[Spectrum and bleeding complications of sonographically guided interventions of the liver and pancreas]. / Spektrum und Blutungskomplikationen sonografisch gesteuerter Interventionen an Leber und Pankreas.

PURPOSE: Sonographically guided fine-needle punctures (p.) are considered to be a low risk procedure. Interventions with needles with a larger diameter seem to cause more complications. In search of potential complications, we examined 1923 sonographically guided interventions of the liver and pancreas in a retrospective analysis. MATERIALS AND METHODS: We examined the coherence of the kind of intervention and complications. We considered bleeding with a need for transfusion and/or a need for surgical treatment as complications. Diseases and medication increasing the probability of post-interventional bleeding were also detected. RESULTS: 1923 sonographically guided interventions in the abdomen (1800 in the liver, 123 in the pancreas) were analyzed (n = 1696 diagnostic interventions, n = 227 therapeutic interventions). Needles with diameters > 1 mm were primarily used. Drainage and radiofrequency ablation (RFA) (12 % of all interventions) were performed with devices with diameters between 2 - 3.96 mm. A need for transfusion was found in 8 / 1923 patients (0.4 %), predominantly in the first 24 h. There was no significant correlation between coagulation preventing drugs (heparin, NSAIDs, antiaggregants) and bleeding events. Patients who suffered from liver cirrhosis with a thromboplastin time of < 50 % had a higher risk of post-interventional bleeding than patients with liver cirrhosis and a thromboplastin time > 50 %. Furthermore, therapeutic interventions showed higher complication rates than diagnostic procedures. CONCLUSION: Severe bleeding complications with a need for transfusion in sonographically guided procedures are rare (0.4 %). Our results showed that liver cirrhosis with a low thromboplastin time (< 50 %) seems to be the most important risk factor for patients. Overall, sonographically guided interventions are safe and have low complication rates considering careful performance and contraindications.

Beneficial effects of external muscle stimulation on glycaemic control in patients with type 2 diabetes.

Physical activity improves insulin sensitivity and metabolic control in patients with type 2 diabetes. Moreover, regular exercise can reduce systemic levels of immune markers associated with diabetes development. As patients with physical impairments are not able to exercise sufficiently, the aim of this study was to investigate whether high-frequency external muscle stimulation (hfEMS) improves metabolic and immunologic parameters in patients with type 2 diabetes and might therefore serve as complementary lifestyle therapy. Sixteen patients (12 men/4 women, age 57+/-11 years (mean+/-SD); BMI 34.5+/-5.2 kg/m (2); HbA1c 7.4+/-1.1%) on oral antihyperglycaemic therapy were enrolled in this study. After a run-in phase of 2 weeks, every patient received an hfEMS device (HITOP 191, gbo-Medizintechnik AG, Rimbach/Germany) for daily treatment of femoral musculature for 6 weeks. Thereafter, patients were followed up for additional 4 weeks without hfEMS treatment. At each visit, clinical parameters were assessed and blood samples were drawn for metabolic and immunologic parameters. Immune markers (cytokines, chemokines, adipokines and acute-phase proteins) representative for the different arms of the immune system were analysed. hfEMS treatment resulted in significant reductions of body weight (-1.2 kg [-2.7 kg; -0.5 kg]; p<0.05; median [25th percentile; 75th percentile]), BMI (-0.4 kg/m (2) [-0.8 kg/m (2); -0.1 kg/m (2)]; p<0.05) and HbA1c (-0.4% [-0.9%; -0.1%]; p<0.05) which were sustained during the follow-up period. Systemic levels of IL-18 tended to be increased after hfEMS treatment (171 vs. 149 pg/ml; p=0.06), while all other immune markers remained virtually unchanged. Treatment with hfEMS in this first proof-of-principle study has beneficial effects on body weight and improves glycaemic control in patients with type 2 diabetes, which may be associated with changes in subclinical inflammation. Taken together, hfEMS might represent an additional treatment option for patients with type 2 diabetes not being able to exercise.

Percutaneous ultrasound-guided radiofrequency ablation (RFA) using saline-perfused (wet) needle electrodes for the treatment of hepatocellular carcinoma--long term experience.

