The Effects of Sustained Immunosuppression Withdrawal After Liver Transplantation on Metabolic Syndrome.

BACKGROUND: Liver transplant (LT) recipients often experience adverse effects of immunosuppressive (IS) drugs, especially on metabolic profiles. Selected LT recipients can achieve successful IS withdrawal; however, its effects on metabolic syndrome (MS) are unknown. METHODS: This is a retrospective single-center study investigating the incidence and/or regression of MS in 75 selected LT recipients who were previously enrolled in prospective IS withdrawal trials between 1999 and 2017. Patients who were transplanted due to nonalcoholic steatohepatitis/metabolic-associated fatty liver disease were excluded, as well as those with a follow-up <3 y after IS weaning. RESULTS: Forty-four patients (58.7%) achieved sustained withdrawal or minimization of immunosuppression (WMIS) and 31 patients (41.3%) required reintroduction of immunosuppression (no-WMIS). Among LT recipients who were metabolically healthy (n = 52, 69.3%) before the start of IS weaning, there was a significantly lower rate of de novo MS in WMIS patients compared with no-WMIS patients after 5 y (8.3% and 47.8%, respectively, P = 0.034). Of 23 LT recipients (30.7%) who had MS at the time of commencing IS withdrawal, complete regression of MS was observed in 47.1% of WMIS patients and in none (0%) of the no-WMIS patients after 5 y (P = 0.054). Furthermore, individual components of MS were better controlled in IS-weaned patients, such as arterial hypertension and abnormal serum lipids. CONCLUSIONS: Achievement of sustained IS withdrawal reduces the incidence of de novo MS development in metabolically healthy patients and increases the likelihood of MS regression in patients with established MS. The foreseeable long-term beneficial effects of these favorable metabolic changes on morbidity and mortality of LT recipients require further investigation.

What Is the Role of Minimally Invasive Liver Surgery in Treating Patients with Hepatocellular Carcinoma on Cirrhosis?

Minimally invasive liver surgery (MILS) has been slowly introduced in the past two decades and today represents a major weapon in the fight against HCC, for several reasons. This narrative review conveys the major emerging concepts in the field. The rise in metabolic-associated steatotic liver disease (MASLD)-related HCC means that patients with significant cardiovascular risk will benefit more profoundly from MILS. The advent of efficacious therapy is leading to conversion from non-resectable to resectable cases, and therefore more patients will be able to undergo MILS. In fact, resection outcomes with MILS are superior compared to open surgery both in the short and long term. Furthermore, indications to surgery may be further expanded by its use in Child B7 patients and by the use of laparoscopic ablation, a curative technique, instead of trans-arterial approaches in cases not amenable to radiofrequency. Therefore, in a promising new approach, multi-parametric treatment hierarchy, MILS is hierarchically superior to open surgery and comes second only to liver transplantation.

Evaluation of Humoral Response following SARS-CoV-2 mRNA-Based Vaccination in Liver Transplant Recipients Receiving Tailored Immunosuppressive Therapy.

Background: The role of tailored immunosuppression (IS) in the development of the humoral response (HR) to SARS-CoV-2 mRNA-based vaccination in liver transplant (LT) recipients is unknown. Methods: This is a single-centre prospective study of patients who underwent LT between January 2015 and December 2021 and who have received three doses of mRNA-based SARS-CoV-2 vaccination. Patients undergoing Tacrolimus-based immunosuppression (TAC-IS) were compared with those undergoing Everolimus-based immunosuppression (EVR-IS). Patients receiving the TAC-EVR combination were divided into two groups based on trough TAC concentrations, i.e., above or below 5 ng/mL. HR (analysed with ECLIA) was assessed at 30 to 135 days after vaccination. The primary outcome was the presence of a positive antibody titre (≥0.8 U/mL). Secondary outcomes were the presence of a highly protective antibody titre (≥142 U/mL), median antibody titre, and incidence of COVID-19. Results: Sixty-one participants were included. Twenty-four (40%) were receiving TAC-IS and thirty-seven (60%) were receiving EVR-IS. At the median follow-up of 116 (range: 89-154) days, there were no significant differences in positive antibody titre (95.8% vs. 94.6%; p = 0.8269), highly-protective antibody titre (83.3% vs. 81.1%; p = 0.8231), median antibody titre (2410 [IQ range 350-2500] vs. 1670 [IQ range 380-2500]; p = 0.9450), and COVID-19 incidence (0% vs. 5.4%; p = 0.5148). High serum creatinine and low estimated glomerular filtration rate were risk factors for a weak or absent HR. Conclusions: Three doses of mRNA-based SARS-CoV-2 vaccination yielded a highly protective HR in LT recipients. The use of TAC or EVR-based IS does not appear to influence HR or antibody titre, while renal disease is a risk factor for a weak or null HR.

