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ABSTRACT: Interleukin-10 (IL-10) treatment has been shown to have beneficial effects on the immune function after hemorrhagic shock and to improve survival after subsequent sepsis in young male mice, but not in young females. Although it was demonstrated that the immune function under these conditions is reversed with age, it remains unclear whether the observed gender-related effect of IL-10 treatment continues to exist in aged mice.
Aged male and female CBA/J mice (18-19 months) were subjected to hemorrhage (35 +/- 5 mmHg for 90 min) or sham operation. At resuscitation, each received either 10-microg recombinant murine (rm)IL-10 or placebo i.p. At 48 h after resuscitation, either the mice were killed and the plasma, splenic macrophages (sM phi), and splenocytes were harvested or polymicrobial sepsis was induced by cecal ligation and puncture (CLP). After CLP, either survival over 10 days was determined or, 4 h after CLP, tissues were again harvested and cytokine-released in vitro were assessed by enzyme-linked immunosorbent assay.
Early IL-10 treatment restored depressed proinflammatory immune response (TNF-alpha, IL-1 beta) and Th1 response of splenocytes in aged females after hemorrhage, whereas having no effects or having suppressive effects in aged males. Subsequent sepsis combined with placebo treatment led to a significant suppression of proinflammatory cytokine release of sM phi and a significant increase of Th2 response in both males and females associated with high mortality (80-100%, respectively) after CLP. These effects were not influenced by early rmIL-10 treatment.
After hemorrhage, early rmIL-10 treatment restored immune function in aged females, but not in males. However, in contrast to young mice, rmIL-10 treatment had no effect on survival and immune function after CLP in aged mice.
Langenbeck s Archives of Surgery 10/2007; 392(5):629-38. · 1.81 Impact Factor
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Clemens Schafmayer,
Stephan Buch,
Jan Hendrik Egberts,
Andre Franke,
Mario Brosch,
Abdou El Sharawy,
Mareike Conring,
Maralde Koschnick,
Sven Schwiedernoch,
Alexander Katalinic, Bernd Kremer,
Ulrich R Fölsch,
Michael Krawczak,
Fred Fändrich,
Stefan Schreiber,
Jürgen Tepel,
Jochen Hampe
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ABSTRACT: Mutations in DNA repair genes have previously been identified as causative factors for hereditary nonpolyposis colon cancer (HNPCC). Recent evidence also supports an association between DNA sequence variation in these genes and sporadic colorectal carcinoma (CRC). Genetic investigation of DNA repair genes PMS2, MLH1, MSH2, MSH6, MUTYH, OGG1 and MTH1, as possible susceptibility factors for sporadic CRC, was done using both a haplotype tagging and a candidate (i.e. coding) single nucleotide polymorphism (SNP) approach. Some 1,068 patients with operated CRC (median age at diagnosis: 59 years) were compared to 738 sex-matched control individuals (median age: 67 years). Haplotype tagging SNPs, previously reported risk variants and all known coding SNPs with a minor allele frequency >0.005 were genotyped in PMS2 (N = 10), MLH1 (N = 11), MSH2 (N = 18), MSH6 (N = 15), MUTYH (N = 7), OGG1 (N = 11) and MTH1 (N = 3). No evidence for an association between CRC and any of the 7 genes was detected, neither with the tagging or coding SNPs nor in a sliding window haplotype analysis (all nominal p-values >0.05). The previously reported risk variants D132H in MLH1 and R154H in OGG1 were not even observed in the German population. Genetic CRC risk factors so far identified in DNA repair genes seem to be rare and population-specific. Their association with the disease could not be replicated in German CRC samples. It remains to be elucidated by more systematic, large-scale experiments whether common variants in the same genes, but present across populations, represent risk factors for sporadic CRC.
