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Biomedical subjects

R Klapdor

Publications and source records attributed to R Klapdor.

At least 55 records · Page 3Linked to original sources

Radioimmunotherapy of xenografts of human pancreatic carcinomas--intravenous and intratumoral application of 131I-labelled monoclonal antibodies.

The effects of radioimmunotherapy were tested in xenografts of 2 different human pancreatic carcinomas comparing the intravenous and intratumoral application. On principle, intravenous injections of high doses of 131I-anti-CA 19-9 or -BW 494/32 may inhibit tumor growth. In view of the low direct radiation dose (360-2100 rad), however, other factors than direct toxic effects have to be discussed, e.g. systemic effects due to the high whole-body irradiation. Intratumoral application, however, may induce tumor regression or growth inhibition due to the high local irradiation dose. Consequently, this treatment modality might be of clinical value at least in some patients.

Animals↗

Creatine kinase isoenzymes: biochemical findings after therapeutical embolization of the hepatic artery in two patients with liver metastasis of an islet cell carcinoma or a carcinoid tumor.

An atypical creatine kinase (CK) isoenzyme migrating cathodically to CK-MM in the electrophoresis was observed as response to the embolization of the right hepatic artery in two patients with liver metastasis. The time course of the atypical CK release was compared to that of tumor secretion products, i.e., insulin and 5-hydroxy-in-dol-acetic acid. The CK isoenzyme probably reflects a mitochondrial breakdown of the metastasis in question. The influence of the treatment on liver function was characterized by a marginal augmentation of ASAT and ALAT and by a small but significant leakage of mitochondrial glutamate dehydrogenase. In addition to the atypical CK, CK-BB, and CK-MB isoenzymes were found in the serum of the patient with primary carcinoid carcinoma.

Adenoma, Islet Cell↗

Multiparametric tumor marker (CA 19-9, CEA, AFP, POA) analyses of pancreatic juices and sera in pancreatic diseases.

With respect to their diagnostic utility CA 19-9, CEA, AFP and POA were determined in pancreatic secretions and serum of patients suffering from pancreatic cancer (n = 76/55) or chronic pancreatitis (n = 79/45) and of controls (n = 81/42), respectively. While the determination of AFP and POA both in pancreatic secretions and serum does not permit a differential diagnosis, serum CEA (greater than 10 ng/ml) and CA 19-9 (greater than 50 U/ml) levels were indicative of pancreatic cancer in 30% and 83%, respectively, with a rate of false positive results of 5% and 8.5% confined to the chronic pancreatitis patients. A combination of tumor marker analyses, that is, serum CA 19-9 (greater than 50 U/ml) and pancreatic secretion CEA (greater than 70 ng/ml), proved to be positive in 92.9% of tumor patients with a maximum of 10.5% false positives. Likewise, values of serum CA 19-9 (greater than 50 U/ml) and serum CEA (greater than 10 ng/ml) were found in 85.8% of the pancreatic cancer patients with only 8.8% false positives, which were confined to the chronic pancreatitis patients. These results indicate the superiority of multiparametric tumor marker analyses for the diagnosis of pancreatic cancer, especially when including new monoclonal antibody defined tumor markers.

Antigens, Neoplasm↗

[Immunoscintigraphy and radioimmunotherapy of transplanted pancreatic carcinoma. Experimental animal studies with 131I-labeled monoclonal antibodies against CA 19-9, CEA and CA 125].

The immunoscintigraphic results in 12 human pancreatic carcinomas established on nude mice (Nu-Nu-Balb-C) are reported. The transplanted tumors corresponded to the human cancers concerning histology, grading, immunohistochemistry and secretion of tumor-associated antigens. 131I-labeled monoclonal antibodies against CA 19-9, CEA and CA 125 were used. These antigens are found in the serum of more than 90% of patients with pancreatic carcinoma at the time of first diagnosis. The result show that pancreatic carcinomas are detectable with the antibodies applied here. The quality of the scintigraphic detection depends, among other factors, on the antibody affinity to the tumor, the localization and the size of the tumor. Preliminary results of the studies on radioimmunotherapy of pancreatic cancer with 131I-anti-CA 19-9 indicate that effective absorbed doses in the tumor may be achieved via intravenous application only in cases with a rather high expression of the tumor antigen. But direct instillation into the tumor enables therapeutic radiation doses to the tumor even with moderate affinity and a low whole-body burden, as shown by experiments in 8 mice bearing 4 different human pancreatic carcinomas, 3 with positive and 1 with negative affinity to CA 19-9: the tumor retentions and the effective half-lives of 131I-anti-CA 19-9 were measured after intratumoral (100 microCi/mg tumor) or intravenous (30 and 190 microCi/g body weight) application.

