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F Köckerling

Publications and source records attributed to F Köckerling.

At least 19 recordsLinked to original sources
PubMed1998

Microchimerism after liver transplantation: prevalence and methodological aspects of detection.

BACKGROUND: Microchimerism after liver transplantation is a readily observed phenomenon. The immunological implications, however, remain unclear. Moreover, methodological approaches and their detection limits in the study of allogeneic microchimerism have not been studied in detail. METHODS: Therefore, the aim of this study was to evaluate the single-step and nested formats of the polymerase chain reaction/sequence-specific priming (PCR-SSP) approach under standardized conditions. For that purpose, a panel of recombinant plasmid clones was generated by PCR cloning. The panel contained the allelic sequences of the second exon of DRB1 covering all DR specificities on a low-resolution level. Using this panel, limiting dilution assays for various DR sequences in the presence and absence of competitor DNA were carried out to determine the minimal number of copies required for detection by single-step and nested PCR-SSP. Subsequently, 22 liver transplant recipients were analyzed in a retrospective study for the presence of allogeneic microchimerism by nested PCR-SSP. RESULTS: Although at least 10 copies of template DNA could be detected by nested PCR-SSP overall, single-step PCR-SSP was on average 10(2) to 10(3) times less sensitive. Upon the addition of human competitor DNA, the detection limits decreased on average by a factor of 10. In addition, sequence-specific differences in amplification efficiency could be appreciated. Using nested PCR-SSP, peripheral blood allogeneic microchimerism could be observed in 17 of 22 HLA-DR-mismatched liver recipients. Recombinants representing recipient DRB1 specificities were used to exclude false-positive results by lack of cross-reactivities of the donor-specific primers and to evaluate negative results due to sample-related reduced amplification efficiencies in microchimerism-negative recipients. In donor/recipient combinations that differed by at least one DR specificity, allogeneic microchimerism was seen in 87.5% of the cases. In five chimerism-negative cases, sample-related problems were detected in two cases. CONCLUSION: The optimization and standardization of the detection of genomic HLA sequences at low copy number may be greatly facilitated using a clonal reference system. Furthermore, a clonal reference system may be used to conduct cross-priming experiments to exclude false-positive results and may allow the determination of sample-specific detection limits for donor-derived HLA-DR specificities in chimerism-negative patients. Our evaluation of the PCR-SSP approach for the study of allogeneic microchimerism indicated that nested PCR-SSP provides the most sensitive format when HLA sequences are targeted. Yet, the detection sensitivity may vary between individual alleles and specificities. Allogeneic microchimerism in liver recipients can be observed in the majority of patients. However, the detection may be subject to the degree of mismatching, the HLA-DR alleles involved, and sample-related impaired PCR amplification efficiency.

Alleles↗
PubMed1998

Apoptosis, proliferation, bax, bcl-2 and p53 status prior to and after preoperative radiochemotherapy for locally advanced rectal cancer.

