Publications by authors named "Timothy M Pawlik"

1,303 Publications

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Development of a Prognostic Nomogram and Nomogram Software Application Tool to Predict Overall Survival and Disease-Free Survival After Curative-Intent Gastrectomy for Gastric Cancer.

Ann Surg Oncol 2021 Sep 14. Epub 2021 Sep 14.

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

Background: We sought to derive and validate a prediction model of survival and recurrence among Western patients undergoing resection of gastric cancer.

Methods: Patients who underwent curative-intent surgery for gastric cancer at seven US institutions and a major Italian center from 2000 to 2020 were included. Variables included in the multivariable Cox models were identified using an automated model selection procedure based on an algorithm. Best models were selected using the Bayesian information criterion (BIC). The performance of the models was internally cross-validated via the bootstrap resampling procedure. Discrimination was evaluated using the Harrell's Concordance Index and accuracy was evaluated using calibration plots. Nomograms were made available as online tools.

Results: Overall, 895 patients met inclusion criteria. Age (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.17-1.84), presence of preoperative comorbidities (HR 1.66, 95% CI 1.14-2.41), lymph node ratio (LNR; HR 1.72, 95% CI 1.42-2.01), and lymphovascular invasion (HR 1.81, 95% CI 1.33-2.45) were associated with overall survival (OS; all p < 0.01), whereas tumor location (HR 1.93, 95% CI 1.23-3.02), T category (Tis-T1 vs. T3: HR 0.31, 95% CI 0.14-0.66), LNR (HR 1.82, 95% CI 1.45-2.28), and lymphovascular invasion (HR 1.49; 95% CI 1.01-2.22) were associated with disease-free survival (DFS; all p < 0.05) The models demonstrated good discrimination on internal validation relative to OS (C-index 0.70) and DFS (C-index 0.74).

Conclusions: A web-based nomograms to predict OS and DFS among gastric cancer patients following resection demonstrated good accuracy and discrimination and good performance on internal validation.
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http://dx.doi.org/10.1245/s10434-021-10768-7DOI Listing
September 2021

Does the Volume-Outcome Association in Pancreas Cancer Surgery Justify Regionalization of Care? A Review of Current Controversies.

Ann Surg Oncol 2021 Sep 14. Epub 2021 Sep 14.

Department of Surgery, The Ohio State University College of Medicine, The James Comprehensive Cancer Center, Columbus, OH, USA.

Introduction: Increasing hospital or surgeon volume is associated with improved outcomes among patients with pancreatic cancer. Promotion of regionalized care is based on this volume-outcome association. However, other research has exposed nuances and complexities inherent to this association that should be considered when promoting regionalized care models. We herein provide a critical review of the literature on the volume-outcome association and a discussion of areas of ongoing controversy.

Methods: A PubMed literature search was conducted for the years 1995-2020. Peer reviewed original research studies were selected for critical review based on study design, potential to draw meaningful conclusions from the data, and discussion of current knowledge gaps.

Results: Based on the cumulative published literature, hospital/surgeon volume and patient mortality are inversely related. However, it remains unclear whether volume is a proxy for other more causative variables inherent in high-volume centers. Interpretation of the volume-outcome association is made more difficult to interpret due to the large variation in the definition of high volume, difficulty in isolating the individual impact of surgeon versus hospital volume, challenges in quantifying health system processes related to volume, and the fact that some low-volume centers consistently achieve excellent clinical results. Implementation of true regionalized care models has been rare, likely reflecting both health system and patient level challenges.

Conclusion: The volume-outcome association has been consistently demonstrated to be important to the care of patients with pancreas cancer. The underlying mechanism of this association to explain the overall benefit is likely multifactorial. Better understanding of what drives the volume-outcome association may increase access to optimized care for a broader range of hospital systems and patients.
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http://dx.doi.org/10.1245/s10434-021-10765-wDOI Listing
September 2021

MG53 suppresses tumor progression and stress granule formation by modulating G3BP2 activity in non-small cell lung cancer.

Mol Cancer 2021 09 14;20(1):118. Epub 2021 Sep 14.

Department of Surgery, The Ohio State University College of Medicine, Columbus, OH, 43210, USA.

Background: Cancer cells develop resistance to chemotherapeutic intervention by excessive formation of stress granules (SGs), which are modulated by an oncogenic protein G3BP2. Selective control of G3BP2/SG signaling is a potential means to treat non-small cell lung cancer (NSCLC).

