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Biomedical subjects

K H Bohuslavizki

Publications and source records attributed to K H Bohuslavizki.

At least 19 recordsLinked to original sources

The role of nuclear medicine in the diagnosis of cancer of unknown origin.

Cancer of unknown origin (CUO) is defined by the absence of any primary tumour in biopsy-proved metastatic cancer. CUO accounts for a 5-10% of all malignancies. These tumors have a specific biology with clinical characteristics of rapid progression and atypical metastases. Diagnostic evaluation is directed at the identification of treatable subset. Accurate diagnostic workup is crucial because both prognosis and survival rates depend mainly on detection of the primary tumor site. Although these patients undergo extensive imaging procedures, nuclear medicine techniques are under-utilized despite their ability of providing molecular information. Positron emission tomography has an emerging role in this clinical challenge along with other nuclear medicine methods including, bone scan, thyroid scintigraphy.

Biomarkers, Tumor↗

[Reducing late toxicity with amifostine in fractionated irradiation of the rat salivary glands].

Clinical studies show that amifostine can reduce xerostomia and mucositis during radiotherapy of head and neck cancers. The aim of this study was to evaluate the radioprotective potency of amifostine with respect to late toxicity of salivary glands of rats. The head-neck-area of 8 male WAG/RijH rats (295 +/- 7 g) were irradiated with 60Co-gamma-rays (60 Gy/30 f/6 weeks). Amifostine (250 mg/m2 body surface) was applied via a venous port 15 min before each irradiation. Rats of a control group were irradiated with the same schedule with equal volumes of physiological saline. The morphological and sialoscintigraphical findings clearly demonstrate that amifostine has a remarkable cytoprotective effect on the late toxicity of irradiated salivary glands.

Amifostine↗

Comparison of fluorodeoxyglucose positron emission tomography and "conventional diagnostic procedures" for the detection of distant metastases in breast cancer patients.

The presence of distant metastases is the main prognostic factor in patients with breast cancer and has a significant influence in the choice of therapy. Therefore, chest X-ray, bone scintigraphy and ultrasound of the abdomen are performed to detect distant metastases at diagnosis and follow-up. Fluorodeoxyglucose positron emission tomography (FDG PET) has been shown to provide sensitive detection of primary tumour and metastases for many tumour entities, but little information is available about the diagnostic value for breast cancer patients. This study retrospectively compared FDG PET for detection of metastatic disease with chest X-ray, bone scintigraphy and ultrasound of the abdomen, referred to as "conventional diagnostic procedures" (CDPs), in 50 breast cancer patients. Imaging procedures were analysed in a blinded fashion with the results classified as "no evidence of metastases", "equivocal" and "evidence of metastases". Clinical follow-up and the results of other imaging modalities including computed tomography and magnetic resonance imaging were used to determine if metastases were present. FDG PET identified metastatic disease with a sensitivity and specificity of 86% and 90% as compared to 36% and 95% for CDPs, respectively. Regarding "equivocal" and "evidence of metastases" as positive, the sensitivity of CDPs increased to 57% with a corresponding specificity of 81%, whereas sensitivity and specificity of FDG PET remained unchanged. Regarding different localities of metastases the sensitivity of FDG PET was superior in the detection of pulmonary metastases and especially of lymph node metastases of the mediastinum in comparison to chest X-ray, whereas the sensitivity of FDG PET in the detection of bone and liver metastases was of the same magnitude as compared with bone scintigraphy and ultrasound of the abdomen.

Adult↗

Multiple application of drugs in rats--a new port system.

The implantation of a small port system for repeated intravenous applications of drugs in rats is described. The system basically consists of a Teflon catheter which is inserted into the right internal jugular vein. The open end of the catheter under the right foreleg is subcutaneously carried through to the back and closed by a small port. The port then is implanted into a skin pocket on the back of the rat. The advantage of this method is that repeated intravenous injections of drugs into rats can easily be applied with high accuracy. Complications were rarely observed (7%) and could be mastered successfully in all cases.

