Szabolcs Szakáll

Coeliac disease in Sjögren's syndrome—a study of 111 Hungarian patients

Recent studies report that in patients with Sjögrens syndrome (SS), concomitant coeliac disease (CD) is more frequent than in the average healthy population, with dominance of the latent/silent form. We further investigated this to characterise the clinical and immunolaboratory features of SS patients with CD. One hundred and eleven patients with SS were involved in the study. After detailed history, blood samples were taken for antibodies to gliadin, endomysium, and tissue transglutaminase. Of them, six had positive serology for CD and underwent jejunoscopy and small bowel biopsy to confirm the diagnosis of CD. In five patients, the diagnosis was established histologically. The frequency of CD in the SS population was significantly higher than in the non-SS European population (4.5:100 vs 4.5–5.5:1,000). Laboratory findings in these patients showed significantly higher erythrocyte sedimentation rates and IgG, IgA, and IgM levels. On the basis of these findings, we recommend screening, follow-up, and regular gastrointestinal care of SS patients to identify CD cases and help them to avoid severe malnutrition and intestinal malignancies.

The possible role of F-18 FDG positron emission tomography in the differential diagnosis of focal pancreatic lesions

Purpose To compare the diagnostic values of different methods for the differentiation of malignant from benign pancreatic lesions. Methods In 22 patients with focal pancreatic lesions, the carbohydrate antigen (CA) 19-9 level was measured; abdominal ultrasound (US), computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) were performed; and the value of these methods were analyzed for their use in cancer diagnosis. Results Malignant lesions were identified in six patients and verified by surgery or clinical follow-up. The CA 19-9 level was elevated in four of the five patients examined (sensitivity, 80%). In all six cases, US and CT revealed hypoechogenic and hypodense areas (sensitivity, 100%). In one patient, ERCP was unsuccessful but yielded true-positive results in three others (sensitivity, 60%). The sensitivity of FDG PET was 100%. Sixteen focal cases of pancreatic disease proved to be benign. The CA 19-9 level was elevated in four of them (specificity, 73%). Hypoechogenic and hypodense areas were evident on US and CT in eight patients. The specificity of CT was 50% (8 of 16 cases). The specificity of US was 47% (7 of 15 cases). The specificity of successful ERCP was 92%. Fourteen negative FDG-PET results were truly negative. In two patients, however, the PET findings proved to be falsely positive (specificity, 88%). Conclusions FDG-PET is an effective tool to differentiate malignant from benign focal pancreatic lesions. In persons with focal pancreatic hypoechogenic or hypodense lesions detected by CT or US and an elevated CA 19-9 level, FDG PET should be the next step in the diagnostic strategy.

Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study ☆

The pharmacological effects of the neuroprotective drug vinpocetine, administered intravenously in a 14-day long treatment regime, on the cerebral blood flow and cerebral glucose metabolism in chronic ischemic stroke patients (n=13) were studied with positron emission tomography in a double-blind design. The regional and global cerebral metabolic rates of glucose (CMRglc) and cerebral blood flow (CBF) as well as vital physiological parameters, clinical performance scales, and transcranial Doppler parameters were measured before and after the treatment period in patient groups treated with daily intravenous infusion with or without vinpocetine. While the global CMRglc values did not change markedly as a result of the infusion treatment with (n=6) or without (n=7) vinpocetine, the global CBF increased and regional CMRglc and CBF values showed marked changes in several brain structures in both cases, with more accentuated changes when the infusion contained vinpocetine. In the latter case the highest rCBF changes were observed in those structures in which the highest regional uptake of labelled vinpocetine was measured in other PET studies (thalamus and caudate nucleus: increases amounting to 36% and 37%, respectively). The findings indicate that a 2-week long intravenous vinpocetine treatment can contribute effectively to the redistribution of rCBF in chronic ischemic stroke patients. The effects are most pronounced in those brain regions with the highest uptake of the drug.

Investigation of c-myc and K-ras amplification in renal clear cell adenocarcinoma.

