Biomedical subjects

Andreas Thalheimer

Publications and source records attributed to Andreas Thalheimer.

11 recordsLinked to original sources

PubMed2024

Associations between (pharmaco-)genetic markers and postoperative pain after inguinal hernia repair - a prospective study protocol.

BACKGROUND: Postoperative pain is a common complication following surgery, with severity and duration varying between patients. Chronic postoperative pain after inguinal hernia surgery has an incidence rate of approximately 10%. Risk factors for acute and chronic pain following hernia surgery include age, sex, psychosocial factors, and demographic background. Additionally, genetic polymorphisms in enzymes involved in pain mechanisms, as well as the metabolism of analgesics might influence pain perception, pain development, and response to pain medications. Key enzymes include the catechol-o-methyltransferase (COMT), the µ-opioid receptor 1 (OPRM1), and the cytochrome P450 2D6 (CYP2D6). CYP2D6 plays a crucial role in metabolizing analgesics such as tramadol, codeine, and oxycodone. It is also suspected to be involved in the synthesis of catecholamines and endogenous morphines suggesting a potential role in pathophysiology of pain. We hypothesize that the CYP2D6 activity influences the development of postoperative pain after hernia surgery. METHODS: This study is a prospective, observational, multicenter association study investigating adult patients scheduled for inguinal hernia surgery using a robotic-assisted (rTAPP) approach. Patients are enrolled during the preoperative surgical consultation. A buccal swab is collected for genetic testing at this time. Pain at the site of the hernia is assessed using the validated EuraHSQoL score preoperatively and at 2, 4, and 6 weeks postoperatively. Additionally, information on co-medication and details of the surgery will be collected. The planned number of participants is 350 patients. The primary objective is to analyze the association between different genotype-predicted CYP2D6 phenotypes and patient-reported pain intensity 6 weeks after surgery. Secondary objectives include the association between further genetic variants, such as the COMT rs4680 and OPRM1 rs1799971 genotype, and pain severity. Additionally, the potential of pharmacogenetic panel testing to optimize analgesic therapy in hernia surgery patients will be explored. DISCUSSION: The findings of this study are expected to provide valuable insights into identifying patients at higher risk for postoperative pain before surgery. This knowledge could pave the way for tailored interventions during and after surgery for these specific patients. TRIAL REGISTRATION: Deutsches Register Klinischer Studien https://www.drks.de/DRKS00034796 Registered on August 07, 2024.

Genetic Association Studies↗

PubMed2007

Comparative analysis of predictive biomarkers for therapeutical strategies in colorectal cancer.

BACKGROUND: Prognostic information regarding the risk of postoperative tumor recurrence defined by a profile of serological, morphological and/or molecular markers can have potential value, particularly for patients with colorectal carcinoma (CRC) of the International Union Against Cancer (UICC) stage II/III who may benefit from adjuvant chemotherapy after surgery. METHODS: A retrospective study of 783 patients with CRC (UICC I-III) including a subgroup analysis of 116 subjects was conducted to determine preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and p53 serum levels. In addition, protein and gene expression of p53, CEA, and adenomatous polyposis coli (APC) was assessed in the tumors of those patients. The values of all serological, morphological, and molecular parameters were correlated with clinicopathological characteristics for their predictive value of tumor recurrence over a mean follow-up period of 32 +/- 6.2 months. RESULTS: Serum CEA but not CA 19-9 or p53 was a significant prognostic factor for disease-free survival, along with UICC and T/N stage. When comparing elevated CEA, CA 19-9, and p53 serum levels with expression of the markers in the tumors, their overall expression was found to be 61.3% in the serum versus 93.5% in the tumor in analyzed patients (n = 116). In particular, all patients in UICC stages I-III who demonstrated at least three elevated markers (CEA/CA 19-9/p53) in serum and/or in the tumor presented with tumor recurrence/metastases. CONCLUSION: Overall increased p53, CEA, and CA 19-9 serum levels and their marker expression in the tumor may be used at the time of primary tumor removal for defining patients at risk for tumor recurrence.

Adenocarcinoma↗

PubMed2006

Transfusion-related acute lung injury (TRALI)--an important, severe transfusion-related complication.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is an immune-mediated transfusion reaction that can cause severe complications or even death. It is now the leading cause of transfusion-related death in the United States. METHODS: The TRALI syndrome is presented in two cases in a surgical intensive care unit and discussed against the background of the present literature. In both cases, concomitant diseases led to an extremely difficult course of TRALI. CONCLUSIONS: Knowledge of the TRALI syndrome is necessary to enable early diagnosis and treatment. It should be taken into consideration at any time when cardiopulmonary instability occurs after transfusion of blood products, which is a frequent event on surgical Intensive Care Units. TRALI remains a clinical diagnosis supported by serologic studies if these are available. Against the background of this potentially life-threatening complication, every single indication to transfuse blood products needs to be scrutinized carefully.

