Model to predict major complications following liver resection for HCC in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. AIMS: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. MATERIALS AND METHODS: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. RESULTS: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) ( https://childb.shinyapps.io/NomogramMajorMorbidity90days/ ). CONCLUSIONS: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Local recurrence risk factors and outcomes in minimally invasive thermal ablation for liver tumors: a single-institution analysis.

BACKGROUND: Minimally Invasive thermal ablation (MITA) of liver tumors is a commonly performed procedure, alone or in combination with liver resection. Despite being a first-option strategy for small lesions, it is technically demanding, and many concerns still exist about local disease control. METHODS: Consecutive patients undergoing MITA from 1-2019 to 12-2022 were retrospectively enrolled. Risk factors of local recurrence were investigated through univariate and multivariable cox regression analysis. RESULTS: At the multivariable analysis of the 207 nodules undergoing MITA, RFA was associated with worse local Recurrence Free Survival (lRFS) than MWA (HR 2.87 [95 % CI 0.96-8.66], p = 0.05), as well as a concomitant surgical resection (HR 3.89 [95 % CI 1.06-9.77], p = 0.02). A concomitant surgical resection showed worse lRFS in the subgroup analysis of both HCC (HR 3.98 [95 % CI 1.16-13.62], p = 0.02) and CRLM patients (HR 2.68 [95 % CI 0.66-5.92], p = 0.04). Interestingly, a tumor size between 30 and 40 mm was not associated to worse lRFS. CONCLUSION: MWA may reduce the risk of local recurrence in comparison to RFA, while MITA associated to liver resection may face an increased risk of local recurrence. Further prospective studies are needed to confirm such results.

Minimally Invasive Versus Open Liver Resections for Hepatocellular Carcinoma in Patients With Metabolic Syndrome.

OBJECTIVE: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS). BACKGROUND: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist. MATERIAL AND METHODS: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated. RESULTS: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P =0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P =0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P =0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P =0.015), posthepatectomy liver failure (0.6% vs 4.3%, P =0.008), and bile leaks (2.2% vs 6.4%, P =0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P =0.002) and day 3 (3.1% vs 11.4%, P <0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P <0.001). There was no significant difference in overall survival and disease-free survival. CONCLUSIONS: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible.

Preoperative planning and intraoperative real-time navigation with indocyanine green fluorescence in robotic liver surgery.

PURPOSE: We aimed at exploring indocyanine green (ICG) fluorescence wide spectrum of applications in hepatobiliary surgery as can result particularly useful in robotic liver resections (RLR) in order to overcome some technical limitations, increasing safety, and efficacy. METHODS: We describe our experience of 76 RLR performed between March 2020 and December 2022 exploring all the possible applications of pre- and intraoperative ICG administration. RESULTS: Hepatocellular carcinoma and colorectal liver metastases were the most common indications for RLR (34.2% and 26.7% of patients, respectively), and 51.3% of cases were complex resections with high IWATE difficulty scores. ICG was administered preoperatively in 61 patients (80.3%), intraoperatively in 42 patients (55.3%) and in both contexts in 25 patients (32.9%), with no observed adverse events. The most frequent ICG goal was to achieve tumor enhancement (59 patients, 77.6%), with a success rate of 94.9% and the detection of 3 additional malignant lesions. ICG facilitated evaluation of the resection margin for residual tumor and perfusion adequacy in 33.9% and 32.9% of cases, respectively, mandating a resection enlargement in 7.9% of patients. ICG fluorescence allowed the identification of the transection plane through negative staining in the 25% of cases. Vascular and biliary structures were visualized in 21.1% and 9.2% of patients, with a success rate of 81.3% and 85.7%, respectively. CONCLUSION: RLR can benefit from the routine integration of ICG fluoresce evaluation according to each individual patient and condition-specific goals and issues, allowing liver functional assessment, anatomical and vascular evaluation, tumor detection, and resection margins assessment.

Role of preoperative 3D rendering for minimally invasive parenchyma sparing liver resections.

