Publications by authors named "Maria B Majella Doyle"

22 Publications

  • Page 1 of 1

Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors.

J Am Coll Surg 2021 Apr 13;232(4):361-371. Epub 2020 Dec 13.

Washington University in St Louis, Saint Louis, MO.

Background: Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multicenter collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA.

Study Design: Liver transplant and resection outcomes for HCC (n = 2,998) and cHCC-CCA (n = 208) were compared in a 12-center retrospective review (2009 to 2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis.

Results: Liver transplantation for cHCC-CCA (n = 67) and HCC (n = 1,814) within Milan had no significant difference in overall survival (5-year cHCC-CCA 70.1%, HCC 73.4%, p = 0.806), despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5 years, p < 0.001). Irrespective of tumor burden, cHCC-CCA tumor patient undergoing liver transplant had significantly superior overall survival (p = 0.047) and disease-free survival (p < 0.001) than those having resection. For cHCC-CCA within Milan, liver transplant was associated with improved disease-free survival over resection (70.3% vs 33.6% 5 years, p < 0.001).

Conclusions: Regardless of tumor burden, outcomes after liver transplantation are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC result in similar overall survival, justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population.
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http://dx.doi.org/10.1016/j.jamcollsurg.2020.11.017DOI Listing
April 2021

Economic evaluation of the specialized donor care facility for thoracic organ donor management.

J Thorac Dis 2020 Oct;12(10):5709-5717

Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO, USA.

Background: Over the last decade two alternative models of donor care have emerged in the United States: the conventional model, whereby donors are managed at the hospital where brain death occurs, and the specialized donor care facility (SDCF), in which brain dead donors are transferred to a SDCF for medical optimization and organ procurement. Despite increasing use of the SDCF model, its cost-effectiveness in comparison to the conventional model remains unknown.

Methods: We performed an economic evaluation of the SDCF and conventional model of donor care from the perspective of U.S. transplant centers over a 2-year study period. In this analysis, we utilized nationwide data from the Scientific Registry of Transplant Recipients and controlled for donor characteristics and patterns of organ sharing across the nation's organ procurement organizations (OPOs). Subgroup analysis was performed to determine the impact of the SDCF model on thoracic organ transplants.

Results: A total of 38,944 organ transplants were performed in the U.S. during the study period from 13,539 donors with an observed total organ cost of $1.36 billion. If every OPO assumed the cost and effectiveness of the SDCF model, a predicted 39,155 organ transplants (+211) would have been performed with a predicted total organ cost of $1.26 billion (-$100 million). Subgroup analysis of thoracic organs revealed that the SDCF model would lead to a predicted 156 additional transplants with a cost saving of $24.6 million.

Conclusions: The U.S. SDCF model may be a less costly and more effective means of multi-organ donor management, particularly for thoracic organ donors, compared to the conventional hospital-based model.
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http://dx.doi.org/10.21037/jtd-20-1575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656378PMC
October 2020

Contemporary Imaging of the Surgically Placed Hepatic Arterial Infusion Chemotherapy Pump.

AJR Am J Roentgenol 2020 Oct 7. Epub 2020 Oct 7.

Mallinckrodt Institute of Radiology, Washington University School of Medicine. 510 S. Kingshighway Blvd, Campus Box 8131, St. Louis, Missouri 63110. (314) 362-2927.

Hepatic arterial infusion (HAI) of chemotherapy is a locoregional treatment strategy for hepatic malignancy involving placement of a surgically implanted pump or percutaneous port-catheter device into a branch of the hepatic artery. HAI has been used for metastatic colorectal cancer for decades but has recently attracted new attention due to its potential impact on survival, when combined with systemic therapy, in patients presenting with unresectable hepatic disease. Although various HAI device related complications have been described, little attention has been given to their appearance on imaging. Radiologists are uniquely positioned to identify these complications given that patients receiving HAI therapy typically undergo frequent imaging and may have complications that are delayed or clinically unsuspected. This article therefore reviews the multimodality imaging considerations of surgically implanted HAI devices. The role of imaging in routine perioperative assessment, including the normal postoperative appearance of the device, is described. The imaging findings of potential complications, including pump pocket complications, catheter or arterial complications, and toxic or ischemic complications, are presented, with a focus on CT. Familiarity with the device and its complications will aid radiologists in playing an important role in the management of patients undergoing HAI therapy.
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http://dx.doi.org/10.2214/AJR.20.24437DOI Listing
October 2020

