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Biomedical subjects

P Kienle

Publications and source records attributed to P Kienle.

At least 19 recordsLinked to original sources
PubMed2005

Microsatellite instability in colorectal cancer is associated with local lymphocyte infiltration and low frequency of distant metastases.

Colorectal carcinomas (CRCs) with high microsatellite instability (MSI-H) share clinicopathological features distinctly different from their microsatellite stable (MSS) counterparts. Unlike MSS cancers, MSI-H CRCs occur predominantly in the right-sided colon and are often characterised by a strong lymphocyte infiltration. A poor differentiation pattern is found in most MSI-H CRCs, even though patients with MSI-H carcinomas seem to have a significantly longer survival after surgical resection. To clarify which factors contribute to the obvious paradoxon of a more favourable prognosis of MSI tumours, several clinical and histopathological features as well as the microsatellite status were evaluated in 120 colorectal cancer cases fulfilling clinical criteria (Bethesda) indicative for familial colorectal cancer. Microsatellite instability status and lymphocyte infiltration were related to tumour stage and patients' follow-up. Statistical analysis confirmed well-known relations, such as enhanced lymphocyte infiltration accompanied by Crohn's like reaction (CLR) in MSI-H cancers (CLR+ in 27 out of 47 MSI-H vs 14 out of 71 MSS CRCs, P<0.001). However, after stratification for depth of local invasion and penetration of the primary tumour, T3 tumours displaying MSI had a significantly lower rate of distant metastases (M1 in four out of 35 MSI-H vs 20 out of 41 MSS CRCs, P<0.001). A similar tendency was observed for CLR-positive CRCs (M1 in six out of 29 CLR+ vs 17 out of 45 CLR- CRCs, P=0.13). In a logistic regression model, the MSI-H phenotype and the presence of CLR were independent predictors of a low UICC stage (P=0.006 and 0.04, respectively). These data, together with the recent definition of highly immunogenic neo-antigens expressed in MSI-H tumour cells, suggest that MSI-H CRCs elicit a protective host response that may prevent metastasis formation.

Adult↗
PubMed2005

Laparoscopic restorative proctocolectomy.

BACKGROUND: Restorative proctocolectomy is increasingly being performed using minimally invasive surgery. In published series laparoscopically assisted techniques have usually included a suprapubic incision to enable major parts of the operation to be done openly. METHODS: Fifty consecutive patients with familial adenomatous polyposis or ulcerative colitis underwent laparoscopic restorative proctocolectomy using only a small perumbilical incision of 4 cm or less for vascular dissection and pouch formation; all other steps were performed entirely laparoscopically. Logistic regression was used for statistical analysis. RESULTS: In four patients (8 per cent) the operation was converted to an open procedure. The diagnosis of ulcerative colitis was associated with a higher overall rate of complications (P = 0.011), and an increased body mass index (BMI) with a higher rate of major complications (P = 0.050). The occurrence of wound infection was related to the diagnosis of ulcerative colitis (P = 0.049). Conversion resulted in greater blood loss (P = 0.004), but not in a higher complication rate. No patient required a blood transfusion. Patients with an increased BMI and those taking immunosuppressive therapy had a longer hospital stay (P = 0.043). CONCLUSION: Laparoscopic restorative proctocolectomy is technically feasible. Patients with ulcerative colitis and increased BMI have a higher risk of complications. This minimally invasive technique may reduce the need for perioperative blood transfusion.

Adenomatous Polyposis Coli↗
PubMed2005

[Surgical strategies for the prevention of gastrointestinal tumours].

Over many decades the surgical treatment of gastrointestinal tumours was limited to cases of manifest malignancy and was performed with curative or palliative intent. Molecular diagnostics have now led to an optimised characterisation of different sporadic and hereditary tumour entities. Furthermore, a number of diseases which are an obligatory precancerosis or which carry a very high risk of cancer in their long courses have now been identified. Parallel to these developments, a dramatic reduction of morbidity has been achieved in major abdominal surgery due to more subtle and blood-sparing surgical techniques and mortality has been reduced to a minimum even in the most major procedures. This combination nowadays safely allows preventive or preventive extended surgical measures in cases where interventional therapy cannot be adequately employed.

