AFP-producing adenocarcinoma of the esophagogastric junction: report of a case with atypical immunohistochemical findings responding to palliative chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT regime).

AFP-producing adenocarcinoma of the esophagus and esophagogastric junction are rare tumor diseases. These tumors show an aggressive behavior characterized by early occurrence of liver metastases and mimic hepatocellular carcinoma (HCC). A general recommendation for palliative therapy is not established for these special tumors.Here we report about a 61-year-old man with multiple liver metastases and high serum alpha-fetoprotein (AFP) level. First, HCC was suspected, but further evaluation showed an AFP-producing adenocarcinoma of the esophagogastric junction with unusual findings on further immunohistochemical analysis. Palliative chemotherapy with FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) regime showed a 9 month duration of partial response.

Forms of energy delivery during cryo-cooled radiofrequency ablation for optimization of the ablation result.

PURPOSE: Energy transfer from radiofrequency (RF) applicator to tissue is both precondition and limiting factor. The purpose of this ex vivo study was to examine the influence of form of energy delivery on ablation result during RF ablation with cryo-cooled applicators. MATERIALS AND METHODS: One hundred eight ablations were performed in ex vivo bovine liver under continuous energy delivery (A), pulsed energy delivery with reduced current during ablation pause (B) and impedance-dependent energy delivery. Maximum ablation time was 20 min. Early termination of ablation in case of loss of conductivity. Optimal ablation parameters were assessed. Short axis diameter of the ablation zone and ablation duration were determined. Ablation results under mode A, B and C were compared with analysis of variance and Tukey-Kramer HSD test. Influence of ablation duration on short axis diameter was evaluated with regression analysis. RESULTS: Significantly largest short axis diameter (51.1 mm ± SD 2.3; p = 0.01) was reached with impedance-dependent energy delivery (pulsed: 46.1 mm ± SD 5.6; continuous: 44.4 mm ± SD 4.1). Significantly longest ablation duration (1061.6 s ± SD 42.4; p = 0.01) was reached with impedance-dependent energy delivery (pulsed: 815.7 s ±â€Š41.3; continuous: 715.3 s ± SD 82.2). Linear correlation between ablation duration and short axis diameter was calculated (R = 0.7). CONCLUSION: Modification of energy delivery during RF ablation with cryo-cooled applicators improves energy transfer to tissue and enables larger ablation zones. KEY POINTS: • Impedance-dependent energy delivery prevents early termination in kryo-based RF-ablation,• Impedance-dependent energy delivery enables larger ablation zones than continuous energy delivery,• Reduced current during ablation pause does not improve ablation results.

[Image-guided therapy with closed MRI: an update]. / Image-Guided Therapy am geschlossenen MRT: Ein Update.

STANDARD RADIOLOGICAL METHODS: Standard imaging modalities for percutaneous minimally invasive therapy are ultrasound, fluoroscopy and computed tomography. METHODICAL INNOVATIONS: Magnetic resonance imaging is becoming increasingly more popular for minimally invasive procedures. The advantages are high soft-tissue contrast, the possibility of free selection of multiple imaging slices, multiple tools for intrainterventional monitoring and the absence of ionizing radiation for the patient and the interventional radiologist. ACHIEVEMENTS: Magnetic resonance imaging is a promising imaging modality for minimally invasive procedures. The most common clinical applications are thermoablative procedures for treatment of hepatic, renal and prostatic malignancies.

[Microwave tumor ablation. New devices, new applications?]. / Mikrowellenablation. Neue Systeme, neue Einsatzgebiete?

