Biomedical subjects

Werner Hohenberger

Publications and source records attributed to Werner Hohenberger.

At least 19 recordsLinked to original sources

PubMed2007

Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer.

PURPOSE: To evaluate the activity and safety of preoperative radiotherapy (RT) and concurrent capecitabine and oxaliplatin (XELOX-RT) plus four cycles of adjuvant XELOX in patients with rectal cancer. PATIENTS AND METHODS: One hundred ten patients with T3/T4 or N+ rectal cancer were entered onto the trial in 11 investigator sites and received preoperative RT (50.4 Gy in 28 fractions). Capecitabine was administered concurrently at 1,650 mg/m2 on days 1 to 14 and 22 to 35, and oxaliplatin was administered at 50 mg/m2 on days 1, 8, 22, and 29. Surgery was scheduled 4 to 6 weeks after completion of XELOX-RT. Four cycles of adjuvant XELOX (capecitabine 1,000 mg/m2 bid on days 1 to 14; oxaliplatin 130 mg/m2 on day 1) were administered. The main end points were activity as assessed by the pathologic complete response (pCR) rate and the feasibility of postoperative XELOX chemotherapy. RESULTS: After XELOX-RT, 103 of 104 eligible patients underwent surgery; pCR was achieved in 17 patients (16%), one patient had ypT0N1 disease, and 53 patients showed tumor regression of more than 50% of the tumor mass. R0 resections were achieved in 95% of patients, and sphincter preservation was accomplished in 77%. Full-dose preoperative XELOX-RT was administered in 96%. Grade 3 or 4 diarrhea occurred in 12% of patients. Postoperative complication occurred in 43% of patients. Sixty percent of patients received all four cycles of adjuvant XELOX, with sensory neuropathy (18%) and diarrhea (12%) being the main grade 3 or 4 toxicities. CONCLUSION: Preoperative XELOX-RT plus four cycles of adjuvant XELOX is an active and feasible treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based treatment with XELOX- based multimodality treatment.

Adult↗

PubMed2007

Laser-induced thermotherapy (LITT) elevates mRNA expression of connective tissue growth factor (CTGF) associated with reduced tumor growth of liver metastases compared to hepatic resection.

BACKGROUND AND OBJECTIVES: Proliferation and synthesis of hepatocellular tissue after tissue damage are promoted by specific growth factors such as hepatic tissue growth factor (HGF) and connective growth factor (CTGF). Laser-induced thermotherapy (LITT) for the treatment of liver metastases is deemed to be a parenchyma-saving procedure compared to hepatic resection. The aim of this study was to compare the impact of LITT and hepatic resection on intrahepatic residual tumor tissue and expression levels of mRNA HGF/CTGF within liver and tumor tissue. STUDY DESIGN/MATERIALS AND METHODS: Two independent adenocarcinomas (CC531) were implanted into 75 WAG rats, one in the right (untreated tumor) and one in the left liver lobe (treated tumor). The left lobe tumor was treated either by LITT or partial hepatectomy. The control tumor was submitted to in-situ hybridization of HGF and CTGF 24-96 hours and 14 days after intervention. RESULTS: Volumes of the untreated tumors prior to intervention were 38+/-8 mm(3) in group I (laser), 39 +/- 7 mm(3) in group II (resection), and 42 +/- 12 mm(3) in group III (control) and did not differ significantly (P > 0.05). Fourteen days after the intervention the mean tumor+/-SEM volume of untreated tumor in group I (laser) [223 +/- 36] was smaller than in group II (resection) [1233.28 +/- 181.52; P < 0.001], and in group III (control) [978.92 +/- 87.57; P < 0.003]. Forty-eight hours after the intervention intrahepatic mRNA expression level of HGF in group II (resection) was almost twofold higher than in group I (laser) [7.2 +/- 1.0 c/mf vs. 3.9 +/- 0.4 c/mf; P<0.01]. Fourteen days after the intervention intrahepatic mRNA expression level of CTGF in group I (laser) was higher than in group II (resection) [13.89 +/- 0.77 c/mf vs. 9.09 +/- 0.78 c/mf; P < 0.003]. CONCLUSIONS: LITT leads to a decrease of residual tumor growth in comparison to hepatic resection. Accelerated tumor growth after hepatic resection is associated with higher mRNA level of HGF and reduced tumor growth after LITT with higher mRNA level of CTGF. The increased CTGF-mediated regulation of ECM may cause reduced residual tumor growth after LITT.

