Publications by authors named "Andrea Ruzzenente"

110 Publications

Surgery for Bismuth-Corlette Type 4 Perihilar Cholangiocarcinoma: Results from a Western Multicenter Collaborative Group.

Ann Surg Oncol 2021 May 6. Epub 2021 May 6.

Department of Surgery, Unit of Hepato-Pancreato-Biliary Surgery, University of Verona Medical School, Verona, Italy.

Background: Although Bismuth-Corlette (BC) type 4 perihilar cholangiocarcinoma (pCCA) is no longer considered a contraindication for curative surgery, few data are available from Western series to indicate the outcomes for these patients. This study aimed to compare the short- and long-term outcomes for patients with BC type 4 versus BC types 2 and 3 pCCA undergoing surgical resection using a multi-institutional international database.

Methods: Uni- and multivariable analyses of patients undergoing surgery at 20 Western centers for BC types 2 and 3 pCCA and BC type 4 pCCA.

Results: Among 1138 pCCA patients included in the study, 826 (73%) had BC type 2 or 3 disease and 312 (27%) had type 4 disease. The two groups demonstrated significant differences in terms of clinicopathologic characteristics (i.e., portal vein embolization, extended hepatectomy, and positive margin). The incidence of severe complications was 46% for the BC types 2 and 3 patients and 51% for the BC type 4 patients (p = 0.1). Moreover, the 90-day mortality was 13% for the BC types 2 and 3 patients and 12% for the BC type 4 patients (p = 0.57). Lymph-node metastasis (N1; hazard-ratio [HR], 1.62), positive margins (R1; HR, 1.36), perineural invasion (HR, 1.53), and poor grade of differentiation (HR, 1.25) were predictors of survival (all p ≤0.004), but BC type was not associated with prognosis. Among the N0 and R0 patients, the 5-year overall survival was 43% for the patients with BC types 2 and 3 pCCA and 41% for those with BC type 4 pCCA (p = 0.60).

Conclusions: In this analysis of a large Western multi-institutional cohort, resection was shown to be an acceptable curative treatment option for selected patients with BC type 4 pCCA although a more technically challenging surgical approach was required.
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http://dx.doi.org/10.1245/s10434-021-09905-zDOI Listing
May 2021

An Overview of Artificial Intelligence Applications in Liver and Pancreatic Imaging.

Cancers (Basel) 2021 Apr 30;13(9). Epub 2021 Apr 30.

Department of Radiology, G.B. Rossi University Hospital, University of Verona, 37129 Verona, Italy.

Artificial intelligence (AI) is one of the most promising fields of research in medical imaging so far. By means of specific algorithms, it can be used to help radiologists in their routine workflow. There are several papers that describe AI approaches to solve different problems in liver and pancreatic imaging. These problems may be summarized in four different categories: segmentation, quantification, characterization and image quality improvement. Segmentation is usually the first step of successive elaborations. If done manually, it is a time-consuming process. Therefore, the semi-automatic and automatic creation of a liver or a pancreatic mask may save time for other evaluations, such as quantification of various parameters, from organs volume to their textural features. The alterations of normal liver and pancreas structure may give a clue to the presence of a diffuse or focal pathology. AI can be trained to recognize these alterations and propose a diagnosis, which may then be confirmed or not by radiologists. Finally, AI may be applied in medical image reconstruction in order to increase image quality, decrease dose administration (referring to computed tomography) and reduce scan times. In this article, we report the state of the art of AI applications in these four main categories.
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http://dx.doi.org/10.3390/cancers13092162DOI Listing
April 2021

Effect of Diameter and Number of Hepatocellular Carcinomas on Survival After Resection, Transarterial Chemoembolization, and Ablation.

Am J Gastroenterol 2021 Apr 21. Epub 2021 Apr 21.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan; Department of Biostatistics, School of Public Health, the University of Tokyo, Tokyo, Japan; Department of Surgery, Division of General and Hepatobiliary Surgery, G.B. Rossi Hospital, University of Verona Medical School, Verona, Italy; School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; Department of Surgery, San Gerardo Hospital, Monza, Italy; Hepatobiliary Surgery Unit, Foundation "Policlinico Universitario A. Gemelli" IRCCS, Catholic University of the Sacred Heart, Rome, Italy; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Diagnostic Radiology, Saitama Medical University International Medical Center, Saitama, Japan; Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan; Departments of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan; Department of Pathology, Keio University School of Medicine, Tokyo, Japan; Department of Gastroenterology, The Juntendo University, Tokyo, Japan; Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan; Department of Clinical Laboratory Medicine, Kurume University Hospital, Fukuoka, Japan; Department of Radiology, Kobe University Graduate School of Medicine, Hyogo, Japan; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; General and Transplant Surgery Unit, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka, Japan; National Center for Global Health and Medicine, Tokyo, Japan.

Introduction: Most studies predicting survival after resection, transarterial chemoembolization (TACE), and ablation analyzed diameter and number of hepatocellular carcinomas (HCCs) as dichotomous variables, resulting in an underestimation of risk variation. We aimed to develop and validate a new prognostic model for patients with HCC using largest diameter and number of HCCs as continuous variables.

Methods: The prognostic model was developed using data from patients undergoing resection, TACE, and ablation in 645 Japanese institutions. The model results were shown after balanced using the inverse probability of treatment-weighted analysis and were externally validated in an international multi-institution cohort.

Results: Of 77,268 patients, 43,904 patients, including 15,313 (34.9%) undergoing liver resection, 13,375 (30.5%) undergoing TACE, and 15,216 (34.7%) undergoing ablation, met the inclusion criteria. Our model (http://www.u-tokyo-hbp-transplant-surgery.jp/about/calculation.html) showed that the 5-year overall survival (OS) in patients with HCC undergoing these procedures decreased with progressive incremental increases in diameter and number of HCCs. For patients undergoing resection, the inverse probability of treatment-weighted-adjusted 5-year OS probabilities were 10%-20% higher compared with patients undergoing TACE for 1-6 HCC lesions <10 cm and were also 10%-20% higher compared with patients undergoing ablation when the HCC diameter was 2-3 cm. For patients undergoing resection and TACE, the model performed well in the external cohort.

Discussion: Our novel prognostic model performed well in predicting OS after resection and TACE for HCC and demonstrated that resection may have a survival benefit over TACE and ablation based on the diameter and number of HCCs.
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http://dx.doi.org/10.14309/ajg.0000000000001256DOI Listing
April 2021

Comparison of Short-term Results after Laparoscopic Complete Mesocolic Excision and Standard Colectomy for Right-Sided Colon Cancer: Analysis of a Western Center Cohort.