PURPOSE: To investigate the relationship between apoptotic cell death, proliferative activity, and the expression of apoptosis regulating proteins in rectal cancer prior to and after radiochemotherapy. MATERIALS AND METHODS: In 32 patients dispositioned to receive preoperative radiochemotherapy for locally advanced rectal carcinoma, pretherapy biopsies and the final resected specimen after radiochemotherapy were available for analyses. Apoptotic cells were identified and quantified using in situ end labeling (ISEL) technique. The expression of the bax protein was assessed immunohistochemically. Additionally, double immunostaining was performed for apoptotic cells and bax expression. The proliferative activity was determined by immunohistochemical assessment of the Ki67 (MIB-1) and the proliferating cell nuclear antigen (PCNA). p53- and bcl-2 expression was analyzed immunohistochemically. A clinical-to-pathologic downstaging after radiochemotherapy was achieved in 25 of 32 patients (78%). During follow-up, tumor recurrence was observed in six cases. In one case, no residual tumor was detected after radiochemotherapy. RESULTS: After radiochemotherapy, the apoptotic index increased significantly in almost every case examined. In contrast, the proliferative activity was significantly decreased in resected specimens as compared to biopsies. Bax immunostaining was detected in 12/31 (39%) biopsies and in 26/31 (84%) resected specimens. In the resected specimen, significantly more apoptotic cells that were bax-positive were found than in biopsies. Bcl-2 immunostaining occurred in 15/31 biopsies and 12/31 resected specimens, respectively. Tumors that were immunohistochemically negative for p53 (20/31 [65%]) generally exhibited a higher apoptotic index and a high expression level of bax than p53-positive tumors (11/31 [35%]). However, we did not find any correlation between the (pre- and post-therapeutic) rate of apoptosis or the level of bax expression and the degree of clinical-to-pathologic downstaging or the frequency of tumor recurrence. CONCLUSION: Our results indicate that radiochemotherapy is associated with an increase in bax expression and also in apoptotic cell death. The observation of higher rates of apoptosis and bax in p53-negative tumors suggests that p53 might be a possible regulating factor of apoptosis in rectal cancer.

Adult↗
PubMed1998

Plasma separation and bilirubin adsorption after complicated liver transplantation: a therapeutic approach to excessive hyperbilirubinemia.

BACKGROUND: Severe hyperbilirubinemia is known to exert multiple toxic effects. Thus, a reduction in bilirubin by use of various adsorbent columns has been reported for a variety of hepatic disorders, but no experience with liver transplant patients is available as yet. METHODS: Plasma separation and bilirubin adsorption by an anion-exchange adsorbent column (BR-350) were performed in two patients with severe jaundice (total serum bilirubin > 55 mg/dl) and multiple organ failure that had developed after orthotopic liver transplantation. RESULTS: The procedure resulted in an 18% to 35% reduction in total bilirubin after each session, accompanied by a remarkable clinical improvement. Both patients finally recovered and had a favorable outcome. No complications or side effects of bilirubin adsorption were observed during any of the six sessions. CONCLUSIONS: Bilirubin adsorption is a safe and effective treatment. It should be considered as supportive therapy for excessive hyperbilirubinemia after liver transplantation. In selected cases, retransplantation may thus be avoided.

Adsorption↗
PubMed1998

DCC protein as a predictor of distant metastases after curative surgery for rectal cancer.

PURPOSE: The aim of this study was to determine the value of DCC (deleted in colorectal cancer) protein for predicting metachronous distant metastases after curative surgery for rectal cancer. The DCC protein--for which a gene has been located on chromosome 18q--has recently been reported to have a prognostic value in colorectal cancer. This finding might have implications for treatment of International Union Against Cancer Stage II rectal carcinoma, in which distant metastases will develop in 14 percent of patients despite optimal surgery. METHODS: Paraffin-embedded tissues from 85 patients who developed distant metastases, but no local recurrence, after curative surgery for rectal cancer were matched with 85 samples from patients who remained disease-free. Matching criteria were tumor stage, age, gender, and date of surgery. Expression of DCC protein was assessed using immunohistochemistry. End points of follow-up were recurrence of disease and death. Mean follow-up was 9.6 years. No patient received either local or systemic adjuvant therapy. RESULTS: The DCC protein was found to be expressed in 64.9 percent of tumor samples. Nonexpression of DCC protein had an negative influence on survival (P = 0.03). For all tumor stages together, sensitivity of the test for subsequent occurrence of distant metastases was 42 percent and specificity was 71 percent. In Stage II cancers, the positive predictive value was 19 percent, and the negative predictive value was 88 percent. CONCLUSIONS: Our results confirm that DCC protein is a useful prognostic marker in patients with rectal carcinomas, but the positive predictive value of DCC protein for occurrence of metachronous metastases does not appear to be sufficient to justify adjuvant therapeutic measures in Stage II rectal cancer.

