CT Fluoroscopy-Guided Drain Placement to Treat Infected Gastric Leakage after Sleeve Gastrectomy: Technical and Clinical Outcome of 31 Procedures.

PURPOSE: To observe the technical and clinical outcome as well as safety of CT fluoroscopy-guided drain placement in the multimodal clinical complication management of superinfected gastric leakage after sleeve gastrectomy. MATERIALS AND METHODS: All consecutive patients who underwent CT fluoroscopy-guided drain placement to treat superinfected postoperative leakage after sleeve gastrectomy in our department between 2007 and 2014 were included in this retrospective study. All interventions were performed on a 16- or 128-row CT scanner under intermittent CT fluoroscopy guidance (15-25 mAs, 120 kV). The technical and clinical success rates as well as complications, additional therapies and patient radiation dose were analyzed. RESULTS: 14 patients (mean age: 43.8 ±â€Š11.3 years, mean BMI: 52.9 ±â€Š13.5, 7 women) who underwent a total of 31 CT fluoroscopy-guided drain placement procedures were included. 30 of 31 interventions (96.8 %) were technically successful. 7 patients underwent more than one intervention due to drain obstruction or secondary dislocation or as further treatment. During and after the intervention no procedure-associated complications occurred. In all patients, inflammation parameters decreased within days after the CT-guided intervention. The total interventional dose length product (DLP) was 1561 ±â€Š1035 mGy*cm. CONCLUSION: CT fluoroscopy-guided drain placement has been shown to be a safe minimally invasive procedure that rarely leads to complications for treating superinfected gastric leakage occurring after sleeve gastrectomy. We assume that operative revisions in a high-risk patient group can be avoided using this procedure. KEY POINTS: · CT fluoroscopy-guided drain placement in obese - often medically highly complex - patients is a technically feasible procedure.. · Multimodal treatment (CT intervention, endoscopy and surgery) is required to successfully treat gastric leakage after bariatric surgery.. · High-risk surgery might be avoided by the CT-guided drain placement.. CITATION FORMAT: · Schwarz J, Strobl FF, Paprottka PM et al. CT Fluoroscopy-Guided Drain Placement to Treat Infected Gastric Leakage after Sleeve Gastrectomy: Technical and Clinical Outcome of 31 Procedures. Fortschr Röntgenstr 2020; 192: 163 - 170.

Preoperative serum markers for individual patient prognosis in stage I-III colon cancer.

Carcinoembryonic antigen (CEA) remains the only recommended biomarker for follow-up care of colorectal cancer (CRC), but besides CEA, several other serological parameters have been proposed as prognostic markers for CRC. The present retrospective analysis investigates a comprehensive set of serum markers with regard to cancer-specific survival (CSS) and disease-free survival (DFS). A total of 472 patients with colon cancer underwent surgery for curative intent between January 1988 and June 2007. Preoperative serum was analyzed for the following parameters: albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin (ßhCG), bilirubin, cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9), CA 72-4, CEA, C-reactive protein (CRP), cytokeratin-19 soluble fragment (CYFRA 21-1), ferritin, gamma-glutamyltransferase (γGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate dehydrogenase (LDH), serum amyloid A (SAA), and 25-hydroxyvitamin D. After a median follow-up period of 5.9 years, the overall 3- and 5-year CSS was 91.7 and 84.9 % and DFS rates were 82.7 % (3 years) and 77.6 % (5 years). Multivariate analyses confirmed preoperative CEA as an independent prognostic factor with regard to CSS and DFS. CA 19-9 and γGT also provided prognostic value for CSS and DFS, respectively. Younger age was negatively associated with DFS. According to UICC stage, CEA provided significant prognostic value with regard to CSS and DFS, while CA 19-9 was only prognostic for CSS. Combined analysis is able to identify patients with favorable prognosis. In addition to tumor baseline parameters, preoperative CEA could be confirmed as prognostic marker in colon cancer. CA 19-9 and γGT also provide additional prognostic value with regard to survival and recurrence in stage III and stage I disease, respectively. The combined use of CEA together with CA 19-9 and γGT improve risk-adapted post-op surveillance.

