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Biomedical subjects

M Gundlach

Publications and source records attributed to M Gundlach.

At least 19 recordsLinked to original sources

Klatskin tumors and Klatskin mimicking lesions of the biliary tree.

AIM: We report on the preoperative capability of imaging modalities and clinical assessment to differentiate between Klatskin tumors and Klatskin mimicking lesions of the biliary tree. Adenocarcinomas of the hepatic ducts (Klatskin tumors) mimic benign fibrosing cholangitis. Extensive resections carry a substantial risk but offer the only chance for cure in patients with a Klatskin tumor. METHODS: Thirty-three consecutive patients who underwent resection for suspicion of a malignant tumor of the hepatic hilum were reviewed. All patients underwent preoperative ultrasonography, computed tomography, ERCP and angiography. The patients were divided into a group of true Klatskin tumors and a group of benign Klatskin mimicking lesions. RESULTS: Twenty-seven of the resected specimens were malignant tumors, and six lesions showed only fibrosing cholangitis. Preoperative clinical presentation and imaging modalities were very similar between Klatskin tumors and fibrosing cholangitis. CONCLUSIONS: Management of obstruction of the liver hilum is dictated by the suspicion of malignancy. Complete removal of the tumor remains the therapeutic aim but clinical presentation and imaging modalities cannot help to differentiate between Klatskin tumors and Klatskin mimicking lesions prior to surgery.

Aged↗

Hepatic involvement in hereditary hemorrhagic telangiectasia: an unusual indication for liver transplantation.

Hereditary hemorrhagic telangiectasia (HHT) is a vascular disease with multiple organ manifestations. Severe hepatic involvement is an unusal indication for liver transplantation. We report on a 39-year-old woman diagnosed with HHT and decompensation of the disease during her second pregnancy. After delivery, hemobilia occurred, followed by severe therapy-resistant cholangitis and progressive liver dysfunction. Because of progressive loss of liver function, orthotopic liver transplantation needed to be performed. The various aspects of liver involvement in Osler's disease, diagnosis, and therapy are discussed.

Adult↗

Is there still a need for living-related liver transplantation in children?

OBJECTIVE: To assess and compare the value of split-liver transplantation (SLT) and living-related liver transplantation (LRT). SUMMARY BACKGROUND DATA: The concept of SLT results from the development of reduced-size transplantation. A further development of SLT, the in situ split technique, is derived from LRT, which itself marks the optimized outcome in terms of postoperative graft function and survival. The combination of SLT and LRT has abolished deaths on the waiting list, thus raising the question whether living donor liver transplantation is still necessary. METHODS: Outcomes and postoperative liver function of 43 primary LRT patients were compared with those of 49 primary SLT patients (14 ex situ, 35 in situ) with known graft weight performed between April 1996 and December 2000. Survival rates were analyzed using the Kaplan-Meier method. RESULTS: After a median follow-up of 35 months, actual patient survival rates were 82% in the SLT group and 88% in the LRT group. Actual graft survival rates were 76% and 81%, respectively. The incidence of primary nonfunction was 12% in the SLT group and 2.3% in the LRT group. Liver function parameters (prothrombin time, factor V, bilirubin clearance) and surgical complication rates did not differ significantly. In the SLT group, mean cold ischemic time was longer than in the LRT group. Serum values of alanine aminotransferase during the first postoperative week were significantly higher in the SLT group. In the LRT group, there were more grafts with signs of fatty degeneration than in the SLT group. CONCLUSIONS: The short- and long-term outcomes after LRT and SLT did not differ significantly. To avoid the risk for the donor in LRT, SLT represents the first-line therapy in pediatric liver transplantation in countries where cadaveric organs are available. LRT provides a solution for urgent cases in which a cadaveric graft cannot be found in time or if the choice of the optimal time point for transplantation is vital.

Adolescent↗

In vitro function of islets of Langerhans encapsulated with a membrane of porcine chondrocytes for immunoisolation.

