0000000000025694
AUTHOR
Thomas C. Böttger
Prognostic Value of Immunohistochemical Expression of Beta-1 Integrin in Pancreatic Carcinoma
<i>Background: </i>Prognostically relevant factors based on the histological assessment of the resected pancreas are known. However, the knowledge of additional factors associated with the prognosis is helpful in planning the therapy for an individual patient. β<sub>1</sub> Integrin expression is known to have a prognostic influence in some malignant tumors. No data are, however, available on the prognostic value of β<sub>1</sub> integrins in pancreatic carcinoma. <i>Method: </i>We investigated paraffin-embedded specimens of 19 patients undergoing surgical treatment for periampullary carcinoma and of 42 patients for ductal pancreatic carcinoma…
Langzeitergebnisse nach rekonstruktiven Eingriffen im aortoiliakalen Abschnitt
Im Zeitraum von September 1985 bis Februar 1994 wurde bei 183 Patienten ein rekonstruktiver Eingriff im aortoiliakalen Bereich durchgefuhrt. Die Grunderkrankung war in 108 Fallen eine arterielle Verschluskrankheit, in 75 Fallen ein abdominales Aortenaneurysma. Bei 120 Patienten wurde eine Bifurkationsprothese, bei 63 Patienten eine Rohrprothese implantiert. Die Fruh- und Spatkomplikationen werden beschrieben, differenziert nach chirurgisch und nichtchirurgisch, wobei die chirurgischen Komplikationen im wesentlichen durch die Prothesenart und durch den Leistenanschlus bedingt waren, wahrend die nichtchirurgischen Komplikationen vom Risikoprofil des Krankenguts abhangig waren. Die Unterschied…
A small-bowel segment as a total extrahepatic bile duct replacement.
• The effect of a small-bowel segment as a total extrahepatic bile duct replacement, with preservation of the bile passage through the papilla of Vater, was examined in 12 pigs followed up for 420 days. No complications during or after surgery were observed in any of the animals. The laboratory parameters were within normal range during the entire observation period. No anastomotic stenosis was evident on percutaneous transhepatic cholangiography in animals examined 2, 6, or 12 months after surgery. The intrahepatic biliary tract was not dilated. There was obvious peristalsis of the grafted small-bowel toward the papilla of Vater. Autopsies showed that the grafts had healed without any sign…
Cryotherapy for liver metastases
Cryotherapy is undergoing a renaissance in the treatment of nonresectable liver tumors. In a prospective case control study we assessed the morbidity, mortality, and efficacy of hepatic cryotherapy for liver metastases. Between January 1996 and September 1999 a total of 54 cryosurgical procedures were performed on 49 patients (median age 66 years, 21 women) with liver metastases. Patient, tumor, and operative details were recorded prospectively. Liver metastases originated from colorectal cancer (n=37), gastric cancer (n=3), renal cell carcinoma (n=2), and other primaries (n=7). Median follow-up was 13 months (1-32). The median number of liver metastases was 3 (range 1-10) with a median dia…
Cryopreserved primary hepatocytes as a constantly available in vitro model for the evaluation of human and animal drug metabolism and enzyme induction.
The use of primary hepatocytes is now well established for both studies of drug metabolism and enzyme induction. Cryopreservation of primary hepatocytes decreases the need for fresh liver tissue. This is especially important for research with human hepatocytes because availability of human liver tissue is limited. In this review, we summarize our research on optimization and validation of cryopreservation techniques. The critical elements for successful cryopreservation of hepatocytes are (1) the freezing protocol, (2) the concentration of the cryoprotectant [10% dimethyl-sulfoxide (DMSO)], (3) slow addition and removal of DMSO, (4) carbogen equilibration during isolation of hepatocytes and…
Treatment of tumors of the pancreatic head with suspected but unproved malignancy: is a nihilistic approach justified?
