[Stem cell-induced liver regeneration]. / Stammzell-induzierte Leberregeneration.

BACKGROUND: The liver has an excellent regenerative capacity after resection. However, below a critical level of future liver remnant volume (FLRV), partial hepatectomy is accompanied by a significant increase of postoperative liver failure. There is accumulating evidence for the contribution of bone marrow stem cells (BMSC) to participate in liver regeneration. Here we report our experience with portal vein embolisation (PVE) and CD133+ BMSC administration to the liver, compared with PVE alone, to augment hepatic regeneration in patients with critically low FLRV or impaired liver function. PATIENTS AND METHODS: Eleven patients underwent PVE of liver segments I and IV-VIII to stimulate hepatic regeneration prior to extended right hepatectomy. In these 11 patients with a FLRV below 25% and/or limited quality of hepatic parenchyma, PVE alone did not promise adequate proliferation. These patients underwent additional BMSC administration to segments II and III. Two radiologists blinded to patients' identity and each other's results measured liver and tumour volumes with helical computed tomography. Absolute, relative and daily FLRV gains were compared with a group of patients that underwent PVE alone. RESULTS: The increase of the mean absolute FLRV after PVE with BMSC application from 239.3 mL±103.5 (standard deviation) to 417.1 mL±150.4 was significantly higher than that from 286.3 mL±77.1 to 395.9 mL±94.1 after PVE alone (p<0.05). Also the relative gain of FLRV in this group (77.3%±38.2%) was significantly higher than that after PVE alone (39.1%±20.4%) (P=0.039). In addition, the daily hepatic growth rate after PVE and BMSC application (9.5±4.3 mL/d) was significantly superior to that after PVE alone (4.1±1.9 mL/d) (p=0.03). Time to surgery was 27 days±11 in this group and 45 days±21 after PVE alone (p=0.02). Short- and long-term survival were not negatively influenced by the shorter waiting period. CONCLUSION: In patients with malignant liver lesions, the combination of PVE with CD133+ BMSC administration substantially increased hepatic regeneration compared with PVE alone. This procedure bears the potential to allow the safe resection of patients with a curative intention that would otherwise carry the risk post-operative liver failure.

Transmyocardial laser revascularization combined with intramyocardial endothelial progenitor cell transplantation in patients with intractable ischemic heart disease ineligible for conventional revascularization: preliminary results in a highly selected small patient cohort.

OBJECTIVE: Transmyocardial laser revascularization for angina relief and intramyocardial autologous endothelial progenitor cell injection for neoangiogenesis may offer a new treatment strategy for patients with intractable ischemic heart disease. METHODS: Transmyocardial laser revascularization and intramyocardial injection of bone marrow-derived CD133+ cells was performed in six highly symptomatic patients. Transmyocardial laser channels were created and isolated CD133+ cells were injected intramyocardially. All patients were followed up for a minimum of 6 months postoperatively. RESULTS: One patient died shortly after the operation due to refractory heart failure. In the five survivors, CCS class improved as well as left ventricular ejection fraction. Left ventricular end-diastolic volume and myocardial perfusion varied between the patients. All patients described a considerable improvement in quality of life postoperatively. Repeated 24-hour Holter monitoring revealed no significant arrhythmias. CONCLUSIONS: In this small patient cohort, intramyocardial CD 133+ cell injection combined with transmyocardial laser revascularization led to an improvement in clinical symptomatology in all patients and in left ventricular function in 4 out of 5 patients, with an unclear effect on myocardial perfusion. Caution is advised when employing this therapy in patients with severely depressed left ventricular function.

Transplanted human cord blood-derived unrestricted somatic stem cells improve left-ventricular function and prevent left-ventricular dilation and scar formation after acute myocardial infarction.

