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ABSTRACT: Positron emission tomography (PET) using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) is used as a functional imaging technique for the staging and follow-up of lymphomas. However, additional information about the tumor proliferation rate using 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) may be useful for the assessment of prognosis. We enrolled 48 patients with Hodgkin's (n = 15) and non-Hodgkin's lymphoma (n = 33) with residual masses >2 cm examined by tracer studies with FDG and FLT. The results were related to median overall and progression-free survival. In 15 out of 48 patients analysed using FDG, positive results were found. Using FLT, 10 out of 48 patients were positive. 33 patients were FDG negative. Eight patients were positive both using FDG and FLT. Overall survival for patients with a negative PET scan was significantly higher than for patients with positive PET, irrespective of the tracer used. FLT alone was able to discriminate between patients with long or short overall survival. However, there was no statistical significance comparing FDG/FLT negative versus FDG negative alone. Although FDG detected more lesions than did FLT, the additional biological characterization of tumor tissue with respect to proliferation by FLT might be useful by providing complementary information for the identification of recurrence. However, the present data show no advantage of combined FDG/FLT studies over FDG alone with respect to the prediction of survival.
Leukemia and Lymphoma 04/2007; 48(4):746-53. · 2.58 Impact Factor
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ABSTRACT: The aim of this study was to determine whether anti-p53 antibodies are of clinical significance as a serological marker in the diagnosis and monitoring of malignancies. A total of 1874 serum samples from 591 patients with various types of cancer, esophageal, gastric, colorectal, pancreatic, hepatocellular, breast, and urogenital cancer, and 436 control individuals were analyzed by immunoblot for antibodies against p53. The anti-p53 antibody test was correlated with expression of conventional tumor markers, survival and the clinicopathological features of malignant disease. Anti-p53 antibodies were found in 23.4% (138/591) of the sera of patients with malignant disease (range 11.5-34%). The detection of anti-p53 serum antibodies had a specificity of 100% for malignancy (p<0.0001). The overall sensitivity of measuring established tumor markers was 62.9% (372/591). The elevation of conventional tumor markers and the presence of anti-p53 antibodies in the sera of patients with malignant disease turned out to be an independent variable (p<0.05). Combination of established tumor markers with the anti-p53 antibody test led to an increase in diagnostic sensitivity of 8% (49/591) (p<0.01). Thus, the independence of anti-p53 antibodies from established tumor markers allows the serological detection of additional tumor patients. Kaplan-Meier analysis revealed a trend toward a poorer prognosis in hepatocellular carcinoma and breast cancer patients who were anti-p53 serum positive. In conclusion, testing for anti-p53 antibodies can increase the diagnostic sensitivity when used in combination with measurement of conventional tumor markers. This increase is achieved without a parallel decrease in specificity.
International Journal of Oncology 10/2006; 29(4):973-80. · 2.40 Impact Factor
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ABSTRACT: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Surgery has been the only effective therapy. However, many patients still eventually die of disease recurrence. Chemotherapy and radiation therapy have been of limited value. Imatinib mesylate (Glivec) is an orally administered competitive inhibitor of tyrosine kinases associated with the KIT, ABL protein, licensed for the treatment of metastatic GIST since 2002 in Germany.
We summarized the data of 16 patients with advanced or metastatic GIST treated with imatinib mesylate in palliative and neoadjuvant settings.
Overall response was 81%, with no evidence of disease (NED) in 3/16 (19%), partial response (PR) in 9/16 (56%) and stable disease (SD) in 1/16 (6%), whereas 3/16 patients (19%) suffered from progressive disease (PD). Mean follow-up was 18.6 months [range: 4-30]. Mean progression-free survival (PFS) was 17.6 months [range: 0-30], mean overall survival (OS) from initial diagnosis was 32.3 months [range: 5-122]. Most common side effects were periorbital edema and skin rash.
Imatinib mesylate is well tolerated in a dose of up to 800 mg/day and has significant activity during long- term treatment of patients with advanced or metastatic GIST.
Digestive Diseases 02/2006; 24(1-2):207-11. · 2.37 Impact Factor
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ABSTRACT: 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).
FDG-PET might be used as an adjunctive tool (in addition to biopsy and radiologic tomography) in the preoperative prognostic assessment of resectable STS.
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.
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).
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.