PURPOSE: For many reasons, resection of hepatocellular cancer (HCC) is not feasible in most cases. Radiofrequency (RFA) ablation has proven to be an effective minimally invasive alternative. It has been shown in ex vivo and animal trials that needle applicators perfused with isotonic saline solution could be an effective approach to enlarging the coagulation zone. However, long term survival data for the treatment of HCC are not yet available. MATERIALS AND METHODS: 37 patients with a total of 64 histologically proven HCC with a maximum of 3 tumors of up to 6 cm and a contraindication to partial liver resection or orthotopic liver transplantation were treated with the Integra HiTT106 using wet monopolar single, wet bipolar double or wet triple needle electrodes. The mean HCC size was 37.7 mm (range 15 to 60 mm). Follow-up examinations were performed 2 days and 1, 3, 6, 9 months after RFA and every 6 months thereafter. The survival rate was calculated from the time of the first RFA session. RESULTS: 1, 2 and 5-year survival was 24/32 (75%), 14/31 (45%) and 3/21 (14%) overall; 18/19 (95%), 12/18 (67%) and 3/10 (30%) for HCC Child A; and 6/13 (46%), 2/13 (15%) and 0/11 (0%), for HCC Child B. Complete remission was achieved in 86.5 % of the patients (total: 32 out of 37, multi-needle 18 / 21, single needle 14 / 16). Distant recurrence occurred overall in 20 out of 37 patients (54%), including 9 of 21 treated with multiple needles (43% of patients) and 11 of the 16 patients treated with a single electrode (69%). The overall complication rate was 10.8%. Local recurrence was found for tumors measuring 3 cm-5 cm (n=28) in 7 out of 13 cases after single electrode RFA and in 1 out of 15 after multiple electrode treatment (significant, p=0.009). No significant difference between the single and multi-needle group was found for tumors >5 cm and <3 cm. CONCLUSION: RFA using multiple wet electrodes shows promise as an effective method for treating inoperable HCC especially in cases with well-preserved liver function. Multiple electrodes seem to be superior to single electrodes with respect to the local recurrence rate for tumors between 3 and 5 cm.

Radiofrequency ablation using perfused needle electrodes - study of intermittent and continuous triple needle application ex vivo.

To increase necrotic zones, bovine livers were treated by means of three parallel-oriented radiofrequency ablation (RFA) needles spaced at 3 cm using a puncture guide. The triple application was varied as a continuous and intermittent energy application compared to a single needle applicator. In all three study arms the applied energy (60 W) and the perfusion rate (240 ml/h) were kept constant. After treatment the smallest necrosis diameter was determined. In addition, temperature and the device's power output were monitored. Our study shows that synchronous use of three RFA application needles achieves significantly larger necrosis zones ex vivo than does single needle application. Intermittent energy application heats up the necrosis faster and more evenly with highest average temperature than continuous energy application.

Contrast-enhanced sonography for the characterisation of hepatocellular carcinomas--correlation with histological differentiation.

AIM: We aimed to characterise the vascularisation patterns of hepatocellular carcinomas in contrast-enhanced sonography in correlation to the histological differentiation of hepatocellular carcinomas (HCC), and we also compared the diagnostic value of contrast-enhanced sonography in addition to B-scan sonography and power Doppler sonography. METHODS: 51 hepatocellular carcinomas (21 well differentiated, 27 moderately differentiated, 3 poorly differentiated) were examined: by B-scan sonography, power Doppler sonography and contrast-enhanced sonography using phase or pulse inversion harmonic imaging with a low mechanical index (< 0.3) and second generation microbubble contrast medium (Optison, Sonovue) as echo-enhancing agent. Lesion vascularity and the kinetics of contrast enhancement within the lesions in the early arterial phase, arterial phase, portal phase and late phase were analysed. The final diagnosis of a HCC was assessed after B-scan sonography, power Doppler sonography and contrast-enhanced sonography. RESULTS: Hypervascularisation and/or irregular tumour vascularisation could be detected in 18/48 HCCs (37.5%) by power Doppler sonography. After contrast application, 46/51 HCCs (90.2%) were identified as hyperechoic lesions during the early arterial or arterial phase with no correlation to histological differentiation. In the portal phase and late phase, the echogenicity of HCCs after contrast application was variable. A hypoechoic appearance was noted in 17/51 HCCs (33.3%) in the portal phase and in 21/51 HCCs (41.2%) in the late phase. Moderately differentiated HCCs were more often hypoechoic than well differentiated HCCs (p = 0.04). CONCLUSION: Contrast-enhanced sonography is highly efficient for the detection of tumour vascularity in HCCs. The majority of HCCs--regardless of histological differentiation--can be characterised as hypervascular lesions in the early arterial and arterial phase with irregular tumour vessels using contrast-enhanced sonography. In addition to B-scan sonomorphology, contrast-enhanced sonography may offer helpful information in patients with liver cirrhosis and focal liver lesions.

