Biomedical subjects

S Pauwels

Publications and source records attributed to S Pauwels.

At least 19 recordsLinked to original sources

PubMed2003

Intragastric distribution of a standardized meal in health and functional dyspepsia: correlation with specific symptoms.

In functional dyspepsia, abnormal intragastric distribution of a test meal has been identified but has never been correlated to any symptom pattern. The aim of this study was to compare the intragastric distribution of a meal between functional dyspepsia patients and controls, and to correlate distribution with symptom patterns, using scintigraphic gastric emptying studies. In forty patients with functional dyspepsia and 29 healthy volunteers, scintigraphic planar images were obtained immediately after ingestion of a mixed radiolabelled test meal and every 20 min for 2 h. The images of the stomach were divided into proximal and distal compartments. The mean intragastric distribution was similar in patients and controls. Over the whole test, 18 (45%) and 20 (50%) patients had a distal redistribution of the solid and liquid phase of the meal, respectively, while proximal retention of these phases was found in 13 (33%) and 9 (23%) patients. Early satiety was associated with early distal redistribution of the liquid phase and fullness was associated with late proximal retention. This study shows similar intragastric distribution of a test meal in health and functional dyspepsia. Within the patient group, an association between abnormal intragastric distribution patterns and symptom profiles was found, which might be related to different pathophysiological mechanisms.

Adult↗

PubMed2001

An unusual metastatic motilin-secreting neuroendocrine tumour with a 20-year survival. Pathological, biochemical and motility features.

Motilin-secreting neuroendocrine tumours have been rarely described. Immunohistochemical, biochemical and motility investigations were performed in a 62-year-old man with liver and bone metastases of a motilin-secreting neuroendocrine tumour originating from a rectal polyp removed 14 years previously. Symptoms related to liver metastases were reduced by a right hepatectomy whereas plasma motilin levels were decreased. The patient also underwent two operations for spinal cord decompression and survived 6 more years under medical treatment, mainly octreotide. Immunohistochemistry revealed predominant expression of motilin-containing cells, with rare cells expressing somatostatin and pancreatic polypeptide, and staining for only one panendocrine marker, neurone-specific enolase. A liver tumour extract contained 17.9 microg motilin per gram of tissue, which permitted to isolate and characterize human motilin, which was identical to porcine motilin. Plasma column gel chromatography revealed a main peak corresponding apparently to porcine motilin. The patient had no symptoms of disturbed motility. Gastric emptying and gastroduodenojejunal motility were found within normal limits. The absence of alterations of gut motility was perhaps related to sustained autonomous motilin production. The long evolution of this type of tumour suggests that plasma motilin determination should be added to the investigations for neuroendocrine tumours.

Bone Neoplasms↗

PubMed2000

The role of radioactive somatostatin and its analogues in the control of tumor growth.

Peptide receptor scintigraphy with the radioactive somatostatin analogue [111In-DTPA-D-Phe1]octreotide is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumors. With this technique primary tumors and metastases of neuroendocrine cancers as well as of many other cancer types can be localized. This technique is currently used to assess the possibility of peptide receptor radionuclide therapy with repeated administration of high doses of [111In-DTPA-D-Phe1]octreotide. 111In emits Auger and conversion electrons, having a tissue penetration of 0.02-10 microns and 200-500 microns, respectively. Thirty end-stage patients with mostly neuroendocrine progressing tumors were treated with [111In-DTPA-D-Phe1]octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase-I trial. There were no major clinical side effects after up to 2 years of treatment, except that in a few patients a transient decline in platelet counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production, and tumor proliferation were found. Of the 21 patients who received a cumulative dose of more than 20 GBq, eight showed stabilization of disease and six others a reduction in tumor size. There is a tendency towards better results in patients whose tumors have a higher accumulation of the radioligand. Peptide receptor radionuclide therapy is also feasible with 111In as the radionuclide. Theoretically, depending on the homogeneity of distribution of tumor cells expressing peptide receptors and the size of the tumor, beta-emitting radionuclides, e.g., 90Y, labeled to DOTA-chelated peptides may be more effective than 111In for peptide receptor radionuclide therapy. The first peptide receptor radionuclide therapy trials with [90Y-DOTA-Tyr3]octreotide started recently.