OBJECTIVE: Functional improvement after acute myocardial ischaemia (MI) has been achieved by transplantation of different adult stem and progenitor cell types. It is controversial whether these cell types are able to form novel functional myocardium. Alternatively, graft-related or immune-related paracrine mechanisms may preserve existing myocardium, improve neovascularisation, affect tissue remodelling or induce endogenous de novo formation of functional myocardium. We have applied an alternative somatic cell type, human cord-blood-derived unrestricted somatic stem cells (USSCs) in a porcine model of acute MI. METHODS: USSCs were transplanted into the acutely ischaemic lateral wall of the left ventricle (LV). LV dimension and function were assessed by transoesophageal echocardiography (TEE) pre-MI, immediately post-MI, 48 hours and 8 weeks after USSC injection. Additionally, apoptosis, mitosis and recruitment of macrophages were examined 48 hours post-engraftment. RESULTS: Gender-specific and species-specific FISH/immunostaining failed to detect engrafted donor cells 8 weeks post-MI. Nevertheless, cell treatment effectively preserved natural myocardial architecture. Global left ventricular ejection fraction (LVEF) before MI was 60% (7%). Post-MI, LVEF decreased to 34% (8%). After 8 weeks, LVEF had further decreased to 27% (6%) in the control group and recovered to 52% (2%) in the USSC group (p<0.01). Left-ventricular end-diastolic volume (LVEDV) before MI was 28 (2) ml. 8 weeks post-MI, LVEDV had increased to 77 (4) ml in the control group. No LV dilation was detected in the USSC group (LVEDV: 26 (2) ml, p<0.01). Neither apoptosis nor recruitment of macrophages and mitosis were different in either groups. CONCLUSIONS: Transplantation of USSCs significantly improved LV function and prevented scar formation as well as LV dilation. Since differentiation, apoptosis and macrophage mobilisation at infarct site were excluded as underlying mechanisms, paracrine effects are most likely to account for the observed effects of USSC treatment.

Intramyocardial implantation of CD133+ stem cells improved cardiac function without bypass surgery.

INTRODUCTION: Cell transplantation for myocardial regeneration has been shown to have beneficial effects on cardiac function after myocardial infarction. Most clinical studies of intramyocardial cell transplantation were performed in combination with coronary artery bypass grafting (CABG). The contribution of implanted stem cells could yet not be clearly distinguished from the effect of the CABG surgery. Our current phase 1 clinical study has focused on the safety and feasibility of CD133+-enriched stem cell transplantation without CABG and its potential beneficial effect on cardiac function. METHOD AND RESULTS: Ten patients with end-stage chronic ischemic cardiomyopathy (ejection fraction <22%) were enrolled in the study. Bone marrow (up to 380 mL) was harvested from the iliac crest. CD133+ cells were purified from bone marrow cells using the CliniMACS device with purities up to 99%. Autologous bone marrow CD133+ cells (1.5-9.7 X 106 cells) were injected into predefined regions. Cardiac functions prior to and 3, 6, and 9 months after cell transplantation were assessed by cardiac magnetic resonance imaging. Stem cell transplantation typically improved the heart function stage from New York Heart Association/Canadian Cardiovascular Society class III-IV to I-II. The mean preoperative and postoperative ventricular ejection fractions were 15.8 +/- 5% and 24.8 +/- 5%, respectively. CONCLUSION: CD133+ injection into ischemic myocardium was feasible and safe. Stem cell transplantation alone improved cardiac function in all patients. This technique might hold promise as an alternative to medical management in patients with severe ischemic heart failure who are ineligible for conventional revascularization.

Autologous transplantation of CD133+ BM-derived stem cells as a therapeutic option for dilatative cardiomyopathy.

We report the case of a 58-year-old man with end-stage non-ischemic cardiomyopathy. Baseline transthoracic echocardiography (TTE) and cardiac magnetic resonance (cMRI) revealed a markedly depressed left ventricle systolic function. He underwent autologous CD133+ BM-derived cell transplantation through a minimally invasive approach. During surgery 19 x 10(6) BM-derived stem cells were injected by the transepimyocardial route. Six months after the operation TTE and cMRI showed a clear improvement in left ventricular contractility.

Intraoperative isolation and processing of BM-derived stem cells.

To improve tissue regeneration of ischemic myocardium, autologous bone marrow-derived stem cells have been injected intramyocardially in five patients undergoing coronary artery bypass grafting and transmyocardial laser revascularization. An innovative method for the intraoperative isolation of CD133(+)-stem cells in less than 3 hours has been established. After induction of general anesthesia, approx. 60-240 ml of bone marrow were harvested from the posterior iliac crest and processed in the operating room under GMP conditions using the automated cell selection device Clini-MACS. Following standard CABG surgery, LASER channels were shot in predefined areas within the hibernating myocardium. Subsequently, autologous CD133(+)-stem cells (1.9-9.7 x 10(6) cells; purity up to 97%) were injected in a predefined pattern around the laser channels. Through the intraoperative isolation of CD133(+)-cells, this effective treatment of ischemic myocardium can be applied to patients scheduled both for elective and for emergency revascularisation procedures.

Autologous bone marrow-derived stem cell therapy in combination with TMLR. A novel therapeutic option for endstage coronary heart disease: report on 2 cases.

