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Biomedical subjects

R Raab

Publications and source records attributed to R Raab.

At least 37 records · Page 2Linked to original sources

[Results of surgical therapy of primary adenocarcinoma of the duodenum].

Between January 1983 and August 1998, a total of 18 patients (14 men, 4 women; median age 58 years, range 36-75 years) with primary adenocarcinoma of the duodenum underwent surgical therapy. Main clinical symptoms were upper abdominal pain (61%), weight loss (44%) and anaemia (38%). The tumors were resectable in 10 patients (56%), and eight Whipple operations and two segmental duodenectomies were performed. Tumor classification according to the TNM system was pT2 (n = 2), pT3 (n = 6) and pT4 (n = 2). In eight patients, local lymph nodes were tumor positive (pN1), and in two patients synchronous liver metastases were excised. The UICC stage of the resected tumors was: stage I (n = 1), stage II (n = 1), stage III (n = 6) and stage IV (n = 2). In irresectable cases (n = 8), the patients underwent palliative (n = 6) or explorative (n = 2) operations. With no operative mortality, overall morbidity was 22% (4/18). Patients' survival was 90%, 66.7% and 53.3%, respectively, at 1, 3 and 5 years after resection. None of the patients with irresectable tumors survived longer than 25 months. Survival was significantly better for the resection group (P = 0.0027). Due to the often unspecific symptoms, the diagnosis of duodenal adenocarcinoma is frequently established at advanced tumor stages, resulting in a low resectability rate. Radical surgical resection of the tumors, however, is able to provide a more favorable prognosis for duodenal carcinoma than for other periampullary tumors.

Adenocarcinoma↗

Total hepatectomy and liver transplantation for metastatic neuroendocrine tumors of the pancreas - a single center experience with ten patients.

BACKGROUND: Metastatic neuroendocrine pancreatic tumors have a poor prognosis. We have studied retrospectively the efficacy of liver transplantation as ultimate therapy of otherwise untreatable symptomatic neuroendocrine hepatic metastases originating in the pancreas. METHODS: We reviewed our experience of liver transplantation (LTx) for hepatic metastases of neuroendocrine pancreatic tumors in ten patients. The indication for liver grafting was seen in cases of irresectable metastases and when patients were suffering from otherwise untreatable tumor-associated symptoms due to massive hormonal release or large intra-abdominal tumor bulk. RESULTS: In four patients, the primary tumors had been removed before LTx, in five patients simultaneously with LTx and in one case 46 months after grafting. There was no operative mortality. After hepatectomy and LTx, all patients had complete relief of symptoms and all preoperatively increased hormonal levels returned to normal. In nine of ten patients, the transplant procedure had the potential for cure, whereas, in one patient, the primary tumor had remained in situ at LTx and was removed 46 months later by an R2-resection. At present, nine patients are alive with a median follow-up of 33 months (range 13.5 months to 117 months). The one patient in whom the primary tumor was removed after transplantation died due to massive intra-abdominal tumor spread 68 months after LTx. Currently, two patients are without evidence of disease, but one of them after re-operation because of lymph-node metastases 8 months after transplantation. The longest disease-free survival is now more than 7 years. In seven of nine patients, tumor recurred between 1.5 months and 48 months after transplantation. CONCLUSIONS: Patients with otherwise untreatable symptomatic neuroendocrine hepatic metastases of pancreatic origin may benefit from total hepatectomy and liver transplantation with regard to symptomatic relief and long-term survival, despite frequent recurrence of disease. In some patients, liver transplantation may even offer the chance for cure.

Disease-Free Survival↗

Attitude of patients toward transplantation of xenogeneic organs.

