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Objective: The aim of the present study is to assess the effectiveness of indocyanine-green (ICG)-guided lymphography (ICG-Lg) in reducing the incidence of chyle leak (CL) after esophagectomy., Background: Chylothorax may severely impact esophageal cancer surgery, and the pre-emptive ligation of the thoracic duct (TD) is the most widespread control of this complication. Intraoperative ICG-Lg has been recently embedded in minimally invasive esophagectomy to facilitate TD detection and pre-emptive ligation., Methods: This retrospective analysis included consecutive patients who underwent minimally invasive Ivor Lewis esophagectomy for cancer at a tertiary referral center between January 2018 and August 2023. Patients were routinely submitted to extended lymphadenectomy with TD ligation and removal. All patients treated after January 2021 underwent ICG-Lg for TD identification and ligation (ICG group) and compared with the previous series (no-ICG group). The primary outcome was the incidence of postoperative CL, while univariate and backward stepwise multivariate logistic regression models were performed to identify associated factors., Results: After including 320 patients, 151 (ICG group) were submitted to ICG-Lg before the pre-emptive TD ligation. Both groups presented similar characteristics, except for neoadjuvant therapy ( P <0.001) and preoperative comorbidities ( P =0.045). Intraoperative ICG-Lg significantly reduced the incidence of postoperative CL (11.8% vs 4.6%, P =0.026) and was significantly associated with shorter median length of hospital stay (13 vs 9 d, P =0.006). However, CL after ICG-Lg was more likely to require repairing reoperation ( P =0.050)., Conclusions: Intraoperative ICG-Lg demonstrated significantly lower rates of CL after total minimally invasive esophagectomy and, therefore, it should be routinely embedded in the standardized surgical technique of high-volume centers for esophageal cancer., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pancreatogenic diabetes, a consequence of pancreatic tissue loss following pancreatectomy, poses a significant challenge for patients undergoing pancreatic surgery. Islet autotransplantation (IAT) offers a promising approach to prevent or alleviate pancreatogenic diabetes, but its application has been limited to individuals with painful chronic pancreatitis., Methods: This study presents a 15-y clinical experience with the Milan Protocol, which expands IAT after pancreatectomy to a broader spectrum of patients with malignant and nonmalignant pancreatic diseases. The analysis evaluates feasibility, efficacy, and safety of IAT. Modified Igls criteria validated through the arginine test and mixed meal tolerance tests were used to assess long-term metabolic outcomes., Results: Between November 2008 and June 2023, IAT procedures were performed on 114 of 147 candidates. IAT-related complications occurred in 19 of 114 patients (16.7%), with 5 being potentially serious. Patients exhibited sustained C-peptide secretion over the 10-y follow-up period, demonstrating a prevalence of optimal and good beta-cell function. Individuals who underwent partial pancreatectomy demonstrated superior metabolic outcomes, including sustained C-peptide secretion and a reduced risk of developing diabetes or insulin dependence compared with those who underwent total pancreatectomy. For patients who had total pancreatectomy, the quantity of infused islets and tissue volume were identified as critical factors influencing metabolic outcomes. An increased risk of recurrence or progression of baseline diseases was not observed in subjects with neoplasms., Conclusions: These findings provide valuable insights into the benefits and applications of IAT as a therapeutic option for pancreatogenic diabetes after pancreatic surgery, expanding its potential beyond painful chronic pancreatitis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To compare pancreaticoduodenectomy (PD) and total pancreatectomy (TP) with islet autotransplantation (IAT) in patients at high risk of postoperative