Biomedical subjects

Johann Hauss

Publications and source records attributed to Johann Hauss.

31 records · Page 2Linked to original sources

PubMed2003

Outcome after duodenum-preserving pancreatic head resection is improved compared with classic Whipple procedure in the treatment of chronic pancreatitis.

BACKGROUND: There is no consensus in the surgical management of chronic pancreatitis (cP) as to whether techniques preserving the duodenum are superior to pancreatoduodenectomy. This prospective study compared the outcome of standard pancreatoduodenectomy (PD) and duodenum-preserving pancreatic head resection (DPPHR) in treatment of selected patients with cP. METHODS: Inclusion criteria for this prospective controlled, nonrandomized study were patients suffering from cP centered in the head and with severe pain. Seventy consecutive patients underwent DPPHR (n = 38) or, if there was suspicion of malignancy, classic PD (n = 32). A multidimensional, psychometric questionnaire was used to measure the quality of life (QoL). QoL was compared with that of the general German population. Pain intensity was evaluated on the basis of the frequency of pain attacks, analgesic medication, and self-assessed pain score. Assessment of endocrine and exocrine function as well as nutritional status included oral glucose tolerance test, fecal elastase, stool frequency, and body mass index. The median follow-up was 34 months. RESULTS: Multiple clinical characteristics did not differ between the two groups except for age (P =.04), the tumor marker carbohydrate antigen 19-9 (P =.02), and the parameter suspicion of malignancy. There was no hospital mortality. Surgical morbidity was 19% in the PD group and 8% in the DPPHR group (P =.60). PD resulted in a longer median hospital stay than DPPHR (19 vs 15 days, P =.04). Complications of adjacent organs were definitively treated in 100% after PD and in 97% after DPPHR. Postoperative pain intensity as self-assessed by the patients was significantly less in the DPPHR group (P <.001), whereas the frequency of acute episodes (P =.27) and analgesic medication (P =.43) did not differ between the two groups. After surgery, symptom and functional scales of the DPPHR group were significantly better than those in the PD group and were similar to those of the overall German population. No significant difference was found between the two groups with regard to endocrine and exocrine function. Postoperative increase of body mass index was significantly higher in the DPPHR group (P <.001). CONCLUSIONS: DPPHR provides better results in the treatment of cP than PD in terms of QoL, pain intensity as self-assessed by the patients, nutritional status, and length of hospital stay.

Adult↗

PubMed2003

Esophageal perforation during left atrial radiofrequency ablation: Is the risk too high?

OBJECTIVE: Intraoperative radiofrequency ablation of atrial fibrillation (IRAAF) is a recently developed procedure being performed in an increasing number of patients. We have performed left atrial IRAAF in 387 patients since August 1998. The purpose of this article is to describe a serious complication of this procedure, namely IRAAF-induced esophageal perforation, in detail to identify possible risk factors. METHODS: Left atrial IRAAF was performed with a commercially available unipolar probe as an isolated procedure (n = 129) or in combination with mitral valve surgery (n = 163) or other surgical procedures (n = 95). Operations were performed either through a conventional sternotomy or right minithoracotomy. RESULTS: Four (1%) patients had esophageal perforation after radiofrequency ablation. All 4 patients presented after an initially unremarkable postoperative course, with sudden neurologic symptoms from esophagoatrial air embolization occurring in 3 of the patients. Three patients were successfully treated with extensive esophageal resection, and one died from massive air embolism. All perforations occurred in patients undergoing minimally invasive IRAAF. Comparison with other patients undergoing isolated minimally invasive IRAAF (n = 129) failed to reveal any reliable predictors of esophageal injury, including patient body size, operating times, or radiofrequency biophysical parameters. CONCLUSIONS: Left atrial IRAAF is associated with a small but definite risk of esophageal perforation. Unfortunately, we were unable to identify any risk factors for this life-threatening complication. A high degree of vigilance must be maintained for esophageal injury after IRAAF, particularly in patients with new neurologic deficits. Until safer methods of ablation are developed, we currently recommend against the use of IRAAF in patients undergoing cardiac surgery.

Adult↗

PubMed2003

Endothelin(A) receptor blockade reduces ischemia/reperfusion injury in pig pancreas transplantation.