Animals↗

Fluorine-18 fluorodeoxyglucose positron emission tomography in medullary thyroid cancer: results of a multicentre study.

The aim of this study was to evaluate the clinical use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in medullary thyroid cancer (MTC) on the basis of comparison with findings obtained using indium-111 pentetreotide (SMS), pentavalent technetium-99m dimercaptosuccinic acid (DMSA), technetium-99m sestamibi (MIBI), computed tomography (CT) and magnetic resonance imaging (MRI). One hundred FDG-PET examinations in 85 patients (40 males, 45 females) with elevated tumour marker levels and/or pathological findings on other imaging methods were evaluated retrospectively. Eighty-two patients were examined after total thyroidectomy, and the remaining three patients prior to surgery. Overall, 181 lesions could be identified with at least one of the imaging techniques. Fifty-five lesions were confirmed histologically. FDG-PET detected 123 of 181 sites, which is a lesion detection probability of 68%. In the 55 cases with histological confirmation, we found 32 true positive, 3 false positive, 11 true negative and 9 false negative lesions using FDG-PET, resulting in a sensitivity of 78% and a specificity of 79%. Sensitivity and specificity were, respectively, 25% and 92% for SMS, 33% and 78% for DMSA, 25% and 100% for MIBI, 50% and 20% for CT and 82% and 67% for MRI. Compared with morphological techniques and functional imaging methods with single-photon emitters, FDG-PET showed the highest lesion detection probability for MTC tissue, with a high sensitivity and specificity. It is concluded that FDG-PET is a useful method in the staging and follow-up of MTC.

Adult↗

18FDG-PET following treatment as valid predictor for disease-free survival in Hodgkin's lymphoma.

PURPOSE: The value of 18FDG-PET to predict the outcome after therapy in Hodgkin's lymphoma was compared to morphologic staging and ESR. PATIENTS AND METHODS: A total of 50 concurrent 18FDG-PET and CT studies were performed in 37 patients with Hodgkin's lymphoma. ESR was evaluated 32 times after treatment was completed. RESULTS: Out of 39 residual masses found by CT 8 relapses could be proven. Out of 11 CT exams with CR 3 relapses occurred. CT turned out to show a sensitivity, specificity, PPV, NPV, and accuracy of 72%, 21%, 21%, 73%, and 32%, with respect to predict disease-free survival (DFS). 18FDG-PET was positive in 22 examinations with 10 recurrences in this group. Out of 28 negative 18FDG-PET 1 relapse developed 3 years later. 18FDG-PET turned out to show promising sensitivity, specificity, PPV, NPV, and accuracy of 91%, 69%, 46%, 96%, 74%, with respect to predict DFS. ESR was elevated in 12 studies of which 5 relapses could be proven, while out of 20 normal ESR-studies 3 relapses occurred. Thus, ESR turned out to show sensitivity, specificity, PPV, NPV, and accuracy of 63%, 71%, 42%, 85%, and 75%, with respect to predict DFS. In summary, only 18FDG-PET was able to predict DFS statistically significant. CONCLUSION: 18FDG-PET can be very useful in patients with residual masses after treatment.

Adolescent↗

Long-term results of radiation synovectomy: a clinical follow-up study.

Radiation synovectomy by intra-articular injection of beta-emitting radionuclides is a reliable and easy-to-perform therapy without harmful side effects for the treatment of inflammatory rheumatoid as well as degenerative joint diseases. The indication for radiation synovectomy is based on both clinical symptoms and on proven hyperperfusion, with active synovitis being seen on a pre-therapeutic three-phase bone scan. In this study, the clinical response after 6-18 months, evaluated by a standardized questionnaire, was compared with the reduction of synovitis seen on three-phase bone scintigraphy after treatment of 475 joints in 151 patients. The best clinical results were obtained in cases of true rheumatoid arthritis (73.4%), with less in other kinds of arthritis (48.8%) such as psoriatic or reactive arthritis. Because of the inflamed synovium being the main target tissue, clinical results in osteoarthritis with severe bone destruction are poorer (33.9%). However, synovitis can be markedly reduced (in approximately 70%), regardless of the underlying diagnosis, as shown by post-therapeutic three-phase bone scanning. Radiation synovectomy can be recommended in all kinds of arthritis. It should also be considered in cases of osteoarthritis as a last therapeutic option prior to joint replacement.