Adenomatous Polyposis Coli↗
PubMed2004

Precision spectroscopy of pionic 1s states of Sn nuclei and evidence for partial restoration of chiral symmetry in the nuclear medium.

Deeply bound 1s states of pi(-) in (115,119,123)Sn were preferentially observed using the Sn(d,3He) pion-transfer reaction under the recoil-free condition. The 1s binding energies and widths were precisely determined and were used to deduce the isovector parameter of the s-wave pion-nucleus potential to be b1=-(0.115+/-0.007)m(-1)(pi). The observed enhancement of |b(1)| over the free piN value (b(free)1/b1=0.78+/-0.05) indicates a reduction of the chiral order parameter, f*pi(rho)2/f2pi approximately 0.64, at the normal nuclear density, rho=rho(0).

Journal Article↗
PubMed2004

Hematogenous tumor cell dissemination during colonoscopy for colorectal cancer.

BACKGROUND: It has long been suspected that mechanical influences may enhance the release of viable colorectal cancer cells into the circulation. The objective of this study was to determine the extent of hematogenous tumor cell spread in colorectal cancer patients during colonoscopy. METHODS: Peripheral venous blood samples were taken before and after colonoscopy from 44 patients with colorectal cancer. Blood samples were examined using a reverse-transcriptase polymerase chain reaction assay to amplify cytokeratin 20 transcripts. RESULTS: Eleven patients with colorectal cancer displayed circulating tumor cells before and after colonoscopy (25%), whereas tumor cells were detected in six of 44 patients (14%) only after the procedure (p = 0.03, McNemar's test: tumor cell detection before after colonoscopy). All control samples consistently tested negative. CONCLUSIONS: Mechanical forces may result in enhanced release of viable colorectal cancer cells into the circulation; however, the clinical significance of these results needs to be clarified.

Adenocarcinoma↗
PubMed2004

Detection of disseminated tumour cells as a potential surrogate-marker for monitoring palliative chemotherapy in colorectal cancer patients.

In a pilot study the effect of palliative chemotherapy on the detection rates of circulating tumour cells in peripheral venous blood of stage IV colorectal cancer patients was investigated. The results indicate a recruitment of tumour cells during chemotherapy and suggest a poorer survival for tumour cell positive patients. Circulating tumour cells have been shown to be a potential prognostic factor in patients who undergo curative resection for colorectal cancer. The effect of chemotherapy on the detection rates of disseminated tumour cells in blood has not yet been adequately investigated. Objective of this pilot-study was to analyze circulating tumour cells in peripheral venous blood of colorectal cancer patients undergoing chemotherapy in order to evaluate its potential value as a surrogate-marker for predicting clinical outcome after chemotherapy. Our hypothesis was that chemotherapy results in a reduction of the detection rates of circulating tumour cells in colorectal cancer patients. Forty-two Stage IV patients were examined at three different time points before and during palliative chemotherapy for the presence of disseminated tumour cells, using a previously described RT-PCR-assay for cytokeratin 20. 80.1% of the patients showed disseminated tumour cells at least once. Before chemotherapy, patients with multi-organ metastases were positive in 62.5%, patients with locally limited disease in only 14.3%. After the first chemotherapy, the detection rates in the latter group increased to 62.5%, for all patients in the same time from 46.3% to 57.5%. Clinical therapy responders showed an increase in the detection rates from 28.5% before to 71.4% after chemotherapy. In contrast, chemotherapy had no effect on tumour cell detection rates of patients with progressive disease (57% before vs. 60% after therapy). Patients with detected circulating tumour cells showed a shorter overall survival than patients without circulating tumour cells (83 vs. 53 weeks). Clinical therapy responders on average lived only 3 weeks longer than non-responders. In contrast to the original hypothesis, our data suggest a recruiting of circulating tumour cells during chemotherapy in advanced colorectal cancer. Further investigations are needed to clarify the potential role of circulating tumour cells for monitoring chemotherapy in these patients.

Antineoplastic Agents↗
PubMed2003

Accuracy of diagnostic laparoscopy for early diagnosis of abdominal complications after cardiac surgery.

