Single large hepatocellular carcinoma > 5 cm with surgical indication: is it mandatory a major hepatectomy? a propensity-score weighted analysis.

PURPOSE: Single large hepatocellular carcinoma >5cm (SLHCC) traditionally requires a major liver resection. Minor resections are often performed with the goal to reduce morbidity and mortality. Aim of the study was to establish if a major resection should be considered the best treatment for SLHCC or a more limited resection should be preferred. METHODS: A multicenter retrospective analysis of the HE.RC.O.LE.S. Group register was performed. All collected patients with surgically treated SLHCC were divided in 5 groups of treatment (major hepatectomy, sectorectomy, left lateral sectionectomy, segmentectomy, non-anatomical resection) and compared for baseline characteristics, short and long-term results. A propensity-score weighted analysis was performed. RESULTS: 535 patients were enrolled in the study. Major resection was associated with significantly increased major complications compared to left lateral sectionanectomy, segmentectomy and non-anatomical resection (all p<0.05) and borderline significant increased major complications compared to sectorectomy (p=0.08). Left lateral sectionectomy showed better overall survival compared to major resection (p=0.02), while other groups of treatment resulted similar to major hepatectomy group for the same item. Absence of oncological benefit after major resection and similar outcomes among the 5 groups of treatment was confirmed even in the sub-population excluding patients with macrovascular invasion. CONCLUSION: Major resection was associated to increased major post-operative morbidity without long-term survival benefit; when technically feasible and oncologically adequate, minor resections should be preferred for the surgical treatment of SLHCC.

Predictive value of preoperative albumin-bilirubin score and other risk factors for short-term outcomes after open pancreatoduodenectomy.

BACKGROUND: Pancreatoduodenectomy represents a complex procedure involving extensive organ resection and multiple alimentary reconstructions. It is still associated with high morbidity, even in high-volume centres. Prediction tools including preoperative patient-related factors to preoperatively identify patients at high risk for postoperative complications could enable tailored perioperative management and improve patient outcomes. AIM: To evaluate the clinical significance of preoperative albumin-bilirubin score and other risk factors in relation to short-term postoperative outcomes in patients after open pancreatoduodenectomy. METHODS: This retrospective study included all patients who underwent open pancreatic head resection (pylorus-preserving pancreatoduodenectomy or Whipple resection) for various pathologies during a five-year period (2017-2021) in a tertiary care setting at University Medical Centre Ljubljana, Slovenia and Cattinara Hospital, Trieste, Italy. Short-term postoperative outcomes, namely, postoperative complications, postoperative pancreatic fistula, reoperation, and mortality, were evaluated in association with albumin-bilirubin score and other risk factors. Multiple logistic regression models were built to identify risk factors associated with these short-term postoperative outcomes. RESULTS: Data from 347 patients were collected. Postoperative complications, major postoperative complications, postoperative pancreatic fistula, reoperation, and mortality were observed in 52.7%, 22.2%, 23.9%, 21.3%, and 5.2% of patients, respectively. There was no statistically significant association between the albumin-bilirubin score and any of these short-term postoperative complications based on univariate analysis. When controlling for other predictor variables in a logistic regression model, soft pancreatic texture was statistically significantly associated with postoperative complications [odds ratio (OR): 2.09; 95% confidence interval (95%CI): 1.19-3.67]; male gender (OR: 2.12; 95%CI: 1.15-3.93), soft pancreatic texture (OR: 3.06; 95%CI: 1.56-5.97), and blood loss (OR: 1.07; 95%CI: 1.00-1.14) were statistically significantly associated with major postoperative complications; soft pancreatic texture was statistically significantly associated with the development of postoperative pancreatic fistula (OR: 5.11; 95%CI: 2.38-10.95); male gender (OR: 1.97; 95%CI: 1.01-3.83), soft pancreatic texture (OR: 2.95; 95%CI: 1.42-6.11), blood loss (OR: 1.08; 95%CI: 1.01-1.16), and resection due to duodenal carcinoma (OR: 6.58; 95%CI: 1.20-36.15) were statistically significantly associated with reoperation. CONCLUSION: The albumin-bilirubin score failed to predict short-term postoperative outcomes in patients undergoing pancreatoduodenectomy. However, other risk factors seem to influence postoperative outcomes, including male sex, soft pancreatic texture, blood loss, and resection due to duodenal carcinoma.

