Radiomics in pancreatic neuroendocrine tumors: methodological issues and clinical significance.

PURPOSE: To present the state-of-art of radiomics in the context of pancreatic neuroendocrine tumors (PanNETs), with a focus on the methodological and technical approaches used, to support the search of guidelines for optimal applications. Furthermore, an up-to-date overview of the current clinical applications of radiomics in the field of PanNETs is provided. METHODS: Original articles were searched on PubMed and Science Direct with specific keywords. Evaluations of the selected studies have been focused mainly on (i) the general radiomic workflow and the assessment of radiomic features robustness/reproducibility, as well as on the major clinical applications and investigations accomplished so far with radiomics in the field of PanNETs: (ii) grade prediction, (iii) differential diagnosis from other neoplasms, (iv) assessment of tumor behavior and aggressiveness, and (v) treatment response prediction. RESULTS: Thirty-one articles involving PanNETs radiomic-related objectives were selected. In regard to the grade differentiation task, yielded AUCs are currently in the range of 0.7-0.9. For differential diagnosis, the majority of studies are still focused on the preliminary identification of discriminative radiomic features. Limited information is known on the prediction of tumors aggressiveness and of treatment response. CONCLUSIONS: Radiomics is recently expanding in the setting of PanNETs. From the analysis of the published data, it is emerging how, prior to clinical application, further validations are necessary and methodological implementations require optimization. Nevertheless, this new discipline might have the potential in assisting the current urgent need of improving the management strategies in PanNETs patients.

Decommissioning procedures for an 11 MeV self-shielded medical cyclotron after 16 years of working time.

The present article describes the decommissioning of a compact, self-shielded, 11 MeV medical cyclotron. A Monte Carlo simulation of the possible nuclear reactions was performed in order to plan the decommissioning activities. In the course of the cyclotron dismantling, cyclotron components, shields, and floor concrete samples were measured. Residual activities were analyzed with a Ge(Li) detector and compared with simulation data. Doses to staff involved in the decommissioning procedure were monitored by individual TL dosimeters. The simulations identified five radioactive nuclides in shields and floor concrete: 55Fe and 45Ca (beta emitters, total specific activity: 2.29 x 10(4) Bq kg) and 152Eu, 154Eu, 60Co (gamma emitters, total specific activity: 1.62 x 10(3) Bq kg-1). Gamma-ray spectrometry confirmed the presence of gamma emitters, corresponding to a total specific activity of 3.40 x 10(2) Bq kg-1. The presence of the radioisotope 124Sb in the lead contained in the shield structure, corresponding to a simulated specific activity of 9.38 x 10(3) Bq kg-1, was experimentally confirmed. The measured dose from external exposure of the involved staff was <20 muSv, in accordance with the expected range of values between 10 and 20 muSv. The measured dose from intake was negligible. Finally, the decommissioning of the 11 MeV cyclotron does not represent a risk for the involved staff, but due to the presence of long-lived radioisotopes, the cyclotron components are to be treated as low level radioactive waste and stored in an authorized storage area.

Symptom-limited exercise testing causes sustained diastolic dysfunction in patients with coronary disease and low effort tolerance.

Exercise stress testing is routinely used for the noninvasive assessment of coronary artery disease and is considered a safe procedure. However, the provocation of severe ischemia might potentially cause delayed recovery of myocardial function. To investigate the possibility that maximal exercise testing could induce prolonged impairment of left ventricular function, 15 patients with angiographically proved coronary disease and 9 age-matched control subjects with atypical chest pain and normal coronary arteries were studied. Radionuclide ventriculography was performed at rest, at peak exercise, during recovery and 2 and 7 days after exercise. Ejection fraction, peak filling and peak emptying rates and left ventricular wall motion were analyzed. All control subjects had a normal exercise test at maximal work loads and improved left ventricular function on exercise. Patients developed 1 mm ST depression at 217 +/- 161 s at a work load of 70 +/- 30 W and a rate-pressure product of 18,530 +/- 4,465 mm Hg x beats/min. Although exercise was discontinued when angina or equivalent symptoms occurred, in all patients diagnostic ST depression (greater than or equal to 1 mm) developed much earlier than symptoms. Predictably, at peak exercise patients showed a decrease in ejection fraction and peak emptying and filling rates. Ejection fraction and peak emptying rate normalized within the recovery period, whereas peak filling rate remained depressed throughout recovery (p less than 0.002) and was still reduced 2 days after exercise (p less than 0.02). In conclusion, in patients with severe impairement of coronary flow reserve, maximal exercise may cause sustained impairement of diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo demonstration of insulin-receptor defect with 123I-labeled insulin and scintigraphic scanning in severe insulin resistance.