International Journal of Cancer 08/2007; 121(3):555-8. · 5.44 Impact Factor
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Clemens Schafmayer,
Jürgen Tepel,
Andre Franke,
Stephan Buch,
Sören Lieb,
Marcus Seeger,
Frank Lammert, Bernd Kremer,
Ulrich R Fölsch,
Fred Fändrich,
Stefan Schreiber,
Jochen Hampe
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ABSTRACT: Genetic susceptibility in the causation of gallbladder diseases was recognized as early as 1937. A major gallstone susceptibility locus (Lith1) was identified in 1995 by quantitative trait locus mapping in mice. Two attractive positional and functional candidate genes in LXRA and ABCB11 are located in this interval. ABCB11 is associated with progressive familial cholestasis. This study was undertaken to investigate LXRA and ABCB11 as candidate genes for gallstone disease in humans. Eight hundred and ten patients who underwent cholecystectomy for symptomatic gallstone disease (median age of onset, 50 years) were compared with 718 sex-matched control individuals. Control individuals were sonographically free of gallstones. Haplotype tagging and all known coding single nucleotide polymorphisms (SNPs) were genotyped for ABCB11 (n=29) and LXRA (n=10). The investigated high-risk patient sample provides a power of greater than 80% for the detection of odds ratios down to 1.55. No evidence of association of the two genes in the single point tagging markers, coding variants or in the sliding window haplotype analysis was detected (all nominal single-point P values>or=.08). In conclusion, in the investigated German sample, no evidence of association of ABCB11 and LXRA to gallstone susceptibility was detected. The gallstone trait is not allelic to progressive familial cholestasis at the ABCB11 locus. Systematic fine mapping of the Lith1 region is required to identify the causative genetic variants for gallstone in mice and humans.
Hepatology 09/2006; 44(3):650-7. · 11.66 Impact Factor
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ABSTRACT: The prognosis of digestive cancers is poor mainly due to intraperitoneal relapse by cells which may have already been seeded at the time of surgery. Using immunocytology we investigated the peritoneal cavity and, as a comparison, the bone marrow of 147 patients with gastric, colorectal and pancreatic cancer for micrometastatic cells. Cytological samples from peritoneal cavity lavages and bone marrow aspirates were analyzed using monoclonal antibodies (MAbs) against tumor-associated antigens (TAA) (CEA, CA-19-9, 17-1-A, C-54-0, Ra96) and compared to a MAb staining cytokeratins (KL-I). Patients with benign diseases served as controls.Intraperitoneal micrometastatic cells were detected in 27% of colorectal, 43% of gastric and 58% of pancreatic cancer patients. In the bone marrow, the corresponding data were 29% for colorectal, 25% for gastric and 58% for pancreatic cancer patients. Combined evaluation of both compartments increased the detection rate significantly (colorectal cancer: 40%, gastric cancer: 52%, pancreatic cancer: 72%). No unwarranted reactions were found in the control group. Combining 3 antibodies (CA-19-9, Ra96, C-54-0) enabled good detection for peritoneal cavity samples. In the bone marrow, the use of 2 antibodies (KL-I and CA-19-9) detected 94% of all positive samples, whereas KL-I and CA-19-9 stained approx. 70% of all positive samples in each case. The occurence of stained cells in the peritoneal cavity correlated with classical prognostic factors (TNM classification). © 1994 Wiley-Liss, Inc.
International Journal of Cancer 07/2006; 57(3):330 - 335. · 5.44 Impact Factor
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ABSTRACT: Anti-cancer therapy in pancreatic ductal adenocarcinoma (PDAC) is mostly based on surgical removal or palliative therapy using antimetabolites, like 5'-fluorouracil or gemcitabine. Adjuvant treatment using these chemotherapeutics has recently proven a beneficial concept, though general survival rates are still poor. Most recently, combination therapy of gemcitabine with other targeted drugs was evaluated in clinical trials. We present here a study performed in a mouse orthotopic xenotransplant model of PDAC, using an oligo-nucleotide-based approach. We have shown previously that antisense oligonucleotides against p53 reduce the weight of orthotopic pancreatic tumours in immune-deficient mice. We further characterised terminal modifications of phosphorothioate oligonucleotides in vitro and found a random, unrelated control sequence carrying a D,L-alpha-tocopherol modification at the 5' and 3' ends to be most efficient in induction of cell death in PancTu-1 cells. Modified random oligonucleotide (MRON) were thus further tested in vivo. MRON showed a reduction of tumour weight in established primary orthotopic tumours in SCID/bg mice. In a surgically adapted pre-clinical model, where primary tumours were resected and animals received adjuvant treatment, MRON was very efficient in suppression of relapse and metastasis, when combined with gemcitabine. While the exact molecular mechanism of MRON activity still needs to be elucidated, the compound showed a remarkable preference for uptake into tumour cells in vivo.