pancreatic fistula (POPF)., Background: Criteria to predict the risk of POPF occurrence after PD are available. However, even when a high risk of POPF is predicted, TP is not currently accepted as an alternative to PD, because of its severe consequences on glycaemic control. Combining IAT with TP may mitigate such consequences., Methods: Randomized, open-label, controlled, bicentric trial (NCT01346098). Candidates for PD at high-risk pancreatic anastomosis (ie, soft pancreas and duct diameter ≤3 mm) were randomly assigned (1:1) to undergo either PD or TP-IAT. The primary endpoint was the incidence of complications within 90 days after surgery., Results: Between 2010 and 2019, 61 patients were assigned to PD (n=31) or TP-IAT (n=30). In the intention-to-treat analysis, morbidity rate was 90·3% after PD and 60% after TP-IAT ( P =0.008). According to complications' severity, PD was associated with an increased risk of grade ≥2 [odds ratio (OR)=7.64 (95% CI: 1.35-43.3), P =0.022], while the OR for grade ≥3 complications was 2.82 (95% CI: 0.86-9.24, P =0.086). After TP-IAT, the postoperative stay was shorter [median: 10.5 vs 16.0 days; P <0.001). No differences were observed in disease-free survival, site of recurrence, disease-specific survival, and overall survival. TP-IAT was associated with a higher risk of diabetes [hazard ratio=9.1 (95% CI: 3.76-21.9), P <0.0001], but most patients maintained good metabolic control and showed sustained C-peptide production over time., Conclusions: TP-IAT may become the standard treatment in candidates for PD, when a high risk of POPF is predicted., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To determine the accuracy of preoperative imaging, including contrast-enhanced computed tomography (CE-CT), endoscopic ultrasound (EUS), and 68 Gallium-DOTATOC positron emission tomography ( 68 Ga-DOTATOC PET), in identifying nodal metastases (N+) in sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs)., Background: An accurate preoperative identification of N+ in NF-PanNETs is critical for surgical planning. The accuracy of different imaging techniques in detecting lymph node (LN) metastases in NF-PanNETs has been poorly investigated., Methods: All consecutive patients undergoing surgery for sporadic NF-PanNETs (2018-2021) were enrolled in a prospective study (DETECTYON; NCT03918759). The accuracy of preoperative imaging techniques in detecting N+ was assessed through sensitivity, specificity positive and negative predictive values., Results: Overall, 100 patients with NF-PanNETs underwent CE-CT, EUS, and 68 Ga-DOTATOC PET before pancreatic resection. LN metastases were found in 42 cases (42%). Sensitivity, specificity, positive predictive value, and negative predictive value of different imaging techniques were 26%, 95%, 79%, 64% for CE-CT, 19%, 98%, 89%, 63% for EUS, and 12%, 95%, 63%, 60% for 68 Ga-DOTATOC PET, respectively. Radiologic tumor size >4 cm and the presence of radiologic N+ at ≥1 imaging were independent predictors of N+ at pathology. The identification of N+ at ≥1 imaging technique was associated with a higher number of positive LNs compared with negative imaging (4 vs 2) ( P =0.012)., Conclusions: CE-CT, EUS, and 68 Ga-DOTATOC PET are poorly sensitive in predicting nodal status in NF-PanNETs despite a high specificity., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: The aim of this study was to evaluate the sensitivity of right ventricular endomyocardial biopsy (EMB) in myocarditis patients with cardiac magnetic resonance (CMR) and electroanatomical mapping (EAM) showing left ventricular abnormalities., Methods: We performed right ventricular EMB in 144 consecutive patients (66% men, age 43 ± 15 years) with acute symptoms and CMR-proved diagnosis of left ventricular myocarditis. Right ventricular EMB sensitivity has been evaluated in patients with different localization and extension of abnormal substrate at both CMR and -- when performed -- EAM. Abnormal substrate was defined, respectively, by late gadolinium enhancement (LGE) and low-voltage areas (LVAs)., Results: Globally, right ventricular EMB sensitivity was 