Cell Division↗

PubMed2000

The Place of Whole-Body PET FDG for the Diagnosis of Distant Recurrence of Breast Cancer.

Purpose: To study the role of positron emission tomography 18F-fluorodeoxyglucose (PET FDG) imaging in patients with a suspicion of breast cancer recurrence.Procedures: Whole-body PET FDG was performed in 39 women. Thirty-four were included because of asymptomatic tumor marker increase. PET findings were confirmed by oriented imaging or by biopsy. Follow-up data were collected over a period of at least 12 months.Results: PET FDG depicted 37/39 sites in 31/33 patients with recurrence. PET missed one locoregional recurrence and in one patient peritoneal carcinomatosis developed 6 months after a negative PET. False positive PET FDG corresponded to lung infection, degenerative bone disease, and reconstruction artifact. The conventional imaging work-up depicted sites of recurrence in 6/33 patients.Conclusion: Whole-body PET FDG is highly sensitive for the detection of distant breast cancer recurrence. Prospective studies are mandatory to address its potential impact on patient management and survival.

Journal Article↗

PubMed2000

Positron emission tomography with fluorodeoxyglucose for suspected head and neck tumor recurrence in the symptomatic patient.

OBJECTIVE: To analyze the impact of positron emission tomography with fluorodeoxyglucose (FDG-PET) in the treatment of patients suspected of having head and neck cancer recurrence. STUDY DESIGN: Prospective and consecutive inclusion of 44 patients presenting with clinical symptoms suggestive of head and neck tumor recurrence. METHODS: FDG-PET was compared with combined computed tomography (CT) plus magnetic resonance imaging (MRI) procedures for the differential diagnosis between tumor recurrence and benign post-therapeutic changes. For FDG-PET, the potential additional value of semiquantitative indexes was studied. The impact on patient treatment (i.e., their ability to accurately select patients for panendoscopic exploration) was analyzed retrospectively for both CT+MRI and PET workups. RESULTS: The diagnostic accuracy was found higher for PET than for combined CT+MRI: sensitivity ranged from 96% to 73%, specificity from 61% to 50%, and accuracy from 81% to 64% for PET and CT+MRI, respectively. The accuracy of FDG-PET was the highest (94%) in patients included more than 12 weeks after the end of therapy. In 15 discordant cases, PET was correct in 11 and CT+MRI in 4. Patient selection for panendoscopic exploration and biopsy was correct in 79% and 50% of patients with FDG-PET and CT+MRI, respectively. Quantification of FDG uptake had no additional value over visual analysis alone, although we found that a SUVlbm (standardized uptake value corrected for lean body mass) threshold of 3 could be helpful in patients scanned less than 12 weeks after the end of therapy. CONCLUSION: FDG-PET has a major additional diagnostic value to CT+MRI for the evaluation of the symptomatic patient suspected of having head and neck cancer recurrence. PET could have a direct impact on management by correctly selecting patients in whom a panendoscopic exploration with biopsy is indicated.

Adult↗

PubMed2000

OctreoTher: ongoing early clinical development of a somatostatin-receptor-targeted radionuclide antineoplastic therapy.

OctreoTher ((90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide, a.k.a. (90)Y-SMT 487) consists of a somatostatin peptide analogue (Tyr(3)-octreotide), coupled with a complexing moiety (DOTA), and labeled with a tightly bound beta-emitter (yttrium-90). By targeting somatostatin receptor-positive tumors (as imaged by OctreaScan it may deliver a tumoricidal dose of radiation. Phase I clinical trials, conducted in patients with neuroendocrine tumors, established the safety and tolerability of the dose selected for further study and demonstrated the capacity of OctreoTher to deliver radiation doses to tumors that resulted in significant neuroendocrine tumor shrinkage. Novartis-sponsored phase II studies will soon begin to test the efficacy of OctreoTher in breast and small cell lung cancer. A fixed-dose regimen of 120 mCi/cycle x 3 cycles administered with concomitant amino acid infusion has been chosen for the study. Phase I data and published literature support that this fixed dose regimen will be safely tolerated.