Evaluation of preoperative serum markers for individual patient prognosis in stage I-III rectal cancer.

Several independent serum biomarkers have been proposed as prognostic and/or predictive markers for colorectal cancer (CRC). To this date, carcinoembryonic antigen (CEA) remains the only recommended serological CRC biomarker. The present retrospective analysis investigates the prognostic value of several serum markers. A total of 256 patients with rectal cancer underwent surgery for curative intent in a university cancer center between January 1988 and June 2007. Preoperative serum was retrospectively analyzed for albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin, bilirubin, CA 125, cancer antigen 19-9, cancer antigen 72-4 (CA 72-4), CEA, CRP, CYFRA 21-1, ferritin, gamma-glutamyl transpeptidase, glutamate oxaloacetate transanunase, glutamate pyruvate transaminase, hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate-dehydrogenase, serum amyloid A (SAA), and 25-hydroxyvitamin D. Cancer-specific survival (CSS) and disease-free survival (DFS) were estimated. Median follow-up time was 8.4 years. Overall 3- and 5-year CSS was 88.6 and 78.9 %, respectively. DFS rates were 72.8 % (3 years) and 67.5 % (5 years). Univariate analysis of CSS indicated aP, CA 72-4, CEA, and SAA as prognostic factors, while aP, CEA, and SAA were also prognostic with regard to DFS. Multivariate analysis confirmed SAA together with T and N stage as prognostic factors. According to UICC stage, CEA and SAA add prognostic value in stages II and III with regard to DFS and CSS, respectively. The combined use of CEA and SAA is able to identify patients with favorable and poor prognosis. In addition to tumor baseline parameters, routine analysis of SAA together with CEA provided markedly improved prognostic value on CSS and DFS in resected rectal cancer.

Down Syndrome: what do pregnant women know about their individual risk? A prospective trial.

INTRODUCTION: Down Syndrome is the most common chromosomal abnormality causing intellectual disability in western countries. The incidence relates directly to maternal age. Mothers have to face two risks when prenatal diagnosis is concerned: the probability of a congenital aneuploidy in their fetus, on the one hand, and the procedure-related risk of an invasive prenatal intervention, on the other hand. Women need precise information to deal with these risks. The aim of the study was to evaluate women's knowledge about the individual risk of their fetus being affected by Down Syndrome. MATERIALS AND METHODS: A structured questionnaire was distributed among all pregnant women who visited the prenatal care unit at Munich University Hospital, Campus Großhadern. Data evaluation was performed using Microsoft Excel 2003 and SPSS 12.0 for Windows. Statistical analysis was achieved by applying the Student t test, with statistical significance defined as p < 0.05. RESULTS: The data of 237 out of 246 women (96 %) were analyzed. The median gestational age of the study group was 20 (5/7) weeks of gestation [range 5 (1/7)-38 (4/7)]. The median maternal age was 32 years (range 20-41). The collective consisted of 52 % nulliparous, 34 % primiparous and 14 % multiparous women. Their educational history varied with 57 % women who attended high school and 43 % secondary school. Seventy-eight percent (185/237) of these mothers were aware of the fact that a risk of fetal aneuploidy exists, but 22 % (51/237) had never even considered this as an individual risk in their fetus. Most study participants (84 %, 155/185) realized the risk of fetal aneuploidy before conception or at least in early pregnancy. Only 5 % (10/185) of women within late pregnancy considered a chromosomal abnormality as a forthcoming risk for the first time as late as in the second or third trimester. Overall, the women estimated the risk of Down Syndrome being present in their fetus in a ratio of 1:33 (range 1-9,000:10,000); 67 % overestimated the risk and 23 % underrated their individual risk by at least a factor of 2. Only 10 % of the women had a realistic idea (within double standard deviation) of their age-dependent specific risk (p < 0.001). The patient's self-risk assessment was influenced by factors such as personal experience (69 %), counseling by health-care professionals (19 %) or information from different media (19 %). The mother's self-risk assessment was independent of maternal age, education parity or gestational age. DISCUSSION: Information transfer to patients concerning prenatal medicine is only successful to a certain extent, as pregnant women substantially overrate the risk of congenital handicaps in their fetuses. The need for a more comprehensive instruction of parents is not limited to particular subgroups. Health-care professionals and media are called upon to compensate for the apparent information deficits in parents and improve the public awareness of Down Syndrome.