Annals of Surgery 02/2005; 241(2):286-94. · 7.49 Impact Factor
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ABSTRACT: The biliary epithelium of bile ducts and gallbladder modifies the composition of primary hepatic bile by absorption and secretion of an electrolyte-rich fluid. The underlying transport mechanisms, however, are still incompletely understood. We investigated the expression, the cellular localization, and the functional role of guanylin, a bioactive intestinal peptide involved in the cystic fibrosis transmembrane conductance regulator (CFTR)-regulated electrolyte/water secretion, in the human gallbladder.
Peptide-specific antibodies were raised to localize guanylin and its affiliated signaling proteins, i.e., the guanylin receptor, guanylate cyclase C (GC-C), cGMP-dependent protein kinase type II (cGKII), and CFTR in the human gallbladder and cholangiocarcinoma cells (Mz-Cha-1) by RT-PCR, Western blot, and immunocytochemistry. A sensitive ELISA was used to assess the range of guanylin concentration in human bile fluid. The functional role of guanylin was investigated in subconfluent Mz-Cha-1 cell monolayers by isotope efflux experiments.
Guanylin and its affiliated signaling proteins are highly expressed in the human gallbladder. Guanylin is localized to secretory epithelial cells of the gallbladder and is present in the bile, whereas GC-C, cGKII, and CFTR are confined exclusively to the apical membrane of the same epithelial cells. Functional studies in Mz-Cha-1 cells identify guanylin as a specific regulator of biliary Cl(-) secretion that very likely is mediated by an intracellular increase of cGMP-concentration.
Based on the present findings and on the functional role of guanylin in other epithelia, it is likely that gallbladder epithelial cells synthesize and release guanylin into the bile to regulate electrolyte secretion by a paracrine/luminocrine signaling pathway.
Gastroenterology 03/2004; 126(3):732-40. · 11.68 Impact Factor
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ABSTRACT: Gastrointestinal stromal tumours (GISTs), the most common mesenchymal tumours of the digestive tract, are largely resistant to chemo- and radiotherapy. They are currently defined by their overexpression of the KIT receptor tyrosine kinase (CD117), a member of the family of receptor tyrosine kinases (RTKs), and exhibit KIT mutations in more than 85% of cases. Additionally, in more than one-third of KIT wild-type GISTs, mutations of platelet-derived growth factor receptor alpha (PDGF-R alpha), which also belongs to the family of RTKs, were recently found. Since these data indicate that uncontrolled RTK signalling may be implicated in the pathogenesis of GISTs, RTKs and the activated downstream signalling cascades are attractive targets in the therapy of these tumours. Imatinib is a small-molecule inhibitor that selectively blocks the activity of the PDGF-R, ABL and KIT receptor tyrosine kinases by competitive binding to the adenosine triphosphate binding site of their catalytic domains. We herein review the molecular pathological, preclinical and clinical data that identify imatinib as a valuable new agent in the treatment of GISTs.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 03/2004; 444(2):108-18. · 2.49 Impact Factor
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Henning Schulze-Bergkamen,
Andreas Untergasser,
Andreas Dax,
Heiko Vogel,
Peter Büchler,
Ernst Klar, Thomas Lehnert,
Helmut Friess,
Markus W Büchler,
Michael Kirschfink,
Wolfgang Stremmel,
Peter H Krammer,
Martina Müller,
Ulrike Protzer
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ABSTRACT: Apoptosis is a key event in the pathophysiology of many liver diseases. Primary human hepatocytes (PHH) provide a useful model to study physiological and pathophysiological processes in the liver. Our aim was to optimize PHH cultures to allow studies on induction of apoptosis and of hepatitis B virus (HBV) infection.
PHH were isolated from human liver tissue by two-step collagenase perfusion. PHH and hepatoma cells were treated with different apoptosis-inducing agents in parallel. PHH cultures were infected with wild type HBV and transduced with HBV genomes using adenoviral vectors.
PHH were successfully isolated from 40 different tissue samples with high viability and purity. Perfusion time and seeding density turned out to be critical parameters for optimal cell yield and culture conditions, respectively. Serum addition to the medium reduced viability of PHH. PHH allowed reproducible studies of CD95-dependent and -independent apoptosis. Sensitivity towards CD95-mediated apoptosis was markedly higher than in hepatoma cells. PHH could efficiently be infected with HBV, but infection did neither induce apoptosis nor prevent CD95-induced cell death.