Methods: Co-immunoprecipitation was conducted to identify the interaction of MG53 and G3BP2. Immunohistochemistry and live cell imaging were performed to visualize the subcellular expression or co-localization. We used shRNA to knock-down the expression MG53 or G3BP2 to test the cell migration and colony formation. The expression level of MG53 and G3BP2 in human NSCLC tissues was tested by western blot analysis. The ATO-induced oxidative stress model was used to examine the effect of rhMG53 on SG formation. Moue NSCLC allograft experiments were performed on wild type and transgenic mice with either knockout of MG53, or overexpression of MG53. Human NSCLC xenograft model in mice was used to evaluate the effect of MG53 overexpression on tumorigenesis.

Results: We show that MG53, a member of the TRIM protein family (TRIM72), modulates G3BP2 activity to control lung cancer progression. Loss of MG53 results in the progressive development of lung cancer in mg53 mice. Transgenic mice with sustained elevation of MG53 in the bloodstream demonstrate reduced tumor growth following allograft transplantation of mouse NSCLC cells. Biochemical assay reveals physical interaction between G3BP2 and MG53 through the TRIM domain of MG53. Knockdown of MG53 enhances proliferation and migration of NSCLC cells, whereas reduced tumorigenicity is seen in NSCLC cells with knockdown of G3BP2 expression. The recombinant human MG53 (rhMG53) protein can enter the NSCLC cells to induce nuclear translation of G3BP2 and block arsenic trioxide-induced SG formation. The anti-proliferative effect of rhMG53 on NSCLC cells was abolished with knockout of G3BP2. rhMG53 can enhance sensitivity of NSCLC cells to undergo cell death upon treatment with cisplatin. Tailored induction of MG53 expression in NSCLC cells suppresses lung cancer growth via reduced SG formation in a xenograft model.

Conclusion: Overall, these findings support the notion that MG53 functions as a tumor suppressor by targeting G3BP2/SG activity in NSCLCs.
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http://dx.doi.org/10.1186/s12943-021-01418-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439062PMC
September 2021

Pancreatic Cancer.

Authors:
Timothy M Pawlik

Surg Oncol Clin N Am 2021 Oct;30(4):xiii-xv

Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Departments of Surgery, Oncology, and Health Services Management and Policy, The Ohio State University Wexner Medical Center, 395 West 12th Avenue, Suite 670, Columbus, OH 43210, USA. Electronic address:

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http://dx.doi.org/10.1016/j.soc.2021.07.002DOI Listing
October 2021

Trends in Textbook Outcomes over Time: Are Optimal Outcomes Following Complex Gastrointestinal Surgery for Cancer Increasing?

J Gastrointest Surg 2021 Sep 10. Epub 2021 Sep 10.

Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center and Solove Research Institute, 395 W. 12th Ave., Suite 670, Columbus, OH, USA.

Background: The use of composite measures like "textbook outcome" (TO) may provide a more accurate measure of surgical quality. We sought to determine if TO has improved over time and to characterize the association of achieving a TO with trends in survival among patients undergoing complex gastrointestinal surgery for cancer.

Methods: Medicare beneficiaries who underwent pancreas, liver, or colon resection for a cancer diagnosis between 2004 and 2016 were identified using the SEER-Medicare database. Rates of TO (no complication, extended length of stay, 90-day readmission, or 90-day mortality) were assessed over time.

Results: Among 94,329 patients, 6765 (7.2%), 1985 (2.1%), and 85,579 (90.7%) patients underwent resection for primary pancreatic, hepatic, or colon cancer, respectively. In total, 53,464 (56.7%) patients achieved a TO; achievement of TO varied by procedure (pancreatectomy: 48.1% vs. hepatectomy: 55.2% vs. colectomy: 57.4%, p < 0.001). The proportion of patients achieving a textbook outcome increased over time for all patients (2004-2007, 53.3% vs. 2008-2011, 56.5% vs. 2012-2016, 60.1%) (5-year increase: OR 1.16 95%CI 1.13-1.18) (p < 0.001). Survival at 1-year following pancreatic, liver, or colon resection for cancer had improved over time among both patients who did and did not achieve a postoperative TO. TO was independently associated with a marked reduction in hazard of death (HR 0.44, 95%CI 0.43-0.45). The association of TO and survival was consistent among patients stratified by procedure.

