Christoph Düber

Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma in consideration of concomitant stage of liver cirrhosis.

Goals and Background The multikinase inhibitor sorafenib provides survival benefit for patients with advanced hepatocellular carcinoma (HCC) and liver cirrhosis (LCI) Child-Pugh A. We report our experiences with sorafenib in advanced HCC, particularly in patients with LCI Child-Pugh B/C, where only limited data are available in regard to safety and efficacy of sorafenib. Methods Thirty-four patients with advanced HCC were treated with sorafenib regardless of liver function and prior anticancer therapy. Adverse events (AEs) were graded using Common Toxicity Criteria version 3.0, tumor response was assessed according to Response Evaluation Criteria in Solid Tumors. Results Fifteen patients presented without LCI or with LCI Child-Pugh A, 15/4 patients had LCI Child-Pugh B/C. Barcelona Clinic Liver Cancer stage was B/C/D in 4/22/8 patients. During treatment period (median 2.2 mo), therapy was discontinued in 61.8% of patients due to tumor progression (32.3%), death (17.6%), AEs (8.8%), or noncompliance (2.9%). Most common grade 3/4 AEs included liver dysfunction (23.5%), diarrhea (14.7%), increased lipase (8.8%), fatigue (8.8%), and hand-foot skin reaction (5.9%). Worsening liver dysfunction/failure was more frequent (P=0.036) in patients with LCI Child-Pugh B/C compared with patients with maintained liver function (no LCI/LCI Child-Pugh A). Median overall survival was 7.2 months for patients with maintained liver function versus 3.3/3.4 months for patients with LCI Child-Pugh B/C. Conclusions These data do not support the use of sorafenib in patients with LCI Child-Pugh C, and patients with LCI Child-Pugh B should be treated with caution until larger trials provide more safety data and a clinically relevant survival benefit under sorafenib therapy.

Multi-slice spiral CT in routine diagnosis of suspected acute left-sided colonic diverticulitis: a prospective study of 120 patients

This prospective study evaluated the use of multi-slice CT (MSCT) for detection of clinically suspected left-sided colonic diverticulitis with regard to diagnosis, complications and alternative diagnoses. One hundred twenty patients with clinically suspected acute left-colonic diverticulitis underwent MSCT of the lower abdomen with IV contrast after rectal application of iodic contrast. The MSCT results were compared with histopathological and intraoperative findings or other radiological or endoscopic methods and clinical outcome. Acute diverticulitis was proven in 67 of the 120 (55.8%) patients, which was detected by MSCT with an accuracy of 98% (sensitivity 97%, specificity 98%). Contained perforation or abscess formation were detected with an accuracy of 96% (sensitivity 100%, specificity 91%) and 98% (sensitivity 100%, specificity 97%), respectively. In 31 of 120 (25.8%) patients diagnoses other than diverticulitis caused abdominal pain, which was correctly diagnosed by MSCT in 71%. The MSCT as well as other concurrently performed diagnostic methods showed normal findings and no causes for the patients symptoms in 22 of the 120 (18.4%) patients. Multi-slice CT is reliable in detecting diverticulitis, including extracolic complications, and often reveals other diagnoses; therefore, MSCT is recommended as standard diagnostic procedure in suspected acute diverticulitis.

Radiofrequency ablation as first-line treatment in patients with early colorectal liver metastases amenable to surgery.

