Biomedical subjects

Moritz Koch

Publications and source records attributed to Moritz Koch.

17 recordsLinked to original sources

PubMed2007

Detection of disseminated tumor cells in liver biopsies of colorectal cancer patients is not associated with a worse prognosis.

BACKGROUND: Liver metastases occur frequently in colorectal cancer and are probably caused by disseminated tumor cells having been trapped in the liver. The prognostic significance of hematogenous tumor cell dissemination has already been demonstrated for blood and bone marrow of patients with colorectal cancer. The aim of this study was to investigate the frequency and prognostic significance of disseminated tumor cells in liver biopsies of colorectal cancer patients. METHODS: Liver biopsies from 100 patients with UICC stage I-III colorectal cancer were taken prospectively during resection of the primary tumor. Liver biopsies obtained from 16 patients with benign gastrointestinal diseases served as negative controls. Liver samples from seven patients with liver cirrhosis were additionally taken. Liver biopsies were examined using a reverse transcriptase (RT)-PCR assay to amplify cytokeratin (CK) 20 transcripts. The median follow-up of the patients was 55 months. RESULTS: Disseminated tumor cells were detected in liver samples of 10/100 (10%) patients with UICC stage I-III colorectal cancer. Liver specimens from all seven patients with liver cirrhosis were CK 20-positive, whereas 16 patients with other benign gastrointestinal diseases were all CK 20-negative. There was no correlation between tumor cell detection in liver biopsies and survival of the patients. The only significant prognostic factor on uni- and multivariate analysis was the UICC stage. CONCLUSIONS: This study demonstrates that detection of disseminated tumor cells in liver samples from patients with UICC stage I-III colorectal cancer has no prognostic influence. UICC classification was the strongest prognostic factor in this patient series.

Aged↗

PubMed2006

Totally laparoscopic versus conventional ileoanal pouch procedure--design of a single-centre, expertise based randomised controlled trial to compare the laparoscopic and conventional surgical approach in patients undergoing primary elective restorative proctocolectomy--LapConPouch-Trial.

BACKGROUND: Restorative proctocolectomy is increasingly being performed minimal invasively but a totally laparoscopic technique has not yet been compared to the standard open technique in a randomized study. METHODS/DESIGN: This is a two armed, single centre, expertise based, preoperatively randomized, patient blinded study. It is designed as a two-group parallel superiority study. Power calculation revealed 80 patients per group in order to recruit the 65 patients to be analysed for the primary endpoint. The primary objective is to investigate intra-operative blood loss and the need for blood transfusions. We hypothesise that intra-operative blood loss and the need for peri-operative blood transfusions are significantly higher in the conventional group. Additionally a set of surgical and non-surgical parameters related to the operation will be analysed as secondary objectives. These will include operative time, complications, postoperative pain, lung function, postoperative length of hospital stay, a cosmetic score and pre-and postoperative quality of life. DISCUSSION: The trial will answer the question whether there is indeed an advantage in the laparoscopic group in regard to blood loss and the need for blood transfusions. Moreover, it will generate data on the safety and potential advantages and disadvantages of the minimally invasive approach.

Adenomatous Polyposis Coli↗

PubMed2006

Prognostic impact of hematogenous tumor cell dissemination in patients with stage II colorectal cancer.

Adjuvant chemotherapy is not routinely recommended in patients with colorectal cancer stage UICC II. Some of these patients, however, develop recurrent disease. Therefore, valid prognostic criteria are needed to identify high-risk patients who might benefit from adjuvant therapy. Disseminated tumor cells, detected in blood and bone marrow, may prove to be a valid marker, however, the prognostic relevance of these cells remains debated. In our study, we examined the prognostic significance of disseminated tumor cells in blood and bone marrow of patients with stage II colorectal cancer. Ninety patients with potentially curative (R0) resection of colorectal cancer stage II were prospectively enrolled into the study. Bone marrow and blood samples were examined for disseminated tumor cells by CK 20 RT-PCR. Patient, tumor and treatment factors were analyzed as prognostic factors. Multivariate analysis confirmed tumor cell detection in blood (hazard ratio 2.1, p = 0.03) and T-category (hazard ratio 2.2, p = 0.02) to be independent prognostic factors for relapse-free survival. Tumor cell detection in postoperative blood samples (hazard ratio 7.7, p < 0.001) and number of removed lymph nodes (hazard ratio 6.4, p < 0.001) were independent prognostic factors for disease-specific survival. Detection of circulating tumor cells in blood samples of patients with stage II colorectal cancer identifies patients with poor outcome. This finding should be confirmed by further studies and could then be used as a basis for conducting a randomized trial evaluating the effect of adjuvant chemotherapy in stage II patients.