OBJECTIVE: The effect of prophylactic administration of a selective endothelin(A) receptor antagonist (ET(A)-RA) on ischemia/reperfusion injury in an experimental model of graft pancreatitis after pancreas transplantation was evaluated. SUMMARY BACKGROUND DATA: It is well established that endothelin-1 (ET-1), a powerful vasoconstrictor, plays an important role in the development of pancreatitis. Recent studies have shown a beneficial effect of endothelin receptor antagonists in the therapy for experimental pancreatitis. METHODS: Relevant ischemia/reperfusion injury was induced in pig pancreas transplants after 6 hours hypothermic preservation in University of Wisconsin solution. The recipients were randomized into 2 groups: control pigs received isotonic saline and the treated group received the selective ET(A)-RA BSF 208075 at the beginning of reperfusion. On postoperative days 2 and 5, animals were relaparotomized to obtain tissue specimens. Blood monitoring included lipase, amylase, C-reactive protein, trypsinogen-activation peptide, thiobarbituric acid-reacting substances, and ET-1. Partial oxygen tension (p(ti)O(2)) was measured by a Clarke-type electrode and blood flow by laser doppler. A semiquantitative score index was used for assessment of histologic injury and for immunohistochemical analysis of ET-1 and ET(A) receptor expression. Tissue mRNA levels of prepro ET-1, ET(A) receptor, pro-interleukin (IL)-6, and pro-IL-1beta were quantified using TaqMan real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Prophylactic treatment with ET(A)-RA significantly reduced the severity of graft pancreatitis evidenced by C-reactive protein. The finding of transient capillary perfusion at the beginning of reperfusion supports the application of the ET(A)-RA during this period. The dramatic increase of plasma ET-1 in the therapy group is a clear evidence of effective receptor blockade. Mean trypsinogen-activation peptide levels from the portal venous effluent, but not mean systemic plasma TAP values were significantly lower in the treated group. Analysis of p(ti)O(2) and blood flow revealed a significant improvement of capillary perfusion and blood flow in the treated group and was associated with relevant reduction of tissue injury. Intrapancreatic ET-1 and IL-6 mRNA expression and ET-1 protein levels were significantly lower in the therapy group as compared with the control group. In contrast, ET(A) mRNA showed a marked up-regulation by ET(A) receptor blockade. CONCLUSION: Application of a ET(A)-RA reduces ischemia/reperfusion induced graft pancreatitis in a pig transplantation model by improving microcirculation and reducing tissue injury.

Amylases↗

PubMed2002

Induction therapy including antithymocyte globulin induces marked alterations in T lymphocyte subpopulations after liver transplantation: results of a long-term study.

Various immunosuppressive regimens aim to reduce the incidence of acute rejection after liver transplantation. The efficacy of antithymocyte globulin (ATG) induction therapy and short-term effects on the cellular response have been demonstrated in several studies. Nevertheless, information about long-term effects of ATG therapy on cellular responses and frequency of complications is limited. Therefore, we analyzed the effect of ATG administration within a cyclosporine-based induction therapy, including azathioprine and prednisolone, on lymphocyte subsets and activation markers. We divided 35 liver transplant recipients into two groups according to their initial postoperative immunosuppression: a triple group without ( n=15) and a quadruple group with ATG ( n=20). The minimum observation time (flow cytometry analysis, clinical follow-up) was 2 years. Patients treated with ATG had persistently lower percentages of T cells for at least 2 years postoperatively ( P<0.001). The CD4/CD8 ratios were lower in the quadruple group ( P<0.005). The patients in the ATG group revealed a drop in CD25(+) T cells within 2 years ( P<0.05). However, the percentage of CD71(+) and HLA-DR(+) T cells was temporarily higher in patients with ATG treatment ( P<0.05). Patients with ATG treatment showed persistently higher levels of CD8(+)/CD57(+) double positive cells in the late postoperative phase ( P<0.05). In contrast, no differences could be observed between the two groups for major parameters of clinical outcome (acute rejections, severe infections, patient survival). We conclude that ATG therapy induces long-lasting alterations in T-cell subset composition. However, no beneficial clinical effect could be confirmed after liver transplantation.