OBJECTIVE: Insulin-receptor function in humans is usually studied in vitro on readily available cells, e.g., erythrocytes and fibroblasts. Although these cells are not metabolically important targets for insulin action, information derived from them are often taken as representative of other tissues. The aim of this study was to investigate insulin receptors in vitro on erythrocytes and in vivo on one of the main insulin-target organs, the liver. RESEARCH DESIGN AND METHODS: A 16-yr-old girl affected by severe insulin resistance was identified. Insulin receptor binding was measured on the erythrocytes of the patient and of 6 nondiabetic volunteers. The biodistribution of 123I-labeled insulin was studied in vivo by scintigraphic scanning in the insulin-resistant patient and in 10 nondiabetic volunteers. RESULTS: Erythrocytes of this patient displayed a markedly reduced [125I]insulin binding. In vivo 123I-insulin biodistribution was characterized by lack of hormone uptake by the liver (4 vs. 21% of the injected dose in control subjects) contrasting with intense accumulation of radioactivity in the kidneys. CONCLUSIONS: Our studies show that defects of insulin binding can be directly demonstrated in vivo on liver receptors with a noninvasive technique with low radiotoxicity.

Imaging of the buffering effect of insulin antibodies in the autoimmune hypoglycemic syndrome.

Insulin autoimmune hypoglycemia is characterized by recurrent hypoglycemia and high levels of immunoreactive insulin in the presence of insulin autoantibodies. The mechanisms inducing hypoglycemia are largely unknown. An [123I]insulin scintigraphic scanning was performed to directly demonstrate the effect of antibodies on insulin biodistribution in one patient with this syndrome both before and after treatment. The patient had insulin autoantibodies IgG3 lambda, which had a single site dissociation constant (Kd = 10(-7) mol/L, by Scatchard analysis), a very fast dissociation rate of immune complexes, and a very rapid association of [125I]insulin. Insulin receptors on red blood cells were down-regulated. The [123I]insulin scintigraphic study imaged the buffering effect of antibodies on insulin bioavailability. [123I]Insulin was not removed from the blood, and no liver or kidney uptake of the hormone occurred. The frequency and severity of hypoglycemic episodes required treatment. Insulin antibody levels decreased and [123I]insulin biodistribution improved after treatment with plasmapheresis and prednisone. Improved hormone bioavailability was further evidenced by the reduction in the hypoglycemic delay after i.v. insulin from 90 min before any treatment to 60 min after plasmapheresis and 30 min after steroid administration. Glucose tolerance was normal after treatment. Plasmapheresis followed by steroid treatment can lower the insulin antibody concentration, abolish severe hypoglycemia, and improve insulin biodistribution and glucose tolerance in insulin autoimmune hypoglycemia.

Sequential assessment of regional cerebral blood flow, regional cerebral blood volume, and blood-brain barrier in focal cerebral ischemia: a case report.

Regional CBF (rCBF) and regional cerebral blood volume (rCBV) were evaluated by N,N,N'-trimethyl-N'-(2)-hydroxy-3-methyl-5-[123I]iodobenzyl-1, 3-propanediamine-2 HCl- and 99mTC-labeled red blood cells, respectively, and single-photon emission computerized tomography (SPECT) in a patient with focal cerebral ischemia. Sequential transmission computerized tomography (TCT) and SPECT functional data were compared with clinical findings to monitor the pathophysiological events occurring in stroke. A lack of correlation between rCBF-rCBV distributions and blood-brain barrier (BBB) breakdown was found in the acute phase. In the face of more prolonged alteration of BBB, as seen by TCT enhancement, a rapid evolution of transient phenomena such as luxury perfusion was shown by SPECT studies. Follow-up of the patient demonstrated a correlation between the neurological recovery and a parallel relative improvement of the cerebral perfusion.

Development of nonreducible technetium-99m(III) cations as myocardial perfusion imaging agents: initial experience in humans.