BACKGROUND/AIMS: Widespread clinical application of islet transplantation remains restricted, because of insufficient methods to prevent rejection and autoimmune destruction of islet grafts. In this study we demonstrate long-term function of islets of Langerhans within a capsule of porcine chondrocytes which may serve as an immunoisolation barrier utilizing the immunoprivileged properties of the chondrocyte matrix. METHODS: Islets of Langerhans were isolated from Lewis rats, seeded on biodegradable polyglycolic acid polymer, and encapsulated with a monolayer of porcine chondrocytes. The encapsulated constructs and controls were kept in culture for 5 weeks. One group was exposed to a glucose challenge every 5th day. The insulin concentration of the culture medium was measured. Histological and insulin-immunohistochemical studies were performed. RESULTS: Hematoxylin and eosin histology demonstrated viability of the islets of Langerhans. The intact morphology was demonstrated by Heidenhain staining. Toluidine blue showed viability of surrounding chondrocyte layers. Immunohistochemistry was positive for insulin within the beta cells of the islets. Both encapsulated constructs and nonencapsulated controls showed increasing insulin levels after glucose challenge. CONCLUSIONS: We can tissue engineer a chondrocyte encapsulation membrane which permits diffusion of glucose and insulin. Islets of Langerhans survive within the chondrocyte capsule, and the glucose/insulin feedback mechanism remains intact.

Animals↗

[Colorectal liver metastases: does the number of metastases determine of resection is oncologically indicated?].

Complete surgical removal of colorectal liver metastases offers the patient the only curative option as long as there is no extrahepatic spread. Apparently the number of parameters of prognostic significance is unlimited. Consequently their importance for the individual prognosis remains questionable. One of the most frequently discussed parameters is the number of lesions in the liver. The aim of this study was therefore to review the literature and to analyze our own patients with colorectal liver metastases. For 302 patients a complete follow-up was available. The patients were grouped according to the number of lesions and the status of resection (R0, R1, R2, Exploration). The groups were compared by Kaplan Meier Analyses with log rank tests. The literature was reviewed until December 1998. The number of metastases was confirmed to be of prognostic value. Three or more metastases made a resection without residual tumor more unlikely than if there were only two or less (17.8% versus 67.2%). 5-year survival after curative resection was reduced in the group with more metastases from 36% to 9% and 10-year survival was reduced from 18% to 0% without reaching statistical significance (p < 0.07). The number of liver metastases may have some prognostic impact for patients after colorectal cancer. However, even if more than four metastases were resected with clear margins some patients did survive for a long time. The most important parameter to predict an oncological benefit is resection without residual tumor. If this is technically and functionally possible the patient should not be denied surgery, his only chance for cure.

Colorectal Neoplasms↗

Split-cava technique: liver splitting for two adult recipients.

Split-liver transplantation for 2 adult recipients is a challenging procedure because of the need to split through the midplane of the donor liver. In applied techniques, usually the middle hepatic vein is retained with the left split and the vena cava retained with the right split graft, particularly to avoid serious venous congestion of the right graft after reperfusion. The indispensable division of the caudate lobe veins lead to uncertain viability of liver segment I, and resection might be necessary. To provide optimal venous drainage of both hemiliver grafts, we developed the split-cava technique. This article describes our new technique of liver splitting, which has been successfully used in 2 in situ harvesting procedures.

Adult↗

Split liver transplantation (SLT).

OBJECTIVES: In the last three decades liver transplantation (LT) has become a standard procedure for terminal liver failure. Anyway the procedure is highly limited by the availability of donor organs. The use of segmental liver grafts from living or cadaver donors are an attractive way to increase the donor pool for LT in adults and children. METHODS: Between 1991 and April 1999 we performed 647 liver transplantations in 416 adults and 231 children. 431 OLT, 124 SLT and 92 LRLT. Commonly used segmental liver grafts are the full right graft, the full left graft, the left lateral lobe graft and the right extended graft from living or cadaver donors respectively. RESULTS: The 1-year survival of elective SLT in adults is 80.5% and in children 84.3% (SLT + LRLT). CONCLUSIONS: Splitting procedures in liver transplantation are a promising completion to whole organ transplantations. The results of split liver (SLT) and living related liver transplantations (LRLT) are comparable to whole organ transplantations. These methods are able to increase the organ pool and thus decrease the pretransplant mortality both in children and adults.