Adult↗

PubMed2002

Comparison of Celsior and UW solution in experimental pancreas preservation.

BACKGROUND: The University of Wisconsin solution (UW) is the gold standard for pancreas preservation. Celsior (CEL) was formulated specifically for heart preservation. Recently, experimental and clinical experience has been reported on the application of CEL to abdominal organs. In this animal study, pancreas preservation with CEL was compared with that in UW solution. PATIENTS AND MATERIALS: Heterotopic, allogeneic pancreaticoduodenal transplantation was performed in female Göttingen Minipigs (n = 12 donors, n = 12 recipients). The grafts were flushed and stored for 6 h at 4 degrees C in UW or CEL. The recipients were randomized into two groups receiving either UW (n = 6)- or CEL (n = 6)-preserved grafts with a follow-up of 5 days. Blood flow (laser Doppler), partial oxygen tension, histological changes, endothelin-1 (plasma, immunohistochemistry), lipase, amylase, trypsinogen activation peptide, and C-reactive protein (CRP) were measured. RESULTS: Partial oxygen tension was lower in the CEL group (P < 0.05). However, blood flow did not differ between UW- and CEL-preserved organs. The histomorphologic analysis of the pancreatic grafts revealed significantly less edema in the UW-preserved organs. Serum levels of amylase, lipase, CRP, and TAP taken from the central venous blood were comparable in the two groups, except for higher amylase values 36 h after reperfusion in the CEL group compared to the UW group (P < 0.05). Likewise, TAP taken from the portal venous effluent of the graft was found to be higher in the CEL group than in UW (P < 0.05). Endothelin-1 serum levels rose significantly during reperfusion without differences between the two groups. ET-1 immunohistochemistry revealed increased local ET-1 during reperfusion in all grafts. However, the ET-1 immunostaining in the CEL group was more pronounced than that in the UW group (P < 0.05). CONCLUSIONS: Our results suggest that CEL solution is not as effective in preventing pancreatic ischemia/reperfusion damage as the standard UW solution in experimental pancreas transplantation. Increased ET-1 immunostaining and reduced p(ti)O(2) in the CEL group indicate increased microcirculatory damage in the CEL group.

Adenosine↗

PubMed2002

Measurement of 4-hydroxylation of ifosfamide in human liver microsomes using the estimation of free and protein-bound acrolein and codetermination of keto- and carboxyifosfamide.

PURPOSE: The aim of the present study was to determine the turnover (4-hydroxylation and N-dechloroethylation) of ifosfamide in a total of 25 human liver microsomal preparations in which the codetermination of keto- and carboxyifosfamide as well as the calculation of free and protein-bound acrolein was carried out for the first time. METHODS: The 4-hydroxylation of ifosfamide was estimated by using acrolein (free and protein-bound) and a newly developed procedure involving the codetermination of keto- and carboxyifosfamide (LC/MS). The ifosfamide N-dechloroethylation was determined as the sum of 2- and 3-dechloroethylifosfamide (LC/MS). RESULTS: Using the usual estimation of liberated free acrolein in 25 human liver microsomal preparations, the 4-hydroxylation of ifosfamide amounted to 0.28+/-0.16 nmol/min. nmol(P450). However, after calculating the 4-hydroxylation as the sum of free and protein-bound acrolein and keto- and carboxyifosfamide, a ninefold higher activity (2.40+/-0.73 nmol/min. nmol(P450)) was found. The percentage of the inactive metabolites keto- (25/25) and carboxyifosfamide (5/25) in the 4-hydroxylation amounted to only 0.79-5.25% (mean 2.90%). The ifosfamide N-dechloroethylation (mean 0.21+/-0.11 nmol/min. nmol(P450)) determined as the sum of 2- and 3-dechloroethylifosfamide was estimated as 8.3+/-4.3% of the total ifosfamide turnover. The application of the relative substrate-activity factor (RSF)-approach and the calculation of the contribution of various isoforms in the ifosfamide 4-hydroxylation yielded the following results: CYP 3A4: 58+/-31%, CYP 2A6: 25+/-15%, and CYP 2C9: 5+/-2% of the total measured 4-hydroxylation. A correlation between 4-hydroxylation and the N-dechloroethylation rates of ifosfamide and the activities of isoenzymes indicates the involvement of both CYP 3A4 ( P=0.026) and CYP 2C9 ( P=0.012) in the 4-hydroxylation reaction and of CYP 3A4 ( P<0.01) in the N-dechloroethylation reaction. CONCLUSIONS: The estimation of protein-bound acrolein should be included in the calculation of the ifosfamide 4-hydroxylation besides liberated free acrolein. Because of the small amounts of the inactive metabolites keto- and carboxyifosfamide, the exclusive determination of acrolein only (free and protein-bound) seems to suffice for the calculation of total ifosfamide hydroxylation. Using this method the hepatic in vitro turnover of ifosfamide was estimated as 92% for 4-hydroxylation (CYP 3A4 and CYP 2A6 mediated) and 8% for N-dechloroethylation (CYP 3A4 mediated), and in this way, a relative overestimation of the N-dechloroethylation of ifosfamide on the whole metabolism is avoided.

