Differential diagnosis in inflammatory bowel disease colitis:State of the art and future perspectives

Distinction between Crohn's disease of the colonrectum and ulcerative colitis or inflammatory bowel disease(IBD) type unclassified can be of pivotal importance for a tailored clinical management,as each entity often involves specific therapeutic strategies and prognosis.Nonetheless,no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations.Hence,we have performed a literature search to address the problem of differential diagnosis in IBD colitis,revised current and emerging diagnostic tools and refined disease classification strategies.Nowadays,the differential diagnosis is an untangled issue,and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis.This topic is receiving emerging attention,as medical therapies,surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients.The optimization of standard diagnostic approaches based on clinical features,biomarkers,radiology,endoscopy and histopathology appears to provide only marginal benefits.Conversely,emerging diagnostic techniques in the field of gastrointestinal endoscopy,molecular pathology,genetics,epigenetics,metabolomics and proteomics have already shown promising results.Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD,better reflecting diverse disease behaviors based on specific pathogenic pathways.

Neurological disorders and inflammatory bowel diseases

Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease(IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms.

Imaging of the small bowel in Crohn's disease: A review of old and new techniques

The investigation of small bowel morphology is often mandatory in many patients with Crohn's disease. Traditional radiological techniques (small bowel enteroclysis and small bowel follow-through) have long been the only suitable methods for this purpose. In recent years, several alternative imaging techniques have been proposed. To review the most recent advances in imaging studies of the small bowel, with particular reference to their possible application in Crohn's disease, we conducted a complete review of the most important studies in which traditional and newer imaging methods were performed and compared in patients with Crohn's disease. Several radiological and endoscopic techniques are now available for the study of the small bowel; each of them is characterized by a distinct profile of favourable and unfavourable features. In some cases, they may also be used as complementary rather than alternative techniques. In everyday practice, the choice of the technique to be used stands upon its availability and a careful evaluation of diagnostic accuracy, clinical usefulness, safety and cost. The recent development ofinnovative imaging techniques has opened a new and exciting area in the exploration of the small bowel in Crohn's disease patients.

Advanced gastrointestinal endoscopic imaging forinflammatory bowel diseases

Gastrointestinal luminal endoscopy is of paramount importance for diagnosis, monitoring and dysplasia surveillance in patients with both, Crohn's disease and ulcerative colitis. Moreover, with the recent recognition that mucosal healing is directly linked to the clinical outcome of patients with inflammatory bowel disorders, a growing demand exists for the precise, timely and detailed endoscopic assessment of superficial mucosal layer. Further, the novel field of molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy, now encompassing not only diagnosis, surveillance, and treatment but also the prediction of individual therapeutic responses. Within this review, we describe how novel endoscopic approaches and advanced endoscopic imaging methods such as high definition and high magnification endoscopy, dye-based and dye-less chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and molecular imaging now allow for the precise and ultrastructural assessment of mucosal inflammation and describe the potential of these techniques for dysplasia detection.

Validation of a novel imaging approach using multi-slice CT and cone-beam CT to follow-up on condylar remodeling after bimaxillary surgery

The main goal of this study was to introduce a novel three-dimensional procedure to objectively quantify both inner and outer condylar remodelling on preoperative multi-slice computed tomography （MSCT） and postoperative cone-beam computed tomography （CBCT） images. Second, the reliability and accuracy of this condylar volume quantification method was assessed. The mandibles of 20 patients （11 female and 9 male） who underwent bimaxillary surgery were semi-automatically extracted from MSCT/CBCT scans and rendered in 3D. The resulting condyles were spatially matched by using an anatomical landmark-based registration procedure. A standardized sphere was created around each condyle, and the condylar bone volume within this selected region of interest was automatically calculated. To investigate the reproducibility of the method, inter- and intra-observer reliability was calculated for assessments made by two experienced radiologists twice five months apart in a set of ten randomly selected patients. To test the accuracy of the bone segmentation, the inner and outer bone structures of one dry mandible, scanned according to the clinical set-up, were compared with the gold standard, micro-CT. Thirty-eight condyles showed a significant （P〈O.05） mean bone volume decrease of 26.4%_ 11.4% （502.9 mm3＋ 268.1 mm3）. No significant effects of side, sex or age were found. Good to excellent （ICC〉 0.6） intra- and inter-observer reliability was observed for both MSCT and CBCT. Moreover, the bone segmentation accuracy was less than one voxel （0.4 mm） for MSCT （0.3 mm __. 0.2 mm） and CBCT （0.4 mm _ 0.3 mm）, thus indicating the clinical potential of this method for objective follow-up in pathological condylar resorption.