Ann Coloproctol 2021 Apr 22. Epub 2021 Apr 22.

Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology, and Pediatrics, University of Verona Hospital Trust, University of Verona, Italy.

Purpose: Laparoscopic complete mesocolic excision (CME) right colectomy is a technically demanding procedure infrequently employed in Western centers. This retrospective cohort study aims to analyze the safety of laparoscopic CME colectomy compared to standard colectomy for right-sided colon cancer in a Western series.

Methods: Prospectively collected data from 60 patients who underwent laparoscopic CME right colectomy were compared to the ones of 55 patients who underwent laparoscopic standard right colectomy.

Results: No differences in clinical characteristics were observed between the CME and standard right colectomy groups. No differences were demonstrated in terms of blood loss (P = 0.060), intraoperative complications (P = 1), conversion rate (P = 0.102), and operative time (P = 0.473). No deaths were observed in either group, while complication rate was 40.0% in the CME and 49.1% in the standard group (P = 0.353). Severe complications occurred in 10.0% vs. 9.1% (P = 0.842), redo surgery in 5.0% vs. 7.3% (P = 0.708), and unplanned readmission in 5.0% vs. 5.5% (P = 1) after CME and standard colectomy, respectively. A significant difference in favor of CME was observed in the total length of specimen (P < 0.001), proximal (P = 0.018), and distal margins (P = 0.037). The number of lymph nodes harvested was significantly higher in the CME group (27 vs. 22, P = 0.037).

Conclusion: In Western series, where patients have less favorable clinical characteristics, laparoscopic CME allows to obtain better quality surgical specimens and comparable short-term outcomes compared to standard right colectomy.
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http://dx.doi.org/10.3393/ac.2020.05.18DOI Listing
April 2021

The Role of Surgery in the Treatment of Bismuth-Corlette Type IV Perihilar Cholangiocarcinoma.

Ann Surg Oncol 2021 Apr 21. Epub 2021 Apr 21.

Department of Surgery, Unit of Hepato-Pancreato-Biliary Surgery, University of Verona Medical School, Verona, Italy.

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http://dx.doi.org/10.1245/s10434-021-09980-2DOI Listing
April 2021

Technical feasibility and short-term outcomes of laparoscopic isolated caudate lobe resection: an IgoMILS (Italian Group of Minimally Invasive Liver Surgery) registry-based study.

Surg Endosc 2021 Mar 31. Epub 2021 Mar 31.

Department of Hepatobiliary Surgery, Unit of Hepato-Pancreato-Biliary Surgery, G. B. Rossi Hospital, University of Verona Medical School, Verona, Italy.

Background: Although isolated caudate lobe (CL) liver resection is not a contraindication for minimally invasive liver surgery (MILS), feasibility and safety of the procedure are still poorly investigated. To address this gap, we evaluate data on the Italian prospective maintained database on laparoscopic liver surgery (IgoMILS) and compare outcomes between MILS and open group.

Methods: Perioperative data of patients with malignancies, as colorectal liver metastases (CRLM), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), non-colorectal liver metastases (NCRLM) and benign liver disease, were retrospectively analyzed. A propensity score matching (PSM) analysis was performed to balance the potential selection bias for MILS and open group.

Results: A total of 224 patients were included in the study, 47 and 177 patients underwent MILS and open isolated CL resection, respectively. The overall complication rate was comparable between the two groups; however, severe complication rate (Dindo-Clavien grade ≥ 3) was lower in the MILS group (0% versus 6.8%, P = ns). In-hospital mortality was 0% in both groups and mean hospital stay was significantly shorter in the MILS group (P = 0.01). After selection of 42 MILS and 43 open CL resections by PSM analysis, intraoperative and postoperative outcomes remained similar except for the hospital stay which was not significantly shorter in MILS group.

Conclusions: This multi-institutional cohort study shows that MILS CL resection is feasible and safe. The surgical procedure can be technically demanding compared to open resection, whereas good perioperative outcomes can be achieved in highly selected patients.
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http://dx.doi.org/10.1007/s00464-021-08434-wDOI Listing
March 2021

Artificial neural networks for multi-omics classifications of hepato-pancreato-biliary cancers: towards the clinical application of genetic data.

Eur J Cancer 2021 May 26;148:348-358. Epub 2021 Mar 26.

Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA. Electronic address:

Purpose: Several multi-omics classifications have been proposed for hepato-pancreato-biliary (HPB) cancers, but these classifications have not proven their role in the clinical practice and been validated in external cohorts.

Patients And Methods: Data from whole-exome sequencing (WES) of The Cancer Genome Atlas (TCGA) patients were used as an input for the artificial neural network (ANN) to predict the anatomical site, iClusters (cell-of-origin patterns) and molecular subtype classifications. The Ohio State University (OSU) and the International Cancer Genome Consortium (ICGC) patients with HPB cancer were included in external validation cohorts. TCGA, OSU and ICGC data were merged, and survival analyses were performed using both the 'classic' survival analysis and a machine learning algorithm (random survival forest).

Results: Although the ANN predicting the anatomical site of the tumour (i.e. cholangiocarcinoma, hepatocellular carcinoma of the liver, pancreatic ductal adenocarcinoma) demonstrated a low accuracy in TCGA test cohort, the ANNs predicting the iClusters (cell-of-origin patterns) and molecular subtype classifications demonstrated a good accuracy of 75% and 82% in TCGA test cohort, respectively. The random survival forest analysis and Cox' multivariable survival models demonstrated that models for HPB cancers that integrated clinical data with molecular classifications (iClusters, molecular subtypes) had an increased prognostic accuracy compared with standard staging systems.

Conclusion: The analyses of genetic status (i.e. WES, gene panels) of patients with HPB cancers might predict the classifications proposed by TCGA project and help to select patients suitable to targeted therapies. The molecular classifications of HPB cancers when integrated with clinical information could improve the ability to predict the prognosis of patients with HPB cancer.
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http://dx.doi.org/10.1016/j.ejca.2021.01.049DOI Listing
May 2021

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

J Gastrointest Surg 2021 Mar 9. Epub 2021 Mar 9.

Department of Surgery, Monza Policlinic, Monza, Italy.