CT fluoroscopy guided percutaneous gastrostomy or jejunostomy without (CT-PG/PJ) or with simultaneous endoscopy (CT-PEG/PEJ) in otherwise untreatable patients.

PURPOSE: Percutaneous endoscopic gastrostomy (PEG) or percutaneous endoscopic jejunostomy (PEJ) are substantial for patients with swallowing disorders to maintain enteral nutrition or to decompress palliatively intractable small bowel obstruction. Endoscopic placement can be impossible due to previous (gastric) operation, obesity, hepato-splenomegaly, peritoneal carcinosis, inadequate transillumination, or obstructed passage. Computed tomography (CT)-fluoroscopic guidance with or without endoscopy can enable placement of CT-PG/CT-PJ or CT-PEG/CT-PEJ if endoscopically guided placement fails. In this retrospective study, we will evaluate the feasibility and safety of this method. METHODS: A total of 101 consecutive patients were referred to our department for feeding support (n = 87) or decompression (n = 14). Reasons were: ENT tumor (n = 51), esophageal cancer (n = 19), mediastinal mass (n = 2), neurological disorder (n = 15). Decompression tubes were placed because of cancer (n = 13) or Crohn's disease (n = 1). The following approaches were chosen: CT fluoroscopy and simultaneous gastroscopy (n = 61), inflation of the stomach via nasogastric tube (n = 29), and direct puncture under CT-fluoroscopic guidance (n = 11). RESULTS: CT fluoroscopy-guided gastrostomy was feasible in 89 of 101 patients. No procedure-related mortality was observed. One tube was misplaced into the colon in a patient with a history of gastrectomy. No complication was seen after removal. Minor complications: dislodgement (n = 17), peristomal leakage (n = 7), wound infection (n = 1), superficial skin infection (n = 6), tube obstruction (n = 2). CONCLUSIONS: CT fluoroscopy-guided PG/PJ or PEG/PEJ is feasible and safe and provides adequate feeding support or decompression. It offers the benefits of minimally invasive therapy even in patients with contraindications to established endoscopic methods, combining the advantages of both techniques. Long-term complications-mainly tube-related problems-are easily treated.

Prognostic role of methylated free circulating DNA in colorectal cancer.

DNA hypermethylation is frequently found in colorectal cancer (CRC). Methylation of helicase-like transcription factor (HLTF) and hyperplastic polyposis 1 (HPP1) are potential and carcinoembryonic antigen (CEA) is an established prognostic factor in serum of patients with CRC. The aim of this study was to perform a direct comparison of the prognostic roles of these markers. Methylation status of HLTF and HPP1 was examined in pretherapeutic sera of 311 patients with CRC and matched primary tissues of 54 stage IV patients using methylation-specific quantitative PCR. CEA was determined using an immunoenzymometric assay. Methylation of HLTF and HPP1 DNA in serum significantly correlated with tumor size, stage, grade and metastatic disease. HPP1 methylation correlated with nodal status. Overall survival was shortened in case of methylation of HLTF or HPP1 or elevated levels of CEA (p < 0.0001 for all). In stage IV, patients survival was impaired if HLTF (p = 0.0005) or HPP1 (p = 0.0003) were methylated or CEA was above the median of 27 ng/ml (p = 0.002). Multivariate analysis revealed that methylation of HLTF [hazard ratio (HR) 1.8, p = 0.0438], HPP1 (HR 1.6, p = 0.0495) and CEA >27 ng/ml (HR 1.7, p = 0.0317) were independent prognostic factors in stage IV. The combination of any two or all three of these factors outperformed each marker on its own. In conclusion, the presence of methylated DNA of the genes HLTF or HPP1 in serum are independent prognostic factors in metastasized CRC. Prospective validation is required to determine their usefulness in clinical routine along with the established marker CEA.

