Search

ImportanceClear indications on how to select retreatments for recurrent hepatocellular carcinoma (HCC) are still lacking.ObjectiveTo create a machine learning predictive model of survival after HCC recurrence to allocate patients to their best potential treatment.Design, Setting, and ParticipantsReal-life data were obtained from an Italian registry of hepatocellular carcinoma between January 2008 and December 2019 after a median (IQR) follow-up of 27 (12-51) months. External validation was made on data derived by another Italian cohort and a Japanese cohort. Patients who experienced a recurrent HCC after a first surgical approach were included. Patients were profiled, and factors predicting survival after recurrence under different treatments that acted also as treatment effect modifiers were assessed. The model was then fitted individually to identify the best potential treatment. Analysis took place between January and April 2021.ExposuresPatients were enrolled if treated by reoperative hepatectomy or thermoablation, chemoembolization, or sorafenib.Main Outcomes and MeasuresSurvival after recurrence was the end point.ResultsA total of 701 patients with recurrent HCC were enrolled (mean [SD] age, 71 [9] years; 151 [21.5%] female). Of those, 293 patients (41.8%) received reoperative hepatectomy or thermoablation, 188 (26.8%) received sorafenib, and 220 (31.4%) received chemoembolization. Treatment, age, cirrhosis, number, size, and lobar localization of the recurrent nodules, extrahepatic spread, and time to recurrence were all treatment effect modifiers and survival after recurrence predictors. The area under the receiver operating characteristic curve of the predictive model was 78.5% (95% CI, 71.7%-85.3%) at 5 years after recurrence. According to the model, 611 patients (87.2%) would have benefited from reoperative hepatectomy or thermoablation, 37 (5.2%) from sorafenib, and 53 (7.6%) from chemoembolization in terms of potential survival after recurrence. Compared with patients for which the best potential treatment was reoperative hepatectomy or thermoablation, sorafenib and chemoembolization would be the best potential treatment for older patients (median [IQR] age, 78.5 [75.2-83.4] years, 77.02 [73.89-80.46] years, and 71.59 [64.76-76.06] years for sorafenib, chemoembolization, and reoperative hepatectomy or thermoablation, respectively), with a lower median (IQR) number of multiple recurrent nodules (1.00 [1.00-2.00] for sorafenib, 1.00 [1.00-2.00] for chemoembolization, and 2.00 [1.00-3.00] for reoperative hepatectomy or thermoablation). Extrahepatic recurrence was observed in 43.2% (n = 16) for sorafenib as the best potential treatment vs 14.6% (n = 89) for reoperative hepatectomy or thermoablation as the best potential treatment and 0% for chemoembolization as the best potential treatment. Those profiles were used to constitute a patient-tailored algorithm for the best potential treatment allocation.Conclusions and RelevanceThe herein presented algorithm should help in allocating patients with recurrent HCC to the best potential treatment according to their specific characteristics in a treatment hierarchy fashion.

Benchmark analysis for open liver surgery for cirrhotic patients with hepatocellular carcinoma (HCC) is still undefined.Patients were identified from the Italian national registry HE.RC.O.LE.S. The Achievable Benchmark of Care (ABC) method was employed to identify the benchmarks. The outcomes assessed were the rate of complications, major comorbidities, post-operative ascites (POA), post-hepatectomy liver failure (PHLF), 90-day mortality. Benchmarking was stratified for surgical complexity (CP1, CP2 and CP3).A total of 978 of 2698 patients fulfilled the inclusion criteria. 431 (44.1%) patients were treated with CP1 procedures, 239 (24.4%) with CP2 and 308 (31.5%) with CP3 procedures. Patients submitted to CP1 had a worse underlying liver function, while the tumor burden was more severe in CP3 cases. The ABC for complications (13.1%, 19.2% and 28.1% for CP1, CP2 and CP3 respectively), major complications (7.6%, 11.1%, 12.5%) and 90-day mortality (0%, 3.3%, 3.6%) increased with the surgical difficulty, but not POA (4.4%, 3.3% and 2.6% respectively) and PHLF (0% for all groups).We propose benchmarks for open liver resections in HCC cirrhotic patients, stratified for surgical complexity. The difference between the benchmark values and the results obtained during everyday practice reflects the room for potential growth, with the aim to encourage constant improvement among liver surgeons.

