Phase II study on combined intravenous and intra-arterial chemotherapy with gemcitabine and mitomycin C in patients with advanced pancreatic cancer.

BACKGROUND/AIMS: This prospective phase II study on a combination of intraarterial (i.a.) and systemic chemotherapy was performed to test whether regional chemotherapy may overcome the chemoresistance of pancreatic cancer. METHODOLOGY: One treatment cycle consisted of an i.a. infusion through an angiographic catheter into the celiac artery of 8.5mg/m2 mitomycin C (MMC) and 500 mg/m2 gemcitabine on days 1 and 22, and intravenous infusions of 500 mg/m2 gemcitabine on days 8 and 15. Study-endpoints were overall survival and tumor response as measured by computed tomography (CT). Treatment was continued until disease progression or complete remission on CT. RESULTS: Thirty-seven treatment cycles were performed in 17 patients. The most frequent side effects were hematological with 18 episodes of grade III/IV toxicities. According to radiographic and tumor marker criteria, four (24%) and seven patients (41%), respectively, demonstrated an objective response. The median actual progression-free and overall survivals were 4.6 and 9.1 months, respectively. Patients without distant metastases had a longer median survival (15 months) than those with distant metastases (7.1 months, p = 0.037). CONCLUSIONS: This combination treatment was well tolerated and resulted in tumor response rates, median overall- and progression-free survival times superior to systemic gemcitabine chemotherapy, and comparable to the more toxic FOLFIRINOX regimen.

Role of transarterial chemoembolization for hepatocellular carcinoma before liver transplantation with special consideration of tumor necrosis.

Several authors suggest that local ablative therapies, specifically transarterial chemoembolization (TACE), may control tumor progression of hepatocellular carcinoma (HCC) in patients who are on the waiting list for liver transplantation (orthotopic liver transplantation, OLT). There is still no evidence if TACE followed by OLT is able to prevent recurrence of tumor, to prolong survival rate of the patients on the waiting list, or to improve the survival after OLT. We report 27 patients with HCC who underwent OLT. From these patients, 15 were pre-treated with TACE alone or in combination with percutaneous ethanol injection (PEI) or laser-induced thermo therapy (LITT). Mean time on the waiting list was 214 d for treated patients and 133 d for untreated patients. Comparing pre-operative imaging and histopathological staging post-transplant, we found 13 patients with tumor progression out of which five were treated with TACE. In two of the TACE patients a decrease of lesions could be achieved. In a single patient, there was no evidence of any residual tumor. Only one patient displayed tumor progression prior to OLT despite undergoing TACE. Comparison of outcome in patients undergoing TACE or having no TACE was not statistically significant (p = 0.5). In addition, our analysis showed that progression either in the total study population or in the TACE group alone is associated with a significant poorer outcome concerning overall survival (p = 0.02 and p = 0.02).

Postinterventional percutaneous closure of femoral artery access sites using the Clo-Sur PAD device: initial findings.

The purpose of this study was to evaluate a percutaneous hemostatic device in patients to achieve immediate hemostasis at the vascular access site as well as early ambulation after vascular interventional procedures. In a randomized trial, a hemostatic device (Clo-Sur PAD, Medtronic AVE, Inc., Santa Rosa, CA, USA; n=60) was compared with manual compression (n=60) in patients after endoluminal intervention through an inguinal access (sheath sizes: 5-7 French). Device safety was evaluated by assessing complications within 24 h and 14 days. System efficacy was measured by the percentage of achieved immediate hemostasis and early ambulation. Device application was possible in 57 cases (95.0%), with 93.3% (56/60) of the patients rising 2 h after application. Hemostasis time was 10.15+/-1.96 min (control group: 16.20+/-1.79 min), with a pressure bandage time of 3.47+/-5.53 h (control group: 13.8+/-4.32 h). Ambulation was possible after 2.13+/-0.50 h (control group: 8.57+/-3.47 h). Complications encountered were access-site bleeding with hematoma (device: n=3; control: n=9). All complications were managed conventionally without blood transfusion or surgical intervention. The system is an easy to use device permitting early ambulation without additional pressure bandaging in the majority of patients. Preliminary data show that hemostasis does not depend on the level of anticoagulation.