BACKGROUND: 3D rendering (3DR) represents a promising approach to plan surgical strategies. The study aimed to compare the results of minimally invasive liver resections (MILS) in patients with 3DR versus conventional 2D CT-scan. METHODS: We performed 118 3DR for various indications; the patients underwent a preoperative tri-phasic CT-scan and rendered with Synapse3D® Software. Fifty-six patients undergoing MILS with pre-operative 3DR were compared to a similar cohort of 127 patients undergoing conventional pre-operative 2D CT-scan using the propensity score matching (PSM) analysis. RESULTS: The 3DR mandated pre-operative surgical plan variations in 33.9% cases, contraindicated surgery in 12.7%, providing a new surgical indication in 5.9% previously excluded cases. PSM identified 39 patients in both groups with comparable results in terms of conversion rates, blood loss, blood transfusions, parenchymal R1-margins, grade ≥3 Clavien-Dindo complications, 90-days mortality, and hospital stay respectively in 3DR and conventional 2D. Operative time was significantly increased in the 3DR group (402 vs. 347 min, p = 0.020). Vascular R1 resections were 25.6% vs 7.7% (p = 0.068), while the conversion rate was 0% vs 10.2% (p = 0.058), respectively, for 3DR group vs conventional 2D. CONCLUSION: 3DR may help in surgical planning increasing resectability rate while reducing conversion rates, allowing the precise identification of anatomical landmarks in minimally invasive parenchyma-preserving liver resections.

Robotic central pancreatectomy: a systematic review and meta-analysis.

BACKGROUND: Central pancreatectomy is usually performed to excise lesions of the neck or proximal body of the pancreas. In the last decade, thanks to the advent of novel technologies, surgeons have started to perform this procedure robotically. This review aims to appraise the results and outcomes of robotic central pancreatectomies (RCP) through a systematic review and meta-analysis. METHODS: A systematic search of MEDLINE, Embase, and Web Of Science identified studies reporting outcomes of RCP. Pooled prevalence rates of postoperative complications and mortality were computed using random-effect modelling. RESULTS: Thirteen series involving 265 patients were included. In all cases but one, RCP was performed to excise benign or low-grade tumours. Clinically relevant post-operative pancreatic fistula (POPF) occurred in 42.3% of patients. While overall complications were reported in 57.5% of patients, only 9.4% had a Clavien-Dindo score ≥ III. Re-operation was necessary in 0.7% of the patients. New-onset diabetes occurred postoperatively in 0.3% of patients and negligible mortality and open conversion rates were observed. CONCLUSION: RCP is safe and associated with low perioperative mortality and well preserved postoperative pancreatic function, although burdened by high overall morbidity and POPF rates.

Systematic review, meta-analysis and single-centre experience of the diagnostic accuracy of intraoperative near-infrared indocyanine green-fluorescence in detecting pancreatic tumours.

BACKGROUND: During pancreatic resections assessing tumour boundaries and identifying the ideal resection margins can be challenging due to the associated pancreatic gland inflammation and texture. This is particularly true in the context of minimally invasive surgery, where there is a very limited or absent tactile feedback. Indocyanine green (ICG) fluorescence imaging can assist surgeons by simply providing valuable real-time intraoperative information at low cost with minimal side effects. This meta-analysis summarises the available evidence on the use of near-infrared fluorescence imaging with ICG for the intraoperative visualization of pancreatic tumours (PROSPERO ID: CRD42021247203). METHODS: MEDLINE, Embase, and Web Of Science electronic databases were searched to identify manuscripts where ICG was intravenously administered prior to or during pancreatic surgery and reporting the prevalence of pancreatic lesions visualised through fluorescence imaging. RESULTS: Six studies with 7 series' reporting data on 64 pancreatic lesions were included in the analysis. MINOR scores ranged from 6 to 10, with a median of 8. The most frequent indications were pancreatic adenocarcinoma and neuroendocrine tumours. In most cases (67.2%) ICG was administered during surgery. ICG fluorescence identified 48/64 lesions (75%) with 81.3% accuracy, 0.788 (95%CI 0.361-0.961) sensitivity, 1 (95%CI 0.072-1) specificity and positive predictive value of 0.982 (95%CI 0.532-1). In line with the literature, ICG fluorescence identified 5/6 (83.3%) of pancreatic lesions during robotic pancreatic resections performed at our Institution. CONCLUSION: This meta-analysis is the first summarising the results of ICG immunofluorescence in detecting pancreatic tumours during surgery, showing good accuracy. Additional research is needed to define optimal ICG administration strategies and fluorescence intensity cut-offs.