A series of 15 nonreducible technetium-99m(III) complexes of formula tr-[99mTcL(Y)2]+ has been prepared by a general synthetic route based on reductive addition of Y to the technetium-99m (99mTc) intermediate [99mTcL(O)]+. In these complexes, selected for potential use as myocardial imaging agents, L represents one of the two tetradentate Schiff base ligands N,N'-ethylenebis(acetylacetone iminato), (en), or N,N'-propylene-1,2-bis(acetylacetone iminato), (pn), while Y represents a monodentate phosphine, phosphite or isonitrile ligand as exemplified by P(CH3)3, P(OCH3)3 and CN-C(CH3)3. Of these 15 complexes, several with octanol/saline partition coefficients in the range 0.04-20 exhibit significant myocardial uptake in rats and dogs. Of these, none exhibit detectable myocardial washout, providing strong support for the hypothesis that myocardial washout occurs only for those 99mTc(III) cations that undergo in vivo reduction to the neutral 99mTc(II) form. Evaluation of the prototypical complex tr-[99mTc(en)(P(CH3)3)2]+ in seven normal volunteers and patients establishes that it is only a mediocre myocardial imaging agent in man.

Evaluation in dogs and humans of three potential technetium-99m myocardial perfusion agents.

The biodistribution of the three cationic 99mTc complexes [99mTc(TMP)6]+, [99mTc(POM-POM)3]+, and [99mTc(TBIN)6]+--where TMP represents trimethylphosphite, POM-POM represents 1,2-bis(dimethyoxyphosphino)ethane, and TBIN represents t-butylisonitrile--have been evaluated in humans and dogs. Each agent was studied in three normal volunteers at rest, while [99mTc(POM-POM)3]+ and [99mTc(TBIN)6]+ were each studied in one normal volunteer at exercise. Even though all three agents yield good myocardial images in dogs, none appear suitable for clinical use as myocardial perfusion imaging radiopharmaceuticals. In humans, [99mTc(TMP)6]+ and [99mTc(POM-POM)3]+ clear very slowly from the blood and provide myocardial images only several hours after injection. [99mTc(TBIN)6]+ clears rapidly from the blood, but accumulation in the lung obscures the myocardial image for the first hour after injection; at later times, activity in the liver and spleen masks the apical wall. These results correlate with the blood-binding properties of the three complexes. [99mTc(TMP)6]+ and [99mTc(POM-POM)3]+ bind tightly to the plasma of human blood, but not to the plasma of dog blood; [99mTc(TBIN)6]+ does not bind tightly to the plasma of either dog or human blood. Among the Tc(I) complexes studied to date in humans, [99mTc(TBIN)6]+ appears to be unique in biodistribution pattern, blood-binding properties, and the fact that exercise improves the ultimate myocardial image. All the Tc(I) complexes appear to undergo myocardial accumulation by a mechanism different from that utilized by Tc(III) complexes. Animal studies alone are not adequate to evaluate the potential utility of 99mTc cationic complexes for myocardial perfusion studies.

Comparison of dual-head coincidence PET versus ring PET in tumor patients.

UNLABELLED: This study compared the multiring detector (Ring-PET) and the dual-head coincidence imaging system (DH-PET) for staging/ restaging neoplastic patients before or after surgery or radiochemotherapy. METHODS: Seventy patients with suspected tumor recurrence or metastatic dissemination received an intravenous dose of 18F-fluorodeoxyglucose (FDG) under overnight fasting and were studied in sequence with a dedicated positron emission tomograph with Ring-PET and a DH-PET. Ring-PET studies were performed 45-75 min postinjection and were followed by a DH-PET scan approximately 3 h postinjection. Number and location of the hypermetabolic lesions detected on DH-PET and Ring-PET reconstructed images were blindly assessed by three independent observers. RESULTS: DH-PET identified all 14 head lesions detected by Ring-PET, 53 of 63 thoracic lesions and 36 of 45 abdominal lesions. Of the 19 lesions not identified by DH-PET, 6 were smaller than 10 mm, 8 were between 10 and 15 mm and 1 was 18 mm; dimensions of 4 bone lesions were not available. A concordant restaging, based on location and number of lesions detected, was found in all 14 patients with head tumors, in 28 of 30 patients with thoracic tumors and in 24 of 26 patients with abdominal tumors. CONCLUSION: We found a good agreement between Ring-PET and DH-PET assessment of oncologic patients in detecting hypermetabolic lesions > or = 10-15 mm.

99mTc-2GAM: a tracer for renal imaging.