Acrolein↗

PubMed2002

Splenohepatic arterial steal syndrome in liver transplantation: clinical features and management.

Well-known arterial complications after liver transplantation comprise thrombosis and major stenosis, which usually necessitate a retransplantation procedure. In our institution, in a series of 165 consecutive liver transplantations, we report the first recognized case of a splenohepatic arterial steal syndrome. This is characterized by an arterial malperfusion of the hepatic graft caused by a marked diversion of blood flow to a significantly enlarged spleen, which leads to major ischemic damage of the hepatic graft. After splenectomy the perfusion through the hepatic artery increased substantially and the graft was salvaged, with a following favorable clinical course. Splenohepatic arterial steal syndrome may ultimately result in graft loss if it is falsely diagnosed or recognized too late. A post-transplantation splenectomy represents a successful therapeutic approach; alternatively a primary arterial anastomosis to the aorta prevents the development of this condition.

Adult↗

PubMed2002

Genetic and epigenetic alterations of the INK4a-ARF pathway in cholangiocarcinoma.

The INK4a-ARF locus, located on chromosome 9p21, encodes two cell-cycle regulatory proteins, p16(INK4a) and p14(ARF), acting through the Rb-CDK4 and p53 pathways. To study the contribution of each pathway in the tumourigenesis of cholangiocarcinoma, the alterations of p14(ARF), p16(INK4a), p53, and pRb were analysed. After microdissection, DNAs from 51 cholangiocarcinomas were analysed by methylation-specific PCR (MSP), restriction-enzyme related polymerase chain reaction (RE-PCR), microsatellite analysis, mRNA expression, and DNA sequencing. Immunohistochemistry of p14(ARF), p16(INK4a), p53, and pRb was also performed. Promoter methylation of p14(ARF) was found in 13/51 cases (25%) and p16(INK4a) showed aberrant promoter methylation in 39/51 cases (76%) which correlated with loss of mRNA transcription. Two tumours (4%) had homozygous deletion of the INK4a-ARF locus. Specific mutations of both exons were not detected. p14(ARF) inactivation appeared in the context of an unmethylated p16(INK4a) promoter in eight of 13 cases (61%) of the carcinomas methylated at p14(ARF). Mutations of p53 were found in 19 of 51 tumours (37%), and four of them (21%) harboured p14(ARF) inactivation. The pRb protein was detected in 30/51 (59%) tumours examined. The absence of pRB protein did not correlate with any of the examined parameters. Alterations of the INK4a-ARF locus, pRB or p53 status could not be established as independent prognostic factors in these tumours. These findings indicate that the INK4a-ARF locus is frequently inactivated in cholangiocarcinoma of the liver and occurs independently of the status of p53 or pRb.

Bile Duct Neoplasms↗

PubMed2002

Prospective evaluation of circulating hepatocytes by alpha-fetoprotein messenger RNA in patients with hepatocellular carcinoma.

