[Molecular and metabolic changes in human clear cell liver foci]. / Molekulare und metabolische Veränderungen in humanen klarzelligen Leberherden.

Activation of the AKT/mTOR and Ras/MAPK pathways and the lipogenic phenotype are evident both in human hepatocellular carcinoma and in the rat model of insulin-induced hepatocarcinogenesis in the earliest preneoplastic lesions, i.e. clear cell foci (CCF) of altered hepatocytes. These CCFs have also been described in the human liver but characterization of molecular and metabolic changes are still pending. In this study, human sporadic CCFs were investigated in a collection of human non-cirrhotic liver specimens using histology, histochemistry, immunohistochemistry, electron microscopy and molecular pathological analysis. Human CCFs occurred in approximately 33 % of non-cirrhotic livers and stored masses of glycogen in the cytoplasm, largely due to reduced activity of glucose-6-phosphatase. Hepatocytes revealed an upregulation of the AKT/mTOR and the Ras/MAPK pathways, the insulin receptor, glucose transporters and enzymes of glycolysis and de novo lipogenesis. Proliferative activity was 2-fold higher than in extrafocal tissue. The CCFs of altered hepatocytes are metabolically and proliferatively active lesions even in humans. They resemble the well-known preneoplastic lesions from experimental models in terms of morphology, glycogen storage, overexpression of protooncogenic signaling pathways and activation of the lipogenic phenotype, which are also known in human hepatocellular carcinoma. This suggests that hepatic CCFs also represent very early lesions of hepatocarcinogenesis in humans.

Laparoscopic ultrasound navigation in liver surgery: technical aspects and accuracy.

The functional-anatomic structure of the liver according to Couinaud classification based on the intrahepatical course of the vascular structures is the basis of all modern liver surgery. Consequently, the use of intraoperative ultrasound is an undisputed requirement for every liver resection. Exact following of the planned resection plane can be realized only with the application of permanent online navigation based on intraoperative ultrasound during the dissection of the hepatical tissue. Now that the authors have established ultrasound navigated resection in open liver surgery using a navigated parenchymal dissecting instrument, they intend to transfer this technique from open to laparoscopic liver surgery. A special adapter was developed to connect an ultrasound-based navigation system to laparoscopic instruments. The authors present the first results in terms of technical aspects and feasibility.

Influence of operator experience in radiofrequency ablation of malignant liver tumours on treatment outcome.

AIMS: Radiofrequency ablation is gaining popularity as the interventional therapy of choice for unresectable hepatic malignancies. However, little attention has been paid to the importance of operator experience in this therapy. This study aims to evaluate the results of RFA treatment dependent on operator experience and learning curve. PATIENTS AND METHODS: Between 2/2000 and 11/2004 we have undertaken 116 RFA procedures to ablate 404 unresectable primary or metastatic liver tumours in 84 patients. The clinical data of all patients were recorded prospectively and treatment results of the first 42 patients (group I) and the second 42 patients (group II) were compared. All patients were treated by the same surgeon or interventional radiologist. RESULTS: RFA was performed percutaneously in 44 procedures (group I n = 35, group II n = 9), via laparotomy in 64 procedures (group I n = 27, group II n = 37) and via laparoscopy in eight procedures (group I n = 1, group II n = 7). The complication rate was comparable in both groups with 7.9% in group I and 7.5% in group II. Group II had a higher complete ablation rate (96.2 vs 93.7%) than group I. One- and two-year survival rates of 92 and 89% in group II were significantly higher than in group I with 69 and 46% (p = 0.015). CONCLUSION: By the experience conditional optimization of indication and performance by a specialized RFA team the results could be improved significantly. The data on hand speak for a considerable learning curve in the RFA and demonstrate the importance of the experience of the therapist for the outcome of the patients.

[Pulmonary zygomycosis--a rare angioinvasive fungal infection]. / Pulmonale Zygomykose--eine seltene angioinvasive Pilzinfektion.