Role of yttrium-90 selective internal radiation therapy in the treatment of liver-dominant metastatic colorectal cancer: an evidence-based expert consensus algorithm.

J Gastrointest Oncol 2020 Apr;11(2):443-460

Department of Surgery, Stanford University Medical Center, CA, USA.

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a comprehensive, evidence-based treatment algorithm that includes appropriate treatment options for patients stratified by their eligibility for surgical treatment. The group coined a novel, more inclusive phrase for targeted locoregional tumor treatment (a blanket term for resection, ablation, and other emerging locoregional treatments): . The expert panel proposed new nomenclature for 3 distinct disease categories of liver-dominant metastatic colorectal cancer that is consistent with other tumor types: (I) surgically treatable (resectable); (II) surgically untreatable (borderline resectable); (III) advanced surgically untreatable (unresectable) disease. Patients may present at any point in the algorithm and move between categories depending on their response to therapy. The broad intent of therapy is to transition patients toward individualized treatments where possible, given the survival advantage that resection offers in the context of a comprehensive treatment plan. This article reviews what is known about the role of SIRT with Y-90 as neoadjuvant, definitive, or palliative therapy in these different clinical situations and provides insight into when treatment with SIRT with Y-90 may be appropriate and useful, organized into distinct treatment algorithm steps.
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http://dx.doi.org/10.21037/jgo.2020.01.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212103PMC
April 2020

Assessment of Hepatic Arterial Infusion of Floxuridine in Combination With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial.

JAMA Oncol 2019 Oct 31. Epub 2019 Oct 31.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: Unresectable intrahepatic cholangiocarcinoma (IHC) carries a poor prognosis, with a median overall survival (OS) of 11 months. Hepatic arterial infusion (HAI) of high-dose chemotherapy may have potential benefit in these patients.

Objective: To evaluate clinical outcomes when HAI chemotherapy is combined with systemic chemotherapy in patients with unresectable IHC.

Design, Setting, And Participants: A single-institution, phase 2 clinical trial including 38 patients was conducted with HAI floxuridine plus systemic gemcitabine and oxaliplatin in patients with unresectable IHC at Memorial Sloan Kettering Cancer Center between May 20, 2013, and June 27, 2019. A confirmatory phase 1/2 study using the same therapy was conducted during the same time period at Washington University in St Louis. Patients with histologically confirmed, unresectable IHC were eligible. Resectable metastatic disease to regional lymph nodes and prior systemic therapy were permitted. Patients with distant metastatic disease were excluded.

Interventions: Hepatic arterial infusion of floxuridine and systemic administration of gemcitabine and oxaliplatin.

Main Outcomes And Measures: The primary outcome was progression-free survival (PFS) of 80% at 6 months.