BACKGROUND: The prospect of xenotransplantation has stimulated considerable hopes as well as major concerns. The question of whether or not patients accept xenografts is influenced not only by scientific facts but also by psychological factors. It was the aim of this study to analyze the attitudes of patients toward transplantation of xenogeneic organs and evaluate factors influencing these attitudes. METHODS: To this end, attitudes toward xenogeneic compared with allogeneic organ grafts were evaluated by means of detailed questionnaires in 1049 patients in Germany, who either had received transplants (n=722) or were on the waiting list for various organ grafts (n=327). Answers were correlated to demographic data as well as to the physical and mental conditions of the patients. RESULTS: The survey indicates that 77% of patients would accept xenografts while 7% would refuse them if results of xenotransplantation were comparable with those of allotransplantation. If xenotransplantation were associated with increased risks due to more intensive medication 58% would still basically accept xenografts. Acceptance of xenografts was significantly higher in patients who had received transplants and among males. Age, religion, waiting time, and type of organ were not found to influence acceptance rates. Xenografts were thought to be associated with considerable or severe emotional stress by 23% of patients, versus 3% for allografts. The pig was the preferred donor animal, and gene therapeutic manipulation for improvement of results would be accepted by 84%. Inadequate graft function/increased risk of rejection and risk of disease transmission were the major concerns for 60% and 52% of patients, respectively; emotional concerns were the major concerns for 24% and animal-rights concerns for 15%. CONCLUSIONS: These findings show that the potential acceptance rate of xenografts would be quite high, with a more positive attitude in transplanted patients than in waiting-list patients; there was no major difference in acceptance rate for various types of organs. Major concerns about xenotransplantation currently are functional inferiority and transmission of diseases.

Adult↗

Invasive differentiated thyroid carcinoma: tracheal resection and reconstruction procedures in the hands of the endocrine surgeon.

BACKGROUND: Although differentiated carcinoma of the thyroid gland is a relatively benign tumor, up to 20% of patients are endangered by potentially fatal complications resulting from infiltrating tumor growth into the upper aerodigestive tract. METHODS: This study included 33 patients who underwent 34 tracheal or laryngotracheal procedures for invasive differentiated thyroid carcinoma under the direction of a single surgeon (G.F.W.S.). From 1990 to 1994, radical tumor extirpation was performed by "window" resection, and from 1995 to 1998, radical surgery consisted of either circumferential sleeve resection or laryngotracheal "step" resection--a novel method of reconstruction in cases of unilateral tumor infiltration into the larynx and trachea. Resection was limited to laminar ablation in 17 cases. The mean follow-up of 16 patients who survived was 42.5 months (range, 2 months to 8.9 years). RESULTS: Procedures resulting in primary end-to-end anastomosis of the upper airways were associated with lower perioperative morbidity and improved recurrence-free survival when compared with "window" resections with muscle flap reconstruction. In cases of superficial tracheal tumor infiltration, laminar ablations were sufficient for local tumor control. CONCLUSIONS: Radical eradication of differentiated thyroid carcinoma infiltrating the upper airways followed by radioiodine application should be considered the treatment of choice. Laryngotracheal "step" resection allows tumor extirpation with preservation of neural and muscular structures of the larynx.

Adult↗

Reconstructive surgery for ischemic-type lesions at the bile duct bifurcation after liver transplantation.

OBJECTIVE: To assess the feasibility, morbidity, mortality, and clinical success rate of surgical reconstruction of the biliary system in patients with ischemic-type biliary lesions in their liver graft. SUMMARY BACKGROUND DATA: After liver transplantation, strictures in the biliary tree with secondary sludge formation can occur in the absence of vascular problems. Jaundice, pruritus, and recurrent cholangitis are predominant clinical features leading to considerable morbidity. Interventional measures are the first-line treatment but are frequently only of transient success. Retransplantation is usually considered when interventional treatment is not effective. METHODS: Surgical exploration and reconstruction was performed in 17 patients with ischemic-type biliary strictures at a median of 2 years after liver transplantation. Findings during surgery, surgical strategies, and postsurgical courses are described. Clinical symptoms and biochemical parameters of cholestasis and liver function were analyzed in the postsurgical course. RESULTS: During surgery, all 17 patients were found to have strictures or sclerotic changes involving the hepatic bifurcation and extrahepatic bile duct. Sludge or stones were present in nine patients. In 14 patients with viable bile ducts proximal to the bifurcation, surgical reconstruction was performed by resection of the bifurcation and hepaticojejunostomy. In three patients with more extensive biliary destruction, portoenterostomy with or without peripheral hepatojejunostomy was performed. The prevalence rate of biliary infection at surgery was 93%; the predominant organisms were Candida and enterococci. The perioperative mortality rate was 0%. Clinical symptoms and biochemical parameters became normal or were considerably improved in 14 of 16 patients (88%). CONCLUSIONS: The hepatic bifurcation seems to be a predominant site for ischemic-type biliary changes after liver transplantation. Surgical treatment by resection of the bifurcation and reconstruction by high hepaticojejunostomy is a safe and highly effective approach leading to cure or persistent major improvement in most patients.