We propose a renal imaging agent, the 99mTc complex of the bidentate-N,S chelate N-(mercaptoacetyl)glycine (99mTc-2GAM), with the imaging characteristics of 99mTc-DMSA but a faster kidney uptake; chemical evidence supports the formulation of 99mTc-2GAM as [Tc(v)(O)(GAM)2]-. After biodistribution and toxicity studies in animals, 99mTc-2GAM was evaluated in five normal volunteers. 99mTc-2GAM is rapidly cleared from the blood (t1/2 = 9 min) and 50% of the ID is excreted in the urine in the first 2 h. Dynamic data show a rapid renal uptake that increases up to 1 h with no significant wash-out between 1 and 8 h. The uptake in each kidney ranges from 11.3% to 20.7% ID. Low, stable liver uptake is observed. No significant activity is detected in other organs. We showed no differences between 99mTc-2GAM and 99mTc-DMSA compared in three patients with unilateral kidney disease. We conclude that 99mTc-2GAM has good practical and dosimetric features for renal imaging.

Lack of prognostic value of 99mTc MIBI rest, 18F FDG and 201TL rest/redistribution on PTCA outcome of patients with moderate left ventricle dysfunction.

BACKGROUND: The clinical work-out of patients undergoing coronary revascularization includes the assessment of myocardial viability. This approach has to be defined in the different classes of patients. The aim of this study was to evaluate the predictive prognostic value of different techniques on outcome following PTCA in patients with moderate left ventricle dysfunction (left ventricle EF > or = 40%). METHODS: Seventeen patients with EF > or = 40% and undergoing PTCA were studied by 201Tl rest/redistribution, 18F-FDG and 99mTc-MIBI rest. Regional kinesis was scored by echo, dividing left ventricle in 11 segments. The echo evaluation was repeated at 1 and 6 months after revascularization. RESULTS: Global EF was 52.5 +/- 7% and 69 segments had abnormal kinesis. Patients underwent stress/rest 99mTc-MIBI SPET, rest/redistribution 201Tl SPET and rest 18F-FDG PET. Among the 11 segments defined on echo-matched tomographic images, the one with the highest activity at stress was assumed as reference (activity = 100%). If > 50% of reference segment, 18F-FDG and 201Tl uptakes were considered significant. After PTCA, the echo-follow-up did not demonstrated significant improvement of left ventricle function at 30 days after PTCA (EF 56 +/- 6%) as well as at 6 months (EF 56 +/- 9%). The positive predictive value under these conditions resulted: 46.5% with 99mTc-MIBI rest, 47.4% with 201Tl rest-redistribution and 45.7% with 18F-FDG. CONCLUSIONS: In summary, in the class of patients with moderately compromised function, considering as reference the improved regional kinesis after PTCA, 99mTc-MIBI at rest, 201Tl rest/redistribution and 18F-FDG do not exhibit a clear predictive value; patient population is then a highly relevant point to establish the accuracy of these diagnostic procedures.

Insulin receptor antibodies inhibit insulin uptake by the liver: in vivo 123I-insulin scintigraphic scanning and in vitro characterization in autoimmune hypoglycemia.

BACKGROUND: Insulin receptor antibodies can induce severe hypoglycemia or insulin resistance in rare autoimmune syndromes. In vitro properties of these antibodies occasionally explain the clinical features of the syndrome, but direct evidence of their in vivo activity is poor. We studied a 58-year-old male with rheumatoid arthritis who presented with hypoglycemic coma. METHODS AND RESULTS: Antibodies were detected by inhibition of 125I-insulin binding to human insulin receptor-3T3 cells by the patient's serum. By immunofluorescence, they were immunoglobulin G of all four subclasses, immunoprecipitated insulin receptors from biotin-labeled cells, and triggered phosphorylation of the beta subunit of the insulin receptor. Insulin binding on the patient's red blood cells was markedly reduced. A biodistribution study after intravenous 123I-Tyr A14 insulin showed a marked inhibition of tracer uptake by the liver, reaching 10% of the injected dose (controls, mean +/- SD, 21.1 +/- 1.7%; n = 10). Time activity curves generated on the liver and on the heart were parallel, with a T1/2 of 11.5 minutes for both, suggesting that no specific uptake occurred in the liver, where tracer activity represented only the blood pool. Clearance of insulin from the blood was indeed slower than in controls and mainly occurred through the kidneys. Analysis of plasma 123I-insulin immunoreactivity and trichloroacetic acid precipitate showed that insulin degradation did not occur as in normal controls. CONCLUSIONS: In this patient with hypoglycemic syndrome, insulin receptor antibodies with in vitro insulin-like activity are capable of blocking in vivo the access of insulin to the liver receptor compartment, as directly demonstrated by the markedly altered biodistribution of intravenously injected 123I-insulin.

