Topsoil structure stability in a restored floodplain: Impacts of fluctuating water levels, soil parameters and ecosystem engineers.

Ecosystem services provided by floodplains are strongly controlled by the structural stability of soils. The development of a stable structure in floodplain soils is affected by a complex and poorly understood interplay of hydrological, physico-chemical and biological processes. This paper aims at analysing relations between fluctuating groundwater levels, soil physico-chemical and biological parameters on soil structure stability in a restored floodplain. Water level fluctuations in the soil are modelled using a numerical surface-water-groundwater flow model and correlated to soil physico-chemical parameters and abundances of plants and earthworms. Causal relations and multiple interactions between the investigated parameters are tested through structural equation modelling (SEM). Fluctuating water levels in the soil did not directly affect the topsoil structure stability, but indirectly through affecting plant roots and soil parameters that in turn determine topsoil structure stability. These relations remain significant for mean annual days of complete and partial (>25%) water saturation. Ecosystem functioning of a restored floodplain might already be affected by the fluctuation of groundwater levels alone, and not only through complete flooding by surface water during a flood period. Surprisingly, abundances of earthworms did not show any relation to other variables in the SEM. These findings emphasise that earthworms have efficiently adapted to periodic stress and harsh environmental conditions. Variability of the topsoil structure stability is thus stronger driven by the influence of fluctuating water levels on plants than by the abundance of earthworms. This knowledge about the functional network of soil engineering organisms, soil parameters and fluctuating water levels and how they affect soil structural stability is of fundamental importance to define management strategies of near-natural or restored floodplains in the future.

Liver perfusion scintigraphy prior to and after transjugular intrahepatic portosystemic shunts (TIPS) in patients with portal hypertension.

PURPOSE: This investigation was performed to compare the hemodynamic results of the transjugular intrahepatic portosystemic shunt, a new interventional treatment for portal hypertension, with those observed after the established surgical shunt interventions. METHODS: We examined 22 patients with portal hypertension due to liver cirrhosis before and after elective TIPS by liver perfusion scintigraphy. The relative portal perfusion was determined before and after the shunt procedure. Additionally, we measured the portal pressure gradient (PPG: portal-central venous pressure, mmHg). RESULTS: Prior to TIPS, the relative portal perfusion was significantly reduced to 22 +/- 9.1%. After the intervention we calculated values of 23.1 +/- 10.7% in the TIPS-group (p = 0.67; not significant). In spite of unchanged portal perfusion, the portal pressure was significantly (p < 0.001) reduced from 25.6 +/- 5.3 to 14.8 +/- 4 mm Hg. CONCLUSION: These results suggest that the reduction of portal hypertension by TIPS is effective. The portal perfusion is maintained by TIPS suggesting that liver perfusion is preserved to a higher degree.

Possible role of FDG-PET in the early prediction of therapy outcome in liver metastases of colorectal cancer.

Nonresectable colorectal cancer metastases in the liver respond to chemotherapy in 20-25% only. Early identification of nonresponders might allow the use of other regimens. In a limited feasibility study, it should be determined whether (a) a single high-dose chemotherapy application has an early effect on glucose-utilization, detectable and quantitatable by noninvasive positron emission tomography using [18F]-Fluoro-deoxyglucose (FDG-PET) and (b) assess its value as a predictor of the final therapeutic outcome. A total of 10 patients with documented nonresectable liver metastases of a colorectal cancer were studied by FDG-PET, prior and 72 h after a single infusion of 5-Fluorouracil and Folinic acid (5-FU/FA). Glucose utilization was quantitated by determination of standard-uptake values and correlated with final therapy outcome following completion of the anticipated therapy cycle. Patients were followed up for at least 6 months. All metastases responding to therapy (n = 6) exerted a statistically significant decrease of FDG uptake (-22+/-10%), metastases (n = 2) showing a short-term effect (duration of tumor reduction <3 months) had a slightly diminished, and progressing metastases (n = 3) an enhanced FDG uptake (13+/-17%). Our preliminary data indicate that acute changes of glucose utilization-as detected by FDG-PET-following a single application of chemotherapy, seems to be indicative for the final therapeutic outcome, at least in liver metastases of colorectal cancer.