We report 2 cases in which patients with coronary heart disease not amenable for conventional revascularization underwent transmyocardial laser revascularization (TMLR) and implantation of AC133+ bone-marrow stem cells. The reason for using TMLR in combination with stem cell application is to take advantage of the synergistic angiogenic effect. The local inflammatory reaction induced by TMLR should serve as an informational platform for stem cells and may trigger their angiogenic differentiation. Functional analysis of myocardial performance after treatment in these 2 cases revealed dramatic improvement of the wall motion at the site of the TMLR and stem cell application. Because TMLR does not enhance myocardial contractility and there was no angiographic evidence of major collaterals to the ischemic region in either patient, we assume that the synergistic effect of stem cells and TMLR-induced angiogenesis occurred; however, our assumption is of a speculative nature. We think that TMLR in combination with stem cell transplantation might become a novel revascularization therapy for ischemic myocardium.

[Sprengel deformity in a nine-year-old boy: diagnosis and therapy]. / Sprengel-Deformität bei einem neunjährigen Jungen: Diagnostik und Therapie.

Sprengel deformity is a congenital malformation with usually unilateral elevation and medial rotation of the scapula. An omovertebral bone is generally present. Associated skeletal malformations are frequently present. Though functional impairment is mild, the cosmetic and psycho-social impairment can be considerable. The prognosis of early surgical therapy is good. The presented case also justifies surgical correction in the older child.

Clinical significance of three-dimensional helical CT in neurosurgery.

The authors report about a 3-years experience with helical CT and 3-D surface reconstruction applied in neurosurgical patients. All examinations were performed in addition to preexisting diagnostic CT, MRI, or angiography. The aim of this study was to assess the clinical value of this method with regard to planning of the surgical approach to anterior, middle, and posterior skull base and spinal lesions. 75 examinations of 55 patients were analysed and ranked as follows: A = examination with significant additional information for neurosurgical planning of skull base or spinal procedures or for postoperative evaluation of the neurosurgical approach, B = examination with some useful information for the neurosurgical planning or postoperative control, however, without significant advantage as compared to established diagnostic methods, C = examination without significant additional information. Classification was performed independently by two experienced surgeons. Examinations of anterior, middle, and posterior skull base lesions including cerebral aneurysms were in the majority rated as helpful and significantly informative, (A = 21, B = 24, C = 9, n = 54). Three-dimensional imaging of the spine was of clinical value only in specific cases (A = 6, B = 6, C = 9, n = 21). The authors conclude that three-dimensional imaging is a valuable diagnostic tool for pre- and postoperative imaging of tumorous and vascular lesions adjacent to the skull base, allowing for optimal surgical approaches with minimal invasiveness.

Pattern recognition system for focal liver lesions using "crisp" and "fuzzy" classifiers.

RATIONALE AND OBJECTIVES: To determine the diagnostic performance of an artificial intelligence system for classification of focal liver lesions, in comparison to human observers. METHODS: One hundred forty-three focal hepatic lesions were evaluated with dynamic computed tomography. The study comprised 59 hemangiomas, 24 other benign lesions (focal nodular hyperplasia, adenoma), and 60 malignant liver lesions (18 primary, 42 secondary). All lesions but the hemangiomas were histologically examined by needle biopsy. For delineation of the lesion, a region of interest was defined interactively. The pattern recognition was performed in two steps with initial extraction of textural features: training of a classifier and classification of the lesions. The accuracy of classification of hepatic lesions into three groups (hemangioma, other benign processes, malignant lesions) was tested. The results were compared with those achieved by human observers using receiver operating characteristic statistical analysis. RESULTS: The accuracy (total rate of correct diagnoses) was 90.2%. False classifications were found owing to small size, weak contrast enhancement after bolus injection, respiratory movement, and atypical morphology of the lesion. The area under the receiver operating characteristic curve was not significantly different for computer and human observers. CONCLUSIONS: The system demonstrated a diagnostic accuracy comparable to human observers. Further improvement with increasing numbers of typical computed tomographic series for training of the classifier can be expected.

Microsurgical management of ventral and ventrolateral foramen magnum meningiomas.

The authors report their experiences gained from 19 patients with ventral or ventrolateral foramen magnum meningiomas operated on via the dorsolateral, suboccipital transcondylar access route. It is emphasized that the microsurgical management of these lesions includes two important aspects which increase the safety of the procedure: a meticulous preoperative planning based on the microanatomical details of each patient, as well as an individualized tailoring of the surgical approach. There were no deaths, and, in the past 5 years, no neurological complications in this series. Gross total removal of the tumour was achieved in each case. It is concluded that microsurgical removal of ventral or ventrolateral foramen magnum meningiomas with this technique constitutes a safe and recommendable procedure.

Image- and model-based surgical planning in otolaryngology.