Biomechanics of the female pelvic floor: a prospective trail of the alteration of force-displacement-vectors in parous and nulliparous women.

OBJECTIVE: We hypothesize that the holistic and multiplanar depiction of pelvic floor structures by dynamic MRI is of particular value in rendering information about the extent of functional changes that can lead to pelvic floor dysfunction. METHODS: 134 women were prospectively included for assessment of their pelvic floor function. RESULTS: Study groups differed significantly in the direction of their force-displacement-vectors. A shift from ventral to dorsal is present depending on parity, mode of delivery and age. Maternal age and body height correlated to the force-displacement-vector, whereas maternal weight did not. Pressing direction proved to be dependent on the inclination of the pelvis and the aperture of the levator hiatus while remaining independent from the aperture of the abdominal wall. CONCLUSION: Biomechanical data interpretation uncovered the pathogenetic relevance of progressive retroflection of the force-displacement-vector. This is responsible for the onset of a vicious cycle of trauma-related force deflection perpetuating pelvic floor traumatization.

Anastomotic leakage after esophageal resection: new treatment options by endoluminal vacuum therapy.

BACKGROUND: Anastomotic leakage after esophagectomy is an important determinant of early and late morbidity and mortality. Control of the septic focus is essential when treating patients with anastomotic leakages. Surgical and endoscopic treatment options are limited. METHODS: Between 2005 and 2009, we treated 6 patients who experienced an intrathoracic anastomotic leakage after esophageal resection. After all established therapeutic measures had failed, we explored the feasibility of an endoscopically assisted mediastinal vacuum therapy. RESULTS: We were able to heal intrathoracic esophageal leakages in all 6 patients without any local complications and without the need for reoperation. One patient died because of a progressive pneumonia. CONCLUSIONS: Endoscopic vacuum-assisted closure of anastomotic leakages may help to overcome the limitations that are associated with intermittent endoscopic treatment and conventional drainage therapy. Our preliminary results suggest that this new concept may be suitable for those patients.

Relation of gallbladder motility to viscosity and composition of gallbladder bile in patients with cholesterol gallstones.

BACKGROUND/AIMS: Increased viscosity and supersaturation of cholesterol in gallbladder bile, as well as an impaired motility of the gallbladder, are considered to be important factors in the pathogenesis of cholesterol gallstones. However, the relation of these parameters has not yet been determined. MATERIAL AND METHODS: Bile viscosity (mPa s) was measured by rotation viscosimetry and the composition of gallbladder bile was determined using standard methodology. Gallbladder motility was calculated as ejection fraction in percent of total volume 45 min after a test meal using ultrasonography in patients with gallstones prior to elective cholecystectomy. RESULTS: The study included 35 patients with cholesterol gallstones. Viscosity of gallbladder bile ranged between 0.9 and 12.5 mPa s (median 2.2 mPa s) and an ejection fraction of the gallbladder of 55.4 +/- 18.3% (mean +/- SD) was determined. No significant correlation (r = 0.19, p < 0.2) between the 2 parameters could be calculated. Analysis of the composition of gallbladder bile revealed a positive correlation of all components to biliary viscosity but not to the motility of the gallbladder, with the exceptions of a negative correlation (r = 0.39, p < 0.02) between mucin concentration and the ejection fraction at 45 min after the test meal. CONCLUSIONS: The motility of the gallbladder appears to be unrelated to the viscosity of gallbladder bile or gallbladder bile composition. The negative correlation between the ejection fraction of the gallbladder and mucin concentration of gallbladder bile suggests that chronic inflammation of the gallbladder wall is associated with both an impaired motility of the gallbladder and increased mucin release into gallbladder bile.

DNA integrity in plasma and serum of patients with malignant and benign diseases.

