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Peter Kienle

Publications and source records attributed to Peter Kienle.

At least 19 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

Huge primitive neuroectodermal tumor of the pancreas: report of a case and review of the literature.

Primitive neuroectodermal tumor (PNET) of the pancreas is an extremely rare tumor that usually occurs in children or young adults. We report a case of a 33-year-old male patient with an 18 cm multiply 18 cm multiply 16 cm mass arising from the pancreatic body and tail with a one-day history of abdominal pain. Initial CT scan showed no signs of metastatic tumor spread. The tumor caused intrabdominal bleeding and the patient underwent primary tumor resection including partial gastrectomy, left pancreatic resection and splenectomy. Diagnosis of PNET was confirmed by histology, immunohistochemistry and FISH analysis. All neoplastic cells were stained positive for MIC2-protein (CD99). Approximately one month after surgery, several liver metastases were observed and the patient underwent chemotherapy according to the Euro-Ewing protocol. Subsequent relaparotomy excluded any residual hepatic or extrahepatic abdominal metastases. Although PNET in the pancreas is an extremely rare entity, it should be considered in the differential diagnosis of pancreatic masses, especially in young patients. This alarming case particularly illustrates that PNET in the pancreas although in an advanced stage can present with only a short history of mild symptoms.

12E7 Antigen↗
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

Novel strategy for optimal sequential application of clinical criteria, immunohistochemistry and microsatellite analysis in the diagnosis of hereditary nonpolyposis colorectal cancer.

Clinical criteria, microsatellite analysis (MSA) and immunohistochemistry (IHC) are important diagnostic tools for identification of hereditary nonpolyposis colorectal cancer (HNPCC) patients who are likely to carry pathogenic germline mutations in mismatch repair genes. Based on MSA and IHC results and subsequent mutation analyses of 1,119 unrelated index patients meeting the Amsterdam II criteria or the classical Bethesda guidelines, we analyzed the value of these tools to predict MLH1 and MSH2 mutations with the aim of establishing optimal strategies for their most efficient sequential use. The overall prevalence of pathogenic germline mutations in our cohort was 20.6% (95% CI = 18.3-23.0%) and 61.8% (95% CI = 56.8-66.6%), respectively, after MSA/IHC-based preselection. IHC was highly predictive (99.1%) and specific (99.6%) with regard to MSA. However, 14 out of 230 mutations (6%) escaped detection by IHC. Thus, IHC cannot be recommended to substitute MSA fully. Nonetheless, IHC is important to indicate the gene that is likely to be affected. To combine both methods efficiently, we propose a novel screening strategy that provides 2 alternative ways of sequential IHC and MSA application, either using IHC or MSA in the first place. A logistic regression model based on the age of the index patient at first tumor diagnosis and the number of fulfilled HNPCC criteria is used to allocate individual patients to that alternative pathway that is expected to be least expensive. A cost analysis reveals that about 25% of the costs can be saved using this strategy.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Surgical technique for totally implantable access ports (TIAP) needs improvement: a multivariate analysis of 400 patients.

BACKGROUND: The objective of this study was to analyze factors that may have an impact on the failure rate of the surgical implantation technique for totally implantable access ports (TIAP) and to assess whether morbidity rates differ between a primarily successful surgical and a secondary Seldinger approach. METHODS: Four hundred consecutive patients receiving a primary TIAP in local anesthesia were included into this retrospective cohort study. A logistic regression-model was used to evaluate reasons for failure of the TIAP method. RESULTS: Three hundred eighteen (79.5%) patients had a successful TIAP procedure, 82 patients were intraoperatively converted to a Seldinger technique. Reasons for failure were: correct positioning impossible n = 54, no or only an undersized vessel for insertion available n = 17, other reasons n = 11. Logistic regression analysis did not reveal any significant factor for failure of the primary surgical approach. In the group with primarily successful TIAP, 8 of 318 patients (3%) developed complications compared to 7 of 82 patients (9%) converted to a Seldinger technique. CONCLUSION: Failure of the surgical approach for implanting totally implantable access ports is related to insertion and positioning. Conversion to a Seldinger technique results in a higher complication rate. A modified approach for surgical port placement should be considered in order to reduce complications.

