Klaus J. Klose

Combination therapy with octreotide and α-interferon : Effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors

OBJECTIVE We investigated the antiproliferative efficacy of the addition of alpha-interferon to the somatostatin analogue octreotide in patients with metastasized gastroenteropancreatic tumors unresponsive to octreotide monotherapy. METHODS In an open prospective trial, 21 patients with metastasized neuroendocrine gastroenteropancreatic tumors (nine patients with carcinoid syndrome, eight with nonfunctioning tumors, four with gastrinoma) were treated with 5 x 10(6) IU alpha-interferon tiw in addition to 200 microg of octreotide tid. All patients, including 16 patients with preceding monotherapy with 200 microg of octreotide tid, had tumor progression documented by computed tomography before entering the study. Growth response (computed tomography documented) and biochemical response were assessed at 3-month intervals. RESULTS Inhibition of tumor growth was observed in 14 patients (67%), 11 of whom had preceding octreotide monotherapy; complete regression was observed in one patient lasting for 49 months and stable disease (stand-still) in 13 patients lasting for 3 to 52 months (median, 12 months). Seven patients failing this combination therapy exhibited a significantly shorter overall survival (median, 23 months; range, 5 to 42 months) than the 14 patients responding to this regimen (median, 68 months; range, 12 to 112 months; p = 0.007). Two patients are still alive. Biochemical response was achieved in 69% of patients with functioning tumors: in three of four patients with gastrinoma and in six of nine patients with carcinoid syndrome. CONCLUSIONS These data suggest that the addition of alpha-interferon to octreotide has antiproliferative efficacy in a subgroup of patients with advanced metastatic disease unresponsive to octreotide monotherapy. Prolonged survival was seen in the responder group.

Deregulation of tumor angiogenesis and blockade of tumor growth in PPARβ-deficient mice

The peroxisome proliferator‐activated receptor‐β (PPARβ) has been implicated in tumorigenesis, but its precise role remains unclear. Here, we show that the growth of syngeneic Pparb wild‐type tumors is impaired in Pparb−/− mice, concomitant with a diminished blood flow and an abundance of hyperplastic microvascular structures. Matrigel plugs containing pro‐angiogenic growth factors harbor increased numbers of morphologically immature, proliferating endothelial cells in Pparb−/− mice, and retroviral transduction of Pparb triggers microvessel maturation. We have identified the Cdkn1c gene encoding the cell cycle inhibitor p57Kip2 as a PPARβ target gene and a mediator of the PPARβ‐mediated inhibition of cell proliferation, which provides a possible mechanistic explanation for the observed tumor endothelial hyperplasia and deregulation of tumor angiogenesis in Pparb−/− mice. Our data point to an unexpected essential role for PPARβ in constraining tumor endothelial cell proliferation to allow for the formation of functional tumor microvessels.

Prospective Evaluation of the Value of Magnetic Resonance Imaging in Suspected Acute Sigmoid Diverticulitis

PurposeThe purpose of this study was to prospectively investigate patients with suspected acute colonic diverticulitis and to provide sensitivity, specificity, and interobserver agreement in a blinded trial.MethodsFifty-five patients (29 men; 59 ± 13 (range, 29–76) years) who reported to the emergency room with clinically suspected acute colonic diverticulitis were prospectively included in the study. All patients underwent magnetic resonance imaging scans of their abdomen before and after contrast agent administration. Two assessors blinded to all clinical, laboratory, and radiologic results evaluated the images separately.ResultsThe assessors reported colonic wall thickening, segmental narrowing of the colon, presence of diverticula, pericolic fatty infiltration, ascites, and abscesses. The assessors had to diagnose or rule out acute colonic diverticulitis. Sensitivities, specificities, positive, and negative likelihood ratios were derived. To determine interobserver agreement, a Cohen’s kappa coefficient was calculated. The two assessors exhibited sensitivities of more than 94 percent, specificities of 88 percent, positive likelihood ratios of more than 7.5, and negative likelihood ratios of less than 0.07. The kappa coefficient showed a significant, strong correlation between both assessors (κ = 0.68).ConclusionsMagnetic resonance imaging is investigator independent and provides high sensitivity and specificity for the diagnosis of acute colonic diverticulitis.