Animals↗

PubMed2006

Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: results of study CAO/ARO/AIO-94.

PURPOSE: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. METHODS AND MATERIALS: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, and delivery of RT were analyzed as endpoints in multivariate analysis. RESULTS: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% +/- 7.8%; inadequate RT, 21.2% +/- 5.6%; adequate RT, 6.8% +/- 1.4%; p = 0.0001) and DFS (no RT, 55.1% +/- 9.1%; inadequate RT, 57.4% +/- 6.3%; adequate RT, 69.1% +/- 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. CONCLUSION: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.

Aged↗

PubMed2006

Surgical management of pulmonary metastases from colorectal cancer in 153 patients.

BACKGROUND: Surgery has become a recognized therapeutic means in selected patients with pulmonary metastases from colorectal origin. We reviewed our experience in the surgical treatment of 153 patients with pulmonary colorectal metastases and investigated factors affecting survival. METHODS: A retrospective analysis of the records of all patients (n = 153) with pulmonary metastases from colorectal cancer who underwent thoracotomy between 1978 and 2003 at a single surgical center was performed. RESULTS: One hundred fifty-three patients with pulmonary metastases from colon (n = 61) or rectal (n = 92) cancer underwent 180 thoracotomies. The 2- and 5-year probabilities of survival after the first thoracotomy were 64% and 37%, respectively. Sex, age, site, International Union Against Cancer stage of the primary tumor, prethoracotomy carcinoembryonic antigen level, size of metastases, and previous resection of hepatic metastases were not found to be statistically significant prognostic factors. Number of metastases (solitary vs. multiple), mode of operation (wedge vs. anatomical resection), disease-free interval (DFI; > 36 months), negative hilar or mediastinal lymph node status, resection margin > 10 mm, and administration of intraoperative blood substitution were predictors of a longer survival duration by univariate analysis, but only number of metastases (P = .019), mode of operation (P = .004), DFI (P = .027), and intraoperative blood substitution (P = .002) were identified as independent prognostic factors by multivariate analysis. CONCLUSIONS: Pulmonary resection for metastases from colorectal cancer is safe and results in long-term survival in selected patients. Single metastases, anatomical resection, intraoperative blood substitution, and DFI > 36 months seem to be the most reliable predictors of survival.

Adult↗

PubMed2006

Changes in surgical therapy for Crohn's disease over 33 years: a prospective longitudinal study.

INTRODUCTION: Changes in surgery for Crohn's disease were analyzed in a single institution over a period of 33 years. MATERIALS AND METHODS: The data of all patients undergoing abdominal surgery for Crohn's disease between 1970 and 2002 were collected prospectively in an electronic database. The study period was divided into three periods of 11 years, each (group 1, 1970-1980; group 2, 1981-1991; group 3, 1992-2002). RESULTS: There was an increase in patients' age at time of hospital admission from 32.0+/-0.9 to 32.4+/-0.5 and 37.7+/-0.7 years, in the duration of disease from 4.9+/-0.3 to 7.3+/-0.3 and 8.8+/-0.5 years, and in the number of drug-induced remissions before surgery from 3.1+/-0.5 to 6.1+/-0.2 and 4.9+/-0.3 in groups 1, 2, and 3, respectively (p<0.01). The rates of elective surgery compared to urgent or emergency surgery increased from 69.5 to 81.4 and 80.9% in the corresponding groups (p<0.01). A significant decrease in hospital mortality was observed. The analysis of Crohn's complications demanding surgery revealed a significant increase of rates of stenosis and subileus. Furthermore, there was a significant increase in serious acute complications like free bowel perforations and peritonitis. CONCLUSION: Improved medical treatment may lead to higher rates of elective operations. However, prolonged conservative treatment may also increase the number of serious complications before surgery. Therefore, a multidisciplinary approach with early involvement of the surgeon is important to avoid any delay in indication to surgery.

