Germano Perotti

Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease

The role played by the gut in nonalcoholic fatty liver disease (NAFLD) is still a matter of debate, although animal and human studies suggest that gut‐derived endotoxin may be important. We investigated intestinal permeability in patients with NAFLD and evaluated the correlations between this phenomenon and the stage of the disease, the integrity of tight junctions within the small intestine, and prevalence of small intestinal bacterial overgrowth (SIBO). We examined 35 consecutive patients with biopsy‐proven NAFLD, 27 with untreated celiac disease (as a model of intestinal hyperpermeability) and 24 healthy volunteers. We assessed the presence of SIBO by glucose breath testing (GBT), intestinal permeability by means of urinary excretion of 51Cr‐ethylene diamine tetraacetate (51Cr‐EDTA) test, and the integrity of tight junctions within the gut by immunohistochemical analysis of zona occludens‐1 (ZO‐1) expression in duodenal biopsy specimens. Patients with NAFLD had significantly increased gut permeability (compared with healthy subjects; P < 0.001) and a higher prevalence of SIBO, although both were lower than in the untreated celiac patients. In patients with NAFLD, both gut permeability and the prevalence of SIBO correlated with the severity of steatosis but not with presence of NASH. Conclusions: Our results provide the first evidence that NAFLD in humans is associated with increased gut permeability and that this abnormality is related to the increased prevalence of SIBO in these patients. The increased permeability appears to be caused by disruption of intercellular tight junctions in the intestine, and it may play an important role in the pathogenesis of hepatic fat deposition. (HEPATOLOGY 2009.)

Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma

PurposeTo retrospectively evaluate and compare 18F-FDG, 18F-DOPA and 68Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels.MethodsIncluded in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis.ResultsAt least one focus of abnormal uptake was observed on PET/CT in 13 patients with 18F-DOPA (72.2% sensitivity), in 6 patients with 68Ga-somatostatin analogues (33.3%) and in 3 patients with 18F-FDG (16.7%) (p < 0.01). There was a statistically significant difference in sensitivity between 18F-DOPA and 18F-FDG PET/CT (p < 0.01) and between 18F-DOPA and 68Ga-somatostatin analogue PET/CT (p = 0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. 18F-DOPA PET/CT detected 85% of lesions (61 of 72), 68Ga-somatostatin analogue PET/CT 20% (14 of 72) and 18F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers (p < 0.01). In particular, post-hoc tests showed a significant difference in the number of lymph node, liver and bone lesions detected by 18F-DOPA PET/CT and 18F-FDG PET/CT (p < 0.01 for all the analyses) and by 18F-DOPA PET/CT and 68Ga-somatostatin analogue PET/CT (p < 0.01 for all the analyses). The PET/CT results led to a change in management of eight patients (44%).Conclusion18F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than 18F-FDG and 68Ga-somatostatin analogue PET/CT. 18F-FDG may complement 18F-DOPA in patients with an aggressive tumour.

Intestinal permeability in cirrhotic patients with and without spontaneous bacterial peritonitis: is the ring closed?

OBJECTIVES:Impaired intestinal permeability (IP) may have a role in the pathogenesis of ascites and in spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis (LC). The aim of this study was to assess IP in LC patients with respect to healthy controls.METHODS:IP was evaluated by the 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) permeability test in 52 LC patients and in 48 sex- and age-matched controls. The presence of 51Cr-EDTA was also evaluated in ascitic fluid after therapeutic paracentesis in all LC patients with ascites.RESULTS:An altered IP was found in 45% of LC patients compared with 4% of controls (P<0.00001). IP impairment was significantly associated with Child–Pugh status (75% of Child C patients vs. 39% of Child B and 22% of Child A patients), with the presence of ascites (60% in ascitic patients vs. 31% in nonascitic patients), and with a history of SBP (100% of patients with SBP vs. 50% of those without SBP). 51Cr-EDTA was present in all ascitic samples obtained from patients with SBP compared with 22% of patients without SBP.CONCLUSIONS:IP derangement was a common finding in LC, especially in patients with more advanced disease (presence of ascites and history of SBP). The presence of 51Cr-EDTA in ascites in patients with SBP suggests an altered permeability of splancnic vessels and/or peritoneal membranes. Further studies are required to assess 51Cr-EDTA urine and ascite cutoffs to set up SBP preventive strategies.