Hepatic intraarterial chemotherapy with gemcitabine in patients with unresectable cholangiocarcinomas and liver metastases of pancreatic cancer: a clinical study on maximum tolerable dose and treatment efficacy.

PURPOSE: To define the maximum tolerated dose (MTD) of hepatic intraarterial chemotherapy with gemcitabine, administered with and without starch microspheres, in patients with inoperable intrahepatic cholangiocarcinomas and liver metastases of pancreatic carcinomas. METHODS: Gemcitabine was administered on days 1 and 8 with intervals of 2 weeks between the cycles. In group A the initial gemcitabine dose of 1,000 mg/m(2) (without microspheres) was increased in 200-mg/m(2) steps up to a maximum dose of 2,000 mg/m(2). In group B the MTD with microspheres was assessed by giving an additional microsphere dose according to tumor extent and body weight, increasing gemcitabine starting from a dose-step below the MTD with microspheres. The MTD was evaluated via clinical and laboratory findings. RESULTS: Twenty-four patients were enrolled (12 males, 12 females, mean age 59.17 years; intrahepatic cholangiocarcinoma: n = 17, liver metastases of pancreatic carcinoma: n = 7). The MTD of gemcitabine without microspheres was reached at 1,400 mg/m(2), and of gemcitabine with microspheres at 1,800 mg/m(2). The comparative evaluation revealed statistically significant better data for the time to progression (p < 0.01) and survival for the group with microspheres (6.8 and 20.2 months) in comparison to the group without microspheres (4.2 and 13.5 months). CONCLUSION: This clinical study indicates that the intraarterial application of gemcitabine with doses higher than the recommended 1,000 mg/m(2) is well tolerated if combined with microspheres, and yields respectable results in patients who do not respond to systemic chemotherapy.

Staging of Klatskin tumours (hilar cholangiocarcinomas): comparison of MR cholangiography, MR imaging, and endoscopic retrograde cholangiography.

The aim of the study was to compare prospectively magnetic resonance cholangiography (MRC) and magnetic resonance imaging (MRI) with endoscopic retrograde cholangiography (ERC) in the diagnosis and staging of Klatskin tumours of the biliary tree (hilar cholangiocarcinomas). Forty-six patients with suspected Klatskin tumours of the biliary tract underwent MRI and heavily T2-weighted, non-breathhold, respiratory-triggered fast spin-echo MRC. Forty-two patients underwent ERC within 24 h; in four patients, ERC was not feasible, and percutaneous trans-hepatic cholangiography (PTC) was carried out instead. Two independent investigators evaluated imaging results for the presence of tumour, bile duct dilatation, and stenosis. Clinical and histopathological correlation revealed Klatskin tumours in 33 patients. MRI revealed a slightly hyperintense signal of infiltrated bile ducts in T2-weighted fast spin-echo sequences. The malignant lesion was regularly visualized as a hypointense area in T1-weighted gradient-echo sequences with substantial contrast enhancement along the involved bile duct walls. MRC revealed the location and extension of the tumour in 31 of 33 cases correctly (sensitivity 94%, specificity 100%, diagnostic accuracy 95%). In 27 of 31 cases, ERC enabled accurate staging and diagnosis of Klatskin tumours with a sensitivity of 87%. ERC and PTC combined yielded a sensitivity of 84% and a specificity of 97%. Tumours were grouped according to the Bismuth classification, with MRC allowing correct identification of type I tumour in seven patients, type II tumour in four patients, type III tumour in 12 patients, and type IV tumour in ten patients. MRC provided superior visualization of completely obstructed peripheral systems. MRC in combination with MRI is a reliable non-invasive diagnostic method for the pre-therapeutic staging of Klatskin tumours.

Progress in CT imaging for the cardiac surgeon.