Our data show that PHH provide an excellent tool for the investigation of apoptosis induced by agents like death receptor-ligands and hepatotropic viruses.
Journal of Hepatology 07/2003; 38(6):736-44. · 9.26 Impact Factor
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ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells and may be involved in protection from metastases. TRAIL receptor (TRAIL-R) 1 and TRAIL-R2, but not TRAIL-R3 and TRAIL-R4, mediate apoptosis. We examined the expression of TRAIL and its receptors in normal and neoplastic colon epithelium, and studied its correlation with prognosis in colon cancer.
Immunohistochemistry was performed on normal colon mucosa (n = 10), colon adenomas (n = 20), and R0-resected Unio Internationale Contra Cancrum stage II/III colon carcinomas (n = 129). Disease-free survival was examined by Kaplan-Meier estimates and the log-rank test. Prognostic factors were determined by multivariate Cox-analysis.
In normal colon mucosa, TRAIL and TRAIL-R2 were expressed mostly in the surface epithelium, whereas TRAIL-R1 and TRAIL-R4 were detected all along the crypt axis. In adenomas, this expression pattern was mostly retained, although some adenomas also neoexpressed TRAIL-R3. In carcinomas, the expression of TRAIL and TRAIL receptors was much more variable. TRAIL, TRAIL-R2, TRAIL-R3, and TRAIL-R4 expression did not correlate statistically with disease-free survival (multivariate analysis: P = 0.54, P = 0.67, P = 0.45, and P = 0.69, respectively), but TRAIL-R1 expression was significantly associated with disease-free survival in colon cancer (multivariate analysis: P = 0.003).
TRAIL-R1 is an independent prognostic factor in R0-resected Unio Internationale Contra Cancrum stage II/III colon cancer.
Clinical Cancer Research 01/2003; 8(12):3734-40. · 7.74 Impact Factor
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Ralf J Rieker,
Stefan Joos,
Christine Bartsch,
Frank Willeke,
Matthias Schwarzbach,
Marta Otaño-Joos,
Sybille Ohl,
Josef Högel, Thomas Lehnert,
Peter Lichter,
Herwart F Otto,
Gunhild Mechtersheimer
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ABSTRACT: Using comparative genomic hybridization, DNA copy number changes were studied in 14 pleomorphic liposarcomas and compared to those detected in high-grade areas of 9 dedifferentiated liposarcomas. A total of 251 gains and 84 losses were detected. The most frequent gains involved subregions of chromosomal arms 12q and 20q (70% each), 5p (57%), 6q and 9q (52% each), 1q, 7p and 17p (48% each), 1p (43%), 6p and 17q (39% each), 20p and 22q (35% each) as well as 7q and 12p (30% each). The same subregions were also affected by 30 high level amplifications. The most frequent losses were found in subregions of chromosomal arms 13q (35%) as well as 11q and 12p (30% each). Overall, gains of chromosomal material were more frequent than losses (p < 0.001). There were significant differences in the frequency and distribution of recurrent chromosomal imbalances between pleomorphic liposarcomas and the dedifferentiated areas of dedifferentiated liposarcomas. Gains of chromosomal material detected predominantly in pleomorphic liposarcomas involved subbands 5p13-p15 (p < 0.010), 1p21 (p < 0.019), 1q21-q22 (p < 0.040) and 7q22 (p < 0.049). Conversely, high level amplifications within chromosomal subregion 12q13-q21 were only found in the dedifferentiated components of dedifferentiated liposarcomas (p < 0.001). Overall, both gains and the less pronounced losses of chromosomal material were more frequent in pleomorphic than in dedifferentiated liposarcomas (p < 0.001 and p < 0.025, respectively). These results show that pleomorphic liposarcomas display a considerable number of recurrent chromosomal imbalances that are essentially different from those present in high-grade areas of dedifferentiated liposarcomas. Therefore, genetic data are considered as a helpful diagnostic adjunct for the discrimination between these 2 types of liposarcoma. The overall higher frequency of chromosomal imbalances in pleomorphic as compared to dedifferentiated liposarcomas could account for the more aggressive biological behavior of pleomorphic relative to dedifferentiated liposarcoma types.