Adult↗

Peripheral hepatojejunostomy as palliative treatment for irresectable malignant tumors of the liver hilum.

OBJECTIVE: To evaluate the concept of surgical decompression of the biliary tree by peripheral hepatojejunostomy for palliative treatment of jaundice in patients with irresectable malignant tumors of the liver hilum. SUMMARY BACKGROUND DATA: Jaundice, pruritus, and recurrent cholangitis are major clinical complications in patients with obstructive cholestasis resulting from malignant tumors of the liver hilum. Methods for palliative treatment include endoscopic stenting, percutaneous transhepatic drainage, and surgical decompression. The palliative treatment of choice should be safe, effective, and comfortable for the patient. METHODS: In a retrospective study, surgical technique, perioperative complications, and efficacy of treatment were analyzed for 56 patients who had received a peripheral hepatojejunostomy between 1982 and 1997. Laparotomy in all of these patients had been performed as an attempt for curative resection. RESULTS: Hepatojejunostomy was exclusively palliative in 50 patients and was used for bridging to resection or transplantation in 7. Anastomosis was bilateral in 36 patients and unilateral in 20. The 1-month mortality in the study group was 9%; median survival was 6 months. In patients surviving >1 month, a marked and persistent decrease in cholestasis was achieved in 87%, although complete return to normal was rare. Among the patients with a marked decrease in cholestasis, 72% had no or only mild clinical symptoms such as fever or jaundice. CONCLUSIONS: Peripheral hepatojejunostomy is a feasible and reasonably effective palliative treatment for patients with irresectable tumors of the liver hilum. In patients undergoing exploratory laparotomy for attempted curative resection, this procedure frequently leads to persistent-although rarely complete-decompression of the biliary tree. In a few cases it may also be used for bridging to transplantation or liver resection after relief of cholestasis.

Adult↗

Mast cells are an important cellular source of tumour necrosis factor alpha in human intestinal tissue.

BACKGROUND: Several inflammatory disorders of the intestine are characterised by enhanced expression of tumour necrosis factor alpha (TNF-alpha). Monocytes and macrophages have been suggested as a major cellular source of TNF-alpha in human gut, whereas mast cells, although known to be capable of producing TNF-alpha, have been poorly examined in this respect. AIMS: To investigate whether human intestinal mast cells can produce TNF-alpha, and which factors regulate TNF-alpha production in these cells. METHODS: Mast cells were isolated from surgery tissue specimens of patients undergoing bowel resection because of cancer. Immunohistochemical studies were performed in biopsy specimens derived from 13 patients (two healthy controls, four with Crohn's disease, four with ulcerative colitis, three others). TNF-alpha mRNA and protein expression were studied in vitro by polymerase chain reaction, RNAse protection assay, western blot, and enzyme linked immunosorbent assay in isolated purified human intestinal mast cells stimulated by IgE receptor crosslinking, intestinal bacteria, and lipopolysaccharide. Cellular localisation of TNF-alpha was examined by immunohistochemistry. RESULTS: TNF-alpha mRNA and protein were expressed constitutively in isolated human intestinal mast cells. Expression of TNF-alpha mRNA and release of TNF-alpha protein were substantially enhanced by IgE receptor crosslinking and by coculture of mast cells with intestinal bacteria; lipopolysaccharide had only marginal effects. Immunohistochemical studies revealed that approximately 60% of the lamina propria cells with immunoreactivity for TNF-alpha were mast cells. CONCLUSIONS: The data show that mast cells are an important source of TNF-alpha in the human intestinal mucosa.

