BACKGROUND:According to the current literature, biliary lithiasis is a worldwide-diffused condition that affects almost 20% of the general population. The rate of common bile duct stones(CBDS) in patients with symptom...BACKGROUND:According to the current literature, biliary lithiasis is a worldwide-diffused condition that affects almost 20% of the general population. The rate of common bile duct stones(CBDS) in patients with symptomatic cholelithiasis is estimated to be 10% to 33%, depending on patient’s age.Compared to stones in the gallbladder, the natural history of secondary CBDS is still not completely understood. It is not clear whether an asymptomatic choledocholithiasis requires treatment or not. For many years, open cholecystectomy with choledochotomy and/or surgical sphincterotomy and cleaning of the bile duct were the gold standard to treat both pathologies. Development of both endoscopic retrograde cholangiopancreatography(ERCP) and laparoscopic surgery,together with improvements in diagnostic procedures, influenced new approaches to the management of CBDS in association with gallstones.DATA SOURCES:We decided to systematically review the literature in order to identify all the current therapeutic options for CBDS. A systematic literature search was performed independently by two authors using Pub Med, EMBASE, Scopus and the Cochrane Library Central.RESULTS:The therapeutic approach nowadays varies greatly according to the availability of experience and expertise in each center, and includes open or laparoscopic common bile duct exploration, various combinations of laparoscopic cholecystectomy and ERCP and combined laparoendoscopic rendezvous.CONCLUSIONS:Although ERCP followed by laparoscopic cholecystectomy is currently preferred in the majority of hospitals worldwide, the optimal treatment for concomitant gallstones and CBDS is still under debate, and greatly varies among different centers.展开更多
AIM: To evaluate the relationship between hepatocellular carcinoma(HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence.METHODS: This retrospect...AIM: To evaluate the relationship between hepatocellular carcinoma(HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence.METHODS: This retrospective study included 165 patients(143 men, 22 women; median age 56.8 years, range 28-70.4 years) transplanted for HCC who had a follow-up period longer than 2 mo. Pre-transplantation dynamic computed tomography or magnetic resonance examinations were retrospectively reviewed, classifying HCC imaging enhancement pattern into hypervascular and hypovascular based on presence of wash-in during arterial phase. All pathologic reports of the explanted livers were reviewed, collecting data about HCC differentiation degree. The association between imaging vascular pattern and pathological grade was estimated using the Fisher exact test. All follow-up clinical and imaging data were reviewed for evidence of recurrence. Recurrence rate was calculated and imaging features of recurrent tumor were collected, classifying early and late recurrences based on timing(< or ≥ 2 years after transplantation) and intrahepatic, extrahepatic and both intrahepatic and extrahepatic recurrences based onlocation. All intrahepatic recurrences were classified as hypervascular or hypovascular and the differentiation degree was collected where available. The presence of variations in imaging enhancement pattern and pathological grade between the primary tumor and the intrahepatic recurrence was evaluated and the association between imaging and histopatholgical variations was estimated by using the χ2 test. RESULTS: Of the 163 patients with imaging evidence of viable tumor, 156(95.7%) had hypervascular and 7(4.3%) hypovascular HCC. Among the 125 patients with evidence of viable tumor in the explanted liver, 19(15.2%) had grade 1, 56(44.8%) grade 2, 40(32%) grade 3 and 4(3.2%) grade 4 HCC, while the differentiation degree was not assessable for 6 patients(4.8%). A significant association was found between imaging vascularity and pathological grade(P = 0.035). Post-transplantation recurrence rate was 14.55%(24/165). All recurrences occurred in patients who had a hypervascular primary tumor. Three patients(12.5%) experienced late recurrence; the location of the first recurrence was extrahepatic in 14 patients(58.3%), intrahepatic in 7 patients(29.2%) and both intrahepatic and extrahepatic in 3 patients(12.5%). Two patients had a variation in imaging characteristics between the primary HCC(hypervascular) and the intrahepatic recurrent HCC(hypovascular), while 1 patient had a variation of histopathological characteristics(from moderate to poor differentiation), however no association was found between imaging and histopathological variations.CONCLUSION: A correlation was found between HCC grade and vascularity; some degree of variability may exist between the primary and the recurrence imaging/histopathological characteristics, apparently not correlated.展开更多
BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patie...BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patients(>70 years)with HCC in Milan criteria,which underwent liver resection(LR)or RFA.METHODS The study included 594 patients with HCC in Milan criteria(429 in LR group and 165 in RFA group)managed in 10 European centers.Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching(PSM)and Cox regression.RESULTS After PSM,we compared 136 patients in the LR group with 136 patients in the RFA group.Overall survival at 1,3,and 5 years was 91%,80%,and 76%in the LR group and 97%,67%,and 41%in the RFA group respectively(P=0.001).Diseasefree survival at 1,3,and 5 years was 84%,60%and 44%for the LR group,and 63%,36%,and 25%for the RFA group(P=0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group(1%vs 11%,P=0.001)in association with a shorter length of stay(2 d vs 7 d,P=0.001).In multivariate analysis,Model for End-stage Liver Disease(MELD)score(>10)[odds ratio(OR)=1.89],increased value of international normalized ratio(>1.3)(OR=1.60),treatment with radiofrequency(OR=1.46),and multiple nodules(OR=1.19)were independent predictors of a poor overall survival while a high MELD score(>10)(OR=1.51)and radiofrequency(OR=1.37)were independent factors associated with a higher recurrence rate.CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications,surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients(>70 years)with HCC in Milan criteria.展开更多
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,inciden...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.展开更多
BACKGROUND Liver resection and radiofrequency ablation are considered curative options for hepatocellular carcinoma.The choice between these techniques is still controversial especially in cases of hepatocellular carc...BACKGROUND Liver resection and radiofrequency ablation are considered curative options for hepatocellular carcinoma.The choice between these techniques is still controversial especially in cases of hepatocellular carcinoma affecting posterosuperior segments in elderly patients.AIM To compare post-operative outcomes between liver resection and radiofrequency ablation in elderly with single hepatocellular carcinoma located in posterosuperior segments.METHODS A retrospective multicentric study was performed enrolling 77 patients age≥70-years-old with single hepatocellular carcinoma(≤30 mm),located in posterosuperior segments(4a,7,8).Patients were divided into liver resection and radiofrequency ablation groups and preoperative,peri-operative and long-term outcomes were retrospectively analyzed and compared using a 1:1 propensity score matching.RESULTS After propensity score matching,twenty-six patients were included in each group.Operative time and overall postoperative complications were higher in the resection group compared to the ablation group(165 min vs 20 min,P<0.01;54%vs 19%P=0.02 respectively).A median hospital stay was significantly longer in the resection group than in the ablation group(7.5 d vs 3 d,P<0.01).Ninety-day mortality was comparable between the two groups.There were no significant differences between resection and ablation group in terms of overall survival and disease free survival at 1,3,and 5 years.CONCLUSION Radiofrequency ablation in posterosuperior segments in elderly is safe and feasible and ensures a short hospital stay,better quality of life and does not modify the overall and disease-free survival.展开更多
BACKGROUND The impact of obesity on surgical outcomes in elderly patients candidate for liver surgery is still debated.AIM To evaluate the impact of high body mass index(BMI)on perioperative and oncological outcome in...BACKGROUND The impact of obesity on surgical outcomes in elderly patients candidate for liver surgery is still debated.AIM To evaluate the impact of high body mass index(BMI)on perioperative and oncological outcome in elderly patients(>70 years old)treated with laparoscopic liver resection for hepatocellular carcinoma(HCC).METHODS Retrospective multicenter study including 224 elderly patients(>70 years old)operated by laparoscopy for HCC(196 with a BMI<30 and 28 with BMI≥30),observed from January 2009 to January 2019.RESULTS After propensity score matching,patients in two groups presented comparable results,in terms of operative time(median range:200 min vs 205 min,P=0.7 respectively in non-obese and obese patients),complications rate(22%vs 26%,P=1.0),length of hospital stay(median range:4.5 d vs 6.0 d,P=0.1).There are no significant differences in terms of short-and long-term postoperative results.CONCLUSION The present study showed that BMI did not impact perioperative and oncologic outcomes in elderly patients treated by laparoscopic resection for HCC.展开更多
BACKGROUND Liver resection is the mainstay for a curative treatment for patients with resectable hepatocellular carcinoma(HCC),also in elderly population.Despite this,the evaluation of patient condition,liver function...BACKGROUND Liver resection is the mainstay for a curative treatment for patients with resectable hepatocellular carcinoma(HCC),also in elderly population.Despite this,the evaluation of patient condition,liver function and extent of disease remains a demanding process with the aim to reduce postoperative morbidity and mortality.AIM To identify new perioperative risk factors that could be associated with higher 90-and 180-d mortality in elderly patients eligible for liver resection for HCC considering traditional perioperative risk scores and to develop a risk score.METHODS A multicentric,retrospective study was performed by reviewing the medical records of patients aged 70 years or older who electively underwent liver resection for HCC;several independent variables correlated with death from all causes at 90 and 180 d were studied.The coefficients of Cox regression proportional-hazards model for sixmonth mortality were rounded to the nearest integer to assign risk factors'weights and derive the scoring algorithm.RESULTS Multivariate analysis found variables(American Society of Anesthesiology score,high rate of comorbidities,Mayo end stage liver disease score and size of biggest lesion)that had independent correlations with increased 90-and 180-d mortality.A clinical risk score was developed with survival profiles.CONCLUSION This score can aid in stratifying this population in order to assess who can benefit from surgical treatment in terms of postoperative mortality.展开更多
