Publications by authors named "Alfredo Guglielmi"

176 Publications

Outcome after resection for perihilar cholangiocarcinoma in patients with primary sclerosing cholangitis: an international multicentre study.

HPB (Oxford) 2021 Apr 28. Epub 2021 Apr 28.

Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Background: Resection for perihilar cholangiocarcinoma (pCCA) in primary sclerosing cholangitis (PSC) has been reported to lead to worse outcomes than resection for non-PSC pCCA. The aim of this study was to compare prognostic factors and outcomes after resection in patients with PSC-associated pCCA and non-PSC pCCA.

Methods: The international retrospective cohort comprised patients resected for pCCA from 21 centres (2000-2020). Patients operated with hepatobiliary resection, with pCCA verified by histology and with data on PSC status, were included. The primary outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications.

Results: Of 1128 pCCA patients, 34 (3.0%) had underlying PSC. Median overall survival after resection was 33 months for PSC patients and 29 months for non-PSC patients (p = .630). Complications (Clavien-Dindo grade ≥ 3) were more frequent in PSC pCCA (71% versus 44%, p = .003). The rate of posthepatectomy liver failure (21% versus 17%, p = .530) and 90-day mortality (12% versus 13%, p = 1.000) was similar for PSC and non-PSC patients.

Conclusion: Median overall survival after resection for pCCA was similar in patients with underlying PSC and non-PSC patients. Complications were more frequent after resection for PSC-associated pCCA, with no difference in postoperative mortality.
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http://dx.doi.org/10.1016/j.hpb.2021.04.011DOI Listing
April 2021

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

Serum α-Fetoprotein Levels at Time of Recurrence Predict Post-Recurrence Outcomes Following Resection of Hepatocellular Carcinoma.

Ann Surg Oncol 2021 Apr 27. Epub 2021 Apr 27.

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

Introduction: Although preoperative α-fetoprotein (AFP) has been recognized as an important tumor marker among patients with hepatocellular carcinoma (HCC), the predictive value of AFP levels at the time of recurrence (rAFP) on post-recurrence outcomes has not been well examined.

Methods: Patients undergoing curative-intent resection of HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of rAFP on post-recurrence survival, as well as the impact of rAFP relative to the timing and treatment of HCC recurrence were examined.

Results: Among 852 patients who underwent resection of HCC, 307 (36.0%) individuals developed a recurrence. The median rAFP level was 8 ng/mL (interquartile range 3-100). Among the 307 patients who developed recurrence, 3-year post-recurrence survival was 48.5%. Patients with rAFP > 10 ng/mL had worse 3-year post-recurrence survival compared with individuals with rAFP < 10 ng/mL (28.7% vs. 65.5%, p < 0.001). rAFP correlated with survival among patients who had early (3-year survival; rAFP > 10 vs. < 10 ng/mL: 30.1% vs. 60.2%, p < 0.001) or late (18.0% vs. 78.7%, p = 0.03) recurrence. Furthermore, rAFP levels predicted 3-year post-recurrence survival among patients independent of the therapeutic modality used to treat the recurrent HCC (rAFP > 10 vs. < 10 ng/mL; ablation: 41.1% vs. 76.0%; intra-arterial therapy: 12.9% vs. 46.1%; resection: 37.5% vs. 100%; salvage transplantation: 60% vs. 100%; all p < 0.05). After adjusting for competing risk factors, patients with rAFP > 10 ng/mL had a twofold higher hazard of death in the post-recurrence setting (hazard ratio 1.96, 95% confidence interval 1.26-3.04).

Conclusion: AFP levels at the time of recurrence following resection of HCC predicted post-recurrence survival independent of the secondary treatment modality used. Evaluating AFP levels at the time of recurrence can help inform post-recurrence risk stratification of patients with recurrent HCC.
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http://dx.doi.org/10.1245/s10434-021-09977-xDOI 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

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

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

Synergistic Impact of Alpha-Fetoprotein and Tumor Burden on Long-Term Outcomes Following Curative-Intent Resection of Hepatocellular Carcinoma.

