Image guided respiratory gated hypofractionated Stereotactic Body Radiation Therapy (H-SBRT) for liver and lung tumors: Initial experience.

To evaluate our initial experience with image guided respiratory gated H-SBRT for liver and lung tumors. The system combines a stereoscopic x-ray imaging system (ExacTrac X-Ray 6D) with a dedicated conformal stereotactic radiosurgery and radiotherapy linear accelerator (Novalis) and ExacTrac Adaptive Gating for dynamic adaptive treatment. Moving targets are located and tracked by x-ray imaging of implanted fiducial markers defined in the treatment planning computed tomography (CT). The marker position is compared with the position in verification stereoscopic x-ray images, using fully automated marker detection software. The required shift for a correct, gated set-up is calculated and automatically applied. We present our acceptance testing and initial experience in patients with liver and lung tumors. For treatment planning CT and Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) as well as magnetic resonance imaging (MRI) taken at free breathing and expiration breath hold with internal and external fiducials present were used. Patients were treated with 8-11 consecutive fractions to a dose of 74.8-79.2 Gy. Phantom tests demonstrated targeting accuracy with a moving target to within +/-1 mm. Inter- and intrafractional patient set-up displacements, as corrected by the gated set-up and not detectable by a conventional set-up, were up to 30 mm. Verification imaging to determine target location during treatment showed an average marker position deviation from the expected position of up to 4 mm on real patients. This initial evaluation shows the accuracy of the system and feasibility of image guided real-time respiratory gated H-SBRT for liver and lung tumors.

Sonographic findings in hepatic involvement of hereditary haemorrhagic telangiectasia.

AIM: Hereditary haemorrhagic telangiectasia, or Rendu-Osler-Weber disease, is an autosomal-dominant disorder characterised by angiodysplastic lesions (telangiectases and arteriovenous malformations) which affect many organs including the skin, lungs, gastrointestinal tract, and brain. A broad spectrum of vascular and structural changes have been reported. Our objective was to systematically examine the prevalence of sonographic findings in hepatic involvement in patients with hereditary haemorrhagic telangiectasia (HHT). METHODS: We studied 22 consecutive patients with hereditary haemorrhagic telangiectasia by ultrasonography in combination with colour-Doppler and pulsed wave-Doppler for liver involvement. The clinical diagnosis of HHT was based on the Curaçon criteria. RESULTS: Sixteen of the 22 patients had signs of hepatic involvement including prominent common hepatic artery (14 of 16), dilatation of the intrahepatic part of the hepatic arteries (15 of 16) and intrahepatic AV-shunts (16 of 16). Ectasia of the hepatic vein, fibrotic parenchymal changes, left accessory hepatic artery and focal hepatic lesions were found less frequently. CONCLUSION: Diagnosis of liver involvement in HHT can be made by sonography with colour-Doppler. The main features of this involvement include prominent common hepatic artery, dilatation of the intrahepatic part of the hepatic arteries and intrahepatic AV-shunts.

Perforation of a pancreatic pseudocyst induced by abdominal sonography.

A fifty-year-old man complained of abdominal pain, nausea, loss of appetite, postprandial vomiting and loss of weight. Abdominal sonography revealed a chronic calcifying pancreatitis with a tubular stenosis of the common bile duct, dilatation of the pancreatic duct and multiple pancreatic duct stones. Distal of the pylorus there was an intramural pseudocyst, which had led to the obstruction of the duodenal lumen. Shortly after the ultrasound examination abdominal pain increased. In addition, an elevation of serum lipase levels was noted, but reclined rapidly the next day and was normalized a few days later. The patient was well the next morning, the symptoms of gastric retention disappeared and he had a good appetite. A CT of the abdomen two days later showed the chronic pancreatitis but could not confirm the pseudocyst and a subsequent repeat sonography revealed only a remnant of the pseudocyst. In conclusion it can be assumed that the intramural pseudocyst ruptured when pressure was applied with the ultrasound transducer to displace interfering colonic gas. Although it cannot be advised as a treatment measure for a pseudocyst, regression of a pseudocyst due to emptying into the gastrointestinal tract has to be expected.

High-resolution ultrasound in combination with colour-Doppler sonography for preoperative localization of parathyroid adenomas in patients with primary hyperparathyroidism.

