Pancreatic metastases from renal cell carcinoma:The state of the art

Pancreatic metastases are rare,with a reported incidence varying from 1.6%to 11%in autopsy studies of patients with advanced malignancy.In clinical series,the frequency of pancreatic metastases ranges from 2%to 5%of all pancreatic malignant tumors.However,the pancreas is an elective site for metastases from carcinoma of the kidney and this peculiarity has been reported by several studies.The epidemiology,clinical presentation,and treatment of pancreatic metastases from renal cell carcinoma are known from singleinstitution case reports and literature reviews.Thereis currently very limited experience with the surgical resection of isolated pancreatic metastasis,and the role of surgery in the management of these patients has not been clearly defined.In fact,for many years pancreatic resections were associated with high rates of morbidity and mortality,and metastatic disease to the pancreas was considered to be a terminal-stage condition.More recently,a significant reduction in the operative risk following major pancreatic surgery has been demonstrated,thus extending the indication for these operations to patients with metastatic disease.

Outcomes of robotic vs laparoscopic hepatectomy:A systematic review and meta-analysis

AIM: To perform a systematic review and metaanalysis on robotic-assisted vs laparoscopic liver resections.METHODS: A systematic literature search was performed using Pub Med, Scopus and the Cochrane Library Central. Participants of any age and sex, who underwent robotic or laparoscopic liver resection were considered following these criteria:(1) studies comparing robotic and laparoscopic liver resection;(2) studies reporting at least one perioperative outcome; and(3) if more than one study was reported by the same institute, only the most recent was included. The primary outcome measures were set for estimated blood loss, operative time, conversion rate, R1 resection rate, morbidity and mortality rates, hospital stay and major hepatectomy rates.RESULTS: A total of 7 articles, published between 2010 and 2014, fulfilled the selection criteria. The laparoscopic approach was associated with a significant reduction in blood loss and lower operative time(MD = 83.96, 95%CI: 10.51-157.41, P = 0.03; MD = 68.43, 95%CI: 39.22-97.65, P < 0.00001, respectively). No differences were found with respect to conversion rate, R1 resection rate, morbidity and hospital stay.CONCLUSION: Laparoscopic liver resection resulted in reduced blood loss and shorter surgical times compared to robotic liver resections. There was no difference in conversion rate, R1 resection rate, morbidity and length of postoperative stay.

Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation

AIM:To assess the possible effect of two different types of preoperative transcatheter arterial chemoembolization(TACE)on recurrence-free survival after liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and to analyze the effects of TACE on tumor histology.METHODS:We retrospectively analyzed the histological features of 130 HCC nodules in 63 native livers removed at transplantation.Patients who received any other type of treatment such as radiofrequency tumor ablation,percutaneous ethanol ablation or who were not treated at all were excluded.All patients in the present study were within the Milan Criteria at the last imaging findings before transplantation.Doxorubicineluting bead TACE(DEB-TACE)was performed in 22patients(38 nodules),and conventional TACE(c-TACE)in 16(25 nodules).Patients’and tumors’characteristics were retrospectively reviewed.We performed a pernodule analysis of the explanted livers to establish the mean percentage of necrosis of any nodule treated by TACE(conventional or DEB)and a per-patient analysis to establish the percentage of necrosis in the cumulative tumor area,including 21 nodules not reached by TACE.Inflammatory and fibrotic changes in the tissue surrounding the tumor nodule were analyzed and categorized as poor/absent,moderate and enhanced reaction.Uni-and multivariate analysis of risk factors for HCC-recurrence were performed.RESULTS:The number and diameter of the nodules,the time spent on the waiting list and the number of treatments were similar in the two groups.A trend towards higher appropriate response rates(necrosis≥90%)was observed in the DEB-TACE group(44.7%vs32.0%,P=0.2834).The mean percentage of necrosis in the cumulative tumor area was 58.8%±36.6%in the DEB-TACE group and 50.2%±38.1%in the c-TACE group(P=0.4856).Fibrotic and inflammatory reactions surrounding the tumor nodule were markedly more common in the DEB-TACE group(P<0.0001,for both the parameters).The three-year recurrence-free survival was higher in DEB-TACE-treated patients than in conventionally treated patients(87.4%vs 61.5%,P=0.0493).Other factors affecting recurrence-free survival included viable tumor beyond Milan Criteria on histopathological examination,the percentage of necrosis on CTA≤50%and a pre-transplant serum-fetoprotein level greater than 70 ng/mL.On multivariate analysis,the lack of treatment with DEB-TACE,high levels of-fetoprotein and viable tumor beyond Milan Criteria at histology examination were identified as independent predictors of tumor recurrence.CONCLUSION:DEB-TACE can effectively promote tumor necrosis and improves recurrence-free survival after LT in HCC.