International Journal of Cancer 05/2002; 99(1):68-73. · 5.44 Impact Factor
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ABSTRACT: To review a single-center experience with 201 multivisceral resections for primary colorectal cancer to determine the accuracy of intraoperative prediction of potential curability, to identify prognostic factors, and to examine the effect of surgical experience on immediate outcome and long-term results.
Locally advanced colorectal cancer may require an intraoperative decision for en bloc resection of surrounding organs or structures to achieve complete tumor removal. This decision must weigh the risk of complications and death of multivisceral resection against a potential survival benefit. Little is known about prognostic factors and the influence of surgical experience on the outcome of multivisceral resection for colorectal cancer.
Patients undergoing multivisceral resection for primary colon or rectal cancer between 1982 and 1998 were identified from a prospective database. Patients were followed up according to a standard protocol.
Multivisceral resection was performed in 201 of 2,712 patients with a median age of 64 years. Postoperative rates of complications and death in 201 patients were 33% and 7.5%, respectively. A potentially curative resection was possible in 130 of 201 patients (65%) and histologic tumor infiltration was shown in 44% of patients with curative resection. Intraoperative assessment of curability was unreliable. After curative resection, the local recurrence rate was 11% and the overall 5-year survival rate was 51%. Multivariate analysis identified intraoperative blood loss (relative risk 1.7-6.4, P <.001), age 64 years or older (RR 3.7; P <.001), and UICC stage as independent prognostic factors (RR 2.0; P =.009). No prognostic significance was found for histologic tumor infiltration, the number of resected organs, or surgical experience.
Multivisceral resection is safe, and long-term survival after curative resection is similar to that after standard resection. Because palliative resections cannot be predicted accurately at the time of surgery, every effort should be made to achieve complete tumor resection. Major blood loss but not surgical experience per se is an independent prognostic factor.
Annals of Surgery 03/2002; 235(2):217-25. · 7.49 Impact Factor
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ABSTRACT: Local and multimodal therapeutic strategies for tumours of the oesophagus and gastric cardia, require precise preoperative staging. Endosonography is considered the most accurate staging method, while computed tomography (CT) has limitations especially in the evaluation of local infiltration. Macroscopic endoscopic evaluation was reported to be accurate in selected series, but no study has yet compared all three staging modalities.
One hundred and seventeen unselected patients with tumours of the oesophagus and gastric cardia were prospectively staged first by the endoscopic macroscopic appearance and then by endosonography. All patients had preoperative CT scans, however, only the 36 patients receiving the scans at our institution were included in the study. The preoperative staging results were then compared to postoperative histology which was available as the gold standard in all included patients. Kappa statistics were used to exclude chance agreement of the clinical staging results with the pathohistological findings. Differences between the resulting kappa values for the different staging modalities were analysed with a jack-knife test.
Endoscopic macroscopic staging and endosonography (accuracy 67 and 69%, weighted kappa 0.78 and 0.84) were significantly more accurate than CT (accuracy 33%, weighted kappa 0.44) for determination of the T category (p = 0.006 and p = 0.001). After exclusion of tumours of the cardia (n = 33), the accuracy of macroscopic and endosonographic staging (accuracy 72 and 75%, weighted kappa 0.86 and 0.88) increased and remained more accurate than CT (accuracy 50%, weighted kappa 0.62). The main pitfall in our series in staging the T category was the overestimation of T2 tumours in the cardia as T3 or even as T4 tumours due to the inability to visualise the serosa. The accuracy of predicting lymph node metastasis was 68% for macroscopic endoscopic, 79% for endosonographic, and 67% for CT staging. Only endosonographic staging was significantly different from chance agreement with histology (weighted kappa = 0.56). Endosonographic staging was significantly more accurate than endoscopic macroscopic and CT staging (p = 0.03).
Endosonography is the most accurate staging modality for overall preoperative staging of oesophageal and cardial tumours. Endoscopic macroscopic staging allows a reasonably accurate assessment of the T category.