Adult↗

PubMed2006

Collagen foil (TissuFoil E) reduces the formation of adhesions when using polypropylene mesh for the repair of experimental abdominal wall defects.

BACKGROUND AND AIMS: Polypropylene meshes (PPMs) are routinely used in the treatment of incisional hernias to achieve a tension-free closure of the abdominal wall. Severe adhesions are a common cause of intestinal obstruction, or even intestinal fistulas. Using a porcine model, we investigated whether applying a collagen foil (CF) to the undersurface of a PPM will reduce adhesion formation. METHODS: In ten domestic pigs (20-25 kg), a median laparotomy was performed. In each animal the abdominal wall was reconstructed using three types of closure: simple closure by a running suture (control), PPM only, and PPM covered with CF (PPM-CF). After 6 weeks, the abdominal wall with adherent tissue was resected en bloc for macroscopic (quality and quantity of adhesion formation) and histological work-up. RESULTS: The PPM-CF showed significantly less severe (1.9 vs 3.0 according to a scoring system), and also less extended (23.8 vs 55.9% total coverage of the mesh), adhesions to the resected abdominal wall. Histological examination revealed fewer and less severe inflammatory reactions, necrosis, and foreign body reactions for the mesh and CF (PPM-CF). CONCLUSION: To combine meshes with the anti-adhesion properties of a CF may be another option to achieve more physiological and more tolerable prosthetic materials.

Animals↗

PubMed2006

Weight reduction after an early version of the open gastric bypass for morbid obesity: results after 23 years.

BACKGROUND: While numerous promising short-term results of open gastric bypass for morbid obesity were published, the long-term outcome of earlier versions was somewhat disappointing. Thus, it was not until 1993 that this procedure was reintroduced with current modifications and now performed laparoscopically. Published long-term results of gastric bypass are still lacking. METHODS: Out of an original population of 195 patients, we retrospectively analyzed the outcome of 98 patients (82 women, 16 men, mean age 32 years [range 17-54], mean weight 132 kg [range 65-200], mean BMI 46.6 kg/m2) operated on in Erlangen with mean follow-up 22.9 years (range 16.5-25.4). 3 different bariatric operations were performed: horizontal gastroplasty (HGP, n=18), stapled Roux-en-Y gastric bypass (S-RYGBP, n=14) and transected Roux-en-Y gastric bypass (T-RYGBP, n=66). BMI and percentage of excess weight loss (%EWL) were calculated at time 0, and after 1, 2, 3, 10, 15, 20 and 25 years. RESULTS: Statistically significant weight loss was found for the whole patient population at every postoperative time-point compared to preoperative values. Maximal weight loss was achieved mainly during the first 3 years. However, initial and long-term outcome after HGP was significantly worse than after S-RYGBP or T-RYGBP. Gender did not significantly influence the results. CONCLUSION: Traditional open gastric bypass resulted in acceptable and safe long-term weight reduction. It may be assumed that laparoscopic gastric bypass with modern tiny pouch volumes based on the lesser curvature achieves even better and life-long weight reduction.

Adolescent↗

PubMed2006

[Uniform calculation of local recurrence rates--requirement for quality management in rectal carcinoma].

The local recurrence rate is an important indicator in the quality management of rectal carcinoma. The data of the German Study Group for Colorectal Carcinoma (SGCRC) and the Erlangen Registry for Colorectal Carcinoma (ERCRC) were used to demonstrate the influence of different calculation methods on the level of local recurrence rates. The application of uniform definitions, rules and presentations is necessary to enable national and international comparisons. Only 5-year local recurrence rates allow treatment quality to be definitely judged, especially when multimodal treatment was applied.