International Journal of Oncology 06/2006; 28(5):1105-12. · 2.40 Impact Factor
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ABSTRACT: The high rate of local recurrence after radical resection of pancreatic adenocarcinoma fosters intensive efforts to develop new approaches for adjuvant treatment. The established animal models show significant limitations in simulating an adjuvant therapeutic setting. For optimal approximation to the clinical situation we therefore improved a murine orthotopic human xenotransplantation model.
Subtotal pancreatectomy in mice was performed after orthotopic inoculation of human pancreatic cancer cells and manifestation of solid tumours. The natural course of disease, tumour growth and metastases were analysed. Gemcitabine as a cytotoxic drug was tested in vitro on the cell line used in this model and the effect of adjuvant treatment with gemcitabine in vivo was investigated.
All tumour-resected animals showed local recurrence. Organ metastases occurred in 67% in resected compared to 25% of non-resected animals. Gemcitabine in vitro was ineffective, but as adjuvant monotherapy resulted in a highly significant reduction of tumour weight and metastatic events.
Subtotal pancreatectomy for xenotransplanted pancreatic cancer in SCID beige mice is feasible. Due to high rates of local recurrence and increased organ metastases, this model offers a relevant option for preclinical adjuvant testing, especially as in vitro and in vivo effects of cytotoxic drugs differ enormously.
Pancreatology 02/2006; 6(3):240-7. · 1.99 Impact Factor
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ABSTRACT: To determine how quality of life changes over time and to assess gender-related differences in quality of life of rectal cancer patients we conducted a 5-year study. Little is known about how quality of life (QoL) changes over time in patients after surgery for rectal cancer, and whether gender of the patients is associated with a different perception of QoL. The aim of this study was to assess prospectively, changes in quality of life after surgery for rectal cancer, with a focus on gender related differences. Over a 5-year period, the EORTC-QLQ-C-30 and a tumor-specific module were prospectively administered to patients before surgery, at discharge, 3, 6, 12, and 24 months postoperatively. Comparisons were made between female and male patients. A total of 519 patients participated in the study, 264 men and 255 women. The two groups were comparable in terms of surgical procedures, adjuvant treatment, tumor stage, and histology. Most QoL scores dropped significantly below baseline in the early postoperative period. From the third month onward, global health, emotional and physical functioning, improved. Female gender was associated with significantly worse global health and physical functioning and with higher scores on treatment strain and fatigue. Men reported difficulties with sexual enjoyment; furthermore, over time, sexual problems created high levels of strain in men, worse than baseline levels in the early postoperative period. These problems tended to continue over the course of time. The findings in this study confirm that QoL changes after surgery and differs between men and women. Women appear to be affected by impaired physical functioning and global health. Female gender is associated with significantly higher fatigue levels and increased strain values after surgery. Through impaired sexual enjoyment, men are put more under strain than woman.
World Journal of Surgery 01/2006; 29(12):1630-41. · 2.36 Impact Factor
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Clemens Schafmayer,
Jürgen Hartleb,
Jürgen Tepel,
Stefan Albers,
Sandra Freitag,
Henry Völzke,
Stephan Buch,
Markus Seeger,
Birgit Timm, Bernd Kremer,
Ulrich R Fölsch,
Fred Fändrich,
Michael Krawczak,
Stefan Schreiber,
Jochen Hampe
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ABSTRACT: Gallstones represent a prevalent and costly health problem. The changing epidemiology and the emerging non-surgical interventions for gallstone disease necessitate the definition of target populations for future therapies. This study aimed to define patterns of gallstone composition and identify demographic predictors of gallstone composition in a large sample of symptomatic gallstones from Northern Germany.
One thousand and seventy-four post-cholecystectomy gallstone specimens were obtained. Demographic and clinical information was provided by questionnaire (N = 1025 independent individuals with complete information). Two samples from each gallstone were analyzed using Fourier transformed infrared spectrometry.