Digestion 02/2002; 66(4):230-6. · 2.05 Impact Factor
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ABSTRACT: Peripheral nerve sheath tumors arise either sporadically or in association with neurofibromatosis type 1 (von Recklinghausen's neurofibromatosis, NF1) or type 2. In this study, comprehensive screening for relative chromosome copy number changes was performed on 10 benign and 19 malignant peripheral nerve sheath tumors (MPNSTs) by applying comparative genomic hybridization (CGH). In benign tumors, no chromosomal imbalances were found by CGH, whereas in MPNSTs chromosomal gains and losses were frequently detected. No differences regarding the frequency and distribution of chromosomal imbalances were observed between the 13 sporadic and 6 NF1-associated MPNSTs analyzed. In both, the number of gains was significantly higher than the number of losses, suggesting a predominant role of proto-oncogene activation during MPNST progression. Candidate regions with potentially relevant proto-oncogenes included chromosomal bands 17q24–q25, 7p11–p13, 5p15, 8q22–q24, and 12q21–q24; those with putative tumor suppressor genes were 9p21–p24, 13q14–q22, and 1p. High-level amplifications were restricted to sporadic tumors and affected eight different chromosomal subregions. In three of these MPNSTs, identical subregions on chromosomal arms 5p and 12q were coamplified. This study revealed a number of new characteristic chromosomal imbalances and provides a basis for molecular identification of oncogenes and tumor suppressor genes of pathogenetic relevance in both sporadic and NF1-associated MPNSTs. Genes Chromosomes Cancer 25:362–369, 1999. © 1999 Wiley-Liss, Inc.
Genes Chromosomes and Cancer 07/1999; 25(4):362 - 369. · 3.31 Impact Factor
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Frank Willeke,
Ruediger Ridder,
Peer Bork,
Ruediger Klaes,
Gunhild Mechtersheimer,
Matthias Schwarzbach,
Dagmar Zimmer,
Matthias Kloor, Thomas Lehnert,
Christian Herfarth,
Magnus von Knebel Doeberitz
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ABSTRACT: Inactivation of the TSG101 gene was recently shown to induce malignant transformation of NIH/3T3 fibroblasts. Abnormal TSG101 transcription profiles were observed in various human cancers, and large intragenic deletions of the TSG101 gene were reported for a series of human breast cancer specimens, pointing to a potential tumor-suppressive activity of TSG101. However, subsequent more detailed studies on a large panel of breast carcinoma samples did not confirm the tumor-associated genomic deletions. Here we analyzed the transcription patterns of the TSG101 gene in soft-tissue sarcomas and non-neoplastic human tissues. Forty-five of 71 soft tissue sarcoma samples (63%) displayed variant transcripts; however, identical aberrant transcripts were also detected in seven of 15 non-neoplastic control tissues. Restriction fragment length polymorphism analysis of the TSG101 gene excluded major genomic rearrangements in the soft tissue sarcoma samples. Northern blot analysis revealed a very low abundance of variant transcripts as compared with the wild-type TSG101 transcript. These data point to aberrant splicing of the TSG101 mRNA in normal and transformed human mesenchymal tissues rather than tumor specific alterations of the TSG101 gene. In summary, this analyses does not support a pathogenic role for altered TSG101 expression in human soft tissue sarcomas. Mol. Carcinog. 23:195–200, 1998. © 1998 Wiley-Liss, Inc.
Molecular Carcinogenesis 01/1999; 23(4):195 - 200. · 3.16 Impact Factor
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Frank Willeke,
Ruediger Ridder,
Peer Bork,
Ruediger Klaes,
Gunhild Mechtersheimer,
Matthias Schwarzbach,
Dagmar Zimmer,
Matthias Kloor, Thomas Lehnert,
Christian Herfarth,
Magnus von Knebel Doeberitz
Molecular Carcinogenesis - MOL CARCINOGEN. 01/1998; 23(4):195-200.