Liver transplant for hepatitis B virus(HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list f...Liver transplant for hepatitis B virus(HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28(2%) received the graft from hepatitis B surface antigen positive(HBs Ag)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary nonfunction, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3-and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBs Agpositive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.展开更多
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 a...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.展开更多
Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and are characterized by a broad spectrum of clinical, histological and molecular features at presentatio...Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and are characterized by a broad spectrum of clinical, histological and molecular features at presentation. Although focal and scattered calcifications are not uncommon within the primary tumor mass, heavy calcification within a GIST is rarely described in the literature and the clinical-biological meaning of this feature remains unclear. Cases with such an atypical presentation are challenging and may be associated with diagnostic pitfalls. Herein, we report a gastric GIST with the unusual presentation of prominent calcifications that was identified incidentally on imaging during a post-trauma diagnostic work-up. The patient underwent laparoscopic surgery with a radical resection of the mass, which was subsequently characterized by histological analysis as spindle-shaped tumor cells, positive for CD117/c-KIT, CD34 and DOG1, and with calcified areas. Given the intermediate risk of recurrence, no adjuvant therapy was recommended andthe patient underwent regular follow-up for 22 mo, with no evidence of relapse. Our case can be considered of interest because of the rarity of clinical presentation and the uniquely large size of the GIST at diagnosis(longest diameter exceeding 9 cm). In closing, we discuss the pathophysiology and clinical implications of calcifications in GISTs by reviewing the most up-to-date relevant literature.展开更多
Bouveret's syndrome, defined as gastric outlet obstruction due to a large gallstone, is still one of the most dramatic biliary gallstone complications. Although new radiological and endoscopic techniques have made...Bouveret's syndrome, defined as gastric outlet obstruction due to a large gallstone, is still one of the most dramatic biliary gallstone complications. Although new radiological and endoscopic techniques have made pre-surgical diagnosis possible in most cases and the death rate has dropped dramatically, "one-stage surgery" (biliary surgery carried out at the same time as the removal of the gut obstruction) should be still considered as the gold standard for the treatment of gallstone ileus.In this case, partial gastric outlet obstruction resulted in an atypical and insidious clinical presentation that allowed us to perform the conventional one-stage laparatomic procedure that completely solved the problem, thus avoiding any further complications.展开更多
The role of minimally invasive liver surgery as a bridge to transplantation is very promising but still underestimated. However, it should be noted that surgical approach for hepatocellular carcinomas(HCC) is not mere...The role of minimally invasive liver surgery as a bridge to transplantation is very promising but still underestimated. However, it should be noted that surgical approach for hepatocellular carcinomas(HCC) is not merely a technical or technological issue. Nowadays, the epidemiology of HCC is evolving due to the increasing role of non-alcoholic fatty-liver-disease, and the emerging concerns on direct-acting antivirals against hepatitis C virus in terms of HCC incidence. Therefore, a fully multidisciplinary study of the cirrhotic patient is currently more important than ever before, and the management of those patients should be reserved to tertiary referral hepatobiliary centers. In particular, minimally invasive approach to the liver showed several advantages compared to the classical open procedure, in terms of:(1) the small impact on abdominal wall;(2) the gentle manipulation on the liver;(3) the limited surgical trauma; and(4) the respect of venous shunts. Therefore, more direct indications should be outlined also in the Barcelona Clinic Liver Cancer model. We believe that treatment of HCC in cirrhotic patients should be reserved to tertiary referral hepatobiliary centers, that should offer patient-tailored approaches to the liver disease, in order to provide the best care for each case, according to the individual comorbidities, risk factors, and personal quality of life expectations.