Animals↗

[Immunoscintigraphy and SPECT in patients with pancreatic cancer].

Encouraged by reports on immunoscintigraphy of colorectal carcinomas and by the results of our own immunohistochemical and immunoscintigraphic studies in nude mice with transplanted pancreatic carcinoma, we studied the diagnostic potential of immunoscintigraphy with a cocktail of 131I-labeled monoclonal antibodies against the tumor markers CA 19-9 and CEA in 21 patients with pancreatic cancer disease. The results were compared with those of 10 patients suffering from colorectal tumors, 2 cases with bile duct carcinoma and 1 with gastric cancer. Planar scintigraphy with 2-4 views was done repeatedly within 6 days after i.v infusion of 2 mCi of the antibody cocktail. SPECT was performed 3-4 days p.i., recently at 1 or 2 days, too. Primary tumors and metastases in the upper abdominal parts were more difficult to detect and to localise in comparison to colorectal cancer in the lower parts of the abdomen, because of relatively high tracer accumulation in kidneys, liver and spleen. Tumor enhancement in planar scintigrams was, in most cases, not recognized prior to 5 or 6 days p.i., but by SPECT 3 days p.i. or even earlier. Localisation and topographic determination were much easier and more frequent with SPECT, so that tumor detection became more reliable and sensitive. Large tumors could be detected in some cases without tumor marker concentrations in serum being elevated. Immunoscintigraphy of pancreatic carcinomas and of other cancer manifestations in the upper abdomen up to now seems to be of limited diagnostic value, the techniques involved need to be improved.

Adult↗

[Diagnostic imaging of the remission of a metastasized hormone-producing pancreatic carcinoma (PPom) as affected by polychemotherapy].

The pros and cons of various imaging methods (sonography: plain CT, with contrast medium intravenously/serial CT; x-ray angiography or digital subtraction angiography) in recognising a slow but steady remission of a primary tumour and of liver metastases are discussed, basing on the course of disease in a female patient with a metastasised gastrointestinal malignoma under chemotherapy. Initial chemotherapeutic treatment lasted for two years. Renewed progression after another 2 1/2 years had meanwhile been stopped again by chemotherapy. Sonography and CT control follow-ups were performed on a three-month basis for a total period of more than five years. In sonography, remission was noticeable on the one hand by changes of echo-internal structure of the tumour and liver metastases, and on the other hand by size reduction. Sonography possesses the advantage over CT that sections can be performed multidirectionally and are reproducible, for example for the purpose of documenting the largest tumour diameter. A drawback is in our opinion the lack of information supplied by the method in respect of the vascular situation within the area of malignant space-occupying growths. A valuable asset of computed tomography is the possibility of demonstrating hypervascularisation in a solid space-occupying growth by using an intravenously applied contrast medium which is easily passed through the kidneys, especially in "serial CT" procedures. This is similarly true for angiography, which, however, does not play any significant part in closely-meshed follow-up schedules because if its invasiveness. As a matter of fact, it can even simulate a florid tumour or metastasising process.

Angiography↗

[CA 12-5 in cancer of the digestive tract. A comparison with CA 19-9 and CEA in cancer of the pancreas and colon].

In 42 control subjects and 134 patients with benign or malignant disease of the pancreas or large intestine, the recently produced tumour-associated antigen CA 12-5 was determined together with CEA and CA 19-9. Only 4% of controls and patients with benign disease (except those with acute pancreatitis) had CA 12-5 values above 35 U/ml, compared with 60% of patients with pancreas carcinoma and 21% with colon carcinoma. For the former (pancreas carcinoma) there was also a good correlation to stage of tumour (0 of 6 tumours stage TxN0M0, 7 of 11 TxN1M0, 16 of 20 TxN1M1 greater than 35 U/ml) and progression of the malignancy. Simultaneous determination of all three antigens increased the rate of tumour-marker positive patients from 87% (CA 19-9) to 92% for pancreas carcinoma and from 25% (CEA) to 51% for colon carcinoma.

Acute Disease↗

[Morphologic criteria of the growth behavior of pancreatic cancers. Experimental and clinico-pathologic studies].