Results: For the phase 2 clinical trial at Memorial Sloan Kettering Cancer Center, 42 patients with unresectable IHC were included and, of these, 38 patients were treated (13 [34%] men; median [range] age at diagnosis, 64 [39-81] years). The median follow-up was 30.5 months. Twenty-two patients (58%) achieved a partial radiographic response, and 32 patients (84%) achieved disease control at 6 months. Four patients had sufficient response to undergo resection, and 1 patient had a complete pathologic response. The median PFS was 11.8 months (1-sided 90% CI, 11.1) with a 6-month PFS rate of 84.1% (90% CI, 74.8%-infinity), thereby meeting the primary end point (6-month PFS rate, 80%). The median OS was 25.0 months (95% CI, 20.6-not reached), and the 1-year OS rate was 89.5% (95% CI, 80.2%-99.8%). Patients with resectable regional lymph nodes (18 [47%]) showed no difference in OS compared with patients with node-negative disease (24-month OS: lymph node negative: 60%; 95% CI, 40%-91% vs lymph node positive: 50%; 95% CI, 30%-83%; P = .66). Four patients (11%) had grade 4 toxic effects requiring removal from the study (1 portal hypertension, 2 gastroduodenal artery aneurysms, 1 infection in the pump pocket). Subgroup analysis showed significant improvement in survival in patients with IDH1/2 mutated tumors (2-year OS, 90%; 95% CI, 73%-99%) vs wild-type (2-year OS, 33%; 95% CI, 18%-63%) (P = .01). In the Washington University in St Louis confirmatory cohort, 9 patients (90%) achieved disease control at 6 months; the most common grade 3 toxic effect was elevated results of liver function tests, and median PFS was 12.8 months (1-sided 90% CI, 6.4).

Conclusions And Relevance: Hepatic arterial infusion plus systemic chemotherapy appears to be highly active and tolerable in patients with unresectable IHC; further evaluation is warranted.
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http://dx.doi.org/10.1001/jamaoncol.2019.3718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824231PMC
October 2019

Systemic Therapy for Combined Hepatocellular-Cholangiocarcinoma: A Single-Institution Experience.

J Natl Compr Canc Netw 2018 10;16(10):1193-1199

Combined hepatocellular-cholangiocarcinoma tumors (cHCC-CCA) are a heterogeneous group of rare malignancies that have no established optimal treatment. We identified patients with cHCC-CCA treated at a tertiary center and retrospectively examined their histology, interventions, and outcomes. We calculated disease control rate (DCR), disease progression, overall survival, and progression-free survival (PFS) between treatment subgroups. A total of 123 patients were evaluable. Interventions included resection, locoregional therapy, transplant, chemotherapy, and targeted agents. Ultimately, 68 patients received systemic treatment-57 with gemcitabine plus either 5-fluoropyrimidine (5-FU) or a platinum combination. Disease progression was more common in the gemcitabine/5-FU group versus gemcitabine/platinum (=.028), whereas DCR favored gemcitabine/platinum (78.4% vs 38.5%; =.0143). Median PFS from time of initial diagnosis favored the gemcitabine/platinum group, but the difference did not reach statistical significance. Targeted agents had minimal to no effect on survival metrics. Gemcitabine/platinum seems to be a superior regimen for patients with cHCC-CCA who require systemic treatment. Further studies are needed to clarify the regimen's efficacy and applicability in patient subgroups.
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http://dx.doi.org/10.6004/jnccn.2018.7053DOI Listing
October 2018

Organ procurement center allows for daytime liver transplantation with less resource utilization: May address burnout, pipeline, and safety for field of transplantation.

Am J Transplant 2019 05 19;19(5):1296-1304. Epub 2018 Oct 19.

Division of Abdominal Organ Transplantation, Department of Surgery, Washington University School of Medicine, Saint Louis, Missouri.

Abdominal organ transplantation faces several challenges: burnout, limited pipeline of future surgeons, changes in liver allocation potentially impacting organ procurement travel, and travel safety. The organ procurement center (OPC) model may be one way to mitigate these issues. Liver transplants from 2009 to 2016 were reviewed. There were 755 liver transplants performed with 525 OPC and 230 in-hospital procurements. The majority of transplants (87.4%) were started during daytime hours (5 am-7 pm). Transplants with any portion occurring after-hours were more likely to have procurements in-hospital (P < .001). Daytime cases (n = 400) had more OPC procured livers and hepatitis C recipients and were less likely to have a donation after circulatory death donor (all P < .05). In adjusted analyses, daytime cases were independently associated with extubation in the operating room and less postoperative transfusion. There were no significant differences in short- or long-term postoperative outcomes. For exported livers, 54.3% were procured by a local team, saving 137 flights (151 559 miles). The OPC resulted in optimally timed liver transplants and decreased resource utilization with no negative impact on patient outcomes. It allows for ease in exporting organs procured by local surgeons, and potentially addresses provider burnout, the transplant surgery pipeline, and surgeon travel.
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http://dx.doi.org/10.1111/ajt.15129DOI Listing
May 2019

The importance of early recognition in management of ERCP-related perforations.

