Network alterations in temporal lobe epilepsy during non-rapid eye movement sleep and wakefulness.

OBJECTIVE: Investigate sleep and temporal lobe epilepsy (TLE) effects on brain networks derived from electroencephalography (EEG). METHODS: High-density EEG was recorded during non-rapid eye movement (NREM) sleep stage 2 (N2) and wakefulness in 23 patients and healthy controls (HC). Epochs without epileptic discharges were source-reconstructed in 72 brain regions and connectivity was estimated. We calculated network integration and segregation at global (global efficiency, GE; average clustering coefficient, avgCC) and hemispheric level. These were compared between groups across frequency bands and correlated with the individual proportion of wakefulness- or sleep-related seizures. RESULTS: At the global level, patients had higher delta GE, delta avgCC and theta avgCC than controls, irrespective of the vigilance state. During wakefulness, theta GE of patients was higher than controls and, for patients, theta GE during wakefulness was higher than during N2. Wake-to-sleep differences in TLE were notable only in the ipsilateral hemisphere. Only measures from wakefulness recordings correlated with the proportion of wakefulness- or sleep-related seizures. CONCLUSIONS: TLE network alterations are more prominent during wakefulness and at lower frequencies. Increased integration and segregation suggest a pathological 'small world' configuration with a possible inhibitory role. SIGNIFICANCE: Network alterations in TLE occur and are easier to detect during wakefulness.

Cervical pessary for preterm birth prevention after an episode of arrested preterm labor: a retrospective cohort study with targeted maximum likelihood estimation of the average treatment effect.

OBJECTIVE: To evaluate whether cervical pessary effectively reduces the preterm birth < 37 weeks rate in patients who have not delivered after an episode of arrested preterm labor. PATIENTS AND METHODS: Retrospective cohort study was conducted on singleton pregnant patients admitted to our institution between January 2016 and June 2021 for threatened preterm labor and who had a cervical length < 25 mm. Women in whom a cervical pessary was placed were considered as exposed, while women in whom expectant management was preferred were considered as unexposed. The primary outcome was the rate of preterm birth before 37 weeks. A targeted maximum likelihood estimation was used to estimate the average treatment effect of cervical pessary by adjusting for a-priori-defined confounders. RESULTS: A cervical pessary was placed in 152 (36.6%) patients (exposed), while the remaining 263 (63.4%) were managed expectantly (unexposed). The adjusted average treatment effect was -14% (-18 to -11%), -17% (-20 to -13%), and -16% (-20 to -12%) for preterm birth < 37 weeks, < 34 weeks, and < 32 weeks, respectively. The average treatment effect for adverse neonatal outcomes was -7% (-8 to -5%). No difference in gestational weeks at delivery between exposed and unexposed emerged when gestational age at first admission was > 30.1 gestational weeks. CONCLUSIONS: The positioning of a cervical pessary placement may be evaluated to reduce the risk of a subsequent preterm birth after an episode of arrested preterm labor in pregnant patients with onset of symptoms before 30 gestational weeks.

Practice variation in the diagnosis of acute rejection among pediatric heart transplant centers: An analysis of the pediatric heart transplant society (PHTS) registry.

BACKGROUND: Freedom from rejection in pediatric heart transplant recipients is highly variable across centers. This study aimed to assess the center variation in methods used to diagnose rejection in the first-year post-transplant and determine the impact of this variation on patient outcomes. METHODS: The PHTS registry was queried for all rejection episodes in the first-year post-transplant (2010-2019). The primary method for rejection diagnosis was determined for each event as surveillance biopsy, echo diagnosis, or clinical. The percentage of first-year rejection events diagnosed by surveillance biopsy was used to approximate the surveillance strategy across centers. Methods of rejection diagnosis were described and patient outcomes were assessed based on surveillance biopsy utilization among centers. RESULTS: A total of 3985 patients from 56 centers were included. Of this group, 873 (22%) developed rejection within the first-year post-transplant. Surveillance biopsy was the most common method of rejection diagnosis (71.7%), but practices were highly variable across centers. The majority (73.6%) of first rejection events occurred within 3-months of transplantation. Diagnosis modality in the first-year was not independently associated with freedom from rejection, freedom from rejection with hemodynamic compromise, or overall graft survival. CONCLUSIONS: Rejection in the first-year after pediatric heart transplant occurs in 22% of patients and most commonly in the first 3 months post-transplant. Significant variation exists across centers in the methods used to diagnose rejection in pediatric heart transplant recipients, however, these variable strategies are not independently associated with freedom from rejection, rejection with hemodynamic compromise, or overall graft survival.