Aged↗

PubMed2006

Increased detection rate and potential prognostic impact of disseminated tumor cells in patients undergoing endorectal ultrasound for rectal cancer.

BACKGROUND: Hematogenous tumor-cell dissemination during diagnostic and therapeutic procedures in patients with colorectal cancer has been demonstrated. OBJECTIVE: The aim of this study was to investigate the extent of disseminated tumor cells in blood samples of rectal cancer patients after endorectal ultrasound and to determine its prognostic relevance. MATERIALS AND METHODS: Peripheral venous blood samples from 45 patients with rectal cancer were taken before and after endorectal ultrasound. Blood samples were examined using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay to amplify cytokeratin 20 transcripts. Overall survival of the patients was calculated by the Kaplan-Meier method. RESULTS: Disseminated tumor cells were detected in peripheral blood samples of 17 of 45 (38%) patients before and after endorectal ultrasound. Circulating tumor cells were found in 11 of 45 (24%) patients only after endorectal ultrasound (p=0.006). There was a clear trend toward a worse prognosis in patients with tumor cells in blood samples after endorectal ultrasound, but this difference was not statistically significant. CONCLUSION: This study demonstrates significantly increased hematogenous tumor-cell dissemination after endorectal ultrasound in rectal cancer patients. Patients with tumor cells in blood samples after endorectal ultrasound tend to have a worse prognosis. The potential prognostic impact of this finding is presently unclear and has to be further validated in larger clinical trials.

Endoscopy, Gastrointestinal↗

PubMed2006

Expression of cytokeratin-20 in pancreatic cancer: an indicator of poor outcome after R0 resection.

BACKGROUND: After complete removal of the neoplasm (R0 resection), approximately 80% of pancreatic cancer patients will die of the disease within 5 years. The expression panel of cytokeratins (CK) is linked closely with cell differentiation. The aim of the study was to investigate the expression of CK-20 in pancreatic cancer tissue and to correlate CK-20 expression with survival in R0-resected pancreatic cancer patients. METHODS: Tissue samples of 63 patients with pancreatic cancer were subjected to CK-20 reverse-transcription polymerase chain reaction. Thirty-four of 63 patients underwent R0 resection and were followed-up for survival statistics. From these 34 patients, 26 (76%) neoplasms were CK-20 positive and 8 (24%) samples were CK-20 negative. The mean follow-up period for the entire group was 17 months (range, 4-36 mo), the follow-up period in censored patients was 23 months (range, 10-36 mo). RESULTS: In the R0-resected group, 3 of 8 (38%) patients with CK-20-negative neoplasms, and 16 of 26 (62%) patients with CK-20-positive neoplasms (P = .15) died of recurrent disease. The median survival time of patients with CK-20-positive neoplasms was 13 months (range, 4-36), the median survival in R0-resected patients with CK-20-negative neoplasm was 26 months (range, 13-35; P = .06). The survival difference observed in patients with CK-20-negative neoplasms could not be attributed to intergroup variations in tumor stage or tumor grade. CONCLUSIONS: A majority of primary ductal pancreatic adenocarcinomas express CK-20. This seems to be associated with poorer survival in R0-resected patients. Our data suggest that ductal pancreatic adenocarcinomas negative for CK-20 constitute a subgroup of patients showing a more favorable disease outcome. The expression of CK-20 in resected pancreatic cancer may be of interest as a prognostic parameter.

Carcinoma, Pancreatic Ductal↗

PubMed2006

Tumor infiltrating T lymphocytes in colorectal cancer: Tumor-selective activation and cytotoxic activity in situ.