Proteomic insights on the metabolism in inflammatory bowel disease

Inflammatory bowel diseases(IBD)are chronic and relapsing inflammatory conditions of the gut that include Crohn's disease and ulcerative colitis.The pathogenesis of IBD is not completely unraveled,IBD are multi-factorial diseases with reported alterations in the gut microbiota,activation of different immune cell types,changes in the vascular endothelium,and alterations in the tight junctions’structure of the colonic epithelial cells.Proteomics represents a useful tool to enhance our biological understanding and to discover biomarkers in blood and intestinal specimens.It is expected to provide reproducible and quantitative data that can support clinical assessments and help clinicians in the diagnosis and treatment of IBD.Sometimes a differential diagnosis of Crohn's disease and ulcerative colitis and the prediction of treatment response can be deducted by finding meaningful biomarkers.Although some non-invasive biomarkers have been described,none can be considered as the“gold standard”for IBD diagnosis,disease activity and therapy outcome.For these reason new studies have proposed an“IBD signature”,which consists in a panel of biomarkers used to assess IBD.The above described approach characterizes“omics”and in this review we will focus on proteomics.

Reporting rotator cuff tears on magnetic resonance arthrography using the Snyder's arthroscopic classification

AIM To determine diagnostic performance of magnetic resonance arthrography(MRA) in evaluating rotator cuff tears(RCTs) using Snyder's classification for reporting.METHODS One hundred and twenty-six patients(64 males, 62 females; median age 55 years) underwent shoulder MRA and arthroscopy, which represented our reference standard. Surgical arthroscopic reports were reviewed and the reported Snyder's classification was recorded. MRA examinations were evaluated by two independent radiologists(14 and 5 years' experience) using Snyder's classification system, blinded to arthroscopy. Agreement between arthroscopy and MRA on partial-and fullthickness tears was calculated, first regardless of their extent. Then, analysis took into account also the extent of the tear. Interobserver agreement was also calculated the quadratically-weighted Cohen kappa statistics.RESULTS On arthroscopy, 71/126 patients(56%) had a fullthickness RCT. The remaining 55/126 patients(44%) had a partial-thickness RCT. Regardless of tear extent, out of 71 patients with arthroscopically-confirmed fullthickness RCTs, 66(93%) were correctly scored by both readers. All 55 patients with arthroscopic diagnosis of partial-thickness RCT were correctly assigned as having a partial-thickness RCT at MRA by both readers. Interobserver reproducibility analysis showed total agreement between the two readers in distinguishing partial-thickness from full-thickness RCTs, regardless of tear extent(k = 1.000). With regard to tear extent, in patients in whom a complete tear was correctly diagnosed, correct tear extent was detected in 61/66 cases(92%); in the remaining 5/66 cases(8%), tear extent was underestimated. Agreement was k = 0.955. Interobserver agreement was total(k = 1.000).CONCLUSION MRA shows high diagnostic accuracy and reproducibility in evaluating RCTs using the Snyder's classification for reporting. Snyder's classification may be adopted for routine reporting of MRA.