Blotting, Western↗

Prenatal nicotine increases pulmonary alpha7 nicotinic receptor expression and alters fetal lung development in monkeys.

It is well established that maternal smoking during pregnancy is a leading preventable cause of low birth weight and prematurity. Less appreciated is that maternal smoking during pregnancy is also associated with alterations in pulmonary function at birth and greater incidence of respiratory illnesses after birth. To determine if this is the direct result of nicotine interacting with nicotinic cholinergic receptors (nAChRs) during lung development, rhesus monkeys were treated with 1 mg/kg/day of nicotine from days 26 to 134 of pregnancy. Nicotine administration caused lung hypoplasia and reduced surface complexity of developing alveoli. Immunohistochemistry and in situ alpha-bungarotoxin (alphaBGT) binding showed that alpha7 nAChRs are present in the developing lung in airway epithelial cells, cells surrounding large airways and blood vessels, alveolar type II cells, free alveolar macrophages, and pulmonary neuroendocrine cells (PNEC). As detected both by immunohistochemistry and by alphaBGT binding, nicotine administration markedly increased alpha7 receptor subunit expression and binding in the fetal lung. Correlating with areas of increased alpha7 expression, collagen expression surrounding large airways and vessels was significantly increased. Nicotine also significantly increased numbers of type II cells and neuroendocrine cells in neuroepithelial bodies. These findings demonstrate that nicotine can alter fetal monkey lung development by crossing the placenta to interact directly with nicotinic receptors on non-neuronal cells in the developing lung, and that similar effects likely occur in human infants whose mothers smoke during pregnancy.

Animals↗

Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation.

PURPOSE: Tumor recurrence is the major limitation of long-term survival after liver transplantation for hepatocellular carcinoma (HCC) or fibrolamellar carcinoma (FLC). Understanding tumor-biologic characteristics is important for selection of patients and for development of adjuvant therapeutic strategies. PATIENTS AND METHODS: The study included 69 patients who underwent potentially curative liver transplantation for HCC/FLC and survived for more than 150 days; minimum follow-up was 33 months. Frequency, localization, and timing of recurrence were analyzed and compared with primary tumor and patient characteristics. RESULTS: Tumor recurrence was observed in 39 patients at 67 locations. Hematogenous spread was the major route of tumor recurrence (87%), and the most frequent sites were the liver (62%), lung (56%), and bone (18%). Parameters associated with recurrence were absence of cirrhosis, tumor size greater than 5 cm, more than five nodules, vascular infiltration, and International Union Against Cancer (UICC) stage IVA. Selective intrahepatic recurrence was found in nine patients (23%); it was associated with highly differentiated tumors, lack of vascular infiltration, and male sex. Recurrence at multiple sites was found predominantly in young patients (< or = 40 years) and for multicentric (> 5) primary tumors. Recurrences were observed within a wide time range after transplantation (43 to 3,204 days; median, 441 days); late recurrences (> 1,000 days, n = 8) were associated with highly differentiated or fibrolamellar tumors and low UICC stages. Surgical treatment was the only therapeutic option associated with prolonged survival after recurrence. CONCLUSION: In transplant recipients, hepatocellular carcinomas vary considerably in their pattern and kinetics of metastases. Tumor cells may persist in a dormant state for long time periods before giving rise to clinical metastases. Surgical treatment of recurrence should be considered whenever possible.

Adult↗

Arterial chemoembolization before liver transplantation in patients with hepatocellular carcinoma: marked tumor necrosis, but no survival benefit?

