[Diagnosis and treatment of colorectal liver metastases - workflow]. / Diagnostik und Therapie von Lebermetastasen kolorektaler Karzinome - Workflow.

In this review, standards of diagnosis and treatment of colorectal liver metastases are described on the basis of a workshop discussion. Algorithms of care for patients with synchronous / metachronous colorectal liver metastases or locoregional recurrent tumour are presented. Surgical resection is the procedure of choice in the curative treatment of liver metastases. The decision about the resection of liver metastases should consider the following parameters: 1. General operability of the patient (comorbidity); 2. Achievability of an R 0 situation: i. if necessary, in combination with ablative methods, ii. if necessary, neoadjuvant chemotherapy, iii. the ability to eradicate extrahepatic tumour manifestations; 3. Sufficient volume of the liver remaining after resection ("future liver remnant = FLR): i. if necessary, in combination with portal vein embolisation or two-stage hepatectomy; 4. The feasibility to preserve two contiguous hepatic segments with adequate vascular inflow and outflow as well as biliary drainage; 5. Tumour biological aspects ("prognostic variables"); 6. Experience of the surgeon and centre! Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases provided a complete resection of both intra- and extrahepatic disease is feasible. Even in bilobar colorectal metastases and 5 or more tumours in the liver, a complete tumour resection has been described. The type of resection (hepatic wedge resection or anatomic resection) does not influence the recurrence rate. Preoperative volumetry is indicated when major hepatic resection is planned. The FLR should be 25 % in patients with normal liver, 40 % in patients who have received intensive chemotherapy or in cases of fatty liver, liver fibrosis or diabetes, and 50-60 % in patients with cirrhosis. In patients with initially unresectable colorectal liver metastases, preoperative chemotherapy enables complete resection in 15-30 % of the cases, whereas the value of neoadjuvant chemotherapy in patients with resectable liver metastases has not been sufficiently supported. In situ ablative procedures (radiofrequency ablation = RFA and laser-induced interstitial thermotherapy = LITT) are local therapy options in selected patients who are not candidates for resection (central recurrent liver metastases, bilobar multiple metastases and high-risk resection or restricted patient operability). Patients with tumours larger than 3 cm have a high local recurrence rate after percutaneous RFA and are not optimal candidates for this procedure. The physician's experience influences the results significantly, both after hepatectomy and after in situ ablation. Therefore, patients with colorectal liver metastases should be treated in centres with experience in liver surgery.

[Positron emission tomography (PET) for diagnosis and monitoring of treatment for urological tumors]. / Positronenemissionstomographie (PET) zur Diagnostik und zum Therapiemonitoring bei urologischen Tumoren.

Positron emission tomography (PET) using ((18)F)2-fluoro-D-2-desoxyglucose (FDG) has been shown to be a highly sensitive and specific imaging modality in the diagnosis of primary and recurrent tumors and in the control of therapies in numerous non-urologic cancers. It was the aim of this review to validate the significance of PET as a diagnostic tool in malignant tumors of the urogenital tract. A systematic review of the current literature concerning the role of PET for malignant tumors of the kidney, testicles, prostate, and bladder was carried out. The role of FDG PET for renal cell cancer can be seen in the detection of recurrences after definitive local therapy and metastases. The higher sensitivity of PET in comparison to other therapeutic modalities (CT, ultrasound, MRI) in recurrent and metastatic renal cell cancer suggests a supplemental role of this diagnostic procedure to complement other imaging modalities.The clinical value of PET is established for the identification of vital tumor tissue after chemotherapy of seminomatous germ cell tumors. This diagnostic method has little significance for primary tumor staging and diagnosis of non-seminomatous germ cell tumor because of the high probability of false-negative results in adult teratomas. FDG PET is not sensitive enough in the diagnosis of primary or recurrent tumors in prostate or bladder cancer. Also PET did not prove to be superior to conventional bone scintigram in the detection of mostly osteoblastic metastases in prostate cancer. The recent use of alternative tracers, which are partly not eliminated by urinary secretion (acetate, choline) has increased the sensitivity and specificity of PET also in this tumor entity so that further clinical investigations are needed to validate these technical modifications in their significance for this imaging modality. PET appears to be sufficiently evaluated only for the diagnostic follow-up of patients with seminomatous germ cell tumors after chemotherapy to regard it is the diagnostic tool of first choice. For all other tumors of the urogenital tract this proof is still awaited.

Monitoring isotretinoin therapy in thyroid cancer using 18F-FDG PET.

Treatment with isotretinoin (13-cis-retinoic acid, 13-cis-RA) is a recent additional option in advanced, otherwise intractable differentiated thyroid cancers. The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the prediction and the monitoring of response to 13-cis-RA therapy. Twenty-one patients with advanced differentiated thyroid cancers were investigated using 18F-FDG PET and iodine-131 whole-body scans before and 3, 6 and 9 months after initiation of 13-cis-RA therapy. After 9 months, 13-cis-RA treatment was discontinued and imaging procedures repeated 3 months later. Average 18F-FDG uptake (SUV) decreased significantly during 13-cis-RA therapy but subsequently increased in five of eight patients after withdrawal of 13-cis-RA. 18F-FDG uptake (SUV) 3 months after onset of 13-cis-RA therapy was significantly lower in patients who developed increased 131I uptake in their tumour sites than in patients with no subsequent increase in 131I uptake. There was no relationship between serum thyroglobulin level on the one hand and simultaneously measured 131I or 18F-FDG uptake on the other hand. There was a tendency towards lower 18F-FDG uptake in tumour manifestations with a better outcome. Therefore, 18F-FDG PET at 3 months after the start of treatment promises to differentiate between those patients who will eventually benefit from 13-cis-RA and those who will not. In conclusion, these data indicate that 18F-FDG PET is a useful tool for the evaluation and monitoring of adjuvant therapy with 13-cis-RA in thyroid cancer.