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient supplies.PDAC aggressiveness largely relies on its extraord...Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient supplies.PDAC aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor microenvironment.Dysregulation of the onco-suppressor miR-15a has been extensively documented in PDAC.Here,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient deprivation.We report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC patients.Mechanistically,we discovered that miR-15a repressed IGF1R expression via Fra-2 targeting.In miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient deprivation.In a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet restriction.Consistently,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent manner.Overall,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.展开更多
Pancreas surgery was historically considered the most challenging type of surgery for surgeons all over the world.It is related to higher morbidity and mortality rates as compared to other surgical procedures and surv...Pancreas surgery was historically considered the most challenging type of surgery for surgeons all over the world.It is related to higher morbidity and mortality rates as compared to other surgical procedures and survival rates for pancreatic adenocarcinoma are still disappointing(1).展开更多
Background:The use of laparoscopic(LLR)and robotic liver resections(RLR)has been safely performed in many institutions for liver tumours.A large scale international multicenter study would provide stronger evidence an...Background:The use of laparoscopic(LLR)and robotic liver resections(RLR)has been safely performed in many institutions for liver tumours.A large scale international multicenter study would provide stronger evidence and insight into application of these techniques for huge liver tumours≥10 cm.Methods:This was a retrospective review of 971 patients who underwent LLR and RLR for huge(≥10 cm)tumors at 42 international centers between 2002-2020.Results:One hundred RLR and 699 LLR which met study criteria were included.The comparison between the 2 approaches for patients with huge tumors were performed using 1:3 propensity-score matching(PSM)(73 vs.219).Before PSM,LLR was associated with significantly increased frequency of previous abdominal surgery,malignant pathology,liver cirrhosis and increased median blood.After PSM,RLR and LLR was associated with no significant difference in key perioperative outcomes including media operation time(242 vs.290 min,P=0.286),transfusion rate rate(19.2%vs.16.9%,P=0.652),median blood loss(200 vs.300 mL,P=0.694),open conversion rate(8.2%vs.11.0%,P=0.519),morbidity(28.8%vs.21.9%,P=0.221),major morbidity(4.1%vs.9.6%,P=0.152),mortality and postoperative length of stay(6 vs.6 days,P=0.435).Conclusions:RLR and LLR can be performed safely for selected patients with huge liver tumours with excellent outcomes.There was no significant difference in perioperative outcomes after RLR or LLR.展开更多
We are glad to contribute with an editorial on the important topic of therapeutic opportunities for hepatocellular carcinoma(HCC).The increasing diffusion of minimally invasive approaches to the liver and the growing ...We are glad to contribute with an editorial on the important topic of therapeutic opportunities for hepatocellular carcinoma(HCC).The increasing diffusion of minimally invasive approaches to the liver and the growing experience worldwide have progressively changed our curative strategies for patients affected by primary and metastatic liver tumors(1).展开更多
The advent of minimally invasive technologies to approachliver diseases changed some paradigms of liver surgeryduring the last two decades.They allow to safely treatpatients with poor liver function,portal hypertensio...The advent of minimally invasive technologies to approachliver diseases changed some paradigms of liver surgeryduring the last two decades.They allow to safely treatpatients with poor liver function,portal hypertension andcirrhosis,reducing the risk of decompensation(1).However,those potential benefits resulted to be in contrast with theactual application of such technologies in the real-life(2,3).展开更多
Treatment of peri-hilar cholangiocarcinoma(PHC)is one of the most critical challenges in the modern era of liver surgery(1).In addition to the highly demanding technique and insidious diagnostic work-up,the procedure ...Treatment of peri-hilar cholangiocarcinoma(PHC)is one of the most critical challenges in the modern era of liver surgery(1).In addition to the highly demanding technique and insidious diagnostic work-up,the procedure is often complicated by potentially life-threatening post-operative sequelae.展开更多
Liver transplant(LT)is considered the best option for patients with hepatocellular carcinoma(HCC)confined into the liver and generally associated with liver cirrhosis(1).The Milan criteria(MC)represent a milestone in ...Liver transplant(LT)is considered the best option for patients with hepatocellular carcinoma(HCC)confined into the liver and generally associated with liver cirrhosis(1).The Milan criteria(MC)represent a milestone in the selection of these patients(2).Therefore,basing on MC,the 5-year survival rate after LT could increase to 70%,with a HCC recurrence rate lower than 10%(2).Despite that,too many patients affected by HCC may not benefit from LT due to a tumor stage beyond the selection criteria.Over the last two decades,authors and physicians tried to overcome the MC exploring the opportunity to safely transplant patients beyond(3).Notably,the donor shortage and the competition between patients listed due to HCC and those listed for other indications,force physicians in selecting candidates with the best transplant benefit(3).展开更多