BACKGROUND/AIMS: Hepatic artery chemoembolization was introduced in the treatment of patients with unresectable hepatocellular carcinoma waiting for liver transplantation. The rationale for this preoperative treatment was to control tumor growth during the waiting period and to improve long-term survival. This study aimed to investigate whether preoperative chemoembolization not only induces marked tumor necrosis but also has a survival benefit. METHODS: In this study 21 patients with hepatocellular carcinoma who underwent pretransplant chemoembolization (group I) were compared with 21 historical control patients (group II) without preoperative chemoembolization in a case-control study. The number of pretransplant chemoembolizations in each patient in group I varied between 1 and 5 with a mean of 2.44+/-1.15. In addition, six patients of this group received preoperative systemic chemotherapy. RESULTS: Overall, there were no differences in survival between the groups with and without pretransplant chemoembolization at 1 year (60.8% vs 61.5%) and at 3 years (48.4% vs 53.9%). In group I, three patients developed unexplained severe pneumonia, leading to death very early after liver transplantation. Marked tumor necrosis (>50%) was found in 14 cases in group I. In 6 out of these 14 patients, total tumor necrosis was observed. CONCLUSION: Although preoperative chemoembolization or chemotherapy induced marked tumor necrosis, these patients showed no benefit in survival compared to historical controls, and appeared to be at higher risk of developing immediate postoperative infective complications.

Carcinoma, Hepatocellular↗

Appraisal of transplantation for malignant tumours of the liver with special reference to early stage hepatocellular carcinoma.

The enthusiasm to treat or even cure patients with unresectable hepatobiliary malignancy by total hepatectomy and liver transplantation has considerably diminished. Nowadays, due to organ-donor shortage, patients have to be selected with predictable likelihood for long-term survival. According to own experience and a review of the literature, liver transplantation may be considered in unresectable early stage hepatocellular and proximal bile duct carcinoma, the uncommon entities fibrolamellar carcinoma, epithelioid haemangioendothelioma and hepatoblastoma as well as in liver metastases from neuroendocrine tumours. At present, advanced stages of hepatocellular and proximal bile duct carcinoma, as well as intrahepatic bile duct carcinoma, haemangiosarcoma and metastases from nonendocrine tumours, should be excluded from transplantation. In order to cure the cancer-bearing disease, liver transplantation might be the ideal treatment for small but still resectable hepatocellular carcinoma with underlying cirrhosis. Our retrospective comparison of survival after resection and transplantation for early stage hepatocellular carcinoma does not reveal a significant difference. Although a tendency has been observed in favour of transplantation, resection of these tumours is still justifiable, not least because of donor organ shortage.

Actuarial Analysis↗

Monoclonal antibody therapy for resected Dukes' C colorectal cancer: seven-year outcome of a multicenter randomized trial.

PURPOSE: As previously shown, antibody treatment increased survival of patients with resected colorectal cancer of stage Dukes' C. Since the 5-year analysis was criticized because of the wide range (2.7 to 7.5 years) of follow-up time, we performed a 7-year analysis with only four of 189 patients monitored for less than 5 years. PATIENTS AND METHODS: A total of 189 patients with resected Dukes' C colorectal cancer were randomly allocated to infusions of a total of 900 mg 17-1A antibody, 500 mg postoperatively followed by 4 monthly doses of 100 mg (n=99), or to observation only (n=90). Primary end points were overall survival and disease-free interval. Patients were stratified by a dynamic randomization according to center, sex, location of tumor, number of affected lymph nodes, and preoperative carcinoembryonic antigen concentration. RESULTS: Randomization produced balanced distribution of risk factors. After 7 years of follow-up evaluation, treatment had reduced overall mortality by 32% (Cox's proportional hazard, P < .01; log-rank, P=.01) and decreased the recurrence rate by 23% (Cox's proportional hazard, P < .04; log-rank, P=.07). The intention-to-treat analysis gave a significant effect for overall survival (Cox's proportional hazard, P < .01; log-rank, P=.02) and disease-free survival (Cox's proportional hazard, P=.02; log-rank, P=.11 ). While distant metastases were significantly reduced (Cox's proportional hazard, P=.004; log-rank, P=.004), local relapses were not (Cox's proportional hazard, P=.65; log-rank, P=.52). This differential effect of 17-1A antibody on disseminated isolated tumor cells versus occult local satellites may explain the increased significance seen in the overall survival. CONCLUSION: The now-matured study shows that 17-1A antibody administered after surgery prevents the development of distant metastasis in approximately one third of patients. The therapeutic effect is maintained after 7 years of follow-up evaluation.