Incidence and outcome of colorectal cancer in liver transplant recipients: A national, multicentre analysis on 8115 patients.

BACKGROUND & AIMS: De novo malignancies after liver transplantation represent one of the leading causes of death in the long-term. It remains unclear whether liver transplant recipients have an increased risk of colorectal cancer and whether this negatively impacts on survival, particularly in those patients affected by primary sclerosing cholangitis and ulcerative colitis. METHODS: In this national multicentre cohort retrospective study, the incidence of colorectal cancer in 8115 evaluable adult patients undergoing a liver transplantation between 1 January 1990 and 31 December 2010 was compared to the incidence in the general population through standardised incidence ratios. RESULTS: Fifty-two (0.6%) cases of colorectal cancer were identified at a median of 5.6 years postliver transplantation, predominantly grade 2 (76.9%) and stage T3 (50%) at diagnosis. The incidence rate of colorectal cancer in the whole liver transplant population was similar to the general UK population (SIR: 0.92), but significantly higher (SIR: 7.0) in the group of patients affected by primary sclerosing cholangitis/ulcerative colitis. One-, five- and ten-year survival rates from colorectal cancer diagnosis were 71%, 48% and 31%, respectively, and the majority of colorectal cancer patients died of cancer-specific causes. CONCLUSIONS: Liver transplantation alone is not associated with an increased risk of colorectal cancer development. The primary sclerosing cholangitis/ulcerative colitis liver transplant population showed a significantly higher risk of colorectal cancer development than the general population, with a high proportion of advanced stage at diagnosis and a reduced patient survival.

Serum amylase and lipase and urinary trypsinogen and amylase for diagnosis of acute pancreatitis.

BACKGROUND: The treatment of people with acute abdominal pain differs if they have acute pancreatitis. It is important to know the diagnostic accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the diagnosis of acute pancreatitis, so that an informed decision can be made as to whether the person with abdominal pain has acute pancreatitis. There is currently no Cochrane review of the diagnostic test accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the diagnosis of acute pancreatitis. OBJECTIVES: To compare the diagnostic accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase, either alone or in combination, in the diagnosis of acute pancreatitis in people with acute onset of a persistent, severe epigastric pain or diffuse abdominal pain. SEARCH METHODS: We searched MEDLINE, Embase, Science Citation Index Expanded, National Institute for Health Research (NIHR HTA and DARE), and other databases until March 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase. SELECTION CRITERIA: We included all studies that evaluated the diagnostic test accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the diagnosis of acute pancreatitis. We excluded case-control studies because these studies are prone to bias. We accepted any of the following reference standards: biopsy, consensus conference definition, radiological features of acute pancreatitis, diagnosis of acute pancreatitis during laparotomy or autopsy, and organ failure. At least two review authors independently searched and screened the references located by the search to identify relevant studies. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included studies. The thresholds used for the diagnosis of acute pancreatitis varied in the trials, resulting in sparse data for each index test. Because of sparse data, we used -2 log likelihood values to determine which model to use for meta-analysis. We calculated and reported the sensitivity, specificity, post-test probability of a positive and negative index test along with 95% confidence interval (CI) for each cutoff, but have reported only the results of the recommended cutoff of three times normal for serum amylase and serum lipase, and the manufacturer-recommended cutoff of 50 mg/mL for urinary trypsinogen-2 in the abstract. MAIN RESULTS: Ten studies including 5056 participants met the inclusion criteria for this review and assessed the diagnostic accuracy of the index tests in people presenting to the emergency department with acute abdominal pain. The risk of bias was unclear or high for all of the included studies. The study that contributed approximately two-thirds of the participants included in this review was excluded from the results of the analysis presented below due to major concerns about the participants included in the study. We have presented only the results where at least two studies were included in the analysis.Serum amylase, serum lipase, and urinary trypsinogen-2 at the standard threshold levels of more than three times normal for serum amylase and serum lipase, and a threshold of 50 ng/mL for urinary trypsinogen-2 appear to have similar sensitivities (0.72 (95% CI 0.59 to 0.82); 0.79 (95% CI 0.54 to 0.92); and 0.72 (95% CI 0.56 to 0.84), respectively) and specificities (0.93 (95% CI 0.66 to 0.99); 0.89 (95% CI 0.46 to 0.99); and 0.90 (95% CI 0.85 to 0.93), respectively). At the median prevalence of 22.6% of acute pancreatitis in the studies, out of 100 people with positive test, serum amylase (more than three times normal), serum lipase (more than three times normal), and urinary trypsinogen (more than 50 ng/mL), 74 (95% CI 33 to 94); 68 (95% CI 21 to 94); and 67 (95% CI 57 to 76) people have acute pancreatitis, respectively; out of 100 people with negative test, serum amylase (more than three times normal), serum lipase (more than three times normal), and urinary trypsinogen (more than 50 ng/mL), 8 (95% CI 5 to 12); 7 (95% CI 3 to 15); and 8 (95% CI 5 to 13) people have acute pancreatitis, respectively. We were not able to compare these tests formally because of sparse data. AUTHORS' CONCLUSIONS: As about a quarter of people with acute pancreatitis fail to be diagnosed as having acute pancreatitis with the evaluated tests, one should have a low threshold to admit the patient and treat them for acute pancreatitis if the symptoms are suggestive of acute pancreatitis, even if these tests are normal. About 1 in 10 patients without acute pancreatitis may be wrongly diagnosed as having acute pancreatitis with these tests, therefore it is important to consider other conditions that require urgent surgical intervention, such as perforated viscus, even if these tests are abnormal.The diagnostic performance of these tests decreases even further with the progression of time, and one should have an even lower threshold to perform additional investigations if the symptoms are suggestive of acute pancreatitis.