Adult↗

Mycophenolate mofetil for prevention of liver allograft rejection: initial results of a controlled clinical trial.

UNLABELLED: Mycophenolate Mofetil (M MF) is a new immunosuppressive agent with proven efficacy for the prevention of kidney allograft rejection. However, only little experience is available with the use of MMF in liver transplant recipients. OBJECTIVES: In this prospective, controlled trial the efficacy and safety of MMF and Azathioprine (AZA) were compared in a Neoral based quadruple immunosuppressive regimen after orthotopic liver transplantation. METHODS: Between 12/96 and 12/98 57 adult patients were enrolled in the study at the University of Hamburg. 28 patients were randomised to MMF, 29 patients to AZA in combination with equivalent doses of lymphocyte antibodies, Neoral and methylprednisolone. RESULTS: After a median follow-up of 10+/-3.2 months patient or graft survival did not differ significantly between the MMF and AZA group. However, MMF treated patients experienced less frequently acute rejection episodes (MMF: 6/28; 21.4% versus AZA: 13/29; 44.8%) (p=0.06). Furthermore, thrombocytopenia (MMF: 6/28; 21.4% versus AZA: 14/29; 48.3%) (p<0.05) and leukopenia (MMF: 2/28; 7.1% versus AZA: 6/29; 20%) (p=0.14) were less often observed under MMF compared to AZA. The incidence of serious bacterial infections and cytomegalovirus infections was almost identical in both groups. These preliminary data suggest that after liver transplantation primary immunosuppression with MMF is advantageous over AZA with regard to safety and efficacy.

Adult↗

[Hepatocellular carcinoma: surgical treatment].

Worldwide the hepatocellular carcinoma (HCC) is one of the most common malignancies. There is a coincidence with liver cirrhosis or chronic hepatitis B/C in most cases. HCC can be suspected by ultrasound and by rise of the tumor marker (AFP). Further investigations, like biopsies, are not necessary if angiography or computed tomography in combination with patient history and elevated AFP levels are positive. The prognosis of untreated HCC is extremely poor. Live expectancy of symptomatic patients is only a couple of weeks. Radical tumor removal by liver resection or transplantation is the only treatment with curative intent. However these options are only suitable for patients with limited disease. Five year survival after curative liver resection depends on the tumor stage, ranging from 25% to 67%. The results after liver transplantation are similar for small cancer. Large, symptomatic tumors are in most cases only suitable for palliative treatment (chemoembolisation, ethanol injection, chemotherapy, immunotherapy). The strong dependence of prognosis on tumor extent underlines the importance of screening patients with elevated risk of developing an HCC. The early recognition of small tumors allows curative therapy with good results.

Carcinoma, Hepatocellular↗

[Surgical therapy of primary and secondary liver tumors].

Advances in operative, diagnostic and post-operative care technique have rendered liver resections safe. Consecutively, indications for operative interventions in primary and secondary liver tumors have changed. A current state of the art is presented. Focal nodular hyperplasia, if found incidentally during laparotomy, should be removed en-passant. Large or central lesions should be biopsied and can be observed if they remain asymptomatic and stable in size. Symptomatic or growing FNH should be removed. If the diagnosis is evasive resection should be favored. Most patients with hepatocellular adenoma are symptomatic and the lesion should therefore be removed. Hemangiomas are rarely causing symptoms. In case they truly are, or if they cause complications they should be excised. Anatomical resections for hepatocellular carcinoma are only feasible in non-cirrhotic livers or in patients with cirrhosis and compensated liver function. Other patients are candidates for liver transplantation if the cancer is stage I or II. Stage III and IVa lesions are subject of current studies. Surgical resection remains the only potentially curative treatment for intrahepatic cholangiocellular carcinoma. Because of their dismal prognosis these patients are not candidates for transplantation. Resection continues to be the most effective therapy for colorectal metastases to the liver. Patients with non-colorectal, non-neuroendocrine metastases are usually only candidates for surgical palliation. Cure can be achieved in patients with renal cell carcinoma or Wilms' tumor. Additionally, neuroendocrine metastases to the liver can be resected in curative intent if extrahepatic disease was excluded. In the few symptomatic patients in whom extrahepatic disease was excluded, symptomatic treatment has failed, and the lesions are not resectable, liver transplantation can provide a reasonable therapeutic choice.