Adult↗

PubMed2006

Morbidity of temporary loop ileostomy in patients with colorectal cancer.

PURPOSE: This study was designed to quantify the temporary loop ileostomy-related morbidity in patients with colorectal cancer and contrast the morbidity rates after ileostomy closure before, during, and after the start of adjuvant therapy. METHODS: Between 1997 and 2004, 120 patients with colorectal carcinoma underwent colorectal resection and creation of a temporary loop ileostomy to protect the low anastomosis. Stoma-related complications and perioperative morbidity after ileostomy closure were assessed retrospectively by reviewing the medical records. RESULTS: Sixteen of the 120 patients (13.3 percent) suffered stoma-related complications, requiring early ileostomy closure in three. After ileostomy closure, anastomotic leakage of the ileoileostomy occurred in 3 of the 120 patients (2.5 percent), 2 of them died postoperatively (1.7 percent). The rate of minor complications (16.7 percent in all patients) was much higher in patients undergoing adjuvant chemotherapy or radiochemotherapy (25.5 percent) than in patients receiving no additional therapy (9.2 percent). In the former patients, there was a trend toward fewer complications when ileostomy closure was performed before (12.5 percent), rather than during (42.9 percent) or after (21.2 percent), the start of adjuvant therapy. CONCLUSIONS: The morbidity following closure of a temporary loop ileostomy in colorectal cancer patients is much higher in patients receiving adjuvant chemotherapy or radiochemotherapy. The morbidity, however, might possibly be lowered to the level of patients receiving no additional therapy if ileostomy closure is performed before the start of adjuvant therapy.

Adult↗

PubMed2006

Band erosion and passage, causing small bowel obstruction.

A rare complication of adjustable gastric banding is reported. A 65-year-old man developed recurrent vomiting, epigastric pain, and small-bowel obstruction 13 months after laparoscopic adjustable gastric banding for morbid obesity. Investigation revealed that the band had migrated completely into the gastric lumen and had passed far down the jejunum. The band was still connected by the tubing to the port chamber. By laparoscopy, the band was cut at the stomach, and removed via a jejunotomy. Postoperative course was uneventful. Complete band migration requires early removal of the band.

Aged↗

PubMed2006

T-cell response to p53 tumor-associated antigen in patients with colorectal carcinoma.

Despite the radical surgical resection performed in patients with colorectal carcinoma, there is a high rate of tumor recurrence. Over an observation period of 3 years, 18% of the patients in our collective suffered a tumor relapse with local or distinct metastases after initial R0-resection. Some evidence suggests that this may be due to suppression of anti-tumor responses, a phenomenon that might be attributed to regulatory T cells. The aim of our study was to investigate the tumor-specific immune response depending on the UICC stage of patients with colorectal cancer. The cellular immune responses against defined antigens that are overexpressed in most of the patients with colorectal cancer were characterized. For this purpose, the tumor suppressor gene, p53, was chosen as the tumor-associated antigen that exhibits mutations and overexpression in up to 60% of colorectal carcinoma. We observed that p53 induced both IFN-gamma and IL-10 secretion. The predominance of IL-10 production indicated that regulatory T cells directly participate in modulating the anti-tumor immune response. IL-10 levels in the blood as well as the expression of regulatory T-cell specific genes at the tumor site correlate with the UICC stage of the disease. These results may provide an explanation for the poor prognosis and increased recurrence rate in patients with advanced carcinoma.

Antibodies, Neoplasm↗

PubMed2006

Feasibility and limits of an orthotopic human colon cancer model in nude mice.

We sought to develop an accurate colorectal cancer model in nude mice with stable local growth, tumor cell dissemination, and reproducible metastatic capacity. To this end, we orthotopically transplanted histologically intact human colorectal cancer tissue from 10 human patients into nude mice. After successful local tumor growth, tumor tissues were retransplanted as many as 9 times in serial passage. All specimens were transplanted using microsurgical techniques. Histologic, immunohistochemical, and polymerase chain reaction techniques were used to determine tumor growth rates and kinetics, development of regional lymph node and distant hepatic metastases, and the induction of minimal residual disease (MRD). Stable local tumor growth rates with variable growth kinetics were detected in 73.4% of all mice. The lymph node and hepatic metastasis rates were low, at 18.4% and 4.9%, respectively. MRD, as reflected by CK20 positivity of the bone marrow in animals with lymph node and hepatic metastases, was present in 22.2%. The orthotopic colorectal cancer model described here is feasible for the induction of reproducible local tumor growth but is limited by variable growth kinetics and the low rate of lymph node and hepatic metastases. Cytokeratin-positive cells indicative of MRD could be detected in the bone marrow of approximately 25% of the nude mice with metastases. The observed induction of MRD after orthotopic implantation of intact human colon cancer in animals with lymph node and hepatic metastases might be improved if established colon cancer cell lines were used.