Surg Endosc 2018 12 16;32(12):4841-4849. Epub 2018 May 16.

Division of Gastroenterology, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8124, St. Louis, MO, 63110, USA.

Background: Iatrogenic perforations related to endoscopic retrograde cholangiopancreatography (ERCP) are rare events, carrying with it a mortality of up to 8%. Given the rarity of this adverse event, there remains limited data and continued uncertainties when choosing therapeutic strategies. Our aims were to evaluate the management of ERCP-related perforations and compare outcomes based on timing of recognition.

Methods: The endoscopic databases of two tertiary care centers were interrogated to identify consecutive adult patients who sustained ERCP-related perforation over a 10-year period from 2006 to 2016. Electronic medical records were reviewed to extract demographic data, perforation type, management strategies, clinical data, and patient outcomes.

Results: 14,045 ERCP's were performed during our 10-year study period. Sixty-three patients (average age 62.3 ± 2.38 years, 76% female) with ERCP-related perforations were included. Stapfer I perforations were found in 14 (22.2%) patients, Stapfer II in 24 (38.1%), and Stapfer III and IV perforations were identified in 16 (25.4%) and 9 (14.28%), respectively. Forty-seven (74.6%) perforations were recognized immediately during the ERCP, whereas 16 (25.4%) were recognized late. Endoscopic therapy was attempted in 35 patients in whom perforations were identified immediately, and was technically successful in 33 (94.3%). In all, 4 (1 immediate/ 3 delayed) patients required percutaneous drainage and 9 (5 immediate/ 4 delayed) surgery. Length of hospital stay, ICU admission were significantly shorter and incidence of SIRS was significantly lower when perforation was recognized immediately.

Conclusions: Immediate recognition of ERCP-related perforations leads to more favorable patient outcomes; with lower incidence of SIRS, less need for ICU level care, and shorter hospital stay.
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http://dx.doi.org/10.1007/s00464-018-6235-8DOI Listing
December 2018

Patient and Graft Survival: Biliary Complications after Liver Transplantation.

J Am Coll Surg 2018 04 31;226(4):484-494. Epub 2018 Jan 31.

Section of Transplant Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO. Electronic address:

Background: Biliary complications (BCs) affect up to to 34% of liver transplant recipients and are a major source of morbidity and cost. This is a 13-year review of BCs after liver transplantation (LT) at a tertiary care center.

Study Design: We conducted a single-center retrospective review of our prospective database to assess BCs in adult (aged 18 years or older) liver transplant recipients during a 13-year period (2002 to 2014). Biliary complications were divided into 3 subgroups: leak alone (L), stricture alone (S), and both leak and strictures (LS). Controls (no BCs) were used for comparison.

Results: There were 1,041 adult LTs performed during the study period; BCs developed in 239 (23%) of these patients: 55 (23%) L, 148 (62%) S, and 36 (15%) LS. One hundred and two (43%) were early (less than 30 d). Surgical revision was required in 42 cases (17%) (30 L, 10 LS, and 2 S), while the remaining 197 (83%) were managed nonsurgically (25 L, 26 LS, and 146 S), with a mean of 4.2 interventions/patient. One-, 3-, and 5-year overall patient and graft survival was significantly reduced in patients with bile leaks (84%, 71%, and 68% and 76%, 67%, and 64%, respectively) compared with controls (90%, 84%, and 78% and 88%, 81%, and 76%, respectively [p < 0.05]). Patients with BCs had higher incidence of cholestatic liver disease, higher pre-LT bilirubin, higher use of T-tubes, higher use of donor after cardiac death grafts, and higher rates of acute rejection (p < 0.05). Patients with BCs had longer ICU and hospital stays and higher rates of 30- and 90-day readmissions (p < 0.01). Multivariate analysis identified cholestatic liver disease, Roux-en-Y anastomosis, donor risk index >2, and T-tubes as independent BC predictors.