Covered nitinol stents for the treatment of esophageal strictures and leaks

AIM:To compare 2 different types of covered esophageal nitinol stents(Ultraflex and Choostent) in terms of efficacy,complications,and long-term outcome.METHODS:A retrospective review of a consecutive series of 65 patients who underwent endoscopic placement of an Ultraflex stent(n = 33) or a Choostent(n = 32) from June 2001 to October 2009 was conducted.RESULTS:Stent placement was successful in all patients without hospital mortality.No significant differences in patient discomfort and complications were observed between the Ultraflex stent and Choostent groups.The median follow-up time was 6 mo(interquartile range 3-16 mo).Endoscopic reintervention was required in 9 patients(14%) because of stent migration or food obstruction.No significant difference in the rate of reintervention between the 2 groups was observed(P = 0.8).The mean dysphagia score 1 mo after stent placement was 1.9 ± 0.3 for the Ultraflex stent and 2.1 ± 0.4 for the Choostent(P = 0.6).At 1-mo follow-up endoscopy,the cover membrane of the stent appeared to be damaged more frequently in the Choostent group(P = 0.34).Removal of the Choostent was possible up to 8 wk without difficulty.CONCLUSION:Ultraflex and Choostent proved to be equally reliable for palliation of dysphagia and leaks.Removal of the Choostent was easy and safe under mild sedation.

Current status of minimally invasive endoscopic management for Zenker diverticulum

Surgical resection has been the mainstay of treatment of pharyngoesophageal(Zenker) diverticula over the past century. Developments in minimally invasive surgery and new endoscopic devices have led to a paradigm change. The concept of dividing the septum between the esophagus and the pouch rather than resecting the pouch itself has been revisited during the last three decades and new technologies have been investigated to make the transoral operation safe and effective. The internal pharyngoesophageal myotomy accomplishedthrough the transoral stapling approach has been shown to effectively relieve outflow obstruction and restore physiological bolus transit in patients with medium size diverticula. Transoral techniques, either through a rigid device or by flexible endoscopy, are gaining popularity over the open surgical approach due the low morbidity, the fast recovery time and the fact that the procedure can be safely repeated. We provide an analysis of the the current status of minimally invasive endoscopic management of Zenker diverticulum.

Efficacy and tolerability of high and low-volume bowel preparation compared:A real-life single-blinded large-population study

BACKGROUND Low-volume preparations for colonoscopy have shown similar efficacy compared to high-volume ones in randomized controlled trials(RCT).However,most RCTs do not provide data about clinical outcomes including lesions detection rate.Moreover,real-life comparisons are lacking.AIM To compare efficacy(both in terms of adequate bowel preparation and detection of colorectal lesions)and tolerability of a high-volume(HV:4 L polyethylene glycol,PEG)and a low-volume(LV:2 L PEG plus bisacodyl)bowel preparation in a real-life setting.METHODS Consecutive outpatients referred for colonoscopy were prospectively enrolled between 1 December 2014 and 31 December 2016.Patients could choose either LV or HV preparation,with a day-before schedule for morning colonoscopies and a split-dose for afternoon procedures.Adequate bowel preparation according to Boston Bowel Preparation Scale(BBPS),clinical outcomes including polyp detection rate(PDR),adenoma detection rate(ADR),advanced adenoma detection rate(AADR),sessile/serrated lesion detection rate(SDR)and cancer detection rate and self-reported tolerability of HV and LV were blindly assessed.RESULTS Total 2040 patients were enrolled and 1815(mean age 60.6 years,50.2%men)finally included.LV was chosen by 52%of patients(50.8%of men,54.9%of women).Split-dose schedule was more common with HV(44.7%vs 38.2%,P=0.005).High-definition scopes were used in 33.4%of patients,without difference in the two groups(P=0.605).HV and LV preparations showed similar adequate bowel preparation rates(89.2%vs 86.6%,P=0.098),also considering the two different schedules(HV split-dose 93.8%vs LV split-dose 93.6%,P=1;HV daybefore 85.5%vs LV day-before 82.3%,P=0.182).Mean global BBPS score was higher for HV preparations(7.1±1.7 vs 6.8±1.6,P<0.001).After adjustment for sex,age and indications for colonoscopy,HV preparation resulted higher in PDR[Odds ratio(OR)1.32,95%CI:1.07-1.63,P=0.011]and ADR(OR 1.29,95%CI 1.02–1.63,P=0.038)and comparable to LV in AADR(OR 1.51,95%CI 0.97-2.35,P=0.069),SDR and cancer detection rate.The use of standard-definition colonoscopes was associated to lower PDR(adjusted OR 1.59,95%CI:1.22-2.08,P<0.001),ADR(adjusted OR 1.71,95%CI:1.26–2.30,P<0.001)and AADR(adjusted OR 1.97,95%CI:1.09-3.56,P=0.025)in patients receiving LV preparation.Mean Visual Analogue Scale tolerability scored equally(7,P=0.627)but a≥75%dose intake was more frequent with LV(94.6%vs 92.1%,P=0.003).CONCLUSION In a real-life setting,PEG-based low-volume preparation with bisacodyl showed similar efficacy and tolerability compared to standard HV preparation.However,with higher PDR and ADR,HV should still be considered as the reference standard for clinical trials and the preferred option in screening colonoscopy,especially when colonoscopy is performed with standard resolution imaging.