Neurological complications after liver transplantation as a consequence of immunosuppression: univariate and multivariate analysis of risk factors.

Neurological complications (NCs) can frequently and significantly affect morbidity and mortality of liver transplant (LT) recipients. We analysed incidence, risk factors, outcome and impact of the immunosuppressive therapy on NC development after LT. We analysed 478 LT in 440 patients, and 93 (19.5%) were followed by NCs. The average LOS was longer in patients experiencing NCs. The 1-, 3- and 5-year graft survival and patient survival were similar in patients with or without a NC. Multivariate analysis showed the following as independent risk factors for NC: a MELD score ≥20 (OR = 1.934, CI = 1.186-3.153) and an immunosuppressive regimen based on calcineurin inhibitors (CNIs) (OR = 1.669, CI = 1.009-2.760). Among patients receiving an everolimus-based immunosuppression, the 7.1% developed NCs, vs. the 16.9% in those receiving a CNI (P = 0.039). There was a 1-, 3- and 5-year NC-free survival of 81.7%, 81.1% and 77.7% in patients receiving a CNI-based regimen and 95.1%, 93.6% and 92.7% in those not receiving a CNI-based regimen (P < 0.001). In patients undergoing a LT and presenting with nonmodifiable risk factors for developing NCs, an immunosuppressive regimen based on CNIs is likely to result in a higher rate of NCs compared to mTOR inhibitors.

Benchmark Outcomes in Deceased Donor Kidney Transplantation: A Multicenter Analysis of 80 996 Transplants From 126 Centers.