Conclusion: Less than two-thirds of patients undergoing complex gastrointestinal surgery for a malignant indication achieved a TO. The likelihood of achieving a TO increased over time and was associated with improved survival.
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http://dx.doi.org/10.1007/s11605-021-05129-4DOI Listing
September 2021

Dream big, think little: the impact of the AHPBA.

Authors:
Timothy M Pawlik

HPB (Oxford) 2021 Aug 17. Epub 2021 Aug 17.

Chair Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research Professor of Surgery, Oncology, Health Services Management and Policy, Surgeon-in-Chief, The Ohio State University, Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA. Electronic address:

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http://dx.doi.org/10.1016/j.hpb.2021.08.815DOI Listing
August 2021

Inspirational Women in Surgery: Olga Jonasson, the Legacy of the First Female Chair of an Academic Department of Surgery.

World J Surg 2021 Sep 2. Epub 2021 Sep 2.

Department of Surgery, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, 395 W. 12th Ave., Suite 654, Columbus, OH, USA.

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http://dx.doi.org/10.1007/s00268-021-06302-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410170PMC
September 2021

The State of Immunotherapy in Hepatobiliary Cancers.

Cells 2021 Aug 15;10(8). Epub 2021 Aug 15.

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

Hepatobiliary cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder carcinoma (GBC), are lethal cancers with limited therapeutic options. Curative-intent treatment typically involves surgery, yet recurrence is common and many patients present with advanced disease not amenable to an operation. Immunotherapy represents a promising approach to improve outcomes, but the immunosuppressive tumor microenvironment of the liver characteristic of hepatobiliary cancers has hampered the development and implementation of this therapeutic approach. Current immunotherapies under investigation include immune checkpoint inhibitors (ICI), the adoptive transfer of immune cells, bispecific antibodies, vaccines, and oncolytic viruses. Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two ICIs that have demonstrated utility in HCC, and newer immune checkpoint targets are being tested in clinical trials. In advanced CCA and GBC, PD-1 ICIs have resulted in antitumor responses, but only in a minority of select patients. Other ICIs are being investigated for patients with CCA and GBC. Adoptive transfer may hold promise, with reports of complete durable regression in metastatic CCA, yet this therapeutic approach may not be generalizable. Alternative approaches have been developed and promising results have been observed, but clinical trials are needed to validate their utility. While the treatment of hepatobiliary cancers involves unique challenges that these cancers present, the progress seen with ICIs and adoptive transfer has solidified immunotherapy as an important approach in these challenging patients with few other effective treatment options.
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http://dx.doi.org/10.3390/cells10082096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393650PMC
August 2021

Trends in the use of adjuvant therapy for resected intrahepatic cholangiocarcinoma: getting ahead of the data.

Hepatobiliary Surg Nutr 2021 Aug;10(4):515-517

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

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http://dx.doi.org/10.21037/hbsn-2021-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351004PMC
August 2021

Geographic Disparities in Oncologic Treatment and Outcomes: The Urban-Rural Divide.

Ann Surg Oncol 2021 Aug 22. Epub 2021 Aug 22.

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

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http://dx.doi.org/10.1245/s10434-021-10653-3DOI Listing
August 2021

Assessment of Textbook Outcome After Surgery for Stage I/II Non-small Cell Lung Cancer.

Semin Thorac Cardiovasc Surg 2021 Aug 16. Epub 2021 Aug 16.

Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Maywood, Illinois.

``Outcomes after cancer resection are traditionally measured individually. Composite metrics, or textbook outcomes, bundle outcomes into a single value to facilitate assessments of quality. We propose a composite outcome for non-small cell lung cancer resections, examine factors associated with the outcome, and evaluate its effect on overall survival. We queried the National Cancer Database for patients with stage I/II non-small cell lung cancer who underwent sublobar resection, lobectomy, or pneumonectomy from 2010 to 2016. We defined the metric as margin-negative resection, sampling of ≥10 lymph nodes, length of stay <75th percentile, no 30-day mortality, no readmission, and receipt of indicated adjuvant therapy. Multivariable logistic regression, Cox proportional hazards modeling, survival analyses, and propensity score matching were used to identify factors associated with the outcome and overall survival. Of 88,208 patients, 70,149 underwent lobectomy, 14,922 underwent sublobar resection, and 3,137 underwent pneumonectomy. Textbook outcome was achieved in 26.3% of patients. Failure to achieve the outcome was most commonly driven by inadequate nodal assessment. Textbook outcome was more likely after minimally invasive surgical approaches (aOR = 1.47; P< 0.001) relative to open resection and less likely after sublobar resection (aOR = 0.20; P< 0.001) relative to lobectomy. Achievement of textbook outcome was associated with an 9.6% increase in 5-year survival (P< 0.001), was independently associated with improved survival (aHR = 0.72; P < 0.001), and remained strongly associated with survival independent of resection extent after propensity matching. One in 4 patients undergoing non-small cell lung cancer resection achieve textbook outcome. Textbook outcome is associated with improved survival and has value as a quality metric.
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http://dx.doi.org/10.1053/j.semtcvs.2021.08.009DOI Listing
August 2021