Zygomycosis caused by Rhizopus species is an aggressive and rapidly progressive opportunistic fungal infection in immunocompromised patients. It comprises mucocutaneous, rhinocerebral, pulmonary, urological and disseminated infections. Predisposing factors are immunosuppression owing to severe diseases, immunological defects or metabolic disturbances like diabetic ketoacidosis. Rhizopus infections are characterized by angioinvasive growth, necroses of infected tissue and perineural invasion. The histopathologic demonstrable invasion of blood vessels is remarkable for a fungal infection. The mortality of zygomycosis is very high, especially for disseminated disease and when immunosuppression cannot be corrected. We report about two cases of pulmonary zygomycosis, caused by Rhizopus spp.: patient 1, female 73 years old: Delayed clinical course according to hip arthroplasty infection and infection of a femoropopliteal bypass of the right leg, eventually exarticulation of the right hip joint, Pseudomonas pneumonia, severe sepsis caused by staphylococci, acute respiratory distress syndrome (ARDs), acute renal failure and multiple use of antibiotics. Subsequently detection of Rhizopus spp. in the bronchoalveolar lavage and treatment with amphotericin B for this reason. Patient 2, male 68 years old: transplantation of kidney in past medical history, presenting with acute renal failure and with quite a few infections before. In the sequel development of abscessing pneumonia on the right side with a pleural empyema. Rhizopus spp. were detected by microbiological testing in the empyema fluid. These findings required surgical intervention, resection of the lower lobe of the right lung and within the same operation of the renal graft because of rejection. The patient was treated with caspofungin. The further course was delayed by several septic phases. Both patients died later on in spite of all efforts. The very rarely seen pulmonary zygomycosis caused by infection with Rhizopus spp. developed in both patients owing to immunosuppression, in one patient iatrogenically induced by immunosuppressive drugs after organ transplantation, in the other as a result of prolonged severe sepsis. In comparison with other mycoses treatment of Rhizopus infections remains difficult. The affinity to blood vessels, where the fungi multiply, and their feature of vascular invasion with thrombosis and infarction complicate therapeutic efforts.

[Surgical therapy in right-sided diverticulitis]. / Chirurgische Therapie der Rechtsdivertikulitis.

INTRODUCTION: Left-sided diverticulitis is a common disease in Western countries, whereas right-sided diverticultitis is rare and symptoms are often similar to the clinical signs of an acute appendicitis. It was the aim of this study to analyse surgical experience in right-sided diverticulitis. METHODS: All patients who underwent resectional surgery for both right-sided and sigmoid diverticular disease were entered prospectively in a registry database (8-year observation period, 1996-2003). For the current study, a retrospective analysis of all patients who underwent ileocolic resection or right colectomy for right-sided colonic diverticulitis was performed, specifically focussing on incidence, clinical symptoms, indication for surgery, type of procedure, and histopathological parameters including immunohistochemistry, and outcome in right-sided diverticulitis. RESULTS: Within eight years, 481 patients were treated surgically for chronically recurrent or acute complicated diverticular disease: 468 patients with sigmoid diverticulitis, 12 patients with right-sided diverticulitis, and 1 patient with combined right-sided and sigmoid diverticular disease. This corresponds to an incidence of right-sided diverticulitis of 2.5 % related to the total number of resections for diverticulitis, and an incidence of 1.3 % in relation to the appendectomies in our patients. In 4 patients, acute appendicitis was presumed preoperatively. Most common diagnostic tool was ultrasonography. Right colectomy was performed in 9 patients with complicated cecal diverticulitis, whereas ileocolic resection was performed in 2 patients and simultaneous ileocolic and sigmoid resection was carried out in one patient. Postoperatively, no morbidity occurred. Histopathological assessment showed local perforation in 75 % (9/12). Hypoganglionosis or aganglionosis was detected in 5 of 12 resected specimen. DISCUSSION: As right-sided diverticulitis is a rare colonic disease in Western countries, the differentiation from acute appendicitis can be difficult. In general, there is no difference in the treatment of right-sided diverticulitis compared to left-sided diverticulitis, and surgery is only indicated in complicated right-sided diverticulitis. Resection of the inflamed colon with primary anastomosis is safe and can be performed by laparoscopy in experienced centers. At present, it can only be speculated whether hypoganglionosis or aganglionosis are causative factors in the etiology of right-sided diverticulitis.