We read with great interest the paper by Chen and colleagues entitled "Use of robotics in liver donor right hepatectomy" (1). The authors currently represent the leading group performing robotic living donor...We read with great interest the paper by Chen and colleagues entitled "Use of robotics in liver donor right hepatectomy" (1). The authors currently represent the leading group performing robotic living donor liver procurements with 15 procedures completed to date (2).展开更多
文摘BACKGROUND:According to the current literature, biliary lithiasis is a worldwide-diffused condition that affects almost 20% of the general population. The rate of common bile duct stones(CBDS) in patients with symptomatic cholelithiasis is estimated to be 10% to 33%, depending on patient’s age.Compared to stones in the gallbladder, the natural history of secondary CBDS is still not completely understood. It is not clear whether an asymptomatic choledocholithiasis requires treatment or not. For many years, open cholecystectomy with choledochotomy and/or surgical sphincterotomy and cleaning of the bile duct were the gold standard to treat both pathologies. Development of both endoscopic retrograde cholangiopancreatography(ERCP) and laparoscopic surgery,together with improvements in diagnostic procedures, influenced new approaches to the management of CBDS in association with gallstones.DATA SOURCES:We decided to systematically review the literature in order to identify all the current therapeutic options for CBDS. A systematic literature search was performed independently by two authors using Pub Med, EMBASE, Scopus and the Cochrane Library Central.RESULTS:The therapeutic approach nowadays varies greatly according to the availability of experience and expertise in each center, and includes open or laparoscopic common bile duct exploration, various combinations of laparoscopic cholecystectomy and ERCP and combined laparoendoscopic rendezvous.CONCLUSIONS:Although ERCP followed by laparoscopic cholecystectomy is currently preferred in the majority of hospitals worldwide, the optimal treatment for concomitant gallstones and CBDS is still under debate, and greatly varies among different centers.
文摘AIM: To evaluate the relationship between hepatocellular carcinoma(HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence.METHODS: This retrospective study included 165 patients(143 men, 22 women; median age 56.8 years, range 28-70.4 years) transplanted for HCC who had a follow-up period longer than 2 mo. Pre-transplantation dynamic computed tomography or magnetic resonance examinations were retrospectively reviewed, classifying HCC imaging enhancement pattern into hypervascular and hypovascular based on presence of wash-in during arterial phase. All pathologic reports of the explanted livers were reviewed, collecting data about HCC differentiation degree. The association between imaging vascular pattern and pathological grade was estimated using the Fisher exact test. All follow-up clinical and imaging data were reviewed for evidence of recurrence. Recurrence rate was calculated and imaging features of recurrent tumor were collected, classifying early and late recurrences based on timing(< or ≥ 2 years after transplantation) and intrahepatic, extrahepatic and both intrahepatic and extrahepatic recurrences based onlocation. All intrahepatic recurrences were classified as hypervascular or hypovascular and the differentiation degree was collected where available. The presence of variations in imaging enhancement pattern and pathological grade between the primary tumor and the intrahepatic recurrence was evaluated and the association between imaging and histopatholgical variations was estimated by using the χ2 test. RESULTS: Of the 163 patients with imaging evidence of viable tumor, 156(95.7%) had hypervascular and 7(4.3%) hypovascular HCC. Among the 125 patients with evidence of viable tumor in the explanted liver, 19(15.2%) had grade 1, 56(44.8%) grade 2, 40(32%) grade 3 and 4(3.2%) grade 4 HCC, while the differentiation degree was not assessable for 6 patients(4.8%). A significant association was found between imaging vascularity and pathological grade(P = 0.035). Post-transplantation recurrence rate was 14.55%(24/165). All recurrences occurred in patients who had a hypervascular primary tumor. Three patients(12.5%) experienced late recurrence; the location of the first recurrence was extrahepatic in 14 patients(58.3%), intrahepatic in 7 patients(29.2%) and both intrahepatic and extrahepatic in 3 patients(12.5%). Two patients had a variation in imaging characteristics between the primary HCC(hypervascular) and the intrahepatic recurrent HCC(hypovascular), while 1 patient had a variation of histopathological characteristics(from moderate to poor differentiation), however no association was found between imaging and histopathological variations.CONCLUSION: A correlation was found between HCC grade and vascularity; some degree of variability may exist between the primary and the recurrence imaging/histopathological characteristics, apparently not correlated.
