PubMed Health⌕ Search

Biomedical subjects

Christian Herfarth

Publications and source records attributed to Christian Herfarth.

At least 19 recordsLinked to original sources

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↗

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↗

The vital threat of an upper gastrointestinal bleeding: Risk factor analysis of 121 consecutive patients.

AIM: To analyze the importance in predicting patients risk of mortality due to upper gastrointestinal (UGI) bleeding under today's therapeutic regimen. METHODS: From 1998 to 2001, 121 patients with the diagnosis of UGI bleeding were treated in our hospital. Based on the patients' data, a retrospective multivariate data analysis with initially more than 270 single factors was performed. Subsequently, the following potential risk factors underwent a logistic regression analysis: age, gender, initial hemoglobin, coumarines, liver cirrhosis, prothrombin time (PT), gastric ulcer (small curvature), duodenal ulcer (bulbus back wall), Forrest classification, vascular stump, variceal bleeding, Mallory-Weiss syndrome, RBC substitution, recurrent bleeding, conservative and surgical therapy. RESULTS: Seventy male (58%) and 51 female (42%) patients with a median age of 70 (range: 21-96) years were treated. Their in-hospital mortality was 14%. While 12% (11/91) of the patients died after conservative therapy, 20% (6/30) died after undergoing surgical therapy. UGI bleeding occurred due to duodenal ulcer (n = 36; 30%), gastric ulcer (n = 35; 29%), esophageal varicosis (n = 12; 10%), Mallory-Weiss syndrome (n = 8; 7%), erosive lesions of the mucosa (n = 20; 17%), cancer (n = 5; 4%), coagulopathy (n = 4; 3%), lymphoma (n = 2; 2%), benign tumor (n = 2; 2%) and unknown reason (n = 1; 1%). A logistic regression analysis of all aforementioned factors revealed that liver cirrhosis and duodenal ulcer (bulbus back wall) were associated risk factors for a fatal course after UGI bleeding. Prior to endoscopy, only liver cirrhosis was an assessable risk factor. Thereafter, liver cirrhosis, the location of a bleeding ulcer (bulbus back wall) and patients' gender (male) were of prognostic importance for the clinical outcome (mortality) of patients with a bleeding ulcer. CONCLUSION: Most prognostic parameters used in clinical routine today are not reliable enough in predicting a patient's vital threat posed by an UGI bleeding. Liver cirrhosis, on the other hand, is significantly more frequently associated with an increased risk to die after bleeding of an ulcer located at the posterior duodenal wall.

Adult↗

Differential expression of toll-like receptor 3 and 5 in ileal pouch mucosa of ulcerative colitis patients.

BACKGROUND AND AIMS: The pathogenesis of pouchitis, major complication after restorative proctocolectomy, and ileal J pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is still unclear. Changes in intraluminal bacterial colonization and correlated changes of pouch mucosa are thought to play an important role. Toll-like receptors (TLRs) as part of the innate immune system are capable of recognizing bacterial antigens. Their activation can lead to secretion of proinflammatory mediators. In this study, TLR2, 3, 4, and 5 expression profiles in the pouch mucosa of patients with UC and IPAA were analyzed and correlated with pouchitis. MATERIALS AND METHODS: Clinical symptoms, endoscopy, and histology were assessed in 35 patients using the Heidelberg Pouchitis Activity Score to classify patients as either having pouchitis or not. TLR mRNA expression in normal ileal mucosa and pouch mucosa was investigated by performing semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The results of RT-PCR were associated with the pouchitis score. RESULTS: In the analysis of all patients, TLR3 expression was decreased significantly whereas TLR5 expression was increased significantly in pouch mucosa compared to normal ileal mucosa (p-values 0.0076 and 0.016, respectively). A more detailed analysis upon dividing the patients into patients with and without pouchitis showed decreased TLR3 expression in the pouch mucosa only of patients without pouchitis (p-value=0.0067). TLR5 expression was increased in the pouch mucosa only of patients with pouchitis (p-value=0.023). No differences in TLR2 and 4 expression were found in either group. CONCLUSION: Differential expression of TLR3 and 5 suggests bacterial involvement in the pathogenesis of pouchitis in patients with UC.