[Present state of radio frequency ablation of liver tumors in Germany]. / Aktueller Stand der Radiofrequenzablation von Lebertumoren. Eine deutschlandweite Umfrage.

INTRODUCTION: Radio frequency ablation (RFA) represents a new technique for local destruction of liver tumors. Indication and procedure are poorly validated at present. METHOD: To record the actual nationwide RFA application in Germany, a survey of 2026 hospitals with standardized questionnaires was conducted. RESULTS: With a respond rate of 17.5%, results from 58 hospitals covering 1700 ablated patients were analyzed. In 25.9% of them, RFA is already used in potentially curative resectable tumors, in 22.4% even when incomplete ablation for tumor mass reduction is expected. Of the 58 hospitals, 75% combine resection and RFA to reach a so-called R-0 situation. The maximal tumor sizes they quoted for achieving complete ablation ranged from <3 cm to 11 cm. In contraindications for RFA, the tumor size, number of tumors, critical localization of the tumor, and disorders of liver function were mentioned the most. CONCLUSION: This survey documents significant discrepancies in indication, application, procedure, and results in RFA for liver tumors. The lack of general standards and an overestimation of the method may lead to uncritical application, neglect of standard therapy, or unsatisfying results.

[Ultrasound-guided interventions using magnetic field navigation. First experiences with Ultra-Guide 2000 under operative conditions]. / Ultraschallgesteuerte Interventionen unter virtueller Führung. Erste Ergebnisse mit dem US-Guide 2000 unter operativen Bedingungen.

AIM: Ultrasound-guided interventions are presently performed as free-hand-type procedures or using biopsy transducers. In this article we report on our experience with a new navigation-system for sonographically guided interventional procedures under OR-conditions. METHODS: The US-Guide 2000 trade mark is an electromagnetic guidance system that assists physicians in ultrasound-guided interventional procedures. This system accommodates both in-plane and out-of-plane needle placement. We evaluated this system for the first time under OR-conditions. Overall, for 39 interventional procedures (23 thermoablations of malignant liver lesions, 16 diagnostic punctures) were performed. RESULTS: All targets were reached successfully without any complications. No interactions with other OR-devices were seen. CONCLUSION: The US-Guide 2000 trade mark as a virtual needle-guiding system allows a safe and accurate sonographically assisted intervention. The major advantage is the possibility of out-of-plane needle placement and the combination of flexibility of free-hand-type procedures with the accuracy of a biopsy transducer. This increases the safety of punctures especially when lesions are difficult to reach and/or are situated next to vulnerable structures. It also reduces the interventional trauma.

[Significance of lymph nodes in tumor surgery. Value of minimally invasive staging]. / Die Bedeutung der Lymphknoten in der Tumorchirurgie. Stellenwert des minimal-invasiven Stagings.

Malignant tumors require an exact staging in order to initiate individual tumor related therapeutic concepts to avoid unnecessary explorative laparotomy and to compare different treatment regimes. The assessment of the lymph node status with regard to tumor involvement using any of the actual imaging methods is quite unsatisfactory. For the improvement of the pretherapeutic tumor staging including N-classification the diagnostic laparoscopy and laparoscopic sonography are presently being evaluated. Both methods should be carried out according to a standardized investigation record. When limited to the pure diagnostic aspect, the morbidity is approx. 2%. Low patient figures with different tumor entities, insufficient information on the simultaneous occurrence of lymph node and distant metastases and/or of a peritoneal carcinomatosis as well as on the extent of the lymphadenectomy and histopathologic outcomes restrict the signifying value of many studies. It seems to be only clear that, when using the laparoscopic sonography, the sensitivity of the evidence of lymph node metastases increases in comparison with the sole laparoscopy. Definite recommendations based upon the outcomes with the required evidence, can presently neither be made with regard to the use of the method in general nor for the laparoscopic lymph node staging in particular. The use with regard to a lymph node assessment from today's point of view seems to be appropriate above all in case of: Suspect of an advanced tumor stage (existence of M1 lymphomas) For the indication in case of justified application of multimodal therapeutic concepts (exact tumor staging/N-classification). Beyond this, the laparoscopy for lymph node staging should only be used in conjunction with prospective randomized studies. Sufficient experience in the field of laparoscopic surgery and sonography as well as compliance with the rules of action for the prevention of tumor cell conveyance should be demanded.