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.
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http://dx.doi.org/10.1007/s11605-021-04952-zDOI Listing
March 2021

Trends and outcomes of simultaneous versus staged resection of synchronous colorectal cancer and colorectal liver metastases.

Surgery 2021 Mar 2. Epub 2021 Mar 2.

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH. Electronic address:

Background: The objective of this study was to assess trends in the use as well as the outcomes of patients undergoing simultaneous versus staged resection for synchronous colorectal liver metastases.

Methods: Patients undergoing resection for colorectal liver metastases between 2008 and 2018 were identified using a multi-institutional database. Trends in use and outcomes of simultaneous resection of colorectal liver metastases were examined over time and compared with that of staged resection after propensity score matching.

Results: Among 1,116 patients undergoing resection for colorectal liver metastases, 690 (61.8%) patients had synchronous disease. Among them, 314 (45.5%) patients underwent simultaneous resection, while 376 (54.5%) had staged resection. The proportion of patients undergoing simultaneous resection for synchronous colorectal liver metastases increased over time (2008: 37.2% vs 2018: 47.4%; p = 0.02). After propensity score matching (n = 201 per group), patients undergoing simultaneous resection for synchronous colorectal liver metastases had a higher incidence of overall (44.8% vs 34.3%; P = .03) and severe complications (Clavien-Dindo ≥III) (16.9% vs 7.0%; P = .002) yet comparable 90-day mortality (3.5% vs 1.0%; P = .09) compared with patients undergoing staged resection. The incidence of severe morbidity decreased over time (2008: 50% vs 2018: 11.1%; p = 0.02). Survival was comparable among patients undergoing simultaneous versus staged resection of colorectal liver metastases (3-year overall survival: 66.1% vs 62.3%; P = .67). Following simultaneous resection, severe morbidity and mortality increased incrementally based on the extent of liver resection and complexity of colectomy.

Conclusion: While simultaneous resection was associated with increased morbidity, the incidence of severe morbidity decreased over time. Long-term survival was comparable after simultaneous resection versus staged resection of colorectal liver metastases.
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http://dx.doi.org/10.1016/j.surg.2021.01.041DOI Listing
March 2021

Conditional Recurrence-Free Survival after Oncologic Extended Resection for Gallbladder Cancer: An International Multicenter Analysis.

Ann Surg Oncol 2021 May 5;28(5):2675-2682. Epub 2021 Mar 5.

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Data to guide surveillance following oncologic extended resection (OER) for gallbladder cancer (GBC) are lacking. Conditional recurrence-free survival (C-RFS) can inform surveillance. We aimed to estimate C-RFS and identify factors affecting conditional RFS after OER for GBC.

Patients And Methods: Patients with ≥ T1b GBC who underwent curative-intent surgery in 2000-2018 at four countries were identified. Risk factors for recurrence and RFS were evaluated at initial resection in all patients and at 12 and 24 months after resection in patients remaining recurrence-free.

Results: Of the 1071 patients who underwent OER, 484 met the inclusion criteria; 290 (60%) were recurrence-free at 12 months, and 199 (41%) were recurrence-free at 24 months. Median follow-up was 24.5 months for all patients and 47.21 months in survivors at analysis. Five-year RFS rates were 47% for the overall population, 71% for patients recurrence-free at 12 months, and 87% for the patients without recurrence at 24 months. In the entire cohort, the risk of recurrence peaked at 8 months. T3-T4 disease was independently associated with recurrence in all groups: entire cohort [hazard ratio (HR) 2.16, 95% confidence interval (CI) 1.49-3.13, P < 0.001], 12-month recurrence-free (HR 3.42, 95% CI 1.88-6.23, P < 0.001), and 24-month recurrence-free (HR 2.71, 95% CI 1.11-6.62, P = 0.029). Of the 125 patients without these risk factors, only 2 had recurrence after 36 months.

Conclusion: C-RFS improves over time, and only T3-T4 disease remains a risk factor for recurrence at 24 months after OER for GBC. For all recurrence-free survivors after 36 months, the probability of recurrence is similar regardless of T category or disease stage.
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http://dx.doi.org/10.1245/s10434-021-09626-3DOI Listing
May 2021

Liver resection for perihilar cholangiocarcinoma: Impact of biliary drainage failure on postoperative outcome. Results of an Italian multicenter study.

Surgery 2021 Feb 20. Epub 2021 Feb 20.

Department of General Surgery, Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy.

Background: Preoperative biliary drainage may be essential to reduce the risk of postoperative liver failure after hepatectomy for perihilar cholangiocarcinoma. However, infectious complications related to preoperative biliary drainage may increase the risk of postoperative mortality. The strategy and optimal drainage method continues to be controversial.

Methods: This is a retrospective multicenter study including patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2000 and 2016 at 14 Italian referral hepatobiliary centers. The primary end point was to evaluate independent predictors for postoperative outcome in patients undergoing liver resection for perihilar cholangiocarcinoma after preoperative biliary drainage.

Results: Of the 639 enrolled patients, 441 (69.0%) underwent preoperative biliary drainage. Postoperative mortality was 8.9% (12.5% after right-side hepatectomy versus 5.7% after left-side hepatectomy; P = .003). Of the patients, 40.5% underwent preoperative biliary drainage at the first admitting hospital, before evaluation at referral centers. Use of percutaneous preoperative biliary drainage was significantly more frequent at referral centers than at community hospitals where endoscopic preoperative biliary drainage was the most frequent type. The overall failure rate after preoperative biliary drainage was 43.3%, significantly higher at community hospitals than that at referral centers (52.7% v 36.9%; P = .002). Failure of the first preoperative biliary drainage was one of the strongest predictors for postoperative complications after right-side and left-side hepatectomies and for mortality after right-side hepatectomy. Type of preoperative biliary drainage (percutaneous versus endoscopic) was not associated with significantly different risk of mortality.

Conclusion: Failure of preoperative biliary drainage was significantly more frequent at community hospitals and it was an independent predictor for postoperative outcome. Centers' experience in preoperative biliary drainage management is crucial to reduce the risk of failure that is closely associated with postoperative morbidity and mortality.
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http://dx.doi.org/10.1016/j.surg.2021.01.021DOI Listing
February 2021

Trace Elements Status and Metallothioneins DNA Methylation Influence Human Hepatocellular Carcinoma Survival Rate.

Front Oncol 2020 28;10:596040. Epub 2021 Jan 28.

Department of Medicine, University of Verona, Verona, Italy.