Enrichment of Autotrophic Denitrifiers From Anaerobic Sludge Using Sulfurous Electron Donors.

This study compared the rates and microbial community development in batch bioassays on autotrophic denitrification using elemental sulfur (S0), pyrite (FeS2), thiosulfate (S2O3 2-), and sulfide (S2-) as electron donor. The performance of two inocula was compared: digested sludge (DS) from a wastewater treatment plant of a dairy industry and anaerobic granular sludge (GS) from a UASB reactor treating dairy wastewater. All electron donors supported the development of a microbial community with predominance of autotrophic denitrifiers during the enrichments, except for sulfide. For the first time, pyrite revealed to be a suitable substrate for the growth of autotrophic denitrifiers developing a microbial community with predominance of the genera Thiobacillus, Thioprofundum, and Ignavibacterium. Thiosulfate gave the highest denitrification rates removing 10.94 mM NO3 - day-1 and 8.98 mM NO3 - day-1 by DS and GS, respectively. This was 1.5 and 6 times faster than elemental sulfur and pyrite, respectively. Despite the highest denitrification rates observed in thiosulfate-fed enrichments, an evaluation of the most relevant parameters for a technological application revealed elemental sulfur as the best electron donor for autotrophic denitrification with a total cost of 0.38 € per m3 of wastewater treated.

Modulation of epileptic networks by transient interictal epileptic activity: A dynamic approach to simultaneous EEG-fMRI.

Epileptic networks, defined as brain regions involved in epileptic brain activity, have been mapped by functional connectivity in simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) recordings. This technique allows to define brain hemodynamic changes, measured by the Blood Oxygen Level Dependent (BOLD) signal, associated to the interictal epileptic discharges (IED), which together with ictal events constitute a signature of epileptic disease. Given the highly time-varying nature of epileptic activity, a dynamic functional connectivity (dFC) analysis of EEG-fMRI data appears particularly suitable, having the potential to identify transitory features of specific connections in epileptic networks. In the present study, we propose a novel method, defined dFC-EEG, that integrates dFC assessed by fMRI with the information recorded by simultaneous scalp EEG, in order to identify the connections characterised by a dynamic profile correlated with the occurrence of IED, forming the dynamic epileptic subnetwork. Ten patients with drug-resistant focal epilepsy were included, with different aetiology and showing a widespread (or multilobar) BOLD activation, defined as involving at least two distinct clusters, located in two different lobes and/or extended to the hemisphere contralateral to the epileptic focus. The epileptic focus was defined from the IED-related BOLD map. Regions involved in the occurrence of interictal epileptic activity; i.e., forming the epileptic network, were identified by a general linear model considering the timecourse of the fMRI-defined focus as main regressor. dFC between these regions was assessed with a sliding-window approach. dFC timecourses were then correlated with the sliding-window variance of the IED signal (VarIED), to identify connections whose dynamics related to the epileptic activity; i.e., the dynamic epileptic subnetwork. As expected, given the very different clinical picture of each individual, the extent of this subnetwork was highly variable across patients, but was but was reduced of at least 30% with respect to the initially identified epileptic network in 9/10 patients. The connections of the dynamic subnetwork were most commonly close to the epileptic focus, as reflected by the laterality index of the subnetwork connections, reported higher than the one within the original epileptic network. Moreover, the correlation between dFC timecourses and VarIED was predominantly positive, suggesting a strengthening of the dynamic subnetwork associated to the occurrence of IED. The integration of dFC and scalp IED offers a more specific description of the epileptic network, identifying connections strongly influenced by IED. These findings could be relevant in the pre-surgical evaluation for the resection or disconnection of the epileptogenic zone and help in reaching a better post-surgical outcome. This would be particularly important for patients characterised by a widespread pathological brain activity which challenges the surgical intervention.

The network integration of epileptic activity in relation to surgical outcome.