Regional cerebral blood flow single-photon emission tomography with 99mTc-HMPAO and the acetazolamide test in the evaluation of vascular and Alzheimer's dementia.

The diagnostic potential of technetium-99m hexamethylpropylene amine oxime (HMPAO) following systemic administration of the cerebral vasodilator acetazolamide (acetazolamide test) was evaluated by regional cerebral blood flow (rCBF) single-photon emission tomography (SPET) in patients with Alzheimer's disease (AD) or vascular dementia (VD). An initial, high-resolution SPET study was performed with 99mTc-HMPAO, and after 2 days the patients were re-evaluated with 99mTc-HMPAO following systemic administration of acetazolamide. Reconstructed SPET slices were evaluated visually and semiquantitatively by a semi-automatic rCBF map method. When 99mTc-HMPAO alone was used, bilateral hypoperfusion was found in the temporal and/or parietal regions in 33% (6/18) of the VD patients and in 70% (23/33) of the AD patients. The corresponding data obtained by quantitative evaluation were 41% (7/17) and 71% (15/21), respectively. The vascular reserve capacity, as determined with the acetazolamide test, was preserved visually in 22% (4/18) and quantitatively in 29% (5/17) of the VD patients, but in 73% (24/33) and 76% (16/21) of the AD patients. The differences in the perfusion patterns between the VD and AD patients were statistically significant (P<0.01, Fischer's exact test). Of the VD patients with hypoperfusion (bilateral temporal and/or parietal), 4/6 (67%, visual evaluation) and 4/7 (57%, quantitative evaluation) had a decreased vascular reserve capacity as determined with the acetazolamide test. In the AD group of patients the corresponding results were 3/23 (13%) and 4/15 (27%). It is concluded that the acetazolamide test is promising in rCBF SPET to differentiate VD from AD.

Fluorodeoxyglucose whole-body positron emission tomography in colorectal cancer patients studied in routine daily practice.

PURPOSE: To evaluate the routine clinical value of attenuation-corrected whole-body fluorodeoxyglucose positron emission tomography in colorectal cancer, a total of 59 patients who were referred for evaluation of suspected or proven colorectal cancers were studied. METHODS: Positron emission tomography scans were recorded using a Siemens ECAT Exact 921/47. RESULTS: Median follow-up after the positron emission tomography study was 11 (mean, 12.3; range, 1-21) months. According to computed tomography, coloscopy, and ultrasound, we recorded eight apparently false-positive results. During later follow-up, however, three of those cases, which were negative with computed tomography, magnetic resonance imaging, sonography, or laparoscopy, turned out to be true-positive instead. In 3 patients, a primary colorectal cancer was suspected; in 26 patients, a recurrence of colorectal cancer was suspected. Eight patients were studied for follow-up after the history of colorectal cancer with no suspicion of recurrence. In 12 patients, the rise of serum tumor marker concentrations was the reason for the positron emission tomography study; 12 patients with known metastatic disease were also included ("restaging"). With regard to the entire patient population, we found an overall sensitivity of 100 percent, a specificity of 67 percent, and positive and negative predictive values of 92 and 100 percent, respectively. Being merely confirmative with respect to tumor recurrence or distant metastases in the majority of patients, positron emission tomography revealed a primary tumor in one patient and confirmed metastatic foci in several patients that had not been delineated by other imaging modalities. CONCLUSION: A whole-body positron emission tomography scan provides optimum conditions to locate metastatic lesions that might not be seen otherwise. There is a trend showing that positron emission tomography diagnostics as a consequence of early increased tumor markers is a highly sensitive combination, because computed tomography and magnetic resonance imaging were not as sensitive in early recurrences. Positron emission tomography, as performed in daily clinical practice, proved to be a powerful diagnostic tool in our subset of colorectal cancer patients.

Possible role of FDG-PET in the evaluation of urologic malignancies.