Background: Mechanisms underlying hepatocellular carcinoma (HCC) development are largely unknown. The role of trace elements and proteins regulating metal ions homeostasis, i.e. metallothioneins (MTs), recently gained an increased interest. Object of the study was to investigate the role of promoter DNA methylation in MTs transcriptional regulation and the possible prognostic significance of serum trace elements in HCC.

Methods: Forty-nine HCC patients were enrolled and clinically characterized. Cu, Se, and Zn contents were measured by Inductively Coupled Plasma Mass Spectrometry in the serum and, for a subset of 27 patients, in HCC and homologous non-neoplastic liver (N) tissues. and gene expression in hepatic tissues was assessed by Real-Time RT-PCR and the specific promoter DNA methylation by Bisulfite-Amplicon Sequencing.

Results: Patients with Cu serum concentration above the 80 percentile had a significantly decreased survival rate (P < 0.001) with a marked increased hazard ratio for mortality (HR 6.88 with 95% CI 2.60-18.23, P < 0.001). Se and Zn levels were significantly lower in HCC as compared to N tissues (P < 0.0001). and gene expression was significantly down-regulated in HCC as compared to N tissues (P < 0.05). MTs promoter was hypermethylated in 9 out of the 19 HCC tissues showing MTs down-regulation and methylation levels of three specific CpGs paralleled to an increased mortality rate among the 23 patients analyzed (P = 0.015).

Conclusions: and act as potential tumor suppressor genes regulated through promoter DNA methylation and, together with serum Cu concentrations, be related to survival rate in HCC.
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http://dx.doi.org/10.3389/fonc.2020.596040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876470PMC
January 2021

Dose-escalation strategy in refractory metastatic colorectal cancer: A change in terms of cost-effectiveness.

J Oncol Pharm Pract 2021 Feb 4:1078155221992546. Epub 2021 Feb 4.

Department of Oncology, Mater Salutis Hospital, Legnago, Italy.

The analysis was conducted to assess the pharmacological costs of regorafenib and trifluridine/tipiracil in the treatment of refractory metastatic colorectal cancer (mCRC). Pivotal phase III randomized controlled trials (RCTs) of regorafenib and trifluridine/tipiracil in the treatment of refractory mCRC were considered. We have also considered the ReDOS trial, in order to verify if the dose-escalation strategy (practice changing for regorafenib) could influences the results. Differences in OS (expressed in months) between the different arms were calculated and compared with the pharmacological costs (at the Pharmacy of our Hospital and expressed in euros (€)) needed to get one month of OS. Trifluridine/tipiracil resulted the less expensive, with 1167.50 €per month OS-gained. The ReDOS trial further reduce costs with 510.41 €per month OS-gained in favour of regorafenib with the escalation-dose strategy. Both regorafenib and trifluridine/tipiracil can be considered economically sustainable treatments for refractory mCRC, apparently with a lower cost of trifluridine/tipiracil. The adoption of a dose-escalation strategy (ReDOS trial) could reverse the situation making regorafenib more cost-effective than trifluridine/tipiracil.
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http://dx.doi.org/10.1177/1078155221992546DOI Listing
February 2021

Resection of Colorectal Liver Metastasis: Prognostic Impact of Tumor Burden vs KRAS Mutational Status.

J Am Coll Surg 2021 Apr 28;232(4):590-598. Epub 2020 Dec 28.

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH. Electronic address:

Background: The prognostic impact of colorectal liver metastasis (CRLM) morphologic characteristics relative to KRAS mutational status after hepatic resection remains ill defined.

Study Design: Patients undergoing hepatectomy for CRLM between 2001 and 2018 were identified using an international multi-institutional database. Tumor burden score (TBS) was defined as distance from origin on a Cartesian plane that incorporated maximum tumor size (x-axis) and number of lesions (y-axis). Impact of TBS on overall survival (OS) relative to KRAS status (wild type [wtKRAS] vs mutated [mutKRAS]) was assessed.

Results: Among 1,361 patients, the median number of metastatic lesions was 2 (interquartile range [IQR] 1-3), and median size of the largest metastatic lesion was 3.0 cm (IQR 2.0-5.0 cm), resulting in a median TBS of 4.1 (IQR 2.8-6.1); KRAS status was wtKRAS (n = 420, 30.9%), mutKRAS (n = 251, 18.4%), and unknown (n = 690, 50.7%). Overall median and 5-year OS were 49.5 months (95%CI 45.2-53.8) and 43.2%, respectively. In examining the entire cohort, TBS was associated with long-term prognosis (5-year OS, low TBS: 49.4% vs high TBS: 36.7%), as was KRAS mutational status (5-year OS, wtKRAS: 48.2% vs mutKRAS: 31.1%; unknown KRAS: 44.0%)(both p < 0.01). Among patients with wtKRAS tumors, TBS was strongly associated with improved OS (5-year OS, low TBS: 59.1% vs high TBS: 38.4%, p = 0.002); however, TBS failed to discriminate long-term prognosis among patients with mutKRAS tumors (5-year OS, low TBS: 37.4% vs high TBS: 26.7%, p = 0.19). In fact, patients with high TBS/wtKRAS CRLM had comparable outcomes to patients with low TBS/mutKRAS tumors (5-year OS, 38.4% vs 37.4%, respectively; p = 0.59). On multivariable analysis, while TBS was associated with OS among patients with wtKRAS CRLM (hazard ratio 1.43, 95%CI 1.02-2.00; p = 0.03), TBS was not an independent predictor of survival among patients with mutKRAS CRLM (HR 1.36, 95%CI 0.92-1.99; p = 0.12).

Conclusions: While TBS was associated with survival among patients with wtKRAS tumors, CRLM morphology was not predictive of long-term outcomes among patients with mutKRAS CRLM.
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http://dx.doi.org/10.1016/j.jamcollsurg.2020.11.023DOI Listing
April 2021

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

Cancers (Basel) 2020 Dec 21;12(12). Epub 2020 Dec 21.

Department of Emergency and Robotic Surgery, ASST Lecco, 23900 Lecco, Italy.

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.
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http://dx.doi.org/10.3390/cancers12123868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767420PMC
December 2020

Effect of peri-operative blood transfusions on long-term prognosis of patients with colorectal cancer.

Blood Transfus 2020 Dec 22. Epub 2020 Dec 22.

Department of Surgical Sciences, Dentistry, Gynaecology and Paediatrics, Unit of General and Hepatobiliary Surgery, University of Verona, Verona, Italy.