Combined Modality Therapy↗

PubMed2005

Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer.

PURPOSE: We assessed the impact of tumor regression grading (TRG) and its value in correlation to established prognostic factors in a cohort of rectal carcinoma patients treated by preoperative chemoradiotherapy (CRT). PATIENTS AND METHODS: TRG was evaluated on surgical specimens of 385 patients treated within the preoperative CRT arm of the CAO/ARO/AIO-94 trial: 50.4 Gy was delivered, fluorouracil was given in the first and fifth week, and surgery was performed 6 weeks thereafter. TRG was determined by the amount of viable tumor versus fibrosis, ranging from TRG 4 when no viable tumor cells were detected, to TRG 0 when fibrosis was completely absent. TRG 3 was defined as regression more than 50% with fibrosis outgrowing the tumor mass, TRG 2 was defined as regression less than 50%, and TRG 1 was defined basically as a morphologically unaltered tumor mass. We performed an initially unplanned, hypothesis-generating analysis with respect to the prognostic value of this TRG system. RESULTS: TRG 4, 3, 2, 1, 0 was found in 10.4%, 52.2%, 13.8%, 15.3%, and 8.3% of the resected specimens, respectively. Five-year disease-free survival (DFS) after CRT and curative resection was 86% for TRG 4, 75% for grouped TRG 2 + 3, and 63% for grouped TRG 0 + 1 (P = .006). On multivariate analysis, the pathologic T category and the nodal status after CRT were the most important independent prognostic factors for DFS. CONCLUSION: In this exploratory analysis, complete (TRG 4) and intermediate pathologic response (TRG 2 + 3) suggested improved DFS after preoperative CRT. TRG assessment should be implemented in pathologic evaluation and prospectively validated in further studies.

Adenocarcinoma↗

PubMed2005

Prediction of lymph node metastasis in colorectal carcinoma by expressionof chemokine receptor CCR7.

Chemokine receptors are known to regulate homing of lymphocytes into secondary lymphoid organs and may also be involved in the lymphatic spread of solid tumors. Therefore, the assessment of chemokine receptor expression on colorectal carcinomas could potentially improve the prediction of lymph node spread. This is of great importance for the selection of patients for local therapy without the need for concomitant lymphatic dissection. Currently, only 5% of all patients can be selected for this desirable treatment option by established prognosticators. In a retrospective study, expression levels of the chemokine receptors CCR7, CXCR4 and CXCR5 were determined by immunohistochemistry on paraffin-embedded specimens of 99 colorectal carcinomas, which were curatively operated on, comprising all stages of the disease. Receptor expressions (absent vs. positive) from the overall tumor (OT) and from the invasion front (IF) including further prognosticators were correlated with lymph node status by uni- and multivariate analysis. Data were also correlated with synchronous distant metastases and overall survival. Median follow-up was 64 months. In univariate analysis, lymph node status correlated significantly with lymphovascular invasion, the expression of CCR7 IF, CCR7 OT, CXCR4 IF and CXCR4 OT, as well as pT category. Multivariate analysis revealed a significant correlation of lymph node status with lymphovascular invasion and CCR7 IF expression level. Most interestingly, CCR7 IF expression was significantly linked to decreased survival. CCR7 plays an important role in the mechanism of lymph node spread in colorectal carcinoma. Evaluation of the chemokine receptor expression profile seems to be appropriate to improve the selection of patients suited for local treatment and might constitute targets for nonsurgical therapy.

Adult↗

PubMed2005

Changes in indication and results after resection of hepatic metastases from noncolorectal primary tumors: a single-institutional review.