Guidance of percutaneous pulmonary biopsies with real-time CT fluoroscopy

OBJECTIVE Clinical evaluation of computed tomography (CT) fluoroscopy and comparison with conventional CT guidance for monitoring of percutaneous pulmonary biopsy procedures. METHODS Twenty CT-guided pulmonary biopsy procedures were conducted. The interventions have prospectively been performed either with CT fluoroscopy or with conventional CT guidance. About 120 kV and 50 mA with a frame-rate of eight images per second were used for CT fluoroscopy. Number of pleural needle passages, procedure times, radiation doses and histologic results were analyzed separately for both methods. RESULTS Compared with conventional CT guidance, CT fluoroscopy was associated with less pleural needle passages (1.8+/-0.6 vs. 1.1+/-0.3; P=0.003, t-test) and procedure times were shorter than for conventional CT guidance (12.7+/-2.2 min vs. 26.7+/-16.4 min; P=0.02). Analysis of estimated patient related radiation exposure and histologic outcome showed no significant difference between conventional and fluoroscopic CT-guided procedures (P>0.05). CONCLUSION CT fluoroscopy facilitates guidance of percutaneous pulmonary biopsy procedures. Compared with conventional CT assistance, procedure times are decreased and less pleural needle passages are required. While patient-related radiation exposure is similar, operator-related radiation exposure remains a disadvantage associated with CT fluoroscopy.

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.

18F-FDG PET, somatostatin receptor scintigraphy, and CT in metastatic medullary thyroid carcinoma: a clinical study and an analysis of the literature.

AimTo determine the clinical potential of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) in patients with medullary thyroid carcinoma (MTC), we compared it to computed tomography (CT), and somatostatin receptor scintigraphy (SRS). Patients and methodsBlinded evaluation of PET, CT and SRS images obtained from 26 patients with histologically proven metastatic MTC was done by nuclear medicine and radiology specialists. Sites of tumour involvement were classified as ‘sure’ or ‘suspicious’. The data were analysed in comparison to two different standards. Either those sites classified as ‘sure’ by at least one of the methods were defined as the standard or those sites of involvement which were classified as ‘sure’ by at least two methods. ResultsDependent on the type of data analysis performed, PET was able to demonstrate 56.8%/80.6% of the tumour sites, CT showed 64.5%/79.6%, and SRS showed 47.5%/69.9% of the tumour sites. ConclusionOverall, CT is similar or better than PET in our patients (dependent on the standard) while SRS is inferior to both other techniques. Our data are in agreement with publications that consider CT superior to PET in the diagnosis of metastatic MTC while other studies show superiority of PET. However, a combination of CT and PET seems to be the most appropriate non-invasive diagnostic approach in patients with MTC.

Occurrence of late gadolinium enhancement is associated with increased left ventricular wall stress and mass in patients with non-ischaemic dilated cardiomyopathy.

Occurrence of late gadolinium enhancement (LGE) as assessed by cardiac magnetic resonance (CMR) imaging has been attributed to various myocardial injuries. We hypothesized that LGE is associated with left ventricular (LV) wall stress.

Intravenous Iodinated Contrast Agents Amplify DNA Radiation Damage at CT

PURPOSE To determine the effect of the use of iodinated contrast agents on the formation of DNA double-strand breaks during chest computed tomography (CT). MATERIALS AND METHODS This study was approved by the institutional review board, and written informed consent was obtained from all patients. This single-center study was performed at a university hospital. A total of 179 patients underwent contrast material-enhanced CT, and 66 patients underwent unenhanced CT. Blood samples were taken from these patients prior to and immediately after CT. In these blood samples, the average number of phosphorylated histone H2AX (γH2AX) foci per lymphocyte was determined with fluorescence microscopy. Significant differences between the number of foci that developed in both the presence and the absence of the contrast agent were tested by using an independent sample t test. RESULTS γH2AX foci levels were increased in both groups after CT. Patients who underwent contrast-enhanced CT had an increased amount of DNA radiation damage (mean increase ± standard error of the mean, 0.056 foci per cell ± 0.009). This increase was 107% ± 19 higher than that in patients who underwent unenhanced CT (mean increase, 0.027 foci per cell ± 0.014). CONCLUSION The application of iodinated contrast agents during diagnostic x-ray procedures, such as chest CT, leads to a clear increase in the level of radiation-induced DNA damage as assessed with γH2AX foci formation.