Intermittent activity-induced hemobilia caused by liver hemangioma.

BACKGROUND: Intestinal bleeding of unknown origin can lead to a difficult workup. Abdominal colic, melena/hematemesis, and jaundice represent the pathognomonic triad for hemobilia, but clinical presentation and etiology of this entity are varying. Seldom all of these symptoms are present, and rarely does hemobilia cause melena or hematemesis. Often the correct diagnosis is missed. Patients frequently have a long history of complaints and inadequate therapy. CASE REPORT: We report on a patient who complained of repeated, severe epigastric pain and massive melena induced by exercise activity. After 2 years of complaints and an unnecessary operation, ultrasound detected a liver hemangioma. It was supposed that the hemangioma was causing hemobilia during strenuous physical activity. The patient underwent a partial liver resection to eliminate the hemangioma. All complaints resolved, and the patient remained asymptomatic postoperatively. CONCLUSIONS: Physicians should be aware of hemobilia as a rare cause of upper gastrointestinal bleeding, especially if esophagogastroduodenoscopy cannot demonstrate any bleeding source. Ultrasound is able to visualize many diseases leading to hemobilia and should be integrated into the early workup of unclear intestinal bleedings.

Vascular injuries within the hepatoduodenal ligament: recognition by laparoscopic color Doppler ultrasound.

BACKGROUND: Lesions of vascular structures are rare but serious complications of laparoscopic cholecystectomy. The purpose of this blind randomized animal study was to investigate the possibility of detecting different vascular lesions within the hepatoduodenal ligament using laparoscopic color Doppler ultrasound (LCDU). METHODS: Twenty-four lesions of the hepatic artery and portal vein were created laparoscopically in six farmer pigs using titanium clips. The following injuries were studied: (a) partial occlusion of the hepatic artery (eight cases), (b) complete occlusion of the hepatic artery (eight cases), (c) partial occlusion of the portal vein (eight cases). There were also eight cases without lesions of the vascular vessels. The order in which the injuries were created was randomly assigned. The study was performed in a blind fashion. Recognition of the injuries was attempted with LCDU. RESULTS: All injuries were recognized correctly by LCDU. There were no false positive results. The clips were reliably located. Using color Doppler imaging, partial occlusions of the hepatic artery and portal vein were visualized by changes of the blood flow from laminar to turbulent behind the clip. Complete occlusion of the hepatic artery was recognized as a complete cessation of the colored blood flow. CONCLUSION: LCDU is a very efficient tool for visualizing vascular structures and evaluating the bloodstream. Partial or complete vascular occlusion by clips that may occur as a result of difficult dissection during laparoscopic cholecystectomy can be visualized reliably using this technique.

[Biliary endo-to-end anastomosis with extramucosal titanium clips. Initial results of a new technique]. / Die biliäre End-zu-End-Anastomosierung mit extramukösen Titan-Clips. Erste Ergebnisse einer neuen Technik.

BACKGROUND: Bile duct anastomoses are still associated with a high failure rate. Although following iatrogenic bile duct transection only a positive selected group of patients get a primary end-to-end reconstruction, long-term results demonstrate an incidence of postoperative strictures up to 78%. Also in orthotopic liver transplantation biliary tract complications remain a significant cause of morbidity with an incidence of up to 49%. Since these complications can also be seen under optimal circumstances, the methodically based disadvantages of the conventional hand suturing like perforating needle injury of the choledochal wall with intraluminal suture material, the suboptimal approximation of the mucosal edges and an inhibited blood flow in the choledochal stumps caused by a suture related tissue strangulation may also responsible. Thus there is a search for alternative anastomosis techniques. METHOD: To test extramucous placed titanium clips for biliary reconstruction after complete division of the bile duct we performed an end-to-end-anastomosis in 9 pigs. Therefore we used the VCS (Vascular Closure Staples)-instruments (Auto Suture). RESULTS: The application of the VCS-clips (medium size) permitted the technical realization of a tension free, everted anastomosis with an exact approximation of the mucosal edges. One of the animals died from aero embolism intraoperatively. All the others showed a complication-free postoperative period without any signs of anastomotic leakage or stenosis (follow-up: 6 months). At histological examination there were smooth and intact mucosal surfaces in all pigs and--especially important for the development of strictures--only a very mild fibrosis and inflammation. CONCLUSIONS: The potential advantage of the VCS-clip-technique is the non-penetrating tissue approximation with optimal contact of the mucosal layers that does not compromise the blood flow in the choledochal stumps. Before clinical use can be recommended further studies are required.