Cancers (Basel) 2021 Feb 11;13(4). Epub 2021 Feb 11.

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.

Introduction: The prognostic role of tumor burden score (TBS) relative to pre-operative α -fetoprotein (AFP) levels among patients undergoing curative-intent resection of HCC has not been examined.

Methods: Patients who underwent curative-intent resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS on overall survival (OS) and cumulative recurrence relative to serum AFP levels was assessed.

Results: Among 898 patients, 233 (25.9%) patients had low TBS, 572 (63.7%) had medium TBS and 93 (10.4%) had high TBS. Both TBS (5-year OS; low TBS: 76.9%, medium TBS: 60.9%, high TBS: 39.1%) and AFP (>400 ng/mL vs. <400 ng/mL: 48.5% vs. 66.1%) were strong predictors of outcomes (both < 0.001). Lower TBS was associated with better OS among patients with both low (5-year OS, low-medium TBS: 68.0% vs. high TBS: 47.7%, < 0.001) and high AFP levels (5-year OS, low-medium TBS: 53.7% vs. high TBS: not reached, < 0.001). Patients with low-medium TBS/high AFP had worse OS compared with individuals with low-medium TBS/low AFP (5-year OS, 53.7% vs. 68.0%, = 0.003). Similarly, patients with high TBS/high AFP had worse outcomes compared with patients with high TBS/low AFP (5-year OS, not reached vs. 47.7%, = 0.015). Patients with high TBS/low AFP and low TBS/high AFP had comparable outcomes (5-year OS, 47.7% vs. 53.7%, = 0.24). The positive predictive value of certain TBS groups relative to the risk of early recurrence and 5-year mortality after HCC resection increased with higher AFP levels.

Conclusion: Both TBS and serum AFP were important predictors of prognosis among patients with resectable HCC. Serum AFP and TBS had a synergistic impact on prognosis following HCC resection with higher serum AFP predicting worse outcomes among patients with HCC of a certain TBS class.
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http://dx.doi.org/10.3390/cancers13040747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916953PMC
February 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

Proposal of a New Comprehensive Notation for Hepatectomy: The "New World" Terminology.

Ann Surg 2021 Feb 12. Epub 2021 Feb 12.

Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA Department of General, Visceral and Transplant Surgery, University Hospital Mainz, Mainz, Germany Hôpital Paul Brousse, APHP - Université Paris - Saclay, Villejuif, France Department of HPB- and Liver Transplantation Surgery, University College London, Royal Free Hospitals, London, UK Department of Surgery & Transplantation, University Hospital Zurich, Zurich, Switzerland Hepatobiliary Surgery Division, Department of Surgery, IRCCS San Raffaele Hospital, School of Medicine, Milan, Italy Department of Hepatobiliary and Digestive Surgery, Rennes University Hospital, Rennes, France Section of Transplantation Surgery, Siteman Cancer Center, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, USA Department of Surgery, University of California at San Diego, San Diego, USA Department of Surgery, Division of HPB Surgery, Liver Transplant Unit, Italian Hospital of Buenos Aires, Buenos Aires, Argentina Hepato-pancreato-biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA Department of Surgery, General and Hepatobiliary Surgery, University of Verona, Verona, Italy Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, USA HepatoBiliary Surgery & Liver Transplantation, Asan Medical Center, Ulsan University, Seoul, Republic of Korea HPB and Transplant Unit, St. James's University Hospital, Leeds, UK Department of General and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany Center for Abdominal Transplantation Weston, Cleveland Clinic Florida, Weston, USA Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands Department of HPB Surgery and Liver Transplant, Beaujon Hospital, Clichy, France.

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http://dx.doi.org/10.1097/SLA.0000000000004808DOI Listing
February 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

Endoscopic Ultrasound Through-the-Needle Biopsy for the Diagnosis of an Abdominal Bronchogenic Cyst.

Clin Endosc 2021 Feb 17. Epub 2021 Feb 17.