ASO Author Reflections: Postoperative Infectious Complications Worsen Long-Term Survival After Curative-Intent Resection for Hepatocellular Carcinoma.

Ann Surg Oncol 2021 Aug 18. Epub 2021 Aug 18.

Department of Surgery, 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.

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http://dx.doi.org/10.1245/s10434-021-10632-8DOI Listing
August 2021

Preoperative Estimated Risk of Microvascular Invasion is Associated with Prognostic Differences Following Liver Resection Versus Radiofrequency Ablation for Early Hepatitis B Virus-Related Hepatocellular Carcinoma.

Ann Surg Oncol 2021 Aug 18. Epub 2021 Aug 18.

Department of Hepatic Surgery IV, the Eastern Hepatobiliary Surgery Hospital and National Center for Liver Cancer, Second Military Medical University, Shanghai, China.

Objectives: The aim of this study was to examine prognostic differences between liver resection (LR) and percutaneous radiofrequency ablation (PRFA) for hepatocellular carcinoma (HCC) based on preoperative predicted microvascular invasion (MVI) risk.

Methods: Data on consecutive patients who underwent LR (n = 1344) or PRFA (n = 853) for hepatitis B virus-related HCC within the Milan criteria (MC) were analyzed. A preoperative nomogram was used to estimate MVI risk. Overall survival (OS), time to recurrence, and patterns of recurrence were compared using propensity score matching.

Results: The concordance indices of the nomogram to predict MVI were 0.813 and 0.781 among LR patients with HCC within the MC or ≤ 3 cm, respectively. LR and PRFA resulted in similar 5-year recurrence and OS for patients with nomogram-predicted low-risk of MVI. LR provided better 5-year recurrence and OS versus PRFA for patients with high-risk of MVI (71.6% vs. 80.7%, p = 0.013; 47.9% vs. 34.0%, p = 0.002, for HCC within the MC; 62.3% vs. 78.8%, p = 0.020; 63.6% vs. 38.3%, p = 0.015, for HCC ≤ 3 cm). Among high-risk patients, LR was associated with lower recurrence and improved OS compared with PRFA, on multivariate analysis [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.63-0.97, and HR 0.68, 95% CI 0.52-0.88, for HCC within the MC; HR 0.51, 95% CI 0.32-0.81, and HR 0.47, 95% CI 0.26-0.84, for HCC ≤ 3 cm], and resulted in less early and local recurrence than PRFA (42.4% vs. 54.8%, p = 0.007, and 31.2% vs. 46.1%, p = 0.007, for HCC within the MC; 27.9% vs. 50.8%, p = 0.016, and 15.6% vs. 39.5%, p = 0.046, for HCC ≤ 3 cm).

Conclusions: LR was oncologically superior over PRFA for early HCC patients with predicted high-risk of MVI. LR was associated with better local disease control than PRFA in these patients.
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http://dx.doi.org/10.1245/s10434-021-09901-3DOI Listing
August 2021

Cancer Care in the Incarcerated Population: Barriers to Quality Care and Opportunities for Improvement.

JAMA Surg 2021 Aug 18. Epub 2021 Aug 18.

Division of Surgical Oncology, Department of Surgery, Ohio State University Wexner Medical Center, Columbus.

Importance: Cancer is the leading cause of mortality in incarcerated individuals older than 45 years and the fourth leading cause of mortality overall. Health care professionals face increasing challenges to provide high-quality care under the confines of prison regulations and procedures.

