Immunosuppression in pancreas transplantation: the Euro SPK trials and beyond.

The Immunosuppression in Pancreas Transplantation was historically based on the fact that the pancreas is an extremely immunogenic organ. Quadruple drug therapy with polyclonal or monoclonal antibodies induction was the mainstay therapy since the introduction of Cyclosporine A. In the modern era of Immunosuppression, Mycophenolate Mofetil replaced Azathioprine while Tacrolimus-another potent calcineurin inhibitor-had-and still has-a difficult challenge to replaced Cyclosporine A, due to its potential diabetogenic effect. Thanks to the first two EuroSPK studies which prospectively tried to answer several questions in that field. But, the future challenge will be in understanding the impact of innate immunity and ischemic reperfusion injuries on the long-term graft function. Hopefully, new drugs will be available and tested to block unspecific deleterious reactions to attenuate the proinflammatory response. It will be the aim of the third Euro SPK Study.

[Morbidity following simultaneous pancreas/kidney transplantation]. / Morbidität der kombinierten Pankreas-/Nierentransplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) is still associated with the highest rate of morbidity among solid organ transplantations. Although improved long-term survival following SPK has been proven in IDDM patients, a further decrease in morbidity would be desirable. METHODS: A retrospective, single-center study was performed to investigate the morbidity following SPK and to compare the results to kidney transplantation alone (KTA). Parameters included the rates of relaparotomies, septic complications (urinary tract infection, wound infection, pneumonia), and graft function. RESULTS: Between September 2000 and August 2001, 99 patients underwent transplantation (34 SPK, 63 KTA, 2 pancreas transplants alone). Relaparotomies were performed in six SPK patients (17.6%), mostly due to complications related to the pancreatic graft (n=5). Three reoperations (4.8%) were necessary in KTA patients (p=0.085). Septic complications occurred more often in SPK than in KTA patients (55.9% vs 30.2%, p<0.05). This difference resulted from the high rate of wound infections in SPK patients (35.3%). No intra-abdominal infection or sepsis occurred in any patient. There was one hospital death in SPK and KTA patients, respectively. The rejection rate was similar in SPK (17.6%) and KTA (12.7%, p=0.72). At discharge 91.2% of SPK patients were insulin free and 97.1% free of dialysis. At discharge 96.8% of KTA patients were free of dialysis. CONCLUSION: SPK is still associated with a higher morbidity (relaparotomies, septic complications) than KTA, although life-threatening complications were rare. There was no increased mortality following SPK.

Simultaneous pancreas-kidney transplantation in patients with antiphospholipid syndrome.

BACKGROUND: Graft thrombosis is one of the main reasons of graft loss following simultaneous pancreas-kidney transplantation (SPK). Although antiphospholipid syndrome (APLS) is known as a high risk for graft thrombosis in kidney transplants alone, little is known about APLS in SPK. METHODS: Between September 2000 and December 2001, 45 SPK were performed. The treatment and clinical course of 2 patients with APLS is presented. RESULTS: In one patient, APLS was known before transplantation. After SPK, she was treated by systemic heparin followed by coumarin. Both grafts are doing well 5 months posttransplant. The second patient underwent SPK without knowledge of APLS. The patient developed a deep vein thrombosis 5 weeks posttransplant. Hypercoagulability screening revealed APLS. Treatment consisted of systemic anticoagulation. Grafts were not affected. CONCLUSION: SPK can successfully be performed in APLS patients if anticoagulation is performed consistently. To reduce the risk of graft thrombosis, a pretransplant screening for APLS would probably be of benefit.

[Intensive care treatment of post-traumatic liver failure]. / Intensivmedizinische Behandlung des posttraumatischen Leberversagens.

Liver failure following trauma or surgery is associated with a mortality of between 15-->50%, depending on the extent of the operation, pre-operative functional impairment of the liver as well as the occurrence of concomitant infectious disease. The liver can be the source as well as the target of posttraumatic liver failure (PLF). PLF can be caused by a reduction of liver perfusion due to hypotension, catecholamines or increased intraabdominal pressure. Further contributing factors include prolonged parenteral nutrition, endotoxemia, and potentially hepatotoxic drugs (sedatives, anticonvulsive drugs, antibiotics etc.). PLF is mostly associated with MOF. The Child classification and the APACHE score may predict prognosis before surgery and serum bilirubin levels thereafter. Prevention and therapy is based on treatment of shock and tissue hypoxia. It should be accompanied by appropriate diagnostic measures and followed by an aggressive medical and surgical approach.

[Development of primary malignancies after liver and kidney transplantation and the treatment approach]. / Entwicklung primärer Malignome nach Leber- und Nierentransplantation und ihre Behandlungsstrategie.

Primary malignancy after solid organ transplantation has a more than three-fold incidence compared to the normal population. Causes are intensity and duration of immunosuppression, pre-operatively undetected, occult malignancy or pre-cancerous lesions in the recipient, direct or indirect tumor transmission via the transplant and environmental factors. Measures for prevention comprise antiviral treatment of individuals at risk for primary EBV-infection and prevention of sun exposure. Early detection follows general medical guidelines and, in addition, selective screening of certain risk groups of patients. Treatment of solid tumors follows established guidelines of professional working parties. Post-transplant lymphoproliferative disorders can often be treated with anti-CD antibody (rituximab). Antiproliferative immunosuppressants like rapamycin may seem promising with regard to a possibly reduced incidence of de-novo malignancy in the future.

Initially unresectable hilar cholangiocarcinoma: hepatic regeneration after transarterial embolization.