Multimodal treatment of hepatocellular carcinoma on cirrhosis: An update

Hepatocellular carcinoma(HCC)is the most frequent primary liver tumor,and overall,it is one of the most frequent cancers.The association of HCC with chronic liver disease,and cirrhosis in particular,is well known,making treatment complex and challenging.The treatment of HCC must take into account the presence and stage of chronic liver disease,with the aim of preserving hepatic function that is often already impaired,the stage of HCC and the clinical condition of the patient.The different treatment options include surgical resection,transplantation,local ablation,chemoembolization,radioembolization and molecular targeted therapies;these treatments can be combined in various ways to achieve different goals.Ideally,liver transplantation is best treatment for early stage HCC on cirrhosis because it removes both the tumor and the chronic disease that produced it;however,the application of this powerful tool is limited by the scarcity of donors.Downstaging and bridging are different strategies for the management of HCC patients who will undergo liver transplantation.Several professionals,including gastroenterologists,radiologists and surgeons,are involved in the choice of the most appropriate treatment for a single case,and a multidisciplinary approach is necessary to optimize the outcome.The purpose of this review is to provide a comprehensive description of the current treatment options for patients with HCC by analyzing the advantages,disadvantages and rationale for their use.

Perioperative thromboprophylaxis in liver transplant patients

Improvements in surgical and anesthetic procedures have increased patient survival after liver transplantation(LT). However, the perioperative period of LT can still be affected by several complications. Among these, thromboembolic complications(intracardiac thrombosis, pulmonary embolism, hepatic artery and portal vein thrombosis) are relatively common causes of increased morbidity and mortality. The benefit of thromboprophylaxis in general surgical patients has already been established, but it is not the standard of care in LT recipients. LT is associated with a high bleeding risk, as it is performed in a setting of already unstable hemostasis. For this reason, the role of routine perioperative prophylactic anticoagulation is usually restricted. However, recent data have shown that the bleeding tendency of cirrhotic patients is not an expression of an acquired bleeding disorder but rather of coexisting factors(portal hypertension, hypervolemia and infections). Furthermore, in cirrhotic patients, the new paradigm of ‘‘rebalanced hemostasis' ' can easily tip towards hypercoagulability because of the recently described enhanced thrombin generation, procoagulant changes in fibrin structure and platelet hyperreactivity. This new coagulation balance, along with improvements in surgical techniques and critical support, has led to a dramatic reduction in transfusion requirements, and the intraoperative thromboembolic-favoring factors(venous stasis, vessels clamping, surgical injury) have increased the awareness of thrombotic complications and led clinicians to reconsider the limited use of anticoagulants or antiplatelets in the postoperative period of LT.

Predictive factors of short term outcome after liver transplantation: A review

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early posttransplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests(platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores(model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1th and the 5th day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function.

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.