99Tcm-MIBI single photon emission tomography (SPET) for detecting myocardial ischaemia and necrosis in patients with significant coronary artery disease.

The ability of 99Tcm-methoxyisobutylisonitrile (MIBI) single photon emission tomography (SPET) to detect myocardial ischaemia and necrosis was assessed in 56 patients (45 male, 11 female, aged 55 +/- 5 years), with clinically recognized ischaemic heart disease (IHD). All underwent coronary angiography (CA) and left ventriculography (LV). SPET images were obtained at rest and at peak exercise (Modified Bruce) 90 min after injection of 99Tcm-MIBI (650-850 MBq). Data were acquired in 30 min over 180 degrees (from 45 degrees RAO to 45 degrees LPO) with no correction for attenuation, using a 64 x 64 matrix. The presence of persistent (P) or reversible (R) perfusion defects (PD) was then correlated to the resting and exercise ECG and to the results of CA and LV. Of the 56 patients, 34 had reversible underperfusion (RPD), 46 persistent underperfusion (PPD) and 31 had both. The occurrence of RPD correlated well with the occurrence of exercise-induced ST segment depression and/or angina (27 patients of 34 patients, 79%) and with the presence of significant coronary artery disease (CAD) (33 of 44, 73%). In 45 of 46 patients (98%) PPD corresponded to akinetic or severely hypokinetic segments (LV) usually explored by ECG leads exhibiting diagnostic Q waves (42 of 46 patients, 91%). The scan was normal both at rest and after stress in four of 11 patients with no CAD, and in two of 45 patients with CAD. Finally, an abnormal resting scan was seen in seven of 11 patients with normal coronary arteries, of whom six had regional wall motion abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of SPECT and PET cardiac images by a surface matching registration technique.

Complementary information provided by Single Photon and Positron Emission Tomography (SPECT and PET) in nuclear cardiology allows a better comprehension of the physiopathology of the heart. In this work a surface matching registration technique is evaluated in the spatial correlation of SPECT and PET cardiac images. The method is based on matching correspondent anatomical surfaces extracted from transmission (TR) SPECT and PET studies, usually performed for attenuation correction. The accuracy of the technique was evaluated by phantom experiments and on patient data (201Tl SPECT and 13NH3 PET perfusion studies). An application of the method is presented for the correlation of SPECT 201Tl perfusion and PET 18FDG metabolic studies in the evaluation of myocardial viability.

Acetylcysteine therapy for chronic hepatitis C: are its effects synergistic with interferon alpha? A pilot study.

OBJECTIVE: This trial reports the 6-month results of a pilot study using lymphoblastoid interferon alpha (IFNalpha) and acetylcysteine (N-acetylcysteine) separately and in combination in patients with chronic hepatitis C, genotype 1b, who were nonresponders to previous treatment with recombinant IFNalpha alone. PATIENTS AND METHODS: 21 patients were randomly divided into three groups of seven each. Group A was treated with lymphoblastoid IFNalpha 6MU three times a week for 6 months; group B received the same schedule of lymphoblastoid IFNalpha as group A plus acetylcysteine 1200 mg/day per os in two administrations, and group C received only acetylcysteine 1200 mg/day per os in two administrations. RESULTS: Mean serum alanine aminotransferase (ALT) levels at 6 months in groups A and B, but not in group C, were significantly lower than baseline values (p < 0.05 and p < 0.03, respectively). Two patients in group A (28.6%) and three in group B (42.9%), but none in group C, had normalised ALT levels at 6 months. During follow-up, levels flared in one group A and in one group B patient. Thus, at the end of follow-up one group A and two group B patients were sustained responders. At the end of therapy and follow-up, hepatitis C virus (HCV)-RNA was negative in one patient in group A and two patients in group B. As no serious adverse effects were observed, therapy was never interrupted or suspended. CONCLUSION: Acetylcysteine alone had no effect on hepatic cytolysis and viral replication; lymphoblastoid IFNalpha showed a modest, but better, response than recombinant IFNalpha, and the combination therapy, although in a limited number of patients, appeared to be more efficient than lymphoblastoid IFNalpha alone.