CLINICAL ISSUE: The majority of patients with hepatic malignancies are not amenable to surgical resection. In some of these cases minimally invasive ablative therapies are a treatment option. STANDARD TREATMENT: Besides radiofrequency ablation, the most common ablative therapies are cryoablation, laser ablation and microwave ablation. TREATMENT INNOVATIONS: The classic fields of application of microwave ablation are the treatment of malignancies of the liver, kidneys and lungs. Furthermore, cases of treatment of bone tumors and tumors of the adrenal gland have been reported as well as treatment of secondary hypersplenism. PERFORMANCE: The manufacturers of microwave systems pursue different strategies to reach an optimal ablation zone, such as water or gas cooling of the antenna, the simultaneous use of different antennas or an automatic modulation of the microwave energy and frequency. ACHIEVEMENTS: In contrast to other tumor ablation methods microwave ablation causes a direct heating of a tissue volume, thus this method is less vulnerable to the cooling effect of vessels in the ablation zone. Moreover the electric conductivity of the treated tissue does not influence microwave radiation so that microwave ablation has advantages for the treatment of high-resistance organs, such as the lungs or bone. Some publications have shown that microwave ablation causes larger ablation zones in less time in comparison to radiofrequency ablation. PRACTICAL RECOMMENDATIONS: Classic indications for microwave ablation are the treatment of malignancies of the liver, lungs and kidneys. Initial technical problems have been solved, so that an increasing significance of the microwave ablation among the ablative therapies is to be expected.

[CT-guided radiofrequency (RF) ablation of osteoid osteoma: clinical long-term results]. / CT-gesteuerte Radiofrequenz (RF)-Ablation von Osteoidosteomen: klinische Langzeitergebnisse.

PURPOSE: To evaluate CT-guided radiofrequency (RF) ablation of osteoid osteoma using internally cooled monopolar RF electrodes for technical success, complications and clinical long-term success. MATERIALS AND METHODS: Between April 1999 and July 2006, 23 patients were treated under general anesthesia with CT-guided RF ablation using an internally cooled monopolar single RF electrode (Cool-tip, Valleylab, TycoHealthcare, Boulder, USA; active tip: 10 mm). For the removal of the nidus, we used either a manual or an automated drill. The technical success was evaluated by a CT scan (MSCT, Siemens Medical Solutions, Forchheim). The clinical long-term success was investigated by questioning patients prior to discharge, and after 6, 12 and 18 months. After 18 months, patients were interviewed on an annual basis. RESULTS: The technical success rate was 100 %. The nidus was located in n = 19 cases at the lower extremity and in n = 4 cases at the upper extremity. Minor complications were observed for n = 2 patients. The mean hospitalization time was 1.5 d (1-2 d). The mean follow-up was 75.9 months (18-120 months) for n = 23 patients. No local recurrence was observed. One patient had intermediate pain one week after RF ablation without recurrent symptoms. CONCLUSION: CT-guided RF ablation using an internally cooled monopolar single RF electrode is an effective and safe minimally invasive method for the treatment of osteoid osteoma with excellent clinical long-term success.

[Metastases of colorectal carcinoma]. / Metastasen des kolorektalen Karzinoms.

Metastases of colorectal cancer represent an interdisciplinary therapeutic challenge. Evidence-based guidelines are supportive of treatment decisions in specific situations with the objective to improve the therapeutic outcome for patients. Interventional tumor therapies are increasingly applied therapeutic options in the treatment of colorectal metastases. The current literature indicates that thermoablation of colorectal liver metastasis can lead to an improved survival in selected patients. However, recommendation of thermoablation as a part of guidelines for the therapy of colorectal metastases is restricted due to a shortcoming of randomized controlled trials. Therefore, interventional tumor therapies have to be evaluated in comparison with standard therapies, particularly with regard to surgical resection and chemotherapy. Moreover, the interdisciplinary combination of tumor ablation, surgical resection, and chemotherapy is a promising approach for the optimization of oncological therapy strategies in the treatment of colorectal metastases.

Real-time MR fluoroscopy-navigated lumbar facet joint injections: feasibility and technical properties.