Conclusions: Biliary complications after LT can significantly decrease patient and graft survival rates. Careful donor and recipient selection and attention to anastomotic technique can reduce BCs and improve outcomes.
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http://dx.doi.org/10.1016/j.jamcollsurg.2017.12.039DOI Listing
April 2018

The influence of functional warm ischemia time on DCD liver transplant recipients' outcomes.

Clin Transplant 2017 Oct 29;31(10). Epub 2017 Aug 29.

Division of Transplantation, University of Rochester, Rochester, NY, USA.

Background: Duration of functional warm ischemia (f-WIT) is thought to have a causal effect on outcomes in controlled donation after circulatory death (DCD) liver transplantation (LT).

Methods: A retrospective cohort study was conducted at five centers. Data were extracted on donor and recipient characteristics, with attention to parameters recorded during withdrawal of life support to in situ cold perfusion. F-WIT was the time elapsed from any of the hemodynamic and oxygenation parameters to the start of in situ cold perfusion. Parameters were as follows: MAP ≤ 50 mm Hg; SBP ≤ 50 mm Hg; and SPO2 ≤ 60%. The primary endpoint was a composite of disseminated ischemic cholangiopathy (IC), primary non-function (PNF), and early graft failure.

Results: 35 patients (14%) developed one or more of the primary outcomes. On univariate analysis, older donors and longer WITs were associated with greater likelihood of complications. Of the f-WIT variations analyzed, only f-WIT with SpO2 ≤ 60% was longer among patients with complications. On multivariate analysis, only donor age was a significant predictor of complications.

Conclusion: This study demonstrates that, of the f-WITs, f-WIT with SpO2 ≤ 60% is most predictive of post-DCD complications. However, results suggest that there may be an alternate etiology for poor outcomes, and that donor age plays a key role.
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http://dx.doi.org/10.1111/ctr.13068DOI Listing
October 2017

Prediction of Hepatocellular Carcinoma Recurrence Beyond Milan Criteria After Resection: Validation of a Clinical Risk Score in an International Cohort.

Ann Surg 2017 10;266(4):693-701

*Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY †Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY ‡Department of Surgery, Washington University School of Medicine, St. Louis, MO §Department of Surgery, Université de Montréal, Montreal, Quebec, Canada ¶Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands ||Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore **Division of Surgical Oncology, National Cancer Center, Singapore, Singapore.

Objective: This study aims to validate a previously reported recurrence clinical risk score (CRS).

Summary Of Background Data: Salvage transplantation after hepatocellular carcinoma (HCC) resection is limited to patients who recur within Milan criteria (MC). Predicting recurrence patterns may guide treatment recommendations.

Methods: An international, multicenter cohort of R0 resected HCC patients were categorized by MC status at presentation. CRS was calculated by assigning 1 point each for initial disease beyond MC, multinodularity, and microvascular invasion. Recurrence incidences were estimated using competing risks methodology, and conditional recurrence probabilities were estimated using the Bayes theorem.

Results: From 1992 to 2015, 1023 patients were identified, of whom 613 (60%) recurred at a median follow-up of 50 months. CRS was well validated in that all 3 factors remained independent predictors of recurrence beyond MC (hazard ratio 1.5-2.1, all P < 0.001) and accurately stratified recurrence risk beyond MC, ranging from 19% (CRS 0) to 67% (CRS 3) at 5 years. Among patients with CRS 0, no other factors were significantly associated with recurrence beyond MC. The majority recurred within 2 years. After 2 years of recurrence-free survival, the cumulative risk of recurrence beyond MC within the next 5 years for all patients was 14%. This risk was 12% for patients with initial disease within MC and 17% for patients with initial disease beyond MC.