Biomarkers, Tumor↗
PubMed1998

Prospective multicenter study of the quality of oncologic resections in patients undergoing laparoscopic colorectal surgery for cancer. The Laparoscopic Colorectal Surgery Study Group.

PURPOSE: Laparoscopic colorectal surgery for cancer is currently under discussion. Results of large, randomized studies will not be available for a number of years yet. This study analyses the results of such resections in consecutive patients operated on by unselected surgeons. METHODS: A prospective, observational, multicenter study was initiated on August 1, 1995, in the German-speaking countries of Europe. One year after initiation of the study, findings are presented with respect to the quality of oncologic resections. RESULTS: Of 500 operations, 231 (46 percent) were performed for cancer, 167 (33 percent) with a curative intent. The most common curative resections were as follows: 63 anterior rectum resections (38 percent), 51 sigmoid resections (30 percent), and 27 abdominoperineal resections (16 percent). Segmental resections were performed in 20 patients (12 percent). Intraoperative tumor spillage was reported in 2 percent. Mean number of lymph nodes harvested was 13 (confidence interval, 5-95 percent; range, 11.5-14.6) and positive lymph nodes harvested was 2.2 (confidence interval, 5-95 percent; range, 0.9-3.4). Significant differences were noted between participating centers in terms of number of lymph nodes resected (P < 0.0001). Distal and proximal resection margins were tumor-free in every case. Lateral margins were tumor free when examined. In the case of 63 curative anterior resections, the mean distal resection margin was 39 (confidence interval, 5-95 percent; range, 33-45) mm, and in 8 of these resections, it was less than 20 min. Mean blood loss was 344 (confidence interval, 5-95 percent; 292-396) ml, and 21 percent of patients received blood transfusion. CONCLUSIONS: These data document that the average quality of laparoscopic colorectal procedures for cancer is satisfactory but differs among surgeons.

Aged↗
PubMed1998

Predictive value of nuclear beta-catenin expression for the occurrence of distant metastases in rectal cancer.

PURPOSE: Adenomatous polyposis coli protein, glycogen synthetase kinase-3-beta, T cell transcription factor/lymphoid enhancer-binding factor, and beta-catenin modulate cell differentiation and proliferation via the expression of effector genes. It has recently been postulated that beta-catenin is a potent oncogene of sporadic colorectal carcinogenesis and a prognostic tumor marker. Our aim was to investigate whether the nuclear overexpression of beta-catenin, possibly caused by mutations in exon 3 of beta-catenin (CTNNB1), is correlated with distant metastatic spread or disease-free survival in rectal carcinoma. METHODS: Immunohistochemical analysis was performed with an anti-beta-catenin-monoclonal antibody on paraffin sections of two groups of patients (n = 2 x 77) with rectal carcinoma curatively treated by surgery alone. The patients selected were all free of local disease, to exclude surgical influence. Patient groups were matched for age, gender, International Union Against Cancer stage, and year of operation (1982 to 1991) and differed only in subsequent metachronous distant metastatic spread. Follow-up was prospective (median, 9.6 years). Three staining patterns were defined: membranous (normal), diffuse cytoplasmic (pathologic), and intense nuclear staining (pathologic). When intense nuclear staining was defined, the specimen was microdissected. Then, DNA was isolated, polymerase chain reaction-amplified, and sequenced to detect mutations in exon 3. RESULTS: Nuclear overexpression of beta-catenin correlated neither with distant metastatic spread (chi-squared, 0.37; P = 0.79) nor with disease-free survival (log-rank with trend, P = 0.62). No mutations were found in the area of the serine/threonine-kinase glycogen synthetase kinase-3-beta-phosphorylation site in exon 3 (CTNNB1) of beta-catenin. CONCLUSION: Although beta-catenin seems to play an important role in early colorectal carcinogenesis, its value as a prognostic marker is questionable. It must be assumed that metastatic ability is determined by other factors than the disturbance of the beta-catenin T cell transcription factor/lymphoid enhancer-binding factor cascade and that other mechanisms might cause the observed nuclear translocation of beta-catenin.