文摘BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patients(>70 years)with HCC in Milan criteria,which underwent liver resection(LR)or RFA.METHODS The study included 594 patients with HCC in Milan criteria(429 in LR group and 165 in RFA group)managed in 10 European centers.Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching(PSM)and Cox regression.RESULTS After PSM,we compared 136 patients in the LR group with 136 patients in the RFA group.Overall survival at 1,3,and 5 years was 91%,80%,and 76%in the LR group and 97%,67%,and 41%in the RFA group respectively(P=0.001).Diseasefree survival at 1,3,and 5 years was 84%,60%and 44%for the LR group,and 63%,36%,and 25%for the RFA group(P=0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group(1%vs 11%,P=0.001)in association with a shorter length of stay(2 d vs 7 d,P=0.001).In multivariate analysis,Model for End-stage Liver Disease(MELD)score(>10)[odds ratio(OR)=1.89],increased value of international normalized ratio(>1.3)(OR=1.60),treatment with radiofrequency(OR=1.46),and multiple nodules(OR=1.19)were independent predictors of a poor overall survival while a high MELD score(>10)(OR=1.51)and radiofrequency(OR=1.37)were independent factors associated with a higher recurrence rate.CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications,surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients(>70 years)with HCC in Milan criteria.
文摘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.
文摘BACKGROUND Liver resection and radiofrequency ablation are considered curative options for hepatocellular carcinoma.The choice between these techniques is still controversial especially in cases of hepatocellular carcinoma affecting posterosuperior segments in elderly patients.AIM To compare post-operative outcomes between liver resection and radiofrequency ablation in elderly with single hepatocellular carcinoma located in posterosuperior segments.METHODS A retrospective multicentric study was performed enrolling 77 patients age≥70-years-old with single hepatocellular carcinoma(≤30 mm),located in posterosuperior segments(4a,7,8).Patients were divided into liver resection and radiofrequency ablation groups and preoperative,peri-operative and long-term outcomes were retrospectively analyzed and compared using a 1:1 propensity score matching.RESULTS After propensity score matching,twenty-six patients were included in each group.Operative time and overall postoperative complications were higher in the resection group compared to the ablation group(165 min vs 20 min,P<0.01;54%vs 19%P=0.02 respectively).A median hospital stay was significantly longer in the resection group than in the ablation group(7.5 d vs 3 d,P<0.01).Ninety-day mortality was comparable between the two groups.There were no significant differences between resection and ablation group in terms of overall survival and disease free survival at 1,3,and 5 years.CONCLUSION Radiofrequency ablation in posterosuperior segments in elderly is safe and feasible and ensures a short hospital stay,better quality of life and does not modify the overall and disease-free survival.
文摘BACKGROUND The impact of obesity on surgical outcomes in elderly patients candidate for liver surgery is still debated.AIM To evaluate the impact of high body mass index(BMI)on perioperative and oncological outcome in elderly patients(>70 years old)treated with laparoscopic liver resection for hepatocellular carcinoma(HCC).METHODS Retrospective multicenter study including 224 elderly patients(>70 years old)operated by laparoscopy for HCC(196 with a BMI<30 and 28 with BMI≥30),observed from January 2009 to January 2019.RESULTS After propensity score matching,patients in two groups presented comparable results,in terms of operative time(median range:200 min vs 205 min,P=0.7 respectively in non-obese and obese patients),complications rate(22%vs 26%,P=1.0),length of hospital stay(median range:4.5 d vs 6.0 d,P=0.1).There are no significant differences in terms of short-and long-term postoperative results.CONCLUSION The present study showed that BMI did not impact perioperative and oncologic outcomes in elderly patients treated by laparoscopic resection for HCC.