Adenocarcinoma↗

[De novo hepatitis B infection after liver transplantation--evidence for the need of active hepatitis B vaccination of liver transplantation candidates].

BACKGROUND: Liver transplantation (LTX) is a generally accepted therapy in the treatment of acute and chronic end-stage liver diseases. Recurrent and de-novo hepatitis B and C virus infection following liver transplantation have been shown. PATIENTS AND METHODS: We analyzed retrospectively the course of patients treated at our transplant center between 01.01.1992 and 31.12.1997, who does not show any markers of an active hepatitis B (HBV) infection prior to liver transplantation but developed replicative HBV infection afterwards. During this period 544 liver transplantations were performed in 452 patients, 395 of whom were HBs-Ag negative prior to transplantation. RESULTS: Six patients were identified who underwent LTX for non-hepatitis B-induced liver disease, and who subsequently developed a highly replicative de-novo HBV-infection six to twelve months (mean 8.5 months) after LTX. In each of the patients HBV de-novo infection showed clinically and biochemically a mild but chronic course without evidence of liver failure during a maximum follow-up period of 14 to 37 months (mean 26 months). Liver biopsies taken in four patients nine to 22 months after LTX showed chronic active hepatitis (n = 2), chronic portal hepatitis (n = 1), and a mild rejection (n = 1). The source of de-novo HBV infections remained unclear, but inapparent infection of patients pre-LTX was ruled out so that the donor livers or postoperative infection appear to be the likely source. CONCLUSION: In our center the number of HBV de-novo infections (1.5%, 6/395) following liver transplantation was comparable to the results published by other centers, but in our center no inapparent infection of patients prior to LTX was observed. For further minimization of HBV de-novo infection following LTX active HBV immunization of patients awaiting LTX is recommended.

Adult↗

Functional properties of human intestinal mast cells cultured in a new culture system: enhancement of IgE receptor-dependent mediator release and response to stem cell factor.

Culture of human mast cells (MC) in vitro has only been possible to date in the presence of 3T3 fibroblasts. The aim of the present study was to maintain freshly isolated human MC in culture without addition of feeder cells and to study their functional properties. We isolated cell suspensions containing 1 to 11% MC from human intestinal tissue and cultured them in standard medium. MC survived in culture for about 2 wk without cytokine supplementation and for several months with supplementation of medium with stem cell factor (SCF). SCF selectively supported MC survival, whereas the number of contaminating cells declined rapidly during culture. Most interestingly, we found that histamine and leukotriene release induced by IgE receptor cross-linking was substantially enhanced in cultured MC compared with that in MC stimulated directly after cell isolation. Cultured MC, but not freshly isolated MC, released mediators in response to SCF in a concentration-dependent fashion provided that the cells were cultured in SCF-free medium. These findings demonstrate that human MC isolated from intestinal tissue can be maintained in culture in vitro for several weeks. After culture they have different functional properties, which might resemble more closely the functional status of human intestinal MC in vivo than that of freshly isolated cells.

Antibodies, Monoclonal↗

[The efficacy dilemma].

Effectivity and efficiency of medical treatment have conflicting aims which result in a conflict of interests between a patient, interested in maximal effectively and the society, interested in maximal efficiency. The physician cannot solve this conflict because he is primarily obliged to the interests of the individual patient. If rationing is unavoidable in modern health care services, there must be an open discussion in order to reach a broad consensus within the society.

Abdominal Neoplasms↗