Background: Patients with colorectal cancer often present with anaemia and require red blood cell transfusions (RBCT) during their peri-operative course. Evidence suggests a significant association between RBCT and poor long-term outcomes in surgical patients, but the findings in colorectal cancer are contradictory.

Material And Methods: The aim of this retrospective, single-centre, cohort study was to investigate the prognostic role of peri-operative RBCT in a large cohort of patients with stage I-III colorectal cancer submitted to curative surgery between 2005 and 2017. The propensity score matching technique was applied to adjust for potential confounding factors.

Results: Among 1,414 patients operated within the study period, 895 fulfilled the inclusion criteria: 29.6% (n=265) received peri-operative RBCT. The group that received peri-operative RBCT was significantly older (p<0.001), had more comorbidities (p<0.001), more advanced tumours (p<0.001) and more colon tumours (p=0.002) and stayed in hospital longer (p<0.001). Post-operative mortality was 7-fold higher (2.3 vs 0.3%, p=0.01) in this group. Survival outcomes were significantly worse in the group receiving RBCT than in the group not receiving RBCT for both overall (64.5 vs 80.1%, p<0.001) and cancer-specific survival (74.3 vs 85.1%, p<0.001). On multivariable analysis, peri-operative RBCT was significantly associated with poorer overall survival (hazard ratio 1.51, p=0.009). When transfused and non-transfused cases were paired through the propensity score matching technique considering main clinico-pathological features, no differences in overall and cancer-specific survival were found.

Discussion: Our data suggest that, after adjustment for potential confounding factors, no significant association exists between RBCT and prognosis in colorectal cancer.
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http://dx.doi.org/10.2450/2020.0234-20DOI Listing
December 2020

Curative versus palliative treatments for recurrent hepatocellular carcinoma: a multicentric weighted comparison.

HPB (Oxford) 2020 Oct 31. Epub 2020 Oct 31.

Department of Surgery, University of Parma, Parma, Italy.

Background: Management of recurrence after surgery for hepatocellular carcinoma (rHCC) is still a debate. The aim was to compare the Survival after Recurrence (SAR) of curative (surgery or thermoablation) versus palliative (TACE or Sorafenib) treatments for patients with rHCC.

Methods: This is a multicentric Italian study, which collected data between 2007 and 2018 from 16 centers. Selected patients were then divided according to treatment allocation in Curative (CUR) or Palliative (PAL) Group. Inverse Probability Weighting (IPW) was used to weight the groups.

Results: 1,560 patients were evaluated, of which 421 experienced recurrence and were then eligible: 156 in CUR group and 256 in PAL group. Tumor burden and liver function were weighted by IPW, and two pseudo-population were obtained (CUR = 397.5 and PAL = 415.38). SAR rates at 1, 3 and 5 years were respectively 98.3%, 76.7%, 63.8% for CUR and 91.7%, 64.2% and 48.9% for PAL (p = 0.007). Median DFS was 43 months (95%CI = 32-74) for CUR group, while it was 23 months (95%CI = 18-27) for PAL (p = 0.017). Being treated by palliative approach (HR = 1.75; 95%CI = 1.14-2.67; p = 0.01) and having a median size of the recurrent nodule>5 cm (HR = 1.875; 95%CI = 1.22-2.86; p = 0.004) were the only predictors of mortality after recurrence, while time to recurrence was the only protective factor (HR = 0.616; 95%CI = 0.54-0.69; p<0.001).

Conclusion: Curative approaches may guarantee long-term survival in case of recurrence.
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http://dx.doi.org/10.1016/j.hpb.2020.10.007DOI Listing
October 2020

Simultaneous approach for patients with synchronous colon and rectal liver metastases: Impact of site of primary on postoperative and oncological outcomes.

Eur J Surg Oncol 2021 Apr 25;47(4):842-849. Epub 2020 Sep 25.

Department of Surgery, General and Hepatobiliary Surgery, University of Verona, University Hospital G.B. Rossi, 37134, Verona, Italy.

Background And Aims: We aimed to investigate the impact of the site of the primary on postoperative and oncological outcomes in patients undergone simultaneous approach for colon (CC) and rectal cancer (RC) with synchronous liver metastases (SCRLM).

Patients And Methods: Of the 220 patients with SCRLM operated on between Mar 2006 and Dec 2017, 169 patients (76.8%) were treated by a simultaneous approach and were included in the study. Two groups were considered according to the location of primary tumor RC-Group (n = 47) and CC-group (n = 122).

Results: Multiple liver metastases were observed in 70.2% in RC-Group and 77.0% in CC-Group (p = 0.233), whilst median Tumor Burden Score (TBS) was 4.7 in RC-Group and 5.4 CC-Group (p = 0.276). Severe morbidity (p = 0.315) and mortality at 90 days (p = 0.520) were comparable between RC-Group and CC-Group. The 5-year overall survival (OS) rate was similar comparing RC-Group and CC-Group (48.2% vs. 45.3%; p = 0.709), but it was significantly different when considering left-CC, right-CC and RC separately (54.5% vs. 35.2% vs. 48.2%; p = 0.041). Primary tumor location (right-CC, p = 0.001; RC, p = 0.002), microscopic residual (R1) disease at the primary (p < 0.001), TBS ≥6 (p = 0.012), bilobar metastases (p = 0.004), and chemotherapy strategy (preoperative ChT, p = 0.253; postoperative ChT, p = 0.012; and perioperative ChT, p < 0.001) resulted to be independent prognostic factors at multivariable analysis.

Conclusion: In patients with SCRLM, simultaneous resection of the primary tumor and liver metastases seems feasible and safe and allows satisfactory oncological outcomes both in CC and RC. Right-CC shows a worse prognosis when compared to left-CC and RC.
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http://dx.doi.org/10.1016/j.ejso.2020.09.015DOI Listing
April 2021

Pancreatic resections in patients who refuse blood transfusions. The application of a perioperative protocol for a true bloodless surgery.

Pancreatology 2020 Oct 5;20(7):1550-1557. Epub 2020 Sep 5.

Department of Surgery, Division of General and Hepato-Pancreato-Biliary Surgery, University of Verona, School of Medicine, Verona, Italy. Electronic address:

Background: The refusal of blood transfusions compels surgeons to face ethical and clinical issues. A single-institution experience with a dedicated perioperative blood management protocol was reviewed to assess feasibility and short-term outcomes of true bloodless pancreatic surgery.