BACKGROUND AND AIMS: Experienced surgeons have the highest sensitivity in the localization of parathyroid adenomas in patients with primary hyperparathyroidism. Correct preoperative localization, however, allows unilateral neck exploration with subsequently reduced operative time and complication rate. In this prospective study, we investigated the accuracy of preoperative high-resolution ultrasound in combination with colour-Doppler sonography for the detection of parathyroid lesions. SUBJECTS/METHODS: Ninety-eight patients (mean age 59.1 years, range 15-86) who referred to our department with symptomatic primary hyperparathyroidism were included in the study from January 1998 to June 2002. Sonography was performed by experienced examiners. The exact diagnosis was based on surgical findings and histology in all patients. RESULTS: The overall sensitivity for the sonographical localization of the adenomas on the correct side of the neck was 86 %. Twenty-three percent of the adenomas located on the cranial margin of the thyroid gland were diagnosed correctly, as were 92 % of the lesions located caudally (p = 0.0001). The detection of feeding vessels was possible by colour-Doppler sonography in 60 % of the cases. The diagnosis was correct for 93 % of these suspected adenomas. No vessels were detected in the remaining lesions, and only 39 % of these tumours were diagnosed correctly (p = 0.0001). CONCLUSIONS: High-resolution ultrasonography by experienced examiners is a highly sensitive procedure for the preoperative diagnosis of parathyroid adenomas in patients with primary hyperparathyroidism. With this method, a unilateral neck exploration is sufficient in about 90 % of the patients. Additionally, detection of feeding vessels by colour-Doppler sonography is an important indication of a parathyroid lesion. Nonetheless, the experienced surgeon remains the standard of reference.

Differentiation of neuroendocrine tumors from other pancreatic lesions by echo-enhanced power Doppler sonography and somatostatin receptor scintigraphy.

BACKGROUND AND AIMS: Echo-enhanced power Doppler sonography is a noninvasive procedure that has been increasingly used for the differential diagnosis of pancreatic tumors. However, to our knowledge, the diagnostic accuracy of this procedure in comparison with somatostatin receptor scintigraphy for the differentiation of neuroendocrine lesions from other pancreatic tumors has never been investigated in a prospective, controlled study. SUBJECTS AND METHODS: One hundred thirty-seven patients were included in the study; the patients were selected from 190 consecutive patients (mean age, 59.8 years; range, 16-85 years) who presented to our department from January 1998 through June 2001 with suspicion of a pancreatic tumor. An experienced examiner who was unaware of the patients' clinical diagnoses performed sonography. Twenty-nine patients with sonographically and/or clinically suspected neuroendocrine tumors were investigated additionally by somatostatin receptor scintigraphy. The exact diagnosis was based upon histologic evidence from biopsy examination (surgical and transabdominal fine-needle biopsy) or a follow-up of at least 18 months. RESULTS: The sensitivity of echo-enhanced power Doppler sonography for diagnosing a neuroendocrine pancreatic tumor was 94%, and its specificity was 96%. The corresponding values for somatostatin receptor scintigraphy were 54% and 81%, respectively. CONCLUSIONS: Echo-enhanced power Doppler sonography has high sensitivity and high specificity for the differentiation of neuroendocrine lesions from other pancreatic tumors. However, histologic evidence is the standard of reference for the differential diagnosis of pancreatic tumors.

Differentiation of pancreatic tumours by conventional ultrasound, unenhanced and echo-enhanced power Doppler sonography.

BACKGROUND: Echo-enhanced power Doppler sonography (power Doppler sonography after injection of a contrast agent) is a non-invasive and increasingly used procedure for differentiating between pancreatic tumours. However, the diagnostic accuracy of this method compared to conventional ultrasound or unenhanced power Doppler sonography has never been investigated in a large prospective controlled study. METHODS: 137 patients were included in the study, selected from 190 consecutive patients with a mean age of 60 years (range 16-85) who presented at our department in the period January 1998 through June 2001 with clinical suspicion of a pancreatic tumour. Sonography was performed by an experienced examiner blind to the patients' clinical diagnoses. The exact diagnosis was based on histological evidence from biopsy examination (surgical and fine needle biopsy) or on a follow-up of at least 18 months. RESULTS: Of the 137 patients, 47 had pancreatic cancer; 41 had masses associated with pancreatitis; 17 had neuroendocrine tumours; 12 had cystic lesions of the pancreas; and 10 had other pancreatic diseases. A normal pancreas was found in 10 patients. The sensitivity of echo-enhanced power Doppler sonography with respect to diagnosing pancreatic carcinoma was 87% and its specificity 94%. The corresponding values for chronic pancreatitis were 85% and 99%, respectively. CONCLUSIONS: Echo-enhanced power Doppler sonography has a high sensitivity and specificity in the differential diagnosis of pancreatic tumours. However, histology is the standard of reference.