Animals↗

PubMed2000

[Portal hypertension caused by intra-hepatic block during chronic lymphoid leukemia].

Portal hypertension in chronic lymphocytic leukemia is rare. A 66 year-old man was admitted for splenomegaly, thrombopenia and cholestasis. Endoscopy showed esophageal varices. The hepatic venous pressure gradient was 15 mmHg. The liver biopsy showed dense leukemia cells in sinusoidal and portal sites. After splenectomy, the hepatic venous pressure gradient normalized, but esophageal varices and cholestasis persisted. The authors discuss the mechanisms of portal hypertension in chronic lymphocytic leukemia. Previously reported cases are summarized.

Aged↗

PubMed1999

Attenuation correction in whole-body FDG oncological studies: the role of statistical reconstruction.

Whole-body fluorine-18 fluoro-2-d-deoxyglucose positron emission tomography (FDG-PET) is widely used in clinical centres for diagnosis, staging and therapy monitoring in oncology. Images are usually not corrected for attenuation since filtered backprojection (FBP) reconstruction methods require a 10 to 15-min transmission scan per bed position on most current PET devices equipped with germanium-68 rod transmission sources. Such an acquisition protocol would increase the total scanning time beyond acceptable limits. The aim of this work is to validate the use of iterative reconstruction methods, on both transmission and emission scans, in order to obtain a fully corrected whole-body study within a reasonable scanning time of 60 min. Five minute emission and 3-min transmission scans are acquired at each of the seven bed positions. The transmission data are reconstructed with OSEM (ordered subsets expectation maximization) and the last iteration is reprojected to obtain consistent attenuation correction factors (ACFs). The emission image is then also reconstructed with OSEM, using the emission scan corrected for normalization, scatter and decay together with the set of consistent ACFs as inputs. The total processing time is about 35 min, which is acceptable in a clinical environment. The image quality, readability and accuracy of uptake quantification were assessed in 38 patients scanned for various malignancies. The sensitivity for tumour detection was the same for the non-attenuation-corrected (NAC-FBP) and the attenuation-corrected (AC-OSEM) images. The AC-OSEM images were less noisy and easier to interpret. The interobserver reproducibility was significantly increased when compared with non-corrected images (96.1% vs 81.1%, P<0.01). Standardized uptake values (SUVs) measured on images reconstructed with OSEM (AC-OSEM) and filtered backprojection (AC-FBP) were similar in all body regions except in the pelvic area, where SUVs were higher on AC-FBP images (mean increase 7.74%, P<0. 01). Our results show that, when statistical reconstruction is applied to both transmission and emission data, high quality quantitative whole-body images are obtained within a reasonable scanning (60 min) and processing time, making it applicable in clinical practice.

Adult↗

PubMed1999

Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radionuclide therapy.

BACKGROUND: Peptide receptor scintigraphy with the radioactive somatostatin analogue, [111In-DTPA0]octreotide, is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumours. AIM: With this technique primary tumours and metastases of neuroendocrine cancers as well as of many other cancer-types can be localised. This technique is currently used to assess the possibility of peptide receptor radionuclide therapy (PRRT) with repeated administrations of high doses of [111In-DTPA0)octreotide. 111In emits Auger and conversion electrons having a tissue penetration of 0.02-10 microns and 200 to 500 microns, respectively. PATIENTS AND METHODS: Thirty end-stage patients with mostly neuroendocrine progressing tumours were treated with [111In-DTPA0]octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase I trial. RESULTS: There were no major clinical side effects after up to two years treatment, except that in a few patients a transient decline in platelets counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production and tumour proliferation were found. Of the 21 patients who received a cumulative dose of more than 20 GBq, eight patients showed stabilisation of disease and six other patients a reduction in size of tumours. There is a tendency towards better results in patients whose tumours have a higher accumulation of the radioligand. CONCLUSIONS: PRRT is feasible, also with 111In as radionuclide. Depending on the homogeneity of distribution of tumour cells expressing peptide receptors and the size of the tumour, beta-emitting radionuclides, e.g., 90Y, labelled to DOTA-chelated peptides, are also attractive candidates for PRRT. The first PRRT trials with [90Y-DOTA0,Tyr3]octreotide started recently.