87.5%. EMB-negative cases had significantly smaller fragment sizes (cumulative area 2.8 ± 1.7 vs. 3.8 ± 1.8 mm2, P = 0.023), and lower LGE surface extension (24.7 ± 14.2 vs. 38.5 ± 20.2%, P = 0.006) and transmurality (32.0 ± 26.1 vs. 49.3 ± 22.6, P = 0.003). Right ventricular EMB sensitivity in patients with LGE involving both right ventricular and interventricular septum (IVS), isolated right ventricular or IVS, and remote left ventricular areas (n = 10, 49 and 67 cases) was 83.3, 84.4 and 90.5%, respectively (P = 0.522). Overall, 34 patients (23.6%) underwent EAM. On the basis of EAM, right ventricular EMB sensitivity was 85.3%: in detail, it was 50.0, 88.2 and 86.7% in patients with both right ventricular and IVS, isolated right ventricular/IVS and distant left ventricular involvement (n = 2, 17 and 15, respectively, P > 0.05). Sample size area was the only factor associated with right ventricular EMB sensitivity (hazard ratio = 1.6/mm2, 95% confidence interval 1.1-2.4, P = 0.013)., Conclusion: Right ventricular EMB is still an accurate technique to confirm diagnosis in patients with CMR-proved left ventricular myocarditis. In particular, provided there is an adequate sample size, its sensitivity is comparable among patients with heterogeneous LGE or LVA localization., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Cardiovascular magnetic resonance (CMR) has emerged as an accurate diagnostic technique for the evaluation of patients with cardiac disease in the majority of clinical settings, thanks to an established additional diagnostic and prognostic value. This document has been developed by a joined group of experts of the Italian Society of Cardiology (SIC) and Italian Society of Radiology (SIRM) to provide a summary about the current state of technology and clinical applications of CMR, to improve the clinical diagnostic pathways and to promote its inclusion in clinical practice. The writing committee consisted of members and experts of both societies in order to develop a more integrated approach in the field of cardiac imaging. This section 2 will cover myocarditis, pericardial disease, cardiomyopathies and valvular heart disease., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: The aim of the present study is to explore the correlation between PET and MRI parameters of primary tumour and clinicopathological features and to determine their synergic predictive role in patients with endometrial cancer candidate to surgery., Methods: Retrospective study including 27 patients with endometrial cancer and preoperative 18F-fluorodeoxyglucose (18F-FDG)-PET and MRI scan. The following parameters, calculated on the primary tumour, were used for analysis: maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) for PET scans; mean apparent diffusion coefficient (ADCmean) and volume index for MRI scans. FIGO stage, grade, histotype, lymphovascular space invasion (LVSI) and myometrial invasion were the considered clinicopathological features., Results: MRI volume index was a good predictor for deep myometrial invasion [area under the curve (AUC) = 0.85; P = 0.003] and for LVSI (AUC = 0.74; P = 0.039). A cutoff value of 9.555 for MRI volume index was predictive for deep myometrial invasion (sensitivity = 84.6%; specificity = 76.9%); a cutoff of 12.165 was predictive for LVSI (sensitivity = 69.2%; specificity = 83.3%). A TLG cutoff value of 26.03 was predictive for deep myometrial invasion (sensitivity = 84.6%; specificity = 76.9%). A high-direct correlation was found with MRI volume index (rho = 0.722; P < 0.001); low-direct correlation with SUVmax (rho = 0.484; P = 0.012), SUVmean (rho = 0.47; P = 0.015) and TLG (rho = 0.482; P = 0.013) were identified. The SUVmax/ADCmean ratio showed a low-direct correlation with percentage of myometrial invasion (rho = 0.467; P = 0.016)., Conclusion: Volume index, TLG and SUVmax/ADCmean ratio are associated with deep myometrial invasion. As myometrial invasion is the index used to predict lymph node involvement in endometrial cancer, the synergic use of these imaging parameters may be suggested to predict lymphnodal metastases.