Positron-emission tomography (PET) employing 18F-labeled deoxyglucose (FDG) has been found to be a highly sensitive and rather specific tool in the detection of a variety of malignant carcinomas. Due to high resolution and outstanding image quality its complementary and supplementary role as compared to morphological methods has increasingly been acknowledged. Urinary-tract malignancies, with the exception of prostate carcinoma, have a rather low incidence and thus experience with FDG-PET is limited. We have compared the diagnostic accuracy of FDG-PET mainly in the primary staging of malignant testicular carcinoma, prostate and renal cell carcinoma. Our data indicate, that FDG-PET is more accurate in the detection of lymph node metastases in malignant testicular cancer as compared to CT, but also fails to detect micrometastases and highly differentiated teratoma. Its role in prostate carcinoma is questionable due to the low metabolic activity of this type of cancer. In all other urinary tract malignancies no final conclusions can be drawn, due to limited experience.

Value of 18fluoro-deoxyglucose positron emission tomography in the staging of recurrent breast carcinoma.

The aim of the study was to evaluate the feasibility of staging recurrent breast carcinoma employing fluorine-18-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) under routine clinical conditions. In 75 patients with suspected recurrent or metastatic disease, whole-body FDG-PET was performed and results correlated with morphological imaging (CT/MRI) data and verified by histological findings. FDG-PET correctly identified 16 patients with local recurrence, 28 with lymph node involvement, 15 with bone, 5 with lung and 2 with liver metastases. CT/MRI identified 10 patients with local recurrences, 17 with lymph node involvement, 6 with bone, 5 with lung and 1 with liver metastases. FDG-PET detected 6 local recurrences, 8 lymph node, and 7 bone metastases, which were not visualized by CT/MRI. Our data provide the basis for use of FDG-PET in the whole-body restaging of recurrent breast carcinoma in preselected patients under routine clinical conditions.

Effects of diagnostic application of monoclonal antibody on survival in melanoma patients.

Follow-up data of more than 300 melanoma patients were reviewed in which an immunoscintigraphy study had been performed as part of a routine staging protocol. All patients had received a commercially available 99mTc-labeled F(ab')2 fragment specific to a high-molecular-weight melanoma-associated antigen (HMW-MAA). Survival data of patients that had received one injection (group I) were compared with those receiving two or more injections (group II). For better comparison, patients were matched according to the following risk factors: (i) age, (ii) sex, (iii) tumor level according to Clark, (iv) tumor depth according to Breslow, (v) location of primary tumor, and (vi) metastases [and if positive, (vii) location of metastases]. Twenty-eight patient pairs were established that showed no statistically significant differences comparing the above-mentioned risk factors. In addition, no significant difference was found comparing the interval between primary diagnosis of disease and first injection of monoclonal antibody (MAb) in both groups. In contrast, survival time between first diagnosis of melanoma was significantly prolonged in group II (multiple injections) as compared to group I (single injection). This was true for survival time between primary diagnosis as well as from first injection of MAb until death or closing time of study. Our data suggest, that multiple injections of melanoma-specific F(ab')2 fragment have a beneficial effect on median survival in melanoma patients.

"High-dose" radioiodine therapy in advanced differentiated thyroid carcinoma.