[Striatal uptake of I-123-beta-CIT and I-123-IBZM in patients with extrapyramidal symptoms]. / Striatale Aufnahme von I-123-beta-CIT und I-123-IBZM bei Patienten mit extrapyramidaler Symptomatik.

AIM: This pilot study deals with the question whether characteristic changes in local cerebral dopamine transporter function and D2-receptor binding capacity can be shown with SPET in idiopathic Parkinson syndrome (IPS) and secondary Parkinson syndrome (SPS). METHODS: In 16 patients (6 with IPS, 6 with SPS except Wilson's disease, and 4 with Wilson's disease) SPET studies were performed using I-123-beta-CIT and I-123-IBZM and a dual-head gamma camera. Images were obtained 20-24 h and 2 h post injection, respectively. For semiquantitative analysis count density ratios of basal ganglia (BG) and cerebellum (CER) were determined for I-123-beta-CIT and ratios between BG and medial frontal cortex (MFC) for I-123-IBZM. RESULTS: The BG/CER ratio in the I-123-beta-CIT studies averaged 3.04 +/- 0.83 in IPS and 7.73 +/- 3.28 in SPS (p < 0.01) (except Wilson's disease). In patients with IPS, the BG/MFC I-123-IBZM ratios of basal ganglia contralateral to the symptomatic side exceeded that of the individual ipsilateral BGs (1.75 +/- 0.12 vs. 1.61 +/- 0.16); these ratios were significantly reduced when compared with those of SPS patients, although the differences were less pronounced than those of I-123-beta-CIT uptake values. In some of the patients with Wilson's disease the BG/MFC ratio for I-123-IBZM was dramatically reduced (as low as 1.29), whereas I-123-beta-CIT uptake was only slightly reduced when compared with that of SPS patients (8.00 +/- 2.90, p < 0.01). CONCLUSION: It is concluded that the neurochemical changes that can be anticipated in the above diseases can be monitored with SPET. I-123-beta-CIT, however, appears to be more adequate to differentiate IPS from SPS than I-123-IBZM.

Increased thermal response to ultrasound in the Walker carcinosarcoma treated with vasoactive drugs.

In order to evaluate the potential of a highly selective Ca2+ entry blocker (nisoldipine) and of 5-hydroxytryptamine (5-HT) as adjuvant in hyperthermia treatment, we studied the differential flow response and time-course of tumor and normal tissue temperature following the administration of the two substances and during ultrasound heating. In 12 rats bearing Walker 256 carcinomas i.p. injection of 0.2-0.4 mg/kg nisoldipine caused a reduction in the tumor-to-muscle flow relationship of 4.4 +/- 1.9 (SD) to 1.74 +/- 0.86 as determined by intraarterial 133Xe injection; i.p. injection of 2-8 mg/kg 5-HT (N = 13) caused a respective reduction from 3.9 +/- 2.67 to 1.3 +/- 1.59. During a 20-min period of 41 degrees C normal tissue temperature-controlled ultrasound heating without drugs, tumor temperature attained 40.8 +/- 0.9 degrees C (N = 16). Nisoldipine or 5-HT injection at continuing 41 degrees C normal tissue temperature controlled energy delivery produced an instantaneous further increment of tumor temperature, eventually to 44.0 +/- 1.14 degrees C or 44.2 +/- 1.26 degrees C, respectively, after a period of 20 min. Injection of 0.9% NaCl (N = 4) solution caused only insignificant changes. Blood pressure and muscle perfusion were distinctly influenced by nisoldipine, but not by 5-HT. Since both drugs instantaneously increased the temperature differential between tumor and normal tissue, though by different vasoaction, they should be considered as adjuvants in hyperthermia.

Selective drug-induced reduction of blood flow in tumor transplants.

The effect of a calcium antagonist and a physiologic amine on tumor and muscle perfusion was investigated with the aim of improving the preconditions for external hyperthermia treatment of cancer. Nisoldipine (0.04-4.0 mg/kg) and 5-hydroxy tryptamine (5-HT) (0.2-8.0 mg/kg) were administered i.p. in Sprague-Dawley rats bearing Walker 256 carcinoma, Yoshida sarcoma, or a homologous tumor transplant derived from a spontaneous leiomyosarcoma of the uterus. At the maximum dosage used, nisoldipine injection caused a decrease of the regional washout rate of Xenon-133 of 63 +/- 8% (SEM) in the Walker carcinoma and an increase of 80 +/- 41% in the muscle of the hind leg. 5-HT (8 mg/kg) caused a drop of 79 +/- 29% in the Walker carcinoma and only a slight fall of the washout rate in muscle of 14 +/- 4.8%. Tumor-to-muscle uptake ratios of 11C-butanol fell from 5.63 +/- 1.98 to 3.32 +/- 1.21, and from 5.3 +/- 0.56 to 2.98 +/- 0.30, after injection of 0.2 mg/kg nisoldipine and 4 mg/kg 5-HT, respectively. Similar reaction patterns and percentage changes were observed in different tumor lines at constant doses of 0.2 mg/kg nisoldipine and 4 mg/kg 5-HT. Both drugs representing two different rationales of vasomotor action were able to reduce blood flow specifically in transplanted tumors; nisoldipine increased muscle blood flow and decreased arterial blood pressure, whereas 5-HT acted without substantial systemic effects.