OBJECTIVE: Epilepsy is a network disease with epileptic activity and cognitive impairment involving large-scale brain networks. A complex network is involved in the seizure and in the interictal epileptiform discharges (IEDs). Directed connectivity analysis, describing the information transfer between brain regions, and graph analysis are applied to high-density EEG to characterise networks. METHODS: We analysed 19 patients with focal epilepsy who had high-density EEG containing IED and underwent surgery. We estimated cortical activity during IED using electric source analysis in 72 atlas-based cortical regions of the individual brain MRI. We applied directed connectivity analysis (information Partial Directed Coherence) and graph analysis on these sources and compared patients with good vs poor post-operative outcome at global, hemispheric and lobar level. RESULTS: We found lower network integration reflected by global, hemispheric, lobar efficiency during the IED (p < 0.05) in patients with good post-surgical outcome, compared to patients with poor outcome. Prediction was better than using the IED field or the localisation obtained by electric source imaging. CONCLUSIONS: Abnormal network patterns in epilepsy are related to seizure outcome after surgery. SIGNIFICANCE: Our finding may help understand networks related to a more "isolated" epileptic activity, limiting the extent of the epileptic network in patients with subsequent good post-operative outcome.

Inhibition in the somatosensory system: An integrative neuropharmacological and neuroimaging approach.

The presented study investigates the functional role of GABA in somatosensory processing, using a combined neuropharmacological-neuroimaging approach. Three different GABA agonists (GABAA: alprazolam, ethanol; GABAB: baclofen) were investigated in a double blind cross-over design in 16 male participants, accomplishing a tactile perception task. Somatosensory evoked magnetic fields modulated by GABAR-agonists and placebo were recorded using whole-head magnetoencephalography. Peak latencies and amplitudes of primary (SI) and secondary (SII) somatosensory cortex source activities confirmed the previously reported role of GABA as a modulator of somatosensory processing. Significant inhibitory effects on the latency of SII and on the amplitude of SI and SII were found exclusively for alprazolam, a positive allosteric modulator at GABAA receptors. The GABAB agonist baclofen did not have any modulatory effect. Moreover, we investigated whether the observed effects of alprazolam on the level of SII were explainable by the mere propagation of activity from SI to SII modulated by GABAA receptors, independently from any further GABAA-mediated inhibition in SII. By estimating the transfer function between SI and SII activation under placebo conditions, we were able to predict SII activity for the administration of GABA receptors agonists under the assumption that GABA exclusively acts at the level of SI. By comparing measured and predicted data, we propose a model in which the initial activation of SI is modulated through GABAA receptors and subsequently propagated to SII, without any significant further inhibition. In addition, initial GABAA effects in SI appear to be strongly potentiated with time, selectively in SI but not in SII.

Estimating EEG Source Dipole Orientation Based on Singular-value Decomposition for Connectivity Analysis.

In the last decade, the use of high-density electrode arrays for EEG recordings combined with the improvements of source reconstruction algorithms has allowed the investigation of brain networks dynamics at a sub-second scale. One powerful tool for investigating large-scale functional brain networks with EEG is time-varying effective connectivity applied to source signals obtained from electric source imaging. Due to computational and interpretation limitations, the brain is usually parcelled into a limited number of regions of interests (ROIs) before computing EEG connectivity. One specific need and still open problem is how to represent the time- and frequency-content carried by hundreds of dipoles with diverging orientation in each ROI with one unique representative time-series. The main aim of this paper is to provide a method to compute a signal that explains most of the variability of the data contained in each ROI before computing, for instance, time-varying connectivity. As the representative time-series for a ROI, we propose to use the first singular vector computed by a singular-value decomposition of all dipoles belonging to the same ROI. We applied this method to two real datasets (visual evoked potentials and epileptic spikes) and evaluated the time-course and the frequency content of the obtained signals. For each ROI, both the time-course and the frequency content of the proposed method reflected the expected time-course and the scalp-EEG frequency content, representing most of the variability of the sources (~ 80%) and improving connectivity results in comparison to other procedures used so far. We also confirm these results in a simulated dataset with a known ground truth.

Multi analytical technique study of human bones from an archaeological discovery.

In 1953, during the building restoration of San Michele church (Bono, Sardinia, 16th-19th Century), a high number of disarticulated skeletons were recovered. From a group of 412 hip bones, two of these, affected by several pathological lesions, were analysed. The two coxal bones can be referred to the same individual, an adult man. A multi-analytical study, started with the purpose of investigating the bone pathology, was extended to characterize the mineral components of a large representative set of bones from the same ossuary, all attributed to adult men who lived in the region four-two centuries ago. A quantitative ICP-AES analysis for Ca, Fe, Mg, Mn, Na, Pb and Zn was executed, and a chemometric investigation on the results was performed. This approach gave evidence of the effects of diagenesis, allowed some hypothesis of the incidence of the known dietary habits on bone composition, and completely differentiated the pathological bones from those of a normal population on the basis of the mineral composition. Moreover, porosity, crystallinity and FT-IR analysis were conducted on both non- and pathological sample.