[Neoplastic transformation of oral lichen planus. I: Review of the literature]. / La cancerizzazione del lichen planus orale. I: Revisione della letteratura.

Lichen planus is described like a well-characterized dermatological condition affecting the skin and the oral and genital mucosa. Over the years, different authors have expressed the possible oral lichen planus premalignant nature, but this is still controversial. This criticism is due to the insufficiency of the clinical and histopathological data to support the initial diagnosis of oral lichen planus, the occurrence of some wrong diagnostic criteria for this pathology, the contemporary presence in the same region of the oral lichen planus lesions and of neoplasia. The malignant transformation of oral lichen planus rate varies, according to authors, from 0.4 to 3.7%. The aim of this study is to review the literature from 1910 to 1999, focusing on the suggested possible premalignant nature of oral lichen planus.

[Neoplastic transformation of oral lichen planus. II: association with risk co-factors]. / La cancerizzazione del lichen planus orale. II: Associazione con co-fattori di rischio.

The possible malignant transformation of oral lichen planus is still controversial. It is not clear if this is in fact due to the premalignant nature of oral lichen planus or to the presence of some risk-factors in patients with this pathology. The risk co-factors that may he involved in this malignant transformation are numerous. Some authors suggested a correlation between oral lichen planus and HCV or HGV, or with the presence of some oncogenic viruses (EBV, HSV, HPV). Cases of this malignant transformation on oral and genital mucosa with lichen are reported, hut none on the skin lesions. The aim of this study is to investigate, through the literature, these correlations that may have a role in the malignant transformation of oral lichen planus.

[Gingival hypertrophy due to cyclosporine. A clinico-statistical study in 82 patients]. / Ipertrofia gengivale da ciclosporina. Indagine clinico-statistica in 82 pazienti.

Eighty-two patients were observed at the Dental Department at Parma University. Seventy-six of them had renal transplant and 6 liver transplant. They were in immunosuppressive therapy with cyclosporina, 42 of them were also in calcium antagonist therapy. Gingival hypertrophy was observed in 52 subjects (63.4%) 25 (30%) patients underwent surgical operation, 6 of them (24%) showed a relapse about 3 months after the first operation. Clinical data were measured in accordance with 5 indicators: the level of oral hygiene, cyclosporinemia, contemporaneous use of calcium antagonist, the duration of therapy and the DMF index. By the results obtained, it's possible to suppose that the gravity of the disease is related to the contemporaneous use of calcioantagonist, but it wasn't highly significant (p < 0.05). The degree of oral hygiene was decidedly in relation to the most severe forms of gingival hyperplasia (grade 2-3), (p < 0.001). No relation was found for the duration of therapy, distribution of the DMF index and the level of drugs in the blood.

[Burning mouth syndrome. Clinical experience with 75 patients]. / Burning mouth syndrome. Esperienza clinica in 75 pazienti.

The burning mouth syndrome (BMS) is a very common disorder frequently seen in practical dentistry. It is a particular condition with a complex of strange burning sensation localized in the oral mucosa which is clinically normal. It is very important for the dentist to recognize and classify this particular syndrome in order to exclude other factors which can cause the same symptoms. On the basis of personal experience on 75 patients, the complex management of this particular group of patients has been evaluated to make a right diagnosis and a correct treatment.

[The effects of drugs on the oral cavity]. / Effetti delle droghe sul cavo orale.

As shown by the growing numbers of users attending the public drug addiction services, drug abuse is a phenomenon that is constantly spreading. It is important that dentists are aware of the oral problems linked to drug abuse. This study examines the general effects and oral implications of the illegal substances used by the majority of drug addicts. The main dental complications of cannabinoids are the increased incidence of squamous cell carcinomas of the oral cavity, the presence of xerostomia and severe gingivitis. Depending on how it is taken, cocaine may cause ischemic necrosis of the palate, inflammation, ulceration and gingival retraction, as well as an increased incidence of bruxism. Hallucinogens have few direct oral effects, but among these it is worth recalling xerostomia, increased bruxism and oral problems linked to malnutrition caused by ecstasy. Turning to the opioids, heroin is the drug primarily used by the majority of drug addicts. Its oral effects mainly take the form of dental decay, showing a particular form and extent linked either directly or indirectly to heroin use. This results in "typical" or "atypical" caries pathologies directly linked to the effects of heroin. Given the extent of this phenomenon, it is important that dentists are aware of the problems linked to drug abuse that they may have to treat.