The most prevalent substance was cholesterol, which was detected in 95.0% of gallstone specimens. Bilirubin and bilirubinate were present in 30.0% and calcium was detected in 10.0% of the spectra. Ninety-two percent of measurements from the same stone yielded the same "main" substances, indicating a homogenous stone composition in most cases. Female sex and higher body mass index (BMI) were associated with the presence of cholesterol as a main substance in the gallstones (p < 0.001).
The changing epidemiology of gallstone disease is reflected by a marked shift in stone composition: Only two percent of stones in this study were pigment stones as compared to 91% percent of stones containing cholesterol as a main substance. Obese individuals from Germany with a BMI > 30 kg/m2 have in 95% cholesterol-dominant gallstones and represent a potential target population for non-surgical interventions for the prevention or treatment of cholesterol stones.
BMC Gastroenterology 01/2006; 6:36. · 2.42 Impact Factor
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ABSTRACT: A new multimodality treatment concept consisting of extended resection and postoperative fractionated intensity-modulated interstitial brachytherapy (IMBT) was introduced for pelvic recurrence of colorectal carcinoma.
46 patients received extended resection and single plastic tubes were sutured directly onto the tumor bed. IMBT was started within 2 weeks postoperatively with a median dose of 24.5 Gy (5-35 Gy). Patients were treated either with high-dose-rate brachytherapy (HDR; n = 23) or with pulsed-dose-rate brachytherapy (PDR; n = 23). 25 patients received complementary 45-Gy external-beam irradiation (EBRT) to the pelvic region after explanting the plastic tubes.
Median follow-up was 20.6 months (7-107 months) and mean patient survival 25.7 +/- 25.8 months (median 17, range 1-107 months). After 5 years overall survival, disease-free survival and local control rate were 23%, 20% and 33%, significantly influenced by the resectional state. There was a trend in favor of PDR compared to HDR, which reached statistical significance in patients who had not received additional EBRT.
The combination of extended surgery and postoperative interstitial IMBT is feasible and offers effective interdisciplinary treatment of recurrent colorectal cancer. In this small and inhomogeneous cohort of patients PDR seems to be more effective than HDR, particularly when application of complementary EBRT is not possible. None of the patients who required resection of distant metastasis survived > 2 years in this study.
Strahlentherapie und Onkologie 12/2005; 181(11):696-703. · 3.56 Impact Factor
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ABSTRACT: This prospective study evaluates the diagnostic potential of Cytokeratin 20 (CK 20) RT-PCR for the detection of disseminated tumor cells in bone marrow and blood of a large cohort of patients with ductal adenocarcinoma of the pancreas and the prognostic value on overall survival prediction.
Between 1994 and 2003, 172 patients (83 male, 89 female; 13-82 years) with pancreatic ductal adenocarcinoma underwent surgery. Bone marrow samples and venous blood were taken preoperatively and analyzed for disseminated tumor cells by nested CK 20 RT-PCR.
Disseminated tumor cells were detected in 81 (47.1%) of the 172 patients in the bone marrow and/or the venous blood. Overall, in 45 of the 135 (33.3%) bone marrow samples and in 52 of the 154 (33.8%) blood samples, CK 20 positive cells were detected. Detection rates increased with the UICC-tumor stage. According to Kaplan-Meier, univariate survival analysis of all 172 patients (n = 78 R0-; n = 18 R1- and n = 5 R2-resected; n = 71 palliative surgery) showed a statistically significant relationship of overall survival to radicality of the operation (P < 0.0001), the UICC-stage of the tumors (P = 0.0011) and the detection of disseminated tumor cells in bone marrow and/or venous blood (P = 0.05). Patients with well- and moderately- differentiated tumors (G1 and G2) had a significantly longer survival (P = 0.045) than patients suffering from poorly differentiated tumors (G3). A positive CK 20 status in the bone marrow and/or blood within the group of patients with G1 and G2 tumors had a significantly negative prognostic impact on their survival (P = 0.046).
Disseminated tumor cells can be detected in patients with pancreatic ductal adenocarcinoma by CK 20 RT-PCR. Detection rates are stage dependent, and survival analysis demonstrated statistically relevant data. From a clinical point of view, this finding is especially noteworthy for the group of well- and moderately-differentiated tumors.