Background: We defined clinically relevant benchmark values in deceased donor kidney transplantation (KT), to assess the best achievable results in low-risk patient cohorts from experienced centers. Methods: We identified the "ideal" cases from the United Network for Organ Sharing Standard Transplant Analysis and Research files from centers performing ≥50 KT per year between 2010 and 2018. Cases have been selected based on the kidney donor profile index values (<35%), a cold ischemia time (CIT) ≤18 h, a HLA mismatch ≤4, and excluding blood group (ABO) incompatible, dual and combined transplants. The outcomes of the benchmark cohort have been compared with a group of patients excluded from the benchmark cohort because but not meeting 1 or more of the abovementioned criteria. Results: The 171 424 KT patients in the United Network for Organ Sharing Standard Transplant Analysis and Research files were screened and 8694 benchmark cases of a total of 80 996 KT (10.7%) from 126 centers meeting the selection criteria were identified. The benchmarks for 1-, 3-, and 5-y patient survival are ≥97%, ≥92.5%, and ≥86.7%, and ≥95.4%, ≥87.8%, and ≥79.6% for graft survival. Benchmark cutoff for hospital length of stay is ≤5 d, ≤23.6% for delayed graft function, and ≤7.5% and ≤9.1% for 6-mo and 1-y incidence of acute rejection. Overall 1-, 3-, and 5-y actuarial graft survivals were 96.6%, 91.1%, and 84.2% versus 93.5%, 85.4%, and 75.5% in the benchmark and comparison groups, respectively (P < 0.001). Overall 1-, 3-, and 5-y actuarial patient survivals were 98.1%, 94.8%, and 90.0% versus 96.6%, 91.1%, and 83.0% in the benchmark and comparison groups, respectively (P < 0.001). Conclusions: For the first time, we quantified the best achievable postoperative results in an ideal scenario in deceased donor KT, aimed at improving the clinical practice guided by the comparison of center performances with the ideal outcomes defined.

Robotic 8-mm trocar fascial wounds: To close or not to close?

BACKGROUND: The aim of this study was to investigate 8-mm robotic trocar site hernia (TSH) rate over the short and long term, providing aids to manage the related fascial wounds. METHODS: A retrospective analysis of 320 patients undergoing robotic surgery was conducted. The primary outcome was 8-mm TSH rate with a minimum follow-up of 12 months. The secondary outcome was the rate of haematomas and infections related to 8-mm wounds and their association with patient comorbidities and trocar position. RESULTS: One case of TSH was observed (0.31%). There were 15 cases of wound infection (4.68%) and 22 cases of wound haematoma (6.87%). Trocar related complications were significantly associated with patient comorbidities, not with trocar position. CONCLUSIONS: Our results do not justify the 8-mm fascial wound closure. Data concerning the association between trocar-related complications and patient comorbidities strengthen the need to implement the control of metabolic state and correct administration of perioperative therapy in high-risk patients.

Recurrence and tumor-related death after resection of hepatocellular carcinoma in patients with metabolic syndrome.

Background & Aims: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Methods: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. Results: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). Conclusions: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. Impact and implications: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Early use of mammalian target of rapamycin inhibitors is an independent risk factor for incisional hernia development after liver transplantation.

Incisional hernias (IHs) are common complications after liver transplantation (LT) with a reported incidence of 1.7% to 34.3%. The purpose of this retrospective study was to evaluate the risk factors for IH development after LT with a focus on the role of immunosuppressive therapy during the first month after LT. We analyzed 373 patients who underwent LT and divided them into 2 groups according to their postoperative course: an IH group (121 patients or 32.4%) and a no-IH group (252 patients or 67.6%). A univariate analysis demonstrated that the following were risk factors related to IH development: male sex (P = 0.03), a body mass index ≥ 29 kg/m(2) (P = 0.005), LT after 2004 (P = 0.02), a Model for End-Stage Liver Disease (MELD) score ≥ 22 (P = 0.01), and hepatitis B virus infection (P = 0.01). The highest incidence of IHs was found in patients treated with mammalian target of rapamycin (mTOR) inhibitors (54.5%, P = 0.004). A multivariate analysis revealed male sex (P = 0.03), a pretransplant MELD score ≥ 22 (P = 0.04), and the use of mTOR inhibitors (P = 0.001) to be independent risk factors for IHs after LT. In conclusion, immunosuppressive therapy with mTOR inhibitors is an important independent risk factor for IH development after LT. To reduce the incidence of IHs, mTOR inhibitors should be avoided until the fourth month after LT unless their use is deemed to be strictly necessary.

Immunological advantages of everolimus versus cyclosporin A in liver-transplanted recipients, as revealed by polychromatic flow cytometry.

