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In the last few years, innovative technology and health care digitalization played a major role in all medical fields and a great effort worldwide to manage this large amount of data, in terms of security and digital privacy has been made by different national health systems. Blockchain technology, a peer-to-peer distributed database without centralized authority, initially applied to Bitcoin protocol, soon gained popularity, thanks to its distributed immutable nature in several non-medical fields. Therefore, the aim of the present review (PROSPERO N° CRD42022316661) is to establish a putative future role of blockchain and distribution ledger technology (DLT) in the organ transplantation field and its role to overcome inequalities. Preoperative assessment of the deceased donor, supranational crossover programs with the international waitlist databases, and reduction of black-market donations and counterfeit drugs are some of the possible applications of DLT, thanks to its distributed, efficient, secure, trackable, and immutable nature to reduce inequalities and discrimination.

Minimally invasive surgery (MIS) is a widespread approach in general surgery. Computer guiding software, such as the augmented reality (AR), the virtual reality (VR) and mixed reality (MR), has been proposed to help surgeons during MIS. This study aims to report these technologies' current knowledge and diffusion during surgical training in Italy. A web-based survey was developed under the aegis of the Italian Society of Endoscopic Surgery (SICE). Two hundred and seventeen medical doctors' answers were analyzed. Participants were surgeons (138, 63.6%) and residents in surgery (79, 36.4%). The mean knowledge of the role of the VR, AR and MR in surgery was 4.9 ± 2.4 (range 1-10). Most of the participants (122, 56.2%) did not have experience with any proposed technologies. However, although the lack of experience in this field, the answers about the functioning of the technologies were correct in most cases. Most of the participants answered that VR, AR and MR should be used more frequently for the teaching and training and during the clinical activity (170, 80.3%) and that such technologies would make a significant contribution, especially in training (183, 84.3%) and didactic (156, 71.9%). Finally, the main limitations to the diffusion of these technologies were the insufficient knowledge (182, 83.9%) and costs (175, 80.6%). Based on the present study, in Italy, the knowledge and dissemination of these technologies are still limited. Further studies are required to establish the usefulness of AR, VR and MR in surgical training.

The coronavirus disease 2019 (COVID‐19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). COVID‐19 currently affected more than 108 million people worldwide with a fatality rate of 2.2%. Herein, we report the first case of liver transplantation (LT) performed with a liver procured from a SARS‐CoV‐2 positive donor. The recipient was a 35‐year‐old SARS‐CoV‐2 positive female patient affected by severe end‐stage HBV‐HDV‐related liver disease (model of end‐stage liver disease = 32) who had neutralizing SARS‐CoV‐2 antibodies (titers 1:320) at time of LT. The LT was successful, and the graft is functioning two months after surgery. The recipient cleared the SARS‐CoV‐2 infection 1 month after LT. The current case shows that the prompt use of SARS‐CoV‐2 infected liver donors offers an invaluable life‐saving opportunity for SARS‐CoV‐2 positive wait‐listed patients who developed neutralizing SARS‐CoV‐2 antibodies.

The development of new systemic treatment strategies has resulted in a significant increase in the response rates of colorectal liver metastases (CRLM) in the last few years. Although the radiological response is a favorable prognostic factor, complete shrinkage of CRLM, known as disappearing liver metastases (DLM), presents a therapeutic dilemma, and proper management is still debated in the literature. In fact, DLM is not necessarily equal to cure, and when resected, pathological examination reveals in more than 80% of patients a variable percentage of the tumor as residual disease or early recurrence in situ. Moreover, while a higher incidence of intrahepatic recurrence is documented in small series when surgery is avoided, its clinical significance for long-term OS is still under investigation. In light of this, a multidisciplinary approach and, in particular, radiologists’ role is needed to assist the surgeon in the management of DLM, thanks to emerging technology and strategy. Therefore, the aim of this review is to provide an overview of the DLM phenomenon and current management.