The aim of this article is to critically assess the role of multidetector-row CT (MDCT) in the field of cardiothoracic surgery. In the beginning, a short overview is given about technical aspects such as scan protocols, optimal image reconstruction, image reformation techniques, data evaluation, and data presentation. This is followed by sections about possible indications for cardiothoracic surgery and future prospects for this technology. For the cardiac surgeon, the main benefit of MDCT lies in the combination of large scan-volume coverage, high spatial resolution, proper identification of calcifications, and the simultaneous registration of other thoracic structures. Preoperative applications may include the assessment of cardiac valves, noninvasive evaluation of large thoracic vessels, staging of cardiac tumors, and planning of minimally invasive surgical procedures. After surgery, MDCT examinations particularly facilitate an early identification of severe postoperative complications. MDCT may also be used to assess coronary artery bypass graft patency and to identify transplant-related complications in heart transplant recipients at an early stage. New technological developments such as 64-row MDCT or flat panel computed tomography will further increase the field of possible indications.

Extracorporeal shock wave therapy in calcific tendinitis of the shoulder.

OBJECTIVE: To investigate clinical (pain, mobility) and radiological (resolution of calcium deposits) efficacy of different energy levels of extracorporeal shock wave therapy (ESWT) in calcific tendinitis of the shoulder. DESIGN AND PATIENTS: There were 90 study subjects with radiographically verified calcific tendinitis of one shoulder, mean age 52+/-6 years (range 29-65 years; females:males=55:35), all of whom had had symptoms for at least 6 months and substantial restriction of shoulder mobility and pain that required taking anti-inflammatory drugs. Calcium deposits were of type I or type II (clearly circumscribed and dense) and ranged from 1 cm to 3 cm in diameter. Subjects were divided into three groups to receive ESWT at one of two energy levels (E1=0.15 mJ/mm2, E2=0.44 mJ/mm2) or sham treatment. Treatment was given at 6 weekly intervals until symptoms resolved, five treatments had been given or the subject dropped out of the programme. RESULTS: All subjects in groups E1 and E2 completed the programme. Those in group E1 had significantly less pain during treatment but more treatments than those in group E2, and at 6 month follow-up had residual calcification and recurrence of pain (87%). Subjects in group E2 had no residual calcification or recurrence of pain. Sham treatment had no effect. There were no side effects except a small number of haematomas (2 in E1, 6 in E2; maximum size 2 cm). CONCLUSION: ESWT in calcific tendinitis of the shoulder is very effective. It does not have significant side effects at an energy level of E=0.44 mJ/mm2, which can therefore be recommended.

Visualization of the articular disk of the temporomandibular joint in near-real-time MRI: feasibility study.

While static MRI of the TMJ is the method of choice to evaluate the articular disk (AD), dynamic MRI so far has failed to display the AD. The capability of a modified True-FISP sequence to visualize the AD in dynamic near-real-time imaging (NRTI) was evaluated. Twelve healthy subjects and 17 patients were investigated. Besides static routine imaging, sagittal NRTI of both TMJs was performed with a True-FISP sequence at 1.5 T with TE/TR=1.84/3.68 ms. Two temporal resolutions (250/500 ms) were tested. The quality of the visualization of the AD was rated on a four-point scale (1= very good to 4= poor visualization) by two observers in consensus. ADs of the volunteers were visualized with high quality in all stages of movement (score: 1.69). In patients with internal derangement, disk-motion was clearly depicted, including fast reposition movements. Due to degenerative changes of the AD, the quality of the depiction in patients was slightly lower (score: 2.4). According to the preliminary results of this feasibility study, the suggested NRTI True-FISP sequence is capable of visualizing the entire motion of the AD of the TMJ in normal and pathologic stages with high quality. Further studies are needed to prove the clinical usefulness of this new technique.

Interactive computer-training as a therapeutic tool in Alzheimer's disease.

The current study sought to evaluate a novel kind of interactive computer-based cognitive training (ICT) in Alzheimer's disease (AD). AD patients (N = 9), age- and gender-matched patients with a major depressive episode (N = 9), and healthy control subjects (N = 10) were trained to use an ICT program that relates to activities of daily living (ADL). Digital photographs of a shopping route were implemented in a close-to-reality simulation on a computer touch-screen. The task was to find a predefined shopping route, to buy three items, and to answer correctly 10 multiple-choice questions addressing knowledge related to the virtual tasks. Training performance was rated using the number of mistakes (wrong way), time needed for the tasks, number of correct multiple-choice answers, and of repeat of instruction. Compared to normal controls and depressed patients, AD patients performed significantly worse with regard to all variables. Within a 4-week training period including 12 sessions, however, substantial training gains were observed, including a significant reduction of mistakes. Training effects were sustained until follow-up 3 weeks later. The performance of the depressed patients and the normal controls improved as well, with no difference between the two groups. Self-reported effects revealed that the training was well perceived. Thus, the task performance of AD patients improved substantially and subjects appeared to have liked this approach to ICT. New interactive media, therefore, may yield interesting opportunities for rehabilitation and (psycho)therapeutic interventions.