Journal of Cancer Research and Clinical Oncology 11/2005; 131(10):669-76. · 2.56 Impact Factor
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Maren Ruhnke,
Hendrik Ungefroren,
Andreas Nussler,
Franz Martin,
Marc Brulport,
Wiebke Schormann,
Jan G Hengstler,
Wolfram Klapper,
Karin Ulrichs,
James A Hutchinson,
Bernat Soria,
Reza M Parwaresch,
Peter Heeckt, Bernd Kremer,
Fred Fändrich
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ABSTRACT: Adult stem cells provide a promising alternative for the treatment of diabetes mellitus and end-stage liver diseases. We evaluated the differentiation potential of human peripheral blood monocytes into hepatocyte-like and pancreatic islet-like cells.
Monocytes were treated with macrophage colony-stimulating factor and interleukin 3 for 6 days, followed by incubation with hepatocyte and pancreatic islet-specific differentiation media. Cells were characterized by flow cytometry, gene-expression analysis, metabolic assays, and transplantation for their state of differentiation and tissue-specific functions.
In response to macrophage colony-stimulating factor and interleukin 3, monocytes resumed cell division in a CD115-dependent fashion, which was associated with a down-regulation of the PRDM1 and ICSBP genes. These programmable cells of monocytic origin were capable of differentiating into neohepatocytes, which closely resemble primary human hepatocytes with respect to morphology, expression of hepatocyte markers, and specific metabolic functions. After transplantation into the liver of severe combined immunodeficiency disease/nonobese diabetic mice, neohepatocytes integrated well into the liver tissue and showed a morphology and albumin expression similar to that of primary human hepatocytes transplanted under identical conditions. Programmable cells of monocytic origin-derived pancreatic neoislets expressed beta cell-specific transcription factors, secreted insulin and C peptide in a glucose-dependent manner, and normalized blood glucose levels when xenotransplanted into immunocompetent, streptozotocin-treated diabetic mice. Programmable cells of monocytic origin retained monocytic characteristics, notably CD14 expression, a monocyte-specific methylation pattern of the CD115 gene, and expression of the transcription factor PU.1.
The ability to reprogram, expand, and differentiate peripheral blood monocytes in large quantities opens the real possibility of the clinical application of programmable cells of monocytic origin in tissue repair and organ regeneration.
Gastroenterology 07/2005; 128(7):1774-86. · 11.68 Impact Factor
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ABSTRACT: There is growing interest in new therapeutic options for the treatment of end-stage liver diseases. In addition to mechanical devices supporting liver function, such as bioreactors, the transplantation of hepatocyte-like cells derived from (adult) stem cells offer great perspectives. We have generated hepatocyte-like (NeoHep) cells from terminally differentiated peripheral blood monocytes and, in this study, have evaluated these cells as a possible tool for autologous cell therapy.
Peripheral blood monocytes were cultured under conditions that promote hepatocyte-like differentiation and were characterized for hepatocyte marker expression by reverse-transcriptase polymerase chain reaction, immunohistochemistry, and immunoblotting and for specific secretory and metabolic functions with the appropriate biochemical assays.
NeoHep cells resembled primary human hepatocytes with respect to morphology, expression of hepatocyte markers (albumin, cytochrome P450 isoenzymes, asialoglycoprotein receptor, coagulation factor VII), various secretory and metabolic functions (albumin secretion, urea production, lactate formation, and lactate dehydrogenase and aspartate transaminase release), and drug detoxification activities (phase I metabolization of ethoxycoumarin into 7OH-coumarin after stimulation with 3-methylcholanthren, induction of CYP3A4 activity, and phase II metabolization through UDP-glucuronidation of 4-methyl-umbelliferone).
These data convincingly show that NeoHep cells display a phenotype and specific in vitro metabolic functions that are quantitatively and qualitatively comparable in part with those of primary human hepatocytes. These cells could thus be clinically applied in an autologous setting for the treatment of end-stage liver diseases or for improving liver function in patients who have undergone critical liver-mass resection.
Transplantation 06/2005; 79(9):1097-103. · 4.00 Impact Factor
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ABSTRACT: In various studies, type of surgery, age, and gender had different impact on sexuality and quality of life in patients with rectal cancer. This study was designed to investigate how sexuality and quality of life are affected by age, gender, and type of surgery.