Incidence and treatment of mediastinal leakage after esophagectomy:Insights from the multicenter study on mediastinal leaks

BACKGROUND Mediastinal leakage(ML) is one of the most feared complications of esophagectomy. A standard strategy for its diagnosis and treatment has beendifficult to establish because of the great variability in their incidence and mortality rates reported in the existing series.AIM To assess the incidence, predictive factors, treatment, and associated mortality rate of mediastinal leakage using the standardized definition of mediastinal leaks recently proposed by the Esophagectomy Complications Consensus Group(ECCG).METHODS Seven Italian surgical centers(five high-volume, two low-volume) affiliated with the Italian Society for the Study of Esophageal Diseases designed and implemented a retrospective study including all esophagectomies(n = 501) with intrathoracic esophagogastric anastomosis performed from 2014 to 2017.Anastomotic MLs were defined according to the classification recently proposed by the ECCG.RESULTS Fifty-nine cases of ML were recorded, yielding an overall incidence of 11.8%(95%CI: 9.1%-14.9%). The surgical approach significantly influenced the occurrence of ML: the proportion of leakage was 10.5% and 9% after open and hybrid esophagectomy(HE), respectively, and doubled(20%) after totally minimally invasive esophagectomy(TMIE)(P = 0.016). No other predictive factors were found. The 30-and 90-d overall mortality rates were 1.4% and 3.2%,respectively; the 30-and 90-d leak-related mortality rates were 5.1% and 10.2%,respectively; the 90-d mortality rates for TMIE and HE were 5.9% and 1.8%,respectively. Endoscopy was the first-line treatment in 49% of ML cases, with the need for retreatment in 17.2% of cases. Surgery was needed in 44.1% of ML cases.Endoscopic treatment had the lowest mortality rate(6.9%). Removal of the gastric tube with stoma formation was necessary in 8(13.6%) cases.CONCLUSION The incidence of ML after esophagectomy was high mainly in the TMIE group.However, the general and specific(leak-related) mortality rates were low. Early treatment(surgical or endoscopic) of severe leaks is mandatory to limit related mortality.

Long-term outcome and quality of life after transoral stapling for Zenker diverticulum

AIM: To investigate long-term results and quality of life after transoral stapling of Zenker diverticulum.METHODS: The data of all patients admitted to our institution for the surgical treatment of Zenker diverticulum were entered into a prospective database. Demographics, symptoms, intraoperative and post-operative data, morbidity, time to oral feeding, and length of hospital stay were recorded. All patients underwent upper gastrointestinal endoscopy and a barium swallow study to measure the length of the diverticulum from the apex of the septum to the bottom of the pouch. Transoral stapling was performed using a Weerda diverticuloscope under general anesthesia. Over time, the technique was modified by applying traction sutures to ease engagement of the common septum inside the stapler jaws. Perioperative variables, symptoms, long-term outcome, and quality of life were analyzed. The operation was considered successful if the patient reported complete remission(grade 1) or marked improvement(grade 2) of dysphagia, regurgitation, and respiratory symptoms. Statistical analysis was performed using Statistical Package for Social Science(SPSS, Version 15, SPSS, Inc., Chicago, IL).RESULTS: Between 2001 and 2013, the transoral approach was successfully completed in 100 patients with a median age of 75 years. Patients with a larger(≥3 cm) diverticulum were older than those with a smaller pouch(P < 0.038). Complications occurred in 4% of the patients but there was no mortality. A statistically significant improvement of dysphagia and regurgitation scores(P < 0.001) was recorded over a median followup of 63 mo. Similarly, a significant decrease in the median number of pneumonia episodes per year(P < 0.001) was recorded after surgery. The overall longterm success rate of the procedure was 76%. The success rate of the operation was greater in patients of 70 years of age or older compared to younger individuals(P = 0.038). Use of traction sutures on the septum was associated with an improved success rate compared with the standard procedure(P = 0.04). All items of the health related quality of life questionnaire were significantly higher compared to baseline(P < 0.05).CONCLUSION: Transoral stapling is safe and effective. The operation significantly improves patients' quality of life. It appears that elderly patients with large diverticula significantly benefit from the procedure and that the modified surgical technique including traction sutures can further improve the success rate.