Oxytocin nasal spray in fibromyalgic patients.

Fibromyalgia is a pain disorder associated with frequent comorbid mood, anxiety, and sleep disorders. Despite the frequent use of a complex, poly-drug pharmacotherapy, treatment for fibromyalgia is of limited efficacy. Oxytocin has been reported to reduce the severity of pain, anxiety, and depression, and improve the quality of sleep, suggesting that it may be useful to treat fibromyalgia. To evaluate this hypothesis, 14 women affected by fibromyalgia and comorbid disorders, assuming a complex pharmacotherapy, were enrolled in a double-blind, crossover, randomized trial to receive oxytocin and placebo nasal spray daily for 3 weeks for each treatment. Order of treatment (placebo-oxytocin or oxytocin-placebo) was randomly assigned. Patients were visited once a week. At each visit, the following instruments were administered: an adverse drug reaction record card, Visual Analog Scale of Pain Intensity, Spielberger State Anxiety Inventory, Zung Self-rating Depression Scale, and SF-12. Women self-registered painkiller assumption, pain severity, and quality of sleep in a diary. Unlikely, oxytocin nasal spray (80 IU a day) did not induce positive therapeutic effects but resulted to be safe, devoid of toxicity, and easy to handle.

Mesenchymal stem cell interaction with a non-woven hyaluronan-based scaffold suitable for tissue repair.

The fabrication of biodegradable 3-D scaffolds enriched with multipotent stem cells seems to be a promising strategy for the repair of irreversibly injured tissues. The fine mechanisms of the interaction of rat mesenchymal stem cells (rMSCs) with a hyaluronan-based scaffold, i.e. HYAFF(R)11, were investigated to evaluate the potential clinical application of this kind of engineered construct. rMSCs were seeded (2 x 10(6) cells cm(-2)) on the scaffold, cultured up to 21 days and analysed using appropriate techniques. Light (LM), scanning (SEM) and transmission (TEM) electron microscopy of untreated scaffold samples showed that scaffolds have a highly porous structure and are composed of 15-microm-thick microfibres having a rough surface. As detected by trypan blue stain, cell adhesion was high at day 1. rMSCs were viable up to 14 days as shown by CFDA assay and proliferated steadily on the scaffold as revealed by MTT assay. LM showed rMSCs in the innermost portions of the scaffold at day 3. SEM revealed a subconfluent cell monolayer covering 40 +/- 10% of the scaffold surface at day 21. TEM of early culture showed rMSCs wrapping individual fibres with regularly spaced focal contacts, whereas confocal microscopy showed polarized expression of CD44 hyaluronan receptor; TEM of 14-day cultures evidenced fibronexus formation. Immunohistochemistry of 21-day cultures showed that fibronectin was the main matrix protein secreted in the extracellular space; decorin and versican were seen in the cell cytoplasm only and type IV collagen was minimally expressed. The expression of CD90, a marker of mesenchymal stemness, was found unaffected at the end of cell culture. Our results show that HYAFF(R)11 scaffolds support the adhesion, migration and proliferation of rMSCs, as well as the synthesis and delivery of extracellular matrix components under static culture conditions without any chemical induction. The high retention rate and viability of the seeded cells as well as their fine modality of interaction with the substrate suggest that such scaffolds could be potentially useful when wide tissue defects are to be repaired as in the case of cartilage repair, wound healing and large vessel replacement.

[Comparison among ecography, scintigraphy and surgery in the localization of parathyroid glands in uremic patients undergoing parathyroidectomy]. / Confronto tra ecografia, scintigrafia e chirurgia nella localiz- zazione delle ghiandole paratiroidi nei pazienti uremici in dialisi sottoposti a paratiroidectomia.