A total of 516 patients who had undergone surgery for rectal cancer in our department from 1992 to 2002 were included. Within one year after the operation, 117 patients died. Questionnaires were sent to 373 patients 12 to 18 months after surgery. We received quality of life data from 261 patients. Comparisons were made after adjusting age, gender, and type of surgical procedure.
For patients receiving abdominoperineal resection sexuality was most impaired. Significant differences were seen in symptom and function scales between males and females. Females reported more distress from the medical treatment insomnia, fatigue, and constipation. Both genders had impaired sexual life; however, males had significantly higher values and felt more distressed by this impairment. Younger females felt more distress through impaired sexuality. In males sexuality was impaired independent of age. Adjuvant therapy had no influence on sexuality but on quality of life one year after surgery.
Assessing quality of life with general and specific instruments is helpful to determine whether patients improved through the treatment. The study showed that gender, age, and type of surgery influence sexuality and that quality of life after surgery for rectal cancer is impacted. Because quality of life is a predictor for complications and survival, availability of such data may help to direct supportive treatment to improve outcome.
Diseases of the Colon & Rectum 04/2005; 48(3):483-92. · 3.13 Impact Factor
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ABSTRACT: Study results on quality of life (QoL) between patients receiving an anterior resection (AR) or abdominoperineal resection (APR) for rectal cancer vary greatly. A main reason is grounded in unequal methodology. The aims of this study were to assess differences in perceived QoL over time among patients treated with AR or APR with a recommended study design and methodology.
In a prospective study, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and a tumor-specific module were administered to patients with rectal cancer before surgery, at discharge, and 3, 6, and 12 months after the operation. Comparisons were made between patients receiving an AR and those receiving an APR.
Two hundred forty-nine patients were included; 46 patients received an APR and 203 an AR. QoL data were available for 212 patients, of which 112 were female and 100 male. No differences in the distribution of age, sex, or tumor stage were observed between groups. EORTC function scales showed no significant differences, including body image scales, between patients receiving an AR and those receiving an APR. In symptom scores, AR patients had more difficulty with diarrhea and constipation, whereas patients with APR experienced more impaired sexuality and pain in the anoperineal region. At discharge, patients receiving an AR were more confident about their future.
QoL in patients receiving an AR and those receiving an APR is not different. Although patients with APR experience more impaired sexuality, patients receiving an AR experience decreases in QoL because of impaired bowel function.
Annals of Surgical Oncology 03/2005; 12(2):117-23. · 4.17 Impact Factor
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ABSTRACT: Some studies indicate that age at the time of surgery has a general effect on outcomes. The impact of age on the quality of life (QOL) of patients with rectal cancer, however, has not been investigated. The present study was conducted to address this issue. Over a 5-year period the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C-30 and a tumor-specific module were prospectively administered to patients before surgery, at discharge, and at 3, 6, 12, and 24 months postoperatively. Comparisons were made between age groups. A total of 519 patients participated in the study. QOL data were available for 253 patients. Significant differences were observed only between patients aged 69 years and younger (< or =69 years) (169/253) and those aged 70 years and older (> or =70 years) (85/253). Physical and role functioning was better for patients < or =69 years; patients > or =70 years suffered from increased pain and fatigue. Younger patients had more difficulty with sexual enjoyment, and over time sexual strain was worse for patients aged > or =70 years during the early postoperative period but improved, whereas patients aged < or =69 years had increasing levels of strain over time. The findings in this study confirmed that QOL is dynamic over time and that age has an impact on QOL and sexuality. Patients aged > or =70 years are affected by impaired physical functioning, global health, and fatigue, whereas increased treatment strain during the early postoperative period improves over time. Patients aged < or =69 years experience increased strain because of impaired sexual function.
World Journal of Surgery 03/2005; 29(2):190-7. · 2.36 Impact Factor
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ABSTRACT: The aim of this prospective study was to evaluate different diagnostic modalities routinely employed in a district hospital.
Four hundred subsequent patients presenting with acute abdominal pain were included over a period of 18 months. Patient characteristics, diagnostic work-up, intraoperative findings, histology and clinical outcome were documented. Rectal temperature, white cell count (WCC), C-reactive protein (CRP), ultrasonography (US) and Ohmann score were analysed with relation to diagnostic value.