Relevant incidental findings at abdominal multi-detector contrast-enhanced computed tomography:A collateral screening?

AIM: To investigate the prevalence of relevant incidental findings(RIFs) detected during routine abdominal contrast-enhanced computed tomography(Ce CT).METHODS: We retrospectively evaluated the reports of a consecutive series of abdominal Ce CT studies performed between January and May 2013. For each report, patients' age and sex, admission as inpatient or outpatient, clinical suspicion as indicated by the requesting physician, availability of a previous abdominal examination, and name of the reporting radiologist were recorded. Based on the clinical suspicion, the presence and features of any RIFs(if needing additional workup) was noted.RESULTS: One thousand forty abdominal Ce CT were performed in 949 patients(528 males, mean age 66 ±14 years). No significant difference was found between inpatients and outpatients age and sex distribution(P > 0.472). RIFs were found in 195/1040(18.8%) Ce CT [inpatients = 108/470(23.0%); outpatients = 87/570(15.2%); P = 0.002]. RIFs were found in 30/440(6.8%) Ce CT with a previous exam and in 165/600(27.5%) without a previous exam(P < 0.001). Radiologists' distribution between inpatients or outpatients was significantly different(P < 0.001). RIFs prevalence increased with aging, except for a peak in 40-49 year group. Most involved organs were kidneys, gallbladder, and lungs.CONCLUSION: A RIF is detected in 1/5 patients undergoing abdominal Ce CT. Risk of overdiagnosis should be taken into account.

Treatment options for localised renal cell carcinoma of the transplanted kidney

Currently,there is no consensus among the transplant community about the treatment of renal cell carcinoma(RCC)of the transplanted kidney.Until recently,graftectomy was universally considered the golden standard,regardless of the characteristics of the neoplasm.Due to the encouraging results observed in native kidneys,conservative options such as nephron-sparing surgery(NSS)(enucleation and partial nephrectomy)and ablative therapy(radiofrequency ablation,cryoablation,microwave ablation,high-intensity focused ultrasound,and irreversible electroporation)have been progressively used in carefully selected recipients with early-stage allograft RCC.Available reports show excellent patient survival,optimal oncological outcome,and preserved renal function with acceptable complication rates.Nevertheless,the rarity and the heterogeneity of the disease,the number of options available,and the lack of long-term follow-up data do not allow to adequately define treatment-specific advantages and limitations.The role of active surveillance and immunosuppression management remain also debated.In order to offer a better insight into this difficult topic and to help clinicians choose the best therapy for their patients,we performed and extensive review of the literature.We focused on epidemiology,clinical presentation,diagnostic work up,staging strategies,tumour characteristics,treatment modalities,and follow-up protocols.Our research confirms that both NSS and focal ablation represent a valuable alternative to graftectomy for kidney transplant recipients with American Joint Committee on Cancer stage T1aN0M0 RCC.Data on T1bN0M0 lesions are scarce but suggest extra caution.Properly designed multi-centre prospective clinical trials are warranted.

Multimodal Imaging with 3D-Holograms for Preoperative Planning in Pediatric Cardiac Surgery:A Unique Case Report

Multimodal imaging,including augmented or mixed reality,transforms the physicians’interaction with clinical imaging,allowing more accurate data interpretation,better spatial resolution,and depth perception of the patient’s anatomy.We successfully overlay 3D holographic visualization to magnetic resonance imaging images for preoperative decision making of a complex case of cardiac tumour in a 7-year-old girl.