Several immunosuppressive drugs with different mechanisms of action are available to inhibit organ rejection after transplant. We analyzed different phenotypic and functional immunological parameters in liver-transplanted patients who received cyclosporin A (CsA) or Everolimus (Evr). In peripheral blood mononuclear cells (PBMC) from 29 subjects receiving a liver transplant and treated with two different immunosuppressive regimens, we analyzed T cell activation and differentiation, regulatory T cells (Tregs) and Tregs expressing homing receptors such as the chemokine receptor CXCR3. T cell polyfunctionality was studied by stimulating cells with the superantigen staphylococcal enterotoxin B (SEB), and measuring the simultaneous production of interleukin (IL)-2 and interferon (IFN)-γ, along with the expression of a marker of cytotoxicity such as CD107a. The analyses were performed by polychromatic flow cytometry before transplantation, and at different time points, up to 220 days after transplant. Patients taking Evr had a higher percentage of total CD4⁺ and naïve CD4⁺ T cells than those treated with CsA; the percentage of CD8⁺ T cells was lower, but the frequency of naïve CD8⁺ T cells higher. Patients taking Evr showed a significantly higher percentage of Tregs, and Tregs expressing CXCR3. After stimulation with SEB, CD8⁺ T cells from Evr-treated patients displayed a lower total response, and less IFN-γ producing cells. The effects on the immune system, such as the preservation of the naïve T cell pool and the expansion of Tregs (that are extremely useful in inhibiting organ rejection), along with the higher tolerability of Evr, suggest that this drug can be safely used after liver transplantation, and likely offers immunological advantages.

Robotic pancreaticoduodenectomy with biodegradable ductal stenting (Archimedes BPS®).

BACKGROUND: Postoperative Pancreatic Fistula (POPF) development remains a challenge after pancreaticoduodenectomy, occurring in 3-45% of cases [1]. The placement of a trans-anastomotic Wirsung stent is usually done in high-risk patients to decrease incidence and severity of POPF. METHODS: Herein, we present a fully robotic pancreaticoduodenectomy with a biodegradable ductal stent interposition in a 47 y.o. female with a main duct IPMN of the pancreatic head and a fistula risk score of 6 (Moderate-risk). VIDEO: After gastrocolic ligament division and hepatic flexure and duodenum mobilization, the loco-regional lymphadenectomy was performed. Following gastric transection with endo-GIA, the bile duct and gastroduodenal artery have been divided, and the cholecystectomy performed. The neck of the pancreas has been transected, the jejunum divided with endo-GIA and mobilized from the Treitz ligament, and the uncinate process dissected from the mesenteric vessels. A Blumgart anastomosis has been performed between the soft-texture pancreatic stump and the jejunal loop with the interposition of a 6 Fr/60 mm long, medium degrading stent (20 days) in the 2 mm duct (Archimedes BPS®, AMG Int., Winsen-Germany). The hepatico-jejunostomy and gastro-jejunostomy have been performed distally on the same loop. Three abdominal drains have been positioned. RESULTS: Surgery lasted 480 min, with 175 mls blood loss. The patient postoperatively developed a biochemical leak and was discharged home by day 12. She was readmitted a month later for an amylase-negative intra-abdominal abscess that was successfully treated with percutaneous drainage. CONCLUSION: Biodegradable pancreatic stent positioning could be an effective strategy in reducing POPF occurrence in high-risk patients.

Artificial intelligence in the diagnosis and management of colorectal cancer liver metastases.