Aged↗

PubMed2004

Intimal angiosarcoma of the aorta: report of a case and review of the literature.

Although extremely rare, the group of primary malignant tumors of the aorta (PMTA) exhibits enormous histologic heterogeneity. In most cases, diagnosis is established late in the course of the disease; the median survival time is only a few months. We present the case of a 75-year-old patient with an intimal angiosarcoma of the infrarenal abdominal aorta and discuss the clinical presentation, histopathologic diagnosis, and classification of primary aortic sarcomas. A critical review of the diagnostic and therapeutic management in this case revealed that the atypical aortic thrombus should have prompted a comprehensive preoperative diagnostic work-up, specifically with magnetic resonance tomography of the aorta and bone scintigraphy.

Aged↗

PubMed2004

Expression profiling and genetic alterations of the selenoproteins GI-GPx and SePP in colorectal carcinogenesis.

The trace element selenium is discussed as a chemopreventive agent in colorectal carcinogenesis. Selenocysteine-containing proteins, so-called selenoproteins, represent potential molecular targets for nutritive selenium supplementation. Due to their antioxidative potential, the selenoproteins gastrointestinal glutathione peroxidase (GI-GPx) and selenoprotein P (SePP) are considered to provide protection against reactive oxygen species (ROS), thereby reducing DNA damage and preventing development of colon cancer. GI-GPx and SePP are abundantly expressed in normal colon mucosa. Recently, we demonstrated both reduced SePP expression and increased GI-GPx expression in colorectal adenomas. In this study, we investigated the expression of SePP and GI-GPx in colorectal cancers compared with corresponding normal mucosa. Further, the occurrence of genetic alterations within the SePP and GI-GPx genes was analyzed. We observed a significant reduction or loss of SePP mRNA expression in colon cancers, whereas GI-GPx mRNA and protein expression varied between different tumor samples. In addition, we identified novel polymorphisms within the SePP and GI-GPx genes with so far unknown relevance for protein function. Our results argue against a general decrease of selenoprotein expression in colorectal carcinogenesis but imply specific differential regulation of expression of individual selenoproteins.

Adult↗

PubMed2002

Paternity testing after pregnancy termination using laser microdissection of chorionic villi.

We report an unusual case of paternity testing from residues of chorionic villi 5 weeks after pregnancy termination. The autopsy of a 32-year-old female homicide victim revealed the presence of intact chorionic villi at the former placenta implantation site. Fetal cells were selectively isolated by laser-induced microdissection of the remaining villi to avoid contamination with maternal DNA. Simultaneous amplification of 12 STR loci in 2 PCR reactions resulted in a combined probability of paternity of 99.94%. This case demonstrates that laser-assisted microdissection and multiplex STR typing provide tools for paternity testing performed on endometrial mucosa long after the product of conception was removed by therapeutic abortion.

Abortion, Induced↗

PubMed2002

A complex DNA-repeat structure within the Selenoprotein P promoter contains a functionally relevant polymorphism and is genetically unstable under conditions of mismatch repair deficiency.

Epidemiological data, animal studies and interventional studies provide evidence for a potential chemopreventive effect of selenium during development of colorectal cancer. The human glycoprotein Selenoprotein P (SeP) contains up to 50% of plasma selenium content. SeP is expressed in the gastrointestinal tract and the liver, where its expression is downregulated by various proinflammatory cytokines (Il1beta, TGFbeta, IFNgamma). Previously, we have demonstrated dramatically reduced SeP expression in human colon adenomas. Here, we have identified a complex (A)4-C-(A)4-GG-(A)8-GCT-(TC)5-(T)17 (bp -429 to bp - 477) repeat structure within the SeP promoter and we have analysed this regulatory DNA sequence with respect to polymorphisms, genomic instability and functional relevance to promoter activity. As opposed to the (TC)5 variant we identified a novel (TC)3 polymorphism within this repeat in the general population, which conferred significantly reduced basal promoter activity to reporter gene constructs in HepG2 cells. Allelic distribution of this (TC)(n) element was similar in colon carcinoma patients and healthy controls. Additionally, we observed genetic instability within the (T)17 repeat motif in colon cancers of the mutator phenotype. This instability of the (T)17 repeat had no effect on basal promoter activity in reporter gene assays. In conclusion, we characterised a complex repeat structure within the SeP promoter that may be of functional relevance to SeP gene expression. Further studies on the effect of different SeP promoter genotypes on SeP protein expression and disease susceptibility are needed.

Base Pair Mismatch↗