We prospectively evaluated the feasibility and technical properties of a dedicated interventional magnetic resonance (MR) imaging protocol for near-real-time MR fluoroscopy-guided bilateral lumbar facet joint injections. A total of 44 facet joint injections were performed in 22 patients using a C-shaped open 0.2-T MR imaging system (Magnetom Concerto, Siemens Medical Solutions, Erlangen, Germany). A T1/T2-weighted fast-imaging-with-steady-precession (FISP) sequence with an end-to-end latency of 1.2 s facilitated sufficient near real-time MR imaging guidance in all cases. A T1-weighted two dimensional fast-low-angle-shot (FLASH2D) MR sequence identified final needle tip location. Different angles of the needle path had only minimal influence on the appearance of the needle artifact produced by both sequences, resulting in a symmetrical needle tip artifact. The joint cavity was successfully punctured in 79.5% (35/44) of joints, which was followed by intra-articular fluid accumulation in 75% (33/44). Inaccessible joints demonstrated a significantly (p=0.044) higher number of posterior osteophytes (66.7%, 6/9 joints) compared to accessible joints (26%, 9/35 joints). No complications occurred. Table time showed significant shortening over time with average table time of 33 (21-68.5) min. We conclude that MR fluoroscopy-navigated lumbar facet joint injections are feasible and safe.

[Combined therapies including interventional radiology]. / Interventionelle Kombinationstherapien.

Interventional tumor therapies are a therapeutic option that is increasingly applied in the treatment of malignant diseases. Thermoablation of primary and secondary liver tumors is the most widely used of them, and owing to the promising results it has given, it is becoming an increasingly well-accepted treatment procedure. These interventional radiological tumor therapies must be evaluated in comparison with standard therapies, and particularly in comparison with surgical resection, radiotherapy, and systemic chemotherapy. This comparative approach to the evaluation of different therapies is reflected in the current literature. Besides this approach, interdisciplinary combination of therapies is a promising approach to the optimization of oncological therapy strategies. Local thermoablation in association with systemic or local chemotherapy, and surgical resection in association with thermoablation are interdisciplinary therapy concepts that expand the range of therapeutic options available. Against this backdrop, studies to evaluate interventional tumor therapies as part of interdisciplinary combination therapies are necessary.

[Interventional MR imaging in musculoskeletal]. / La Résonance Magnétique Interventionnelle en pathologie ostéoarticulaire.

Magnetic resonance (MR) imaging is well established for the diagnosis of musculoskeletal diseases. The excellent tissue contrast and the multiplanar imaging capability have both contributed to the improvement of this technique. The development of fast acquisition techniques, sufficient patient access obtained with open magnet configurations and advances in the technology of MR compatible instruments allow a new approach to interventional radiology. These recently commercially available open-bored high-field magnets allow standard interventions such as biopsies or intra-articular infiltrations. Moreover, new interventions e.g. preoperative marking of soft tissue or bone marrow tumors are now possible with the better tissue contrast of MR imaging.

[Internally cooled bipolar radiofrequency ablation: is a lower power output more effective?]. / Intern gekühlte bipolare Radiofrequenzablation: Ist eine niedrige Leistung effektiver?

PURPOSE: Evaluation of bipolar radiofrequency (RF) ablation using internally cooled electrodes in an ex-vivo experiment. MATERIALS AND METHODS: Bipolar RF ablations (n = 154) were performed in ex-vivo bovine liver. Both electrodes with a total length of the active tip of 4 cm were located on the same shaft of an internally cooled applicator. The power output was systematically varied between 20 and 100 watts (W). The energy application was continuous or modulated depending on the tissue resistance. In relationship to the maximum power output, the volume of coagulation was assessed. RESULTS: In continuous energy application the induced volume of coagulation was increased at lower power outputs up to 33.7 cm (3) (20 watts). Parallel to an increased volume of coagulation, the required duration of energy application was increased up to a maximum of 51.6 minutes. Modulation of the power output as a function of the tissue resistance enabled application of a wide range of power outputs (40 - 75 watts) leading to a comparable extent of coagulation with a maximum of 14.9 cm (3) (10 min.), 16.8 cm (3) (15 min.), and 19.1 cm (3) (20 min.). CONCLUSION: Continuous application of RF energy leads to an inverse relationship between volume of coagulation and power output. Modulation of the power output as a function of the tissue resistance enables application of a wider range of power outputs compared to continuous application of RF energy.

[Radiofrequency ablation of lung tumors]. / Radiofrequenz-Ablation von Lungentumoren.