OBJECTIVE: To examine whether tumor-selective infiltration, activation, and cytotoxic activity of tumor infiltrating T lymphocytes (TIL) can be demonstrated in situ in colorectal cancer samples. SUMMARY BACKGROUND DATA: Recent studies indicated a correlation between the presence of TIL and an improved prognosis in colorectal cancer. However, tumor-selective activation and cytotoxic activity of CD8 TIL in situ in colorectal cancer patients have not yet been examined. METHODS: Tumor samples from 49 patients and corresponding normal mucosa samples from 23 patients with colorectal cancer (UICC stages II-IV) were examined for TIL. Two-color fluorescence immunohistochemistry and multicolor flowcytometric (FACS) analysis were used for quantification of CD8 T cells and measurement of their activation status (CD69-expression) and cytotoxic activity (CD107a-expression) in situ. Presence of tumor antigen-reactive T cells in tumor, blood, and bone marrow was evaluated by IFN-gamma Elispot analysis. RESULTS: While absolute numbers of CD8 T cells were similar, CD4 T helper cells were significantly increased in tumor tissue compared with normal mucosa. There was a significantly higher proportion of activated and cytotoxically active CD8 TIL in colorectal cancer compared with normal mucosa. Increased activation, cytotoxic activity, and functional reactivity of TIL were correlated with the presence of functional tumor antigen-reactive T cells in the blood and bone marrow. The proportion of activated TIL decreased significantly with higher tumor stage. CONCLUSIONS: Tumor-selective activation and cytotoxic activity of CD8 TIL and tumor-selective migration of CD4 T helper cells were demonstrated in colorectal cancer for the first time. Our data support the immunogenicity of colorectal cancer and suggest clinical significance of tumor-specific immune responses.

Adenocarcinoma↗

PubMed2006

Living-donor kidney transplantation: risks of the donor--benefits of the recipient.

For patients with end-stage renal disease, kidney transplantation is the optimal therapy. Due to organ shortage, however, most patients have to wait on dialysis for a considerable period of time prior to transplantation. Living-donor kidney transplantation is a valid option to expand the organ pool and to reduce waiting time. The risk-benefit ratio of living-donor kidney transplantation needs to be evaluated critically, as healthy persons voluntarily donate an organ for transplantation. The available data from the literature seem to prove that the donor operation can be performed with a minimal perioperative risk. Regarding the long-term course after kidney donation, the published data suggest that the risk is minimal for well-selected healthy donors who are closely followed postoperatively. The potential donor, however, needs to be completely informed regarding the potential short- and long-term risks of kidney donation prior to the planned procedure. From the recipient point of view, transplantation of a kidney from a living donor is a very good if not the optimal option, as the short- and long-term outcomes seem to be favorable compared with cadaveric kidney transplantation. With donor safety being constantly monitored, it seems to be justified to further pursue living-donor kidney transplantation programs.

Graft Survival↗

PubMed2005

Interrupted or continuous slowly absorbable sutures - design of a multi-centre randomised trial to evaluate abdominal closure techniques INSECT-trial [ISRCTN24023541].

BACKGROUND: The closure of the abdomen after median laparotomy is still a matter of debate among surgeons. Further well designed and performed randomised controlled trials determining the optimal method of abdominal fascial closure are needed. DESIGN: This is a three armed, multi-centre, intra-operatively randomised, controlled, patient blinded trial. Over 20 surgical departments will enrol 600 patients who are planned for an elective primary abdominal operation. The objective of this study is to compare the frequency of abdominal incisional hernias between two continuous suture techniques with different, slowly absorbable monofilament materials and an interrupted suture using an absorbable braided suture material at one year postoperatively. CONCLUSION: This trial will answer the question whether the continuous abdominal wall closure with a slowly absorbable material with longitudinal elasticity is superior to the continuous suture with a material lacking elasticity and to interrupted sutures with braided thread.

Abdominal Wall↗

PubMed2005

Short description of an alternative simplified method for screening recombinant clones within the "AdEasy-System" by Duplex-PCR.