Background: To assess feasibility, safety, and metabolic outcome of islet auto transplantation (IAT) in patients undergoing completion pancreatectomy because of sepsis or bleeding after pancreatic surgery., Methods: From November 2008 to October 2016, approximately 22 patients were candidates to salvage IAT during emergency relaparotomy because of postpancreatectomy sepsis (n = 11) or bleeding (n = 11). Feasibility, efficacy, and safety of salvage IAT were compared with those documented in a cohort of 36 patients who were candidate to simultaneous IAT during nonemergency preemptive completion pancreatectomy through the pancreaticoduodenectomy., Results: The percentage of candidates that received the infusion of islets was significantly lower in salvage IAT than simultaneous IAT (59.1% vs 88.9%, P = 0.008), mainly because of a higher rate of inadequate islet preparations. Even if microbial contamination of islet preparation was significantly higher in candidates to salvage IAT than in those to simultaneous IAT (78.9% vs 20%, P < 0.001), there was no evidence of a higher rate of complications related to the procedure. Median follow-up was 5.45 ± 0.52 years. Four (36%) of 11 patients reached insulin independence, 6 patients (56%) had partial graft function, and 1 patient (9%) had primary graft nonfunction. At the last follow-up visit, median fasting C-peptide was 0.43 (0.19-0.93) ng/mL; median insulin requirement was 0.38 (0.04-0.5) U/kg per day, and median HbA1c was 6.6% (5.9%-8.1%). Overall mortality, in-hospital mortality, metabolic outcome, graft survival, and insulin-free survival after salvage IAT were not different from those documented after simultaneous IAT., Conclusions: Our data demonstrate the feasibility, efficacy, and safety of salvage IAT after relaparotomy.

Background: The incidence of angiographic no reflow (NR) and microvascular obstruction (MVO) at cardiac magnetic resonance is significantly different. The aim of this study was to investigate the occurrence of NR and MVO in a cohort of consecutive patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary interventions., Methods and Results: In this prospective study, 88 consecutive ST-segment-elevation myocardial infarction patients were enrolled within 12 hours from symptoms onset. All patients underwent cardiac magnetic resonance between 2 and 5 days after primary percutaneous coronary interventions. NR was defined as thrombolysis in myocardial infarction flow grade ≤2 and as myocardial blush grade <2. Presence of early or late MVO was assessed 4 and 10 to 15 minutes after gadolinium injection. Thirty-one patients (36%) had evidence of NR, whereas 58 (67%) had MVO. One NR patient did not have MVO. In contrast, NR was present in 30 of 58 MVO patients. MVO patients had higher troponin T peak ( P <0.0001), larger late gadolinium enhancement area ( P <0.0001), and lower left ventricular ejection fraction ( P <0.001) because of an increased end-systolic volume ( P =0.015). In contrast, patients with NR had higher troponin T peak ( P =0.006) but similar late gadolinium enhancement area ( P =0.24) compared with those without NR. Major cardiovascular adverse events-free survival was worse in patients with MVO ( P =0.014), although it was similar in patients with and without NR ( P =0.33). The independent predictors of major cardiovascular adverse events were MVO (hazard ratio, 3.418; P =0.046) and ischemic time (hazard ratio, 1.016; P <0.001). MVO was a strong predictor of target lesion revascularization occurrence ( P =0.017 for log-rank test)., Conclusions: Compared with coronary angiography performed soon after recanalization of the culprit artery, cardiac magnetic resonance performed during index hospitalization provides better prognostic stratification of ST-segment-elevation myocardial infarction patients treated with primary percutaneous coronary interventions. Another novel finding of our study is a significantly increased rate of clinically driven target lesion revascularization in the index event culprit vessel in patients with MVO., (© 2017 American Heart Association, Inc.)

Objectives: The aim of this study was to investigate the contribution of smoking and alcohol intake and pancreas divisum on the risk of developing chronic pancreatitis (CP)., Methods: Consecutive patients with CP who underwent secretin-enhanced magnetic resonance cholangiopancreatography were compared with consecutive patients without pancreatic disease who underwent secretin-enhanced magnetic resonance cholangiopancreatography for irritable bowel syndrome., Results: We enrolled 145 consecutive CP patients and 103 irritable bowel syndrome patients from 2010 to 2014. In a univariate analysis, statistically significant differences in sex, mean age, and the duration and amount of cigarette and alcohol use were found. Per a receiver operating characteristic curve analysis, thresholds for cigarette and alcohol consumption were, respectively, 5.5 cigarettes and 13.5 g daily. In a multivariate analysis, independent risk factors for CP were male sex (odds ratio [OR], 2.05), smoking more than 5.5 cigarettes per day (OR, 2.72), and drinking more than 13.5 g/d (OR, 6.35)., Conclusions: In an Italian population, we confirmed smoking and alcohol as cofactors in the development of CP. This study shows that alcohol intake and smoking habits are 2 of the most important risk factors for the development of CP.

