodules, vascular infiltration, and International Union Against Cancer (UICC) stage IVA. Selective intrahepatic recurrence was found in nine patients (23%); it was associated with highly differentiated tumors, lack of vascular infiltration, and male sex. Recurrence at multiple sites was found predominantly in young patients (< or = 40 years) and for multicentric (> 5) primary tumors. Recurrences were observed within a wide time range after transplantation (43 to 3,204 days; median, 441 days); late recurrences (> 1,000 days, n = 8) were associated with highly differentiated or fibrolamellar tumors and low UICC stages. Surgical treatment was the only therapeutic option associated with prolonged survival after recurrence. CONCLUSION: In transplant recipients, hepatocellular carcinomas vary considerably in their pattern and kinetics of metastases. Tumor cells may persist in a dormant state for long time periods before giving rise to clinical metastases. Surgical treatment of recurrence should be considered whenever possible.

Biliodigestive anastomosis after intraoperative irradiation in swine.

A large animal model was established to investigate the feasibility and suitable dosage of intraoperative radiation therapy (IORT) to the hepatic hilum before biliary-enteric anastomosis is performed. Twenty-two Pietrain Hampshire pigs underwent gallbladder and proximal bile duct resection followed by IORT using 20-40 Gy and performing biliary-enteric anastomosis. In the follow-up period of 56 days, pigs developed dose-dependent complications like stenosis of the biliary-enteric anastomosis. Results demonstrate that IORT of the liver hilum up to 20 Gy is safe with acceptable early complications in the presented animal model. The porcine biliary-enteric anastomosis can tolerate intraoperative irradiation up to a dosage of 40 Gy without disruption.

How best to use tacrolimus (FK506) for treatment of steroid- and OKT3-resistant rejection after renal transplantation.

Nineteen patients with biopsy-confirmed ongoing acute rejection of renal allografts were converted from standard immunosuppression to FK506. Eight grafts showed vascular rejection and 11 had cellular rejection on biopsy. All patients had already received intravenous high-dose steroid treatment. Ten patients also had additional OKT3 rescue therapy. Initial FK506 doses were 0.13 +/- 0.06 mg/kg/day; the FK506 whole blood trough level after 3 days of treatment was 9.3 +/- 4.5 ng/ml. After conversion to FK506 all but four patients also received azathioprine, 1.5-2 mg/kg/day, and all patients received oral prednisolone. Concomitant with initiation of FK506, an anti-infective prophylaxis was prescribed, consisting of ganciclovir and trimethoprim/sulfamethoxazole. Sixteen out of 19 of the grafts (84%) were rescued successfully, including two grafts of patients already on hemodialysis at the time of conversion. Graft function of the responders improved from an average serum creatinine level of 364 +/- 109 mumol/L to 154 +/- 49 mumol/L. Of the patients receiving high-dose steroids alone prior to FK506 initiation, 8/9 responded to FK506 treatment, compared with 8/10 of those who had also received OKT3. During the mean follow-up of 35 weeks after conversion, no clinically apparent cytomegalovirus infection and no pneumonia were seen. Treatment with FK506 may successfully suppress ongoing acute rejection, even if antilymphocyte preparations have failed. FK506 can be used at a lower dose than so far recommended without impairing the antirejection potential. An additional anti-infective prophylaxis seems effective in preventing severe complications in the first months after rejection therapy.