Primary versus Salvage Liver Transplantation after Curative-Intent Resection or Radiofrequency Ablation for Hepatocellular Carcinoma: Long-Term Oncological Outcomes.

Liver transplantation for hepatocellular carcinoma (HCC) may be performed ab initio, primary liver transplantation (PLT), or for HCC recurrence after previous treatments such as liver resection (LR) or radiofrequency ablation (RFA), salvage liver transplantation (SLT). The aim of this study was to evaluate the oncological outcomes of SLT vs. PLT. For this, a retrospective study was carried out on patients undergoing liver transplantation for HCC. The outcomes of PLT were compared with those of SLT. The primary outcome was disease-free survival (DFS). The secondary outcomes included overall survival (OS), cancer-specific survival (CSS), and major postoperative complications. A sub-analysis of SLT-LR and SLT-RFA was also performed. In total, 141 patients were included: 96 underwent PLT and 45 SLT. Among the SLT group, 25 patients had undergone previous LR while 20 had had RFA. There were no differences in the major postoperative complications. Unadjusted DFS was significantly longer in the PLT group (p = 0.02), as were OS (p = 0.025) and CSS (p = 0.001). There was no difference in DFS between PLT and SLT-LR groups, while a significant difference was found between the PLT and SLT-RFA groups (p = 0.035). Nonetheless, DFS was no different between the SLT-LR and SLT-RFA groups. PLT appears to offer superior long-term oncological outcomes to SLT. Both SLT-LR and SLT-RFA offer acceptable OS and CSS. Further prospective studies are needed to confirm these results, but the re-direction of grafts and transplant philosophy towards PLT rather than SLT may need to be considered.

The impact of center volume on the utilization and outcomes of machine perfusion technology in liver transplantation: An international survey.

INTRODUCTION: Machine perfusion (MP) was developed to expand the donor pool and improve liver transplantation (LT) outcomes. Despite optimal results in clinical trials, the real-world MP benefit in centers with low-/mid-volume activity (LVCs) is still being determined. METHODS: Online survey on MP for LT, distributed to worldwide LT-centers representatives. Variables of interest included logistics, technicalities, and outcomes. Responders were grouped into high-volume centers (HVCs) (>60 LTs/year) and LVCs and results compared. RESULTS: Sixty-seven centers were included, 36 HVCs and 31 LVCs. Significant differences in MP regarded: (I) existence of an established program (80.6% vs. 41.9%; p = 0.02), (II) presence of a dedicated perfusionist (58.3% vs. 22.6%; p = 0.006), (III) duration (>4 h: 47.2% vs. 16.1%; p = 0.01), (IV) routine use (20%-40% vs. 5%-20%; p = 0.002), (V) graft utilization (>50%: 75% vs. 51.6%; p = 0.009), (VI) 90-day patient-survival (90%-100% vs. 50%-90%; p = 0.001) and (VII) subjectively perceived benefit (always vs. only in selected ECD; p = 0.009). Concordance was found for indications, type, viability tests, graft-salvage, 90-day graft-loss, and major-complications. CONCLUSIONS: This study captured a picture of MP in real-world LT-practice. Significant disparities have surfaced between LVCs and HVCs regarding logistics, utilization, and results. To close this gap, efforts should be made to more efficiently deliver dedicated support, training and mentoring to LVC teams adopting MP technology.

Liver-Specific Contrast-Enhanced Magnetic Resonance Cholangio-Pancreatography (Ce-MRCP) in Non-Invasive Diagnosis of Iatrogenic Biliary Leakage.