[Detection of liver metastases--comparison of contrast--enhanced ultrasound using first versus second generation contrast agents]. / Lebermetastasendetektion. Vergleich Kontrastmittel--Ultraschall mit Echosignalverstärkern der ersten versus zweiten Generation.

AIM: To compare detection rates for liver metastases for conventional ultrasound, US using tissue harmonic imaging (THI), echo-enhanced pulse inversion harmonic imaging using Optison and Levovist. METHOD: In 73 patients with histologically proven gastrointestinal tumors spiral CT (S-CT), conventional US, US in the THI-mode, echo-enhanced ultrasound in the portal venous phase (ECI Optison ) and in the liver specific late phase (ECI Levovist) were performed and reviewed by blinded readers. RESULTS: 73 patients (25 female, 48 male, age 63 +/- 11) were included. S-CT detected 158 liver metastases. Conventional US detected 117, THI 119, ECI Optison 169 and ECI Levovist 166 liver metastases. Especially for small (< 2 cm) liver metastases and metastases near the diaphragm echo-enhanced ultrasound exceeded conventional US (p < 0.001). Between both echo enhancers there was no significant difference. CONCLUSION: Using echo enhancers increases the ultrasound detection rate significantly. Examination in the portalvenous phase using a second generation enhancer (Optison) is equal to a late-phase examination using Levovist.

Radiofrequency ablation of hepatocellular carcinoma with a saline solution perfusion device: a pilot study.

PURPOSE: The majority of patients with hepatocellular carcinoma (HCC) cannot be treated with surgery. This study evaluated the treatment of patients with radiofrequency ablation (RFA) with use of needle applicators perfused with isotonic saline solution. MATERIALS AND METHODS: Twenty patients with a maximum of three HCCs as large as 60 mm and a contraindication to partial liver resection or orthotopic liver transplantation were enrolled in the study. They were treated with ultrasound-guided RFA with use of perfused needle applicators and followed with sonography and computed tomography. RESULTS: Twenty patients (14 men, six women) with a total of 29 HCCs were treated with RFA. In total, 56 RFA treatments were performed. Mean HCC size was 31 mm (range, 10-60 mm). Two cases of self-limiting bleeding requiring transfusion of blood products took place. Complete response (CR) was achieved in 85% of patients (17 of 20). Partial response occurred in three tumors 45 mm in diameter or larger. There was a total of six local recurrences in five patients (25% of patients, 21% of tumors). Six patients (30%) exhibited distant recurrence, two of whom also showed local recurrence. In three patients, repeat treatment led to renewed CR. After a median follow-up of 445 days (range, 114-1,071 days), 12 patients (71% of the 17 patients with initial CR) still showed CR. Twelve patients (60% of all patients, 71% of those with initial CR) survived. Three of the eight patients who died were free of viable tumor at the time of death. CONCLUSIONS: RFA with use of perfused needle applicators shows promise as an effective method for treating inoperable HCC. The most frequent complication was bleeding.

[Radio-frequency-ablation (RFA) with wet electrodes in the treatment of primary and secondary liver tumours]. / Hochfrequenzthermotherapie mit perfundierten Nadelapplikatoren bei der Behandlung primärer und sekundärer Lebertumoren.