Objective: The aim of this study was to assess the potential risk of gadobutrol-enhanced magnetic resonance imaging (MRI) in patients with moderate to severe renal impairment for the development of nephrogenic systemic fibrosis (NSF)., Materials and Methods: We performed a prospective, international, multicenter, open-label study in 55 centers. Patients with moderate to severe renal impairment scheduled for any gadobutrol-enhanced MRI were included. All patients received a single intravenous bolus injection of gadobutrol at a dose of 0.1 mmol/kg body weight. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period., Results: A total of 908 patients were enrolled, including 586 with moderate and 284 with severe renal impairment who are at highest risk for developing NSF. The mean time since renal disease diagnosis was 1.83 and 5.49 years in the moderate and severe renal impairment cohort, respectively. Overall, 184 patients (20.3%) underwent further contrast-enhanced MRI with other gadolinium-based contrast agents within the 2-year follow-up. No patient developed symptoms conclusive of NSF., Conclusions: No safety concerns with gadobutrol in patients with moderate to severe renal impairment were identified. There were no NSF cases., Competing Interests: and source of funding: M.A., H.D., G.B., M.G., R.W., W.K., and F.D.C. have no conflicts of interest to disclose. H.M., B.E.-W., and R.H. received honoraria and/or research grants from Bayer. M.R., T.B., and J.E. are Bayer employees. The study was funded by Bayer Pharma AG.

: Almost invariably associated with chronic HCV infection, cryoglobulinemic vasculitis is a small-vessel vasculitis commonly affecting the skin, kidneys, and peripheral nervous system. Cardiac involvement, possibly due to cardiac microcirculation involvement, is an utterly rare and severe complication. We describe a case of hypertrophic cardiomyopathy secondary to cryoglobulinemic vasculitis. Evaluation with transthoracic cardiac ultrasound and cardiac MRI evidenced severe left ventricular hypertrophy and diffuse hypokinesia, a marked decrease in left ventricular ejection fraction, and a subtle late enhancement of inferior and lateral left ventricular walls. Upon clinical stabilization, the patient received treatment with anti-CD20 monoclonal antibody rituximab. Clinical and radiological follow-up with cardiac ultrasound and cardiac MRI documented a dramatic and sustained clinical improvement, with marked reduction of left ventricular hypertrophy, resolution of late enhancement, recovery of left ventricular contractility and function.

We present the case of a 52-year-old man with normal coronary arteries admitted to our department after being resuscitated from ventricular fibrillation. Transthoracic echocardiography raised suspicion of left-ventricular non-compaction. Cardiac magnetic resonance excluded this, but showed several systolic bulgings of the right ventricle and a characteristic focal 'crinkling' of the right-ventricular outflow tract known as the 'accordion' sign, a specific marker of desmosomal gene mutations, thus suggesting the presence of an arrhythmogenic cardiomyopathy. Extensive mid-myocardial late gadolinium enhancement and fatty infiltration, predominantly of the left ventricle, finally confirmed the diagnosis of left dominant arrhythmogenic cardiomyopathy, a rare variant of arrhythmogenic right-ventricular cardiomyopathy.