Current non-invasive diagnostic modalities of iatrogenic bile leak (BL) are not particularly sensitive and often fail to localise the BL origin. Percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP) are considered the gold standard, yet are invasive studies with potential complications. Ce-MRCP has been not comprehensively studied in this setting but may prove particularly helpful given its non-invasive nature and the anatomical dynamic detail. This paper reports a monocentric retrospective study of BL patients referred between January 2018 and November 2022 submitted to Ce-MRCP followed by PTC. The primary outcome was the accuracy of Ce-MRCP in detecting and localising BL compared to PTC and ERCP. Blood tests, coexisting cholangitis features and time for leak resolution were also investigated. Thirty-nine patients were included. Liver-specific contrast-enhanced MRCP detected BL in 69% of cases. The BL localisation was 100% accurate. Total bilirubin above 4 mg/dL was significantly associated with false negative results of Ce-MRCP. Ce-MRCP is highly accurate in detecting and localising BL, but sensitivity is significantly reduced by a high bilirubin level. Ce-MRCP may be very useful in early BL diagnosis and in accurate pre-treatment planning, but can only be reliably used in selected patients with TB < 4 mg/dL. Non-surgical techniques, both radiological and endoscopic, are proven to be effective in terms of leak resolution.

Therapeutic Strategies and Oncological Outcome of Peritoneal Metastases from Lung Cancer: A Systematic Review and Pooled Analysis.

The peritoneum is an unusual site of metastases from lung cancer, and optimal management at the moment remains unclear and mostly based on palliative strategies. Therefore, the aim of the study was to investigate demographic characteristics, management and overall survival of patients with peritoneal metastases from lung cancer (PCLC). A PRISMA-compliant systematic review and pooled analysis was performed searching all English studies published until December 2022. PROSPERO, CRD42022349362. Inclusion criteria were original articles including patients with peritoneal carcinomatosis from lung cancer, specifying at least one outcome of interest. Exclusion criteria were being unable to retrieve patient data from articles, and the same patient series included in different studies. Among 1746 studies imported for screening, twenty-one were included (2783 patients). Mean overall survival was between 0.5 and 5 months after peritoneal carcinomatosis diagnosis and 9 and 21 months from lung cancer diagnosis. In total, 27% of patients underwent first-line or palliative chemotherapy and 7% of them surgery. Management differs significantly among published studies. The literature on PCLC is scarce. Its incidence is low but appears to be substantially rising and is likely to be an underestimation. Prognosis is very poor and therapeutic strategies have been limited and used in a minority of patients. Subcategories of PCLC patients may have an improved prognosis and may benefit from an aggressive oncological approach, including cytoreductive surgery. Further investigation would be needed in this regard.

Implementation of Blockchain Technology Could Increase Equity and Transparency in Organ Transplantation: A Narrative Review of an Emergent Tool.

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.

Ambulatory laparoscopic colectomies: a systematic review.

AIM: Ambulatory laparoscopic colectomy (ALC), meaning discharge within 24 h of surgical colonic resection, has recently been proposed in a few, selected patients. This systematic review was performed with the aim of reviewing protocols for ALC and assessing feasibility, safety and outcomes after ALC. METHOD: A PRISMA-compliant systematic review and pooled analysis was performed searching all English studies published until October 2022 in PubMed, Cochrane Library, Web of Science (PROSPERO, CRD42022334463). Inclusion criteria were original articles including patients undergoing ALC, specifying at least one outcome of interest. Exclusion criteria were articles reporting a robotic-assisted procedure; unable to retrieve patient data from articles; the same patient series included in different studies. Primary outcomes were success, overall complications and readmission rates. Secondary outcomes included mortality and specific complications such us surgical site infection, anastomotic leak, ileus, bleeding, rate of ALC acceptance, and unscheduled consultation and reoperation rate. RESULTS: Among 1087 studies imported for screening, 11 were included (1296 patients). The success rate was 47% with an overall morbidity of 14%. Readmission and reoperation rates were 5% and 1%, respectively. No mortality was recorded. Protocols of ALC differ significantly among published studies. CONCLUSIONS: Overall, ALC appears to be safe and feasible in selected cases with an acceptable success rate and a low risk of readmission after hospital discharge. Future studies should evaluate patients' benefits and discharge criteria, as well as uniformity and standardization of eligibility criteria. This systematic review may help inform on ALC adoption in clinical practice.

Evolution of Bariatric Surgery in Italy in the Last 11 Years: Data from the SICOB Yearly National Survey.