Animals↗

PubMed1999

Scintigraphy and radionuclide therapy with [indium-111-labelled-diethyl triamine penta-acetic acid-D-Phe1]-octreotide.

Peptide receptor scintigraphy with [111In-DTPA-D-Phe1]-octreotide is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumours. With this technique primary tumours and metastases of neuroendocrine cancers as well as of many other cancer types can be localised. This technique is currently used to assess the possibility of peptide receptor radionuclide therapy with repeated administrations of high doses of [111In-DTPA-D-Phe1]-octreotide. 111In emits Auger and conversion electrons having a tissue penetration of 0.02 to 10 microns and 200 to 500 microns, respectively. Twenty end-stage patients, mostly with neuroendocrine progressing tumours, were treated with [111In-DTPA-D-Phe1]-octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase I trial. Results showed there were no major clinical side-effects after up to 2 years treatment, except that in a few patients a transient decline in platelet counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production and tumour proliferation were found. Of the 16 patients who received a cumulative dose of more than 20 GBq, 5 patients showed stabilisation of disease and 5 other patients a reduction in size of tumours. There is a tendency towards better results in patients whose tumours have a higher accumulation of the radioligand. In conclusion, peptide receptor radionuclide therapy is feasible, also with 111In as radionuclide. Theoretically, depending on the homogeneity of distribution of tumour cells expressing peptide receptors, beta-emitting radionuclides, e.g. 90Y, labelled to DOTA-chelated peptides may be more effective than 111In for peptide receptor radionuclide therapy. The first peptide receptor radionuclide therapy trials with [90Y-DOTA-Tyr3]-octreotide started recently.

Antineoplastic Agents, Hormonal↗

PubMed1999

Dietary restriction of energy and sugar results in a reduction in human cytochrome P450 2E1 activity.

Dietary habits are often considered as a pathogenic factor for fatty liver. The impact of dietary intake and steatosis on drug metabolism remains poorly investigated. Our aim was to assess the effect of dietary intake on in vivo cytochrome P450 (CYP) activities in eleven patients with abnormal liver function tests potentially due to fatty liver and associated with a high-sugar diet. Liver function tests, liver volume, aminopyrine breath test (ABT) and chlorzoxazone (CZ) pharmacokinetics (area under the curve, AUC) which are known to reflect CYP2E1 activity were evaluated before and after 2 months restriction of dietary sugar intake. Features at inclusion were an increased BMI (30.3 (SD 3.2) kg/m2), high hepatic volume (1.96 (SD 0.48) litres), hyperechogenic liver parenchyma, elevated liver enzyme activities (alanine aminotransferase (EC 2.6.1.2) 58.6 (SD 17.4) IU/1 with alanine aminotransferase: aspartate aminotransferase (EC 2.6.1.1) ratio > 1), together with a normal ABT value (0.68 (SD 0.21)% specific activity of administered dose of [14C]aminopyrine in breath after 1 h) and a high CYP2E1 activity (CZ AUC 20.3 (SD 7.1) micrograms/ml per h). A dietary sugar restriction was prescribed. On the basis of repeated interviews by the same dietitian, unaware of any clinical and biochemical data, six patients remained complaint to the diet and exhibited reductions in BMI (P < 0.001), serum alanine aminotransferase (P = 0.008), liver volume (P = 0.002) and CYP2E1 activity (P = 0.007), a significant increase in ABT (P < 0.001) together with the disappearance of liver hyperechogenicity at ultrasound. In contrast, the five non-compliant patients did not show any significant change in any of these variables. In conclusion, CYP2E1 activity is induced in patients with perturbations of liver function tests potentially due to fatty liver. In these patients, effective dietary sugar restriction is associated with a reduction in liver volume, a reduction in CYP2E1 activity and an increased aminopyrine metabolism rate.

Adult↗

PubMed1998

Inadequate detection of accessory spleens and splenosis with laparoscopic splenectomy. A shortcoming of the laparoscopic approach in hematologic diseases.