Adult↗

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↗

Hepatic platelet and leukocyte adherence during endotoxemia.

INTRODUCTION: Liver microcirculation disturbances are a cause of hepatic failure in sepsis. Increased leukocyte-endothelial interaction, platelet adherence and impaired microperfusion cause hepatocellular damage. The time course and reciprocal influences of ongoing microcirculatory events during endotoxemia have not been clarified. METHODS: Male Wistar rats (232 +/- 17 g) underwent cecal ligation and puncture (CLP). Intravital microscopy (IVM) was performed 0, 1, 3, 5, 10 and 20 hours after CLP. Mean erythrocyte velocity, leukocyte and platelet rolling in postsinusoidal venules and sticking of leukocytes and platelets in postsinusoidal venules and hepatic sinusoids were determined. Heart rate (HR), mean arterial pressure (MAP) and portal venous blood flow (PBF) were measured. Blood count and investigation of hepatic enzyme release was performed after each IVM time point. RESULTS: Hepatic platelet-endothelial adherence in liver sinusoids and postsinusoidal venules occurred one hour after the induction of endotoxemia. Leukocyte-endothelial interaction started three to five hours after CLP. A decrease of hepatic microperfusion could be observed at three hours in sinusoids and ten hours in postsinusoidal venules after CLP, although PBF was reduced one hour after CLP. HR remained stable and MAP decreased ten hours after CLP. Hepatic enzymes in blood were significantly elevated ten hours after CLP. CONCLUSION: Hepatic platelet-endothelial interaction is an early event during endotoxemia. Leukocyte adherence occurs later, which underlines the probable involvement of platelets in leukocyte recruitment. Although PBF is reduced immediately after CLP, the later onset of hepatic microperfusion decrease makes the existence of autoregulatory liver mechanisms likely.

Animals↗

Malignant vascular tumors: clinical presentation, surgical therapy, and long-term prognosis.

BACKGROUND: The aim of this study was to analyze the presentation of, surgery for, and prognosis of malignant vascular tumors (MVTs). METHODS: This was an observational single-center study. Patients who underwent operation for MVTs between 1988 and 2004 were included. Data were gathered prospectively in a computerized registry. RESULTS: Of 568 adult patients with soft tissue malignancies, 43 (7.6%) were treated for MVTs. Twenty-four men and 19 women (median age, 55.3 years) were referred for 30 primary tumors and 13 recurrences. Symptoms were observed in 90.7% of the cases (swelling [37.2%], pain [34.9%], extrusion [11.6%], hemorrhage [7%], weight loss [4.7%], loss of energy [4.7%], impaired function [4.7%], and others [30.2%]). Tumors were located in the extremities (n = 16), trunk (n = 3), abdomen (n = 15), retroperitoneum (n = 7), and thyroid gland (n = 2). Twenty-two (51.2%) angiosarcomas, nine (20.9%) malignant hemangiopericytomas, eight (18.6%) malignant epithelioid hemangioendotheliomas, and four (9.3%) lymphangiosarcomas were seen. The median overall survival after surgery was 21.4 months, with 2-, 5-, and 10-year overall survival rates of 41.5%, 38.3%, and 18.8%, respectively. MVTs of the extremities and trunk and localized disease indicated a better prognosis than abdominal or retroperitoneal MVTs (univariate and multivariate analyses: P = .0122 and P = .0287) and metastasized stages (univariate and multivariate analyses: P = .0187 and P = .0287). CONCLUSIONS: A considerable number of patients with soft tissue malignancies undergo surgery for MVT. Various symptoms and a multilocular occurrence are typical. The course of MVTs is aggressive. Tumor site and stage are important prognostic factors. Surgery is potentially curative, especially for localized disease of the extremities and trunk.

Adult↗

Relationships between volume, efficiency, and quality in surgery--a delicate balance from managerial perspectives.