Adult↗

Value of FDG PET in patients with fever of unknown origin.

Fever of unknown origin (FUO) is a diagnostic challenge, because the cause of such fever may be manifold. Studies on the use of positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG), for the diagnosis of inflammation in patients with osteomyelitis or HIV have been promising and suggest its use in patients with FUO. In this study, we used FDG PET in 16 patients with FUO in whom conventional diagnostics had not been conclusive. In 12 patients, (75%) non-physiological accumulations of FDG were found which led to the final diagnosis in 11 patients (69%). FDG PET was negative in four patients (25%). Two of these patients had rheumatic fever, while in the other two patients the origin of fever could not be detected within 3 months after PET by any other laboratory or imaging means. These findings point to the high sensitivity of FDG whole-body PET for the detection of morphologically assessable foci as an origin of FUO. Moreover, they suggest a high negative predictive value of FDG PET in the setting of FUO, since in no patient with a negative FDG PET could a morphological origin of the fever be determined. In conclusion, FDG whole-body PET appears to be a promising diagnostic tool in patients with FUO, in whom conventional diagnostics had been unsuccessful.

Adult↗

Long-term effects of 'ecstasy' abuse on the human brain studied by FDG PET.

The popular recreational drug, 'ecstasy', mainly contains 3,4-methylenedioxymethamphetamine (MDMA) as the psychotropic agent. MDMA is suspected of causing neurotoxic lesions to the serotonergic system as demonstrated by animal studies, examinations of human cerebrospinal fluid, and the first positron emission tomography (PET) studies using the serotonin transporter ligand [11C]-McN5652. Damage of serotonergic afferents might mediate long-lasting alterations of cerebral glucose metabolism as a secondary effect. To study a relationship between ecstasy use and long-lasting alterations, PET using 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) was performed in 93 ecstasy users and 27 subjects without any known history of illicit-drug abuse. As an index of glucose metabolism, mean normalized FDG uptake was determined in both groups using a computerized brain atlas, and was compared for a selected number of brain regions. FDG uptake was normalized in each individual by dividing local FDG uptake by the maximum FDG uptake in the individual's brain. Within the group of ecstasy users we examined the relationship between FDG uptake and cumulative ecstasy dose, time since last ecstasy ingestion at the time of PET scanning, and age at first ecstasy use, respectively. Normalized FDG uptake was reduced within the striatum and amygdala of ecstasy users when compared to controls. No statistically significant correlation of the FDG uptake and the cumulative dose of ecstasy was detected. A positive correlation was found in the cingulate between FDG uptake and the time since last ecstasy ingestion. As compared to the control group, normalized FDG uptake in the cingulate was reduced in ecstasy users who took ecstasy during the last 6 months, while it was elevated in former ecstasy users who did not consume ecstasy for more than 1 year. FDG uptake was significantly more affected in ecstasy users who started to consume ecstasy before the age of 18 years. In conclusion, ecstasy abuse causes long-lasting effects on glucose metabolism in the human brain. These effects are more severe in the case of very early abuse. However, several questions still remain to be answered, i.e. the correlation of the neuronal alterations and the history of ecstasy use (cumulative dose, and time since the last dose) and its reversibility.

Adolescent↗

FDG PET in the diagnosis of hilar cholangiocarcinoma.