BACKGROUND: The isolated occurrence of noncolorectal liver metastases is rare. The available data are inconsistent in terms of indication for surgery, treatment, and outcome, so a generally applicable therapeutic algorithm is currently lacking. METHODS: A total of 162 patients underwent resection for noncolorectal liver metastases between 1978 and 2001. The patients were divided into two groups from different time periods (group 1, 1978-1989; group 2, 1990-2001) that were similar in terms of number of patients, operating surgeons, and surgical techniques used. The groups were compared, and the data were retrospectively analyzed with regard to indication, survival, and factors predictive for survival. RESULTS: Resection was performed to remove liver metastases from noncolorectal gastrointestinal carcinoma (n = 50), neuroendocrine tumors (n = 12), genitourinary primary tumors (n = 11), breast carcinoma (n = 24), leiomyosarcoma (n = 15), and metastases from other primary cancers (n = 50). Extrahepatic tumor involvement was seen in 38 (23%) of the 162 cases. Sixty-two (38%) major hepatectomies and 100 (62%) minor resections were performed. In 100 (62%) of 162 patients, a curative resection (R0) could be achieved. Overall 2- and 5-year survival rates of 49% and 26%, respectively, were observed, and the median survival was 23 months. Survival was significantly longer in patients who underwent an R0 resection. CONCLUSIONS: In selected patients, resection of noncolorectal liver metastases is associated with a 5-year survival rate of up to 50%. Resection of liver metastases from gastrointestinal adenocarcinomas correlates with a poor prognosis. Extrahepatic metastases may be considered a relative contraindication for liver resection.

Adult↗

PubMed2005

Mannan-binding lectin and procalcitonin measurement for prediction of postoperative infection.

INTRODUCTION: Postoperative infection is a major cause of morbidity and mortality. We investigated two serum markers for their ability to identify patients at risk for postoperative infection. Mannan-binding lectin (MBL) is a central molecule of the innate immune system and MBL deficiency is known to predispose to infection. Procalcitonin (PCT) is a sensitive marker for bacterial infection. METHODS: We investigated 162 patients undergoing elective surgery for cancer of the gastrointestinal tract. Patients were classified as having no complications (group A), having infection for unknown reason (group B) or having sepsis after events like aspiration or anastomotic leakage (group C). Analysis was done pre- and postoperatively for serum levels of MBL, PCT and C-reactive-protein. DNA was preoperatively sampled and stored and later analysed for genetic polymorphisms of MBL. RESULTS: The preoperative serum levels of MBL were significantly lower in group B patients than in group A patients (1332 +/- 466 ng/ml versus 2523 +/- 181 ng/ml). PCT measured on day one post-surgery was significantly higher in group B patients than in group A (3.33 +/- 1.08 ng/ml versus 1.38 +/- 0.17 ng/ml). Patients with an aberrant MBL genotype had a significantly higher risk of postoperative infections than wild-type carriers (p < 0.05). CONCLUSION: Preoperative MBL and early postoperative PCT measurement may help identify patients at risk for postoperative infection.

Adult↗

PubMed2005

Microarray versus conventional prediction of lymph node metastasis in colorectal carcinoma.

BACKGROUND: The authors investigated whether microarray-based gene expression analysis of primary tumor biopsy material could be used to predict lymph node status in patients with colorectal carcinoma (CRC). Lymphatic metastasis strongly determines treatment algorithms in CRC. Currently, postoperative histology results are needed to determine lymph node status. Reliable preoperative information would be useful to advance treatment strategies. METHODS: In specimens from 66 patients with CRC from the Erlangen Registry of Colorectal Cancer, 41 shock-frozen samples of International Union Against Cancer (UICC) Stage I-II CRC and 25 samples of UICC Stage III CRC were microdissected manually, RNA was isolated, and gene chips (HG-U133A; Affymetrix) were hybridized. Prediction rates for lymphatic metastasis were calculated using conventional clinicopathologic parameters, gene expression data, and a combination of both. Prediction error, specificity, and sensitivity were analyzed using six different statistical classifiers. RESULTS: Analysis of conventional parameters produced a positive prediction rate that ranged between 53% and 61%, sensitivity of 42%, and specificity of 72%. Microarray prediction rates were between 62% and 67% for lymphatic metastasis. Specificity was between 76% and 83%, and sensitivity was between 38% and 48%, depending on the statistical procedure. The conventional estimates were improved by 9-12% when array data were added. CONCLUSIONS: Current data show that the prediction of lymphatic metastasis can be improved by gene expression profiling of the primary tumor biopsy, alone or in combination with conventional parameters. Gene expression profiling may become valuable increasingly in planning treatment for patients with CRC.