Conclusions: CRS accurately predicted HCC recurrence beyond MC in this international validation. Although the risk of recurrence beyond MC decreased over time, it never reached zero.
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http://dx.doi.org/10.1097/SLA.0000000000002360DOI Listing
October 2017

Liver Resection and Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria.

Ann Surg 2016 10;264(4):650-8

*Division of Surgical Oncology, Section of Hepatobiliary and Pancreatic Surgery, University of Virginia, Charlottesville, VA †Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO ‡Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX §Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY ||Division of Transplantation and Hepatobiliary Surgery, University of California San Diego, San Diego, CA ¶Department of Surgery, Section of Hepatobiliary and Pancreas Surgery, Mayo Clinic College of Medicine, Rochester, MN.

Objectives: To assess survival after liver resection and transplantation in patients with hepatocellular carcinoma (HCC) beyond Milan criteria.

Background: The role of liver resection and transplantation remains controversial for patients with HCC beyond Milan criteria. Resection of advanced tumors and transplantation using extended-criteria are pursued at select high-volume center.

Methods: Patients from 5 liver cancer centers in the United States who had liver resection or transplantation for HCC beyond Milan criteria between 1990 and 2011 were included in the study. Multivariable and propensity-matching analyses estimated the effects of clinical factors and operative selection on survival.

Results: Of 608 patients beyond Milan without vascular invasion, 480 (79%) patients underwent resection and 128 (21%) underwent transplantation. Clinicopathologic profiles between resection and transplant patients differed significantly. Hepatitis C and cirrhosis were more prevalent in transplantation group (P < 0.001). Resection patients had larger tumors [median 9 cm, interquartile range (IQR): 6.5-12.9 cm vs. median 4.1, IQR: 3.4-5.3 cm, P < 0.001]; transplant patients were more likely to have multiple tumors (78% vs 28%, P < 0.001).Overall (OS) and disease-free survival (DFS) were both greater after tumor downstaging and transplantation than resection (all P < 0.001). OS did not differ between liver transplant recipients who were not pretreated or pretreated and failed to downstage compared with propensity-matched liver resection patients (P ≥ 0.176); DFS in this propensity matched cohort was greater after liver transplantation (P ≤ 0.017).

Conclusions: Liver resection and transplantation provide curative options for patients with HCC beyond Milan criteria. Further treatment strategies aimed at the efficiency and durability of tumor downstaging and expansion of the role of transplantation among suitable candidates could improve outcomes in patients with large or multifocal HCC.
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http://dx.doi.org/10.1097/SLA.0000000000001866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5279918PMC
October 2016

Decision Tree for Liver Resection for Hepatocellular Carcinoma.

JAMA Surg 2016 09;151(9):853-4

Washington University, St Louis, Missouri.

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http://dx.doi.org/10.1001/jamasurg.2016.1149DOI Listing
September 2016

A Review and Update of Treatment Options and Controversies in the Management of Hepatocellular Carcinoma.

Ann Surg 2016 Jun;263(6):1112-25

*Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA†Department of Surgery, Division of Surgical Oncology, University of Nebraska Medical Center, Omaha, NE‡Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE§Department of Radiology, University of Nebraska Medical Center, Omaha¶Department of Radiology, Surgery and Oncology, Johns Hopkins School of Medicine, Baltimore, MD||Department of Surgery, Division of General Surgery, Abdominal Transplantation Section, Washington University School of Medicine, St. Louis, MO**Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, NY.

Objective: To review the current management, outline recent advances and address controversies in the management of hepatocellular carcinoma (HCC).

Summary Of Background Data: The treatment of HCC is multidisciplinary involving hepatologists, surgeons, medical oncologists, radiation oncologists, radiologists, interventional radiologists, and other disciplines. Each of these disciplines brings its unique perspective and differing opinions that add to controversies in the management of HCC.