UNLABELLED: There is yet no consensus concerning the appropriate regimen of the application of [131I]sodium iodine (Nal) activities to patients suffering from advanced differentiated thyroid carcinoma. We report on a total of 167 applications of [131I]Nal, including 78 applications of 11.1 GBq. Response to high-activity radioiodine therapy (RIT) is correlated to the course of the disease as well as to the reaction of thyreoglobulin and acute/subacute side effects of radiation. METHODS: Following radioablation of thyroid remnants using 1.85 to 3.7 GBq[131I]Nal, 26 patients with advanced differentiated thyroid carcinoma (follicular, 11; papillary, 4;mixed-cell thyroid carcinoma, 11) were treated with repeated activities of 11.1 GBq[131I]Nal. Initial tumor staging according to UICC showed T4 in 54%, T3 in 19%, T2 in 19% and was not obtained in 8%. Differentiated thyroid carcinoma was multifocal in 23% of patients. Applied accumulated activities ranged from 14.8 to 99.9 GBq with a mean of 55.5 GBq per patient. RESULTS: Mean post-diagnostical follow-up was 73 mo, mean follow-up after diagnosis of metastatic spread was 48 mo. Follicular thyroid carcinoma remained as stable disease in 7 of 11 patients, 6 of whom showed metastatic disease after a mean of 20 mo, and only 1 complete remission was achieved using high-dose therapies, with progressive disease in the remaining patients. Overall, 73% of follicular thyroid carcinoma had progressive disease without major response to high-activity RIT. In contrast, only 20% of papillary thyroid carcinoma/mixed-cell thyroid carcinoma showed progressive disease, and complete remission was achieved in 47% of patients. Pulmonary and lymph node metastases in the majority of patients showed good response to therapy, whereas local recurrences and bone metastases showed minor reactions to RIT. After low-activity therapies 8% of patients showed WHO grade I hematotoxic reactions. After high-activity therapies, 38% of patients had WHO I, 8% WHO II and one patient had WHO III toxicity (4%). CONCLUSION: Use repetitive high-activity RIT with a maximum of 44.4 GBq applied during 1 yr and a maximum of 99.9 GBq accumulated activity resulted in a significant increase of hematotoxicity. However, during the follow-up period (mean, 4 yr), no clinical symptoms possibly related to low blood counts were seen in patients with advanced differentiated thyroid carcinoma. Initiation of high-activity RIT in reaction to metastatic tumor outspread to achieve complete remission was found to be useful in treating papillary thyroid carcinoma and mixed-cell thyroid carcinoma, but only in a minority of follicular thyroid carcinoma patients.

Scintimammography with Tc-99m MIBI in patients with suspicion of primary breast cancer.

The aim of the study was to evaluate the diagnostic accuracy of scintimammography with Tc-99m MIBI for the detection of breast cancer. Patients with a suspicious lesion detected by palpation or mammography were included in the study. Excisional biopsy was performed on all patients. Mammography was performed within 3 weeks prior to scintigraphy. All patients received 740 MBq Tc-99m MIBI intravenously in the arm contralateral to the suspicious breast and were subsequently examined in a prone position. At 5 to 10 min postinjection, planar images were obtained in lateral and anterior views, with an acquisition time of 10 min each. After planar imaging, a SPECT study was performed using a two-head camera. Breast cancer was confirmed in 29 out of 68 patients. The tumor size ranged from 6 to 90 mm in diameter. For scintigraphic studies, the overall sensitivity and specificity was 83% and 84%, respectively. However, sensitivity for palpable lesions was 100%. The smallest detectable tumor measured 9 mm in diameter and could be visualized only in the planar scintigram. Using Tc-99m MIBI, axillary lymph node metastases could be detected with a sensitivity of 82%. Scintigraphy with Tc-99m MIBI has a high diagnostic accuracy for the detection of primary breast cancer in patients with a palpable mass. Scintimammography may be used as a complementary method to mammography and help to decrease the number of unnecessary breast biopsies.

Scintimammography with technetium-99m methoxyisobutylisonitrile: comparison with mammography and magnetic resonance imaging.

The aim of the study was to compare the diagnostic accuracy of scintimammography with technetium-99m methoxyisobutylisonitrile (MIBI; SMM) in the detection of primary breast cancer with that of mammography (MM) and magnetic resonance imaging (MRI). Fifty-six patients with suspected lesions detected by palpation or MM were included in the study. Within the 4 weeks preceding excisional biopsy, MM and MRI were performed in all patients. Between 5 and 10 min after the injection of 740 MBq 99mTc-MIBI, SMM in the prone position was performed. In the total group of 56 patients, 43 lesions were palpable, while 13 were non-palpable but were detected by MM. Breast cancer was confirmed by histopathology in 27 of the patients (22 palpable and 5 non-palpable carcinomas). The tumour size ranged from 6 to 80 mm in diameter. For non-palpable lesions, the sensitivity of SMM, MM and MRI was 60%, 60% and 100%, respectively, while the specificity was 75%, 25% and 50%, respectively. For palpable breast lesions, all methods showed high sensitivity (SMM 91%, MM 95%, MRI 91%) but SMM demonstrated significantly higher specificity (SMM 62%, MM 10%, MRI 15%). In two mammographically negative tumours (dense tissue), SMM showed a positive result. In comparison to MRI, one additional carcinoma could be diagnosed by SMM. It may be concluded that for palpable breast lesions, the diagnostic accuracy of SMM is superior to that of MM and MRI. Through the complementary use of SMM it is possible to increase the sensitivity for the detection of breast cancer and multicentric disease. In patients in whom the status of a palpable breast mass remains unclear, SMM may help to reduce the amount of unnecessary biopsies.