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

A 57-year-old woman with epigastric pain was diagnosed with a 6-cm abdominal cystic lesion of unclear origin on cross-sectional imaging. Endoscopic ultrasound (EUS) demonstrated a unilocular cyst located between the pancreas, gastric wall, and left adrenal gland, with a regular wall filled with dense fluid with multiple hyperechoic floating spots. A 19-G needle was used to puncture the cyst, but no fluid could be aspirated. Therefore, EUS-guided through-the-needle biopsy (EUS-TTNB) was performed. Histological analysis of the retrieved fragments revealed a fibrous wall lined by "respiratory-type" epithelium with ciliated columnar cells, consistent with the diagnosis of a bronchogenic cyst. Laparoscopic excision was performed, and the diagnosis was confirmed based on the findings of the surgical specimen. Abdominal bronchogenic cysts are extremely uncommon, and a definitive diagnosis is commonly obtained after the examination of surgical specimens due to the lack of pathognomonic findings on cross-sectional imaging and poor cellularity on EUS-guided fine-needle aspiration cytology. EUS-TTNB is useful for establishing a preoperative histological diagnosis, thus supporting the decision-making process.
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http://dx.doi.org/10.5946/ce.2020.195DOI 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

Clinical Significance of Preoperative Inflammatory Markers in Prediction of Prognosis in Node-Negative Colon Cancer: Correlation between Neutrophil-to-Lymphocyte Ratio and Poorly Differentiated Clusters.

Biomedicines 2021 Jan 19;9(1). Epub 2021 Jan 19.

Unit of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, 37134 Verona, Italy.

Although stage I and II colon cancers (CC) generally show a very good prognosis, a small proportion of these patients dies from recurrent disease. The identification of high-risk patients, who may benefit from adjuvant chemotherapy, becomes therefore essential. We retrospectively evaluated 107 cases of stage I ( = 28, 26.2%) and II ( = 79, 73.8%) CC for correlations among preoperative inflammatory markers, histopathological factors and long-term prognosis. A neutrophil-to-lymphocyte ratio greater than 3 (H-NLR) and a platelet-to-lymphocyte ratio greater than 150 (H-PLR) were significantly associated with the presence of poorly differentiated clusters (PDC) ( = 0.007 and = 0.039, respectively). In addition, H-NLR and PDC proved to be significant and independent survival prognosticators for overall survival (OS; = 0.007 and < 0.001, respectively), while PDC was the only significant prognostic factor for cancer-specific survival (CSS; < 0.001,). Finally, the combination of H-NLR and PDC allowed an optimal stratification of OS and CSS in our cohort, suggesting a potential role in clinical practice for the identification of high-risk patients with stage I and II CC.
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http://dx.doi.org/10.3390/biomedicines9010094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835814PMC
January 2021

Complications and mortality in a cohort of patients undergoing emergency and elective surgery with perioperative SARS-CoV-2 infection: an Italian multicenter study. Teachings of Phase 1 to be brought in Phase 2 pandemic.

Updates Surg 2021 Apr 3;73(2):745-752. Epub 2021 Jan 3.

Ospedali Riuniti, Ancona, Italy.

Since the beginning of the pandemic due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its related disease, coronavirus disease 2019 (COVID-19), several articles reported negative outcomes in surgery of infected patients. Aim of this study is to report results of patients with COVID-19-positive swab, in the perioperative period after surgery. Data of COVID-19-positive patients undergoing emergent or oncological surgery, were collected in a retrospective, multicenter study, which involved 20 Italian institutions. Collected parameters were age, sex, body mass index, COVID-19-related symptoms, patients' comorbidities, surgical procedure, personal protection equipment (PPE) used in operating rooms, rate of postoperative infection among healthcare staff and complications, within 30-postoperative days. 68 patients, who underwent surgery, resulted COVID-19-positive in the perioperative period. Symptomatic patients were 63 (92.5%). Fever was the main symptom in 36 (52.9%) patients, followed by dyspnoea (26.5%) and cough (13.2%). We recorded 22 (32%) intensive care unit admissions, 23 (33.8%) postoperative pulmonary complications and 15 (22%) acute respiratory distress syndromes. As regards the ten postoperative deaths (14.7%), 6 cases were related to surgical complications. One surgeon, one scrub nurse and two circulating nurses were infected after surgery due to the lack of specific PPE. We reported less surgery-related pulmonary complications and mortality in Sars-CoV-2-infected patients, than in literature. Emergent and oncological surgery should not be postponed, but it is mandatory to use full PPE, and to adopt preoperative screenings and strategies that mitigate the detrimental effect of pulmonary complications, mostly responsible for mortality.
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http://dx.doi.org/10.1007/s13304-020-00909-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778576PMC
April 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