Observations: Adjusted for age, race, sex, and year of diagnosis, the standardized incidence ratio for all cancers is more than 2-fold higher in incarcerated vs general populations. Among deaths occurring in state and federal prison systems, cancer is the overall leading cause of mortality with lung cancer being the leading cause of cancer-related mortality followed by liver, colon, and pancreatic cancers, respectively. Access to high-quality oncological services remains variable; however, cost of care represents about a fifth of overall annual prison expenditures. Given the enormous patient burden, coupled with the rushed discretionary screenings performed by jail and prison nursing staff, early cancer symptoms are often missed altogether or misdiagnosed as a chronic illness or as acute infections. As such, many incarcerated individuals present with more advanced cancer stage. Incarcerated individuals have limited, if any, access to the internet, social media, and other sources of information, which severely limits their ability to research treatment options. Within the prison setting, access to professionals with special skills in assisting with social and spiritual concerns is also generally limited, and less than 4% of prisons have hospice programs. There are no uniform quality-of-care monitoring standards for correctional systems and facilities, nor are there mechanisms for reporting comparable performance data to enforce quality control within correctional health care systems.

Conclusions And Relevance: There is a growing trend in cancer incidence among incarcerated patients, which is multifactorial including barriers in access to care, increased burden of chronic medical conditions, and decreased screening tests. Efforts are needed to ensure quality health care outcomes for incarcerated patients with cancer.
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http://dx.doi.org/10.1001/jamasurg.2021.3754DOI Listing
August 2021

State-of-the-art surgery for hepatocellular carcinoma.

Langenbecks Arch Surg 2021 Aug 18. Epub 2021 Aug 18.

Department of Surgery, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA.

Background: Hepatocellular carcinoma (HCC) is the most commonly diagnosed primary liver tumor with an increasing incidence worldwide. Management of patients with HCC is largely dictated by the presence of cirrhosis, disease stage, underlying liver function, and patient performance status.

Purpose: We provide an update on key aspects of surgical treatment options for patients with HCC. RESULTS & CONCLUSIONS: Liver resection and transplantation remain cornerstone treatment options for patients with early-stage disease and constitute the only potentially curative options for HCC. Selection of patients for surgical treatment should include a thorough evaluation of tumor characteristics and biology, as well as evidence-based use of various available treatment options to achieve optimal long-term outcomes for patients with HCC.
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http://dx.doi.org/10.1007/s00423-021-02298-3DOI Listing
August 2021

Patient Social Vulnerability and Hospital Community Racial/Ethnic Integration: Do All Patients Undergoing Pancreatectomy Receive the Same Care Across Hospitals?

Ann Surg 2021 09;274(3):508-515

Department of Surgery, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio.

Objective: The objective of the current study was to characterize the role of patient social vulnerability relative to hospital racial/ethnic integration on postoperative outcomes among patients undergoing pancreatectomy.

Background: The interplay between patient- and community-level factors on outcomes after complex surgery has not been well-examined.

Methods: Medicare beneficiaries who underwent a pancreatectomy between 2013 and 2017 were identified utilizing 100% Medicare inpatient files. P-SVI was determined using the Centers for Disease Control and Prevention criteria, whereas H-REI was estimated using Shannon Diversity Index. Impact of P-SVI and H-REI on "TO" [ie, no surgical complication/extended length-of-stay (LOS)/90-day mortality/90-day readmission] was assessed.

Results: Among 24,500 beneficiaries who underwent pancreatectomy, 12,890 (52.6%) were male and median age was 72 years (Interquartile range: 68-77); 10,619 (43.3%) patients achieved a TO. The most common adverse postoperative outcome was 90-day readmission (n = 8,066, 32.9%), whereas the least common was 90-day mortality (n = 2282, 9.3%). Complications and extended LOS occurred in 30.4% (n = 7450) and 23.3% (n = 5699) of the cohort, respectively. Patients from an above average SVI county who underwent surgery at a below average REI hospital had 18% lower odds [95% confidence interval (CI): 0.74-0.95] of achieving a TO compared with patients from a below average SVI county who underwent surgery at a hospital with above average REI. Of note, patients from the highest SVI areas who underwent pancreatectomy at hospitals with the lowest REI had 30% lower odds (95% CI: 0.54-0.91) of achieving a TO compared with patients from very low SVI areas who underwent surgery at a hospital with high REI. Further comparisons of these 2 patient groups indicated 76% increased odds of 90-day mortality (95% CI: 1.10-2.82) and 50% increased odds of an extended LOS (95% CI: 1.07-2.11).