BACKGROUND: Sensitivity and specificity of the most widely employed techniques of parathyroid glands localization, namely echography and scintigraphy, are mostly obtained with short-term follow-up data and do not underline the existence of a methodological problem. As a matter of fact, both methods identify only pathological glands, with no "normal" results; therefore "true negatives" cannot be obtained. Aim of our study was to compare, by means of a statistically appropriate approach, the results of echography, scintigraphy and surgery with the data obtained after a mid term follow-up period, enabling us to discover all parathyroid glands. METHODS: Twenty six consecutive dialysis patients (14M/12F; age 50+/-12 years) underwent echography and scintigraphy immediately before a total parathyroidectomy with autotransplantation and were followed-up for 6 months to recognize all the existing glands (PTH levels and scintigraphy). RESULTS: Total identified glands were: 73 by scintigraphy, 86 by echography, 99 by surgery and 103 by follow-up data. The concordance indexes (K0) between the number of glands effectively present in the individual patient (follow-up data) and those identified with each method were rather low with scintigraphy (0.071) and echography (0.218), and acceptable (0.578) with surgery. The number of patients correctly classified was: 9/26 (34,6%) with scintigraphy, 13/26 (50%) with echography and 22/26 (85%) with surgery. Finally, the number of wrongly identified glands (from zero to three) in each patient was similar with scintigraphy (65,4%) and echography (50%) and significantly better with surgery (15,6%; p<0.01). CONCLUSIONS: The most reliable technique to identify parathyroid glands in uremic subjects is surgery, nonetheless a meticulous clinical follow-up is necessary to recognize all of them.

Ventricular arrhythmia in the X-linked cardiomyopathy Barth syndrome.

Barth syndrome is an X-linked disorder characterized by dilated cardiomyopathy, cyclic neutropenia, skeletal myopathy, abnormal mitochondria, and growth deficiency. The primary defect is a mutation in the TAZ gene on the X chromosome at Xq28, resulting in abnormal phospholipid biosynthesis and cardiolipin deficiency. To date, there has been no systematic evaluation of the cardiac phenotype. We report five cases of cardiac arrest and/or placement of an internal cardiac defibrillator with documented ventricular arrhythmia. We suggest that ventricular arrhythmia is part of the primary phenotype of the disorder and that patients should be screened accordingly.

The FLUKA code: new developments and application to 1 GeV/n iron beams.

The modeling of ion transport and interactions in matter is a subject of growing interest, driven by the continuous increase of possible application fields. These include hadron therapy, dosimetry, and space missions, but there are also several issues involving fundamental research, accelerator physics, and cosmic ray physics, where a reliable description of heavy ion induced cascades is important. In the present work, the capabilities of the FLUKA code for ion beams will be briefly recalled and some recent developments presented. Applications of the code to the simulation of therapeutic carbon, nitrogen and oxygen ion beams, and of iron beams, which are of direct interest for space mission related experiments, will be also presented together with interesting consideration relative to the evaluation of dosimetric quantities. Both applications involve ion beams in the AGeV range.

Slow sodium channel inactivation and use-dependent block modulated by the same domain IV S6 residue.

Voltage- and/or conformation-dependent association and dissociation of local anesthetic-class drugs from a putative receptor site in domain IV S6 of the sodium channel and slow conformation transitions of the drug-associated channel have been proposed as mechanisms of use- and frequency-dependent reduction in sodium current. To distinguish these possibilities, we have explored the reactivity to covalent modification by thiols and block of the mutations F1760C and F1760A at the putative receptor site of the cardiac sodium channel expressed as stable cell lines in HEK-293 cells. Both mutations decreased steady-state fast inactivation, shifting V1/2h from -86 +/- 1.3 mV (WT) to -72.3 +/- 1.4 mV (F1760C) and -67.7 +/- 1 mV (F1760A). In the absence of drug, the F1760C mutant channel displayed use-dependent current reduction during pulse-train stimulation, and faster onset of slow inactivation. This mutant also retained some sensitivity to lidocaine. In contrast, the F1760A mutant showed no use-dependent current reduction or sensitivity to lidocaine. The covalent-modifying agent MTS-ET enhanced use-dependent current reduction of the F1760C mutant channel only. The use-dependent reduction in current of the covalently modified channel completely recovered with rest. Lidocaine produced no additional block during exposure to MTS-ET-treated cells (MTS-ET 43 +/- 2.7%: MTS-ET lidocaine 47 +/- 4.5%), implying interaction at a common binding site. The data suggest that use-dependent binding at the F1760 site results in enhanced slow inactivation rather than alteration of drug association and dissociation from that site and may be a general mechanism of action of sodium-channel blocking agents.

The FLUKA code for space applications: recent developments.