Evaluation of the ACS-NSQIP Surgical Risk Calculator in Patients with Hepatic Metastases from Colorectal Cancer Undergoing Liver Resection.

BACKGROUND: The American College of Surgeons National Surgical Quality Improvement Program surgical risk calculator (ACS-NSQIP SRC) has been designed to predict morbidity and mortality and help stratify surgical patients. This study evaluates the performance of the SRC for patients undergoing surgery for colorectal liver metastases (CRLM). METHODS: SRC was retrospectively computed for patients undergoing liver or simultaneous colon and liver surgery for colorectal cancer (CRC) in two high tertiary referral centres from 2011 to 2020. C-statistics and Brier score were calculated as a mean of discrimination and calibration respectively, for both group and for every level of surgeon adjustment score (SAS) for liver resections in case of simultaneous liver-colon surgery. An AUC ≥ 0.7 shows acceptable discrimination; a Brier score next to 0 means the prediction tool has good calibration. RESULTS: Four hundred ten patients were included, 153 underwent simultaneous resection, and 257 underwent liver-only resections. For simultaneous surgery, the ACS-NSQIP SRC showed good calibration and discrimination only for cardiac complication (AUC = 0.720, 0.740, and 0.702 for liver resection unadjusted, SAS-2, and SAS-3 respectively; 0.714 for colon resection; and Brier score = 0.04 in every case). For liver-only surgery, it only showed good calibration for cardiac complications (Brier score = 0.03). The SRC underestimated the incidence of overall complications, pneumonia, cardiac complications, and the length of hospital stay. CONCLUSIONS: ACS-NSQIP SRC showed good predicting capabilities only for 1 out of 5 evaluated outcomes; therefore, it is not a reliable tool for patients undergoing liver surgery for CRLM, both in the simultaneous and staged resections.

Survival benefit of second line therapies for recurrent hepatocellular carcinoma: repeated hepatectomy, thermoablation and second-line transplant referral in a real life national scenario.

BACKGROUND: Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group). METHODS: Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups. RESULTS: 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 - 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 - 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 - 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 - 1.93, p = 0.011). CONCLUSION: It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed.

Machine Learning Predictive Model to Guide Treatment Allocation for Recurrent Hepatocellular Carcinoma After Surgery.

Importance: Clear indications on how to select retreatments for recurrent hepatocellular carcinoma (HCC) are still lacking. Objective: To create a machine learning predictive model of survival after HCC recurrence to allocate patients to their best potential treatment. Design, Setting, and Participants: Real-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. Exposures: Patients were enrolled if treated by reoperative hepatectomy or thermoablation, chemoembolization, or sorafenib. Main Outcomes and Measures: Survival after recurrence was the end point. Results: A 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 Relevance: The 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.

The Effect of a Liver Transplant Program on the Outcomes of Resectable Hepatocellular Carcinoma: A Nationwide Multicenter Analysis.

OBJECTIVE: To evaluate the effect of a liver transplantation (LT) program on the outcomes of resectable hepatocellular carcinoma (HCC). BACKGROUND: Surgical treatment of HCC includes both hepatic resection (HR) and LT. However, the presence of cirrhosis and the possibility of recurrence make the management of this disease complex and probably different according to the presence of a LT program. METHODS: Patients undergoing HR for HCC between January 2005 and December 2019 were identified from a national database of HCC. The main study outcomes were major surgical complications according to the Comprehensive Complication Index, posthepatectomy liver failure (PHLF), 90-day mortality, overall survival, and disease-free survival. Secondary outcomes were salvage liver transplantation (SLT) and postrecurrence survival. RESULTS: A total of 3202 patients were included from 25 hospitals over the study period. Three of 25 (12%) had an LT program. The presence of an LT program within a center was associated with a reduced probability of PHLF (odds ratio=0.38) but not with overall survival and disease-free survival. There was an increased probability of SLT when HR was performed in a transplant hospital (odds ratio=12.05). Among transplant-eligible patients, those who underwent LT had a significantly longer postrecurrence survival. CONCLUSIONS: This study showed that the presence of a LT program was associated with decreased PHLF rates and an increased probability to receive SLT in case of recurrence.

Predictors of Hepatocellular Carcinoma Early Recurrence in Patients Treated with Surgical Resection or Ablation Treatment: A Single-Center Experience.