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

Correspondence on "Benchmark performance of laparoscopic left lateral sectionectomy and right hepatectomy in expert centers".

J Hepatol 2021 Apr 16;74(4):985-986. Epub 2020 Dec 16.

Department of General and Oncological Surgery. Mauriziano Hospital, Turin, Italy.

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http://dx.doi.org/10.1016/j.jhep.2020.11.009DOI Listing
April 2021

Tumor Burden Dictates Prognosis Among Patients Undergoing Resection of Intrahepatic Cholangiocarcinoma: A Tool to Guide Post-Resection Adjuvant Chemotherapy?

Ann Surg Oncol 2021 Apr 1;28(4):1970-1978. Epub 2020 Dec 1.

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

Introduction: While tumor burden (TB) has been associated with outcomes among patients with hepatocellular carcinoma, the role of overall TB in intrahepatic cholangiocarcinoma (ICC) remains poorly defined.

Methods: Patients undergoing curative-intent resection of ICC between 2000 and 2017 were identified from a multi-institutional database. The impact of TB on overall (OS) and disease-free survival (DFS) was evaluated in the multi-institutional database and validated externally.

Results: Among 1101 patients who underwent curative-intent resection of ICC, 624 (56.7%) had low TB, 346 (31.4%) medium TB, and 131 (11.9%) high TB. OS incrementally worsened with higher TB (5-year OS; low TB: 48.3% vs medium TB: 29.8% vs high TB: 17.3%, p < 0.001). Similarly, patients with low TB had better DFS compared with medium and high TB patients (5-year DFS: 38.3% vs 18.7% vs 6.9%, p < 0.001). On multivariable analysis, TB was independently associated with OS (medium TB: HR = 1.40, 95% CI 1.14-1.71; high TB: HR = 1.89, 95% CI 1.46-2.45) and DFS (medium TB, HR = 1.61, 95% CI 1.33-1.96; high TB: HR = 2.03, 95% CI 1.56-2.64). Survival analysis revealed an excellent prognostic discrimination using the TB among the external validation cohort (3-year OS; low TB: 44.8%, medium TB: 29.3%; high TB: 23.3%, p = 0.03; 3-year DFS: low TB: 32.7%, medium TB: 10.7%; high TB: 0%, p < 0.001). While neoadjuvant chemotherapy was not associated with survival across the TB groups, receipt of adjuvant chemotherapy was associated with increased survival among patients with high TB (5-year OS: 24.4% vs 13.4%, p = 0.02).

Conclusion: Overall TB dictated prognosis among patients with resectable ICC. TB may be used as a tool to help guide post-resection treatment strategies.
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http://dx.doi.org/10.1245/s10434-020-09393-7DOI Listing
April 2021

Tumor Necrosis Impacts Prognosis of Patients Undergoing Curative-Intent Hepatocellular Carcinoma.

Ann Surg Oncol 2021 Feb 28;28(2):797-805. Epub 2020 Nov 28.

Department of Surgery, Division of Surgical Oncology, Professor of Surgery, Oncology, Health Services Management and Policy, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.

Background: The impact of tumor necrosis relative to prognosis among patients undergoing curative-intent resection for hepatocellular carcinoma (HCC) remains ill-defined.