Laparoscopic diagnosis of pleural mesothelioma presenting with pseudoachalasia

Pseudoachalasia due to pleural mesothelioma is an extremely rare condition. A 70-year-old woman presented with progressive dysphagia for solid and liquids and a mild weight loss. A barium swallow study revealed an esophageal dilatation and a smoothly narrowed esophagogastric junction. An esophageal manometry showed absence of peristalsis. Endoscopy demonstrated an extrinsic stenosis of the distal esophagus with negative biopsies. A marked thickening of the distal esophagus and a right-sided pleural effusion were evident at computed tomography （CT） scan, but cytological examination of the thoracic fluid was negative. Endoscopic ultrasound showed the disappearance of the distal esophageal wall stratification and thickening of the esophageal wall. The patient underwent an explorative laparoscopy. Biopsies of the esophageal muscle were consistent with the diagnosis of epithelioid type pleural mesothelioma. An esophageal stent was placed for palliation of dysphagia. The patient died four months after the diagnosis. This is the first reported case of pleural mesothelioma diagnosed through laparoscopy.

From the surface to the single cell: Novel endoscopic approaches in inflammatory bowel disease

Inflammatory bowel diseases(IBD) comprise the two major entities Crohn's disease and ulcerative colitis and endoscopic imaging of the gastrointestinal tract has always been an integral and central part in the management of IBD patients. Within the recent years,mucosal healing emerged as a key treatment goal in IBD that substantially decides about the clinical outcome of IBD patients,thereby demanding for a precise,timely and detailed endoscopic assessment of the mucosal inflammation associated with IBD. Further,molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy,now encompassing not only diagnosis,surveillance,and treatment but also the prediction of individual therapy response. Within this review we describe novel endoscopic approaches and advanced endoscopic imaging methods for the diagnosis,treatment and surveillance of IBD patients. We begin by providing an overview over novel and advanced imaging techniques such as magnification endoscopy and dye-based and dye-less chromoendoscopy,endomicroscopy and endocytoscopy. We then describe how these techniques can be utilized for the precise and ultrastructural assessment of mucosal inflammation and dysplasia development associated with IBD and outline how they have enabled the endoscopist to gain insight onto the cellular level in real-time. Finally,we provide an outlook on how molecular imaging has rapidly evolved in the recent past and can be used to make individual predictions about the therapeutic response towards biological treatment.

Laparoscopic resection for incidentally detected Meckel diverticulum

The management of Meckel diverticulum found un-expectedly during an abdominal operation remains controversial. Most published reports have included only patients undergoing diverticulectomy or bowel resection through laparotomy. We report a case of a carcinoid tumor in a Meckel’s diverticulum which was incidentally detected and removed during laparoscopic inguinal hernia repair. Although there is no compelling evidence in the literature to recommend prophylactic diverticulectomy, laparoscopic stapled resection repre-sents a viable and safe approach in healthy individuals undergoing elective surgery for other purposes.

Erectile dysfunction as a predictor of asymptomatic coronary artery disease in elderly men with type 2 diabetes

1 Introduction Erectile dysfunction （ED） and coronary artery disease （CAD） are closely linked, as both conditions share the same cardiovascular risk factors. Indeed, these risk factors can determine endothelial dysfunction that represents the common underlying mechanism of both ED and CAD. The prevalence of ED is about three-fold higher among diabetic patients than in the general population and a higher prevalence of CAD has been observed in people with diabetes when compared to non-diabetic subjects.Some studies showed that ED can be a powerful marker of silent CAD and a strong predictor of cardiovascular events in apparently uncomplicated type 2 diabetic patients Therefore ED is now considered as a sentinel symptom of silent CAD, as ED often precedes the onset of myocardial ischemia itself by many years.

Immunosuppressive therapy in pancreas and islet transplant: Need for simultaneous assessment of insulin sensitivity and secretion

Diabetes mellitus is a metabolic disease possible to treat via pancreas/islet transplantation but most immunosuppressive drugs are diabetogenic. In this letter, we review current up to date methods to assess insulin action and secretion (using the surrogate indexes) suggesting their use in large studies in populations of pancreas/ islets transplanted patients.