Introduction: Hepatocellular carcinoma (HCC) is the sixth most diagnosed malignancy and the fourth leading cause of cancer-related death worldwide, with poor overall survival despite available curative treatments. One of the most crucial factors influencing survival in HCC is recurrence. The current study aims to determine factors associated with early recurrence of HCC in patients with BCLC Stage 0 or Stage A treated with surgical resection or local ablation. Materials and Methods: We retrospectively enrolled 58 consecutive patients diagnosed with HCC within BCLC Stage 0 or Stage A and treated either by surgical resection or local ablation with maximum nodule diameter < 50 mm. In the first year of follow-up after treatment, imaging was performed regularly one month after treatment and then every three months. Each case was discussed collectively by the Liver Multidisciplinary Group to decide diagnosis, treatment, follow-up, and disease recurrence. Variables resulting in statistically significant difference were then studied by Cox regression analysis; univariately and then multivariately based on forward stepwise Cox regression. Results are represented in hazard ratio (H.R.) with 95% confidence interval (C.I.). Results: There was no statistically significant difference in recurrence rates (34.8 vs. 45.7%, log-rank test, p = 0.274) between patients undergoing surgical resection and local ablation, respectively. Early recurrence was associated with male gender (HR 2.5, 95% C.I. 1.9−3.1), nodule diameter > 20 mm (HR 4.5, 95% C.I. 3.9−5.1), platelet count < 125 × 103 cell/mm3 (HR 1.6, 95% C.I. 1.2−1.9), platelet-lymphocyte ratio < 95 (HR 2.1, 95% C.I. 1.7−2.6), lymphocyte-monocyte ratio < 2.5 (HR 1.9, 95% C.I. 1.4−2.5), and neutrophil-lymphocyte ratio > 2 (HR 2.7, 95% C.I. 2.2−3.3). Discussion and Conclusions: Our results are in line with the current literature. Male gender and tumor nodule dimension are the main risk factors associated with early HCC recurrence. Platelet count and other combined scores can be used as predictive tools for early HCC recurrence, although more studies are needed to define cut-offs.

Benchmarking postoperative outcomes after open liver surgery for cirrhotic patients with hepatocellular carcinoma in a national cohort.

BACKGROUND: Benchmark analysis for open liver surgery for cirrhotic patients with hepatocellular carcinoma (HCC) is still undefined. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

The largest western experience on salvage hepatectomy for recurrent hepatocellular carcinoma: propensity score-matched analysis on behalf of He.RC.O.Le.Study Group.

BACKGROUND: We aimed to evaluate, in a large Western cohort, perioperative and long-term oncological outcomes of salvage hepatectomy (SH) for recurrent hepatocellular carcinoma (rHCC) after primary hepatectomy (PH) or locoregional treatments. METHODS: Data were collected from the Hepatocarcinoma Recurrence on the Liver Study Group (He.RC.O.Le.S.) Italian Registry. After 1:1 propensity score-matched analysis (PSM), two groups were compared: the PH group (patients submitted to resection for a first HCC) and the SH group (patients resected for intrahepatic rHCC after previous HCC-related treatments). RESULTS: 2689 patients were enrolled. PH included 2339 patients, SH 350. After PSM, 263 patients were selected in each group with major resected nodule median size, intraoperative blood loss and minimally invasive approach significantly lower in the SH group. Long-term outcomes were compared, with no difference in OS and DFS. Univariate and multivariate analyses revealed only microvascular invasion as an independent prognostic factor for OS. CONCLUSION: SH proved to be equivalent to PH in terms of safety, feasibility and long-term outcomes, consistent with data gathered from East Asia. In the awaiting of reliable treatment-allocating algorithms for rHCC, SH appears to be a suitable alternative in patients fit for surgery, regardless of the previous therapeutic modality implemented.

Hepatectomy for Metabolic Associated Fatty Liver Disease (MAFLD) related HCC: Propensity case-matched analysis with viral- and alcohol-related HCC.

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.

The Impact of Postoperative Ascites on Survival After Surgery for Hepatocellular Carcinoma: a National Study.

BACKGROUND: 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. METHOD: 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. RESULTS: 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 (p < 0.001). POA independently increased the risk of mortality (HR = 1.696, 95%CI = 1.352-2.129, p < 0.001). Relapse risk after surgery was not predicted by the occurrence of POA. Presence of varices (OR = 2.562, 95%CI = 0.921-1.822, p < 0.001) 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, p < 0.001). Ninety-day mortality was higher in the POA group (9.1% vs 1.9% in NO-POA group, p < 0.001). CONCLUSION: 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.