Colorectal cancer (CRC) is the third most common malignancy worldwide, with approximately 50% of patients developing colorectal cancer liver metastasis (CRLM) during the follow-up period. Management of CRLM is best achieved via a multidisciplinary approach and the diagnostic and therapeutic decision-making process is complex. In order to optimize patients' survival and quality of life, there are several unsolved challenges which must be overcome. These primarily include a timely diagnosis and the identification of reliable prognostic factors. Furthermore, to allow optimal treatment options, a precision-medicine, personalized approach is required. The widespread digitalization of healthcare generates a vast amount of data and together with accessible high-performance computing, artificial intelligence (AI) technologies can be applied. By increasing diagnostic accuracy, reducing timings and costs, the application of AI could help mitigate the current shortcomings in CRLM management. In this review we explore the available evidence of the possible role of AI in all phases of the CRLM natural history. Radiomics analysis and convolutional neural networks (CNN) which combine computed tomography (CT) images with clinical data have been developed to predict CRLM development in CRC patients. AI models have also proven themselves to perform similarly or better than expert radiologists in detecting CRLM on CT and magnetic resonance scans or identifying them from the noninvasive analysis of patients' exhaled air. The application of AI and machine learning (ML) in diagnosing CRLM has also been extended to histopathological examination in order to rapidly and accurately identify CRLM tissue and its different histopathological growth patterns. ML and CNN have shown good accuracy in predicting response to chemotherapy, early local tumor progression after ablation treatment, and patient survival after surgical treatment or chemotherapy. Despite the initial enthusiasm and the accumulating evidence, AI technologies' role in healthcare and CRLM management is not yet fully established. Its limitations mainly concern safety and the lack of regulation and ethical considerations. AI is unlikely to fully replace any human role but could be actively integrated to facilitate physicians in their everyday practice. Moving towards a personalized and evidence-based patient approach and management, further larger, prospective and rigorous studies evaluating AI technologies in patients at risk or affected by CRLM are needed.

The Role of Robotic Visceral Surgery in Patients with Adhesions: A Systematic Review and Meta-Analysis.

Abdominal adhesions are a risk factor for conversion to open surgery. An advantage of robotic surgery is the lower rate of unplanned conversions. A systematic review was conducted using the terms "laparoscopic" and "robotic". Inclusion criteria were: comparative studies evaluating patients undergoing laparoscopic and robotic surgery; reporting data on conversion to open surgery for each group due to adhesions and studies including at least five patients in each group. The main outcomes were the conversion rates due to adhesions and surgeons' expertise (novice vs. expert). The meta-analysis included 70 studies from different surgical specialities with 14,329 procedures (6472 robotic and 7857 laparoscopic). The robotic approach was associated with a reduced risk of conversion (OR 1.53, 95% CI 1.12-2.10, p = 0.007). The analysis of the procedures performed by "expert surgeons" showed a statistically significant difference in favour of robotic surgery (OR 1.48, 95% CI 1.03-2.12, p = 0.03). A reduced conversion rate due to adhesions with the robotic approach was observed in patients undergoing colorectal cancer surgery (OR 2.62, 95% CI 1.20-5.72, p = 0.02). The robotic approach could be a valid option in patients with abdominal adhesions, especially in the subgroup of those undergoing colorectal cancer resection performed by expert surgeons.

Robotic versus Laparoscopic Surgery for Spleen-Preserving Distal Pancreatectomies: Systematic Review and Meta-Analysis.

BACKGROUND: When oncologically feasible, avoiding unnecessary splenectomies prevents patients who are undergoing distal pancreatectomy (DP) from facing significant thromboembolic and infective risks. METHODS: A systematic search of MEDLINE, Embase, and Web Of Science identified 11 studies reporting outcomes of 323 patients undergoing intended spleen-preserving minimally invasive robotic DP (SP-RADP) and 362 laparoscopic DP (SP-LADP) in order to compare the spleen preservation rates of the two techniques. The risk of bias was evaluated according to the Newcastle-Ottawa Scale. RESULTS: SP-RADP showed superior results over the laparoscopic approach, with an inferior spleen preservation failure risk difference (RD) of 0.24 (95% CI 0.15, 0.33), reduced open conversion rate (RD of -0.05 (95% CI -0.09, -0.01)), reduced blood loss (mean difference of -138 mL (95% CI -205, -71)), and mean difference in hospital length of stay of -1.5 days (95% CI -2.8, -0.2), with similar operative time, clinically relevant postoperative pancreatic fistula (ISGPS grade B/C), and Clavien-Dindo grade ≥3 postoperative complications. CONCLUSION: Both SP-RADP and SP-LADP proved to be safe and effective procedures, with minimal perioperative mortality and low postoperative morbidity. The robotic approach proved to be superior to the laparoscopic approach in terms of spleen preservation rate, intraoperative blood loss, and hospital length of stay.