BACKGROUND: Bariatric surgery (BS) is a relatively novel surgical field and is in continuous expansion and evolution. PURPOSE: Aim of this study was to report changes in Italian surgical practice in the last decade. METHODS: The Società Italiana di Chirurgia dell'Obesità (SICOB) conducted annual surveys to cense activity of SICOB centers between 2011 and 2021. Primary outcome was to detect differences in frequency of performance of adjustable gastric banding (AGB), sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), one anastomosis gastric bypass (OAGB), bilio-pancreatic diversion (BPD), and gastric plication (GP). Secondary outcome was to detect differences in performance of main non-malabsorptive procedures (AGB + SG) and overall bypass procedures (RYGB + OAGB). Geographical differences were also investigated. RESULTS: Median response rate was 92%. AGB declined from 36% of procedures in 2011 to 5% in 2021 (p < 0.0001). SG increased from 30% in 2011 to 55% in 2021 (p < 0.0001). RYGB declined from 25 to 12% of procedures (p < 0.0001). OAGB rose from 0% of procedures in 2011 to 15% in 2021 (p < 0.0001). BPD underwent decrease from 6.2 to 0.2% in 2011 and 2021, respectively (p < 0.0001). Main non-malabsorptive procedures significantly decreased while overall bypass procedures remained stable. There were significant differences among regions in performance of SG, RYGB, and OAGB. CONCLUSIONS: BS in Italy evolved significantly during the past 10 years. AGB underwent a decline, as did BPD and GP which are disappearing and RYGB which is giving way to OAGB. The latter is rising and is the second most-performed procedure after SG which has been confirmed as the preferred procedure by Italian bariatric surgeons.

Safety and Efficacy of Laparoscopic Vertical Clip Gastroplasty: Early Results of an Italian Multicenter Study.

PURPOSE: Sleeve gastrectomy, the most commonly performed bariatric surgery procedure, carries limitations both short term including postoperative complications such as hemorrhage and gastric fistula and long term such as weight regain and gastroesophageal reflux. A new procedure has been proposed to overcome many of these limitations: laparoscopic vertical clip gastroplasty (LVCG) with BariClip. MATERIALS AND METHODS: Fifty patients were offered LVCG and enrolled for a feasibility study in two referral bariatric centers. Indication was given as for sleeve gastrectomy, after a multidisciplinary path evaluating age, gender, BMI, comorbidities, eating behaviors, and gastroesophageal reflux. The primary outcome was major postoperative complications. Secondary outcomes included weight loss, incidence of de-novo GERD, and comorbidity resolution. RESULTS: Patients had a mean age of 44 years and mean BMI of 37 kg/m2 ± 6.2. All procedures were performed successfully in laparoscopy, with no conversion or intraoperative adverse events. The overall major postoperative complication rate was 6%. Re-operation was required in three patients for slippage. No mortality occurred. Excess weight loss, excess BMI loss, and total weight loss at 6 months were 36%, 57%, and 22%, respectively. There was no instance of de-novo GERD. Resolution of hypertension occurred in 50% of cases, OSAS in 65% of cases, and DMII in 80% of cases. CONCLUSION: The safety of LVCG procedure has been reproduced in a multicentric, multi-surgeon study. Weight loss outcomes appear promising. A randomized trial is needed to fully assess the benefits of LVCG.

Definition and reporting of lymphadenectomy and complete mesocolic excision for radical right colectomy: a systematic review.

BACKGROUND: Several procedures have been proposed to reduce the rates of recurrence in patients with right-sided colon cancer. Different procedures for a radical right colectomy (RRC), including extended D3 lymphadenectomy, complete mesocolic excision and central vascular ligation have been associated with survival benefits by some authors, but results are inconsistent. The aim of this study was to assess the variability in definition and reporting of RRC, which might be responsible for significant differences in outcome evaluation. METHODS: PRISMA-compliant systematic literature review to identify the definitions of RRC. Primary aims were to identify surgical steps and different nomenclature for RRC. Secondary aims were description of heterogeneity and overlap among different RRC techniques. RESULTS: Ninety-nine articles satisfied inclusion criteria. Eight surgical steps were identified and recorded as specific to RRC: Central arterial ligation was described in 100% of the included studies; preservation of mesocolic integrity in 73% and dissection along the SMV plane in 67%. Other surgical steps were inconstantly reported. Six differently named techniques for RRC have been identified. There were 35 definitions for the 6 techniques and 40% of these were used to identify more than one technique. CONCLUSIONS: The only universally adopted surgical step for RRC is central arterial ligation. There is great heterogeneity and consistent overlap among definitions of all RRC techniques. This is likely to jeopardise the interpretation of the outcomes of studies on the topic. Consistent use of definitions and reporting of procedures are needed to obtain reliable conclusions in future trials. PROSPERO CRD42021241650.