Methods: The institutional database was reviewed to identify patients who refused transfusion and were scheduled for elective pancreatic surgery from 2010 through 2018. A protocol to optimize the hemoglobin values by administration of drugs stimulating erythropoiesis was systematically used.

Results: Perioperative outcomes of 32 Jehovah's Witnesses patients were included. Median age was 67 years (range, 31-77). Nineteen (59.4%) patients were treated with preoperative erythropoietin. Twenty-four (75%) patients underwent pylorus-preserving pancreaticoduodenectomy, 4 (12.5%) distal pancreatectomy (DP) with splenectomy, 3 (9.4%) spleen-preserving DP, and 1 (3.1%) total pancreatectomy. Median estimated blood loss and surgical duration were 400 mL (range, 100-1000) and 470 min (range, 290-595), respectively. Median preoperative hemoglobin was 13.9 g/dL (range, 11.7-15.8) while median postoperative nadir hemoglobin was 10.5 g/dL (range, 7.1-14.1). The most common histological diagnosis (n = 15, 46.9%) was pancreatic ductal adenocarcinoma. Clavien-Dindo grade I-II complications occurred in fourteen (43.8%) patients while one (3.1%) patient had a Clavien-Dindo grade IIIa complication wich was an abdominal collection that required percutaneous drainage. Six (18.8%) patients presented biochemical leak or postoperative pancreatic fistula grade B. Median hospital stay was 16 days (range, 8-54) with no patient requiring transfusion or re-operation and no 90-day mortality.

Conclusions: A multidisciplinary approach and specific perioperative management allowed performing pancreatic resections in patients who refused transfusion with good short-term outcomes.
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http://dx.doi.org/10.1016/j.pan.2020.08.020DOI Listing
October 2020

The Impact of Hospital Volume on Failure to Rescue after Liver Resection for Hepatocellular Carcinoma: Analysis from the HE.RC.O.LE.S. Italian Registry.

Ann Surg 2020 11;272(5):840-846

Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli, IRCCS" Catholic University of the Sacred Heart, Rome, Italy.

Objective: The aim of this study was to evaluate correlation between centers' volume and incidence of failure to rescue (FTR) following liver resection for hepatocellular carcinoma (HCC).

Summary Background Data: FTR, defined as the probability of postoperative death among patients with major complication, has been proposed to assess quality of care during hospitalization. Perioperative management is challenging in cirrhotic patients and the ability to recognize and treat a complication may be fundamental to rescue patients from the risk of death.

Methods: Patients undergoing liver resection for HCC between 2008 and 2018 in 18 Centers enrolled in the He.Rc.O.Le.S. Italian register. Early results included major complications (Clavien ≥3), 90-day mortality, and FTR and were analyzed according to center's volume.

Results: Among 1935 included patients, major complication rate was 9.4% (8.6%, 12.3%, and 7.0% for low-, intermediate- and high-volume centers, respectively, P = 0.001). Ninety-day mortality rate was 2.6% (3.7%, 4.2% and 0.9% for low-, intermediate- and high-volume centers, respectively, P < 0.001). FTR was significantly higher at low- and intermediate-volume centers (28.6% and 26.5%, respectively) than at high-volume centers (6.1%, P = 0.002). Independent predictors for major complications were American Society of Anesthesiologists (ASA) >2, portal hypertension, intraoperative blood transfusions, and center's volume. Independent predictors for 90-day mortality were ASA >2, Child-Pugh score B, BCLC stage B-C, and center's volume. Center's volume and BCLC stage were strongly associated with FTR.

Conclusions: Risk of major complications and mortality was related with comorbidities, cirrhosis severity, and complexity of surgery. These factors were not correlated with FTR. Center's volume was the only independent predictor related with severe complications, mortality, and FTR.
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http://dx.doi.org/10.1097/SLA.0000000000004327DOI Listing
November 2020

A Novel Machine-Learning Approach to Predict Recurrence After Resection of Colorectal Liver Metastases.

Ann Surg Oncol 2020 Dec 10;27(13):5139-5147. Epub 2020 Aug 10.

Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.

Background: Surgical resection of hepatic metastases remains the only potentially curative treatment option for patients with colorectal liver metastases (CRLM). Widely adopted prognostic tools may oversimplify the impact of model parameters relative to long-term outcomes.

Methods: Patients with CRLM who underwent a hepatectomy between 2001 and 2018 were identified in an international, multi-institutional database. Bootstrap resampling methodology used in tandem with multivariable mixed-effects logistic regression analysis was applied to construct a prediction model that was validated and compared with scores proposed by Fong and Vauthey.

Results: Among 1406 patients who underwent hepatic resection of CRLM, 842 (59.9%) had recurrence. The full model (based on age, sex, primary tumor location, T stage, receipt of chemotherapy before hepatectomy, lymph node metastases, number of metastatic lesions in the liver, size of the largest hepatic metastases, carcinoembryonic antigen [CEA] level and KRAS status) had good discriminative ability to predict 1-year (area under the receiver operating curve [AUC], 0.693; 95% confidence interval [CI], 0.684-0.704), 3-year (AUC, 0.669; 95% CI, 0.661-0.677), and 5-year (AUC, 0.669; 95% CI, 0.661-0.679) risk of recurrence. Studies analyzing validation cohorts demonstrated similar model performance, with excellent model accuracy. In contrast, the AUCs for the Fong and Vauthey scores to predict 1-year recurrence were only 0.527 (95% CI, 0.514-0.538) and 0.525 (95% CI, 0.514-0.533), respectively. Similar trends were noted for 3- and 5-year recurrence.

Conclusion: The proposed clinical score, derived via machine learning, which included clinical characteristics and morphologic data, as well as information on KRAS status, accurately predicted recurrence after CRLM resection with good discrimination and prognostic ability.
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http://dx.doi.org/10.1245/s10434-020-08991-9DOI Listing
December 2020

Machine Learning Model Comparison in the Screening of Cholangiocarcinoma Using Plasma Bile Acids Profiles.

Diagnostics (Basel) 2020 Aug 2;10(8). Epub 2020 Aug 2.

Clinical Biochemistry Section, Department of Neurological, Biomedical and Movement Sciences, University of Verona, 37134 Verona, Italy.