Preoperative evaluation of any operating field is essential for the preparation of surgical procedures. The relationship between pathology and adjacent structures, and anatomically dangerous sites need to be analyzed for the determination of intraoperative action. For the simulation of surgery using three-dimensional imaging or individually manufactured plastic patient models, the authors have worked out different procedures. A total of 481 surgical interventions in the maxillofacial region, paranasal sinuses, orbit, and the anterior and middle skull base, in addition to neurotologic procedures were presurgically simulated using three-dimensional imaging and image manipulation. An intraoperative simulation device, part of the Aachen Computer-Assisted Surgery System, had been applied in 407 of these cases. In seven patients, stereolithography was used to create plastic patient models for the preparation of reconstructive surgery and prostheses fabrication. The disadvantages of this process include time and cost; however, the advantages included (1) a better understanding of the anatomic relationships, (2) the feasibility of presurgical simulation of the prevailing procedure, (3) an improved intraoperative localization accuracy, (4) prostheses fabrication in reconstructive procedures with an approach to more accuracy, (5) permanent recordings for future requirements or reconstructions, and (6) improved residency education.

Diagnostic imaging of mesenteric infarction.

PURPOSE: To determine the value of diagnostic imaging in the management of mesenteric infarction. MATERIALS AND METHODS: Within 8 years, 54 patients with mesenteric infarction underwent diagnostic imaging before surgery, including plain radiography (n = 45), ultrasound (US) (n = 29), small bowel follow-through examination (n = 7), colon enema study (n = 7), angiography (n = 16), and computed tomography (CT) (n = 22). Clinical course, laboratory values, and imaging findings were considered in diagnosis. RESULTS: Radiography and US allowed correct diagnoses in five of 18 cases (28%). Only one of 14 fluoroscopic examinations contributed to diagnosis. Fourteen of 16 angiography studies (sensitivity, 87.5%) and 18 of 22 CT examinations (82%) were correct. The difference in sensitivity between CT and angiography was not significant (P > .05). CONCLUSION: CT and angiography are highly sensitive, but CT can also be used to rule out other causes of acute abdomen. Careful evaluation of patient history and clinical situation should lead to suspicion of mesenteric ischemia and early indication for CT.

[The computed tomographic morphology of Crohn's disease and ulcerative colitis]. / Computertomographische Morphologie von Morbus Crohn und Colitis ulcerosa.

PURPOSE: To assess the value of computed tomography for the diagnosis of Crohn's disease and ulcerative colitis. METHOD: We analysed the CT examinations of 109 patients with 197 involved bowel locations. 81 patients suffered from Crohn's disease, 28 from ulcerative colitis. Diagnosis was based on the combination of clinical, endoscopic and histopathologic findings. Three radiologists evaluated the CT series concerning the presence of morphologic changes analogous to conventional radiographic findings. RESULTS: In Crohn's disease, we found irregular outer contours in 26% of cases. The bowel wall was thickened in 82%. In acute phases, the bowel wall was thickened in 100%. Abscess and fistula as complications of inflammatory disease were present in 26 and 14% respectively. In ulcerative colitis, a target sign of the bowel wall was present in 40%, whereas in Crohn's disease a homogeneous wall density was present in all but two cases. Reduced attenuation due to submucosal fat deposits was found in 16% and mucosal tunneling in 27% of cases with ulcerative colitis. Even if severe mucosal destructions were found, the outer contour of the gut was smooth and regular in 95% of the ulcerative colitis cases. CONCLUSION: CT can provide additional information on acuity, extent and complications in inflammatory bowel disease. In combination with conventional radiographic findings a three-step classification for Crohn's disease and ulcerative colitis (early changes, acute and chronic phase) can be proposed.

Three-dimensional spiral CT for neurosurgical planning.

We carried out 22 examinations to determine the value of three-dimensional (3D) volumetric CT (spiral CT) for planning neurosurgical procedures. All examinations were carried out on a of the first generation spiral CT. A tube model was used to investigate the influence of different parameter settings. Bolus injection of nonionic contrast medium was used when vessels or strongly enhancing tumours were to be delineated. 3D reconstructions were carried out using the integrated 3D software of the scanner. We found a table feed of 3 mm/s with a slice thickness of 2 mm and an increment of 1 mm to be suitable for most purposes. For larger regions of interest a table feed of 5 mm was the maximum which could be used without blurring of the 3D images. Particular advantages of 3D reconstructed spiral scanning were seen in the planning of approaches to the lower clivus, acquired or congenital bony abnormalities and when the relationship between vessels, tumour and bone was important.