Radiofrequency (RF) ablation is an effective therapy option in the treatment of primary and secondary liver tumors. Percutaneous RF ablation of primary and secondary pulmonary tumors is a possible new indication. Due to the minimally invasive character of percutaneous RF ablation, application in patients who are not candidates for curative radical resection is possible. Moreover, pulmonary RF ablation is a promising palliative therapy option. In this context, an increasing number of results regarding RF ablation of lung tumors were recently published. The present review summarizes and discusses the possible indications, techniques, results, and complications of pulmonary RF ablation.

Magnetic resonance imaging for hepatic radiofrequency ablation.

Image-guided radiofrequency (RF) ablation is a minimally invasive therapy option in the treatment of primary and secondary hepatic malignancies. Magnetic resonance (MR) imaging offers an accurate pre-interventional imaging having important impact on patient selection and planning of the ablation procedure. Peri-interventional imaging is used for targeting, monitoring, and controlling of the ablation procedure. Due to a high soft-tissue contrast offering delineation of tumor tissue and the surrounding anatomy, coupled with multiplanar capabilities, MR imaging is an advantageous targeting technique compared with ultrasonography (US) or computed tomography (CT). MR imaging is sensitive to thermal effects enabling a monitoring of ablation therapy subsequently being supportive to control the ablation procedure. Therefore, MR imaging can fulfil the conditions for overlapping ablations by enabling a precise repositioning of the MR compatible RF applicator if required. Thus, the probability of achieving complete coagulation in larger tumors within a single therapy session is potentially increased. A monitoring of thermal effects is moreover essential in order to prevent unintended tissue damage from critical structures in the surrounding of the target tissue. Post-interventional imaging is performed to assess treatment response after RF ablation and has prognostic impact, as an early detection of treatment failure, e.g. residual tumor tissue, enables immediate therapy. Nevertheless, differential diagnostic difficulties arise from benign periablational enhancement which may cover tumor tissue. Hence, further evaluation and improvement in the assessment of treatment response is essential.

[Radiofrequency ablation of renal cell carcinomas using MR imaging: initial results]. / Radiofrequenzablation des Nierenzellkarzinoms unter MR-Bildgebung: Erste Ergebnisse.

PURPOSE: First results of a study about the efficacy of magnetic resonance-(MR-)guided radiofrequency ablation of renal cell carcinomas (RCC) are presented. MATERIAL AND METHODS: Eight patients (63 to 82 years old) with RCC up to 3.9 cm in diameter were treated by percutaneous RF ablation under MR-guidance in an open MR scanner at 0.2T field strength. For positioning of the RF-electrode, fluoroscopic rapid gradient echo sequences (acquisition time about 2 sec) were used. The ablation was monitored by intermittent imaging with T1- and T2-weighted spin echo sequences. RESULTS: In each patient, the applicator was successfully positioned within the tumor using MR-guidance. Seven of eight patients were completely treated within one single session; one patient had to be retreated for tumor relapse at 13 months. The mean number of electrode repositionings under MR guidance for complete ablation was 2.0; ablation time ranged between 12 and 28 minutes. Maximum diameter (volume) of induced coagulation necrosis within one session was 3.9 cm (30.2 cm (3)) by using cluster electrodes. With single electrodes, maximum short axis diameter of coagulation without repositioning was 2.4 cm (11.6 cm (3)). All patients are now disease-free after a mean follow up of 13 months (5 to 21 months). No major complications occurred during or after the ablation procedure. CONCLUSION: MR-guided RF ablation in an open interventional 0.2T MR-unit is a safe and effective modality for the treatment of RCC. Fast MR-imaging is a convenient method for exact positioning of MR-compatible RF-electrodes. Near on-line MR-monitoring of ablation procedure with T2-weighted imaging allows for immediate assessment of the coagulation extent.

[Magnetic resonance imaging -- guided corticosteroid-infiltration of the sacroiliac joints: pain therapy of sacroiliitis in patients with ankylosing spondylitis]. / Magnetresonanzgesteuerte Kortikosteroid-Infiltration der Sakroiliakalgelenke: Schmerztherapie der Sakroiliitis bei Patienten mit Spondylitis ankylosans.