Increased enddiastolic wall stress precedes left ventricular hypertrophy in dilative heart failure—Use of the volume-based wall stress index

INTRODUCTION To examine a potential interrelation of left ventricular (LV) wall stress and hypertrophy, we assessed increased wall stress in patients with suspected non-ischemic dilative cardiomyopathy and addressed the question whether increased LV wall stress is involved in the development of LV hypertrophy. METHODS We studied 502 consecutive patients in whom LV mass, LV enddiastolic (LVEDV) and endsystolic volume (LVESV) was determined using cardiac magnetic resonance (CMR). Based on a thick-walled sphere, we introduced a myocardial and cavity volume-based wall stress index. Follow up CMR examinations were obtained in a representative subgroup of 71 patients. RESULTS LV mass was correlated with LVEDV (r=0.517, P<0.001) and LVESV (r=0.510, P<0.001). Despite LV hypertrophy, LV mass was not sufficient to compensate for LV dilatation resulting in an increased wall stress. Increased LV enddiastolic wall stress was found in 227 patients (45 %) and increased endsystolic wall stress in 198 (39 %). In patients with normal LV enddiastolic wall stress ≤ 4 kPa at time of enrolment, no changes of LV mass occurred during follow up (142 ± 46 g vs. 141 ± 47 g). In contrast, patients with initially increased LV enddiastolic wall stress >4 kPa developed greater LV hypertrophy (141 ± 48 g vs. 158 ± 60 g, P=0.0247). CONCLUSIONS LV wall stress can be derived from CMR measurements of LV myocardium and cavity using the volume-based wall stress index. Increased LV enddiastolic wall stress leads to LV hypertrophy. Beyond a certain degree of LV dilatation, the extent of hypertrophy does not compensate LV dilatation. The ensuing increased wall stress promotes dilatation and consecutively hypertrophy with an unfavorable prognosis. It is proposed to use the volume-based wall stress index as new diagnostic criterion in heart failure.

Magnetic Resonance Colonography and Virtual Magnetic Resonance Colonoscopy with the 1.0-t System: A Feasibility Study

Saar B, Heverhagen JT, Obst T, et al. Magnetic resonance colonography and virtual magnetic resonance colonoscopy with the 1.0-T system: A feasibility study. Invest Radiol 2000;35:521–526. RATIONALE AND OBJECTIVES.An ex vivo study and a clinical, prospective, patient study were undertaken to evaluate the feasibility of magnetic resonance (MR) colonography with a 1.0-T system. METHODS.An ex vivo colon model was scanned. A cleaned pig colon was prepared with six simulated sessile polyps (diameters of 4–12 mm) and one simulated pedunculated polyp (diameter of 5 mm). Subsequently, five patients (aged 39–81 years; four women, one man) were examined with MR colonography, immediately followed by endoscopic colonoscopy. After preparation for colonoscopy, the colon was filled with a Gd-DTPA/water solution (1:100). A breath-hold 3D gradient-echo sequence was acquired in both the prone and supine positions and after intravenous Gd-DTPA administration. Images were analyzed interactively by using multiplanar projections, maximum-intensity projection, and a virtual endoscopic view. The MR results were compared with the findings of the fiberoptic endoscopy. RESULTS.All seven simulated lesions of the colon model could be detected by MR imaging. In one patient, an advanced colon cancer as well as an additional small polyp was depicted. In the other four patients, single polyps with a diameter of 1 to 2.5 cm and a large adenoma were visualized by MR colonography. Contrast enhancement of the polyps was noted only after subtraction. CONCLUSIONS.The 1.0-T system is feasible for MR colonography. Reduced requirements for hardware could contribute to establish the novel technique as a screening method for colorectal polyps.