Methods: Patients who underwent curative-intent resection for HCC without any prior treatment between 2000 and 2017 were identified from an international multi-institutional database. Tumor necrosis was graded as absent, moderate (< 50% area), or extensive (≥ 50% area) on histological examination. The relationship between tumor necrosis, clinicopathologic characteristics, and long-term survival were analyzed.

Results: Among 919 patients who underwent curative-intent resection for HCC, the median tumor size was 5.0 cm (IQR, 3.0-8.5). Tumor necrosis was present in 367 (39.9%) patients (no necrosis: n = 552, 60.1% vs < 50% necrosis: n = 256, 27.9% vs ≥ 50% necrosis: n = 111, 12.1%). Extent of tumor necrosis was also associated with more advanced tumor characteristics. HCC necrosis was associated with OS (median OS: no necrosis, 84.0 months vs < 50% necrosis, 73.6 months vs ≥ 50% necrosis: 59.3 months; p < 0.001) and RFS (median RFS: no necrosis, 49.6 months vs < 50% necrosis, 38.3 months vs ≥ 50% necrosis: 26.5 months; p < 0.05). Patients with T1 tumors with extensive ≥ 50% necrosis had an OS comparable to patients with T2 tumors (median OS, 62.9 vs 61.8 months; p = 0.645). In addition, patients with T2 disease with necrosis had long-term outcomes comparable to patients with T3 disease (median OS, 61.8 vs 62.4 months; p = 0.713).

Conclusion: Tumor necrosis was associated with worse OS and RFS, as well as T-category upstaging of patients. A modified AJCC T classification that incorporates tumor necrosis should be considered in prognostic stratification of HCC patients.
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http://dx.doi.org/10.1245/s10434-020-09390-wDOI Listing
February 2021

Impact of time-to-surgery on outcomes of patients undergoing curative-intent liver resection for BCLC-0, A and B hepatocellular carcinoma.

J Surg Oncol 2021 Feb 11;123(2):381-388. Epub 2020 Nov 11.

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

Background: The impact of a prolonged time-to-surgery (TTS) among patients with resectable hepatocellular carcinoma (HCC) is not well defined.

Methods: Patients who underwent curative-intent hepatectomy for BCLC-0, A and B HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of prolonged TTS on overall survival (OS) and disease-free survival (DFS) was examined.

Results: Among 775 patients who underwent resection for HCC, 537 (69.3%) had early surgery (TTS < 90 days) and 238 (30.7%) patients had a delayed surgery (TTS ≥ 90 days). Patient- and tumor-related characteristics were similar between the two groups except for a higher proportion of patients undergoing major liver resection in the early surgery group (31.3% vs. 23.8%, p = .04). The percentage of patients with delayed surgery varied from 8.8% to 59.1% among different centers (p < .001). Patients with TTS < 90 days had similar 5-year OS (63.7% vs. 64.9; p = .79) and 5-year DFS (33.5% vs. 42.4; p = .20) with that of patients with TTS ≥ 90 days. On multivariable analysis, delayed surgery was not associated with neither worse OS (BCLC-0/A: adjusted hazards ratio [aHR] = 0.90; 95% confidence interval [CI]: 0.65-1.25 and BCLC-B: aHR = 0.72; 95%CI: 0.30-1.74) nor DFS (BCLC-0/A: aHR = 0.78; 95%CI: 0.60-1.01 and BCLC-B: aHR = 0.67; 95% CI: 0.36-1.25).

Conclusion: Approximately one in three patients diagnosed with resectable HCC had a prolonged TTS. Delayed surgery was not associated with worse outcomes among patients with resectable HCC.
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http://dx.doi.org/10.1002/jso.26297DOI Listing
February 2021

Clinical-Pathologic Characteristics and Long-term Outcomes of Left Flexure Colonic Cancer: A Retrospective Analysis of an International Multicenter Cohort.

Dis Colon Rectum 2020 12;63(12):1593-1601

Department of Surgery, Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota.

Background: Colorectal cancer seldom presents at the splenic flexure. Small series on left flexure tumors reported a high occurrence of negative prognostic factors called into question as causes of poor prognosis. However, because of the small number of cases, no definite conclusions can be drawn.