Standardized uptake values of fluorine-18 fluorodeoxyglucose: the value of different normalization procedures.

While the evident advantages of absolute metabolic rate determinations cannot be equalled by static image analysis of fluorine-18 fluorodeoxyglucose positron emission tomographic (FDG PET) studies, various algorithms for the normalization of static FDG uptake values have been proposed. This study was performed to compare different normalization procedures in terms of dependency on individual patient characteristics. Standardized FDG uptake values (SUVs) were calculated for liver and lung tissue in 126 patients studied with whole-body FDG PET. Uptake values were normalized for total body weight, lean body mass and body surface area. Ranges, means, medians, standard deviations and variation coefficients of these SUV parameters were calculated and their interdependency with total body weight, lean body mass, body surface area, patient height and blood sugar levels was calculated by means of regression analysis. Standardized FDG uptake values normalized for body surface area were clearly superior to SUV parameters normalized for total body weight or lean body mass. Variation and correlation coefficients of body surface area-normalized uptake values were minimal when compared with SUV parameters derived from the other normalization procedures. Normalization for total body weight resulted in uptake values still dependent on body weight and blood sugar levels, while normalization for lean body mass did not eliminate the positive correlation with lean body mass and patient height. It is concluded that normalization of FDG uptake values for body surface area is less dependent on the individual patient characteristics than are FDG uptake values normalized for other parameters, and therefore appears to be preferable for FDG PET studies in oncology.

[Pain therapy with rhenium-186 HEDP in multiple bone metastases]. / Schmerztherapie mit Rhenium-186 HEDP bei multiplen Knochenmetastasen.

AIM: Therapeutic means for patients with painful bony metastases are strongly limited. In these patients, a systemic therapy with isotopes can be helpful. The aim of this study was to evaluate the efficacy of rhenium-186 HEDP for pain palliation in patients with disseminated bone metastases. METHODS: 30 patients taking analgesics because of bone pain received one or more injection of 1295 MBq 186Re HEDP for pain palliation. RESULTS: In 70% of the patients, therapy resulted in a significant reduction of pain. The average duration of pain relief was 4 weeks (1 week-2.5 months). The main side effects of therapy were a decrease of platelets (aver. 30000/microliters) and an increase of pain for 1-2 days (flare-phenomenon). CONCLUSION: Therapy with rhenium-186 HEDP can be used complementarily to analgesic therapy in patients with painful, disseminated bone metastases.

Technetium-99m-MIBI scintimammography for suspicious breast lesions.

UNLABELLED: The aim of this study was to evaluate the diagnostic accuracy of scintimammography with 99mTc-MIBI in patients with suspected primary breast cancer as monitored by SPECT or planar imaging. METHODS: Patients with a suspect lesion detected by palpation or mammography were entered in the study. Excisional biopsy was performed on all patients and a mammography was performed within three weeks prior to scintigraphy. All patients received intravenously 740 MBq 99mTc-MIBI in the arm, contralateral to the suspicious breast, and were subsequently examined in a prone position. At 5-10 min postinjection, planar images were obtained in both the lateral and anterior views with an acquisition time of 10 min. After planar imaging, SPECT imaging was performed using a two-head high-resolution gamma camera. RESULTS: In the total patient group of 54 patients, 40 lesions were palpable and 14 were nonpalpable but were detected by mammography. Breast cancer was confirmed in 24 of the patients and 20 of the palpable masses were found to be carcinomas. The tumor size ranged from 6 to 90 mm in diameter. In scintigraphic studies, the overall sensitivity was 88% for planar imaging and 83% for SPECT. Specificity was 83% and 80%, respectively. Sensitivity for palpable lesions was 100%. The smallest detectable tumor measured was 9 mm in diameter and could only be visualized in the planar scintigram. CONCLUSION: Scintigraphy with 99mTc-MIBI is extremely sensitive for the detection of primary breast cancer in patients with a palpable mass. SPECT, however, did not improve the diagnostic accuracy over planar scintimammography.