Background: Genetic evaluation is essential in assessing colorectal cancer (CRC) and colorectal liver metastasis (CRLM). The aim of this study was to determine the pragmatic value of KRAS on oncological outcomes after CRLM according to the ESMO recommendations and to query whether it is necessary to request KRAS testing in each situation. Methods: A retrospective cohort of 126 patients who underwent surgery for hepatic resection for CRLM between 2009 and 2020 were reviewed. The patients were divided into three categories: wild-type KRAS, mutated KRAS and impractical KRAS according to their oncological variables. The impractical (not tested) KRAS group included patients with metachronous tumours and negative lymph nodes harvested. Disease-free survival (DFS), overall survival (OS) and hepatic recurrence-free survival (HRFS) were calculated by the Kaplan–Meier method, and a multivariable analysis was conducted using the Cox proportional hazards regression model. Results: Of the 108 patients identified, 35 cases had KRAS wild-type, 50 cases had a KRAS mutation and the remaining 23 were classified as impractical KRAS. Significantly longer medians for OS, HRFS and DFS were found in the impractical KRAS group. In the multivariable analyses, the KRAS mutational gene was the only variable that was maintained through OS, HRFS and DFS. For HRFS (HR: 13.63; 95% confidence interval (CI): 1.35–100.62; p = 0.010 for KRAS), for DFS (HR: 10.06; 95% CI: 2.40–42.17; p = 0.002 for KRAS) and for OS (HR: 4.55%; 95% CI: 1.37–15.10; p = 0.013). Conclusion: Our study considers the possibility of unnecessary KRAS testing in patients with metachronous tumours and negative lymph nodes harvested. Combining the genetic mutational profile (i.e., KRAS in specific cases) with tumour characteristics helps patient selection and achieves the best prognosis after CRLM resection.

Morbid obesity is a worldwide epidemic closely linked to Non-Alcoholic Fatty Liver Disease (NAFLD), an ever more relevant indication for Liver Transplantation (LT). Obesity affects an increasing number of LT recipients, but the ideal management of these patients remain unclear. Bariatric surgery (BS) in LT setting is challenging but feasible, although the debate is still open about the best timing of bariatric surgery. Herein we report a case of high-priority LT and simultaneous sleeve gastrectomy (SG) in an obese young adult.A 45 years old man with morbid obesity (BMI 46 kg/mIn selected patients, combined LT and SG present several advantages in terms of transplant outcomes, weight loss and resolution of obesity-related comorbidities. In addition, it can be performed in the high-priority setting in case of severe ESLD with good results in the short- and long-term.

Background Laparoscopic liver resection (LLR) is becoming essential in the treatment of malignant liver tumors but only a few reports exist about LLR for intrahepatic cholangiocarcinoma (IHCC). Methods We present a video of a laparoscopic left hemihepatectomy with lymphadenectomy for IHCC. Case presentation A 67-year-old asymptomatic male underwent a routine abdominal ultrasound, revealing a 15 × 9 mm solid nodular iso-hyperechoic lesion, located in SIII, with SII/III biliary duct dilation. Magnetic resonance imaging confirmed a 32 × 22 mm lesion in SII/III, with mild hyper-intensity on T2-weighted images and strong hypo-intensity on T1-weighted images. After administration of contrast medium, the lesion showed light peripheral enhancement on the portal and delayed phases, and hypo-intensity on the hepatospecific phase. No relevant comorbidities were reported (KPS 100). Laboratory tests showed normal liver function and normal CA19-9 levels. A laparoscopic left hemihepatectomy was indicated. Results Operative time was 330 min. Four intermittent Pringle maneuver cycles were applied and no blood transfusions were administered. Intraoperative ultrasound confirmed preoperative findings and additionally highlighted involvement of the SIV duct. A full replacing right hepatic artery arising from the superior mesenteric artery was identified and was preserved during hilar dissection. Postoperative course was uneventful and the patient was discharged on postoperative day 3. The pathology report indicated cholangiocellular carcinoma pT1bN0. Twelve lymph nodes were retrieved. Conclusions According to recent literature reports and our experience, laparoscopic surgery for intrahepatic cholangiocellular carcinoma should be considered feasible and safe in selected patients. Hepatic artery variations allow for adequate lymphadenectomy. Oncological long-term results require multicenter randomized studies in order to be validated.

Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is influenced by several factors, primarily operator expertise. Formal training in EUS-FNA, as suggested by the European Society of Gastrointestinal Endoscopy and the American Society for Gastrointestinal Endoscopy guidelines, is not always available and is often expensive and time-consuming. In this study we evaluate factors influencing the diagnostic accuracy of pancreatic EUS-FNA.In a retrospective study, 557 consecutive EUS-FNAs were evaluated. Several variables relating to the procedures were considered to calculate the EUS-FNA performance over eight years.A total of 308 out of 557 EUS-FNAs were selected. Overall sensitivity of EUS-FNA was 66% (95% CI: 60.8-71.8), specificity 100%, and diagnostic accuracy 69% (95% CI: 64.0-74.4). An increase in diagnostic accuracy was observed to90% using a new fine-needle biopsy (FNB) needle and in the case of simultaneous sampling of primary and metastatic lesions. Diagnostic accuracy80% was observed after 250 procedures, in the absence of rapid on-site cytopathological examination (ROSE). Multivariate logistic regression analysis confirmed that the FNB needle, operator skill, and double EUS-FNA sampling are associated with high diagnostic accuracy.The learning curve for EUS-FNA may be longer and a considerable number of procedures are needed to achieve high diagnostic accuracy in the absence of ROSE. However, the use of FNB needles and the simultaneous sampling of primary and metastatic lesions can rapidly improve the diagnostic accuracy of the procedure.

BACKGROUND & AIMS Missed or inappropriate referrals of potential candidates for liver transplantation (LT) are common and traditional referral methods (tRs) do not allow for efficient triage. We investigated the effects of a website developed for electronic outpatient referral to LT (eRW-LT) on these issues. METHODS We prospectively collected data on all consecutive outpatient referrals to 2 Italian LT centers from January 2015 to December 2019. In the second half of the study, starting from July 2017, referring physicians had the option of using eRW-LT, quickly obtaining the judgment on the appropriateness and urgency of the visit from a transplant hepatologist. RESULTS In the second half of the study, there were 99 eRW-LTs and 96 traditional referrals (new tRs), representing a 17.4% increase over the 161 traditional referrals (old tRs) of the first half. With eRW-LT, 11.1% of referrals were judged inappropriate online without booking a visit. Appropriateness, judged at the time of the first visit, was 59.6%, 56.2%, and 94.3% with old tRs, new tRs, and eRW-LT, respectively. Considering the appropriate visits, the median waiting time in days between referral date and first visit appointment was significantly shorter for urgent visits referred with eRW-LT (5.0; 95% CI, 4.8-9.3) compared with nonurgent visits sent with the same system (17.0; 95% CI, 11.5-25.0; P < .0001), those referred with old tRs (14.0; 95% CI, 8.0-23.0; P < .001) and with new tRs (16.0; 95% CI, 10.0-23.0; P < .001). CONCLUSIONS eRW-LT allows an increase in the number of referrals for LT, ensuring effective triage and better appropriateness of visits.

Background Ambulatory surgery is an efficient, safe and widely performed procedure; this study would shows the advantages of the ambulatory laparoscopic cholecystectomy procedure from the point of view of patients and the Hospital/National Health System. Materials and Methods: Single-center retrospective cohort study including 288 patients who underwent laparoscopic-cholecystectomy at **** from January 2016 to July 2018. Ambulatory LC were compared to well-matched inpatient procedures performed in the same study period. The primary endpoints was the 30-day readmission rate. Secondary endpoints were the discharge rate in the ambulatory group, the post-operative complications rate and cost effectiveness. Results: 120/288 (41.7%) patients underwent ambulatory laparoscopic cholecystectomy. Thirty-two (26.7%) patients who underwent ambulatory laparoscopic cholecystectomy had major preoperative comorbidities and 35 (29.2%) had undergone prior abdominal surgery. The readmission rates for ambulatory patients and inpatients were 0.8% and 1.7% (p = 0.56), respectively; 104 (86.7%) ambulatory patients were discharged successfully on the same day. The two groups showed the same post-operative complication rate (p = 0.40). Ambulatory procedures resulted in related cost savings of more than 300% for the hospital and a remarkable financial benefit for the National Italian Healthcare System, accounting for savings exceeding € 27 000 per year. Conclusions: Ambulatory laparoscopic cholecystectomy is safe and cost effective. Since a third of ambulatory patients showed comorbidity or previous abdominal surgery, we believe that this procedure may be performed safely in a tertiary HPB centre, even in complex patients., Highlights • Ambulatory laparoscopic cholecistectomy is an efficient, safe and feasible procedure. • Ambulatory Laparoscopic cholecistectomy may also be offered to complex patients. • Ambulatory laparoscopic cholecystectomy is cost effective for both Hospital and National Health System.