BACKGROUND: In the early postoperative period after major cardiac surgery using extracorporal circulation, abdominal complications can have serious consequences with a mortality rate of up to 70%. Early diagnosis and the timely institution of therapy are the most important factors to improve the outcome; however, clinical evaluation of the abdomen is difficult in these patients. Diagnostic laparoscopy is a minimally invasive procedure with low procedure-associated morbidity, even in critically ill patients. The aims of our study were to investigate the safety of laparoscopy in critically ill patients suspected to have intraabdominal pathology following cardiac surgery and to evaluate the accuracy of diagnostic laparoscopy compared to laparotomy in this setting. METHODS: A total of 17 patients were included (13 male, four female, age 52-80 years) in the early (3-30 days) postoperative period after cardiac surgery using extracorporal circulation (10 ACVB, four valve replacement, one aorto-coronary-venous-bypass (ACVB)+ valve replacement, two cardiac transplantation). Clinical and laboratory findings included distended abdomen (17 of 17), elevated white blood cells (12 of 17), elevated C-reactive protein (CRP) (13 of 17), and elevated lactate levels (11 of 17). The decision to perform laparotomy was taken in all patients on the basis of their clinical condition. Diagnostic laparoscopy was always performed immediately before laparotomy. The laparoscopic findings were then compared to the laparotomy findings. RESULTS: In one patient, laparoscopy showed no abnormal findings, this was confirmed on laparotomy. Five patients were found to have massive distension of the large bowel without ischemia on both laparoscopy and laparotomy. Colonic ischemia of the right hemicolon was found laparoscopically in six patients, which was confirmed in all cases by open resection and histological workup. Three patients suffered from acute cholecystitis, which was correctly diagnosed by laparoscopy in all cases. In one patient, laparoscopy revealed fibrinous peritonitis without other findings. Open exploration failed to identify the cause of the peritonitis in this patient. Laparoscopy showed no pathological findings in one patient, but laparotomy then revealed necrotizing pancreatitis confined to the lesser sac. There was one laparoscopy-associated intraoperative complication (6%) in this series. CONCLUSIONS: Diagnostic laparoscopy is a minimally invasive procedure that can be performed at low intraoperative risk in critically ill patients and has a high sensitivity (94%) for the correct diagnosis of intraabdominal complications after major cardiac surgery. These results suggest that bedside laparoscopy should be considered for all patients with equivocal abdominal symptoms in this setting.

Aged↗
PubMed2003

Laparoscopically assisted colectomy and ileoanal pouch procedure with and without protective ileostomy.

BACKGROUND: Apart from an obviously better cosmetic situation, there is controversy on the actual benefit of laparoscopic and laparoscopically assisted techniques in restorative proctocolectomy. The need for a protective ileostomy remains unclear. METHODS: Fifty-nine consecutive patients with ulcerative colitis and familial polyposis were included in this prospective cohort study. The colon was mobilized laparoscopically with a four-trocar technique, facilitating vascular dissection, rectal resection, and ileoanal pouch construction to be done through a Pfannenstiel incision. A protective ileostomy was constructed only in patients where the operation was difficult or where the anastomosis was under tension. Intra- and postoperative data were recorded; statistical analyses were performed by exact logistic regression. RESULTS: Laparoscopic mobilisation was successful in 54 patients (91.2%). Two patients had to be primarily converted because of exceeding the set time limit; 3 other patients had to have an additional median laparotomy. These 5 patients all had an increased body mass index (BMI), which was a statistically significant risk factor for failure of the laparoscopic technique. 18.6% of patients developed major complications (n = 11). Nine patients required secondary ileostomies; all of them either were under high dose immunosuppressants (n = 5) or had an increased BMI (average 28.42 kg/m2). Failure of the laparoscopic technique was associated with major complications. CONCLUSION: Laparoscopically assisted restorative proctocolectomy is technically feasible; an increased BMI is a relevant risk factor for failure. The minimally invasive approach probably does not reduce the need for a protective ileostomy in selected patients. The selection criteria for the addition or omission of a protective ileostomy in minimally invasive restorative proctocolectomy remain to be clearly defined.

Adenomatous Polyposis Coli↗
PubMed2002

Comparison of laparoscopic versus conventional technique in colonic and liver resection in a tumor-bearing small animal model.