The aim of the present prospective observational study was to evaluate the accuracy of preoperative imaging studies and the outcome of patients after pancreaticoduodenectomy for suspected but unproved malignancy. Pancreaticoduodenectomy was performed in 186 patients with a suspected but histologically unproved malignancy of the pancreatic head: 86 with a ductal pancreatic carcinoma, 56 with a periampullary tumor, 18 with a cystadenocarcinoma, 13 with a rare malignant tumor or a metastasis, and 13 with a benign tumor. An accurate differentiation between a ductal pancreatic carcinoma and a nonductal tumor or a benign tumor was neither possible with tumor marker CA 19-9 nor with diagnostic ima…
Cultures with cryopreserved hepatocytes: applicability for studies of enzyme induction
The use of hepatocyte cultures is well established for the study of drug-drug interactions. However, the major hindrance for the use of human hepatocyte cultures is that human hepatocytes are only occasionally available. This problem could be overcome by cryopreservation. Although cryopreserved hepatocytes have been recommended for short term applications in suspension, studies on induction of enzyme activity, requiring a more prolonged maintenance of cryopreserved hepatocytes in culture, represent a new field of research. In the present study, we established a technique that allows preparation of rat hepatocyte co-cultures, using cryopreserved hepatocytes. After incubation with phenobarbit…
Expression von CD44 und seiner Isoformen v4, v5, v6, v7, v10 – neue prognostische Parameter beim duktalen Pankreascarcinom?
Einleitung: Prognostisch relevante Faktoren sind beim Pankreascarcinom, basierend auf klinischen, laborchemischen und histopathomorphologischen Parametern bekannt. Aufgrund der grosen Variabilitat des biologischen Tumorverhaltens sind fur die Beurteilung der individuellen Prognose weitere Parameter notwendig. Ein Zusammenhang zwischen der Expression von CD44v6 und Tumorprogression bzw. Metastasierung konnte bei bestimmten Tumorentitaten nachgewiesen werden. Zum Pankreascarcinom liegen nur einzelne Untersuchungen vor. Methode: Immunhistochemisch wurden an archiviertem paraffineingebetteten Tumormaterial von 40 Patienten, bei welchen wegen eines duktalen Pankreascarcinoms eine partielle Duode…
Transanale endoskopische Operationen bei benignen Rektumpolypen
In einer retrospektiven Untersuchung wurden die Behandlungsergebnisse der transanalen endoskopischen Operationstechnik bei benignen Rektumpolypen analysiert. Im Zeitraum Januar 1986 bis Dezember 1995 wurden an der Klinik fur Allgemein- und Abdominalchirurgie der Johannes-Gutenberg-Universitat Mainz 238 Patienten (115 Manner und 123 Frauen) mit benignen Rektumpolypen transanal endoskopisch operiert (Durchschnittsalter 64 Jahre ±11,5 Jahre). Die durchschnittliche Operationsdauer betrug im Mittel 93,5 min (±54,9 min), die Grose der exzidierten Polypen war 4,2 cm (±2 cm). Die Komplikationsrate lag bei 3%, die Klinikletalitat bei 1,2% Bei einer durchschnittlichen Nachbeobachtungszeit von 56 Mona…
Prognostic significance of tumor ploidy and histomorphological parameters in adenocarcinoma of Barrett's esophagus.
<i>Background:</i> Despite recent advances in surgical and multidisciplinary treatment, the prognosis for patients with adenocarcinoma of Barrett’s esophagus remains poor. The low prognostic accuracy of even surgical pathologic TNM staging suggests that additonal parameters are necessary in determining the prognosis. <i>Method:</i> In a retrospective analysis of 50 patients who underwent transhiatal or transthoracic esophageal resection due to adenocarcinoma of Barrett’s esophagus, a quantitative DNA analysis using image cytometry was performed in addition to the TNM classification and usual morphological criteria. At the time of DNA analysis the histomorphological p…
Preoperative diagnostics in pancreatic carcinoma: would less be better?
Objective: The objective of this study was to investigate the value of preoperative diagnostics in patients with pancreatic carcinoma in terms of tumor diagnosis and evaluation of resectability. Patients/Methods: From 1 September 1985 to 31 December 1997, 408 patients shown by histology to have a ductal (n=330) or periampullary carcinoma (n=78) were treated at our hospital. Results: In determining the presence of tumor, ultrasonography and computed tomography (CT) had a sensitivity of 88.3% and 94.0%, respectively; combined, they had a sensitivity of 96.2%. Endoscopic retrograde cholangiopancreatography (ERCP) had a sensitivity of 96.2%. Preoperative aspiration biopsy cytology had a sensiti…
Factors Influencing Morbidity and Mortality after Pancreaticoduodenectomy: Critical Analysis of 221 Resections
A critical analysis of morbidity and mortality for pancreatico-duodenectomy was performed on 221 patients. During the 1960s and 1970s, the morbidity and mortality for pancreaticoduodenectomy were so high that many thought the operative procedure ought to be abandoned. During the 1980s, however, many centers reported mortality rates around 5% and a morbidity of 25% to 35%. Others still reported a mortality of more than 10% and a morbidity of up to 65%. The reasons for these discrepancies are of major interest. In a prospective case-control study 760 patients with malignant and benign diseases of the pancreas were treated in our hospital between September 1, 1985 and April 30, 1997. In 221 ca…
Wie viele Lymphknoten müssen bei gastrointestinalen Tumoren zur Beurteilung des pN Status entfernt werden?