Background: Our final objective is to develop an adoptive therapy with tolerogenic donor-specific type 1 T regulatory cells for patients with type 1 diabetes undergoing islet transplantation. The achievement of this objective depends on the availability of an immunosuppressive treatment compatible with the survival, function, and expansion of type 1 T regulatory cells., Methods: For this purpose, we designed a single-group, phase 1 to 2 trial with an immunosuppression protocol including: (i) rapamycin treatment before the first islet infusion (starting ≥ 30 days before transplantation); (ii) induction therapy with anti-thymocyte globulin (ATG) instead of anti-interleukin-2Ra monoclonal antibody (after the first islet infusion only); (iii) short-term treatment with steroids and interleukin-1Ra (right before and for 2 weeks after each infusion); rapamycin+mycophenolate mofetil treatment as maintenance therapy. The target enrollment was 10 patients., Results: Ten of 15 patients who started the pretransplant rapamycin treatment completed it. Nine of 10 patients did not complete the induction therapy with ATG, and three of 10 required adaptation of maintenance immunosuppression caused by side effects. Four of 10 patients acquired insulin independence which can be maintained up to year 3 after last infusion. All six other patients have lost their graft, and the early graft loss was associated with lower dose of ATG during induction., Conclusion: This protocol resulted feasible, safe but less efficient in maintaining graft survival during the time than other T-cell depletion-based protocols. An adequate induction at the first infusion should be considered to improve the overall clinical outcome.

Objective: To compare prospective electrocardiogram (ECG)-triggered high-voltage coronary computed tomography (CT) angiography (CTA; 140-kVp P-cCTA) with retrospective ECG-gated standard-voltage cCTA (120-kVp R-cCTA), in patients with coronary stents., Methods: Fifty-two patients with coronary stents were studied with 64-slice multidetector scanner. Ninety-three stents were analyzed: 55 with 140-kVp P-cCTA and 38 with 120-kVp R-cCTA. Image quality (IQ), diagnostic confidence (DC), in-stent assessable lumen, artificial narrowing, and effective radiation dose were compared between techniques., Results: Image quality and DC were significantly better for the 140-kVp P-cCTA in comparison with the 120-kVp R-cCTA (IQ, 1.1 ± 0.36 vs 1.7 ± 0.60, respectively; P < 0.00001. Diagnostic confidence: 1.1 ± 0.29 vs 1.5 ± 0.65 respectively; P < 0.0001). In-stent assessable lumen and artificial narrowing were comparable between the techniques. Effective dose was lower for the 140-kVp P-cCTA (6.7 ± 2.07 mSv vs 15.8 ± 6.89 mSv; P < 0.0001)., Conclusions: High voltage combined with axial prospective ECG-triggered scan improved IQ and DC in stent cCTA imaging but failed to improve the diameter of in-stent assessable lumen and to reduce the artificial narrowing compared with the 120-kVp R-cCTA. Effective dose was 60% lower for the 140-kVp P-cCTA.

Objective: Our goal was to determine the value of MRI in the assessment of vascular invasion in the preoperative staging of pancreatic carcinoma., Materials and Methods: In 53 consecutive patients with an established diagnosis of pancreatic ductal adenocarcinoma, SE T1-weighted and breath-hold gradient echo images at 0.5 T were obtained before and after bolus injection of Gd-DTPA. Major peripancreatic vessels were evaluated for the presence of (a) no tumor invasion, (b) contiguity with tumor, and (c) tumor encasement. All patients subsequently underwent surgery. Results of unenhanced and contrast-enhanced MRI studies were compared with the histologic findings in the resected specimens in 34 cases and with the surgical findings in 19 nonresected cases., Results: In six patients, pathologic examination showed the presence of tumor confined to the pancreas with no vascular invasion. With MRI, five of these cases were correctly evaluated; in the remaining case, tumor-vessel contiguity was erroneously diagnosed. In 21 patients, tumor contiguity with adjacent vessels was found at pathologic examination. At MRI, 16 of these cases were correctly assessed, and 5 were understaged as tumors confined to the pancreas. Of the remaining 26 patients, 7 had vascular encasement by tumor at pathologic examination of the resected specimen; the other 19 patients had unresectable tumors encasing the adjacent vessels at surgical evaluation. MRI detected vascular encasement in 21 of these 26 cases; in the other 5, tumor contiguity was incorrectly diagnosed. The overall accuracy of MRI for determining vascular invasion was 79%., Conclusion: MRI is a helpful method for preoperative assessment of vascular involvement due to pancreatic carcinoma.