Comparison of 123I-MIBG SPECT-CT and 18F-DOPA PET-CT in the evaluation of patients with known or suspected recurrent paraganglioma.

ObjectivesDetection of recurrent disease is essential for treatment planning in patients with paraganglioma. The aim of this study was to compare 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy [whole-body and single-photon emission computed tomography (SPECT) computed tomography (CT) scanning] and fluorine-18-L-dihydroxyphenylalanine positron emission tomography CT (18F-DOPA PET-CT) in the re-staging of patients with known or suspected recurrent paraganglioma. MethodsTwelve patients with known or suspected recurrent paraganglioma after initial surgery were included in the study. 18F-DOPA PET-CT and 123I-MIBG scintigraphy (whole-body and SPECT-CT scanning) were performed in all patients; the results were compared on a per patient and a per lesion basis. Cytohistology (when available) and a combination of laboratory and imaging studies and follow-up were used as reference standard; any modification in treatment planning was recorded. In all cases recurrent disease (local or distant) was confirmed by cytohistology (four cases) or at subsequent follow-up (eight cases). ResultsAll patients had positive 18F-DOPA studies (100% sensitivity) whereas nine had positive 123I-MIBG studies (75% sensitivity; P=not significant). 18F-DOPA detected 98% of lesions, whereas 38% were detected with 123I-MIBG (P=0.04). 18F-DOPA showed more lesions than 123I-MIBG in eight patients; both techniques showed the same number of lesions in two cases whereas in two patients 123I-MIBG showed a greater number of lesions. A change in treatment planning was suggested by 18F-DOPA in one patient. ConclusionThese data support the superiority of 18F-DOPA PET-CT over 123I-MIBG scintigraphy to assess disease extension in patients with recurrent paraganglioma; however, in cases with inoperable disease, 123I-MIBG maintains a unique role in allowing the selection of patients suitable for 131I-MIBG therapy.

Impact of 111In-DTPA-octreotide SPECT/CT fusion images in the management of neuroendocrine tumours

PurposeSomatostatin receptor scintigraphy with [111In]-diethylene triamine pentaacetate acid (DTPA)-octreotide is an accurate method for detecting neuroendocrine tumours (NETs) but often does not provide clear anatomical localisation of lesions. The aim of this study was to assess the clinical usefulness of anatomical-functional image fusion.Materials and methodsFifty-four patients with known or suspected NET were included in the study. Planar and single-photon-emission computed tomography (SPECT) imaging was performed using a dual-head gamma camera equipped with an integrated X-ray transmission system, and the images were first interpreted alone by two nuclear medicine physicians and then compared with SPECT/CT fusion images together with a radiologist. The improvement provided by SPECT/CT in the interpretation of SPECT data alone and any modification in patientmanagement were recorded.ResultsFusion images improved SPECT interpretation in 23 cases, providing precise anatomical localisation of increased tracer uptake in 20 cases and disease exclusion in sites of physiological uptake in 5. In 10 patients, SPECT/CT allowed definition of the functional significance of lesions detected by diagnostic CT. SPECT/CT data modified clinical management in 14 cases by changing the diagnostic approach in 8 and the therapeutic modality in 6.ConclusionsOur study demonstrates that image fusion is clearly superior to SPECT alone, allowing precise localisation of lesions and reducing false-positive results.RiassuntoObiettivoLa scintigrafia con 111In-DTPA-octreotide rappresenta un metodo accurato per la diagnosi dei tumori neuroendocrini, ma spesso non fornisce una corretta localizzazione anatomica delle lesioni. Scopo di questo studio è valutare l’utilità clinica della fusione di immagini SPECT-TC.Materiali e metodiSono stati inclusi 54 pazienti con tumore neuroendocrino sospetto o noto. Le immagini planari e SPECT, ottenute utilizzando una gamma-camera a doppia testata con integrato sistema trasmissivo TC, sono state interpretate prima separatamente da due medici nucleari e poi confrontate con immagini di fusione insieme ad un radiologo, per valutare i miglioramenti apportati dalla fusione nell’interpretazione delle immagini SPECT e nella gestione del paziente.RisultatiLe immagini di fusione hanno migliorato l’interpretazione SPECT in 23 casi, permettendo una precisa localizzazione anatomica dei siti patologici in 20 casi e l’esclusione di malattia in siti di accumulo fisiologico in 5. In 10 pazienti SPECT/TC ha permesso la definizione funzionale di lesioni evidenziate alla TC diagnostica. SPECT/TC ha modificato il management clinico in 14 pazienti, modificando l’approccio diagnostico in 8 e quello terapeutico in 6.ConclusioniIl nostro studio dimostra che la fusione di immagini è chiaramente superiore alla sola SPECT, permettendo una precisa localizzazione delle lesioni individuate e riducendo i risultati falsi positivi.