Tumour DNA samples isolated from 36 patients with renal clear cell carcinoma were investigated for c-myc and K-ras amplification, using a quantitative dot-blot hybridization. The characteristic clinical and histological parameters involved in the statistical analysis were age, sex, histological grade of the tumour, the TNM staging system, tumour size and weight, vascular invasion and the quality of life. The goal of the study was to estimate the prevalence as well as the prognostic value of the amplification of the oncogenes in question. Amplified c-myc (2.47-fold on the average) was found in three specimens (8.3%), showing slight correlation with intravasation (P > 0.05, n.s.). K-ras amplification (2.93-fold) detected in six tumours (16.6%) was shown to significantly correlate with both histological grade (2.2 vs. 1.8, P < 0.05) and tumour size (15 vs. 8 cm, P < 0.05). In cases with amplified K-ras also lymph node involvement was somewhat more frequent (P > 0.05, n.s.). No coamplification of these oncogenes was observed. The results of the study suggest that K-ras amplification may account for a more rapid progression of the disease.

Angiography effectively supports the diagnosis of hepatic metastases in medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) belongs in the group of neuroendocrine tumors with early lymphatic and hepatic dissemination. A high rate of undetectable metastases is hypothesized to be responsible for the frequent mismatch between the apparent relatively small tumor burden and the elevated plasma tumor marker level.

PET identifies transitional metabolic change in the spinal cord following a subthreshold dose of irradiation.

Positron emission tomographic (PET) investigations were performed to obtainin vivo information on symptomless radiation-induced pathological changes in the human spinal cord. PET investigations were carried out prior to radiotherapy and during the regular follow-up in an early hypopharyngeal cancer patient (the spinal cord was irradiated with a biologically effective dose of 80 Gy2), with [18F]fluorodeoxyglucose (FDG), [11C]methionine and [15O]butanol as tracers; radiosensitivity and electroneuronographic (ENG) studies were also performed. A very low background FDG accumulation (mean standardized uptake values, i.e. SUV: 0.84) was observed in the spinal cord before the initiation of radiotherapy. An increased FDG uptake was measured 2 months after the completion of radiotherapy (mean SUV: 1.69), followed by a fall-off, as measured 7 months later (mean SUV: 1.21). By 44 months after completion of irradiation, the FDG accumulation in the irradiated segments of the spinal cord had decreased to a level very close to the initial value (mean SUV: 1.11). The simultaneous [15O]butanol uptake results demonstrated a set of perfusion changes similar to those observed in connection with the FDG accumulation. The patient exhibited an extremely low [11C]methionine uptake within the irradiated and the nonirradiated spinal cord during the clinical course. She has not had any neurological symptoms, and the results of central ENG measurements before radiotherapy and 2 months following its completion proved normal. Radiobiological investigations did not reveal unequivocal signs of an increased radiosensitivity. A transitory increased spinal cord FDG uptake following radiotherapy may be related to the posttherapeutic mild inflammatory and regenerative processes. The normal [11C]methionine accumulation observed is strong evidence against intensive cell proliferation. The high degree of normalization of the temporarily increased FDG uptake of the irradiated spinal cord segments by 44 months is in good agreement with the results of monkey studies, which demonstrated a nearly complete recovery from radiation-induced spinal cord injury.

Miller Fisher syndrome--a presenting clinical manifestation of lung cancer in a previously apparently healthy individual.