Bile acids (BAs) assessments are garnering increasing interest for their potential involvement in development and progression of cholangiocarcinoma (CCA). Since machine learning (ML) algorithms are increasingly used for exploring metabolomic profiles, we evaluated performance of some ML models for dissecting patients with CCA or benign biliary diseases according to their plasma BAs profiles. We used ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) for assessing plasma BAs profile in 112 patients (70 CCA, 42 benign biliary diseases). Twelve normalisation procedures were applied, and performance of six ML algorithms were evaluated (logistic regression, k-nearest neighbors, naïve bayes, RBF SVM, random forest, extreme gradient boosting). Naïve bayes, using direct bilirubin concentration for normalisation of BAs, was the ML model displaying better performance in the holdout set, with an Area Under Curve (AUC) of 0.95, 0.79 sensitivity, 1.00 specificity. This model, also characterised by 1.00 positive predictive value and 0.73 negative predictive value, displayed a globally excellent accuracy (86.4%). The accuracy of the other five models was lower, and AUCs ranged 0.75-0.95. Preliminary results of this study show that application of ML to BAs profile analysis can provide a valuable contribution for characterising bile duct diseases and identifying patients with higher likelihood of having malignant pathologies.
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http://dx.doi.org/10.3390/diagnostics10080551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460348PMC
August 2020

Outcomes of vascular resection associated with curative intent hepatectomy for intrahepatic cholangiocarcinoma.

Eur J Surg Oncol 2020 09 19;46(9):1727-1733. Epub 2020 Apr 19.

Department of Surgery, Division of General and Hepatobiliary Surgery, G.B. Rossi University Hospital, University of Verona, Verona, Italy.

Background And Aims: We aimed to investigate the impact of vascular resection (VR) on postoperative outcomes and survival of patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC).

Methods: A retrospective analysis of a multi-institutional series of 270 patients with resected ICC was carried out. Patients were divided into three groups: portal vein VR (PVR), inferior vena cava VR (CVR) and no VR (NVR). Univariate and multivariate analysis were applied to define the impact of VR on postoperative outcomes and survival.

Results: Thirty-one patients (11.5%) underwent VR: 15 (5.6%) to PVR and 16 (5.9%) to CVR. R0 resection rates were 73.6% in NVR, 73.3% of PVR and 68.8% in CVR. The postoperative mortality rate was increased in VR groups: 2.5% in NVR, 6.7% in PVR and 12.5% in CVR. The 5-years overall survival (OS) rates progressively decreased from 38.4% in NVR, to 30.1% in CVR and to 22.2% in PVR, p = 0.030. However, multivariable analysis did not confirm an association between VR and prognosis. The following prognostic factors were identified: size ≥50 mm, patterns of distribution of hepatic nodules (single, satellites or multifocal), lymph-node metastases (N1) and R1 resections. In the VR group the 5-years OS rate in patients without lymph-node metastases undergoing R0 resection (VRR0N0) was 44.4%, while in N1 patients undergoing R1 resection was 20% (p < 0.001).

Conclusion: Vascular resection (PVR and CVR) is associated with higher operative risk, but seems to be justified by the good survival results, especially in patients without other negative prognostic factors (R0N0 resections).
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http://dx.doi.org/10.1016/j.ejso.2020.04.007DOI Listing
September 2020

Minimally Invasive Versus Open Liver Resection for Hepatocellular Carcinoma in the Setting of Portal Vein Hypertension: Results of an International Multi-institutional Analysis.

Ann Surg Oncol 2020 Sep 9;27(9):3360-3371. Epub 2020 Apr 9.

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Background: Patients with hepatocellular carcinoma (HCC) and portal vein hypertension assessed with platelet count (PVH-PLT; platelet count < 100,000/mL) are often denied surgery even when the disease is technically resectable. Short- and long-term outcomes of patients undergoing minimally invasive surgery (MIS) versus open resection for HCC and PVH-PLT were compared.

Methods: Propensity score matching (PSM) was used to balance the clinicopathological differences between MIS and non-MIS patents. Univariate comparison and standard survival analyses were utilized.

Results: Among 1974 patients who underwent surgery for HCC, 13% had a PVH-PLT and 33% underwent MIS. After 1:1 PSM, 407 MIS and 407 non-MIS patients were analyzed. Incidence of complications and length-of-stay (LoS) were higher among non-MIS versus MIS patients (both p ≤ 0.002). After PSM, among 178 PVH-PLT patients (89 MIS and 89 non-MIS), patients who underwent a non-MIS approach had longer LoS (> 7 days; non-MIS: 55% vs. MIS: 29%), as well as higher morbidity (non-MIS: 42% vs. MIS: 29%) [p <0.001]. In contrast, long-term oncological outcomes were comparable, including 3-year overall survival (non-MIS: 66.2% vs. MIS: 72.9%) and disease-free survival (non-MIS: 47.3% vs. MIS: 50.2%) [both p ≥ 0.08].

Conclusion: An MIS approach was associated with improved short-term outcomes, but similar long-term outcomes, compared with open liver resection for patients with HCC and PVH-PLT. An MIS approach for liver resection should be considered for patients with HCC, even those individuals with PVH-PLT.
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http://dx.doi.org/10.1245/s10434-020-08444-3DOI Listing
September 2020

Hepatopancreatoduodenectomy for Multifocal Cholangiocarcinoma in the Setting of Biliary Papillomatosis.

Ann Surg Oncol 2020 Sep 4;27(9):3356-3357. Epub 2020 Apr 4.

Division of General and HPB Surgery, Department of Surgery, School of Medicine, University of Verona, Verona, Italy.

Background: Hepatopancreatoduodenectomy is performed to achieve curative resection of malignant biliary tumors.1 However, the morbidity and mortality associated with this challenging surgical procedure remain high, and optimal indications remain unclear.24 Biliary papillomatosis (BP) is a precursor lesion of cholangiocarcinoma. This video shows hepatopancreatoduodenecomy for multifocal cholangiocarcinoma in the setting of BP.

Patient: A 75-year-old man with a medical history of cholecystectomy presented with obstructive jaundice. Magnetic resonance colangiopancreatography and computed tomography scan showed diffuse biliary dilation with mild enhancing nodularities in the whole extrahepatic bile duct. Cholangioscopy with biopsies proved cholangiocarcinoma arising from BP at the prepapillary common bile duct (CBD) and the biliary confluence. The second-order right ducts were free of disease. The patient underwent nasobiliary drainage and was considered for hepatopancreatoduodenecomy.