Laparoscopic ultrasonography reliably visualizes bile-duct injuries - a blind randomized porcine study.

INTRODUCTION: Despite use of intraoperative cholangiography (IOC), only one-third or less of bile duct injuries that occur during laparoscopic cholecystectomy are detected at the primary operation. Therefore, there is a need to investigate other intraoperative diagnostic methods, especially laparoscopic ultrasound, for detecting bile-duct injuries. MATERIALS AND METHODS: Detection of different bile-duct injuries by laparoscopic intraoperative ultrasonography was evaluated in a blind, randomized animal study. Fifty bile-duct injuries were created using laparoscopic techniques in 23 pigs. The number of single lesions and the order in which the injuries were created was randomly assigned. The lesions created were: (1) partial occlusion by a clip, (2) complete occlusion by a clip, (3) partial laceration, (4) transection without clips, (5) transection between clips and (6) excision between clips. In addition, there were cases without lesions. Different types of clips were used. A screening of the injuries by laparoscopic ultrasound using a flexible probe was attempted. The study was performed in a blind fashion. RESULTS: Complete ultrasonographical imaging of the hepatic and common bile duct between its bifurcation and its insertion into the duodenum was accomplished in all 23 animals before surgery was performed. Eight cases without lesions were correctly recognized. In 48 of 49 cases, the injuries were detected (sensitivity 98%). In one instance, the injury was obvious without the use of ultrasound. Forty-four cases were correctly diagnosed and, in 12 cases, the injuries were equivocally differentiated (specificity of 100%, overall accuracy of 98.3%). There was only one false diagnosis. The different types of clips were also reliably differentiated. CONCLUSIONS: We conclude that laparoscopic ultrasonography can reliably visualize most relevant bile-duct injuries. A standard for doing the ultrasound examination is proposed. Direct and indirect ultrasound signs of bile-duct injuries are explained.

Common bile duct injuries during laparoscopic cholecystectomy that result in litigation.

BACKGROUND: Iatrogenic common bile duct injury is the worst complication of laparoscopic cholecystectomy. The goal of this study is to increase awareness of the problem and educate surgeons about the consequences of these injuries. METHODS: A total of 46 bile duct injuries were analyzed by review of medical records, cholangiograms, videotapes, and surgeon statements. All cases were involved in malpractice litigation. RESULTS: All types of injuries were represented. There were 15 transections, 11 excisions, 6 lacerations, 8 clip impingements, 3 burns, 2 bile leaks, and 1 cystic duct leak. In all, 72% of these injuries occurred in elective cases in which there was no acute inflammation. Cholangiograms were performed in 16 cases, but they were misinterpreted in 11 of them. Injury type and severity was similar in patients with and without cholangiography. A total of 80% of these injuries were not detected at the initial surgery. The average delay in diagnosis was 10 days. Complications were worse in patients with delayed diagnosis. Primary surgeons had less successful outcomes from repairs than referral surgeons (27% versus 79%). In 86% of cases, litigation was resolved in favor of plaintiffs by settlement or verdicts. The average award was $214,000. CONCLUSIONS: Factors that predispose to lawsuits include treatment failures in immediately recognized injuries, complications that result from delays in diagnosis, and misinterpretation of abnormal cholangiograms. Injury prevention can be improved by increased awareness of common mistakes,. Improved cholangiographic technique and interpretation should decrease injury severity, delays in diagnosis, and subsequent morbidity.