Radiological response and inflammation scores predict tumour recurrence in patients treated with transarterial chemoembolization before liver transplantation

AIM To investigate the prognostic value of the radiological response after transarterial chemoembolization(TACE)and inflammatory markers in patients affected by hepatocellular carcinoma(HCC)awaiting liver transplantation(LT).METHODS We retrospectively evaluated the preoperative pre dictors of HCC recurrence in 70 patients treated with conventional(n=16)or doxorubicin-eluting bead TACE(n=54)before LT.The patient and tumour characteristics,including the static and dynamic alpha-fetoprotein,neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio( LR)measurements,were recorded.Treatment response was classified according to the modified Response Evaluation Criteria in Solid Tumours(m RECIST)and the European Association for the Study of the Liver(EASL)criteria as complete response(CR),partial response( R),stable disease o progressive disease.After examination of the explanted livers,histological necrosis was classified as complete(100%of the cumulative tumour area),partia(50%-99%)or minimal(<50%)and was correlated with the preoperative radiological findings.RESULTS According to the pre-TACE radiological evaluation,22/70(31.4%)and 12/70(17.1%)patients were beyond Milan and University of San Francisco(UCSF)criteria,respectively.After TACE procedures,the objective response(CR+ R)rates were 71.4%and 70.0%according to m RECIST and EASL criteria,respectively.The agreement between the two guidelines in defining the radiological response was rated as very good both for the overall and target lesion response(weighted k-value:0.98 and 0.93,respectively).Complete and partial histological necrosis were achieved in 14/70(20.0%)and 28/70(40.0%)patients,respectively.Using histopathology as the reference standard,m RECIST criteria correctly classified necrosis in 72.9%(51/70)of patients and EASL criteria in 68.6%(48/70)of cases.The m RECIST non-response to TACE[Exp(b)=9.2, =0.012],exceeding UCSF criteria before TACE[Exp(b)=4.7, =0.033]and a preoperative LR>150[Exp(b)=5.9, =0.046]were independent predictors of tumour recurrence.CONCLUSION The radiological response and inflammatory markers are predictive of tumour recurrence and allow the proper selection of TACE-treated candidates for LT.

Intraoperative thromboelastography as a tool to predict postoperative thrombosis during liver transplantation

BACKGROUND Thromboembolic complications are relatively common causes of increased morbidity and mortality in the perioperative period in liver transplant patients.Early postoperative portal vein thrombosis(PVT,incidence 2%-2.6%)and early hepatic artery thrombosis(HAT,incidence 3%-5%)have a poor prognosis in transplant patients,having impacts on graft and patient survival.In the present study,we attempted to identify the predictive factors of these complications for early detection and therefore monitor more closely the patients most at risk of thrombotic complications.AIM To investigate whether intraoperative thromboelastography(TEG)is useful in detecting the risk of early postoperative HAT and PVT in patients undergoing liver transplantation(LT).METHODS We retrospectively collected thromboelastographic traces,in addition to known risk factors(cold ischemic time,intraoperative requirement for red blood cells and fresh-frozen plasma transfusion,prolonged operating time),in 27 patients,selected among 530 patients(≥18 years old),who underwent their first LT from January 2002 to January 2015 at the Liver University Transplant Center and developed an early PVT or HAT(case group).Analyses of the TEG traces were performed before anesthesia and 120 min after reperfusion.We retrospectively compared these patients with the same number of nonconsecutive control patients who underwent LT in the same study period without developing these complications(1:1 match)(control group).The chosen matching parameters were:Patient graft and donor characteristics[age,sex,body mass index(BMI)],indication for transplantation,procedure details,United Network for Organ Sharing classification,BMI,warm ischemia time(WIT),cold ischemia time(CIT),the volume of blood products transfused,and conventional laboratory coagulation analysis.Normally distributed continuous data are reported as the mean±SD and compared using one-way Analysis of Variance(ANOVA).Nonnormally distributed continuous data are reported as the median(interquartile range)and compared using the Mann-Whitney test.Categorical variables were analyzed with Chi-square tests with Yates correction or Fisher’s exact test depending on best applicability.IBM SPSS Statistics version 24(SPSS Inc.,Chicago,IL,United States)was employed for statistical analysis.Statistical significance was set at P<0.05.RESULTS Postoperative thrombotic events were identified as early if they occurred within 21 d postoperatively.The incidence of early hepatic artery occlusion was 3.02%,whereas the incidence of PVT was 2.07%.A comparison between the case and control groups showed some differences in the duration of surgery,which was longer in the case group(P=0.032),whereas transfusion of blood products,red blood cells,fresh frozen plasma,and platelets,was similar between the two study groups.Thromboelastographic parameters did not show any statistically significant difference between the two groups,except for the G value measured at basal and 120’postreperfusion time.It was higher,although within the reference range,in the case group than in the control group(P=0.001 and P<0.001,respectively).In addition,clot lysis at 60 min(LY60)measured at 120’postreperfusion time was lower in the case group than in the control group(P=0.035).This parameter is representative of a fibrinolysis shutdown(LY60=0%-0.80%)in 85%of patients who experienced a thrombotic complication,resulting in a statistical correlation with HAT and PVT.CONCLUSION The end of surgery LY60 and G value may identify those recipients at greater risk of developing early HAT or PVT,suggesting that they may benefit from intense surveillance and eventually anticoagulation prophylaxis in order to prevent these serious complications after LT.