BACKGROUND: Laparoscopic procedures in oncological surgery are either done in curative or palliative intent. We present two experiments comparing laparoscopic to conventional surgery in the curative and palliative setting regarding short-term (stress and immune alteration) and long-term aspects (survival time and recurrence rate). METHODS: We established two syngenic tumor-bearing small animal models for curative liver resection (Morris hepatoma 3924A, ACI rats) and palliative colon resection (BSp73 ASML, BOX rats). Male rats were operated on, performing laparoscopic and conventional liver resection as well as laparoscopic and conventional colon resection; control groups (anesthesia) were included. The following parameters of the stress and immune system were measured: corticosterone, neopterine, Il-1-b, Il-6, and body weight as a parameter of postoperative recovery. Analyzed long-term parameters were survival time, tumor weight, and recurrence rate (histology). RESULTS: After colon resection, analysis of variance showed significant differences in all short-term parameters, including body weight after laparoscopic versus conventional colon resection (p <0.05). In the case of laparoscopic versus conventional liver resection, only Il-6 showed globally statistically significant differences for the short-term parameters (p = 0.05). Long-term parameters were not significantly different between the laparoscopic and conventional groups, regardless of the type of resection (colon or liver) or the operative setting (curative or palliative). However, there were differences after curative liver resection compared to the control group (anesthesia alone). CONCLUSION: These results suggest that the type of intraabdominal operation (colon or liver) may influence the degree of trauma of an operation more than the type of technique (laparoscopic or open). The perioperative alteration of stress and immune function has no implications on the long-term results, such as survival time or recurrence, neither in the curative nor in the palliative setting. The thesis that laparoscopic surgery results in less pain, which in turn means less stress and less alteration of the immune system and therefore results in a lower rate of postoperative metastasis is only valid for laparoscopic colonic resection in our model. The part of the thesis that states that fewer metastases should occur after laparoscopic oncological surgery cannot be confirmed in our study.

Adenocarcinoma↗
PubMed2002

Deeply bound 1s and 2p pionic states in 205Pb and determination of the s-wave part of the pion-nucleus interaction.

We observed well-separated 1s and 2p pi(-) states in 205Pb in the 206Pb(d,3He) reaction at T(d) = 604.3 MeV. The binding energies and the widths determined are B(1s) = 6.762+/-0.061 MeV, Gamma(1s) = 0.764(+0.154)(-0.171) MeV, B(2p) = 5.110+/-0.045 MeV, and Gamma(2p) = 0.321(-0.062)(+0.060) MeV. They are used to deduce the real and imaginary strengths of the s-wave part of the pion-nucleus interaction, which translates into a positive mass shift of pi(-) in 205Pb.

Journal Article↗
PubMed2002

Impact of diagnostic laparoscopy on the management of gastric cancer: prospective study of 120 consecutive patients with primary gastric adenocarcinoma.

BACKGROUND: Peritoneal seeding or liver metastases found at laparotomy usually preclude curative treatment in patients with gastric adenocarcinoma. Such exploratory laparotomies may be avoided by diagnostic laparoscopy. However, routine diagnostic laparoscopy does not benefit those patients who proceed to laparotomy after negative laparoscopy. The aim of this study was to evaluate prospectively the selective use of laparoscopy in uncertain situations. METHODS: One hundred and twenty consecutive patients with primary gastric adenocarcinoma were studied prospectively. Diagnostic laparoscopy was performed in patients with clinical T4 tumours or suspected metastases, unless laparotomy was required for symptomatic disease. RESULTS: Ninety-six of 120 patients were selected for immediate laparotomy with curative intent (n = 81) or for palliation (n = 15). In two of the 81 patients gastrectomy was abandoned because of unexpected peritoneal carcinomatosis. Fifteen patients underwent diagnostic laparoscopy, which identified intra-abdominal metastases in six; the other nine patients proceeded to laparotomy, which revealed peritoneal metastases not detected at laparoscopy in four patients. The remaining nine patients had overt metastases and were referred for systemic chemotherapy without abdominal exploration. CONCLUSION: Diagnostic laparoscopy in selected patients effectively limits the number of unnecessary invasive staging procedures. Routine use of diagnostic laparoscopy in all patients with gastric adenocarcinoma is not warranted.

Adenocarcinoma↗
PubMed2002

Comprehensive genetic counseling for families at risk for HNPCC: impact on distress and perceptions.