Are there disadvantages in administering 131I ablation therapy in patients with differentiated thyroid carcinoma without a preablative diagnostic 131I whole‐body scan?

objective  To evaluate the risk of performing inappropriate 131I ablative therapies for thyroid carcinoma in patients lacking thyroid remnants or metastases, using a strategy of treatment without a preliminary iodine‐131 diagnostic whole‐body scan (DxWBS).

Multicenter comparison of 18F-FDG and 68Ga-DOTA-peptide PET/CT for pulmonary carcinoid

Purpose The aims of this study were to retrospectively evaluate and compare the detection rate (DR) of 68Ga-DOTA-peptide and 18F-FDG PET/CT in the preoperative workup of patients with pulmonary carcinoid (PC) and to assess the utility of various functional indices obtained with the 2 tracers in predicting the histological characterization of PC, that is, typical versus atypical. Methods Thirty-three consecutive patients with confirmed PC referred for 18F-FDG and 68Ga-DOTA-peptide PET/CT in 2 centers between January 2009 and April 2013 were included. The semiquantitative evaluation included the SUVmax, the SUV of the tumor relative to the maximal liver uptake for 18F-FDG (SUVT/L) or the maximal spleen uptake for 68Ga-DOTA-peptides (SUVT/S), the ratio between SUVmax of 68Ga-DOTA-peptides PET/CT, and the SUVmax of 18F-FDG PET/CT (SUVmax ratio). Histology was used as reference standard. Results Definitive diagnosis consisted of 23 typical carcinoids (TCs) and 10 atypical carcinoids. 18F-FDG PET/CT was positive in 18 cases and negative in 15 (55% DR). 68Ga-DOTA-peptide PET/CT was positive in 26 cases and negative in 7 (79% DR). In the subgroup analysis, 68Ga-DOTA-peptide PET/CT was superior in detecting TC (91% DR; P < 0.001), whereas 18F-FDG PET/CT was superior in detecting atypical carcinoid (100% DR; P = 0.04). The SUVmax ratio was the most accurate semiquantitative index in identifying TC. Conclusions Overall diagnostic performance of PET/CT in detecting PC is optimal when integrating 18F-FDG and 68Ga-DOTA-peptide PET/CT findings. In the subgroup analysis, the SUVmax ratio seems to be the most accurate index in predicting TC. Both methods should be performed when PC is suspected or when the histological subtype is undefined.