Prospective randomized comparison of laparoscopic ultrasonography using a flexible-tip ultrasound probe and intraoperative dynamic cholangiography during laparoscopic cholecystectomy.

BACKGROUND: We performed a prospective randomized comparison of laparoscopic intraoperative ultrasonography (LIOU) and dynamic intraoperative cholangiography (IOC) during laparoscopic cholecystectomy (LC). METHODS: LIOU and IOC were attempted in 518 consecutive patients scheduled for laparoscopic cholecystectomy. The order in which the diagnostic procedures were performed was randomly assigned. RESULTS: LIOU failed in two patients (0.4%), and there were 41 (7.9%) failed IOC. The common bile duct (CBD) was visualized reliably with both methods. Our patients showed sensitivities of 83.3% and 100% and specificities of 100% and 98.9%, with an overall accuracy of 99.2% and 98.9% for LIOU as compared to IOC for identifying unsuspected common bile duct stones. The time necessary for the examination was significantly shorter in LIOU than in IOC (7 versus 16 min). CONCLUSION: LIOU performed by experienced surgeons is a good and effective method to assess the CBD, including the neighboring structures of hepatoduodenal ligament. Using powerful, flexible-tip ultrasound probes, CBD exploration can be done in a longitudinal fashion, which is necessary for good anatomical clarity. A lack of adverse effects, shorter examination times, and lower costs are some of the advantages of this method. The most important advantage is the possibility of unlimited repetition, especially if there is difficulty identifying anatomic structures. In addition, there are some indications that LIOU has the potential to recognize major iatrogenic bile duct injuries.

[Online infection recording within the scope of total quality management]. / Online-Infektionserfassung im Rahmen des Total Quality Management.

The continuous and exact recording of infections is a condition sine qua non for total quality management. Therefore, at the Diakoniekrankenhaus Rotenburg (Wümme) a program which offers the possibility of online recording of data was integrated into the hospital intranet. The recording is done with network clients. The recording of data is supported by a series of plausibility controls. The advantage consists in immediate evaluation of up to date and extensive statistics of infections. By integration into the existing system, relevant influences and consequences such as the prolongation of hospitalisation, use of material, and frequency of reoperation can by recognized and immediately considered with high validity.

Laparoscopic transabdominal preperitoneal hernioplasty: results of 1000 consecutive cases.

From October 1992 until September 1995, 859 patients with 1000 inguinal hernias underwent a transabdominal preperitoneal mesh repair (TAPP) in the First Department of Surgery of the Diakonie-Hospital Rotenburg/Wümme, Germany. One hundred and seventeen of these repairs were for recurrences after previous open hernia surgery. There were 76 (7.6%) peri- and postoperative complications, but most of them were minor without necessity for surgical intervention. There were no implant infections or any adverse reaction of the mesh. During the postoperative follow-up period, which ranged from 2-36 months, 11 early recurrences were observed after TAPP, but none were in the recurrent hernia group. Our results support other studies and randomized trials reported in the literature and demonstrate that TAPP is an effective and safe operative procedure especially for the repair of recurrent groin hernias.

Recognition of laparoscopic bile duct injuries by intraoperative ultrasonography.

BACKGROUND: The purpose of this study was to investigate the possibility of detecting bile duct injuries using laparoscopic intraoperative ultrasound (LIOU). METHODS: Fifty bile duct injuries were created using laparoscopic techniques in ten farmer pigs. The lesions created were: (1) partial occlusion, (2) complete occlusion (1 clip), (3) complete occlusion (2 clips), (4) transection between clips, (5) excision between clips. RESULTS: All injuries were easily visualized using LIOU. The relation of clips impinging upon or occluding the bile duct was readily visualized on LIOU in all cases. In some cases it was difficult to distinguish between partial and complete occlusion. It was also difficult to distinguish between transection and excision due to retraction of the severed bile duct. CONCLUSIONS: In cases of iatrogenic occlusion of the bile duct involving hemoclips (including transection or excision between clips), LIOU is a potentially useful modality that may allow earlier recognition and repair. Further studies are needed to evaluate the efficacy of LIOU in detection of bile duct injuries that do not involve hemoclips.