The aim of the study was to explore distress and health beliefs before and after comprehensive interdisciplinary counseling in families at risk for hereditary non-polyposis colorectal cancer (HNPCC). Results reported here were derived from a consecutive sample of 65 counselees [31 patients with colorectal cancer (CRC) and 34 unaffected at-risk persons] who participated in interdisciplinary counseling provided by human geneticists, surgeons, and psycho-oncologists before genetic testing. Data were collected from self-administered questionnaires before, as well as 4-6 weeks after, counseling. Distress and perceptions specific to HNPCC were assessed at both timepoints using standardized as well as author-derived instruments. Distress declined after counseling, as did worries related to HNPCC. An increase was found in personal belief in control of cancer risk, for instance, in the perceived efficacy of early detection of CRC. We also observed a trend toward greater anticipated ability to cope with a positive gene test after counseling. Changes after counseling were generally more pronounced for persons at risk, as compared to patients with cancer. The decrease in distress was partly attributable to an increase in personal self-confidence. One-third of the sample reported enhanced communication specific to hereditary disease within the family after counseling. A substantial minority, however, said they experienced increased worry and physical symptoms after counseling. Overall, counselees demonstrated less stress and perceived cancer threat as well as enhanced beliefs regarding personal control over cancer, suggesting an overall beneficial impact of comprehensive counseling. Further research is needed to identify those individuals most at risk for increased fear and worry related to HNPCC so that they may be most appropriately counseled.

Adult↗
PubMed2001

Comparative analysis of tumor cell dissemination in mesenteric, central, and peripheral venous blood in patients with colorectal cancer.

BACKGROUND: Metastatic disease in colorectal cancer results from hematogenic dissemination of tumor cells. This dissemination can be explained by 2 concepts: (1) regional spread of tumor cells via portal venous drainage into the liver as the first site of metastasis and (2) early spread of tumor cells into central and peripheral venous blood as evidence of systemic hematogenic tumor cell dissemination. HYPOTHESIS: Tumor cell detection in different blood compartments could help to understand the predominant pattern of hematogenic tumor cell dissemination in colorectal cancer. DESIGN: Prospective consecutive series. SETTING: University hospital. PATIENTS AND METHODS: Mesenteric, central, and peripheral venous blood samples from 40 patients with colorectal cancer were examined by cytokeratin 20 reverse transcriptase polymerase chain reaction. MAIN OUTCOME MEASURES: Sensitivity and specificity of cytokeratin 20 reverse transcriptase polymerase chain reaction, and frequency of tumor cell detection in different blood compartments. RESULTS: Tumor cells were found in mesenteric venous blood of 20 of 40 patients, central venous blood of 6 of 40 patients, and peripheral venous blood of 2 of 19 patients. The detection rate in mesenteric venous blood was significantly higher than that in central and peripheral venous blood (P<.001). CONCLUSIONS: The significantly higher detection rate in mesenteric venous blood emphasizes the importance of the filter function of the liver for circulating tumor cells in portal venous blood. Tumor cell detection in central and peripheral venous blood, however, shows that this filtering process is limited and indicates early systemic hematogenic tumor cell dissemination in colorectal cancer.

Biomarkers, Tumor↗
PubMed2001

Association of decreased perfusion of the ileoanal pouch mucosa with early postoperative pouchitis and local septic complications.

BACKGROUND: After ileoanal pouch operation, 5% to 40% of patients with ulcerative colitis and 2% to 8% of patients with familial adenomatous polyposis develop pouchitis. Seven percent to 32% of all patients have local septic complications. Pouch ischemia is discussed as a pathophysiologic factor. Tonometry is a minimally invasive method for estimating intramucosal pH (pHi), with a decreased pHi showing intramucosal acidosis characteristic of hypoperfusion. HYPOTHESIS: Decreased perfusion of the iloanal pouch measured by pHi is associated with local septic complications and the development of pouchitis. DESIGN: Prospective cohort study. SETTING: Surgical department of a university hospital. PATIENTS AND METHODS: The pHi in the ileoanal pouch of 98 patients was measured directly after the pouch procedure and correlated to the clinical course. Endoscopic examination of the pouch with biopsy and blinded histologic assessment, including calculation of a histologic pouchitis score, were routinely performed 3 months postoperatively. MAIN OUTCOME MEASURES: Development of pouchitis and local septic complications in correlation to pHi. RESULTS: A decreased pHi was statistically significantly associated with the development of pouchitis and the rate of local septic complications. All 3 patients with anastomotic stenosis had a pHi less than 7.00. The diagnosis of ulcerative colitis just failed in statistical significance as a risk factor for pouchitis. An increased body mass index just failed as a statistically significant risk factor for complications but was a risk factor for the development of acute pouchitis. CONCLUSION: Pouch hypoperfusion is a risk factor for the development of pouchitis and local septic complications.