Conclusion: Patients with high social vulnerability who underwent pancreatectomy in hospitals located in communities with low racial/ethnic integration had the lowest chance to achieve an "optimal" TO. A focus on both patient- and community-level factors is needed to ensure optimal and equitable patient outcomes.
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http://dx.doi.org/10.1097/SLA.0000000000004989DOI Listing
September 2021

Long-Term Surgical Outcomes of Liver Resection for Hepatocellular Carcinoma in Patients With HBV and HCV Co-Infection: .

Front Oncol 2021 29;11:700228. Epub 2021 Jul 29.

Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, China.

Background: Hepatocellular carcinoma (HCC) is one of the most serious consequences of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study sought to investigate long-term outcomes after liver resection for HCC among patients with HBV/HCV co-infection (HBV/HCV-HCC) compared with patients with HBV infection (HBV-HCC).

Methods: Patients who underwent curative-intent liver resection for HCC were identified from a multicenter Chinese database. Using propensity score matching (PSM), patients with HBV/HCV-HCC were matched one-to-one to patients with HBV-HCC. Overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups before and after PSM.

Results: Among 2,467 patients identified, 93 (3.8%) and 2,374 (96.2%) patients had HBV/HCV-HCC and HBV-HCC, respectively. Compared with patients with HBV-HCC, patients with HBV/HCV-HCC were older, have poorer liver-related characteristics but better tumor-related characteristics. PSM created 88 pairs of patients with comparable liver- and tumor-related characteristics (all > 0.2). In the PSM cohort, the 3- and 5-year RFS rates in patients with HBV/HCV-HCC were 48.3% and 38.9%, which were significantly poorer than patients with HBV-HCC (61.8% and 49.2%, = 0.037). Meanwhile, the 3- and 5-year OS rates in patients with HBV/HCV-HCC were also poorer than patients with HBV-HCC (65.4% and 51.1% 73.7% and 63.0%), with a difference close to be significant between them ( = 0.081).

Conclusion: Comparing to patients with HBV-HCC, liver resection resulted in relatively poorer long-term surgical outcomes in patients with HBV/HCV-HCC.
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http://dx.doi.org/10.3389/fonc.2021.700228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358778PMC
July 2021

Is Textbook Oncologic Outcome a Valid Hospital-Quality Metric after High-Risk Surgical Oncology Procedures?

Ann Surg Oncol 2021 Aug 15. Epub 2021 Aug 15.

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

Background: "Textbook oncologic outcome" (TOO) is a composite quality measure representing the "ideal" outcome for patients undergoing cancer surgery. This study sought to assess the validity of TOO as a metric to evaluate hospital quality.

Methods: Patients who underwent curative-intent resection of gastric, pancreatic, colon, rectal, lung, esophageal, bladder, or ovarian cancer were identified in the National Cancer Database (2006-2017). Cancer site-specific TOO was defined as adequate lymph node yield, R0 resection, non-length-of-stay outlier, no hospital readmission, and receipt of guideline-concordant chemotherapy and/or radiation. Mixed-effects analyses estimated the adjusted TOO rate for each hospital stratified by cancer site. The association between hospital adjusted TOO rates and 5-year overall survival was assessed using mixed-effects Cox proportional hazards analyses.

Results: Among 852,988 cancer resections, the TOO rate varied across cancer sites as follows: stomach (31.8%), pancreas (25%), colon (66.9%), rectum (33.6%), lung (35.1%), esophagus (31.2%), bladder (43%), and ovary (44.7%). After characterization of adjusted hospital TOO rates into quintiles, an incremental improvement in overall survival was observed, with higher adjusted TOO rates. Similarly, with the adjusted hospital TOO rate treated as a continuous variable, there was a significant 4% to 12% improvement in overall survival for every 10% increase in the adjusted hospital TOO rate for gastric (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.85-0.91), pancreatic (HR, 0.90; 95% CI, 0.88-0.93), colon (0.93; 95% CI, 0.91-0.94), rectal (HR, 0.90; 95% CI, 0.87-0.93), lung (HR, 0.96; 95% CI, 0.95-0.97), esophageal (HR, 0.93; 95% CI, 0.90-0.95), bladder (HR, 0.94; 95% CI, 0.91-0.97), and ovarian (HR, 0.96; 95% CI, 0.94-0.98) cancer.