BACKGROUND: Recombinant adenoviral vectors are highly efficient for in vitro and in vivo gene delivery. They can easily be produced in large numbers, transduce a wide variety of cell types and generate high levels of transgene expression. The AdEasy system is a widely used system for generating recombinant adenoviral vectors, which are created with a minimum of enzymatic manipulations and by employing homologous recombination in E. coli. In this paper we describe an alternative simplified method for screening recombinant DNA within the AdEasy system. This Duplex-PCR-method is independent of the transgene or insert and can be used for the complete AdEasy system. It is characterized by a simple standard protocol and the results can be obtained within a few hours. The PCR is run with two different primer sets. The primers KanaFor and KanaRev hybridizise with the Kanamycin resistence gene and AdFor and AdRev detect the adenoviral backbone. In case of recombinant clones, two diagnostic fragments with a size of 384 bp and 768 bp are generated. RESULTS: The practicability of this method was verified with three different transgenes: Cytosin Deaminase (AdCD), p53 (Adp53) and Granulocyte Macrophage Colony Stimulating Factor (AdGM-CSF). Recombinant clones are indicated by two diagnostic fragments and are then suitable for further processing. CONCLUSION: In summary, the presented protocol allows fast detection of recombinants with an easy technique by minimizing the amount of necessary steps for generating a recombinant adenovirus. This method is time sparing and cost-effective.

Adenoviridae↗

PubMed2005

Is the lateral lymph node compartment relevant?

Lateral pelvic lymphadenectomy is routinely performed in advanced lower rectal cancers by Japanese surgeons, whereas in the western world it has not progressed to a frequently performed technique. Claimed benefit for this extensive surgery is an improved locoregional control; on the other hand, low positive lateral lymph node yields, questionable prognostic significance, and high morbidity (urinary and sexual dysfunction) are main reasons against this procedure. Clinical results published on lateral lymphadenectomy in the literature are conflicting. Due to major improvements in local control and survival of rectal cancer patients mainly based on preoperative radiotherapy and total mesorectal excision (TME), only a few patients may profit from lateral lymph node dissection. This article gives an overview of the current status and the clinical relevance of the lateral lymph node compartment in rectal cancer surgery.

Humans↗

PubMed2005

Diagnostics of rectal cancer: endorectal ultrasound.

In rectal cancer, accurate preoperative staging is essential to adequately select patients for different therapeutic regimes. Endosonography has been proven to be an accurate staging modality in multiple prospective studies. A recent large retrospective study, however, has cast doubt on the actual accuracy of endorectal ultrasound for staging rectal cancer in everyday clinical routines. The results of endosonographic staging of rectal tumours over a period of 10 years at the Department of Surgery of the University of Heidelberg are presented. In a first time period, 424 patients with rectal cancer were staged by endosonography and the data recorded prospectively. The examinations were exclusively done by four surgeons with high experience and scientific interest in endosonography. The second time period comprises 332 patients with rectal tumours (including adenomas) having undergone endosonography by six different examiners after introduction of this staging method into the clinical routine. The data here were analysed retrospectively. Accuracy, sensitivity, specificity, and positive and negative predictive values were calculated for the T and N classifications for both series. In the second series, eight factors which have been postulated to influence staging accuracy in the literature were included in a regression analysis in order to identify relevant factors for staging inaccuracies. Accuracy for staging of the T classification was 81% in the first series versus 71.7% in the second series. In the regression analysis of the second series, status post-chemoradiation proved to be the most significant factor for staging inaccuracy (p < 0.0002). When excluding all patients having undergone chemoradiation, the accuracy for staging of the T classification rose to 76%. A major problem of endosonography in this second series was overstaging; the T category was overestimated in 76 cases (22.9% of patients). The main error here was overstaging of adenomas as cancerous lesions (45.5% of all adenomas) and T2-cancers as more advanced cancers (42.2% of all T2-cancers). When excluding the adenomas from this analysis, the accuracy increased to 73.5%. Accuracy for staging of the N classification was 76% in the first series versus 71% in the second series. Status post-chemoradiation again was a relevant factor (p < 0.0003); when excluding these patients the accuracy increased to 73%. The accuracy of endosonography for rectal tumours decreases after introduction of the method into the everyday clinical routine. Nonetheless, apart from magnetic resonance imaging with an endorectal coil, rectal endosonography is still the most accurate staging modality for rectal tumours and allows adequate selection of patients for different therapeutic regimes. As the major problem of rectal endosonography is overstaging, more patients are likely to undergo overtreatment rather than undertreatment. Endosonography is inaccurate in staging patients having undergone chemoradiation.