Adenomatous Polyposis Coli↗
PubMed2001

Minimal residual disease in gastrointestinal cancer.

Tumor progression after curative resection of gastrointestinal carcinomas is probably caused by pre- or intraoperative tumor cell dissemination. Disseminated tumor cells are generally detected by immunohistochemistry- or PCR-based molecular-biology methods. A consensus on which is the most adequate detection method has not yet been found, which makes the comparison of data difficult. The prognostic relevance of disseminated cells has been shown, at least in part, for esophageal, gastric, pancreatic, and colonic cancer. The data regarding hepatocellular cancer is conflicting. This article gives a critical review of tumor cell detection in gastrointestinal cancer.

Gastrointestinal Neoplasms↗
PubMed2001

Evaluation of Bethesda guidelines in relation to microsatellite instability.

PURPOSE: The Bethesda guidelines were developed for selection of patients whose tumors should be tested for high microsatellite instability. This study examined the validity of the different Bethesda criteria in relation to microsatellite instability status to simplify their use in clinical practice. METHODS: A total of 164 patients with colorectal or hereditary nonpolyposis colorectal cancer-associated cancers were registered on the basis of the Amsterdam criteria without age limitations (11 cases), multiple tumors (2 cases), the accumulation of colorectal cancer in the family (no first-degree relatives affected or the index patient's age up to 50 years; 45 cases), an early age at onset up to 50 years (13 cases), morphologic and histopathologic manifestations (right-sided colorectal cancer, mucinous undifferentiated histology; 1 case), and the Bethesda criteria (92 cases). The microsatellite instability status of tumors was determined using the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer marker reference panel. RESULTS: When applying all Bethesda criteria, high microsatellite instability tumors were identified in our hereditary nonpolyposis colorectal cancer registry with a sensitivity of 87 percent. Twenty-nine percent (27/92) of the Bethesda-positive patients displayed high microsatellite instability compared with 6 percent of patients (4/72) not meeting these criteria (P < 0.001). Only Bethesda Criteria 1, 3, and 4 showed a significantly different distribution of the microsatellite instability status when compared with those of the remaining patients registered (P < or = 0.001). These three criteria detected high microsatellite instability tumors in 48 percent (10/21), 50 percent (18/36), and 31 percent (21/67) of patients, respectively. When applying these criteria only, a cumulative detection rate of 77 percent of all (24/31) high microsatellite instability cases was found, thereby identifying 89 percent of high microsatellite instability tumors among the Bethesda-positive patients. Patients matching Criteria 1, 3, and 4 frequently showed hMSH2 or hMLH1 germline mutations and tumor-specific loss of protein expression. CONCLUSION: In our hereditary nonpolyposis colorectal cancer registry the complete Bethesda criteria showed the highest sensitivity to identify patients with high microsatellite instability tumors. However, for general medical practice outside academic centers, three criteria are reasonably accurate for adequate high microsatellite instability tumor selection.

Adult↗
PubMed2001

Sunshine by cooling.

An overview of the development of cooler rings for fast ions with emphasis on electron cooling of heavy ion and radioactive beams is presented. Some of the most important discoveries made with the use of this new experimental tool include the first observation of string-like ordered ion beams, the development of Schottky mass spectrometry for precision mass measurements of radioactive nuclei, the discovery of bound-state beta-decay of highly ionized nuclei and the calibration of the Re/Os cosmochronometer including a determination of the age of our Galaxy. First results of 1 s-state hyperfine interaction, and Lambshift measurements in hydrogen-like heavy ions are presented, together with an outlook on ongoing developments.

Astronomy↗