Resectional surgery offers a curative intent and a survival benefit for patients with hilar cholangiocarcinoma, but is associated with high morbidity. Since morphological imaging cannot solve differential diagnosis preoperatively, in order to exclude patients inappropriate to this aggressive surgery, we evaluated the impact of functional imaging using fluorodeoxyglucose positron emission tomography (FDG PET) in the detection of cholangiocarcinoma and its usefulness in the differentiation from benign Klatskin tumour-mimicking lesions. Fifteen consecutive patients aged 47-78 years underwent standardized whole-body FDG PET with attenuation correction before potentially curative surgery using a conventional full-ring PET scanner with an axial field-of-view of 16.2 cm. FDG PET was evaluated visually and semiquantitatively using tumour-to-background ratios (T/B) ratios. All lesions were evaluated histopathologically. FDG PET presumed to be indicative for carcinoma was positive in 12 of 15 patients, true positive in 10 (T/B ratio, 3.2+/-1.9) and false positive in two of them (T/B ratios, 2.1 and 2.8) with Klatskin tumour-mimicking lesions. While all true positive PET results were seen in the tubular type of cholangiocarcinoma with a high amount of tumour cells and only low production of mucus, a false negative FDG PET in three patients was observed in mucinous adenocarcinoma. Additionally, FDG PET detected locoregional lymph nodes in two patients and distant metastases in a further three patients. Due to false positive results FDG PET does not allow the differentiation of benign from malignant lesions, and FDG PET should be avoided in patients with mucinous cholangiocarcinoma. However, FDG PET may have significant influence on the treatment strategy in as much as 20% of the patients, since it may detect distant metastases.

Aged↗

In vitro function of islets of Langerhans encapsulated with a membrane of porcine chondrocytes for immunoisolation.

BACKGROUND/AIMS: Widespread clinical application of islet transplantation remains restricted, because of insufficient methods to prevent rejection and autoimmune destruction of islet grafts. In this study we demonstrate long-term function of islets of Langerhans within a capsule of porcine chondrocytes which may serve as an immunoisolation barrier utilizing the immunoprivileged properties of the chondrocyte matrix. METHODS: Islets of Langerhans were isolated from Lewis rats, seeded on biodegradable polyglycolic acid polymer, and encapsulated with a monolayer of porcine chondrocytes. The encapsulated constructs and controls were kept in culture for 5 weeks. One group was exposed to a glucose challenge every 5th day. The insulin concentration of the culture medium was measured. Histological and insulin-immunohistochemical studies were performed. RESULTS: Hematoxylin and eosin histology demonstrated viability of the islets of Langerhans. The intact morphology was demonstrated by Heidenhain staining. Toluidine blue showed viability of surrounding chondrocyte layers. Immunohistochemistry was positive for insulin within the beta cells of the islets. Both encapsulated constructs and nonencapsulated controls showed increasing insulin levels after glucose challenge. CONCLUSIONS: We can tissue engineer a chondrocyte encapsulation membrane which permits diffusion of glucose and insulin. Islets of Langerhans survive within the chondrocyte capsule, and the glucose/insulin feedback mechanism remains intact.

Animals↗

Positron emission tomography in the staging of small-cell lung cancer : a preliminary study.

STUDY OBJECTIVES: Small-cell lung cancer (SCLC) has an unfavorable prognosis, especially when the disease is extensive at presentation. Accurate staging procedures are therefore needed for treatment planning. Positron emission tomography (PET) is a modern noninvasive imaging technique, the value of which for the staging of SCLC was investigated in the present study. SETTING: University hospital. PATIENTS: Thirty-one patients with suspected lung cancer were investigated for staging purposes using chest radiography, CT of the thorax and abdomen, abdominal ultrasound, and bone scanning. Twenty-five patients also received PET examinations during the staging procedures. Five of these patients were found to have SCLC, while two patients had mixed lesion types. Further analysis of the latter group was carried out. RESULTS: PET detected the primary tumor in all patients, and lymph nodes in five patients. All lymph nodes were proved to be malignant by endoscopic ultrasonography-guided fine-needle aspiration. Only one patient had distant metastases, which were detected by both CT and PET. CONCLUSIONS: PET appears be a suitable imaging method in SCLC. A potential role for the technique as a standard staging procedure will need to be tested by investigating a larger number of patients in a prospective study.