Sirs: A 54 year-old white male complained of clumsiness of the right upper extremity, diplopia and unsteadiness of gait starting about 6 days before admission. The history was negative except for smoking an average of 2 packs of cigarettes per day in the preceding 40 years. On admission he had right sided complete oculomotor nerve lesion, severe bilateral lower motoneuron facial palsy (Fig. 1A and 1B), absent Achilles reflexes, diminished other deep tendon reflexes and severe gait ataxia. The patient did not have objective sensory loss, major paresis or signs of upper motor neuron lesion. Except for an elevated erythrocyte sedimentation rate (46 mm/hour) and a borderline serum glucose level the routine blood tests were normal. The cerebrospinal fluid (CSF) had an extremely elevated protein content (3.115 g/L) associated with some pleocytosis (256 cells per microliters). The CSF cells were lymphocytes (20 %), macrophages (48 %, a few of them signet-ring cells), monocytes (12 %), and 20 % of the cells were intensely stained, atypical giant cells with large round marginal nuclei. These cells were PAS positive and were also cytokeratin positive with CK7 immunocytochemistry (Fig. 2A). Nerve conduction studies revealed mild axonal sensorimotor neuropathy. On computed tomography contrast enhancement was seen in the right Sylvian fissure (Fig. 2B). MRI detected several small (< 10 mm) contrast enhancing lesions mostly in the cerebral cortex (Fig. 2C, arrows), and in some other CSF-adjacent regions (cerebellar surface, basal ganglia adjacent to the lateral ventricle, periaqueductal gray matter) as well. Chest CT identified a small tumor in the right lung (Fig. 2D). The tumor was removed and appeared to be a carcinoma with adenomatous structure staining with PAS. With immunohistochemical examination the tumor cells were CK7 positive, CK20 negative, exhibited nuclear positivity with TTF-1, and about 5 % of the cells had nuclear positivity with Mib-1. A histological diagnosis of grade 3 bronchial adenocarcinoma was established. Miller Fisher described a syndrome of ophthalmoplegia, ataxia and areflexia as a variant of the Guillain-Barré syndrome [2]. In a series of 50 cases [4] facial palsy was present in about one third of the cases. Although a cerebrospinal fluid (CSF) cell count over 50/μl is rare in Guillain-Barré syndrome, it has been reported in several cases [6]. Axonal, predominantly, sensory neuropathy was found in 5 of 6 patients with Miller Fisher syndrome (MFS) [9]. Therefore, from the clinical signs the diagnosis of MFS could have been considered for our case. In leptomeningeal carcinomatosis the incidence of clinical signs at presentation were 11 % for oculomotor lesion, 11 % for facial nerve involvement and 15–15 % for cerebellar signs and polyradiculopathy [1]. Therefore the probability of the coincidence of the individual signs of MFS is low. There are only 4 published cases where the syndrome was associated with malignant diseases. Leptomeningeal infiltration was described by Guarino et al. [3] in 2 cases. One of them developed the syndrome 6 months after gastrectomy for cancer and the other patient 4 years after thyroidectomy for cancer and 2 years after the diagnosis of acute LETTER TO THE EDITORS

Increased Metabolic Activity in the Spinal Cord of Patients with Long-Standing Lhermitte’s Sign

Purpose:To investigate the pathophysiology of the radiation-induced, chronic Lhermitte’s sign (LS) on the basis of long-standing case histories with partial functional recovery.Patients and Methods:As radiotherapy in two nasopharyngeal cancer patients, a biologically effective dose (BED) of 103.8 Gy2 (case 1) and 94.8 Gy2 (case 2) was delivered to the cervical spinal cord. Neurologic signs relating to the irradiated spinal cord segments developed after 2 months (case 1) and 5 years (case 2), with radiation-induced damage equivalent to grade 3 (case 1) and grade 2 (case 2) toxicity (Common Toxicity Criteria, Version 2.0). The clinical status improved to grade 2 (case 1) and grade 1 (case 2). Positron emission tomography (PET) and fibroblast clonogen assay were applied 25 and 7 years postirradiation, respectively, to characterize this rare clinical picture.Results:PET demonstrated increased [18F]fluorodeoxyglucose (FDG) accumulation and [15O]butanol perfusion, but negligible [11C]methionine uptake in the irradiated spinal cord segments in both patients. In clonogenic assays, fibroblasts from case 1 displayed much higher radiation sensitivity than in healthy controls, while in case 2 the fibroblasts sensitivity was normal.Conclusions:These data suggests a close direct relationship between regional perfusion and metabolism of the spinal cord, similarly as in the brain. The postirradiation recovery may be related to energy-demanding conduction, explaining the increased metabolism and perfusion. The increased radiosensitivity and higher spinal cord BED may have contributed to the more severe sequelae in case 1.Ziel:Untersuchung der Pathophysiologie des strahleninduzierten chronischen Lhermitte-Zeichens auf der Basis der Langzeitbeobachtung von zwei Patienten mit partieller funktioneller Erholung.Patienten und Methodik:Bei zwei Patienten mit Nasopharynxkarzinom wurde die Halswirbelsäule mit einer biologisch effektiven Dosis (BED) von 103,8 Gy2 (Patient 1) bzw. 94,8 Gy2 (Patient 2) bestrahlt. Neurologische Symptome, die auf die bestrahlten Segmente des Zervikalmarks zurückzuführen waren, traten nach 2 Monaten (Patient 1) bzw. nach 5 Jahren (Patient 2) auf, wobei die strahleninduzierte Schädigung einer Grad-3- (Patient 1) bzw. Grad-2-Toxizität (Patient 2) entsprach (Common Toxicity Criteria, Version 2.0). Der klinische Status ging auf Grad 2 (Patient 1) bzw. Grad 1 (Patient 2) zurück. Positronenemissionstomographie (PET) und der Fibroblastenklonogenitätsassay wurden 25 bzw. 7 Jahre nach der Strahlentherapie eingesetzt, um dieses seltene Krankheitsbild zu charakterisieren.Ergebnisse:Im PET zeigten sich bei beiden Patienten eine erhöhte [18F-]Fluorodesoxyglucose-(FDG-)Aufnahme und [15O-] Butanol-Perfusion, jedoch eine vernachlässigbar geringe [11C-]Methionin-Aufnahme in den bestrahlten Segmenten. In den Klonogenitätsassays hatten die Fibroblasten des Patienten 1 eine höhere Strahlungsempfindlichkeit als bei gesunden Kontrollen, während die Fibroblastensensitivität bei Patient 2 normal war.Schlussfolgerungen:Diese Befunde sprechen für eine—ähnlich wie im Gehirn—enge direkte Beziehung zwischen regionaler Perfusion und Metabolismus des Rückenmarks. Die Erholung nach der Strahlentherapie dürfte mit Energie verbrauchenden Prozessen einhergehen, was die Steigerung von Metabolismus und Perfusion erklärt. Die erhöhte Strahlenempfindlichkeit und die höhere BED am Rückenmark können zu den gravierenderen Folgeerscheinungen bei Patient 1 beigetragen haben.