Volume, efficiency, and quality in hospital care are often mixed in debate. We analyze how these dimensions are interrelated in surgical hospital management, with particular focus on volume effects: under financial constraints, efficiency is the best form of cost control. External perception of quality is important to attract patients and gain volumes. There are numerous explicit and implicit notions of surgical quality. The relevance of implicit criteria (functionality, reliability, consistency, customaziability, convenience) can change in the time course of hospital competition. Outcome data theoretically are optimal measures of quality, but surgical quality is multifactorially influenced by case mix, surgical technique, indication, process designs, organizational structures, and volume. As quality of surgery is hard to grade, implicit criteria such as customizability currently often overrule functionality (outcome) as the dominant market driver. Activities and volumes are inputs to produce quality. Capability does not translate to ability in a linear function. Adequate process design is important to realize efficiency and quality. Volumes of activities, degree of standardization, specialization, and customer involvement are relevant estimates for process design in services. Flow-orientated management focuses primarily on resource utilization and efficiency, not on surgical quality. The relationship between volume and outcome in surgery is imperfectly understood. Factors involve learning effects both on process efficiency and quality, increased standardization and task specialization, process flow homogeneity, and potential for process integration. Volume is a structural component to develop efficiency and quality. The specific capabilities and process characteristics that contribute to surgical outcome improvement should be defined and exported. Adequate focus should allow even small institutions to benefit from volume-associated effects. All volumes-based learning within standardized processes will finally lead to a plateauing of quality. Only innovations will then further improve quality. Possessing volume can set the optimal ground for continuous process research, subsequent change, innovation, and optimization, while volume itself appears not to be a quality prerequisite.

Efficiency, Organizational↗

Results of limb-sparing surgery with vascular replacement for soft tissue sarcoma in the lower extremity.

OBJECTIVE: To evaluate limb-salvage surgery with vascular resection for lower extremity soft tissue sarcomas (STS) in adult patients and to classify blood vessel involvement. METHODS: Subjects were consecutive patients (median age, 56 years) who underwent vascular replacement during surgery of STS in the lower limb between January 1988 and December 2003. Blood vessel involvement by STS was classified as follows: type I, artery and vein; type II, artery only; type III, vein only; and type IV, neither artery nor vein (excluded from the analysis). Patient data were prospectively gathered in a computerized database. RESULTS: Twenty-one (9.9%) of 213 patients underwent vascular resections for lower limb STS. Besides 17 type I tumors (81.0%), 3 (14.3%) type II and 1 (4.7%) type III STS were diagnosed. Arterial reconstruction was performed for all type I and II tumors. Venous replacement in type I and III tumors was performed in 66.7% of patients. Autologous vein (n = 8) and synthetic (Dacron and expanded polytetrafluoroethylene; n = 12) bypasses were used with comparable frequency for arterial repair, whereas expanded polytetrafluoroethylene prostheses were implanted in veins. Morbidity was 57.2% (hematoma, thrombosis, and infection), and mortality was 5% (embolism). At a median follow-up of 34 months, the primary and secondary patency rates of arterial (venous) reconstructions were 58.3% (54.9%) and 78.3% (54.9%). Limb salvage was achieved in 94.1% of all cases. The 5-year local control rate and survival rate were 80.4% and 52%, respectively. We observed a 5-year metastasis-free survival rate of 37.7% and found vessel infiltration and higher tumor grade (low-grade vs intermediate grade and high grade tumors) to be negative prognostic factors at univariate and multivariate analysis. CONCLUSIONS: Long-term bypass patency rates, the high percentage of limb salvage, and the oncologic outcome underline the efficacy of en bloc resection of STS involving major vessels in the lower limb. Disease-specific morbidity must be anticipated. The classification of vascular involvement (type I to IV) is useful for surgical management.

Algorithms↗

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↗

Prognostic significance of preoperative [18-F] fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in patients with resectable soft tissue sarcomas.