Negative appendicectomy rate and negative laparotomy rate on the day of admission were 22% and 21%, respectively. Sensitivity was highest for WCC and CRP (0.82 and 0.85) but US showed highest values for specificity (0.92), accuracy (0.85) and odds ratio (13.06). No patient with an Ohmann score below 6.5 suffered from acute appendicitis. With regard to different levels of training in US, experienced surgeons and radiologists had best values for specificity (1.00 and 0.98) and accuracy (0.90 and 0.94). Surprisingly, less-experienced sonographers also achieved good results with regard to specificity (up to 0.96) and positive predictive value (up to 0.89).
Diagnostic accuracy of acute appendicitis remains insufficient, with an unacceptable high rate of unnecessary operations. Only the promotion of routine ultrasonography might contribute to an improvement in the near future.
Langenbeck s Archives of Surgery 07/2004; 389(3):219-24. · 1.81 Impact Factor
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ABSTRACT: Bilio-intestinal drainage is routinely performed by Roux-en-Y reconstruction after resection of the central bile duct. Alternatively reconstruction can be achieved by cholangio-duodenal interposition of an isolated jejunal segment (CDJI). This method offers the benefit of potential endoscopic control and intervention during follow-up. Critics of CDJI assume a higher rate of postoperative cholangitis compared to the Roux-en-Y construction.
Seventy-six patients with malignant tumors (n=56) or benign strictures and choledochal cysts (n=20) were treated between 1989 and 2002 by cholangio-duodenal interposition of an isolated jejunal segment (measuring 15-25 cm) after central bile duct resection. In 22 patients endoscopic control was first performed postoperatively during hospitalization. In 12 patients bilio-intestinal anastomosis could be inspected endoscopically. In the remaining patients the anastomosis could not be visualized endoscopically because of kinking of the jejunal segment, but in all patients it could be evaluated by endoscopic retrograde cholangiography (ERC).
During follow-up, 25 (33%) patients died from extrahepatic tumor recurrence. Three patients receiving CDJI after severe iatrogenic bile duct injury developed anastomotic strictures. Two of these patients were treated by endoscopic pigtail drainage, and one was treated by percutaneous drainage. Two patients who had received CDJI after choledochal cyst resection developed cholestasis postoperatively because of sludge formation (1 patient) and an intrahepatic concrement (1), which could be solved endoscopically. One patient after resection of a Klatskin tumor developed an anastomotic stricture which could not be visualized endoscopically, making percutaneous drainage necessary. The rate of postoperative cholangitis after CDJI in our patients was comparable to that after the Roux-en-Y reconstruction.
Interposition of an isolated jejunal segment for reconstruction after bile duct resection should be performed in patients with a high risk of postoperative stenosis. To benefit endoscopic follow-up the jejunal segment should be shorter than 20 cm
Hepatobiliary & pancreatic diseases international: HBPD INT 06/2004; 3(2):259-64. · 1.08 Impact Factor
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ABSTRACT: Postoperative survival and complication rates have traditionally been the standard parameters of outcome after oncologic surgery. In tumors with poor patient survival, such as esophageal cancer, studies about quality of life are rare. The objectives of this study were to assess outcomes in terms of quality of life in patients with esophageal cancer when investigating differences between two surgical reconstructive procedures: intrathoracic anastomosis and collar anastomosis. A total of 108 patients with esophageal cancer had undergone surgery for esophageal cancer in our department from 1992 to 2000. Median survival was 36 months with no significant differences between patients undergoing collar or intrathoracic anastomosis. After determining the survival status, questionnaires on quality of life were sent to all patients 1 to 2 years after surgery. We received data from 46 patients. The responders were divided into groups of intrathoracic anastomosis ( n = 24) and collar anastomosis ( n = 22). Patients with the collar anastomosis showed significantly better physical and social functioning and global health status. From the viewpoint of postoperative quality of life, reflux-related symptoms were the major problem for patients with an intrathoracic anastomosis. These symptoms cause significant insomnia and impair social and physical function. The study showed that assessing quality of life with specific and general instruments is helpful for determining the differences between surgical procedures where standard parameters such as survival have their limitations.