Methods: A focused literature review was performed to identify recent studies on the management of HCC and thereby summarize relevant information on the various therapeutic modalities and controversies involved in the treatment of HCC.

Results: The main treatment algorithms continue to rely on hepatic resection or transplantation with controversies involving patients harboring early stage disease and borderline hepatic function. The other treatment strategies include locoregional therapies, radiation, and systemic therapy used alone or in combination with other treatment modalities. Recent advances in locoregional therapies, radiation, and systemic therapies have provided better therapeutic options with curative intent potential for some locoregional therapies. Further refinements in combination therapies such as algorithms consisting of locoregional therapies and systemic or radiation therapies are likely to add additional options and improve survival.

Conclusions: The management of HCC has witnessed significant strides with advances in existing options and introduction of several new treatment modalities of various combinations. Further refinements in these treatment options combined with enrollment in clinical trials are essential to improve the management and outcomes of patients with HCC.
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http://dx.doi.org/10.1097/SLA.0000000000001556DOI Listing
June 2016

Polypoid lesions of the gallbladder: disease spectrum with pathologic correlation.

Radiographics 2015 Mar-Apr;35(2):387-99

From the Mallinckrodt Institute of Radiology (V.M.M.), Department of Pathology (E.M.B.), and Department of Surgery (M.B.M.D.),Washington University School of Medicine, 510 S Kingshighway Blvd, Box 8131, St Louis, MO 63110; Department of Radiology, Mayo Clinic, Scottsdale, Ariz (C.O.M., A.K.H., N.D.); Department of Radiology, Indiana University School of Medicine, Indianapolis, Ind (K.S.); Department of Radiology, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada (A.Z.K.); and Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.).

Gallbladder polyps are seen on as many as 7% of gallbladder ultrasonographic images. The differential diagnosis for a polypoid gallbladder mass is wide and includes pseudotumors, as well as benign and malignant tumors. Tumefactive sludge may be mistaken for a gallbladder polyp. Pseudotumors include cholesterol polyps, adenomyomatosis, and inflammatory polyps, and they occur in that order of frequency. The most common benign and malignant tumors are adenomas and primary adenocarcinoma, respectively. Polyp size, shape, and other ancillary imaging findings, such as a wide base, wall thickening, and coexistent gallstones, are pertinent items to report when gallbladder polyps are discovered. These findings, as well as patient age and risk factors for gallbladder cancer, guide clinical decision making. Symptomatic polyps without other cause for symptoms, an age over 50 years, and the presence of gallstones are generally considered indications for cholecystectomy. Incidentally noted pedunculated polyps smaller than 5 mm generally do not require follow-up. Polyps that are 6-10 mm require follow-up, although neither the frequency nor the length of follow-up has been established. Polyps that are larger than 10 mm are typically excised, although lower size thresholds for cholecystectomy may be considered for patients with increased risk for gallbladder carcinoma, such as patients with primary sclerosing cholangitis.
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http://dx.doi.org/10.1148/rg.352140095DOI Listing
January 2016

Surgical treatment of hepatocellular carcinoma in North America: can hepatic resection still be justified?

J Am Coll Surg 2015 Apr 6;220(4):628-37. Epub 2015 Jan 6.

Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.

Background: The incidence of hepatocellular cancer (HCC) is increasing dramatically worldwide. Optimal management remains undefined, especially for well-compensated cirrhosis and HCC.

Study Design: This retrospective analysis included 5 US liver cancer centers. Patients with surgically treated HCC between 1990 and 2011 were analyzed; demographics, tumor characteristics, and survival rates were included.