PURPOSE: To assess with volumetric computed tomography (CT) the pattern and extent of hepatic regeneration induced with transarterial embolization of initially unresectable hilar cholangiocarcinoma (Klatskin tumor). MATERIALS AND METHODS: In this prospective study, 13 patients (four men, nine women) with hilar cholangiocarcinoma, aged 43-74 years (mean +/- 1 standard deviation, 59.9 years +/- 9.6), underwent preoperative embolization of the right hepatic lobe. Embolization was performed transarterially by using four to 15 embolization coils. Volumetric measurements of the entire liver, left hepatic lobe, and spleen were performed with contrast material-enhanced and unenhanced helical CT before and after embolization in all patients. RESULTS: After right lobe embolization, volumetric helical CT measurements revealed a 2%-33% decrease (mean, 10%) in the volume of the affected right hepatic lobe, an 11%-68% increase (mean, 37%) in the volume of left hepatic lobe parenchyma, and variations in splenic volume of -5% to +28% (mean, +11%). Nine patients underwent extended hepatectomy 27-75 days (mean, 44 days) after embolization. No patient had severe complications due to embolization. CONCLUSION: In patients with an initially unresectable bilateral Klatskin tumor, right lobar arterial coil embolization results in enlargement of the left hepatic lobe (as verified with volumetric helical CT), thus allowing right hemihepatectomy.

[Intra-abdominal schwannoma. Diagnosis and surgical therapy]. / Intraabdominelle Schwannome. Diagnostik und chirurgische Therapie.

We report three patients who were operated on because of an intraabdominal schwannoma between February 1991 and October 1994 in our department. In the first case, a benign gastric schwannoma was treated by a distal gastric resection (Billroth II); the main symptom was gastric bleeding. In the second case, a malignant duodenal schwannoma with liver metastasis was treated by wide en-bloc resection of the tumor including retroperitoneal lymphadenectomy and an anatomical resection of the right lobe of the liver. A metachronous metastasis of the liver, appearing 7 months postoperatively, was treated by intraparenchymatous laser coagulation; a local recurrence, appearing 19 months postoperatively, led to another tumor resection. The main symptom was a palpable intraabdominal mass in this case. In the third case, a malignant schwannoma of the abdominal wall was resected in fragments in another clinic. Six months later a local recurrence with infiltration of the liver appeared in spite of postoperative radiation and was resected en bloc. Early peritoneal sarcomatosis was apparent at that time. Postoperative chemotherapy did not prevent quick progression of the tumor. The patient died 18 months after the first operation. The clinical presentation, differential diagnosis and operative strategy for benign and malignant intraabdominal schwannomas are discussed.

[Primary malignant intraluminal tumor of the aorta]. / Primärer maligner intraluminaler Tumor der Aorta.

Primary malignant tumors of the aorta are only rarely reported. We describe here our findings in a 55-year-old patient who was referred to us with progressive renal insufficiency. At angiography, right renal artery occlusion and high-grade stenosis of the left renal artery was found in this patient, who had undergone aortobiliacal reconstruction for acute Leriche syndrome 5 months previously. Histological evaluation of thrombotic material revealed an intraluminal malignant tumor to be the underlying cause. This diagnosis was then confirmed in samples harvested during angiography. CT scan showed an extension beginning 2 cm proximal to the celiac trunk. The patient was treated by thoracoabdominal resection of the aorta, including the paraaortal tissue, left side nephrectomy, and adrenalectomy. A thoracoabdominal aortic prosthesis was inserted up to the iliacal bifurcations and the celiac and superior mesenteric arteries reimplanted. Right nephrectomy followed 3 weeks later. The postoperative course was uneventful.

The effect of FK506 versus cyclosporine on glucose and lipid metabolism--a randomized trial.

In order to evaluate the effect of cyclosporine (CsA) versus FK506 on glucose and lipid metabolism, an oral glucose tolerance test (OGTT) was performed in 101 patients after orthotopic liver transplantation (OLT) (mean interval after OLT: 511 days). The liver graft recipients had been randomized prospectively to two groups prior to OLT to receive either immunosuppression with CsA, azathioprine, and corticosteroids (CsA group) or FK506 and corticosteroids (FK group). Along with the OGTT, serum insulin, insulin C-peptide and glucagon as well as serum lipids were monitored. There was no statistically significant difference in the occurrence of impaired glucose tolerance (IGT) or manifest diabetes mellitus disease between the two groups. In fact, not a single patient developed new-onset diabetes in any group. In male and female patients, serum levels of cholesterol and triglycerides increased significantly under FK506 and CsA treatment after OLT. Cholesterol was significantly higher in the CsA group in men, in women this was marked, but not significant. While triglycerides were significantly higher in women on CsA treatment, there was no such difference in men. In conclusion, both CsA and FK506 proved to have similar effects on glucose metabolism, while there was a different spectrum of serum lipid alterations.

[Improvement of therapeutic results with cast partial prostheses]. / Die Erhöhung der Erfolgssicherheit der Therapie mit gegossenen Teilprothesen.

The requirements for a cast partial denture with a serviceability of many years (6-8 years) are: finding-oriented therapy, exact preparation of the remaining teeth, periodontal-prophylactic shaping of the base and appropriate after-care. The different criteria are presented.

[Aspects of prosthetic therapy in deep bite]. / Einige Aspekte der prothetischen Therapie beim tiefen Bibeta.

The authors deal with the peculiar aspects of prosthetic treatment in case of deep bite. The possibilities of bite-raising depend upon the functional conditions. The necessity is determined by secondary changes in jaw relation and by the kind of treatment. Any correction of the occlusal position must consider the relationships of the anterior teeth.

[The possibility of prosthetic treatment of diastema]. / Die Möglichkeiten der rothetischen Behandlung eines Diastemas.

In so-called late cases, the correction of a diastema will frequently be achieved only by prosthetic measures, co-operation with an orthodontist being recommendable. The various possibilities of treatment are represented by case reports.