World Journal of Surgery 05/2004; 28(4):355-60. · 2.36 Impact Factor
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ABSTRACT: Patients with advanced, incurable gastric cancer may present with mild symptoms or require immediate therapeutic intervention. The influence of the intensity of preoperative symptoms on postoperative survival and quality of life (QoL) was evaluated in a palliative setting. In a historical cohort analysis of 492 patients with gastric cancer treated between 1992 and 2001, a total of 169 (34.4%) patients had incurable disease (i.e., pTxNxM1). Patients were classified as having major symptoms if they presented with upper gastrointestinal bleeding (i.e., hematemesis or bloody stools), gastric inlet or outlet obstruction (i.e., symptomatic and endoscopically proven stenosis), or perforation caused by the tumor. All other patients were defined as having minor symptoms. QoL was assessed prospectively using the EORTC questionnaire. The questionnaire was given to the patients before operation, before discharge, and 3 months after operation; and it was analyzed by the Mann-Whitney U-test. Survival, demographic data, and histopathologic characteristics were assessed and analyzed by the log-rank test and the chi(2) test, respectively. Of the 169 patients, 75 (44.3%) presented with major symptoms and 94 (55.7%) with minor symptoms. The distribution of patients undergoing resection or exploration was comparable for the two groups [major: 61 (81.5%)/14 (18.5%); minor: 77 (81.9%)/17 (18.1%)]. Despite comparable demographic and histopathologic characteristics with equal hospital mortality and morbidity (14.6% vs. 8.5%/49.3% vs. 40.4%), the median survival rates in two groups were 4 and 6 months, respectively ( p < 0.05). This was not influenced by the type of operation. QoL was not different in patients with major or minor symptoms before operation or 3 months thereafter. However, preoperative symptoms such as nausea/vomiting and melena were rated significantly higher in patients with major symptoms. In patients with incurable gastric cancer the preoperative intensity of symptoms has a significant impact on survival and QoL, which is not influenced by the operation. The necessity of surgery in patients with minor symptoms requires careful consideration.
World Journal of Surgery 04/2004; 28(4):369-75. · 2.36 Impact Factor
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ABSTRACT: Palliative chemotherapy with gemcitabine, a common mode of treatment of pancreatic cancer, has little influence on patients' survival. We investigated the impact of anti-apoptotic Bcl-xL protein and its antagonist Bax on gemcitabine-induced apoptosis in human pancreatic carcinoma cells in vitro and in vivo. The level of Bcl-xL and Bax expression was determined in 3 established pancreatic cancer cell lines that differ in their sensitivity to gemcitabine-mediated apoptosis. Bcl-xL and Bax genes were transduced into Colo357 cells by retroviral infection. In addition, cells were transfected with c-FLIP to assess involvement of CD95 and caspase-8. The impact of Bax/Bcl-xL expression on gemcitabine-sensitivity in vivo was evaluated in orthotopic Colo357 tumors in SCID mice. The apoptotic index revealed a strong inverse correlation between Bcl-xL expression and gemcitabine-induced apoptosis in the pancreatic carcinoma cell lines tested. Caspase-8 and Bid were cleaved in Colo357 cells exposed to gemcitabine, and there was no correlation with either Bcl-xL or with Bax expression. In contrast, the lack of mitochondrial transmembrane potential transition, release of cytochrome-c and absence of caspase-9- and PARP-cleavage showed a strong correlation with Bcl-xL expression. Expression of c-FLIP significantly increased the resistance towards gemcitabine. Orthotopically growing Colo357-bcl-xl tumors in SCID mice were refractory to gemcitabine treatment, and in contrast to the in vitro data, Colo357-bax tumors exhibited a 12-fold greater tumor regression than Colo357-wild-type tumors in the control group. Gemcitabine-induced apoptosis involves the mitochondria-mediated signaling pathway. A functional restoration of this pathway appears to be essential to overcome the resistance mechanisms of pancreatic tumor cells and to improve the response to therapy as demonstrated by Bax overexpression in a clinically relevant tumor model.
International Journal of Cancer 04/2004; 109(2):182-8. · 5.44 Impact Factor