Carcinoma, Hepatocellular↗

[Preoperative hemodilution with bovine hemoglobin. Acute hemodynamic effects in liver surgery patients ].

UNLABELLED: Haemoglobin solutions can be an alternative to allogeneic red-cell transfusions because they combine colloid osmotic with oxygen transport properties. Since severe toxic side effects have been overcome by ultrapurification, clinical interest has been focused on haemodynamics changes during application of haemoglobin preparations. The present clinical study examines changes of haemodynamic and oxygen transport parameters during and after haemodilution with ultrapurified polymerized bovine haemoglobin (HBOC-201) in comparison to hydroxyethyl starch (HES). METHODS: After approval of the Ethics Committee, 12 patients (6 males and 6 females, mean age 59 +/- 10 years, ASA 1-2) undergoing elective liver resection were randomly allocated to receive either 3 ml.kg-1 6% HES 70,000/0.5 (group 1) or 0.4 g.kg-1 HBOC-201 (group 2) within 30 min following autologous blood donation of 1 l and substitution with 2 l Ringer's lactate. Measurements of blood gases, haemodynamics, and oxygen transport parameters were performed after induction of general anaesthesia, prior to and after blood donation, during and after infusion, at the beginning of surgery, and in the intensive care unit. RESULTS: Demographic characteristics did not differ between groups. In contrast to the HES group, mean arterial pressure increased by 18% over baseline measurements in group 2. While pulmonary vascular resistance showed a trend to higher values in group 2, systemic vascular resistance increased to a maximum of 42% over baseline in group 2 and was twice as high as in the HES group. The cardiac index was lower in the HBOC-201 group than in the HES group. During and after HBOC-201 infusion, mixed-venous oxygen saturation and content and calculated oxygen delivery were lower in group 2 in comparison to group 1, while the oxygen extraction ratio was higher in group 2. Free haemoglobin reached a maximal concentration of 1.0 +/- 0.2 g.dl-1 30 min after the HBOC-201 infusion was started, but was not detectable in urine over time. The mean intravascular half-life of HBOC-201 was 8.5 h. CONCLUSIONS: Patients did not show any severe complications during and after infusion of HBOC-201. However, vasoconstrictive side effects resulted in increased systemic but not pulmonary resistance. Ongoing studies with higher doses of HBOC-201 applied in a larger number of patients will probably reveal potential clinical consequences of the demonstrated haemodynamic changes.

Adult↗

In situ splitting of cadaveric livers. The ultimate expansion of a limited donor pool.