文摘BACKGROUND Liver resection is the mainstay for a curative treatment for patients with resectable hepatocellular carcinoma(HCC),also in elderly population.Despite this,the evaluation of patient condition,liver function and extent of disease remains a demanding process with the aim to reduce postoperative morbidity and mortality.AIM To identify new perioperative risk factors that could be associated with higher 90-and 180-d mortality in elderly patients eligible for liver resection for HCC considering traditional perioperative risk scores and to develop a risk score.METHODS A multicentric,retrospective study was performed by reviewing the medical records of patients aged 70 years or older who electively underwent liver resection for HCC;several independent variables correlated with death from all causes at 90 and 180 d were studied.The coefficients of Cox regression proportional-hazards model for sixmonth mortality were rounded to the nearest integer to assign risk factors'weights and derive the scoring algorithm.RESULTS Multivariate analysis found variables(American Society of Anesthesiology score,high rate of comorbidities,Mayo end stage liver disease score and size of biggest lesion)that had independent correlations with increased 90-and 180-d mortality.A clinical risk score was developed with survival profiles.CONCLUSION This score can aid in stratifying this population in order to assess who can benefit from surgical treatment in terms of postoperative mortality.
文摘Liver transplant for hepatitis B virus(HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28(2%) received the graft from hepatitis B surface antigen positive(HBs Ag)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary nonfunction, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3-and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBs Agpositive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.
文摘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.
文摘Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and are characterized by a broad spectrum of clinical, histological and molecular features at presentation. Although focal and scattered calcifications are not uncommon within the primary tumor mass, heavy calcification within a GIST is rarely described in the literature and the clinical-biological meaning of this feature remains unclear. Cases with such an atypical presentation are challenging and may be associated with diagnostic pitfalls. Herein, we report a gastric GIST with the unusual presentation of prominent calcifications that was identified incidentally on imaging during a post-trauma diagnostic work-up. The patient underwent laparoscopic surgery with a radical resection of the mass, which was subsequently characterized by histological analysis as spindle-shaped tumor cells, positive for CD117/c-KIT, CD34 and DOG1, and with calcified areas. Given the intermediate risk of recurrence, no adjuvant therapy was recommended andthe patient underwent regular follow-up for 22 mo, with no evidence of relapse. Our case can be considered of interest because of the rarity of clinical presentation and the uniquely large size of the GIST at diagnosis(longest diameter exceeding 9 cm). In closing, we discuss the pathophysiology and clinical implications of calcifications in GISTs by reviewing the most up-to-date relevant literature.
文摘Bouveret's syndrome, defined as gastric outlet obstruction due to a large gallstone, is still one of the most dramatic biliary gallstone complications. Although new radiological and endoscopic techniques have made pre-surgical diagnosis possible in most cases and the death rate has dropped dramatically, "one-stage surgery" (biliary surgery carried out at the same time as the removal of the gut obstruction) should be still considered as the gold standard for the treatment of gallstone ileus.In this case, partial gastric outlet obstruction resulted in an atypical and insidious clinical presentation that allowed us to perform the conventional one-stage laparatomic procedure that completely solved the problem, thus avoiding any further complications.
文摘The role of minimally invasive liver surgery as a bridge to transplantation is very promising but still underestimated. However, it should be noted that surgical approach for hepatocellular carcinomas(HCC) is not merely a technical or technological issue. Nowadays, the epidemiology of HCC is evolving due to the increasing role of non-alcoholic fatty-liver-disease, and the emerging concerns on direct-acting antivirals against hepatitis C virus in terms of HCC incidence. Therefore, a fully multidisciplinary study of the cirrhotic patient is currently more important than ever before, and the management of those patients should be reserved to tertiary referral hepatobiliary centers. In particular, minimally invasive approach to the liver showed several advantages compared to the classical open procedure, in terms of:(1) the small impact on abdominal wall;(2) the gentle manipulation on the liver;(3) the limited surgical trauma; and(4) the respect of venous shunts. Therefore, more direct indications should be outlined also in the Barcelona Clinic Liver Cancer model. We believe that treatment of HCC in cirrhotic patients should be reserved to tertiary referral hepatobiliary centers, that should offer patient-tailored approaches to the liver disease, in order to provide the best care for each case, according to the individual comorbidities, risk factors, and personal quality of life expectations.
基金We thank the Genomic Shared Resource at The Ohio State University Comprehensive cancer Center(OSU CCC),supported by the Cancer Center Support Grant P30CA016058,for conducting the Affymetrix microarray assays,in particular Dr.Paolo FaddaWe acknowledge resources from the Campus Microscopy and Imaging Facility(CMIF)at The Ohio State University,in particular Dr.Jeffrey R.Tonniges for his valuable support+2 种基金This facility is supported in part by grant P30 CA016058,National Cancer Institute,Bethesda,MDHistology and immunohistochemistry services were provided by the Comparative Pathology&Digital Imaging Shared Resource,Department of Veterinary Biosciences and the Comprehensive Cancer Center,The Ohio State University,Columbus,OH.Figs.4a,6g and Supplementary Fig.10a of this manuscript were realized by using the software BioRender.comsupported by NIH/NCI grant R35 CA197706 to C.M.C.G.B.was funded by Ricerca Corrente of Ministero della Salute.