PURPOSE: To evaluate the efficacy and specific properties of MR imaging-guided corticosteroid infiltration of the sacroiliac (SI) joints in the treatment of therapy-refractory sacroiliitis in patients with ankylosing spondylitis. MATERIALS AND METHODS: In this study, 26 patients were prospectively included. Inclusion criteria were AS with therapy refractory acute sacroiliitis and inflammatory back pain > or = 6 months. The intervention was performed using an open low-field MR-scanner. Inflammatory back pain was assessed on a visual analog scale (VAS). Success of the therapy was defined as an absolute reduction of the VAS score or = 35 % and persisting improvement > or = 2 months. The grade of sacroiliitis was documented using high-field MR imaging. Variables were compared using McNemar test and Wilcoxon test. The mean remission time was calculated using a Kaplan-Meier analysis. A p-value < 0.05 was considered statistically significant. RESULTS: The intervention was technically successfully performed in all patients. Following MR imaging-guided corticosteroid infiltration of the SI joints, the VAS score improved from 8 (5 - 10) points to 4.5 (0 - 8) points (- 44 %) in all patients (n = 26), which was statistically significant (p < 0.001). Of 26 patients, 22 (85 %) fulfilled the predefined criteria for successful therapy. This group had a statistically significant (p < 0.01) improvement of the VAS score from 8 (6 - 10) to 3 (0 - 5) (- 63 %). Improvement was seen after 7 (1 - 30) days. There was a marked reduction of the subchondral bone marrow edema (- 38 %). The mean remission time was 12 (4 - 18) months. CONCLUSION: MR imaging-guided corticosteroid infiltration of the SI joints proved to be an effective therapy of inflammatory back pain in patients with therapy refractory AS. With the ability of multiplanar imaging, precise localization of the bone marrow edema and the lack of ionizing radiation, interventional MR imaging currently represents the superior method for the treatment of the predominantly young patient group presenting with ankylosing spondylitis. Owing to short intervention times, open MR-scanners are ideally suited for MR imaging-guided infiltration of the SI joints.

[Radiofrequency ablation of liver metastases]. / Radiofrequenzablation von Lebermetastasen.

The liver is the second only to lymph nodes as the most common site of metastatic disease irrespective of the primary tumor. Up to 50% of all patients with malignant diseases will develop liver metastases with a significant morbidity and mortality. Although the surgical resection leads to an improvement of the survival time, only approximately 20% of the patients are eligible for surgical intervention. Radiofrequency (RF) ablation represents one of the most important alternatives as well as complementary methods for the therapy of liver metastases. RF ablation can lead in a selected patient group to a palliation or to an increased life expectancy. RF ablation appears either safer (vs. cryotherapy) or easier (vs. laser) or more effective (percutaneous ethanol instillation [PEI], transarterial chemoembolisation [TACE]) in comparison with other minimal invasive procedures. RF ablation can be performed percutaneously, laparoscopically or intraoperatively and may be combined with chemotherapy as well as with surgical resection. Permanent technical improvements of RF systems, a better understanding of the underlying electrophysiological principles and an interdisciplinary approach will lead to a prognosis improvement in patients with liver metastases.

Cyclin-dependent kinase inhibitor P27(KIP1) is expressed preferentially in early stages of urothelial carcinoma.

OBJECTIVES: To evaluate the expression of p27(KIP1) and p21(CIP1) and the prognostic values of both markers in urothelial carcinoma. The expression of the cyclin-dependent kinase inhibitor p27(KIP1) characterizes early-stage and well-differentiated carcinomas of the colon, breast, and prostate and is associated with an improved prognosis. In urothelial carcinoma, its expression has not been as well investigated. Another cyclin-dependent kinase inhibitor, p21(CIP1), is expressed in early-stage bladder tumors, but published data on its prognostic value are contradictory. METHODS: Expression of p27(KIP1) and p21(CIP1) was analyzed by immunohistochemistry in 114 urothelial carcinoma specimens from 77 patients. The Ki67 index was determined as an indicator of cell proliferation. The expression of the markers was correlated with tumor recurrence and progression during an average follow-up period of 3.9 years. RESULTS: Expression of p27(KIP1) was significantly more frequent in superficial than in muscle-invasive tumors (chi-square test, P = 0.012; Fisher's exact test, P = 0.014). Although similar overall, the expression pattern of p21(CIP1) did not match on a tumor-by-tumor basis. No correlation was seen with the Ki67 index. Patients with tumors displaying strong positive staining for p27(KIP1) or p21(CIP1) had fewer recurrences and progression events, but the difference was not statistically significant. Instead, a Ki67 index of less than 10% was significantly (P = 0.0335) related to a lack of recurrence. CONCLUSIONS: Neither p27(KIP1) nor p21(CIP1) appear to be good predictors of tumor progression in urothelial carcinoma, even though their expression is strongly decreased in muscle-invasive tumors.