Bone and Bones↗

Impact of FDG PET on patients with differentiated thyroid cancer who present with elevated thyroglobulin and negative 131I scan.

UNLABELLED: FDG PET is increasingly performed in patients with differentiated thyroid cancer who present with elevated human thyroglobulin (hTG) levels and negative 131I scan. The aim of this study was to evaluate the impact of FDG PET on treatment in these patients. METHODS: A total of 118 FDG PET studies were performed on 64 patients, and follow-up data were available for all patients. Whole-body images were acquired 1 h after intravenous injection of 370 MBq (10 mCi) FDG using a PET scanner with an axial field of view of 16.2 cm. Tumor-suspicious FDG PET studies were evaluated by histology, cytology, 131I uptake, CT or MRI, and follow-up of hTg levels. The therapeutic consequence was noted for each patient. Moreover, results of FDG PET were correlated with hTg levels. RESULTS: Forty-four patients had positive scans, which were proven to be true-positive in 34 patients, whereas 7 patients had false-positive findings. Two patients exhibited a secondary malignancy. One patient did not fit in any category, having true-positive, false-positive, and false-negative findings. On the other hand, 20 patients had negative scans. These were true-negative findings in 5 patients, whereas the remaining 15 patients had false-negative results. Accordingly, the positive predictive value of FDG PET was 83% (34/41), whereas the negative predictive value was 25% (5/20). Treatment was directly changed in 19 of 34 patients with true-positive PET studies: 18 patients had further surgery, and 4 patients were referred for external irradiation, 3 of them after incomplete removal of local recurrences. FDG PET showed widespread disease in 7 patients; thus, palliative treatment, rather than curative therapy, was initiated. True-positive FDG PET findings were correlated positively with increasing hTg levels (i.e., FDG PET was true-positive in 11%, 50%, and 93% of patients with hTg levels of <10, 10-20, and >100 microg/L, respectively). CONCLUSION: FDG PET is a valuable diagnostic tool in patients with differentiated thyroid cancer who present with increased hTg levels and negative 131I scans because it permits selection of patients for surgery, which may be curative. FDG PET is most promising at hTg levels of >10 microg/L.

Adult↗

In vitro and in vivo tracer characteristics of an established multidrug-resistant human colon cancer cell line.

UNLABELLED: 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) has been suggested as a tracer for the scintigraphic detection of multidrug resistance (MDR). The aim of this study was to compare MDR characteristics in vitro and in vivo by immunohistochemic and functional uptake assays in established tumor cell lines cultured and grown in severe combined immunodeficient (SCID) mice. METHODS: The presence of MDR was assessed in vitro in drug-resistant HT-29(mdr1) colon carcinoma cells and in nonresistant HT-29(par) cells by JSB-1 immunohistochemistry, uptake of the fluorescent dye Rhodamine 123, and quantitative measurement of 99mTc-MIBI accumulation. For in vivo imaging, SCID mice bearing subcutaneous xenografts of these cell lines were injected with 99mTc-MIBI and 18F-FDG for scintigraphic and PET examination. After imaging, tumors were analyzed by immunohistochemistry and electron microscopy. RESULTS: All HT-29(mdr1) cells cultured in vitro exhibited distinct JSB-1 immunoreactivity, although to a variable degree, whereas HT-29(par) cells were completely devoid of JSB-1 staining. Rhodamine 123 accumulated poorly in HT-29(mdr1) cells but strongly in HT-29(par) cells. Accumulation of 99mTc-MIBI was 0.05% +/- 0.01% of the activity of the external medium in HT-29(mdr1) cells, but about eight times higher in HT-29(par) cells (0.40% +/- 0.09%), a very low percentage compared with other tumor cell lines. No difference in 201TlCl accumulation was observed between both cell lines. In vivo, neither HT-29(par) nor HT-29(mdr1) tumors grown in SCID mice could be detected by 99mTc-MIBI scintigraphy. In FDG PET, both HT-29(mdr1) and HT-29(par) tumors were clearly visible. FDG uptake was, however, markedly higher in HT-29(par) than in HT-29(mdr1) tumors. Both tumor types were poorly vascularized, as shown histologically. JSB-1 immunoreactivity was absent in all HT-29(par) tumors examined, whereas the majority of HT-29(par) tumor cells were stained. Electron microscopy showed that HT-29(par) tumors contained significantly less mitochondria than hepatocytes of the SCID mouse liver, which displayed high 99mTc-MIBI uptake in our scintigraphy studies. CONCLUSION: Sufficient 99mTc-MIBI uptake is the major prerequisite for distinguishing successfully between drug-resistant and sensitive cells. Negative 99mTc-MIBI scintigrams are not necessarily associated with MDR expression. In some tumors, FDG may be an in vivo marker for MDR as suggested by PET.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Molecular biologic and scintigraphic analyses of somatostatin receptor-negative meningiomas.