Die von der UICC vorgegebene Anzahl der zu resezierenden Lymphknoten zur korrekten Festlegung des pN Status von gastrointestinalen Tumoren beruht auf empirischen Werten. Beim Oesophaguskarzinom wird eine Lymphknotenanzahl von mindestens 6 LK empfohlen [1], bem Kolon- und Rektumkarzinom liegt die Richtzahl der zu resezierenden Lymphknoten bei 12 LK [1]. Bei Uberschreiten dieser Richtzahl wird im Umkehrschlus angenommen, das die Wahrscheinlichkeit einer Anderung des Lymphknotenstatus (pN) gering ist, auch im Falle einer ausgedehnteren Lymphknotendissektion. Hier besteht oft eine Diskrepanz zwischen Pathologen und Chirurgen. Von Interesse ist daher, ob diese Vorgaben mittels eines mathematisch…
Veränderungen der extrazellulären Matrix in der Venenwand — Ursache der primären Varikosis?
Die kontraren Theorien zur Entstehung der primaren Varikosis fuhrten zur molekularbiologischen Untersuchung der Venenwand, genauer der extrazellularen Matrix. Das Ziel war, die Matrixexpression zu quantifizieren und die pathologischen Veranderungen der Venenwand mit der klappenorientierten Stadieneinteilung der Varikosis zu vergleichen, um so Hinweise auf eine primare Ursache der Varizenbildung zu erhalten.
DNA image cytometry in stomach carcinoma. Its relation to histomorphologic parameters and its influence on prognosis
BACKGROUND The influence of DNA content on the prognosis in stomach cancer is controversial. METHOD After curative resection of stomach carcinomas (adenocarcinomas [n = 58]; signet ring cell carcinomas [n = 24]; undifferentiated carcinomas [n = 21]), the influence of the DNA content and histomorphologic parameters on the prognosis was examined. RESULTS In the multivariate regression analysis, the prognosis depended on the lymph node status (P = 0.0009), pT stage (P = 0.02), tumor localization (P = 0.03), and histologic type (P = 0.05). The prognosis was independent of the DNA content. Furthermore, the degree of differentiation, operative procedure, safety distance, size of the tumor, and se…
Prognostic value of DNA analysis in colorectal carcinoma.
BACKGROUND Reported experiences regarding the prognostic significance of DNA content in colorectal carcinoma have been a matter of controversy. METHODS DNA analysis with image cytometry was performed in 137 patients with colorectal cancer. Only patients who had resection without tumor residual and who did not die postoperatively as a consequence of the operation were entered in the study. At the time of DNA analysis, neither the histomorphologic data nor the relapse-free survival time of the patients were known. RESULTS In this investigation the DNA content of tumor cells had no univariate or multivariate influence on the relapse-free survival time. The prognosis was dependent on the tumor …
Allgemeine-, Transplantations-, Kinderchirurgie, Intensivmedizin
175 wegen einer infantilen hypertrophischen Pylorusstenose (IHPS) behandelte Patienten wurden 17–25 Jahre nach konservativer (n = 68) bzw. oeprativer (n = 112) Behandlung nachuntersucht. Bei den operativ behandelten Patienten war die Krankenhausaufenthaltsdauer signifikant kurzer. Sowohl nach konservativer als auch nach operativer Therapie der IHPS konnten keine Storungen der Magenmotorik auf Dauer nachgewiesen werden: Symptome einer verzogerten Magenentleerung sowie Ulcera ventriculi bzw. duodeni und verzogerte Magenentleerungsgeschwindigkeiten, welche szintigraphisch fur feste und flussige Nahrung gemessen wurden, fanden sich in beiden Gruppen im Vergleich zu einem Kontrollkollektiv nicht.