Pancreatic cystic neoplasms (PCNs) are a frequent incidental finding during an ultrasound or other radiological investigations. As PCNs may have a potential of malignancy, a precise differential diagnosis between a malignant and benign lesion is crucial to define appropriate management of patients with this kind of lesions. Radiology, with computed tomography (CT) and magnetic resonance imaging, may not be conclusive in the diagnostic assessment of PCNs. Endoscopic ultrasound (EUS), a simple and relatively low invasive technique, is able to identify intra-cystic worrisome features suggesting malignancy. Fine-needle aspiration (FNA) of the cystic fluid or of intra-cystic tissue nodule during EUS is an adjunctive procedure for reaching a conclusive diagnosis. As EUS-FNA is burdened by complications, the use of intravenous contrast may increase the diagnostic accuracy of EUS allowing in many cases a correct diagnosis of PCN at high risk of malignancy, without additional risk of complication during the procedure. The present report deals with the case of a cystic lesion found by CT scan in the pancreatic head of a 59-year-old woman suffering from mild epigastric pain. Once submitted to EUS, malignant nature of PCN was suspected due to the finding of a typical worrisome feature, the presence of a mural nodule. The intravenous administration of contrast medium during the EUS confirmed malignancy and the patient was immediately sent to the surgeon for pancreatic resection. Histology revealed an intraductal papillary mucinous neoplasm, with areas of high-grade dysplasia in the main and secondary ducts, progressed toward an invasive carcinoma.

A platinum salt (oxaliplatin or cisplatin) is widely used to enhance chemoradation (CRT) response. The potential of cisplatin in neoadjuvant CRT for locally advanced rectal cancer (LARC) has not been fully investigated. Consecutive patients with histologically confirmed LARC were treated with standard pelvic radiotherapy and concurrent cisplatin plus capecitabine (CisCape CRT). Surgery and eight cycles of adjuvant FOLFOX4 were offered to all patients after CRT. Common biochemical variables and key germline genetic polymorphisms were analyzed as predictors of pathological complete response (pCR). Fifty-one patients were enrolled. pCR (regression AJCC grade 0) was documented in 7 patients (14%), nearly complete response (AJCC grade 1) in 10 pts. There was a strong association between disease-free survival and AJCC grade (p 0.0047). Grade 3-4 toxicities (mainly diarrhea) was observed in 41% of patients. Among all analyzed variables, baseline hemoglobin (Hb) was significantly associated with AJCC grade 0-1 response (p 0.027). As for the pharmacogenetic analysis, XRCC1 rs25487 polymorphism was significantly associated with AJCC grade 0-1, Odds Ratio 25.8, p 0.049. AJCC grade 0-1 response rate for patients with high Hb and/or XRCC1 rs25487 G/G genotype was as high as 57%. Baseline Hb and XRCC1 polymorphisms are valuable selection criteria for the CisCape CRT regimen, given its otherwise meaningful toxicity.