UNLABELLED: Somatostatin receptor scintigraphy (SRS) using 111In-octreotide has proven useful in the preoperative discrimination of expansive central nervous system lesions. Meningiomas, generally expressing human somatostatin receptor (hsst) on their surface, were detected with a sensitivity of about 100%. This finding was associated with the assumption that meningiomas lack an intact blood-brain barrier. However, this exclusion procedure became questionable when histologically proven meningiomas in which SRS was negative were reported. Therefore, the aim of this study was to discover why these meningiomas gave negative SRS results. METHODS: Before surgery, 46 patients with 47 meningiomas underwent standard MRI and SRS. Thirty-four of these patients with 35 tumors were also examined by 99mTc-diethylenetriaminepentaacetic acid (DTPA) brain scintigraphy. After surgical resection, hsst subtype 2 (hsst2) messenger RNA (mRNA) expression of 4 SRS-positive and 4 SRS-negative meningiomas was estimated semiquantitatively by reverse transcriptase polymerase chain reaction (RT-PCR). Translation of hsst2 mRNA into receptor proteins was proven immunocytochemically on the surface of 1 SRS-positive and 1 SRS-negative meningioma. Tumor specimens used for RNA extraction and RT-PCR and cultivated cells used for hsst2 immunostaining were tested for their meningioma nature by immunochemistry. RESULTS: SRS yielded positive results in 39 meningiomas with a tumor volume of 24.1 +/- 32.8 mL and negative results in 8 meningiomas with a volume of 3.9 +/- 6.5 mL. 99mTc-DTPA scintigraphy visualized 24 of 35 meningiomas. SRS was positive in all of them. In contrast, 11 meningiomas were (99mTc-DTPA negative. In these meningiomas, SRS was negative in 5 cases (5.4 +/- 8.1 mL), whereas the remaining 6 were positive (4.6 +/- 4.5 mL). None of the meningiomas was 99mTc-DTPA positive and SRS negative. RT-PCR revealed no significant difference of hsst2 mRNA expression between SRS-positive and SRS-negative meningiomas but showed varied expression among all meningiomas regardless of SRS results. Furthermore, hsst2 proteins were visualized immunocytochemically on the surface of cultivated cells of SRS-positive and SRS-negative meningiomas. CONCLUSION: SRS-negative meningiomas do express hsst2; thus, in these meningiomas SRS is false-negative. Because an insufficient sensitivity was excluded, 99mTc-DTPA scintigraphy identified a permeability barrier in SRS-negative meningiomas that explains their false-negative SRS results. SRS-negative meningiomas most likely meet the function of their tissue of origin (the meninges) to develop more-or-less intact permeability barriers.

Adult↗