Factors influencing survival after resection of pancreatic cancer. A DNA analysis and a histomorphologic study
BACKGROUND The influence of DNA content on prognosis in stomach cancer has been investigated rarely, and the results are controversial. METHOD The prognostic relevance of the DNA content and histomorphologic parameters was evaluated in 41 patients after resection of pancreatic cancer. RESULTS In the univariate analysis, the DNA content, tumor size, lymph node status, tumor stage, nuclear grade, and type of resection had a statistically significant influence on the prognosis. No association was found between the DNA content and the histomorphologic features. Apart from the operative procedure, the DNA content was the strongest indicator of prognosis in the multivariate analysis. CONCLUSIONS …
Permissive and suppressive effects of dexamethasone on enzyme induction in hepatocyte co-cultures.
1. Steroids are known to act as permissive factors in hepatocytes. This study shows that dexamethasone (DEX) is a permissive factor for induction of CYP2B1/2, CYP3A1, CYP2A1 and probably also CYP2C11 in cultures with primary rat hepatocytes. 2. The induction factor of phenobarbital (PB)-induced formation of 16beta-hydroxytestosterone (OHT), a testosterone biotransformation product predominantly formed by CYP2B1, is increased 18-fold by the addition of 32 nM DEX to the culture medium. Interestingly, higher concentrations of DEX up to 1000 nM led to a concentration-dependent maximally 5-fold decrease (p = 0.002) of phenobarbital-induced 16beta-OHT formation compared with the effect observed w…
DNA-gehalt der tumorzelle
Aufgrund der hohen Morbiditat und Mortalitat nach Leberresektion wegen eines hepatozellularen Karzinoms ist es sinnvoll, prognostisch relevante Faktoren zu evaluieren, um die Patienten zu definieren, die von einer Resektion profitieren um den anderen das Risiko eines komplikationstrachtigen Eingriffs zu ersparen. Am archivierten paraffineingebetteten Tumormaterial von 21 Patienten mit einem hepatozellularen Karzinom wurde nach Leberresektion mittels bildanalytischer DNA-Analyse die Ploidie bestimmt. Im DNA-Histogramm fanden sich diploide, hypotriploide, triploide, hypertriploide, tetraploide und nicht naher klassifizierbare aneuploide Tumoren. Es fand sich eine statistisch signifikante Korr…
Diagnosing and staging of pancreatic carcinoma-what is necessary?
The aim of the present prospective observational study was to diagnose and stage pancreatic carcinoma with a minimum of diagnostic procedures. Our experiences in 307 patients with a histologically confirmed pancreatic carcinoma show that for diagnosing pancreatic carcinoma sonography and computed tomography are sufficient in 95% of the cases. The combination of both has a sensitivity equal to that of endoscopic retrograde cholangiopancreatography (ERCP; 96.8 vs. 98.7%; n.s., χ<sup>2</sup> test). ERCP is only indicated in cases with negative sonography and computed tomography, and suspicion of pancreatic cancer. For tumor staging, the routine performance of angiography cannot be …
Value of Quantitative DNA Analysis in Endocrine Tumors of the Pancreas
The diagnosis of malignancy can be difficult in endocrine tumors of the pancreas. Moreover prognostically relevant factors are not available. The aim of this study was to evaluate retrospectively whether the DNA distribution pattern can differentiate between benign and malignant pancreatic endocrine tumors and secondly whether the DNA content of tumor cells gives prognostic information.Image cytometry of paraffin-embedded tumor material of 42 pancreatic endocrine tumors.In 27 benign endocrine pancreatic tumors (25 insulinomas, 2 benign nonfunctioning endocrine tumors) we could differentiate between 6 diploid, 15 hypotriploid and 6 triploid DNA histograms. In 15 malignant endocrine tumors of…
Hat das Ausmaß der Lymphknotendissektion einen Einfluß auf die Morbidität und Prognose nach Pankreaskopfresektion wegen eines duktalen oder periampullaren Pankreaskarzinoms?
We examined the influence of lymph node dissection on morbidity and mortality of 13 patients after resection of the head of pancreas due to a ductal or periampullary carcinoma. In both groups the radicality of the operation was the main prognostic factor. In ductal pancreatic carcinoma the R-status was able to be determined better by normalisation of the postoperative Ca 19-9 serum level than by the evaluation of the surgeon or pathologist. For prognosis, the quotient of metastatic lymph nodes to resected lymph nodes indicates that an extensive lymph node dissection may increase the long term survival. A lymph node dissection is therefore to be recommended, especially since it does not incr…
DNA image cytometry. A prognostic tool in squamous cell carcinoma of the esophagus?