Background. Normalization of arterial pressure occurs in just a few patients with hypertensive chronic kidney disease undergoing kidney transplantation. Hypertension in kidney transplant recipients may be related to multiple factors. We aimed to assess whether hypertension in kidney-transplanted patients may be linked to reinnervation of renal arteries of the transplanted kidney. Methods. We investigated renal arteries innervation from native and transplanted kidneys in three patients 5 months, 2 years and 11 years after transplantation, respectively. Four transplanted kidneys from non-hypertensive patients on immunosuppressive treatment without evidence of hypertensive arteriolar damage were used as controls. Results . Evidence of nerve sprouting was observed as early as 5 months following transplantation, probably originated from ganglions of recipient patient located near the arterial anastomosis and was associated with mild hypertensive arteriolar damage. Regeneration of periadventitial nerves was already complete 2 years after transplantation. Nerve density tended to reach values observed in native kidney arteries and was associated with hypertension-related arteriolar lesions in transplanted kidneys. Control kidneys, albeit on an immunosuppressive regimen, presented only a modest regeneration of sympathetic nerves. Conclusions . Our results suggest that the considerable increase in sympathetic nerves, as found in patients with severe arterial damage, may be correlated to hypertension rather than to immunosuppressive therapy, thus providing a morphological basis for hypertension recurrence despite renal denervation.

Background Renal denervation represents an emerging treatment for resistant hypertension in patients with end‐stage renal disease, but data about the anatomic substrate of this treatment are lacking. Therefore, the aim of this study was to investigate the morphological basis of sympathetic hyperactivity in the setting of hemodialysis patients to identify an anatomical substrate that could warrant the use of this new therapeutic approach. Methods and Results The distribution of sympathetic nerves was evaluated in the adventitia of 38 renal arteries that were collected at autopsy or during surgery from 25 patients: 9 with end‐stage renal disease on dialysis ( DIAL group) and 16 age‐matched control nondialysis patients ( CTRL group). Patients in the DIAL group showed a significant increase in nerve density in the internal area of the peri‐adventitial tissue (within the first 0.5 mm of the beginning of the adventitia) compared with the CTRL group (4.01±0.30 versus 2.87±0.28×mm 2 , P =0.01). Regardless of dialysis, hypertensive patients with signs of severe arteriolar damage had a greater number of nerve endings in the most internal adventitia, and this number was significantly higher than in patients without hypertensive arteriolar damage (3.90±0.36 versus 2.87±0.41×mm 2 , P =0.04), showing a correlation with hypertensive arteriolar damage rather than with hypertensive clinical history. Conclusions The findings from this study provide a morphological basis underlying sympathetic hyperactivity in patients with end‐stage renal disease and might offer useful information to improve the use of renal denervation in this group of patients.

Highlights • Liver transplantation using a donor with situs inversus totalis is feasible and safe. • The anatomical anomalies in the donor with situs inversus totalis should not be considered a controindication to liver transplantation. • The 1992-Belghiti piggyback technique represents an excellent surgery option for liver transplantation., Introduction The donor situs inversus totalis status was considered an absolute contraindication to liver transplantation due to the technical difficulties involved. Only in recent years has a very young deceased donor with situs inversus totalis been considered as a potential donor. Presentation of case We herein report a single case of 57-year-old male patient with hepatocellular carcinoma who received a liver transplantation from a 73-year-old woman with situs inversus totalis. Liver was implanted using a 1992-Belghiti piggyback technique positioning the larger hemiliver in the left upper quadrant and the left in the liver fossa. We assisted a good graft reperfusion without surgical or anesthetic problems. His hospital stay was relatively uneventful and he was discharged from hospital on postoperative day 7. At 8 months of follow-up the patient is alive and in good clinical condition. Discussion The donor situs inversus totalis does not require any modification of transplant procedure if the donor–recipient size match permits a comfortable placement of the graft in a standard anatomical position. To the best of our knowledge, this is the first case of liver transplantation with a graft from a “marginal” donor with situs inversus totalis using a 1992-Belghiti piggyback technique. Conclusion The donor situs inversus totalis status should not be considered a contraindication for LT and the piggyback technique should be considered the surgery of choice.