Background and aims: We investigated the clinical impact of the newly defined metabolic-associated fatty liver disease (MAFLD) in patients undergoing hepatectomy for HCC (MAFLD-HCC) comparing the characteristics and outcomes of patients with MAFLD-HCC to viral- and alcoholic-related HCC (HCV-HCC, HBV-HCC, A-HCC). Methods: A retrospective analysis of patients included in the He.RC.O.Le.S. Group registry was performed. The characteristics, short- and long-term outcomes of 1315 patients included were compared according to the study group before and after an exact propensity score match (PSM). Results: Among the whole study population, 264 (20.1%) had MAFLD-HCC, 205 (15.6%) had HBV-HCC, 671 (51.0%) had HCV-HCC and 175 (13.3%) had A-HCC. MAFLD-HCC patients had higher BMI (p < 0.001), Charlson Comorbidities Index (p < 0.001), size of tumour (p < 0.001), and presence of cirrhosis (p < 0.001). After PSM, the 90-day mortality and severe morbidity rates were 5.9% and 7.1% in MAFLD-HCC, 2.3% and 7.1% in HBV-HCC, 3.5% and 11.7% in HCV-HCC, and 1.2% and 8.2% in A-HCC (p = 0.061 and p = 0.447, respectively). The 5-year OS and RFS rates were 54.4% and 37.1% in MAFLD-HCC, 64.9% and 32.2% in HBV-HCC, 53.4% and 24.7% in HCV-HCC and 62.0% and 37.8% in A-HCC (p = 0.345 and p = 0.389, respectively). Cirrhosis, multiple tumours, size and satellitosis seems to be the independent predictors of OS. Conclusion: Hepatectomy for MAFLD-HCC seems to have a higher but acceptable operative risk. However, long-term outcomes seems to be related to clinical and pathological factors rather than aetiological risk factors.

Postoperative ascites (POA) is the most common complication after liver surgery for hepatocarcinoma (HCC), but its impact on survival is not reported. The aim of the study is to investigate its impact on overall survival (OS) and disease-free survival (DFS), and secondarily to identify the factors that may predict the occurrence.Data were collected from 23 centers participating in the Italian Surgical HCC Register (HE.RC.O.LE.S. Group) between 2008 and 2018. POA was defined as ≥500 ml of ascites in the drainage after surgery. Survival analysis was conducted by the Kaplan Meier method. Risk adjustment analysis was conducted by Cox regression to investigate the risk factors for mortality and recurrence.Among 2144 patients resected for HCC, 1871(88.5%) patients did not experience POA while 243(11.5%) had the complication. Median OS for NO-POA group was not reached, while it was 50 months (95%CI = 41-71) for those with POA (p0.001). POA independently increased the risk of mortality (HR = 1.696, 95%CI = 1.352-2.129, p0.001). Relapse risk after surgery was not predicted by the occurrence of POA. Presence of varices (OR = 2.562, 95%CI = 0.921-1.822, p0.001) and bilobar disease (OR = 1.940, 95%CI = 0.921-1.822, p: 0.004) were predictors of POA, while laparoscopic surgery was protective (OR = 0.445, 95%CI = 0.295-0.668, p0.001). Ninety-day mortality was higher in the POA group (9.1% vs 1.9% in NO-POA group, p0.001).The occurrence of POA after surgery for HCC strongly increases the risk of long-term mortality and its occurrence is relatively frequent. More efforts in surgical planning should be made to limit its occurrence.

Resection remains the treatment of choice achieving 5-year survival rates of 22% to 40%. The aim of this analysis was to examine the outcomes of patients with solitary ≤5 cm intrahepatic cholangiocarcinoma.A retrospective chart review was performed on 123 patients undergoing resection for primary intrahepatic cholangiocarcinoma from 1995 to 2013. Group 1 included patients with asymptomatic solitary intrahepatic cholangiocarcinoma measuring ≤5 cm.Group 1 (n = 33, 27%) had a greater rate of underlying liver disease, cirrhosis, minor resection, favorable pathologic features including decreased rate of perineural invasion, vascular invasion, lymph node involvement, and satellite nodules (P .05). Factors associated with overall poor outcome were patients in Group 2 (P=.025), positive margin (P=.04), presence of satellite nodules (P = .008), and multinodularity (P=.058). Factors associated with recurrence in Group 1 were presence of satellite nodules (P=.004), and tumor size ≥4 cm (P=.031). Factors associated with decreased survival in Group 1 was transfusion requirement (P = 0.018). The 5-year recurrence and survival rates were (39% vs 67%) and (71% vs 53%) in Group 1 versus Group 2, respectively (P=.111).Resection of solitary intrahepatic cholangiocarcinoma ≤5 cm can achieve 5-year survival rates up to 71%. Results were comparable to those of patients undergoing transplantation for hepatocellular cancer within the Milan criteria.