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ABSTRACT: To evaluate quality of life and functional results following surgery for gastric cancer we studied 104 patients with no evidence of disease at a minimum of 12 months postoperatively. Patients were treated with total gastrectomy and jejunal pouch reconstruction according to Hunt-Lawrence-Rodino (n=59) or simple esophagojejunostomy (n=24) and distal subtotal gastrectomy (n=21). No significant differences were found between total gastrectomy with pouch reconstruction and distal gastric resection with respect to dumping or heartburn, whereas patients with total gastrectomy and restoration with esophagojejunostomy suffered from both. The latter group of patients also had reduced nutritional status. Although there is a lack of a proper definition of quality of life, all instruments applied to its measurement indicated improved results for patients with pouch reconstruction and those after distal gastrectomy, but we could not state any significant differences. We conclude that in terms of postoperative functional results as well as quality of life distal gastric resection has no advantage over total gastrectomy with pouch reconstruction; hence a reduction of surgical radicality in an attempt to improve postoperative results is not justified. Pouch reconstruction should be considered the treatment of choice for reconstruction after total gastrectomy.Con miras a evaluar la calidad de la vida y los resultados funcionales luego de ciruga por cncer gstrico, estudiamos 104 pacientes que se encontraban libres de enfermedad a un mnimo de 12 meses postoperatorios. Los pacientes fueron tratados con gastrectoma total y reconstruccin con una bolsa yeyunal de tipo Hunt-Lawrence-Rodino (n=59) o simple esofagoyeyunostoma (n=24) y gastrectoma subtotal distal (n=21). No se encontraron diferencias significantivas entre los pacientes sometidos a gastrectoma total con reconstruccin con bolsa yeyunal y los sometidos a reseccin distal con respecto a dumping o pirosis, en tanto que los pacientes sometidos a gastrectoma total y restauracin mediante esofagoyeyunostoma exhibieron ambos sntomas. Adems, los ltimos desarrollaron deterioro de su estado nutricional. Aparte de la falta de una adecuada definicin de calidad de la vida, todos los parmetros aplicados para su medicin demostraron mejores resultados en los casos de gastrectoma total con reconstruccin con bolsa yeyunal y en los casos de gastrectoma distal, pero sin que pudiramos hallar diferencias significativas. Nuestra conclusin es que en trminos de los resultados funcionales postoperatorios as como de calidad de la vida, la reseccin gstrica distal no tiene ventaja sobre la operacin con reconstruccin con bolsa yeyunal y que no se justifica una reduccin de la radicalidad quirrgica con el objeto de mejorar los resultados postoperatorios. La reconstruccin con bolsa yeyunal debe ser considerada como el procedimiento de eleccin en la gastrectoma total.Afin d'valuer la qualit de vie et les rsultats fonctionnels aprs chirurgie pour cancer gastrique, nous avons tudi 104 patients qui semblaient guris 12 mois. Les patients ont eu soit une gastrectomic totale suivie ou de la confection d'un nogastre jjunal selon le procd de Hunt-Lawrence-Rodino (n=59) ou une simple anastomose oesojjunale (n=24), soit d'une gastrectomie distale subtotale (n=21). Il n'y avait aucune diffrence significantive entre la gastrectomie totale suivie de reconstruction par nogastre et la gastrectomie distale subtotale en ce qui concerne le dumping syndrome ou le reflux, alors que les patients qui avaient eu une gastrectomie totale suivie d'anastomose oesojjunale avaient les deux. Chez ces derniers, on a galement not une certaine malnutrition. En dpit du manque de dfinition prcise de la qualit de vie, tous les moyens utiliss pour la mesurer ont indiqu um meilleur rsultat pour les patients ayant eu une reconstruction avec nogastre par rapport la gastrectomie distale, sans toutefois atteindre la signification statistique. Nous concluons qu'en terme de rsultats fonctionnels postopratoires ainsi que de la qualit de vie, la gastrectomie distale ne prsente aucun avantage par rapport la gastrectomie totale suivie de nogastre, et une rduction dans l'importance de l'intervention pour amliorer les rsultats fonctionnels n'est pas justifie. La confection d'un nogastre doit tre la mthode de reconstruction de choix aprs gastrectomie totale.