The mRNA Distribution of Cancer Stem Cell Marker CD90/Thy-1 Is Comparable in Hepatocellular Carcinoma of Eastern and Western Populations.

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 < 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 < 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.

Performance of Comprehensive Complication Index and Clavien-Dindo Complication Scoring System in Liver Surgery for Hepatocellular Carcinoma.

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.

Hepatocellular carcinoma surgical and oncological trends in a national multicentric population: the HERCOLES experience.

Liver surgery is the first line treatment for hepatocarcinoma. Hepatocarcinoma Recurrence on the Liver Study (HERCOLES) Group was established in 2018 with the goal to create a network of Italian centres sharing data and promoting scientific research on hepatocellular carcinoma (HCC) in the surgical field. This is the first national report that analyses the trends in surgical and oncological outcomes. Register data were collected by 22 Italian centres between 2008 and 2018. One hundred sixty-four variables were collected, regarding liver functional status, tumour burden, radiological, intraoperative and perioperative data, histological features and oncological follow-up. 2381 Patients were enrolled. Median age was 70 (IQR 63-75) years old. Cirrhosis was present in 1491 patients (62.6%), and Child-A were 89.9% of cases. HCC was staged as BCLC0-A in almost 50% of cases, while BCLC B and C were 20.7% and 17.9% respectively. Major liver resections were 481 (20.2%), and laparoscopy was employed in 753 (31.6%) cases. Severe complications occurred only in 5%. Postoperative ascites was recorded in 10.5% of patients, while posthepatectomy liver failure was observed in 4.9%. Ninety-day mortality was 2.5%. At 5 years, overall survival was 66.1% and disease-free survival was 40.9%. Recurrence was intrahepatic in 74.6% of cases. Redo-surgery and thermoablation for recurrence were performed up to 32% of cases. This is the most updated Italian report of the national experience in surgical treatment for HCC. This dataset is consistently allowing the participating centres in creating multicentric analysis which are already running with a very large sample size and strong power.

Serum Stem Cell Growth Factor Beta for the Prediction of Therapy Response in Hepatocellular Carcinoma.

INTRODUCTION: Chronic inflammatory response is one of major contributors in the development of hepatocellular carcinoma (HCC). Inflammatory molecules, such as cytokines and growth factors in the circulation, can be useful in the diagnosis and prognosis of the patients. The stem cell growth factor beta (SCGFß), a newly found protein, is a secreted sulfated glycoprotein and it functions as a growth factor for primitive hematopoietic progenitor cells. The level of SCGFß had been reported to be elevated in several cancer types. However, there is very few or even no information on this protein in the study of HCC, even more in clinical studies. METHODS: A multiplex immunoassay panel of 48 cytokines and growth factors were utilized to screen 68 sera from 29 HCC patients at pretreatment (T0), 1 month (T1), and 6 months (T6) after treatment by either radiofrequency ablation (RF) or transarterial chemoembolization (TACE). Treatment response was evaluated according to mRECIST criteria. RESULTS: Immunoassay screening showed that the levels of IL-17, CTACK, TNFα, IL-2Rα, IL-8, and SCGFß were different in Complete Responders (CR) and Nonresponders (NR) groups. At T0 and T1, the SCGFß level was significantly the highest in NR (23.8 and 40.7 ng/mL, respectively), followed by early recurrence (25.4 and 25.0 ng/mL), and CR (6.7 and 5.3 ng/mL), independently from HCV, stages, and treatment type. Low basal SCGFß level was associated with longer disease-free survival compared to high SCGFß. CONCLUSION: In this study, for the first time, we demonstrate that the high level of serum SCGFß at pre- and posttreatment is associated with HCC nonresponsiveness.

Outcomes of resection for solitary ≤5 cm intrahepatic cholangiocarcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Prognostic Factors and Patterns of Locoregional Failure After Surgical Resection in Patients With Cholangiocarcinoma Without Adjuvant Radiation Therapy: Optimal Field Design for Adjuvant Radiation Therapy.

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.

Is T4 colon cancer still an absolute contraindication to laparoscopic surgery?

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.

Adhesive and sealant interfaces for general surgery applications.

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.