BACKGROUND: The ultimate goal of surgery for hematological disorders is the complete removal of both the spleen and accessory spleens in order to avoid recurrence of the disease. Whereas splenectomy by open surgery provides excellent results, the validity of laparoscopic splenectomy in this regard remains unknown. OBJECTIVE: The purpose of this study was to evaluate the detection of accessory spleens during laparoscopic splenectomy for hematologic diseases. METHODS: We therefore evaluated the pre-, intra-, and postoperative detection of accessory spleens in a consecutive series of 18 patients treated by elective laparoscopic splenectomy for hematological diseases by using computed tomography (CT) and denatured red blood cell scintigraphy (DRBCS). RESULTS: Preoperative CT, DRBCS, and laparoscopic exploration detected 25%, 25%, and 75% of accessory spleens, respectively. At time of laparoscopy, 16 accessory spleens were detected in seven of the 18 patients (41%). In two patients (11%), laparoscopic exploration failed to detect accessory spleens, whereas preoperative CT (one case) and DRBCS (one case) did reveal them. Postoperatively, during a mean follow-up of 28 months (median, 24; range, 12-44 months), nine patients (50%) showed persistence of splenic tissue by DRBCS, and three of them had signs of disease recurrence. CONCLUSIONS: This prospective clinical study suggests that elective laparoscopic surgery for hematological diseases does not allow complete detection of accessory spleens. Moreover, after such a laparoscopic approach, residual splenic tissue is detectable in half of the patients during the follow-up.

Adolescent↗

PubMed1998

Uptake of In-111 pentetreotide by pleural plaques.

Somatostatin receptor imaging with In-111 pentetreotide has been validated for the diagnosis and staging of chest tumors with neuroendocrine differentiation such as bronchial carcinoid and small cell lung cancer. In-111 pentetreotide uptake is not specific for neuroendocrine tumors because somatostatin receptors are also expressed by white blood cells, leading to the in vivo visualization sites of infection sites or active inflammation. Pleural plaques may be due to asbestos exposure or tuberculosis. Presented here are three cases of In-111 pentetreotide uptake in pleural plaques. This uptake by benign lesions may be misleading in the diagnostic work-up of patients with lung tumors.

Aged↗

PubMed1998

Can dual-headed 18F-FDG SPET imaging reliably supersede PET in clinical oncology? A comparative study in lung and gastrointestinal tract cancer.

In this study, we prospectively compared the sensitivity of PET and planar SPET (collimated gamma camera) 18F-FDG imaging in patients with lung and gastrointestinal tract cancer and analysed their respective impact on patient management. Twenty-eight patients with lung cancer and 14 with gastro-intestinal tract tumours were scanned on the same day with a PET and a collimated planar SPET gamma camera. The planar SPET procedure consisted of whole-body planar views and a tomographic acquisition centred over the torso or the abdomen, with the total imaging time within the same range as the whole-body PET procedure. The staging of lung cancer patients was accurate in 86% with PET and 64% with planar SPET. Planar SPET would have led to inappropriate therapeutic decisions in 8 of 28 patients, mainly due to undetected distant metastases. In patients with suspected gastrointestinal tract cancer, planar SPET identified 7 of 15 (47%) proven tumour sites, whereas PET identified 14 of 15 (93%). Our results suggest that collimated planar SPET cameras are not a substitute for dedicated PET scanners. The sensitivity for the detection of tumours is unacceptably low and can impair patient management. The use of multiple tomographic acquisitions could improve the sensitivity but would require a longer scanning time.

Colorectal Neoplasms↗

PubMed1997

14C-Propoxyphene demethylation in the rat. An example of differences between liver and intestinal drug-presystemic metabolism.