Technique: A right subcostal incision was performed. Intraoperative ultrasound showed BP of the intrapancreatic CBD spreading only to the left bile duct. En bloc resection of the left liver, caudate lobe, and CBD was performed together with pylorus-preserving pancreatoduodenectomy. The reconstruction phase was performed on a single-loop by duct-to-mucosa pancreatojejunostomy, two-duct biliojejunostomy with mucosa-to-mucosa alignment, and duodenojejunostomy. Transanastomotic external stents were used for biliary and pancreatic drainage. Histopathologic examination confirmed foci of cholangiocarcinoma arising from BP. Resection margins were negative. Lymph node metastasis, microvascular invasion, perineural invasion, and mucin secretion were absent. The patient was discharged on postoperative day 14 without complications. At the 2-year follow-up assessment, he was alive and free of disease.

Conclusion: Cholangiocarcinoma arising from BP is a proper indication for hepatopancreatoduodenectomy. The long-term oncologic benefits might outweigh the possible perioperative complications.56.
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http://dx.doi.org/10.1245/s10434-020-08357-1DOI Listing
September 2020

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

Updates Surg 2020 Jun 13;72(2):399-411. Epub 2020 Mar 13.

Department of Surgery, Ponte San Pietro Hospital, Bergamo, Italy.

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.
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http://dx.doi.org/10.1007/s13304-020-00733-6DOI Listing
June 2020

Multigene mutational profiling of biliary tract cancer is related to the pattern of recurrence in surgically resected patients.

Updates Surg 2020 Mar 4;72(1):119-128. Epub 2020 Feb 4.

ARC-Net Research Centre, University of Verona, University Hospital G.B. Rossi, 37134, Verona, Italy.

The aim of the present study was to investigate the relationship between the mutational gene profile and recurrence in biliary tract cancers (BTC). A total of 103 specimens of patients with BTC, who underwent curative surgery in a single tertiary HPB surgery referral center from 1990 to 2012, were assessed for mutational status in 52 cancer-related genes. Considering the different types of BTC, the 5-year recurrence-free survival (RFS) rate was 16.7% (median RFS 7 months) in gallbladder cancer, 42.9% (median RFS 26.4 months) in intrahepatic cholangiocarcinoma, and 19.7% (median RFS 16.5 months) in perihilar cholangiocarcinoma, p = 0.166. At the multivariate analysis including clinical, pathological, and molecular features, the factors independently related to RFS were radicality of surgery (OR 2.050, CI 1.104-3.807, p = 0.023), LN status (OR 1.835, CI 1.006-3.348, p = 0.048), mutational status of ARID1A (OR 2.566, CI 1.174-5.608, p = 0.018), and TP53 (OR 2.805, CI 4.432-5.496, p = 0.003). ARID1A mutation was associated with a local and systemic recurrence in the 43% and 29% of cases, respectively; and TP53 mutation was associated with a local and systemic recurrence in the 29% and 41% of cases. Moreover, TP53 was most commonly mutated in tumor of patients with early recurrence, p = 0.044. ARID1A and TP53 mutations seem to be related to poor outcome after surgery and may be considered molecular predictors of the biological aggressiveness in BTC.
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http://dx.doi.org/10.1007/s13304-020-00718-5DOI Listing
March 2020

Prognostic value of red cell distribution width (RDW) in colorectal cancer. Results from a single-center cohort on 591 patients.

Sci Rep 2020 01 23;10(1):1072. Epub 2020 Jan 23.

Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.

Increasing evidence advocates the prognostic role of RDW in various tumours. We analysed 591 patients to assess whether RDW is a prognostic factor for overall (OS) and cancer-related survival (CRS) for patients with colorectal cancer (CRC). The data were retrieved from a retrospective database. The optimal cut-off value for RDW was set at 14.1%; accordingly, two groups were considered: those with a value equal or lower than 14.1% (L-RDW), and those with a value higher than 14.1% (H-RDW). The mean value of RDW rose from pT1 to pT4 tumours. H-RDW correlated with age above the mean, colonic location of the lesion, pT and TNM stage. Finally, H-RDW was significantly associated with the intent of surgery: almost 50% of patients who underwent a non-curative resection presented H-RDW, compared to 19.3% in R0 resections. OS was significantly lower in patients with H-RDW. CRS was similar in the two groups. Stratifying patients according to TNM stage worse OS was associated with H-RDW only in early stages, whereas there was no difference for stages II-IV. Multivariate analysis confirmed that H-RDW was not an independent prognostic factor. Although H-RDW correlated with some negative clinical-pathological factors, it did not seem to independently influence OS and CRS.
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http://dx.doi.org/10.1038/s41598-020-57721-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978334PMC
January 2020

Patterns of gene mutations in bile duct cancers: is it time to overcome the anatomical classification?

HPB (Oxford) 2019 12 20;21(12):1648-1655. Epub 2019 May 20.

General and Hepatobiliary Surgery, Department of Surgery, University of Verona, School of Medicine, Verona, Italy.

Background: Two recent studies based on multi-omics data analysis identified distinct subtypes of bile-duct cancers (BDC) with important implications in terms of disease classification and patients' treatment.

Methods: Patients with mutations in KRAS, NRAS, TP53, and ARID1A genes were classified in KRAS/TP53 group while patients with mutations in IDH1-2, BAP1, and PBRM1 were classified in IDH1-2/BAP1/PBRM1 group. The aim of this study was to define long-term outcomes among patients stratified by patterns of genes mutated.

Results: Among 105 patients who underwent surgical resection for BDCs, 71 (68%) patients were classified in two groups based on patterns of genes mutated. While in IDH1-2/BAP1/PBRM1 group there were 58%, 22%, and 10% of patients with intrahepatic-cholangiocarcinoma (ICC), perihilar-cholangiocarcinoma (PHCC), and gallbladder cancer (GBC), in KRAS/TP53 group there were 42%, 78%, and 90% of patients with ICC, PHCC, and GBC (p = 0.003), respectively. Patients in IDH1-2/BAP1/PBRM1 group had a 5-year OS of 40% compared with 13% for KRAS/TP53 group (p = 0.032). In a multivariable model adjusted for margins, lymph-node status, microvascular invasion, and tumor grade, patients in KRAS/TP53 group had a 2.1-fold increased risk of death compared with patients in IDH1-2/BAP1/PBRM1 group (p = 0.028).

Conclusions: Genetic data were able to overcome the clinical based staging system in predicting patients' prognosis.
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http://dx.doi.org/10.1016/j.hpb.2019.04.002DOI Listing
December 2019