Preoperative evaluation of malignant liver tumors: comparison of unenhanced and SPIO (Resovist)-enhanced MR imaging with biphasic CTAP and intraoperative US.

The purpose of this study was to evaluate the diagnostic efficacy of iron-oxide-enhanced MRI vs CT during arterial portography (CTAP) and intraoperative ultrasound (IOUS) in detection of liver neoplasms. Seventeen patients with malignant focal liver lesions (liver metastases, n=7), hepatocellular carcinomas (HCC, n=9), and cholangiocellular carcinoma (CCC, n=1) underwent presurgical Resovist-enhanced MRI and CTAP. Two independent observers (A and B) assessed the blinded images of unenhanced and iron-oxide-enhanced MRI vs CTAP for the presence, number, and location of the liver lesions. These results were compared lesion by lesion and segment by segment with the results of intraoperative ultrasound ( n=17) serving as the reference standard. Eighty lesions were detected by intraoperative ultrasound in 17 patients. In comparison with IOUS (lesion-by-lesion analysis) the sensitivity was 86.8% for CTAP, 65% for combined unenhanced MR imaging, and 86.8% for combined Resovist-enhanced MRI as well as 86.8% for the combination of unenhanced and Resovist-enhanced MRI. Compared with the sensitivity of combined unenhanced MRI the sensitivity of CTAP as well as the sensitivity of combined Resovist-enhanced MRI was significantly higher (p<0.05). False-positive results were much higher in CTAP as compared with combined unenhanced and SPIO-enhanced MRI. Using the segment-by-segment analysis the specificity of combined unenhanced MRI with 100% (96.7-100%) as well as combined Resovist-enhanced MRI with 100% (96.7-100%) was significantly higher (p<0.05) in comparison with the specificity of CTAP with 91.1% (83.2-96.1%). The accuracy of combined unenhanced MRI was 100% (93.2-100%), combined Resovist-enhanced MRI 100% (93.6-100%) and of CTAP 85.2% (72.9-93.4%). In the detection of focal liver lesions iron-oxide-enhanced MR imaging is superior to unenhanced MRI and similar to CTAP.

Clinical impact of MRI in acute wrist fractures.

The purpose of this study was to evaluate the clinical impact of MRI in the early diagnosis of wrist trauma. High-resolution MR imaging was performed on a 1.5-T unit (Symphony Quantum, Siemens, Erlangen, Germany) using coronal and axial T1- and T2-weighted fat-saturated turbo-spin-echo sequence via a dedicated wrist coil within a mean of 6.6 days after initial radiographs in 54 patients (56 wrists) with clinical suspicion of wrist fractures and normal plain or indistinct radiographs. Initial radiographs were evaluated independently by two senior radiologists and the hand surgeon without knowledge of the MRI findings. The initial treatment protocol was based on evaluation of plain films and clinical findings by the hand surgeon. Treatment protocol was changed after MRI examination if necessary. In 31 of 56 wrists MRI findings resulted in a change of diagnosis. There were false-positive diagnoses on plain radiographs in nearly one half ( n=25) of the patients. False-negative diagnoses on plain radiographs resulted in 6 cases. Magnetic resonance imaging detected additional injuries of soft tissue in more than one third ( n=20). In 22 of 56 wrists the period of immobilization could be shortened or ended, in 12 of 56 it was prolonged, and in 3 of 56 a surgical intervention was necessary. In 19 wrists MRI had no therapeutic consequences. Our data demonstrate the high clinical impact of MRI in the detection of acute wrist fractures. We recommend MRI of the wrist immediately on the day of trauma if there is clinical suspicion and normal plain radiographs. Accurate diagnosis by MRI examination within the first days following trauma may reduce economic costs due to shortened immobilization time in cases with a suspected fracture but plain radiographs.