This study aimed to test the diagnostic utility of the DNA integrity index for detection of cancer. Matched serum and plasma samples of 42 patients with various forms of cancer and 17 patients with corresponding benign diseases were analyzed. DNA was isolated from 1 mL serum and plasma using the MagNA Pure LC system. Cell-free DNA was quantified by real-time PCR using the reference gene of the LightCycler t(14;18) kit. Subsequently, the DNA integrity index was calculated as the ratio in relative abundance of 347-bp versus 137-bp PCR products. We found that DNA concentrations were not different in plasma (median: 4.5 ng/mL) and serum (67.1 ng/mL) of patients with benign diseases when compared with values in plasma (5.1 ng/mL) and serum (65.4 ng/mL) of cancer patients. Similarly, the DNA integrity index in plasma (0.38), and serum of patients with benign diseases (0.29) was comparable to values in plasma (0.33) and serum (0.37) of cancer patients. Diagnostic sensitivity of DNA (AUC 0.53) and DNA integrity (AUC 0.45) was poor in plasma, and was increased only slightly by the combination of both (AUC 0.57). In serum, sensitivity of DNA (AUC 0.52) and DNA integrity (AUC 0.64) was higher and was further improved by the combination of both (AUC 0.72) reaching a sensitivity of 30% at 100% specificity. In conclusion, we could not confirm a high diagnostic utility of the DNA integrity index. However, a combination with other markers such as DNA may enhance sensitivity for cancer detection.

Does surgical resection of pulmonary metastases of head and neck cancer improve survival?

BACKGROUND: The prognosis of patients with metastasized head and neck cancer is poor. Limited experience exists with the benefit of resection of lung metastases and systematic mediastinal and hilar lymph node dissection on survival of patients with head and neck carcinoma. METHODS: Eighty patients undergoing metastasectomy for pulmonary metastases of primary head and neck cancer entered the study. Multivariate analysis was performed by Cox regression analysis. Survival differences between patients operated and those not operated on were analyzed by matched pair analysis. RESULTS: From 1984 until 2006, pulmonary metastases were diagnosed in 332 patients treated for head and neck cancer; 80 of these were admitted to our department for resection. Metastases of the primary head and neck tumor were confirmed histologically in 67 patients. The median overall survival after resection of lung metastases was 19.4 months and was statistically significantly better compared with patients who were not operated on (P < .001). The multivariate analysis after metastasectomy revealed that incomplete resection of pulmonary lesions, complications associated with surgery, and adjuvant therapy of the primary tumor are independent negative prognostic factors for survival. We observed a trend to improved survival in patients without hilar or mediastinal lymph node metastases. CONCLUSION: The survival rate of patients operated on was statistically significantly higher than that of patients with conservative treatment. Even patients with multiple or bilateral pulmonary lesions after curative treatment of a primary tumor should be operated on if there is no contraindication against an extended surgical procedure and a complete resection of the metastases seems achievable.

Endoscopic vacuum-assisted closure of anastomotic leakage following anterior resection of the rectum: a new method.

BACKGROUND: Conservative treatment of anastomotic leakage after anterior resection of the rectum seems to be possible in patients who have no occurrence of generalized peritonitis. This report describes a new method of endoscopic management of large anastomotic leakage in these patients. METHOD: The main feature of this new method is the endoscopically assisted placement of an open-cell sponge connected to a vacuum device into the abscess cavity via an introducer device. The sponge system is changed every 48-72 h. RESULTS: Twenty-nine patients with an anastomotic leakage after anterior resection were treated with the endoscopic vacuum therapy. The total duration of endovac therapy was 34.4 +/- 19.4 days. The total number of endoscopic sessions per patient was 11.4 +/- 6.3. In 21 of the 29 patients, a protecting stoma was created at the primary operation. Four patients were treated successfully without the need of a secondary stoma. Definitive healing was achieved in 28 of the 29 patients. CONCLUSIONS: Endoscopic vacuum-assisted closure is a new efficacious modality for treating anastomotic leakage following anterior resection due to an effective control of the septic focus. Further studies will show if it is possible to reduce the high mortality rate of patients with anastomotic leakage through the avoidance of surgical reinterventions while at the same time preserving the sphincter function.

Predictors of general complications after video-assisted thoracoscopic surgical procedures.