In 45 patients who underwent an esophagus resection due to a squamous cell carcinoma, in addition to the TNM classification and usual morphologic criteria, the paraffin-embedded material underwent deparaffinization, was rehydrated, and was mechanically and enzymatically processed into a single-cell solution. For evaluating the DNA histogram this was analyzed with the help of automatic single-cell cytophotometric study. The method, contrary to that of flow cytometric study, allows for the selective analysis of tumor cells due to the electronically, previously given selection criteria, whereas artifacts, stroma, and infection cells remain excluded from analysis. The multivariate analysis show…
Stellenwert des Tumormarkers CA 19–9 in der Differentialdiagnose von Raumforderungen im Pankreaskopf
In 96 patients (ductal pancreatic carcinoma, n = 34; periampullary carcinoma, n = 43; chronic pancreatitis, n = 19) the role of CA 19-9 in the diagnosis of lesions of the head of the pancreas were evaluated. The sensitivity for ductal pancreatic carcinoma was 73.3%, for periampullary carcinoma 48.8%, and specificity was 63.2%. Carcinoembryonic antigen was elevated only in every fifth patient. Even when combining the two tumor markers no increase in sensitivity could be observed. The low specificity of 63%, which decreased to 33% in the case of obstructive jaundice, does not allow adequate preoperative differentiation between cancer patients and those with chronic pancreatitis. In cases of p…
Resistance factors in colon cancer tissue and the adjacent normal colon tissue: glutathione S-transferases alpha and pi, glutathione and aldehyde dehydrogenase.
Abstract Glutathione S -transferases (GST) α and π , glutathione (GSH) and aldehyde dehydrogenase (ADH) were determined in colorectal cancer tissue specimens and in the adjacent normal colon tissue. The median contents in normal and cancer tissue were 8.1 (2.3–30.3) (5–95% quantiles) and 15.1 (5.3–50.3) μ g/mg protein for GST π ( P =0.035), 0.0 (0.0–1.4) and 0.4 (0.0–3.5) μ g/mg protein for GST α ( P =0.019), 7.3 (1.3–22.7) and 5.6 (2.3–26.0) μ g/mg protein for GSH ( P =0.171) and 30.8 (13.0–42.0) and 23.2 (9.0–32.9) μ g/mg protein for ADH ( P =0.0017), respectively. Thus, the mean GST α and π both significantly increased in colon cancer compared to the adjacent normal tissue, which underli…
Expression of CD44 variant proteins in adenocarcinoma of Barrett's esophagus and its relation to prognosis
BACKGROUND None of the commonly used staging criteria accurately determine the prognosis of a patient with adenocarcinoma of Barrett's esophagus. The authors therefore assessed the expression pattern and prognostic impact of CD44 standard and CD44 isoforms CD44v4, v5,v6,v7, and v10 in adenocarcinoma of Barrett's esophagus. METHODS Specimens from 41 patients with adenocarcinoma of Barrett's esophagus who underwent esophageal resection were embedded in paraffin and studied immunohistochemically to determine the expression of CD44 splice variants. Histomorphologic parameters and survival time were not known at the time of the investigation. RESULTS Correlations between favorable clinical or hi…
Is preoperative radiographic localization of islet cell tumors in patients with insulinoma necessary?
Preoperative localization tests [sonography, computed tomography, angiography, percutaneous transhepatic portal venous sampling for insulin radioimmunoassay (PTP)] have a sensitivity of 60% to 90% in cases of organic hyperinsulinism. In all publications, however, the sensitivity of intraoperative localization, 75% to 100%, is distinctly higher. With the exception of PTP, all tumors that can be identified by preoperative localization can also be detected using palpation or intraoperative sonography. Preoperative localization diagnosis is therefore not absolutely necessary prior to primary operation in the case of organic hyperinsulinism. It is requested by many surgeons because: (1) only a f…
DNA image cytometry
In 68 patients the DNA content of tumor cells was measured by image cytometry after resection of the rectum because of cancer. In the DNA histogram a differentiation between diploid (n = 19), polyploid (n = 24), hypotriploid (n = 17), and hypertriploid (n = 8) tumors was possible. The best relapse-free survival time was found in patients with diploid tumors. The prognosis worsened from polyploid to hypotriploid and was worse in hypertriploid tumors. Testing for a prognostic advantage of diploid over aneuploid tumors without adjustment for additional factors simply by means of the log-rank statistic gave a (one-sided) P of 0.1013. In a multivariate analysis the degree of differentiation turn…