OBJECTIVE: The objective of this study was to evaluate the prognostic significance of preoperative positron emission tomography (PET) using 2-fluoro-2-deoxy-D-glucose (FDG) by calculating the mean standardized uptake values (SUV) in patients with resectable soft tissue sarcomas (STS). SUMMARY AND BACKGROUND DATA: FDG-PET might be used as an adjunctive tool (in addition to biopsy and radiologic tomography) in the preoperative prognostic assessment of resectable STS. METHODS: A total of 74 adult patients with STS underwent preoperative FDG-PET imaging with calculation of the SUV. Clinicopathologic data and the SUV were analyzed for an association with the clinical outcome. The first and the third quartiles of the SUV distribution function were used as cutoff values (1.59 and 3.6). Survival was estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using log-rank test and the Cox proportional hazards regression model. RESULTS: In 55 cases, STS were completely resected (follow up 40 months): 5-year recurrence-free survival rates in patients with SUV <1.59, 1.59 to <3.6, and > or =3.6 were 66%, 24%, and 11%, respectively (P = 0.0034). SUV was a predictor for overall survival (5-year rates: 84% [SUV <1.59], 45% [SUV 1.59 to <3.6], and 38% [SUV > or =3.6]; P = 0.057) and local tumor control (5-year rates: 93% [SUV <1.59], 43% [SUV 1.59 to <3.6], and 15% [SUV > or =3.6]; P = 0.0017). By multivariate analysis, SUV was found to be predictive for recurrence-free survival. The prognostic differences with respect to the SUV were associated with tumor grade (P = 0.002). CONCLUSION: The semiquantitative FDG uptake, as measured by the mean SUV on preoperative PET images in patients with resectable STS, is a useful prognostic parameter. SUV with cutoff values at the first and the third quartiles of the SUV distribution predicted overall survival, recurrence-free survival, and local tumor control. Therefore, FDG-PET can be used to improve the preoperative prognostic assessment in patients with resectable STS.

Adult↗

Acceptance of and attitude toward genetic testing for hereditary nonpolyposis colorectal cancer: a comparison of participants and nonparticipants in genetic counseling.

PURPOSE: Data on the actual uptake of genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC) in a clinical sample is still inconclusive. The present study aimed to define the actual uptake of genetic counseling and testing offered to an unselected sample of 140 patients with colorectal cancer, fulfilling clinical criteria (Amsterdam or Bethesda) suggestive of HNPCC, and to identify demographic and psychosocial factors associated with the decision to participate in counseling. METHODS: Cross-sectional survey. Eligible subjects had been consecutively enrolled in a regional tumor registry between 1994 and 1998, and were invited to attend an information session for HNPCC at the time genetic testing for HNPCC became available. Participants and nonparticipants in the information session completed a short questionnaire. RESULTS: The actual uptake rate of the information session in this sample was 26 percent. Participants and nonparticipants were comparable with regard to clinical criteria suggestive of HNPCC, awareness of the potential hereditary predisposition, and previous history of cancer in the family. Some 60 percent of participants experienced pronounced distress related to their potential inheritance of the disorder, compared to 35 percent among nonparticipants. Distress reached a clinically significant level in 28 percent of participants. Restricted communication within the family was observed frequently. Irrespective of groups, a positive attitude toward obtaining a gene test result predominated. CONCLUSIONS: Results suggest that expressed intention and attitude toward genetic testing do not reliably predict actual uptake of counseling or testing. Thorough interdisciplinary counseling should be provided to every patient with clinical criteria suggestive of HNPCC. The considerable distress related to the hereditary disorder should be adequately addressed, as should be communication issues.

Adult↗

C1-inhibitor reduces hepatic leukocyte-endothelial interaction and the expression of VCAM-1 in LPS-induced sepsis in the rat.