Aged↗

PubMed2005

Definition of elective lymphatic target volume in ductal carcinoma of the pancreatic head based on histopathologic analysis.

PURPOSE: In chemoradiation for pancreatic carcinoma three-dimensional target volume definitions could maximize tolerability and therapeutic effect at the same time because toxicity correlates with treatment volume. We aimed to define guidelines for elective treatment of nodal areas based on pathologic nodal involvement to optimize treatment volume for this tumor. METHODS AND MATERIALS: Pathologic patterns of regional nodal spread in 175 patients who underwent primary pancreatoduodenectomy with > or =10 assessed nodes and literature data on para-aortic spread were the base of the definition of the target volume. Significant correlations between spread to lymphatic areas and tumor characteristics were determined using Fisher's exact test. Computed tomography scans and a Pinnacle3 (Philips, Best, The Netherlands) system were used for treatment planning. RESULTS: Among 175 resected tumors without pretreatment, 76% had regional nodal metastasis and 22% had spread to distant nodes. High-risk lymphatic areas were identified and selected for elective treatment. A standardized planning procedure was derived and tested under treatment conditions. CONCLUSIONS: Histopathologic data allowed us to develop recommendations for standardized treatment planning for ductal carcinoma of the pancreatic head. These are proposed for quality assurance in multicenter studies and routine use.

Adult↗

PubMed2005

A new survival model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing rats in the treatment of peritoneal carcinomatosis.

BACKGROUND: Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis. METHODS: A new peritoneal perfusion system in tumor bearing rats were tested. For this purpose CC531 colon carcinoma cells were implanted intraperitoneally in Wag/Rija rats. After 10 days of tumor growth the animals were randomized into three groups of six animals each: group 1: control (n = 6), group 2: HIPEC with mitomycin C in a concentration of 15 mg/m2 (n = 6), group III: mitomycin C i.p. as monotherapy in a concentration of 10 mg/m2 (n = 6). After 10 days, total tumor weight and the extent of tumor spread, as classified by the modified Peritoneal Cancer Index (PCI), were assessed by autopsy of the animals. RESULTS: No postoperative deaths were observed. Conjunctivitis, lethargy and loss of appetite were the main side effects in the HIPEC group. No severe locoregional or systemic toxity was observed. All control animals developed massive tumor growth. Tumor load was significantly reduced in the treatment group and was lowest in group II. CONCLUSION: The combination of hyperthermia with MMC resulted in an increased tumoricidal effect in the rat model. The presented model provides an opportunity to study the mechanism and effect of hyperthermic intraperitoneal chemotherapy and new drugs for this treatment modality.

Animals↗

PubMed2005

Arterialisation of the portal vein as a model for the induction of hepatic fibrosis: description of microsurgical models in the rat.