Endosonography↗

PubMed2005

Detection of hematogenous tumor cell dissemination predicts tumor relapse in patients undergoing surgical resection of colorectal liver metastases.

OBJECTIVE: To examine the prognostic significance of disseminated tumor cells in blood and bone marrow of patients undergoing surgical resection of colorectal liver metastases. SUMMARY BACKGROUND DATA: Despite curative hepatic resection of colorectal liver metastases, a high percentage of patients develop tumor recurrence. These recurrences probably originate from disseminated tumor cells released into the circulation before or during surgery. METHODS: Thirty-seven patients with potentially curative (R0) resection of colorectal liver metastases were prospectively enrolled into the study. Preoperative bone marrow samples and preoperative, intraoperative, and postoperative blood samples were examined for disseminated tumor cells by CK20 RT-PCR. RESULTS: Tumor cells were detected in preoperative blood samples in 11 of 37 (30%) patients, in intraoperative blood samples in 17 of 37 (46%) patients, and in postoperative blood samples in 8 of 37 (22%) patients. Four of 25 (16%) patients tested positive for disseminated tumor cells in bone marrow samples. Median follow-up time for all patients was 38 months (range, 10-63 months). Multivariate analysis confirmed tumor cell detection in intraoperative blood (P = 0.009) and in bone marrow samples (P = 0.013) to be independent prognostic factors of tumor relapse. CONCLUSIONS: This is the first study demonstrating that detection of hematogenous tumor cell dissemination during hepatic resection of colorectal cancer metastases predicts tumor relapse. Detection of disseminated tumor cells may help to individualize adjuvant therapy for patients with colorectal liver metastases and to develop surgical strategies to prevent intraoperative hematogenous tumor cell shedding.

Aged↗

PubMed2004

Impact of volume and specialization for cancer surgery.

BACKGROUND/AIMS: The so-called volume/outcome relationship postulates that a higher caseload and specialization results in an improved outcome. The existence of such a relationship, however, is still debated in the literature. The objective of this review is to discuss the available data on this relationship in surgical oncology. METHODS: A Medline analysis was performed using the following terms: volume, outcome, cancer, and surgery. The bibliography of each relevant article was screened for further studies. RESULTS: For most malignancies a volume/outcome relationship was demonstrated in recent years. Components of this improved outcome are decreased perioperative morbidity and mortality, higher quality of life after surgery, improved economic outcome, and a better long-term prognosis for patients with cancer. The magnitude of this relationship, however, varies greatly among different malignancies. The exact reason for the volume/outcome relationship is still unknown. CONCLUSION: Concentrating high-risk procedures in high-volume hospitals might prevent thousands of perioperative deaths per year. This concept seems feasible for rare and high-risk diseases; however, it is unclear what threshold should be used for the definition of a high-volume provider. For common and low-risk diagnoses, it seems more realistic to educate the medical community in order to improve the outcome for the patients.

Clinical Competence↗

PubMed2003

Biofeedback versus electrostimulation in treatment of anal sphincter insufficiency.

The purpose of this study was to prospectively investigate a consecutive patient series (N = 70) with anal sphincter insufficiency and compare the efficacy of biofeedback and electrostimulation as conservative treatment options. Forty patients were treated by biofeedback training, 30 patients by electrostimulation. Patients were not specifically selected for one or the other treatment. Success was evaluated by vector volume manometry, water infusion test, time until stoma closure and clinical incontinence scores. Resting and squeeze pressure and resting and squeeze vector volume all increased significantly after biofeedback training (P < 0.05 and < 0.001). Resting pressure and squeeze vector volume only were significantly improved by electrostimulation (P < 0.05 and < 0.01). The increase in squeeze vector volume was significantly greater in the biofeedback group (P = 0.03). The estimated median time period from commencement of training until stoma closure was 9 months in the biofeedback versus 21 months in the electrostimulation group. Biofeedback training is probably superior to electrostimulation in the conservative treatment of anal sphincter insufficiency, this needs to be confirmed in a randomized study.