Results: There were 1,765 patients who underwent resection (n = 884, 50.1%) or transplantation (n = 881, 49.9%). Overall, 248 (28.1%) resected patients were transplant eligible (1 tumor <5 cm or 2 to 3 tumors all <3 cm, no major vascular invasion); these were compared with 496 transplant patients, matched based on year of transplantation and tumor status. Overall survivals at 5 and 10 years were significantly improved for transplantation patients (74.3% vs 52.8% and 53.7% vs 21.7% respectively, p < 0.001), with greater differences in disease-free survival (71.8% vs 30.1% at 5 years and 53.4% vs 11.7% at 10 years, p < 0.001). Ninety-seven of the 884 (11%) resected patients were within Milan criteria and had cirrhosis; these were compared with the 496 transplantation patients, with similar results to the overall group. On multivariate analysis, type of surgery was an independent variable affecting all survival outcomes.

Conclusions: The increasing incidence of HCC stresses limited resources. Although transplantation results in better long-term survival, limited donor availability precludes widespread application. Hepatic resection will likely remain a standard therapy in selected patients with HCC. In this large series, only about 10% of patients with cirrhosis were transplant-eligible based on tumor status. Although liver transplantation results are significantly improved compared with resection, transplantation is available only for a minority of patients with HCC.
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http://dx.doi.org/10.1016/j.jamcollsurg.2014.12.030DOI Listing
April 2015

Extrapleural pneumonectomy complicated by acute superior mesenteric artery syndrome.

Ann Thorac Surg 2012 Jul;94(1):291-3

Department of Surgery, Washington University in St. Louis, St. Louis, Missouri 63110, USA.

We present a patient who developed an acute superior mesenteric artery (SMA) syndrome following pneumonectomy. Although rarely described, a majority of cases develop insidiously from a gradual loss of retroperitoneal fat in the setting of malnourishment. A postoperative presentation is atypical, however procedures that narrow the aortomesenteric angle have been associated with the development of SMA syndrome. This case illustrates an important anatomic relationship that thoracic surgeons performing lung resection surgery should be aware of in order to avoid predisposing patients to SMA syndrome.
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http://dx.doi.org/10.1016/j.athoracsur.2011.12.023DOI Listing
July 2012

Utilization of hepatitis B core antibody-positive donor liver grafts.

HPB (Oxford) 2012 Jan 2;14(1):42-8. Epub 2011 Nov 2.

Section of Transplant Surgery, Department of Surgery, Washington University in St Louis, MO 63110, USA.

Background: The inclusion of hepatitis B core antibody-positive (HBcAb+) liver donors is a strategy utilized to increase organ availability. This study examined HBcAb+ transplantation practices to identify specific factors influencing outcomes.

Methods: Twenty-five HBcAb+ liver transplants were identified retrospectively among 868 adult transplants performed between 1 January 1997 and 31 December 2009. Twelve (48%) recipients had hepatitis C and five (20%) had hepatitis B. Patient and donor demographics, preoperative morbidity, transplant data and outcomes were examined. Statistical analysis was completed using Student's t-test or the Kaplan-Meier method. A P-value of <0.05 was considered significant.

Results: There was no difference in age, body mass index or comorbidities between HBcAb+ liver recipients and control subjects. Model for End-stage Liver Disease (MELD) scores of >30 were significantly more frequent in HBcAb+ liver recipients (32% vs. 15%; P= 0.04). All patients received immunoglobulin and longterm antiviral therapy as prophylaxis against graft hepatitis B resurgence. No patients who received HBcAb+ livers developed hepatitis B infection on follow-up. Overall survival at 30 days, 1 year and 5 years in HBcAb+ liver recipients was 92%, 74% and 74%, respectively, compared with 96%, 89% and 76%, respectively, in the control group (P= not significant, log-rank test). All except one of the deaths in the HBcAb+ liver recipient group occurred within 90 days postoperatively and in patients with MELD scores >30.

Conclusions: The practice of transplanting HBcAb+ grafts incurs low risk for infection using current methods of prophylaxis. The highest mortality risk was in the early postoperative period, specifically in patients with very high MELD scores. This probably reflects the practice of using positive serology grafts in emergent situations.
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http://dx.doi.org/10.1111/j.1477-2574.2011.00399.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252990PMC
January 2012