Purpose To identify prognostic factors and patterns of local failure in patients with cholangiocarcinoma (CCA), after surgical resection in the absence of adjuvant radiation, for optimal definition of target volumes encompassing the majority of local recurrences. Methods and Materials A chart review was performed in patients who underwent resection for primary CCA (intrahepatic, hilar, and distal) between 1999 and 2014. Local failure was defined as recurrence in a theoretical reasonable postoperative radiation volume. This includes the cut surface of liver, biliary anastomosis, hilum, portal nodes, celiac nodes, peri-pancreatic nodes, gastro-hepatic nodes, and retroperitoneal nodes. Patients who received adjuvant radiation were excluded. Results A total of 189 patients underwent surgical resection for CCA, of whom 145 patients had sufficient follow-up. Median follow-up was 41.6 months (95% confidence interval 35.4-48.7 months). Of the 145 cases, 102 were intrahepatic and 43 were hilar/distal CCA. Adjuvant chemotherapy was given in 38 cases (26%), of which 20 (54%) were gemcitabine-based. Eighty-six patients (59%) had a documented recurrence, of whom 44 (51%) had a locoregional component. Among patients who had a recurrence, 23 (27%) had a recurrence at the biliary anastomosis and/or cut liver surface. Twenty-eight patients (32.6%) had a recurrence in the regional lymph nodes, most prevalent in the portal (16.3%) and retroperitoneal (17.4%) lymph nodes. Univariable analysis identified tumor size, any vascular invasion, presence of satellites, stage/nodal status, and receipt of chemotherapy as significant prognostic factors of overall recurrence among intrahepatic patients. Presence of satellites, and stage 3/Nx status remained statistically significant in multivariable modeling. Conclusions The areas at highest risk for locoregional recurrence after surgical resection for primary CCA are the biliary anastomosis/cut liver surface, portal lymph nodes, and retroperitoneal lymph nodes. Although these results need to be validated, adjuvant radiation should possibly cover these areas to maximize locoregional control.

Background: We aimed to assess the ability of comprehensive complication index (CCI) and Clavien-Dindo complication (CDC) scale to predict excessive length of hospital stay (e-LOS) in patients undergoing liver resection for hepatocellular carcinoma. Methods: Patients were identified from an Italian multi-institutional database and randomly selected to be included in either a derivation or validation set. Multivariate logistic regression models and ROC curve analysis including either CCI or CDC as predictors of e-LOS were fitted to compare predictive performance. E-LOS was defined as a LOS longer than the 75th percentile among patients with at least one complication. Results: A total of 2669 patients were analyzed (1345 for derivation and 1324 for validation). The odds ratio (OR) was 5.590 (95%CI 4.201, 7.438) for CCI and 5.507 (4.152, 7.304) for CDC. The AUC was 0.964 for CCI and 0.893 for CDC in the derivation set and 0.962 vs. 0.890 in the validation set, respectively. In patients with at least two complications, the OR was 2.793 (1.896, 4.115) for CCI and 2.439 (1.666, 3.570) for CDC with an AUC of 0.850 and 0.673, respectively in the derivation cohort. The AUC was 0.806 for CCI and 0.658 for CDC in the validation set. Conclusions: When reporting postoperative morbidity in liver surgery, CCI is a preferable scale.

Epidemiology of hepatocellular carcinoma (HCC) showed a correlation between incidence and geographical-relevant risk factors. This study aims to compare the distributions of cancer stem cells (CSC) in two distant populations in Asia and Europe. We analyzed 52 and 43 selected HCC patients undergoing hepatectomy in Ho Chi Minh City (Vietnam) and Trieste (Italy). Each patient sample consisted of HCC, peri-HCC, and non-tumoral (distal) tissue. Demographic data were recorded together with clinical findings. The protocol for the collection of tissue samples and RNA was standardized in both laboratories and gene expression analysis was performed in a single laboratory with identical PCR conditions. Baseline data showed comparable laboratory findings between the two cohorts. mRNA distribution showed a comparable pattern of all CSC markers analyzed with the expression of CD90 progressively increasing from distal and peri-HCC to be highest in HCC (p &lt, 0.001), confirmed by immunofluorescence data. CD90 mRNA distribution was related to HBV-related HCC and a tumor diameter less than 5 cm. Patients with high tumoral CD90 mRNA had a shorter time (p &lt, 0.05) to tumor recurrence compared to patients with lower CD90. This comparative study showed that CD90 mRNA expressions are comparable between Eastern and Western HCC cases.

The main functions of biological adhesives and sealants are to repair injured tissues, reinforce surgical wounds, or even replace common suturing techniques. In general surgery, adhesives must match several requirements taking into account clinical needs, biological effects, and material features; these requirements can be fulfilled by specific polymers. Natural or synthetic polymeric materials can be employed to generate three-dimensional networks that physically or chemically bind to the target tissues and act as hemostats, sealants, or adhesives. Among them, fibrin, gelatin, dextran, chitosan, cyanoacrylates, polyethylene glycol, and polyurethanes are the most important components of these interfaces; various aspects regarding their adhesion mechanisms, mechanical performance, and resistance to body fluids should be taken into account to choose the most suitable formulation for the target application. This review aims to describe the main adhesives and sealant materials for general surgery applications developed in the past decades and to highlight the most important aspects for the development of future formulations.