Fluorine-18 fluorodeoxyglucose positron emission tomography in the follow-up of differentiated thyroid cancer.

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with 131I) and a negative FDG PET, in four cases 131I-negative lymph node metastases were detectable with PET. Even in the patients with concordant "staging", differences between 131I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of 131I-positive/FDG-negative, 131I-negative/FDG-positive and 131I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours 131I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS.

Are serum neopterin concentrations superior to other parameters in the differential diagnosis and prognostic assessment of Graves' disease?

There is a lack (1.) of a single criterion for the definitive differentiation between immunogenic (IH) and non-immunogenic hyperthyroidism (NIH), and (2.) also a lack of an unequivocal prognostic predictor for the individual course of patients with immunogenic hyperthyroidism. In 152 patients scheduled for iodine-131 therapy, serum neopterin concentrations were measured using a commercially available RIA, and the neopterin concentrations of IH (n = 84) and NIH (n = 42) patients were compared. Of these patients, 83 and 26 per cent respectively were treated with antithyroid drugs which did not have a significant impact on neopterin levels. In patients with IH and NIH, the concentrations [mean +/- SD] of neopterin were 1.89 +/- 0.79 milligrams and 1.98 +/- 0.9 milligrams, respectively (p = 0.4). After therapy with iodine-131, 28% of the IH-patients were euthyroid, 32% hyperthyroid, and 40% hypothyroid. In finally euthyroid patients, pretherapeutic neopterin concentrations were higher (3.1 +/- 2.8 milligrams) than in finally hyperthyroid (1.8 +/- 0.7 milligrams), or hypothyroid (1.6 +/- 0.7 milligrams) patients. These results argue against a relevant clinical role of neopterin concentrations for the differential diagnosis of IH versus NIH in these patients. However, a prognostic significance of neopterin concentrations in patients with IH is suggested.

18FDG PET and acetazolamide-enhanced 99mTc-HMPAO SPET in systemic lupus erythematosus.

In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs. Measurements of cerebral blood flow and metabolism by means of positron emission tomography (PET) and single-photon emission tomography (SPET) can contribute to the diagnostic assessment of the involvement of the central nervous system (CNS) in SLE. Functional imaging has been proven to be more sensitive than morphological imaging (magnetic resonance imaging and computed tomography). In this report, we present the case of a 70-year-old female patient, suffering from SLE without symptoms of CNS involvement. In addition to a SPET study using technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) and a PET scan with fluorine-18 deoxyglucose (18FDG), a SPET study after acetazolamide injection was performed in order to assess the cerebral perfusion reserve. While the PET scan showed no major abnormalities, and the baseline SPET study revealed only minor changes, the acetazolamide-enhanced SPET study revealed a marked reduction of the cortical perfusion reserve, particularly in both frontal lobes. It is concluded that "preclinical" CNS involvement, mainly caused by pathological mechanisms involving the cerebral blood vessels, can be considered to exist in this patient with SLE.

[Scintigraphy of the parathyroid glands with 99mTc-MIBI]. / Nebenschilddrüsenszintigraphie mit 99mTc-MIBI.

AIM: Since about 3 years 99mTc-MIBI is used instead of 201Tl/99mTc subtraction scintigraphy for the localization of parathyroid involvement in hyperparathyroidism (HPT). The sensitivity of the new method was evaluated. PATIENTS AND METHODS: 24 patients aged between 28 and 83 years with surgically confirmed primary HPT were studied. Planar images were acquired 15 minutes and 3 hours after tracer injection. Additionally, in 9 patients dynamic images were obtained for 2 hours to study tracer kinetics. RESULTS: 19 out of 24 adenomas (79%) were identified correctly with 99mTc-MIBI. CONCLUSION: The sensitivity of the scintigraphy using 99mTc-MIBI is in the range of the 201Tl/99mTc subtraction scintigraphy. Because of the superior logistic and the lower radiation exposure, 99mTc-MIBI can replace the 201Tl/99mTc scintigraphy in the preoperative diagnostic assessment.