Catastrophic antiphospholipid syndrome in cancer

Antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies resulting in arterial and venous thromboembolism. Apart from primary cases, this syndrome is often associated with autoimmune diseases. Around 50 cases of catastrophic antiphospholipid antibody syndrome have been reported as yet. Authors describe the first case of catastrophic antiphospholipid syndrome associated with gastric cancer. Apart from presenting the clinical case, authors also discuss the possible pathomechanism of this associated disorder including the role of immunological factors, as well as antiphospholipid antibodies.

Correlation of the value of 18F-FDG uptake, described by SUVmax, SUVavg, metabolic tumour volume and total lesion glycolysis, to clinicopathological prognostic factors and biological subtypes in breast cancer.

ObjectiveThe aim of this study was to observe the relationships between different metabolic parameters and clinicopathological features (CPFs) or immunohistochemically defined biological subtypes (IHC-BS) in breast cancer. Materials and methodsEighty-two women (83 lesions, tumour size >15 mm) underwent PET/computed tomography imaging after a core biopsy. Maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) in the primary tumour were calculated and compared with CPFs and IHC-BS. Tumours with oestrogen receptor (ER) positivity were separately investigated in relation to their progesterone receptor (PR) status. ResultsSignificant correlation was found between all metabolic parameters and high nuclear grade or ER status or IHC-BS. All parameters were higher in PR(−) and triple-negative cases than in PR(+) and non-triple-negative tumours, and the correlation was significant for most of the metabolic parameters (except for SUVavg in the case of PR status and MTV in the case of triple negativity). Significant correlation was found only for SUVmax regarding the human epidermal growth factor receptor 2 (HER2) status. There was moderate correlation between the Ki67 expression and the SUVmax or SUVavg. All metabolic parameters were higher in ER(+)/PR(−)/HER2(−) lesions compared with ER(+)/PR(+)/HER2(−) cancers. However, ER(+)/PR(−)/HER2(+) tumours had lower SUVmax and SUVavg compared with ER(+)/PR(+)/HER2(+) lesions. ConclusionOur study confirms that the fluorine-18 fluorodeoxyglucose uptake in primary tumour is associated with distinct CPFs or IHC-BS in breast cancer. SUVmax may reflect tumour metabolism more reliably compared with SUVavg, MTV or total lesion glycolysis. Our preliminary results suggest different biological properties in ER(+) tumours with different PR statuses.