WAF1/p21 regulates proliferation, but does not mediate p53-dependent apoptosis in urothelial carcinoma cell lines.

The WAF1/p21 gene product is an inhibitor of cyclin-dependent kinases which can be induced by the tumor suppressor p53 and mediate some of its effects, or function in p53-independent pathways of cell cycle regulation. Although a potential tumor suppressor gene, WAF1/p21 is expressed in bladder cancer. To elucidate the function of p21 in tumor cells we have investigated in urothelial carcinoma cell lines: i) WAF1/p21 mRNA and protein expression, ii) the biological effects of p21 overexpression or down-regulation and (iii) whether p21 can be induced by p53. WAF1/p21 mRNA levels examined in four cell lines were comparable to bladder mucosa. One cell line, HT1376, failed to express p21 protein due to a frame shift mutation. Overexpression of WAF1/p21 cDNA inhibited clone formation in three cell lines, whereas transfection with antisense WAF1 increased clone sizes and numbers. WAF1 sense clones showed diminished cell proliferation compared to the parental cell line. Apoptosis- induced wild-type p53 was not inhibited by overexpression of antisense WAF1/p21. In a cell clone derived from line VMCub1 by stable transfection with wild-type p53 under the control of a metallothionein promotor, p21 was induced along with p53 upon activation of the promoter with zinc chloride. This induction was accompanied by a decrease in cell proliferation but by little apoptosis. These data suggest that p21 inhibits proliferation in a p53-dependent or independent manner but does not mediate p53-induced apoptosis in urothelial carcinoma cells.

Frequent and heterogeneous expression of cyclin-dependent kinase inhibitor WAF1/p21 protein and mRNA in urothelial carcinoma.

The inhibitor of cyclin-dependent kinases WAF1/p21 has been shown to mediate cell cycle arrest by p53 and other factors. We have studied its expression in urothelial carcinoma. Immunohistochemistry of paraffin-embedded tissues revealed no detectable p21 protein in normal mucosa, whereas 8 of 17 (47%) carcinomata in situ, 41 of 62 (66%) pTa, 14 of 30 (47%) pT1 and 5 of 15 (33%) muscle-invasive tumours stained positive, usually with a heterogeneous pattern. Expression of p21 was associated with low grade tumours. In contrast, the frequency of p53 accumulation increased with grade and stage as did the frequency of staining for the proliferation marker Ki67. The level of WAF1 mRNA was determined relative to beta-actin mRNA by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in 15 freshly frozen invasive tumours. In eight samples obtained from normal bladder mucosa, the values ranged from 0.93 to 2.19 arbitrary units (AU) (mean 1.54+/-0.37 AU), but varied widely from non-detectable to 16.21 AU (mean 3.02+/-4.44 AU) in the tumour specimens. In accord with the immunohistochemical findings, WAF1 mRNA expression was elevated over the range found in normal mucosa in 5 of 15 advanced tumours. In addition, RNA analysis revealed a decrease in expression in six tumours. No mutations were observed in the WAF1/p21 gene in these tumours, but two were heterozygous for the codon 31 polymorphism. These data indicate that p21 is frequently expressed in superficial, well differentiated urothelial carcinomas, but less often in muscle-invasive urothelial carcinomas, irrespective of their p53 status. The expression of p21 and its prevalence in low-stage tumours may reflect residual growth-regulatory influences potentially impeding but not necessarily inhibiting tumour development.