Chemoimmunotherapy of advanced malignant melanoma: sequential administration of subcutaneous interleukin-2 and interferon-alpha after intravenous dacarbazine and carboplatin or intravenous dacarbazine, cisplatin, carmustine and tamoxifen.

Both chemotherapy and interleukin-2 and/or interferon-alpha produce objective responses in a proportion of advanced malignant melanoma patients. While duration of response to chemotherapy is short, i.e. usually below 4 months, immunotherapy has resulted in a small number of long-lasting remissions in patients with metastatic melanoma. In two consecutive phase II trials in a total of 67 patients, we assessed the potential synergism between both modalities, i.e. chemo- and immunotherapy. Treatment consisted of intravenous (i.v.) carboplatin (CBDCA, 400 mg/m2) and dacarbazine (DTIC, 750 mg/m2) given twice (i.v. bolus over 30 min) at 3-week intervals, or 4 cycles of DTIC (220 mg/m2 i.v. 3 days), cisplatin (DDP, 35 mg/m2 i.v. 3 days), carmustine (BCNU, 150 mg/m2 i.v. cycles 1 and 3) and tamoxifen (TAM, 20 mg oral/daily) at 3-week intervals. Chemotherapy was followed by immunotherapy with combined subcutaneous (s.c.) interleukin-2 (rIL-2) and SC interferon-alpha 2 (rIFN-alpha). Among 40 patients who received a full cycle of chemotherapy with CBDCA/DTIC and sequential immunotherapy, there were 3 (7.5%) complete remissions (CRs) with a median duration of 19 months (range 13-26+). Partial remissions (PRs) were noted in 11 (27.5%) patients with a median response duration of 8 (range 5-14) months. Among 27 patients who received DTIC/DDP/BCNU/TAM and rIL-2/rIFN-alpha, there were 3 (11%) complete remissions and 12 (44.5%) partial remissions. Duration of complete and partial remissions ranged from 9+ to 13+ (median, 11+), and 5 to 15+ (median, 7+) months, respectively. Chemotherapy produced mostly moderate toxicity. Thrombocytopenia was common with the nadir after a median time of 18 days following start of CBDCA/DTIC and DTIC/DDP/BCNU, respectively. 10 patients required transfusion of thrombocytes. Nausea and vomiting due to chemotherapy were well tolerated using concomitant ondansetrone (8 mg i.v.). Immunotherapy was self-administered at home with mild to moderate side effects; malaise, fever, chills, nausea/vomiting, diarrhoea, anorexia and arthralgias were most frequent, but were spontaneously reversible after ending rIL-2/IFN-alpha. A mean 87 and 88% of the projected doses of rIL-2 and rIFN-alpha were administered on either protocol. There were no life-threatening complications and no treatment-related deaths. The sequential combination of chemotherapy and rIL-2 plus rIFN-alpha had at least additive therapeutic activity against metastatic malignant melanoma. The schedules produced long-lasting remissions and were tolerated well overall. These trials substantiate a potential role for low to intermediate dose immunotherapy in maintaining and consolidating therapeutic effects of chemotherapy in metastatic melanoma.

In vivo tumor necrosis factor-alpha as indicator of biologic and clinical response to low-dose SC recombinant interleukin 2.

The effect of low-dose human recombinant interleukin-2 (rIL-2) on the induction of secondary tumor necrosis factor-alpha (TNF-alpha) in vivo was studied in 16 patients with metastatic renal cell carcinoma. In all patients s.c. rIL-2 resulted in a significant increase in TNF-alpha serum levels within 4 to 8 hours, as determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha serum concentrations remained elevated up to 24 hours following single s.c. administration of rIL-2. Total secondary TNF-alpha release, as assessed by the area under the curve (AUC), appeared to be independent of dose distribution of rIL-2 (10 million IU rIL-2 q12 hours versus 20 million IU rIL-2 q24 hours). rIL-2 induced TNF-alpha release was significantly higher in patients who had received prior rIL-2 immunotherapy, while steroids resulted in a significant suppression of TNF-alpha release. Secondary TNF-alpha release was statistically associated with progression-free survival of renal cell carcinoma patients and may be a prognostic factor in patients receiving rIL-2.