Anaesthetic perioperative management of patients with pancreatic cancer

Pancreatic cancer remains a significant and unresolved therapeutic challenge.Currently,the only curative treatment for pancreatic cancer is surgical resection.Pancreatic surgery represents a technically demanding major abdominal procedure that can occasionally lead to a number of pathophysiological alterations resulting in increased morbidity and mortality.Systemic,rather than surgical complications,cause the majority of deaths.Because patients are increasingly referred to surgery with at advanced ages and because pancreatic surgery is extremely complex,anaesthesiologists and surgeons play a crucial role in preoperative evaluations and diagnoses for surgical intervention.The anaesthetist plays a key role in perioperative management and can significantly influence patient outcome.To optimise overall care,patients should be appropriately referred to tertiary centres,where multidisciplinary teams(surgical,medical,radiation oncologists,gastroenterologists,interventional radiologists and anaesthetists)work together and where close cooperation between surgeons and anaesthesiologists promotes the safe performance of major gastrointestinal surgeries with acceptable morbidity and mortality rates.In this review,we sought to provide simple daily recommendations to the clinicians who manage pancreatic surgery patients to make their work easier and suggest a joint approach between surgeons and anaesthesiologists in daily decision making.

Liquid biopsy in cholangiocarcinoma:Current status and future perspectives

Cholangiocarcinoma(CCA)are a heterogeneous group of tumors in terms of aetiology,natural history,morphological subtypes,molecular alterations and management,but all sharing complex diagnosis,management,and poor prognosis.Several mutated genes and epigenetic changes have been detected in CCA,with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets.Accessing tumoral components and genetic material is therefore crucial for the diagnosis,management and selection of targeted therapies;but sampling tumor tissue,when possible,is often risky and difficult to be repeated at different time points.Liquid biopsy(LB)represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples.Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated,allowing a real-time monitoring of the tumor genetic profile or the response to therapy.In this review,we analysis the current evidence on the possible roles of LB(circulating DNA,circulating RNA,exosomes,cytokines)in the diagnosis and management of patients affected by CCA.

Transoesophageal echocardiography during liver transplantation

Liver transplantation(LT) has become the standard of care for patients with end stage liver disease. The allocation of organs, which prioritizes the sickest patients, has made the management of liver trans-plant candidates more complex both as regards their comorbidities and their higher risk of perioperative complications. Patients undergoing LT frequently display considerable physiological changes during the pro-cedures as a result of both the disease process and the surgery. Transoesophageal echocardiography(TEE), which visualizes dynamic cardiac function and overall contractility, has become essential for perioperative LT management and can optimize the anaesthetic management of these highly complex patients. More-over, TEE can provide useful information on volume status and the adequacy of therapeutic interventions and can diagnose early intraoperative complications, such as the embolization of large vessels or development of pulmonary hypertension. In this review, directed at clinicians who manage TEE during LT, we show why the procedure merits a place in challenging anaesthetic environment and how it can provide essential information in the perioperative management of compromised patients undergoing this very complex surgical procedure.

Big size is not all, even better!

We read with interest the article entitled"Comprehensive Complication Index validates improved outcomes over time despiteincreased complexity in 3707 consecutive hepatectomies"by Cloydet al.(1).This article focused on the correlation betweensurgical volume and the development of competency in openliver surgery.