INTRODUCTION: Increased leukocyte-endothelial interaction (LEI) leading to hepatic microperfusion disorders is proposed as major contributor for hepatic failure during sepsis. Recently it has been demonstrated that complement inhibition by C1-inhibitor (C1-INH) is an effective treatment against microcirculatory disturbances in various diseases. The purpose of this study was to investigate the influence of C1-INH on microcirculation and LEI in the liver in a rat model of sepsis. MATERIALS AND METHODS: Rats received lipopolysaccharides (LPS) from Escherichia coli intravenously. Controls received Ringer solution only. Ninety minutes after LPS infusion some animals were treated with C1-INH intravenously (LPS + C1-INH). Others (LPS + SC) and controls (Ringer + SC) received sodium chloride (SC). Hepatic LEI and mean erythrocyte velocity (MEV) were quantified by intravital microscopy (IVM) 90 min after LPS or Ringer infusion (0) and 30, 60, 90 and 120 min following treatment. VCAM-1 m-RNA in hepatic tissue, C3a, TNF-alpha and hepatic enzyme liberation in blood was analysed. RESULTS: Leukocyte sticking to the endothelial wall in postsinusoidal venules was significantly reduced in the LPS + C1-INH vs. the LPS + SC group 30, 60, 90 and 120 min after treatment. VCAM-1 m-RNA expression in the hepatic tissue was markedly and C3a levels in plasma were significantly reduced in the LPS + C1-INH vs. the LPS + SC group. No differences in TNF-alpha levels were detected between these two groups. MEV was improved in the LPS + C1-INH vs. the LPS + SC group. CONCLUSIONS: Our results indicate that even upon delayed treatment hepatic adhesion molecule expression and LEI can be reduced by C1-INH. The multifunctional regulator may reduce hepatic microcirculatory disturbances during sepsis under clinical conditions.

Animals↗

Effects of hemodynamic instability on brain death-induced prepreservation liver damage.

BACKGROUND: Brain death (BD) is an important multifactorial variable contributing to donor-specific liver damage. Our study aimed at assessing the specific effects of hemodynamic instability on systemic and hepatic parameters of perfusion, bowel ischemia, and oxidative stress in a porcine model of BD. METHODS: BD was induced in 16 pigs (German Landrace, 18-28 kg) in two groups (hypotension-BD [HYPO-BD], n=8; normotension-BD [NORM-BD], n=8), which were compared with control animals/living donors (n=6) for a period of 2 hr. We analyzed systemic hemodynamic parameters, bowel ischemia (intramucosal pH in the stomach and colon, plasma endotoxin levels, and endotoxin-neutralizing capacity [ENC]), and oxidative stress (total glutathione levels in erythrocytes) and compared the findings with hepatic parameters of perfusion (hepatic arterial flow, portal venous flow, and microperfusion) and liver oxidative stress (reduced glutathione and oxidized glutathione levels in the liver). RESULTS: Independent of the hemodynamic stability, liver macrocirculation and microcirculation decreased (HYPO-BD, 79+/-6 to 69+/-10 mL/100 g/min; NORM-BD, 81+/-10 to 73+/-7 mL/100 g/min; P<0.05). Hepatocellular damage (aspartate aminotransferase: NORM-BD, 49+/-20 units/L; HYPO-BD, 170+/-140 units/L; P<0.01) and hepatic oxidative stress (reduced glutathione in the liver/oxidized glutathione in the liver: NORM-BD, 29.4+/-2.3 to 13.0+/-1.3; HYPO-BD, 29.4+/-2.3 to 9.05+/-0.81; P<0.001) increased in both BD groups. With dependence on systemic hemodynamic parameters, bowel ischemia increased (intramucosal pH in the colon, 7.22+/-0.01, P<0.01; ENC, 75+/-14 endotoxin-neutralizing units/mL, P<0.01; endotoxin levels, 7+/-2 to 43+/-10 pg/mL, P<0.01) in the HYPO-BD group but not in the NORM-BD group or the living donor group. Furthermore, systemic oxidative stress was increased in the HYPO-BD group only (total glutathione levels in erythrocytes, 2.65+/-0.25 to 0.15+/-0.25 mM; P<0.01). CONCLUSIONS: During BD, liver-specific parameters (portal venous flow, microperfusion, aspartate aminotransferase activity, ENC, and hepatic oxidative stress) were compromised, independent of the hemodynamic status. Therefore, the systemic hemodynamic status does not reflect the functional status of the liver during BD.

Animals↗

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↗

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↗