[Contrast behaviour of a angiomyolipoma of the liver at echo-enhanced power-Doppler sonography]. / Das Kontrastverhalten des Leberangiomyolipoms in der echosignalverstärkten Power-Dopplersonographie.

Angiomyolipomas of the liver are rare tumours. Differentiation from other liver lesions using imaging techniques is difficult. This is the first report describing the contrast behaviour of an angiomyolipoma of the liver with echo-enhanced power-Doppler sonography. A rapid signal enhancement of the arteries within the tumour and an immediate drainage of the blood into the liver veins was demonstrated. Furthermore, spectrums similar to av-fistulas could be detected. Portal venous blood flow, irregular calibre of the vessels or chaotic vascular patterns could not be found.

[Evaluation of Doppler sonographic criteria for the differentiation of hepatocellular carcinomas and regenerative nodules in patients with liver cirrhosis]. / Evaluierung dopplersonographischer Kriterien zur Differenzialdiagnostik von hepatozellulären Karzinomen und Regeneratknoten bei Leberzirrhose.

AIM: In order to improve the differentiation between hepatocellular carcinomas and regenerative nodules in patients with liver cirrhosis, Doppler-sonographic criteria for the tumours were evaluated. METHOD: Patients with histologically proven hepatocellular carcinoma (n = 35) and regenerative nodules (n = 10) were investigated by B-mode sonography as well as fundamental and echo-enhanced power-Doppler sonography focusing on specific properties of the tumours. The results were correlated to the histological findings. RESULTS: Hepatocellular carcinomas and regenerative nodules showed a different contrast behaviour with echo-enhanced power-Doppler sonography. The following features of hepatocellular carcinomas were frequently found: peritumoural signal detection in the early arterial phase, chaotic and centripetal contrast enhancement in the arterial phase, hypervascularization in the capillary phase, and loss of portalvenous blood flow. CONCLUSION: Hepatocellular carcinomas and regenerative nodules display different vascularization patterns in the echo-enhanced power-Doppler sonography. These characteristics can be useful for their differential diagnosis.

[Differential diagnosis of frequent pancreatic tumours with echo-enhanced power-Doppler sonography - presentation of case reports]. / Fallbeispiele zur Erläuterung der Differenzialdiagnostik von häufigen Pankreastumoren mit der echosignalverstärkten Power-Doppler-Sonographie.

UNLABELLED: The echo-enhanced Power-Doppler sonography is useful for the differential diagnosis of pancreatic tumours. Tumour criteria for the differentiation of pancreatic tumours with this procedure are explained using selected cases in the present publication. Ductal carcinomas are often hypovascularised compared with the surrounding tissue. On the other hand, neuroendocrine tumours are hypervascularised lesions. Tumours associated with pancreatitis have a different vascularisation pattern depending on inflammation and necrosis. Cystadenomas frequently show many vessels along the fibrotic strands. CONCLUSIONS: Pancreatic tumours have different vascularisation patterns in the echo-enhanced Power-Doppler sonography. These characteristics can be used for the differential diagnosis.

[Pancreatic metastases of renal cell carcinomas - evaluation of the contrast behavior at echo-enhanced power-Doppler sonography in comparison to primary pancreatic tumors]. / Nierenzellkarzinom-Metastasen des Pankreas - Evaluierung ihres Kontrastverhaltens in der echosignalverstärkten Power-Doppler-Sonographie im Vergleich mit primären Pankreastumoren.

BACKGROUND: Renal cell carcinomas are the most common primary tumors leading to pancreatic metastases. The differentiation of metastases from primary pancreatic tumors is important for the prognosis. Echo-enhanced power-Doppler sonography may be used for the differential diagnosis of tumors. In this study, the contrast behavior of metastases of renal cell carcinomas was evaluated in comparison to primary pancreatic tumors. PATIENTS AND METHODS: Each 5 patients with pancreatic metastases of a renal cell carcinoma, a ductal carcinoma, a neuroendocrine tumor and a pancreatitis-associated mass were investigated by B-mode sonography, fundamental and echo-enhanced power-Doppler sonography. RESULTS: Similar to neuroendocrine tumors, metastases of renal cell carcinomas were found to be hypervascularized. In contrast, ductal carcinomas are hypovascularized compared to the surrounding tissue. Tumors associated with pancreatitis show different vascularization pattern depending on inflammation and necrosis. CONCLUSIONS: Metastases of renal cell carcinomas and ductal carcinomas show different vascularization pattern at echo-enhanced power-Doppler sonography. Renal cell metastases and neuroendocrine tumors have similar contrast behaviors, therefore, clinical symptoms should be referred for their differentiation. However, histology is the standard of reference for the differential diagnosis of pancreatic tumors.