Objective:Aiming at avoidance of futile surgery, we have tested whether radiofrequency ablation (RFA) may be used as first-line treatment in patients with colorectal metastases (CRLM) occurring within the first year after colorectal surgery. Summary Background Data:Surgical resection is the standard treatment in patients with CRLM. Major retrospective analyses have identified the interval between colorectal surgery and the occurrence of CRLM to be of prognostic importance. So far, it is unknown whether survival of the respective patients is hampered if RFA is used as first-line treatment. Methods:According to a clinical pathway, we have treated patients with CRLM detected within the first year after colorectal surgery preferentially by RFA (n = 28). Resection (n = 82) was performed in patients who were deemed not amenable to RFA due to number, size, or location of metastatic lesions. The diameter of lesions differed between the groups. All other characteristics of patients and lesions were comparable. Local recurrence and new hepatic lesions were treated with repeated RFA or surgery whenever possible. Results:Local recurrence at the site of ablation or resection occurred in 32% and 4% (P < 0.001), new metastases apart from the site of previous treatment in 50% and 34% (P = 0.179), and systemic recurrence in 32% and 37% (P = 0.820) of the patients after RFA and surgery, respectively. Time to progression was significantly shorter in patients primarily treated with RFA (203 vs. 416 days; P = 0.017). After primary treatment, 9 RFA patients and 8 surgery patients were amenable to repeated RFA or repeated surgery resulting in identical rates of disease-free patients and identical 3-year overall survival in both treatment groups: 67% and 60%, respectively; P = 0.93. Conclusions:Despite striking differences in local tumor recurrence and shorter time to progression, survival in patients with early CRLM does not depend on the mode of primary hepatic treatment.

Chronic thromboembolic pulmonary hypertension — assessment by magnetic resonance imaging

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe disease that has been ignored for a long time. However, with the development of improved therapeutic modalities, cardiologists and thoracic surgeons have shown increasing interest in the diagnostic work-up of this entity. The diagnosis and management of chronic thromboembolic pulmonary hypertension require a multidisciplinary approach involving the specialties of pulmonary medicine, cardiology, radiology, anesthesiology and thoracic surgery. With this approach, pulmonary endarterectomy (PEA) can be performed with an acceptable mortality rate. This review article describes the developments in magnetic resonance (MR) imaging techniques for the diagnosis of chronic thromboembolic pulmonary hypertension. Techniques include contrast-enhanced MR angiography (ce-MRA), MR perfusion imaging, phase-contrast imaging of the great vessels, cine imaging of the heart and combined perfusion-ventilation MR imaging with hyperpolarized noble gases. It is anticipated that MR imaging will play a central role in the initial diagnosis and follow-up of patients with CTEPH.

Morphology of the coronary arteries after combined thrombolysis and percutaneous transluminal coronary angioplasty for acute myocardial infarction.

Autopsy findings are reported for 6 patients who died early (8, 9, 12, 13 and 14 days) or late (52 days) after combined thrombolysis and percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction. Morphologic changes in the coronary arteries at the site of revascularization included injury to the inner portion of the arterial wall (intimal splitting, subintimal dissection, medial tears and submedial dissection) and necrosis of medial smooth muscle cells. Residual mural thrombi and thrombotic reocclusion were noted within the arterial lumen. There was a beginning neointima formation in all patients who died early and a reobstructing neointima proliferation in the patient who died late after PTCA. The results of this study support the suggestion that both rupture and dissection of the inner arterial wall and necrosis of the tunica media resulting from irreversible dilatation of the grossly intact outer layers are the most important mechanisms of PTCA. Response to arterial wall injury after PTCA is a neointima formation leading to covering of mural thrombi and thrombogenic intimal, medial and adventitial substances and smoothing of the luminal surface. Large residual mural thrombi and excessive neointimal proliferation may cause restenosis within a few weeks.

Percutaneous transluminal angioplasty for occlusion of the subclavian artery: Short-and long-term results

Percutaneous transluminal angioplasty was performed in 8 symptomatic patients with proximal occlusion of the left subclavian artery. Technical and short-term clinical success was achieved in 7 cases. Nonoccluding embolization to the distal subclavian artery and stenosis of the brachial artery after a combined femoral/brachial approach occurred as complications in 2 patients. Three patients are asymptomatic with a patent subclavian artery 25, 28, and 37 months after angioplasty. Reobstructions in 4 patients occurring after 8, 12, and 16 months were retreated by angioplasty (3 patients) and stent implantation (1 patient with a second restenosis) with good technical and clinical success. Long-term patency was less than 50%, but successful retreatment is feasible. Therefore, we consider percutaneous transluminal angioplasty a reasonable therapeutic option in patients who are not surgical candidates.