BACKGROUND: The significance of alpha-fetoprotein (AFP) messenger RNA as a surrogate marker for isolated tumor cells in the blood of patients with hepatocellular carcinoma (HCC) is controversial. Our goals were to correlate AFP mRNA with tumor recurrence and overall survival after patients with HCC received curative operations and to analyze AFP mRNA findings in control patients. METHODS: In this prospective controlled study, RNA was purified from the blood of 85 patients with HCC before, during, and after therapy and from 116 control patients. Complementary DNA synthesis by reverse transcriptase and polymerase chain reaction amplification was performed with primers specifically for the AFP gene. Patients with HCC were divided into 4 subgroups depending on the therapy performed: (1) orthotopic liver transplantation (OLT), (2) resection, (3) transarterial chemoembolization, and (4) no therapy. RESULTS: AFP mRNA was detected in 28% of the patients with HCC and 3% of the control patients (P <.01) before therapy. Of patients with HCC and OLT, 2 of the 6 patients who were AFP mRNA positive had a recurrence; none of the 4 patients who were negative had a recurrence. In the HCC patients who underwent tumor resection or received no therapy, the survival rates did not differ between patients who were AFP mRNA positive and negative (P =.21 and P =.94, respectively). After the tumor resection, no difference in survival at 2 years was evident in patients who were AFP mRNA positive versus those who were AFP mRNA negative. In the HCC patients who had curative operations (OLT and resection) the sensitivity and specificity of this test for tumor recurrence were 73% and 53%, respectively, excluding surgical mortality. The International Union Against Cancer tumor stages in the subgroups of OLT and resection showed no differences between patients with positive and negative findings (P =.76 and P =.15, respectively). AFP mRNA results and serum AFP levels revealed no correlation (P =.45). CONCLUSIONS: The qualitative measurement of AFP mRNA in the blood of patients with HCC is not a clinically relevant method for determining therapy and prognosis, especially if AFP mRNA is detected during the surgical procedure or any other liver manipulation.

Carcinoma, Hepatocellular↗

PubMed2001

Neuroendocrine tumours of the duodenum. Clinical aspects, pathomorphology and therapy.

BACKGROUND AND AIMS: Neuroendocrine tumours (NTs) of the duodenum are uncommon neoplasms. They represent a heterogeneous spectrum of subtypes and may be associated with von Recklinghausen's disease type I (VRD) and multiple endocrine neoplasia type I. There are few studies concerning the biological characteristics and adequate therapy of these tumours. PATIENTS AND METHODS: We report on a retrospective analysis of 12 patients with NTs of the duodenum: six non-ampullary (naNTs) and six ampullary tumours (aNTs). These patients were treated between January 1992 and January 2001. Clinical and histopathological features, therapy and follow-up were evaluated retrospectively and compared with the literature. RESULTS: All tumours were located in the first and second portions of the duodenum. Three of six aNTs presented with jaundice, and four of six naNTs were incidental findings. Two patients with naNTs showed Zollinger-Ellison syndrome and two with aNTs VRD. Of the six patients with naNTs, four were treated by local excision (two endoscopically, two surgical resection), one by Kausch-Whipple operation and in one patient the tumour was an incidental finding in the Billroth II specimen. Four of the six patients with aNTs underwent Kausch-Whipple procedure, one patient ampullectomy (gangliocytic paraganglioma) and one patient palliative chemotherapy. The size of the naNTs were less than 0.6 cm, whereas the size of the aNTs ranged from 1.5 cm to 4 cm. Tumour size of aNTs had no correlation with depth of invasion and metastases. Metastases were found in two aNTs and none of the naNTs. Immunohistochemically tumour cells expressed somatostatin in 5 of 6 aNTs and gastrin in 1 of 6 aNTs and in two gastrinomas. There was no hospital mortality. Two patients died for reasons not related to the tumour. Tumour excision of both patients with gastrinomas was not curative. Three patients with naNTs and four with aNTs are alive without disease. One patient with palliative treatment of a metastasising aNT is alive 66 months after diagnosis. CONCLUSION: Non-ampullary duodenal NTs differ clinically, histologically and immunohistochemically as well as with respect to the extent of resection from NTs of the ampulla of Vater.

Adult↗

PubMedDate not supplied

Management and outcome in patients with Klatskin-mimicking lesions of the biliary tree.