Objective: The aim of this study was to compare clinical-pathologic characteristics and short- and long-term outcomes of left flexure tumors with other colonic locations.

Design: This was a retrospective analysis of consecutive patients who underwent surgery for tumors at the splenic flexure. Each tumor was paired in a 1 to 1 fashion with a right-sided and sigmoid tumor.

Settings: The study was conducted in 10 international centers.

Patients: A total of 641 patients with left flexure tumors were included in the study.

Main Outcome Measures: Overall survival and cancer-specific survival were measured.

Results: Left flexure tumors presented more frequently with stenosis (30.5%; p < 0.001), with lesions infiltrating beyond the serosa (21.9%; p = 0.001) and with a high rate of mucinous histology (8.8%; p = 0.001). Looking at long-term prognosis, no differences were observed among the 3 groups, both considering overall and cancer-specific survival. However, left flexure tumors recurred more frequently as peritoneal carcinomatosis (20.6%; p < 0.001).

Limitations: This study was limited because of its retrospective nature.

Conclusions: Although left flexure tumors display several negative prognostic factors, they are not characterized by a worse prognosis compared with other colon cancer locations. See Video Abstract at http://links.lww.com/DCR/B395. CARACTERÍSTICAS CLÍNICO-PATOLÓGICAS Y RESULTADOS A LARGO PLAZO DEL CÁNCER DE COLON DE ÁNGULO IZQUIERDO: UN ANÁLISIS RETROSPECTIVO DE UNA COHORTE MULTICÉNTRICA INTERNACIONAL: El cáncer colorrectal rara vez se presenta en el ángulo esplénico. Pequeñas series sobre tumores de ángulo izquierdo informaron una alta incidencia de factores pronósticos negativos cuestionados como causas de mal pronóstico. Sin embargo, debido al pequeño número de casos, no se pueden sacar conclusiones definitivas.El objetivo de este estudio fue comparar las características clínico-patológicas, los resultados a corto y largo plazo de los tumores de ángulo izquierdo con otras ubicaciones de colon.Análisis retrospectivo de pacientes consecutivos que se sometieron a cirugía por tumores en el ángulo esplénico. Cada tumor se emparejó de forma individual con un tumor del lado derecho y sigmoide.El estudio se realizó en 10 centros internacionales.Se incluyeron en el estudio un total de 641 pacientes con tumores del ángulo izquierdo.Supervivencia general y específica del cáncerLos tumores de ángulo izquierda se presentaron con mayor frecuencia con estenosis (30.5%, p <0.001), con lesiones infiltradas más allá de la serosa (21.9%, p = 0.001), y con una alta tasa de histología mucinosa (8.8%, p = 0.001). En cuanto al pronóstico a largo plazo, no se observaron diferencias entre los tres grupos, considerando la supervivencia general y específica del cáncer. Sin embargo, los tumores de ángulo izquierdo recurrieron con mayor frecuencia como carcinomatosis peritoneal (20,6%; p <0,001).Este estudio fue limitado debido a su naturaleza retrospectiva.Aunque los tumores de ángulo izquierdo muestran varios factores pronósticos negativos, no se caracterizan por un peor pronóstico en comparación con otras ubicaciones de cáncer de colon. Consulte Video Resumen en http://links.lww.com/DCR/B395.
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http://dx.doi.org/10.1097/DCR.0000000000001785DOI Listing
December 2020

Prediction of tumor recurrence by α-fetoprotein model after curative resection for hepatocellular carcinoma.

Eur J Surg Oncol 2021 Mar 15;47(3 Pt B):660-666. Epub 2020 Oct 15.

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

Background: Preoperative α-fetoprotein (AFP) level levels may help select patients with hepatocellular carcinoma (HCC) for surgery. The objective of the current study was to assess an AFP model to predict tumor recurrence and patient survival after curative resection for HCC.

Methods: Patients undergoing curative-intent resection for HCC between 2000 and 2017 were identified from a multi-institutional database. AFP score was calculated based on the last evaluation before surgery. Probabilities of tumor recurrence and overall survival (OS) were compared according to an AFP model.