Anatomic Changes After Hyoid Suspension for Obstructive Sleep Apnea: An MRI Study

OBJECTIVE: To assess the effects of isolated hyoid suspension on subjective and objective parameters of obstructive sleep apnea and to evaluate changes in upper airway anatomy with the help of standardized magnetic resonance imaging. STUDY DESIGN AND SETTING: Fifteen patients received isolated hyoid suspension. Changes in respiratory disturbance index were assessed with polysomnography, and anatomical changes with standardized magnetic resonance imaging. Snoring, daytime sleepiness, and functional parameters were assessed with questionnaires. Lateral x-ray cephalometry was performed preoperatively. RESULTS: Mean respiratory disturbance index was reduced from 35.2 ± 19.1 to 27.4 ± 26.2. Forty percent of the patients were classified as responders. Daytime sleepiness improved significantly. Relevant changes in upper airway anatomy could not be detected. There were no remarkable differences between responders and nonresponders in regard to imaging. CONCLUSIONS: Hyoid suspension is effective only in a subgroup of patients and does not lead to relevant changes in airway diameters in the awake patient. Magnetic resonance imaging and x-ray cephalometry do not add additional information for patient selection. SIGNIFICANCE: The reported clinical effects of hyoid suspension are more likely due to functional changes in airway collapsibility than to an enlargement of the upper airway.

Volumetric tissue reduction in radiofrequency surgery of the tongue base.

OBJECTIVES: Radiofrequency surgery is a minimally invasive technique for the treatment of the tongue base in sleep-disordered breathing. The aim of this study was to evaluate the changes in upper airway anatomy induced by radiofrequency surgery with MRI. STUDY DESIGN AND SETTING: 10 patients with sleep-disordered breathing were treated with radiofrequency surgery at tongue base. MRI measurements were performed before and after surgery with the help of a recently published protocol. RESULTS: The mean total number of energy delivered per patient was 4750 ± 1641 Joule. Relevant changes could be observed neither for tongue volume or dimension nor for retrolingual space. CONCLUSIONS: Changes in upper airway anatomy could not be demonstrated. The effects of radiofrequency surgery of the tongue base may more likely be a result of changes in upper airway collapsibility. SIGNIFICANCE: Functional effects of surgical interventions in sleep-disordered breathing should be considered in addition to mechanistic concepts alone.

Lesion Formation in Radiofrequency Surgery of the Tongue Base

Objectives Temperature controlled radiofrequency volumetric tissue reduction (RFVTR) of the tongue base is a minimally invasive technique for the treatment of obstructive sleep apnea. But despite its widespread use, little is yet known about in vivo effects in humans. Such knowledge would be essential for evidence‐based criteria in the selection of energy application.

Trends in epidemiology, treatment, and survival of hepatocellular carcinoma patients between 1998 and 2009: an analysis of 1066 cases of a German HCC Registry.

Goals: The aim of this study was to analyze clinical presentation, course of disease, and management of patients with hepatocellular carcinoma (HCC) in a German referral center between 1998 and 2009. Background: HCC is a rare tumor in Germany, but its incidence has increased over the last 30 years. New therapies such as chemoembolization with drug-eluting beads, selective internal radiotherapy, and sorafenib were introduced recently; however, the impact on clinical management and overall survival (OS) is unclear. Study: In this retrospective analysis, 1066 patients with HCC, separated into two 6-year periods (n=385; 1998 to 2003 and n=681; 2004 to 2009) were evaluated. Results: The number of patients presenting each year (64 vs. 114 per year), with an age over 80 years or with nonalcoholic steatohepatitis increased significantly between periods. The main risk factors were alcoholic liver disease in 51.7%, chronic hepatitis C virus in 28.2%, and chronic hepatitis B virus in 13.4% of patients with liver cirrhosis and HCC. Patients presented with more advanced tumor stages and with worse liver function in period 2. The majority (61.6%) of patients received local treatment over a spectrum of Barcelona Clinic Liver-Cancer (BCLC) stages, whereas systemic therapy was offered to a minority (8.8%) and limited to BCLC stage C patients only. OS decreased in BCLC stage A and D and improved in BCLC stage B and C and decreased for all patients from 16.5 to 15.3 months between periods. Conclusions: No improvement of OS was observed when comparing time periods, partly because of the more advanced stage of HCC and because of the increasing age in the second time period. Improved and new therapeutic options and the intensification of surveillance programs are likely to increase survival of HCC patients in the future.