BACKGROUND: The video-assisted thoracoscopic approach has become the preferred method for many procedures due to the reduced trauma, complication rate and morbidity. The aim of this study was a risk evaluation of patients undergoing video-assisted thoracoscopic surgery (VATS) procedures. METHODS: Between 1991 and 2004, 1,008 patients were included in this single-center retrospective analysis. Risk assessment was performed using univariate and multivariate analysis. RESULTS: Multivariate analysis revealed that patient age (p = 0.003), the duration of the VATS procedure (p = 0.008), redo-VATS (p < 0.001) and conversion to open thoracotomy (p < 0.001) correlated significantly with the incidence of complications. Patients with immune deficiency following organ transplantation had the highest complication rate at 31.7%, which was significantly higher than for patients with either benign disease (p = 0.010) or malignant disease (p = 0.019). CONCLUSIONS: VATS is a safe procedure, but extra caution is recommended for patients with a higher risk profile (age, redo-VATS, immune deficiency).

Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis.

BACKGROUND: Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. AIM: To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. PATIENTS: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. METHODS: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. RESULTS: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (<2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. CONCLUSION: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance.

Immunological effects of laparoscopic vs open colorectal surgery: a prospective clinical study.

HYPOTHESIS: Laparoscopy has become a popular approach for the surgical treatment of benign and even malignant colorectal diseases. Several authors have reported better preserved immunity in patients undergoing laparoscopic compared with conventional colorectal surgery. The present study addresses the hypothesis that specific and nonspecific immunity are differently affected by laparoscopic and conventional colorectal surgery. DESIGN: Nonrandomized control trial. SETTING: University hospital. PATIENTS: Seventy prospectively enrolled patients with colorectal diseases undergoing laparoscopic (n = 35) or open (n = 35) surgery. MAIN OUTCOME MEASURES: Blood samples were taken prior to surgery as well as on days 1, 3, and 5 after surgery. Cell numbers of lymphocyte subpopulations as well as natural killer cells were determined by flow cytometry, and interleukin 6 and C-reactive protein serum levels were measured. RESULTS: Significant differences between study and control patients (P<.05) were detected regarding circulating interleukin 6 and C-reactive protein levels with a reduced proinflammatory response to surgery in patients after laparoscopic surgery. Furthermore, postoperative natural killer cell counts were significantly higher in patients after laparoscopic surgery. The levels of B lymphocytes and T lymphocytes and helper T-cell counts and cytotoxic (suppressor) T-cell counts did not show significant differences after open or laparoscopic surgery. CONCLUSIONS: Our findings indicate a less pronounced proinflammatory response to surgical trauma in patients after minimally invasive surgery. The nonspecific immune response appears to be less affected by laparoscopic surgery when compared with open surgery while the specific cell-mediated immunity is equally affected. These findings are important because a divergent effect on specific and nonspecific immunity of laparoscopic surgery for colorectal disease has not been reported before.

Airway anastomosis complications in de novo lung transplantation with sirolimus-based immunosuppression.

A prospective, pilot trial was started to evaluate the effect of a sirolimus-based immunosuppressive regimen on acute and chronic rejection in de novo lung transplant patients. Primary lung transplant (LTx) recipients received a sirolimus- and tacrolimus-based immunosuppressive therapy immediately after transplantation. Both immunosuppressants were administered with trough level adjusted, while steroid administration was minimized. Four patients were enrolled (2 single-lung transplants, 1 double-lung transplant, 1 heart-lung transplant) in the study. Mean ischemia time was 387 +/- 92 minutes. Acute rejection (at least Grade A1 ISHLT) was detected in 1 patient. Incidence of infection was 0.6 infection per 100 patient-days (3 Aspergillus infections). Until hospital discharge mean sirolimus trough level was 6.2 +/- 1.2 ng/ml. Depending upon mean sirolimus trough levels of each patient, severe wound-healing complications were seen in 3 patients, resulting in bronchial airway dehiscence in 2 patients with lethal outcome in 1 patient. As a result of these complications, we revised the study design after inclusion of only 4 patients: Sirolimus administration is now started after completion of bronchial wound-healing. Sirolimus-based immunosuppressive therapy administered immediately after lung transplantation seems to be associated with severe wound-healing complications of the bronchial anastomosis.