The preoperative and even intraoperative differentiation between benign and malignant strictures at the hepatic hilum remains difficult. The aim of this study was to assess clinical, radiologic, intraoperative, and histopathologic findings; surgical treatment; and outcome of patients with Klatskin mimicking benign lesions. Of 49 consecutive patients who were operated on the initial preoperative radiologic diagnosis of hilar adenocarcinoma (Klatskin tumor), 7 (14%) had benign conditions after final histopathologic diagnosis. Pretreatment work-up, therapy, and outcome of these patients were analyzed. Based on preoperative clinical symptoms, imaging assessment, and CA19-9 values, all seven patients were classified as having malignant neoplasms. At laparotomy, the tumors of six patients were judged to be malignant. Five patients underwent hilar resection and concomitant liver resection, and two patients underwent hilar resection alone. There were no operative deaths. The definitive histopathologic examination showed severe cholangitis with extensive periductal fibrosis in all patients. After a median follow-up of 32 months, all patients are well. Clinical presentation and imaging assessment were similar for Klatskin tumors and benign fibrosing disease; therefore, an aggressive resectional approach is justified in any patient with suspicious obstruction of the liver hilum.

Adult↗

PubMedDate not supplied

Quality of life in chronic pancreatitis: a prospective trial comparing classical whipple procedure and duodenum-preserving pancreatic head resection.

Few data are available with respect to quality of life after pancreatic head resection in patients with chronic pancreatitis. The aim of this study was to compare the classical Whipple pancreatoduodenectomy (PD) with the Beger duodenum-preserving pancreatic head resection (DPPHR), in terms of quality of life, using standardized, valid, and reliable questionnaires. Sixty-five consecutive patients were included in this study. The PD procedure was chosen when pancreatic cancer could not be ruled out (n = 30); otherwise DPPHR was performed (n = 35). Quality of life was measured prospectively three times with the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ-C30) and the Gastrointestinal Quality-of-Life Index (GIQLI). Both procedures led to a significant improvement in quality of life, especially with regard to pain status. However, at the second follow-up examination (18 to 24 months postoperatively), all functional scales and the most important symptom scales of the EORTC QLQ-C30 revealed a better quality of life in the DPPHR group compared to the PD group. After classical PD, more patients seem to develop diabetes mellitus. The EORTC QLQ-C30 was found to be a better tool for quality-of-life assessment than the GIQLI in patients with chronic pancreatitis.

Chronic Disease↗

PubMedDate not supplied

Endothelin A receptor blockade reduces hepatic ischemia/reperfusion injury after warm ischemia in a pig model.

It is well established that endothelin-1 (ET-1) is a very potent mediator of vasoconstriction that leads to microcirculatory disturbances. The aim of the study was to evaluate the effect of a selective endothelin A receptor antagonist on severe ischemia/reperfusion injury in a pig model. Fourteen pigs were subjected to 120 minutes of complete vascular exclusion of the liver with a passive bypass. The animals were randomized into two groups: a control group, which was given isotonic saline solution, and a therapy group, which received the selective endothelin A receptor antagonist BSF 208075 at the beginning of reperfusion. On postoperative days 4 and 7, animals were relaparotomized to obtain tissue specimens. Blood monitoring included aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), alkaline phosphatase, and ET-1. Partial oxygen tension (p(ti)O(2)) was measured by a Clarke-type electrode and blood flow by laser Doppler. A semiquantitative scoring index was used for assessment of histologic injury and for immunohistochemical analysis of ET-1. Treatment with the endothelin A receptor antagonist significantly reduced the severity of the ischemia/reperfusion injury, as evidenced by lower levels of AST, ALT, and GLDH. The dramatic increase in plasma ET-1 in the therapy group is clear evidence of effective receptor blockade. Analysis of p(ti)O(2) and blood flow revealed a significant improvement in capillary perfusion and blood flow in the treated group and was associated with relevant reduction of tissue injury. In summary, in the control group we observed serious microcirculatory disturbances and severe histologic damage in the liver after reperfusion. Treatment with a selective endothelin A receptor antagonist attenuated the ischemia/reperfusion injury in a porcine model of severe ischemia/reperfusion, as demonstrated by improved microcirculation, a reduction in histologic damage, and an decrease in liver enzymes.

Alanine Transaminase↗