Background Markers of tumour biology may be valuable prognostic indicators after hepatic resection of colorectal cancer liver metastases (CRLMs). Identification of the aggressiveness of these metastases might inform the appropriateness of hepatic surgery. Methods Patients undergoing liver resection for CRLMs between January 2001 and July 2013 in four tertiary hospitals were reviewed. A mathematical model to estimate CRLM doubling times was constructed for patients with metachronous metastases. Tumour doubling time was investigated in relation to the features of colorectal cancer, including KRAS status. The hazard rate for recurrence and death following hepatectomy was explored through the Kernel-smoothed estimator. Results Of 1063 patients undergoing liver resection for CRLMs, 361 with metachronous metastases undergoing single-stage hepatectomy were analysed. The mean doubling time in patients not receiving chemotherapy between surgery for colorectal cancer and CRLM was 71·4 days. Tumour doubling time was shorter in patients with more advanced primary tumour stages, with mutant KRAS and in those who did not receive chemotherapy. For fast-growing CRLMs (doubling time less than 48 days), the risk of recurrence was highest within the first postoperative year, and was about 7 per cent per month. Conclusion Primary features of colorectal cancer were linked to aggressiveness of CRLMs as measured by doubling time.

Background Laparoscopic surgery is widely accepted for colon cancer resection. However, T4 colon cancers have been considered an absolute contraindication to laparoscopic resection. The aim of this study is to evaluate if laparoscopy should still be considered an absolute contraindication to T4 colon cancer, based on a monocenter series recorded in a prospective database. Methods Of 77 patients undergoing elective resection for T4 colon cancer between 2004 and 2015, 39 were performed laparoscopically and were compared to 38 having undergone open resection. Results Patient age and American Society of Anesthesiologists score were comparable. Eleven patients initially treated laparoscopically were converted to an open approach (28.2%). There were no statistically significant differences between laparoscopy vs. open concerning tumor stage, R0 resections, operative time, metastatic rate, local recurrence rate or hospital stay. Laparoscopic surgery was associated with less postoperative complications than open surgery (25.6% vs. 52.6%; P=0.020). No statistically significant difference was found with regards to the 3-year overall, tumor-specific and disease-free survivals. Conclusions As there were less postoperative complications, while tumor stage, operative time, hospital stay, R0 resection and survival rates after laparoscopic resection for T4 colonic cancer were not statistically significantly different compared to open surgery, T4 colon cancers are no longer an absolute contraindication to laparoscopic resection in our hospital.

no abstract

At present, preservation of the anal sphincter is possible in the majority of low rectal (LR) carcinomas; indeed, by associating neoadjuvant radiochemotherapy (RCT) to TME, it is possible to preserve the sphincter in at least 70% of cases

This chapter relates about surgical strategies in rectal cancer. Laparotomy, laparoscopy, SILS and robotics are detailed as the respective indications for all them. Then are described the different approaches to early cancers, to cancers requiring operation at the first diagnosis, and finally for cancer that are considered as nonresectable at the first evaluation, suggesting multidisiplinar treatments. Downstaging and downsizing are described.

Recurrence of hepatocellular cancer after resection is a significant problem. The optimal treatment of patients with intrahepatic recurrence after resection and well-preserved liver function is not clear. We analyzed the outcomes of patients undergoing a second hepatic resection for recurrent hepatocellular cancer at a single Western center.The records of all patients undergoing primary hepatic resection for hepatocellular cancer between January 1994 and January 2009 were reviewed. Patients with a single intrahepatic recurrence, Child's A liver function, and platelet count100,000/μl underwent a second hepatic resection. Clinical data was recorded and analyzed.Of the 487 patients undergoing primary resection, 221 developed recurrence, and 35 underwent a second hepatic resection. There were no perioperative mortalities. There were 10 deaths during the study period; 5-year overall survival was 67% from second resection. Time to recurrence from primary resection1 year and gross vascular invasion at second resection were predictors of survival and recurrence. Patients with recurrence1 year from primary resection and without gross vascular invasion had a 5-year survival of 81%. There were 17 recurrences with a 3-year recurrence rate of 55%.Second hepatic resection for recurrent hepatocellular cancer is applicable in about 15% of patient with recurrence. The procedure is safe and can achieve excellent results in well-selected patients. Recurrence continues to be a significant problem.