Ultrasound-guided craniotomy for minimally invasive exposure of cerebral convexity lesions.

The authors describe a method of real-time ultrasound-guided craniotomy for an approach to cerebral convexity lesions. During surgery, a specially designed high frequency (7.5 MHz) sector probe with a thin (11 mm), extended tip is used to image the cerebral lesion through a single burr-hole. The distance between burr-hole and lesion and the direction of the target are then determined from the ultrasound images, and craniotomy is completed with the aid of these parameters. Errors in the preoperative planning of the approach, which might result in incorrect placement of the craniotomy, can easily be recognized and corrected at an early stage of the operation, before the craniotomy has been completed. This technique greatly improves the accuracy in placing craniotomy flaps. Since the risk of misplacing the craniotomy is virtually eliminated in lesions which are identifiable on ultrasound images, the technique allows the surgeon to keep the skull opening as limited as possible.

Computed tomographic cholangiography using spiral scanning and 3D image processing.

Volumetric computed tomography (CT) scans ("spiral CT") were performed after intravenous (i.v.) cholangiography followed by additional 3D surface reconstructions of gallbladder and biliary ducts. 34 patients were investigated prior to cholecystectomy. No allergic adverse reactions were observed. The scan time was 24 s. Contrast enhancement in the extrahepatic bile duct and gallbladder were measured. All CT image series were reviewed independently by four experienced physicians (two radiologists, two surgeons) and compared for quality with conventional cholangiography on a three-point scale. The average rating for the demonstration of the biliary tract was significantly better for spiral CT than for conventional cholangiography (p < 0.01). In all cases sufficient contrast was found in the common bile duct (mean 315 HU). 3D imaging was considered to be helpful for intraoperative orientation during laparoscopic surgery.

[The diagnosis of focal liver lesions by the texture analysis of dynamic computed tomograms]. / Diagnostik fokaler Leberläsionen durch Texturanalyse von dynamischen Computertomogrammen.

Characterisation of focal liver lesions on computed tomography (CT) depends on correct interpretation of morphology and dynamic changes during bolus injection of contrast medium. The aim of this study was to develop a texture analysis concept for computer based interpretation of dynamic CT images. 148 focal liver lesions were investigated by serial CT. The study comprised 61 haemangiomas, 25 other benign lesions (FNH/adenomas) and 62 malignant lesions (primary or secondary). FNH, adenomas and malignant lesions were histologically proven. Diameter was 8-145 mm (mean 31 mm). Regions of interest were interactively defined. After extraction of characteristic textural features, a pattern classifier was trained. All CT series were evaluated using the "leaving-one-out" method. 134 of the 148 lesions were correctly classified (positive predictive value 0.9). Sensitivity for the presence of malignancy was 0.93 (80/86), specificity was 0.9 (56/62). False classification of a lesion was found to depend strongly on the quality of the examination (bolus intensity, positional change of the lesion due to respiratory movements).

Double contrast small bowel follow-through with an acid-resistant effervescent agent.

RATIONALE AND OBJECTIVES: A new technique was developed to achieve double contrast examinations in the small bowel without intubation. METHODS: Effervescent granules and tablets were coated with an acid-resistant acrylic lacquer to provide selective enteric gas release. The coating thickness was 15% of dry weight for the granules and 1 to 4.5 mg/cm2 for the tablets. Fifty patients were examined using the method in a controlled study. All examinations were reviewed by two radiologists using a three-step quality score. The results were compared to 20 enteroclysis examinations. RESULTS: Image quality was better for the coated tablets compared with the granules (P < .01). The double-contrast small bowel follow-through (DC-SBFT) provided a better quality examination in the terminal small bowel than in the jejunum. Enteroclysis yielded better results for the jejunum, but was not superior in the terminal ileum. Average time of fluoroscopy was 477 seconds for the DC-SBFT (n = 50) compared with 952 seconds for patients receiving enteroclysis (n = 528). No side effects or adverse reactions occurred due to contrast media application. CONCLUSIONS: The results of this new method are preliminary, yet promising. For young patients and certain indications it may provide a less invasive alternative to enteroclysis.

Stereolithographic modelling for reconstructive head surgery.

Until now, bounds of model creation of medical objects had to be set because of the limited capabilities of available manufacturing equipment. Recently, stereolithography was developed as an alternative to current milling operations. In this process the surface of a photohardening liquid plastic compound is traced by a laser beam and hardened in layers. The models thus produced are extremely accurate and retain excellent detail. Specific implants can be designed and prepared as is illustrated in a case report. If tissue-compatible plastics are used, custom-made implants could soon be manufactured directly with the technique described.