World Journal of Surgery 06/1995; 19(4):558-564. · 2.36 Impact Factor
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ABSTRACT: During the past decade considerable progress has been reported in the treatment of primary and secondary hepatic malignancies. Refined techniques in surgery, transplantation, radiotherapy, and chemotherapy apparently have made the delivery of treatment safer. At the same time improved understanding of tumor biology has been incorporated in treatment strategies. More recently specific and nonspecific, active and passive immunotherapies have excited wide interest, and information from the first randomized studies is now available. We review current treatment options for primary and secondary hepatic malignancies in an attempt to extract plausible treatment guidelines and to identify promising future directions.En el curso del ltimo decenio se ha informado considerable progreso en el tratamiento de los neoplasmas primarios y secundarios del hgado. Neuvas y refinadas tcnicas en ciruga, trasplante, radioterapia y quimioterapia han aportado mayor seguridad a las modalidades de tratamiento. Al mismo tiempo, existe una mejor comprensin de la biologa tumoral, la cual ha sido debidamente incorporada en las estrategias teraputicas. Ms recientemente, se ha despertado gran inters en cuanto a la immunoterapia especfica y no especfica, activa y pasiva, y ya se dispone de informacin sobre los primeros estudios randomizados. En el presente artculo hacemos una revisin de las opciones teraputicas para los neoplasmas primarios y secundarios del hgado con la intencin de definir guas teraputicas plausibles y de identificar modalidades promisorias para el futuro.Pendant la dernire dcennic, d'importants progrs ont t enregistrs dans le traitement des tumeurs malignes primitives et secondaires du foie. Des techniques sophistiques dans les domaines de la chirurgie, des transplantations, de la radiothrapie et de la chimiothrapie ont toutes contribu rendre ce traitement plus sre. De mme, une meillcure connaissance de la biologie tumorale s'est intgre dans la stratgie thrapeutique. Plus rcemment, l'immunothrapie spcifique comme non spcifique, active ou passive, s'est ajoute avec intrt et prsent, les rsultats d'tudes randomises sont disponibles. Les options thrapeutiques des tumeurs malignes primitives ou secondaires du foie sont discutes afin d'extraire les grandes lignes thrapeutiques et d'identifier les directions futures.
World Journal of Surgery 02/1995; 19(2):252-263. · 2.36 Impact Factor
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ABSTRACT: Male Wistar rats were treated concurrently with a combination of the carcinogenN-methyl-N-nitro-N-nitrosoguanidine (MNNG; CAS 70-25-7) and the polyamine-synthesis inhibitor -difluoromethylornithine (DFMO) at two different doses of 0.5% and 1.0% (w/v). Experimental groups were treated with (I) MNNG alone (n=25), (II) MNNG plus 0.5% (w/v) DFMO (n=25), (III) MNNG plus 1.0% (w/v) DFMO (n=25), (IV) 1.0% (w/v) DFMO alone (n=25). Group V represented untreated controls (n=20). Both the carcinogen and DFMO were administered in drinking water. The treatment time with the carcinogen and DFMO was 35 weeks. After treatment was completed animals were followed for an additional 50 weeks to cover a total observation time of 85 weeks. Significantly fewer animals developed gastric adenocarcinoma in the two groups of animals that received a combined treatment of MNNG plus DFMO compared to animals treated with the carcinogen alone (PIt is concluded that concurrent treatment with DFMO prevents the development of malignant gastric epithelial tumors induced by MNNG in rats.
Journal of Cancer Research and Clinical Oncology 09/1993; 119(10):594-598. · 2.56 Impact Factor
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ABSTRACT: Traditionally, liver surgery relies on Couinaud's liver segment classification. As the position and shape of these segments are variable and their borders are hidden within the homogeneous liver mass, the accuracy of segment identification methods needs computer-aided reevaluation.
The segmental liver anatomy of 23 patients receiving diagnostic helical CT scans because of suspected intrahepatic lesion was analyzed with the aid of a computer-based operation-planning system. We compared the standard Couinaud classification, which depends particularly on the main stems of portal and hepatic veins, with a method that calculates the segment borders by analyzing the complete portal venous tree. Volume, shape, and position of the liver segments found by each method were compared.
With reference to the portal vein-based method, segmental volumes were overestimated by the classic Couinaud method by up to 24% and underestimated to 13%. Volumes of Couinaud segments 4a, 7, and 8 were generally larger compared with those obtained by the portal vein-based method, whereas segments 3 and 6 were smaller. Gross variations were found in segments 5, 7, and 8. When shape and position were considered, poor correlation was found for five segments (median kappa = 0.35-0.45). Only segments 2, 7, and 8 had kappa values clearly above 0.45 in the majority of cases. The plane that divides the two hemilivers along the middle hepatic vein and the border between the left sector (segments 2 and 3) and the medial sector (4a and 4b) were found in both methods with very good conformity (kappa > 0.75).
Couinaud's method of dividing the liver into eight autonomous liver segments has to be accepted as a good approximation. Nevertheless, the volume, position, and shape of these segments and their segmental borders show significant variability.
Journal of Computer Assisted Tomography 26(6):962-7. · 1.22 Impact Factor