Results: A total of 825 patients were included. An optimal cut-off AFP score of 2 was identified with an AFP score ≥3 versus ≤2 independently predicting tumor recurrence and OS. Net reclassification improvements indicated the AFP model was superior to the Barcelona Clinic Liver Cancer (BCLC) system to predict recurrence (p < 0.001). Among patients with BCLC B-C, AFP score ≤2 identified a subgroup of patients with AFP levels of ≤100 ng/mL with a low 5-year recurrence risk (≤2 45.2% vs. ≥3 61.8%, p = 0.046) and favorable 5-year OS (≤2 54.5% vs. ≥3 39.4%, p = 0.035). In contrast, among patients within BCLC 0-A, AFP score ≥3 identified a subgroup of patients with AFP values > 1000 ng/mL with a high 5-year recurrence (≥3 47.9% vs. ≤2% 38.4%, p = 0.046) and worse 5-year OS (≥3 47.8% vs. ≤2 65.9%, p < 0.001). In addition, the AFP score independently correlated with vascular invasion, tumor differentiation and capsule invasion.

Conclusions: The AFP model was more accurate than the BCLC system to identify which HCC patients may benefit the most from surgical resection.
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http://dx.doi.org/10.1016/j.ejso.2020.10.017DOI Listing
March 2021

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

Overall Tumor Burden Dictates Outcomes for Patients Undergoing Resection of Multinodular Hepatocellular Carcinoma Beyond the Milan Criteria.

Ann Surg 2020 10;272(4):574-581

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

Objective: The objective of the current study was to define surgical outcomes after resection of multinodular hepatocellular carcinoma (HCC) beyond the Milan criteria, and develop a prediction tool to identify which patients likely benefit the most from resection.

Background: Liver resection for multinodular HCC, especially beyond the Milan criteria, remains controversial. Rigorous selection of the best candidates for resection is essential to achieve optimal outcomes after liver resection of advanced tumors.

Methods: Patients who underwent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Patients were categorized according to Milan criteria status. Pre- and postoperative overall survival (OS) prediction models that included HCC tumor burden score (TBS) among patients with multinodular HCC beyond Milan criteria were developed and validated.

Results: Among 1037 patients who underwent resection for HCC, 164 (15.8%) had multinodular HCC beyond the Milan criteria. Among patients with multinodular HCC, 25 (15.2%) patients experienced a serious complication and 90-day mortality was 3.7% (n = 6). Five-year OS after resection of multinodular HCC beyond Milan criteria was 52.8%. A preoperative TBS-based model (5-year OS: low-risk, 73.7% vs intermediate-risk, 45.1% vs high-risk, 13.1%), and postoperative TBS-based model (5-year OS: low-risk, 80.1% vs intermediate-risk, 37.2% vs high-risk, not reached) categorized patients into distinct prognostic groups relative to long-term prognosis (both P < 0.001). Pre- and postoperative models could accurately stratify OS in an external validation cohort (5-year OS; low vs medium vs high risk; pre: 66.3% vs 25.2% vs not reached, P = 0.012; post: 61.4% vs 42.5% vs not reached, P = 0.045) Predictive accuracy of the pre- and postoperative models was good in the training (c-index; pre: 0.68; post: 0.71), internal validation (n = 2000 resamples) (c-index, pre: 0.70; post: 0.72) and external validation (c-index, pre: 0.67; post 0.68) datasets. TBS alone could stratify patients relative to 5-year OS after resection of multinodular HCC beyond Milan criteria (c-index: 0.65; 5-year OS; low TBS: 70.2% vs medium TBS: 54.7% vs high TBS: 16.7%; P < 0.001). The vast majority of patients with low and intermediate TBS were deemed low or medium risk based on both the preoperative (98.4%) and postoperative risk scores (95.3%).