Adenocarcinoma↗
PubMed1998

[Proliferation and apoptosis before and after preoperative simultaneous radiochemotherapy of rectal carcinomas].

PURPOSE: To investigate the relationship between apoptotic cell death, proliferative activity, and the status of the tumor suppressor gene p53 in rectal cancer before and after radiochemotherapy. MATERIALS AND METHODS: Thirty-two patients dispositioned to receive preoperative radiochemotherapy for locally advanced rectal carcinoma prior to radical surgical tumor resection were analysed. In all cases, pretherapy biopsies and the final resected specimens after radiochemotherapy were available for analyses. Apoptotic cells were identified and quantified using in situ end labeling (ISEL) technique. The proliferative activity was determined by immunohistochemical assessment of the Ki67 (MIB-1) antigen. p53 expression was analysed immunohistochemically as well. A clinical-to-pathologic downstaging after radiochemotherapy was achieved in 25/32 patients (78%). In one case, no residual tumor was detected after radiochemotherapy. RESULTS: After radiochemotherapy, the apoptotic index increased significantly in almost every case examined. In contrast, the proliferative activity was significantly decreased when comparing biopsies and resected specimens. Tumors that were immunohistochemically negative for p53 generally exhibited a higher apoptotic index than p53 positive tumors. However, we did not find any correlation between the (pre- and post-therapeutic) rate of apoptosis and the degree of clinical-to-pathologic downstaging. CONCLUSION: Our results indicate, that radiochemotherapy induces an increase in apoptotic cell death. The observation of higher rates of apoptosis in p53 negative tumors suggests that p53 might be a regular of apoptosis in rectal cancer.

Adenocarcinoma↗
PubMed1998

Close anatomical relationships between nerve fibers and MHC class II-expressing dendritic cells in the rat liver and extrahepatic bile duct.

The anatomical relationships between immunocytochemically identified nerve fibers and MHC class II-expressing antigen presenting dendritic cells were investigated in the rat hepatobiliary system using immunocytochemistry, confocal laser scanning, and electron microscopy. Close proximity of nerve fiber varicosities immunostained for PGP 9.5 and MHC class II-expressing dendritic cells was frequently observed in the wall of extrahepatic bile ducts, in Glisson's area, around central and hepatic veins, and in the liver capsule. Contacts between nerve fibers staining for substance P, calcitonin gene-related peptide, calretinin, and vasoactive intestinal polypeptide and dendritic cells were more often observed around extrahepatic bile ducts than in Glisson's area. Nerve fibers immunostaining for tyrosine hydroxylase and neuropeptide Y were numerous both in the wall of extrahepatic bile ducts and in Glisson's area and frequently contacted dendritic cells there. At the ultrastructural level, close membrane contacts between bare axolemmal areas of unmyelinated nerve fibers and processes of MHC class II-expressing cells were observed. These results demonstrate close anatomical relationships of nerve fibers from various sources with antigen presenting dendritic cells in the visceral domain and suggest modulation of antigen presentation by the autonomic nervous system.

Animals↗
PubMed1998

Early results of a prospective multicenter study on 500 consecutive cases of laparoscopic colorectal surgery. Laparoscopic Colorectal Surgery Study Group (LCSSG).