[Evaluation of doppler ultrasonography criteria for the differential diagnosis of pancreatic tumors]. / Evaluierung dopplersono-graphischer Kriterien zur Differentialdiagnostik von Pankreastumoren.

AIM: In order to improve the differential diagnosis of pancreatic lesions, dopplersonographic criteria for the tumours were evaluated. METHODS: 35 patients diagnosed by conventional ultrasound as having a tumour of pancreas were further investigated by B-mode sonography, fundamental and echo-enhanced power-Doppler sonography focusing on specific properties of the tumours. The results were correlated to the histological findings. RESULTS: Ductal carcinomas and cystadenocarcinomas are often hypovascularized in comparison to the surrounding tissue. In contrast to this, neuroendocrine tumours and cystadenomas are mostly hypervascularized. Tumours associated with pancreatitis show different vascularization patterns depending on inflammation and the extent of necrosis. CONCLUSIONS: Pancreatic tumours display different vascularization patterns in the echo-enhanced power-Doppler sonography. These characteristics can be useful for the differential diagnosis of pancreatic tumours.

Tacrolimus toxicity due to drug interaction with mibefradil in a patient after liver transplantation.

A 54-year-old male liver transplant patient received mibefradil, a novel T-type calcium channel blocker, as antihypertensive treatment while he was on tacrolimus. He subsequently developed dizziness and fatigue of gradual onset as well as shoulder muscle ache. In addition, reversible impairment of renal function occurred with an increase in creatinine and potassium levels. Monitoring of tacrolimus levels, which had been in the desired range (5-8 ng/ml) until recently, revealed an increase to toxic level of 54 ng/ml. After discontinuation of mibefradil, tacrolimus levels returned to the normal range and all symptoms and clinical changes were reversible. Mibefradil and tacrolimus both are metabolized through the cytochrome--P-450 pathway. We suspect that drug interaction due to competitive inhibition of tacrolimus metabolism by mibefradil was responsible for these toxic effects. Therefore, special caution is recommended when administering tacrolimus with other drugs that carry the potential for pharmakokinetic interaction.

Hepatoma with severe non-islet cell tumor hypoglycemia.

We report a 22-yr-old male patient with chronic hepatitis B and a large, well differentiated hepatoma who developed episodes of symptomatic fasting hypoglycemia, which were caused by paraneoplastic secretion of unprocessed "big" insulin-like growth factor-II. Initially, the patient presented with normal liver function, which deteriorated during the clinical course. Therapeutic attempts to reduce tumor mass failed and the patient subsequently died because of metastases of the hepatoma. The pathophysiology of non-islet cell tumor hypoglycemia, differential diagnosis, and therapeutic options are discussed.

Reconstitution of triiodothyronine inhibition in non-triiodothyronine-responsive thyrotropic tumor cells using transfected thyroid hormone receptor isoforms.

The triiodothyronine (T3) inhibitory effect on the thyrotropin (TSH)beta- and alpha-subunit genes is believed to be mediated by binding of T3 to specific nuclear receptors that are present in various isoforms. alphaTSH cells, which are derived from a pure alpha-subunit secreting thyrotropic tumor, contain the same nuclear factors that are important for alpha-subunit gene expression in TSH-expressing T3-responsive thyrotropic cells (TtT97). However, as in the parent tumor, alpha-subunit expression in alphaTSH cells was not inhibited by T3, despite the presence of high-affinity nuclear T3 receptors (TRs) with a similar number of sites per cell as in TtT97. When transcripts coding for the different TR isoforms from the MGH101A tumor were analyzed by Northern blot, TR alpha1 was present, as well as the non-T3-binding variant alpha2, but transcripts encoding the opposite strand Rev-ErbAa were not detectable and neither TR beta1 nor TR beta2 mRNAs were detectable, whereas all these transcripts were detectable in TtT97 tumors. Similar findings were observed in alphaTSH cells, where TR beta1 transcripts were barely detectable in Northern blots and TR beta2 transcripts were detectable only by RT-PCR. The TR beta gene locus is present and unrearranged in the tumor genome. In transient transfection studies conducted in alphaTSH cells overexpression of either TR beta1, TR beta2, or TR alpha1 reconstituted T3-inhibition of the alpha-subunit promoter down to 40% to 50% of control. We conclude that the relative lack of TR beta gene expression correlates with unresponsiveness to T3. The alphaTSH cell line represents a unique model in which to dissect the mechanism of T3 inhibition.