OBJECTIVE: The authors evaluate the safety, applicability, and effectiveness of a new technique for split-liver transplantation. SUMMARY BACKGROUND DATA: Split-liver transplantation offers an attractive way to increase the donor pool for cadaveric liver transplantation. The application of this concept has been hampered by inferior patient and graft survivals and higher complication rates. Without supportive data, the concern about increasing biliary leakage and poor initial graft function persisted. The authors focused on the causes of these complications by presenting a new technique to eliminate these problems. METHODS: Liver splitting was performed in the heart-beating cadaveric organ donor, using the technique described for procurement of the left lateral lobe of a live donor. A detailed description of the technique is presented. A retrospective review of the first 14 transplantations resulting from 7 in situ splitting procedures was collected. The results were compared with 19 conventional split-liver transplants performed during the same period. RESULTS: Six-month patient and graft survivals after in situ split-liver transplantation were 92.8% and 85.7%, respectively. Biliary complications were absent. Postoperative courses were mostly uneventful and characterized by lower peak transaminase levels compared with standard techniques. Early graft function of extrahepatic organs procured simultaneously was excellent. CONCLUSIONS: In situ split-liver transplantation provides superior results, related mainly to reduction of cold ischemic damage of the grafts and avoidance of biliary complications. In situ split-liver transplantation renders graft reduction alone obsolete and opens a donor pool for adults to receive right lobes safely. It allows for long-distance sharing between pediatric and adult liver transplant units because the procedure abolishes ex situ benching and prolonged ischemia time and provides two anatomically perfect grafts with hemostasis accomplished.

Adult↗

[Therapy splitting: are intra-operative cholangiography and surgical bile duct revision still indicated?].

The role of therapeutic splitting in cases of cholecystolithiasis and choledocholithiasis has to be reviewed since laparoscopic bile duct exploration might be an alternative. To assess the need of the new approach we evaluated our results of the therapeutic splitting. Between 1988-1992 a cholecystectomy was performed in 577 cases either as an open (n = 274) or laparoscopic (n = 277) procedure. Pre- or postoperative endoscopic retrograde cholangiopancreatography (ERC/P) was performed if the clinical presentation, laboratory findings or ultrasound showed signs of choledocholithiasis. In the laparoscopic cases no intraoperative cholangiography was carried out. The patient follow-up was evaluated by a questionnaire. 128 patients were suggested to have a common bile duct (CBD) stone and had a preoperative ERC/P. In 68 cases stones were extracted. After cholecystectomy 19 ERC/P's were performed. In 4 patients residual stones after preoperative ERC/P were detected. So far occult stones were found in 5 cases. Intraoperative cholangiography was performed additionally in the patients with open cholecystectomy n = 207¿, of whom two demonstrated choledocholithiasis. Endoscopic clearance of the common bile duct was achieved in all patients. Minor complications occurred after ERC/P in 1.5%. Within a median follow-up time of 48 months patients with endoscopic papillotomy did not develop further CBD stones or a cholangitis. The therapeutical splitting facilitates in all patients with cholecysto- or choledocholithiasis a successful clearance of the CBD. Intraoperative cholangiography is not necessary according to our experience. With an experienced endoscopic team the therapeutic splitting should be the preferred treatment modality compared to the laparoscopic bile duct exploration, which will probably lead to a high complication rate if performed outside specialized centers.

Adolescent↗

[Liver transplants from living donors].

In this article the authors discuss the advantages of Living Related Liver Transplantation (LRLT), criteria for the selection of donors and the standard operation technique. Among a total of 241 liver transplantation (LTx), 42 LRLT were performed at the University of Hamburg between October 1, 1991 and December 19, 1994. The body weight of recipients for LRLT ranged from 4,6 to 39 kg, with 64,2% having less than 10 kg. The volume of the donor left lateral liver lobe ranged from 100 cc to 350 cc. The average one year survival rate among electively operated patients-status 3-4 (UNOS 1995 classification) was 86.7%, two year survival rate 83.3%. The main advantages of LRLT are consired the following: 1. Absence of mortality on the waiting list, 2. Optimal timing of the transplantation (elective procedure, patient in a good condition), 3. Excellent organ (no primary non function), 4. A possible immunologic advantage, 5. Relief of the waiting list for cadaveric organs, 6. Psychological benefit for the family, 7. Cost effectiveness. Potential candidates for living donation with more than one cardiovascular risk factors were excluded. Social and psychological reasons leading to rejection of candidates were as follows: unstable family structure, expected professional or financial difficulties after living donation or withdrawal from consent. LRLT gives parents of a child with TLD a chance to avoid the risk of death on the waiting list or primary non function of the graft. LRLT has therefore established an important place in pediatric liver transplantation.

Adult↗