BACKGROUND: Prospective randomized multicenter studies comparing laparoscopic with open colorectal surgery are not yet available. Reliable data from prospective multicenter studies involving consecutive patients are also lacking. On the basis of the personal caseloads of specialized surgeons or of retrospective analyses, it is difficult to judge the true effectiveness of this new technique. This study aims to investigate the results of laparoscopic colorectal surgery in consecutive patients operated on by unselected surgeons. METHODS: This observational study was begun August 1, 1995, in the German-speaking part of Europe (Germany and Austria) and 43 centers initially agreed to participate. All consecutive cases were documented. All data were rendered anonymous. Analysis was performed on an intention-to-treat basis. The study committee was blinded to the participating center. RESULTS: By the end of the 1st year, 500 patients (M:F ratio 0.83, mean age 62.9 years) had been treated by 18 centers; 269 operations were performed for benign indications and 231 for cancer (palliative and curative). Most operations were done on the distal colon or rectum. An anastomosis was performed in 84%, with an overall leakage rate of 5.3% (colon 3.6% and rectum 11.8%), which required surgical reintervention in 1.7%. The mean operating time was 176 min and showed a decreasing tendency over the period under study. The conversion rate was 7.0% and the overall complication rate 21.4%. The reoperation rate was 6.6%; the most common cause was bleeding. There was one ureteral lesion (0.2%), but urinary tract infections were fairly common (4.8%). A postoperative pneumonia was diagnosed in 1.6% of the cases. No thromboembolic complications were reported. The 30-day mortality rate was 1.4% and overall hospital mortality 1.8%. CONCLUSIONS: Laparoscopic colorectal operations are still rare (about 1% of all colorectal operations in Germany). Laparoscopic procedures are more common on the left colon and rectum than on the right colon. The surgical complication rate is acceptable, comparable with rates reported by others for open surgery. Cardiopulmonary and thromboembolic complications were rarely seen. Mortality and surgical morbidity rates do not differ significantly among participating centers. A learning curve, reflected by a shortening of the operating time and a somewhat lower conversion rate, was observed over the observation period.

Aged↗
PubMed1998

The pneumoperitoneum and its role in tumor seeding.

Port site recurrences (PSR) are abdominal wall recurrences that occur within a trocar site after cancer laparoscopy and that are not associated with peritoneal carcinosis. The short clinical delay of occurrence of PSR (median 190 days in colorectal cancer) suggests a massive cell seeding into the abdominal wall (over 10(6) cells) during the operation. In human and animal studies, CO2 was not able to aerosolize large numbers of tumor cells using pressures of 8-15 mm Hg, even though isolated mesothelial cells have been found in the aerosol. Such large numbers of tumor cells have only been demonstrated on instruments and trocars. PSR occur not only after CO2 laparoscopy, but also after thoracoscopy, where no CO2 is used. Gaseless laparoscopy was able to reduce, but not to eliminate port site contamination in animal models. Tumor growth was enhanced in numerous animal models using CO2, suggesting an adjuvant effect on tumor growth in the trocar wound. Nevertheless, reported clinical incidences between 0 and 21% suggest that PSR might be a surgeon-related variable dependent mainly on experience and technical expertise. Technical measures have been proposed that might reduce the incidence of PSR.

Abdominal Muscles↗
PubMed1998

Influence of surgery on metachronous distant metastases and survival in rectal cancer.

PURPOSE: Total mesorectal excision (TME) and other technical surgical factors reduce local recurrence rate in rectal cancer. Scientific evidence of the positive effect of optimal surgery on survival is locking. Whether a reduction in the incidence of distant metastases can be achieved with optimal surgery is uncertain. We examine the effects of the quality of surgery, as reflected by local recurrence rate, on survival and the incidence of initial distant metastases. PATIENTS AND METHODS: Between 1974 and 1991, 1,581 consecutive patients who underwent curative resection (RO) for rectal carcinoma were monitored for recurrence and survival. TME was introduced in 1985. No patient received adjuvant radiotherapy or chemotherapy. The median follow-up time was greater than 13 years. RESULTS: The local recurrence rate decreased from 39.4% to 9.8% during the study period (P < .0001). The observed 5-year survival rate improved from 50% to 71% (P < .0001). Three hundred six patients with local recurrence had a significantly lower observed 5-year survival rate (P < .0001). A total of 1,285 patients had no local recurrence, but 275 of them developed distant metastases (International Union Against Cancer [UICC] stage I, 8%; stage II, 16%; stage III, 40%). Better-quality surgery had no effect on the incidence of initial distant metastases, which remained constant (P = .44). CONCLUSION: Quality of surgery is an independent prognostic factor for survival in rectal cancer, but has no influence on initial occurrence of distant metastases. Local recurrence cannot be considered an outcome criterion of adjuvant treatment without consideration of the surgeon as a risk factor.