Solitary liver metastasis from Hürthle cell thyroid cancer: A Case Report and review of the literature

Metastasis to the liver from thyroid cancer is a rare event with a reported frequency of 0.5%. Metastatic liver involvement from differentiated thyroid cancer (DTC) is nearly always multiple or diffuse and usually found along with other distant metastases (lung, bone and brain). The authors describe a patient with a solitary liver metastasis from Hürthle cell thyroid cancer, which appeared during long-term follow-up. The lesion was diagnosed by progressive increase of thyroglobulin in the serum and imaged with I-131 whole body scan, ultrasonography, magnetic resonance imaging (MRI) and F-18 fluoro-deoxyglucose positron emission tomography (FDG-PET) scan. For patients with a Tg level above some arbitrary limit, the administration of a large dose (3.7–5.5 GBq; 100–150 mCi) of I-131, in order to obtain a highly sensitive Tx whole body scan (WBS), remains the best diagnostic strategy. However, on very rare occasions, physiological enteric radioactivity can hide possible abdominal lesions and further indepth studies, such as FDG-PET scans, are sometimes necessary.

Thyroid scintigraphy: an old tool is still the gold standard for an effective diagnosis of autonomously functioning thyroid nodules

Background: Patients with autonomously functioning thyroid nodules (AFTN) may not have an abnormal TSH value, particularly in iodine-deficient areas. Aim: To verify the accuracy of TSH as screening test in detecting AFTN and to evaluate ultrasonographic features of thyroid nodules which have resulted autonomously functioning at thyroid scintigraphy (TS). Methods: Seventy-eight patients with nodular goiter, no marker of autoimmunity and at least one AFTN at TS were selected and divided in: Group 1 (no.=25) with TSH>0.35 IU/l, and Group 2 (no.=53) with TSH≤0.35 IU/l. Results: In Group1 the mean nodule diameter was 19.8±9.4 mm; 12 nodules were isoechoic, 2 hyperechoic, and 11 hypoechoic. Vascular pattern was type I in 4, type II in 6 and type III in 15 nodules. In Group 2 the mean nodule diameter was 28.6±14.2 mm; 27 nodules were isoechoic, 9 hyperechoic and 17 hypoechoic. Vascular pattern was type I in 14, type II in 15 and type III in 24 nodules. Conclusion: In our study TSH alone was not able to identify AFTN in 32% of the patients. All hot nodules predominantly showed an isoechoic pattern with peri-intranodular vascularization; however, the presence of this pattern was not statistically significant. Moreover, we noticed a weak inverse correlation between the diameter of AFTN and TSH level. In conclusion, TS is the most sensitive tool to detect AFTN, allowing a precocious diagnosis even in the presence of a normal TSH value.

Determining the appropriate time of execution of an I-131 post-therapy whole-body scan: comparison between early and late imaging.

ObjectiveThe aim of this study was to investigate the appropriate time for performing an iodine-131 post-therapy whole-body scan (TxWBS) through a qualitative and semiquantitative analysis of early and late scans. Materials and methodsThis study evaluated pairs of scans of 134 patients who underwent TxWBS on the third and seventh day. The scans were analyzed to evaluate sites, intensity of uptake, concordance or discordance between the scans, relationship with risk factors, and serum thyroglobulin (Tg) levels. To evaluate early and late radioiodine kinetics in thyroid remnants and metastases, 65/134 pairs of scans (48.5%) were subjected to a semiquantitative analysis. ResultsThe early and late scans furnished concordant images in 108/134 patients (80.5%). In 10/134 patients (7.5%), early scans provided more information compared with late scans, showing lymph node and distant metastases in seven and three patients, respectively. In 16/134 patients (12%), late scans provided more data compared with early scans, with thyroid remnants and lymph node and distant metastases demonstrated in four, seven, and five patients, respectively. Negative early/positive late TxWBS results in patients were found to be significantly correlated (P=0.007) with elevated serum levels of Tg and a high-risk for recurrence (P=0.003). ConclusionThis study suggests that in about 20% of patients early or late TxWBS can miss the visualization of thyroid remnants or lymph node or distant metastases, which can be achieved performing both studies. High-risk patients with elevated serum Tg levels should be considered for a late TxWBS, which can demonstrate a possible metastatic involvement that was not diagnosed or that was downstaged by early TxWBS.