Aged↗
PubMed2006

Influence of intraoperative and postoperative radiotherapy on functional outcome in patients undergoing standard and deep anterior resection for rectal cancer.

PURPOSE: This study was designed to investigate the influence of intraoperative and postoperative radiotherapy on functional outcome after rectal resection for rectal cancer. METHODS: One hundred patients who underwent deep or standard anterior resection for rectal cancer were included in this follow-up study. All patients filled out questionnaires regarding morbidity and functional outcome; a subgroup (n = 63) underwent further clinical evaluation. The results were stratified according to radiation: Group I, no radiation (n = 37); Group II, only intraoperative radiation (n = 12); Group III, intraoperative and postoperative radiation (n = 51). RESULTS: Anal continence measured by Kirwan-Parks classification and Wexner score was significantly different within the three groups (P < 0.005, P < 0.0001), whereas continence impairment was least in Group I and greatest in Group III. Patients in Group III demonstrated a significantly worsecategory in the Kirwan-Parks classification and worse Wexner scores compared with patients in Group I (P < 0.0001). Patients only having undergone intraoperative radiotherapy had a significantly worse continence (Kirwan-Parks classification) than patients without any radiotherapy (P < 0.05). More patients after intraoperative and postoperative radiation therapy complained of fragmented stools (P < 0.05) and urgency (P < 0.05) compared with patients only having undergone surgery; the need to wear pads was higher (P = 0.001). Vector volume manometry revealed better resting sphincter function in Group I compared with Group III (P < or = 0.005). CONCLUSIONS: Patients with anterior resection for rectal cancer who undergo full-dose radiotherapy have significantly more impairment of anorectal function than patients without radiotherapy. Patients who were only exposed to intraoperative radiotherapy showed moderate impairment of continence function, suggesting that the influence of radiotherapy on anal function may be dose-dependent and application-dependent.

Adult↗
PubMed2005

Microsatellite instability of selective target genes in HNPCC-associated colon adenomas.

Microsatellite instability (MSI) occurs in most hereditary nonpolyposis colorectal cancers (HNPCC) and less frequently in sporadic tumors as the result of DNA mismatch repair (MMR) deficiency. Instability at coding microsatellites (cMS) in specific target genes causes frameshift mutations and functional inactivation of affected proteins, thereby providing a selective growth advantage to MMR deficient cells. At present, little is known about Selective Target Gene frameshift mutations in preneoplastic lesions. In this study, we examined 30 HNPCC-associated MSI-H colorectal adenomas of different grades of dysplasia for frameshift mutations in 26 cMS-bearing genes, which, according to our previous model, represent Selective Target genes of MSI. About 30% (8/26) of these genes showed a high mutation frequency (> or =50%) in colorectal adenomas, similar to the frequencies reported for colorectal carcinomas. Mutations in one gene (PTHL3) occurred significantly less frequently in MSI adenomas compared to published mutation rates in MSI carcinomas (36.0 vs 85.7%, P=0.023). Biallelic inactivation was observed in nine genes, thus emphasizing the functional impact of cMS instability on MSI tumorigenesis. Some genes showed a high frequency of frameshift mutations already at early stages of MSI colorectal tumorigenesis that increased with grade of dysplasia and transition to carcinoma. These include known Target Genes like BAX and TGFBR2, as well as three novel candidates, MACS, NDUFC2, and TAF1B. Overall, we have identified genes of potential relevance for the initiation and progression of MSI tumorigenesis, thus representing promising candidates for novel diagnostic and therapeutic approaches directed towards MMR-deficient tumors.

Adenoma↗
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↗
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↗