Within the framework of liver transplantation, arterialisation of the portal vein in the case of non-recanalisable thrombosis has been reactivated. However, one of the consequences of this vascular reconstruction is the development of hepatic fibrosis. Clinical experience has shown that the development of fibrosis can be avoided by reducing portal inflow. We present, as a model for the induction of hepatic fibrosis, techniques of PVA, including transplantation. For PVA, several different techniques were used: the first with reduction of the portal inflow over a stent inserted in the right renal artery (PVA-B), the second with unrestricted flow using an aortic-portal segment (PVA-APS). The third technique was orthotopic liver transplantation with unrestricted portal arterialisation (OLTx-APS). Portal blood flow was measured with an ultrasonic flow probe. To determine the degree of hepatic fibrosis the amount of hydroxyproline was measured. Quantification of relative transcript levels of procollagen I was effected with real-time PCR using the TaqMan technology on a lightcycler instrument. The extracellular matrix was visualised with picro-sirius staining. Measurements with the ultrasonic probe showed a significant increase in flow rates, both with reduced (PVA-B) and unrestricted inflow (PVA-APS; OLTx-APS). The lowest survival rate (58%) was found in the group with unrestricted portal inflow. The reason for this was a high rate of thrombosis in the in the portal vascular tree (4 out of 12). In the OLTx-APS group four animals died within the first 3 postoperative days (69%), as a result of protracted postoperative shock. The overall survival rate was the highest (85%) in the group undergoing PVA with reduction of the portal inflow. PVA with unrestricted inflow was followed by a significant increase in extracellular collagen, which showed a clear correlation with the increase in the amount of hydroxyproline, the level of the mRNA for procollagen I and picro-sirius staining. With the operative PVA techniques presented herein, different arterial flow rates in the portal vein can be investigated. In our opinion these techniques represent an excellent animal model for studying the genesis of fibrosis and antifibrotic substances. By regulating the blood flow in the arterialised portal vein hepatic fibrosis can be reduced or even avoided. After a brief period of learning the microsurgical techniques, the surgeon can limit clamping times and achieve good results with these techniques.

Animals↗

PubMed2005

Characterization of gene expression profiles of T cells during anti-tumor response.

BACKGROUND AND AIMS: T cells of tumor-bearing mice or cancer patients exhibit an immune dysfunction, enabling the tumor to escape immune surveillance. METHODS: The experiments are based on EL4 thymoma cells that were transfected with costimulatory ligands B7-1, B7-2, or both at the same time. We used oligonucleotide-based DNA chip microarrays to characterize the genomic expression profile of peripheral T cells according to their anti-tumor immune response in vivo. These murine T cells were also characterized by ELISA, FACS analysis, and co-stimulatory assays. RESULTS: Using commonly established methods, such as FACS analysis or the analysis of the cytokine profile by ELISA, it was not possible to determine functional differences in the in vivo activity of T lymphocytes against tumor cells. EL4 tumor cells induced multiple anti-tumor immune responses in vivo depending on their B7 expression. We successfully used microarray analysis to identify genes that were differentially expressed in the dysfunctional T cells, which were unable to reject tumors in vivo. Although Th1 and Th2 cytokine expression was not affected, we observed differential expression of genes involved in the regulation of an innate immune response. CONCLUSION: Our results provide evidence that the anti-tumor response can be identified by the "gene profile" of T cells. Genomic scale analysis offers the opportunity to identify subtle changes in gene expression in T cells reflecting a distinct biological behavior in vivo.

Animals↗

PubMed2005

Age and manifestation related symptoms in familial adenomatous polyposis.

BACKGROUND: To identify early symptoms of familial adenomatous polyposis with a view to improve early diagnosis and treatment. Diagnosis on the basis of genetic testing is usually limited to where there is a known family history, so FAP is more usually diagnosed on clinical grounds. Except for those identified via FAP registers, the majority of patients are symptomatic at the time of diagnosis. METHODS: We undertook a retrospective study of 143 FAP patients treated at the Department of Surgery, University of Erlangen between 1971 and 2000. We identified patterns of symptoms, endoscopic findings and extracolonic manifestations in three age groups. RESULTS: FAP was diagnosed clinically on the basis of symptoms in 84% (120/143) of these patients. Most presented with intestinal symptoms such as colonic bleeding (68%) and diarrhea (42%). All but one of the patients between 20 and 40 years old had rectal polyps (98.7%, 75/76), whereas in those over 40 years old the prevalence was 76% (35/46). Non-specific symptoms such as abdominal pain, fatigue and bloating were less frequent and were mainly reported by patients older than 40. CONCLUSION: The commonest presenting features of FAP are alteration of bowel habit and rectal bleeding, but both are found in many other conditions. Patients with these findings need immediate endoscopy to allow prompt diagnosis and prophylactic surgery.

Abdominal Pain↗