Advagraf is a new modified-release once-daily formulation of tacrolimus. The aim of this study was to define the efficacy and safety of switching from Prograf to Advagraf immunosuppression in kidney transplant recipients. The switched dose ratio of Prograf to Advagraf was 1:1. Forty-one patients (34 men and 7 women) were switched at 36.6 ± 16.1 months after kidney transplantation. All patients maintained stable renal function and the conversion. In 16 subjects it was possible to withdraw steroid administration after obtaining adequate Advagraf blood levels, among whom 14 remained steroid free. Adverse events, including dizziness and tinnitus, were reported in 1 patient, who was reverted to Prograf. One patient who was receiving triple therapy with low tacrolimus blood levels experienced are acute rejection episode. The switch to Advagraf was safe and efficacious in kidney transplant recipients with or without steroid administration. Moreover, interruption of steroid was possible and well tolerated after achieving adequate stable blood levels with Advagraf.

The hemolytic uremic syndrome (HUS) is a severe disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. We herein report our experience with a 43-year-old female patient who underwent a second cadaveric kidney transplantation in February 2005, for adult-onset HUS. The first renal transplantation, which was performed in 1996, required removal after 3 weeks for probable recurrence of HUS. The immunosuppressive regimen for the second transplant included basiliximab, tacrolimus, mycophenolate mofetil, and steroids. On postoperative day (POD) 7, she received steroid treatment for an acute rejection episode with improved renal function. On POD 19 due to worsening renal function, a graft biopsy showed HUS recurrence, thus we instituted hemodialysis and then plasmapheresis treatments. At two months after transplantation, the patient continued under plasmapheresis treatment due to clinical evidence of HUS. On POD 80, cytomegalovirus infection was diagnosed and intravenous gancyclovir treatment started for 3 weeks. After 110 days from transplant, a deterioration in renal function was evident: the graft was swollen and painful with Doppler ultrasound showing patency of both the renal artery and vein but, low blood flow. After 2 weeks of hemodialysis, the patient underwent transplantectomy. In adult-onset HUS the recurrence rate reduces graft survival, particularly among patients undergoing second transplantation.

Biliary lipids output is reduced after liver transplantation and tends to normalize thereafter. Cyclosporine A (CyA) is reported to interfere with the normal bile-restoring process after liver grafting, but data are inconclusive, in particular regarding the comparison with the other widely used calcineurin inhibitor tacrolimus (TCR). Furthermore, previous researches were conducted in patients taking multiple immunosuppressive therapies and with a short follow up. In this study we readdressed this issue by comparing biliary lipids in the first 3 months after liver transplant, in 20 patients randomized to receive immunosuppression with CyA or TCR monotherapy. Bile samples, harvested through a T-tube at days 1, 3, 7, 15, 30, 60 and 90 were assessed for cholesterol, phospholipids, and total and individual concentrations of bile acids (BA). Liver and kidney function tests were evaluated as well. We found no differences between CyA and TCR in biochemical findings or in total biliary BAs, cholesterol, and phospholipids. However, CyA-treated patients showed lower levels of glycochenodeoxycholic acid at day 15, compared to those treated with TCR (P < 0.04). This difference normalized thereafter, without any biochemical or clinical effect at 3-month follow up.

Prednisone has been commonly considered the mainstay of immunosuppressive therapy after liver transplantation. Recent data suggest that prednisone withdrawal late after transplant reduces complications without affecting graft function. We report here the preliminary results of an open-label, randomized study aimed at investigating whether prednisone therapy can be completely avoided during the first 3 months after transplantation. Twenty-seven consecutive patients were randomized to receive double (group A: cyclosporine and azathioprine) or triple (group B: prednisone, cyclosporine, and azathioprine) immunosuppressive therapy after liver transplantation. Six patients died within the first 3 weeks in each group and were excluded from the calculations. The present results refer to 10 patients in group A and 11 in group B. The actuarial 1-year survival did not differ between the two groups (90.9% vs 88.8%). There were no differences with respect to infectious complications or episodes of histological acute graft rejections. Only one severe acute rejection occurred in group A and two in group B. During the first month after transplant, liver and kidney functions tended to be better in the group of patients treated without prednisone, although there were no differences in the mean cyclosporine blood levels. These data, though preliminary, indicate that early immunosuppression without the use of prednisone is safe and tends to be associated with improved liver and renal functions compared to conventional triple therapy.