Disappearing Colorectal Liver Metastases: Do We Really Need a Ghostbuster?

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.

Pancreatic Adeno-MiNEN, a Rare Newly Defined Entity with Challenging Diagnosis and Treatment: A Case Report with Systematic Literature Review and Pooled Analysis.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) are a peculiar entity that can occur throughout the whole gastrointestinal trait, and pancreatic localization is rare. Their main characteristic is the presence of at least a neuroendocrine and an epithelial component, each accounting for at least 30% of the tumour mass. The presence of epithelial ductal component defines adeno-MiNEN. We report a case of a 59-year-old woman affected by pancreatic adeno-MiNEN with challenging diagnosis and successfully treated. A systematic literature review and pooled analysis was also performed, aiming to define the management and outcomes of pancreatic adeno-MiNEN. Out of 190 identified records, 15 studies including 28 patients affected by pancreatic-adeno-MiNEN were included in the analysis. Pancreatic adeno-MiNEN occurred mainly in males (82.8%) and at a mean age of 61.7 (range: 24-82) years. Pre-operative diagnosis was possible only in 14.2% of cases. At presentation, the majority had already advanced disease (TNM stage III (53.8%) and stage IV 19.3%). Adjuvant therapy was performed in 55% of patients, and the tumour recurrence rate was in 30% of cases. Median disease-free survival (DFS) was 12 months (range: 0-216 months) with a 5-year DFS of 16.6%, while the median overall survival (OS) was 12 months (range: 0-288 months) with a 5-year OS of 23.5%. Pancreatic adeno-MiNENs are rare; as they have very heterogenous behaviour, they are rarely diagnosed preoperatively and have poor prognosis. Treatment of localised MiNEN still relies on radical surgical resection, which seems essential to achieve a good oncological prognosis. International registry on MiNEN is necessary to improve the knowledge on this rare tumour and to improve its outcomes.

Nutritional Status after Roux-En-Y (Rygb) and One Anastomosis Gastric Bypass (Oagb) at 6-Month Follow-Up: A Comparative Study.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) are two effective bariatric surgical procedures with positive outcomes in terms of weight loss, comorbidities remission, and adverse events profiles. OAGB seems to carry a higher risk of malnutrition, but existing data are controversial. The aim of this study is to objectively evaluate and compare malnutrition in patients undergoing RYGB and OAGB. METHODS: Retrospective monocentric study of obese patients undergoing RYGB or OAGB between the 15 September 2020 and the 31 May 2021. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score and compared between groups. The primary outcome was the mean CONUT score at 6 months. The secondary outcomes included the incidence of malnutrition, comorbidities, including hypertension, insulin resistance and type II diabetes mellitus, and weight loss. RESULTS: 78 patients were included: 30 underwent RYGB and 48 underwent OAGB. At 6-Month Follow-Up there was no difference between groups in the mean CONUT score nor in incidence of malnutrition. In both groups, the nutritional status significantly worsened 6 months after surgery (preoperative and postoperative score of 0.48 ± 0.9 and 1.38 ± 1.5; p = 0.0066 for RYGB and of 0.86 ± 1.5 and 1.45 ± 1.3; p = 0.0422 for OAGB). Type II Diabetes mellitus (DMII) and hypertension remission were significant in the OAGB group with a 100% relative remission in the DMII-OAGB group (p = 0.0265), and a 67% relative remission in the hypertension-OAGB group (p = 0.0031). CONCLUSIONS: No difference in nutritional status has been detected between patients undergoing RYGB or OAGB at the 6-Month Follow-Up. Both procedures may have significant mal-absorptive effects leading to decline in nutritional status. OAGB may be more efficacious in inducing DMII and hypertension remission. Larger prospective studies dedicated specifically to nutritional status after gastric bypass are needed to confirm the impact of different bypass procedures on nutritional status.