文摘Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient supplies.PDAC aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor microenvironment.Dysregulation of the onco-suppressor miR-15a has been extensively documented in PDAC.Here,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient deprivation.We report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC patients.Mechanistically,we discovered that miR-15a repressed IGF1R expression via Fra-2 targeting.In miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient deprivation.In a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet restriction.Consistently,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent manner.Overall,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.
文摘Pancreas surgery was historically considered the most challenging type of surgery for surgeons all over the world.It is related to higher morbidity and mortality rates as compared to other surgical procedures and survival rates for pancreatic adenocarcinoma are still disappointing(1).
基金Dr.T.P.Kingham was partially supported by the US National Cancer Institute MSKCC Core Grant number P30 CA00878 for this study.
文摘Background:The use of laparoscopic(LLR)and robotic liver resections(RLR)has been safely performed in many institutions for liver tumours.A large scale international multicenter study would provide stronger evidence and insight into application of these techniques for huge liver tumours≥10 cm.Methods:This was a retrospective review of 971 patients who underwent LLR and RLR for huge(≥10 cm)tumors at 42 international centers between 2002-2020.Results:One hundred RLR and 699 LLR which met study criteria were included.The comparison between the 2 approaches for patients with huge tumors were performed using 1:3 propensity-score matching(PSM)(73 vs.219).Before PSM,LLR was associated with significantly increased frequency of previous abdominal surgery,malignant pathology,liver cirrhosis and increased median blood.After PSM,RLR and LLR was associated with no significant difference in key perioperative outcomes including media operation time(242 vs.290 min,P=0.286),transfusion rate rate(19.2%vs.16.9%,P=0.652),median blood loss(200 vs.300 mL,P=0.694),open conversion rate(8.2%vs.11.0%,P=0.519),morbidity(28.8%vs.21.9%,P=0.221),major morbidity(4.1%vs.9.6%,P=0.152),mortality and postoperative length of stay(6 vs.6 days,P=0.435).Conclusions:RLR and LLR can be performed safely for selected patients with huge liver tumours with excellent outcomes.There was no significant difference in perioperative outcomes after RLR or LLR.
文摘We are glad to contribute with an editorial on the important topic of therapeutic opportunities for hepatocellular carcinoma(HCC).The increasing diffusion of minimally invasive approaches to the liver and the growing experience worldwide have progressively changed our curative strategies for patients affected by primary and metastatic liver tumors(1).
文摘The advent of minimally invasive technologies to approachliver diseases changed some paradigms of liver surgeryduring the last two decades.They allow to safely treatpatients with poor liver function,portal hypertension andcirrhosis,reducing the risk of decompensation(1).However,those potential benefits resulted to be in contrast with theactual application of such technologies in the real-life(2,3).
文摘Treatment of peri-hilar cholangiocarcinoma(PHC)is one of the most critical challenges in the modern era of liver surgery(1).In addition to the highly demanding technique and insidious diagnostic work-up,the procedure is often complicated by potentially life-threatening post-operative sequelae.
文摘Liver transplant(LT)is considered the best option for patients with hepatocellular carcinoma(HCC)confined into the liver and generally associated with liver cirrhosis(1).The Milan criteria(MC)represent a milestone in the selection of these patients(2).Therefore,basing on MC,the 5-year survival rate after LT could increase to 70%,with a HCC recurrence rate lower than 10%(2).Despite that,too many patients affected by HCC may not benefit from LT due to a tumor stage beyond the selection criteria.Over the last two decades,authors and physicians tried to overcome the MC exploring the opportunity to safely transplant patients beyond(3).Notably,the donor shortage and the competition between patients listed due to HCC and those listed for other indications,force physicians in selecting candidates with the best transplant benefit(3).
文摘We read with great interest the paper by Chen and colleagues entitled "Use of robotics in liver donor right hepatectomy" (1). The authors currently represent the leading group performing robotic living donor liver procurements with 15 procedures completed to date (2).