The FLUKA Monte Carlo transport code is widely used for fundamental research, radioprotection and dosimetry, hybrid nuclear energy system and cosmic ray calculations. The validity of its physical models has been benchmarked against a variety of experimental data over a wide range of energies, ranging from accelerator data to cosmic ray showers in the earth atmosphere. The code is presently undergoing several developments in order to better fit the needs of space applications. The generation of particle spectra according to up-to-date cosmic ray data as well as the effect of the solar and geomagnetic modulation have been implemented and already successfully applied to a variety of problems. The implementation of suitable models for heavy ion nuclear interactions has reached an operational stage. At medium/high energy FLUKA is using the DPMJET model. The major task of incorporating heavy ion interactions from a few GeV/n down to the threshold for inelastic collisions is also progressing and promising results have been obtained using a modified version of the RQMD-2.4 code. This interim solution is now fully operational, while waiting for the development of new models based on the FLUKA hadron-nucleus interaction code, a newly developed QMD code, and the implementation of the Boltzmann master equation theory for low energy ion interactions.

[Objectives of a bloodless surgery program. A comparative study (major surgery vs. minor-medium surgery) in 51 Jehova's Witnesses patients]. / Obiettivi di un programma di chirurgia senza sangue. Studio comparativo (chirurgia maggiore vs chirurgia minore-media) su 51 pazienti testimoni di Geova.

AIM: The purpose of this retrospective review of the charts of 51 Jehovah's Witness patients, who underwent surgery without blood transfusions, was to compare two study groups (major surgery vs minor-medium surgery). METHODS: We compared the following variables: age, sex, length of stay, type of surgical operation, use of intraoperative red cell salvaging devices, hemodilution, number of drainages and their stay, postoperative blood loss, complications, need of reoperation and mortality rate. Between medical variables we focused on blood production therapy and nutritional support (administration of iron, folate, erythropoietin and albumin) and blood tests (at the first day of admission; intraoperative; at the first postoperative day; at the discharge). RESULTS: In the two study groups, we detected statistically significant differences in the following variables: total of postoperative blood loss (p < 0.00001), complications rate (p = 0.0122) and in Hgb values (intraoperative: p = 0.0197; at the first postoperative day: p = 0.0028; at the discharge: p = 0.0100). DISCUSSION: The aims of a bloodless surgery program are: 1) minimize blood loss, reducing iatrogenic anemia and intraoperative hemorrhage loss; 2) maximize blood production by administration of erythropoietin, iron and folate; 3) maximize cardiac output by alternatives to blood transfusions, as crystalloids, colloids and blood substitutes; 4) increase oxygen content; 5) decrease metabolic rate. We focused on advantages and disadvantages of the suggested procedures. Most interesting techniques are the normovolemic hemodilution and the intraoperative red cell salvaging devices, indispensable in emergency. CONCLUSIONS: A close team-work between surgeons, anesthesiologists and hematologists is determinant in a reference center that guarantees experience, organization, professionality, respect for the patients' will and, above all, low morbidity and mortality rates, as those reported by our series.

The new classification of hemorrhoids: PATE 2000-Sorrento. History of the scientific debate.

BACKGROUND: The history of our proposal for a new classification of hemorrhoids is very old: 7 years of scientific debate had a big impact for the study and the definition of hemorrhoids. METHODS: Nowadays many things have changed mainly in the field of treatment of hemorrhoids. New medical and surgical tools are available for the modern proctologist. RESULTS: The new classification of the disease seems to fit the necessity of introducing these modern opportunities. Many authors recognize the fundamental role and claim for the routine use of a new classification, named PATE 2000 Sorrento. Nevertheless many problems are on debate. Their resolution needs the cooperation of all the experts in order to choose the best version of the classification. CONCLUSIONS: For these reasons the authors analyse all the work carried out till now in order to see what we still need to introduce a new classification of the disease.

Transduodenal sphincterotomy in laparoscopic era.

Indications for transduodenal sphincterotomy have been reduced in recent years, mainly because of the development of endoscopic sphincterotomy and laparoscopic procedures. Endoscopic treatment is effective, but it is necessary to carefully evaluate its indications because the incidence of early and late complications is not negligible. Laparoscopic procedures require advanced and expensive technologies and considerable laparoscopic experience. Transduodenal sphincterotomy is safe and effective, if correctly performed. Some risk factors appear to be related to the incidence of complications that do not significantly differ from those following endoscopic sphincterotomy. Transduodenal sphincterotomy may be still indicated in selected cases, and for this reason it should be considered an essential part of the knowledge of a general surgeon.