Conclusion: Prognosis of patients with multinodular HCC was largely dependent on overall tumor burden. Liver resection should be considered among patients with multinodular HCC beyond the Milan criteria who have a low- or intermediate-TBS.
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http://dx.doi.org/10.1097/SLA.0000000000004346DOI Listing
October 2020

Stratification of Major Hepatectomies According to Their Outcome: Analysis of 2212 Consecutive Open Resections in Patients Without Cirrhosis.

Ann Surg 2020 11;272(5):827-833

Department of Medical Sciences, Cancer Epidemiology Unit, University of Torino and CPO-Piemonte, Torino, Italy.

Objective: To stratify major hepatectomies (MajHs) according to their outcomes.

Summary Of Background Data: MajHs are associated with non-negligible operative risks, but they include a wide range of procedures. Detailed depiction of the outcomes of different MajHs is the basis for a new classification of liver resections.

Methods: We retrospectively considered patients that underwent hepatectomy in 17 high-volume centers. Patients with an associated digestive/biliary resection were excluded. We analyzed open MajHs in non-cirrhotic patients. MajHs were classified according to the Brisbane nomenclature. Right hepatectomies (RHs) were reference standards. Outcomes were adjusted for potential confounders, including indication, liver function, preoperative portal vein embolization, and enrolling center.

Results: We analyzed a series of 2212 patients. In comparison with RH, left hepatectomy had lower mortality [0.6% vs 2.2%, odds ratio (OR) = 0.25], severe morbidity (11.7% vs 14.4%, OR = 0.62), and liver failure rates (2.1% vs 11.6%, OR = 0.16). Left hepatectomy+Sg1 and mesohepatectomy+/-Sg1 had outcomes similar to RH, except for higher bile leak rate (31.3% and 13.5% vs 6.7%, OR = 4.36 and OR = 2.29). RH + Sg1 had slightly worse outcomes than RH. Right and left trisectionectomies had higher mortality (5.0% and 7.3% vs 2.2%, OR = 2.07 and OR = 2.71) and liver failure rates than RH (19.0% and 22.0% vs 11.6%, OR = 2.03 and OR = 2.21). Left trisectionectomy had even higher severe morbidity (25.6% vs 14.4%, OR = 2.07) and bile leak rates (14.6% vs 6.7%, OR = 2.31).

Conclusions: The term "major hepatectomy" includes resections having heterogeneous outcome. Different MajHs can be stratified according to their mortality, severe morbidity, liver failure, and bile leak rates.
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http://dx.doi.org/10.1097/SLA.0000000000004338DOI 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

Predicting Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma.

J Gastrointest Surg 2021 May 14;25(5):1156-1163. Epub 2020 Jul 14.

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

Background: The objective of the current study was to develop a model to predict the likelihood of occult lymph node metastasis (LNM) prior to resection of intrahepatic cholangiocarcinoma (ICC).

Methods: Patients who underwent hepatectomy for ICC between 2000 and 2017 were identified using a multi-institutional database. A novel model incorporating clinical and preoperative imaging data was developed to predict LNM.

Results: Among 980 patients who underwent resection of ICC, 190 (19.4%) individuals had at least one LNM identified on final pathology. An enhanced imaging model incorporating clinical and imaging data was developed to predict LNM ( https://k-sahara.shinyapps.io/ICC_imaging/ ). The performance of the enhanced imaging model was very good in the training data set (c-index 0.702), as well as the validation data set with bootstrapping resamples (c-index 0.701) and outperformed the preoperative imaging alone (c-index 0.660). The novel model predicted both 5-year overall survival (OS) (low risk 48.4% vs. high risk 18.4%) and 5-year disease-specific survival (DSS) (low risk 51.9% vs. high risk 25.2%, both p < 0.001). When applied among Nx patients, 5-year OS and DSS of low-risk Nx patients was comparable with that of N0 patients, while high-risk Nx patients had similar outcomes to N1 patients (p > 0.05).

Conclusion: This tool may represent an opportunity to stratify prognosis of Nx patients and can help inform clinical decision-making prior to resection of ICC.
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http://dx.doi.org/10.1007/s11605-020-04720-5DOI Listing
May 2021