INTRODUCTION: The majority of patients with primary and secondary tumours of the liver cannot be treated curatively by surgery. The treatment of these patients with radio-frequency thermoablation using perfused needle applicators (wet electrodes) was evaluated in a feasibility study. METHOD: Patients with primary and secondary tumours of the liver and contraindications against surgery or LTX were included into the feasibility study. RFA was performed percutaneously under ultrasound guidance. The patients were followed up sonographically and by computed tomography. RESULTS: 20 patients (9 male, 11 female) with 35 lesions were treated with RFA. 12 patients (22 tumour locations) suffered from HCC and 8 patients (13 tumour masses) had liver metastases (colorectal, breast, pancreas, carcinoid). The median age was 65.6 years (36 to 83 years). The median tumour size was 33.5 mm. 59 RFTA applications (1.7 applications per tumour mass) were performed. The mean duration of RFTA per patient was 16.2 minutes. During the procedure isotonic saline was injected at a mean flow rate of 6.63 ml/min. All patients received local anaesthesia. In 33 sessions an additional analgosedation was necessary (average dose 63.8 mg Pethidine and 1.4 mg Midazolam). In 2 cases a reduction of the haemoglobin level, occurred, necessitating a blood transfusion. 3/4 of the treated metastases could be eradicated completely. Within a median follow-up of 145 days no intrahepatic local recurrence but 4 distant metastases occurred. 2/3 of the treated HCC could initially be brought into complete remission (CR). After a median follow-up of 329 days 5 of the 8 initially successfully treated patients with HCC were still in complete remission. In 3 cases an intrahepatic local recurrence developed. CONCLUSION: RFA with wet electrodes is a safe, effective and inexpensive treatment for primary and secondary tumours of the liver, measuring less than 4 cm in diameter.

Cellular and vascular reactions in the liver to radio-frequency thermo-ablation with wet needle applicators. Study on juvenile domestic pigs.

UNLABELLED: The aim of this animal experiment was to investigate the cellular and vascular reactions in the liver of juvenile domestic pigs produced by a radio-frequency thermoablation (RFTA) applicator perfused with saline solution. METHODS: A total of 13 coagulation necroses were produced in the liver of 3 anesthetized domestic pigs using RFTA. The pigs were dissected and the coagulations examined. RESULTS: The mean macroscopical length and width of the coagulation zones with a hemorrhagic marginal zone after a 5-minute application time were 34.1 +/- 8 mm (22-46 mm) and 20.8 +/- 4 mm (12 +/- 28 mm) respectively. The sonographically determined diameters correlated significantly (r(length) = 0.741 and r(width) = 0.923). Three areas in the coagulation zones could be histologically distinguished: (1) central necrosis zone, (2) hemorrhagic marginal zone, (3) sublethal damage zone. Large vessels did not show any substantial changes after RFTA. Venous vessels less than 1 mm were completely thermally denatured or destroyed. CONCLUSIONS: Tumors in close proximity to large blood vessels can be treated by RFTA with 'wet electrodes'.

[Treatment of a solitary adenoma of the parathyroid gland with ultrasound-guided percutaneous Radio-Frequency-Tissue-Ablation (RFTA)]. / Behandlung eines solitären Nebenschilddrüsenadenoms mit perkutaner ultraschallkontrollierter Radiofrequenzablation.

Radio-Frequency-Tissue-Ablation (RFTA) for the treatment of primary and secondary tumours of the liver has been used for several years, but this minimally invasive treatment is not limited to the liver. A patient suffering from symptomatic postmenopausal osteoporosis, additionally having primary hyperparathyroidism since 1995, refused a surgical resection of the adenoma of the parathyroid gland. Sonographically a 16 mm hypoechoic tumour dorsal of the right upper pole of the thyroid gland was detected. Osteodensitometry: severe osteoporosis of the lumbar spine (88 % of the norm for this age group). Blood check: Elevation of serum calcium level (3.1mmol/l) and serum parathormone level 274 pg/dl (N: 10-50). A percutaneous ultrasound guided RFTA of the adenoma of the thyroid gland was carried out. After RFTA the serum parathormone levels and the serum calcium levels dropped back to normal. The patient was followed-up for one year. For the first time a sufficient therapy for osteoporosis comprising calcium, etidronate and cholecalciferol could be carried out. The osteodensitometry carried out one year after treatment showed an increase in bone density. For the treatment of symptomatic primary hyperparathyroidism RFTA can be a therapeutic alternative for patients with contraindications for surgery.

Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and folinic acid.

BACKGROUND: In palliative first-line treatment of colorectal cancer, the secondary resection of distant metastases after downstaging has constantly gained in importance. The objective of this prospective study was to examine the tumor response rate, the toxicity, the median survival time and the prognostic impact of metastatic resection after downstaging of consecutively enrolled patients with primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h) infusion of high-dose 5-fluorouracil (5-FU) and folinic acid. PATIENTS AND METHODS: Between January 1995 and July 1997, 53 consecutive patients with primary nonresectable metastases were recruited for a prospective phase II study. The patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once weekly. One treatment cycle comprised six weekly infusions followed by a two week rest. Three cycles were administered, and in the event of complete remission (CR) or partial remission (PR) and good tolerability, a fourth cycle was undertaken. Thereafter, the possibility of performing a curative metastatic resection was investigated. RESULTS: Of the 53 patients treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%). The median survival time was 17 months with a median follow-up of 41 months (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was considered; in 6 patients (11%) curative resection was performed, and 4 patients (8%) showed no evidence of disease for at least three years. CONCLUSION: In this phase II study, we have been able to show prospectively that, after downstaging by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary curative metastatic resection was technically feasible in 11% of the patients. For some of these patients, long-term survival is therefore possible. Secondary metastatic resection should be carried out in close interdisciplinary cooperation, and should be further investigated in prospective phase III studies.

Percutaneous ethanol injection and radio-frequency ablation for the treatment of nonresectable colorectal liver metastases - techniques and results.

BACKGROUND: Percutaneous ethanol injection (PEI) and radio-frequency (RF) ablation are possible palliative treatment modalities for patients with non-resectable liver metastases of colorectal carcinomas. The different techniques are explained and reviewed. RESULTS: PEI did not show promising results for the treatment of liver metastases. RF results were more encouraging; some studies showed improved mean survival times for patients when a complete necrosis of the metastases could be achieved. The maximum diameter of the necrotic area possible in a single session is about 5 cm. CONCLUSION: PEI and RF are palliative last-line treatment strategies for patients with non-resectable liver metastases and should only be applied if chemotherapy is not sufficient or not possible. The long-term efficacy of RF ablation in this group of patients has to be evaluated.

[Ultrasound-controlled interstitial high frequency thermotherapy (HFTT)--in vitro studies of the bovine liver]. / Ultraschallgesteuerte Interstitielle Hochfrequenz-Thermotherapie (HFTT)--in-vitro-Untersuchung an der Rinderleber.

PURPOSE: Sonographically-guided Radio-Frequency Tissue Ablation-applied with a percutaneously placed needle can be used for the palliative treatment of primary or secondary liver tumours. In vitro experiments were carried out to establish the relations of the coagulation zone to histologic findings and sonographic appearance. METHOD: Fresh bovine livers were obtained and radio-frequency was applied under ultrasound guidance. The coagulation zone was dissected and examined by determining its three-dimensional diameters (macroscopically) and the histologic appearance of the coagulation margin to the surrounding tissue. In our series of 50 experiments the application time ranged from 30 seconds to 10 minutes. RESULTS: The coagulation zone increased with increasing application time in a way that can be described as a negative logarithmic function. The largest volume was 4 x 5 x 5 cm (length, width, depth) approximating 50 ml. It was no problem to judge the coagulation zone sonographically. The macroscopically and sonographically determined width and length correlated with coefficients of 0.90 and 0.96. Microscopically the coagulation necrosis showed sharply outlined margins without any vital cells. CONCLUSION: Radio-Frequency Tissue Ablation applied under sonographic guidance has certain features which seem to make it a promising method for the palliative treatment of primary and secondary tumours of the liver.