In order to improve the individual characterization of ductal adenocarcinoma of the pancreas histologic and cytologic criteria of tumour differentiation were correlated with tumour growth. The most relevant parameters of grading were glandular differentiation, nuclear polymorphism and frequency of mitoses (number of mitoses per ten visual fields with magnification through the 40 objective). Using these criteria three grades of tumour (G) were separated. In 7 human adenocarcinomas of the pancreas transplanted onto nude mice GIII tumours showed a tumour replication time of approximately half of that of GI tumours. In an additional clinico-pathological study in 75 partial or total pancreas resection preparations with carcinoma of the head of the pancreas a significantly longer symptomatic time until diagnosis was found in GI tumours (n = 34) than in GII (n = 33) and GIII tumours (n = 8). Besides, GI tumours showed a generally lower staging at the time of operation than did GII and GIII tumours. The median values of postoperative survival time for GI (n = 12) and GII tumours (n = 12) with identical staging was 10.5 and 7 months, respectively. The results indicate that the suggested grading of ductal adenocarcinomas of the pancreas reflects the biological behaviour of these tumours and can thus be used as an additional prognostic parameter in staging.

Adult↗

[Differential sonographic diagnosis. Pancreas (pseudo) cyst--choledochus cyst].

The case of a woman patient with an extended prepapillary choledochal cyst and pancreaticobiliary reflux shows that it is necessary to consider the possibility of a choledochal cyst on detecting a cystic structure in the head of the pancreas (condition after acute pancreatitis); besides this, differential diagnosis will have to consider a pancreatic pseudocyst, hydrops of the gallbladder, a retroperitoneal cyst or even vascular aneurysm. If necessary, the physician should take suitable diagnostic measures before performing any percutaneous cyst drainage which he may have planned, since this may entail the risk of biliary peritonitis.

Common Bile Duct Diseases↗

[Ulcer risk of reflux-preventing reconstruction following stomach resection--an animal experiment study].

In an experimental study on 376 rats the ulcer risk was analyzed after Roux-Y-gastrojejunostomy resp. jejunal interposition. The following results were obtained: 5 to 10 months postoperatively stomal ulcers were found in up to 90%. The longer the jejunal segment, i.e. the lesser the reflux, the higher was the ulcer risk. The interval of ulcer manifestation could be shortened to 7 resp. 10 days by continuous histamine stimulation, while the differences between the groups remained unchanged. An extended resection was of negligible influence on the elevated ulcer risk in long jejunal segments, that means refluxfree conditions. The gastric pH was influenced by the length of the jejunal segment, the longer the segment, the more acid was the pH. With long, refluxfree segments normal pH-values could be observed despite of an extended gastric resection. An additional vagotomy caused a reduction but not an elimination of the ulcer risk. We conclude from our results, that there is a protective role of the postresectional intestino-gastric reflux on the gastrojejunal anastomosis. A refluxpreventive procedure is therefore heavily ulcerprone.

Animals↗

Interdigestive motilin secretion and gallstone disease.

Plasma motilin concentrations were measured in eight controls and 11 patients with radiolucent gallstones over a period of 3-4 h following an overnight fast. In five of these patients the interdigestive motor complex (IDMC) was studied simultaneously. The results indicate: a) cyclical changes of plasma motilin concentrations (mean cycle duration 110 +/- 9.9 and 102 +/- 8.4 min, means +/- SEM) and a significant correlation between the basal intercyclical motilin concentrations and the age (p less than 0.02) in the controls and the gallstone patients studied, and b) a significant correlation between the maximal motilin increase and the age in the controls (p less than 0.01) but not in the gallstone patients. The results therefore suggest a different behaviour of the interdigestive motilin patterns in controls and gallstone patients. As the motilin cycles were accompanied in 90% with an IDMC in the five patients studied this conclusion might include an abnormal interdigestive motor activity within the intestinal tract in gallstone patients.

Cholelithiasis↗

Quantification of tracer kinetics in intra- and extrahepatic bile ducts and of gallbladder filling rates in hepatobiliary dynamic scintigraphy using 99mTc-IDA derivates.

A method is presented of calculating the flow of 99mTc-labelled IDA derivates in intra- and extrahepatic bile ducts. By computer means the superimposed liver parenchymal activity is subtracted from the original sequence data in each pixel and at each time. In addition to known evaluation methods, the described procedure seems to be helpful for clinical application in order to better display anatomical details of intrahepatic structures like bile ducts and to calculate quantitative parameters like appearance times in intra- and extrahepatic regions. Examples are given and the possibility of calculating a gallbladder filling rate for separating normal gallbladders from stone-filled ones is statistically proven.

Adult↗