Adult↗
PubMed1998

[Technique of total extraperitoneal endoscopic hernioplasty of the inguinal canal].

The current end stage in the development of endoscopic treatment of inguinal hernia involves the introduction of a patch into the extraperitoneal space. This may be done via a transabdominal approach (TAPP) or via a total extraperitoneal approach (TEP). The present article describes the TEP technique in detail. In addition to dealing with the ideal case, the authors also discuss the procedure in relation to all know forms of hernia. Furthermore, they provide the reader with suggestions on how to deal with intraoperative technical problems and how to avoid recurrences.

Hernia, Inguinal↗
PubMed1998

[Surgical therapy of liver metastases in breast carcinoma].

The literature contains little information on the surgical treatment of metastases from carcinoma of the breast. Advanced stages of mammary cancer with generalised metastatic spread are considered to be the therapeutic domain of systemic chemotherapy. Patients with isolated liver metastases may, under certain circumstances, be considered candidates for partial resection of the liver. Another therapeutic option in this group of patients is intraarterial chemotherapy via a port catheter system implanted in the hepatic artery. A number of institutions employ a combination of both treatment modalities. Overall 5-year survival rates are low for both the regional and the systemic form of treatment. A carefully selected group of patients may be expected to benefit from partial resection of the liver, intraarterial chemotherapy or a combination of the two by having their survival time prolonged--provided that due consideration is given to all contraindications, and there are no extrahepatic manifestations. Wherever possible, resections should be carried out in curative intent. However, palliative resection may be justified in individual cases where alleviation of symptoms and an improvement in the patient's quality of life is to be expected. The present paper discusses the results achieved in 21 women who underwent liver resection at the surgical department of the University of Erlangen between 1980 and 1997, and compares these results with those reported in the literature. The average age of the patients was 54 years, and 9 had a solitary metastasis. As was to be expected, the R classification had a decisive influence on survival. The 2-year survival rate was 60% for R0 resections as compared with 16.7% for R1 or R2 resections.

Adult↗
PubMed1998

[Anesthesia in laparoscopies: an overview].

In the last few years laparoscopic surgery requiring a different method of anesthesia from laparotomic procedures has been increasingly carried out. Since laparoscopic cholecystectomy was first described in 1985 almost all abdominal organs can now be operated on laparoscopically. At the same time the spectrum of the patients has changed from those who are young and healthy to older ones with many accompanying illnesses. In addition, the length of time this operations require has greatly increased. Consequently the number of critical incidents relevant to anaesthesia, during laparoscopy, has risen. Therefore new studies had been worked out which lead to a better understanding of pathophysiological changes during pneumoperitoneum.

Adult↗
PubMed1998

[Laparoscopic splenectomy].

To date more than 400 laparoscopic splenectomies have been reported in the literature. The main indications for the procedure are benign haematological diseases, in particular idiopathic thrombocytopenic purpura. Laparoscopic splenectomy to treat malignant illnesses is rare and is usually restricted to small or only moderately enlarged spleens. Technically, the lateral abdominal approach with the patient in a right decubitus position has the advantage over the anterior approach in the supine patient of permitting better access to the organ. Under the force of gravity the stomach and intestines drop out of the operating field, and the splenic ligaments are placed under tension. This facilitates dissection with the harmonic scalpel and safe divisioning of the hilar vessels using the linear stapler. The individual steps of the procedure are described in detail.

Humans↗