Adolescent↗

PubMed2003

Decreased detection rate of disseminated tumor cells of rectal cancer patients after preoperative chemoradiation: a first step towards a molecular surrogate marker for neoadjuvant treatment in colorectal cancer.

OBJECTIVE: To compare the detection rates for rectal cancer cells in blood and bone marrow in patients with or without preoperative chemoradiation. SUMMARY BACKGROUND DATA: Previous reports have postulated a resistance of disseminated tumor cells to antiproliferative agents because of tumor cell dormancy. METHODS: Blood samples from 142 patients (pre, intra-, and postoperative samples) and bone marrow samples from 127 patients undergoing resection of rectal adenocarcinoma were analyzed for tumor cells using a cytokeratin (CK) 20-reverse transcription polymerase chain reaction. The results were stratified according to preoperative therapy. RESULTS: In patients without preoperative chemoradiation, tumor cell detection in blood and bone marrow correlated to tumor stage (Cochran Armitage trend test, P < 0.05). Tumor cells were detected in 34 of 103 (33%) bone marrow and 65 of 117 (55.6%) blood samples of patients without neoadjuvant treatment versus in 4 of 24 (16.7%) bone marrow and in 10 of 25 (40%) blood samples of patients with neoadjuvant treatment. The tumor cell detection rate was significantly lower in the group having undergone chemoradiation (binary logistic regression analysis, P < 0.05). The overall and disease-free survival were significantly worse in patients with tumor cell detection in the bone marrow after neoadjuvant therapy. CONCLUSIONS: Preoperative chemoradiation is associated with a decreased detection rate of rectal cancer cells in blood and bone marrow. These findings may explain the observed clinical benefit of patients with rectal cancer receiving chemoradiation. This is the first study suggesting that detection of disseminated rectal cancer cells may be useful for assessing the efficacy of neoadjuvant therapy.

Adenocarcinoma↗

PubMed2002

Are "micrometastases" of the peritoneum equivalent to distant metastases?

Tumor progression after curative resection of gastrointestinal cancer is probably caused by disseminated tumor cells that can be detected in different body compartments, e.g. the peritoneum. The clinical importance and prognostic significance of gross peritoneal metastasis is well known whereas the prognostic relevance of disseminated tumor cells in the peritoneum of patients with gastrointestinal cancer is still unclear. Disseminated tumor cells in the peritoneal cavity are generally detected by cytology, immunohistochemistry or polymerase chain reaction-based molecular methods. A consensus on the most adequate detection method has not yet been found making the comparison of different data difficult. The prognostic relevance of tumor cell dissemination has, at least in part, been shown for gastric, pancreatic and colon cancer, and the prognostic data regarding gastric cancer are most convincing. Peritoneal "micrometastases" are obviously not equivalent to distant metastases as the evidence for their prognostic significance is clearly less than that for gross peritoneal metastases. This article gives a critical review of the detection and prognostic significance of disseminated tumor cells in the peritoneum of patients with gastrointestinal cancer.

Colorectal Neoplasms↗

PubMedDate not supplied

Colorectal cancer.

Every year, more than 945000 people develop colorectal cancer worldwide, and around 492000 patients die. This form of cancer develops sporadically, in the setting of hereditary cancer syndromes, or on the basis of inflammatory bowel diseases. Screening and prevention programmes are available for all these causes and should be more widely publicised. The adenoma-carcinoma sequence is the basis for development of colorectal cancer, and the underlying molecular changes have largely been identified. Prognosis depends on factors related to the patient, treatment, and tumour, and the expertise of the treatment team is one of the major determinants of outcome. New information on the molecular basis of this cancer have led to the development of targeted therapeutic options, which are being tested in clinical trials. Further clinical progress will largely depend on the broader implementation of multidisciplinary treatment strategies following the principles of evidence-based medicine.

Colorectal Neoplasms↗