Presystemic metabolism is believed to occur mainly in the liver with some minor intestinal participation. The aim of this study was to investigate the respective part of each of these two organs in the metabolism of the analgesic d-propoxyphene (DP). Pharmacological doses of DP were given in the duodenum (ID), the portal vein (IP), and the femoral vein (IV) of male Wistar rats. A tracer dose of 14C-DP was also administered either in IV, IP, or ID as well as in hepatectomized rats or rats with bile duct diversion. In vitro demethylation occurring in liver and intestinal microsomes was also studied. Absolute DP bioavailability obtained after oral administration was two times higher than that observed after portal administration (48.9% vs. 23.2%, respectively), an result opposite (i.e. a lower bioavailability) of that expected on the basis of the existence of a liver enzyme saturation phenomenon. The 14CO2 cumulative excretion after 14C-DP administration was significantly lower after IV or ID administration than after injection in the portal vein as a bolus or within 20 min. The biliary excretion of the labeled compound varied in the opposite direction, being greater after IV or ID than after IP administration, suggesting that the metabolism of DP in the liver is influenced by an extrahepatic transformation. This most likely occurs in the gut since the production of 14CO2 after IV administration was similar to that after ID administration. This transformation did not prohibit DP detection in the systemic blood but was sufficient to increase the part eliminated with bile and to decrease the part demethylated into NP. Demethylation mainly occurs in the liver since the production of 14CO2 was nearly abolished in hepatectomized rats. Furthermore, microsomes of hepatic but not of intestinal origin were able to demethylate DP. Our data suggest that the transformation of DP occurring in gut after oral administration is responsible for changes in the hepatic metabolism of the drug.

Analgesics, Opioid↗

PubMed1996

Increased uptake of indium-111 pentetreotide up to 10 years after external thoracic irradiation: report of two cases.

Indium-111 pentetreotide scintigraphy was performed in two patients for the localization of recurrent medullary thyroid carcinoma treated by surgery and external radiotherapy 1 and 10 years earlier. A marked uptake of the radiopharmaceutical was demonstrated in the lung areas that had been irradiated. These cases strongly suggest that this uptake is related to pulmonary fibrosis, a well-known complication of radiotherapy, even long after the irradiation. Therefore, attention must be paid to the avoidance of false-positive interpretation of somatostatin receptor scintigraphy in patients previously treated by radiotherapy.

Aged↗

PubMed1996

A non-negative fast multiplicative algorithm in 3D scatter-compensated SPET reconstruction.

Single-photon emission tomographic (SPET) reconstruction can be improved, especially for noisy images, by using the iterative expectation-maximization of the maximum-likelihood (EM-ML) algorithm. Its application to clinical routine is, however, hampered by the high number of iterations necessary to achieve acceptable results. Therefore various methods have been developed to accelerate the EM-ML algorithm. In this paper a new accelerated EM-ML-like multiplicative algorithm is proposed for SPET reconstruction. Contrary to some other accelerating methods, it preserves two of the most important properties of the EM-ML, namely pixel positivity inside the patient body and null activity outside. The convergence speed is improved by a factor which can reach 100 in high spatial frequency or low count regions. Good estimates in the low count region are obtained without any smoothing, even at typical routine clinical count rates. The algorithm used in conjunction with the 3D effective one scatter path model provides high-quality SPET images and accurate quantitation.

Adult↗

PubMed1996

Radiographic skeletal survey and radionuclide bone scan in Langerhans cell histiocytosis of bone.

BACKGROUND: The lack of a consensus in the literature on the imaging strategy in Langerhans cell histiocytosis (LCH) bone lesions in childhood. OBJECTIVE: To evaluate the relative value of radionuclide bone scan (RBS) and radiographic skeletal survey (RSS) in the detection of LCH bone lesions, both in the initial work-up of the disease and during the follow-up period. MATERIALS AND METHODS: Ten children with bone lesions evaluated by means of RSS and RBS in a retrospective study (1984-1993). RESULTS: Fifty radiologically and/or scintigraphically abnormal foci were detected: 27 anomalies in the initial work-up (12 by both RSS and RBS, 8 by RSS only and 7 by RBS only) and 23 additional anomalies during follow-up (10 by both RSS and RBS, 10 by RSS only and 3 by RBS only). RSS+/RBS- lesions (n = 18) are more frequently encountered in the skull (P = 0.038), and more frequently lack radiologic signs of osteoblastic activity (P = 0.020), than RSS+/RBS+ lesions (n = 22). RSS-/ RBS+ abnormalities (n = 10) were most frequently insignificant. CONCLUSION: In the initial work-up both RSS and RBS should be carried out, while in the follow-up only RSS should be performed.

Adolescent↗