Conclusions: A direct association exists between adjusted hospital TOO rates and survival after high-risk cancer procedures. As a valid hospital metric, TOO can be used to compare the overall quality of cancer care across hospitals.
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http://dx.doi.org/10.1245/s10434-021-10478-0DOI Listing
August 2021

ASO Visual Abstract: Is Textbook Oncologic Outcome a Valid Hospital Quality Metric Following High-Risk Surgical Oncology Procedures?

Ann Surg Oncol 2021 Aug 12. Epub 2021 Aug 12.

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

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http://dx.doi.org/10.1245/s10434-021-10539-4DOI Listing
August 2021

Survival Benefit of Primary Tumor Resection Among Elderly Patients with Pancreatic Neuroendocrine Tumors.

World J Surg 2021 Aug 11. Epub 2021 Aug 11.

Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA.

Background: Pancreatectomy is the main curative therapeutic option for pancreatic neuroendocrine tumors (pNETs). Given the indolent behavior of pNETs and the relatively limited lifetime of elderly patients, the impact of primary site surgery (PSS) of pNETs on long-term outcomes among older patients has been a topic of debate.

Methods: Patients aged 70 or older with pNETs were identified in the Surveillance, Epidemiology and the End Results (SEER) database from 1998 to 2016. Propensity score matching was used to compare overall (OS) and cancer-specific survival (CSS) of patients who did versus did not undergo PSS.

Results: Among 2,319 elderly patients with pNETs, 942 patients (40.6%) underwent PSS, while 1,377 (59.4%) did not undergo PSS (non-PSS: NPSS). After propensity score matching (n = 433 in each group), PSS group had improved survival compared with the NPSS group (5-year OS: 53.4% vs. 37.3%; 5-year CSS: 77.2% vs. 58.1%, both p < 0.001). In contrast, subgroup analysis of individuals aged ≥ 80 revealed no difference in 5-year CSS (PSS: 69.2% vs. NPSS: 67.4%, p = 0.27). A subgroup analysis among patients who had small (≤ 2 cm) non-functional (NF) pNETs noted comparable long-term outcomes among patients who underwent PSS versus NPSS patients (5-year OS: 73.1% vs. 66.5%, p = 0.19; 5-year CSS: 98.5% vs. 95.2%, p = 0.14).

Conclusions: Approximately 2 in 5 elderly patients with pNETs underwent PSS. While PSS was generally associated with prolonged OS and CSS among older patients, PSS was not associated with improved CSS among a subset of patients aged 80 or older, as well as among patients age ≥ 70 years with NF-pNET less than 2 cm.
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http://dx.doi.org/10.1007/s00268-021-06281-3DOI Listing
August 2021

Postoperative Infectious Complications Worsen Long-Term Survival After Curative-Intent Resection for Hepatocellular Carcinoma.

Ann Surg Oncol 2021 Aug 10. Epub 2021 Aug 10.

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

Background: Postoperative infectious complications may be associated with a worse long-term prognosis for patients undergoing surgery for a malignant indication. The current study aimed to characterize the impact of postoperative infectious complications on long-term oncologic outcomes among patients undergoing resection for hepatocellular carcinoma (HCC).

Methods: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The relationship between postoperative infectious complications, overall survival (OS), and recurrence-free survival (RFS) was analyzed.

Results: Among 734 patients who underwent HCC resection, 269 (36.6%) experienced a postoperative complication (Clavien-Dindo grade 1 or 2 [n = 197, 73.2%] vs grade 3 and 4 [n = 69, 25.7%]). An infectious complication was noted in 81 patients (11.0%) and 188 patients (25.6%) had non-infectious complications. The patients with infectious complications had worse OS (median: infectious complications [46.5 months] vs no complications [106.4 months] [p < 0.001] and non-infectious complications [85.7 months] [p < 0.05]) and RFS (median: infectious complications [22.1 months] vs no complications [45.5 months] [p < 0.05] and non-infectious complications [38.3 months] [p = 0.139]) than the patients who had no complication or non-infectious complications. In the multivariable analysis, infectious complications remained an independent risk factor for OS (hazard ratio [HR], 1.7; p = 0.016) and RFS (HR, 1.6; p = 0.013). Among the patients with infectious complications, patients with non-surgical-site infection (SSI) had even worse OS and RFS than patients with SSI (median OS: 19.5 vs 70.9 months [p = 0.010]; median RFS: 12.8 vs 33.9 months [p = 0.033]).

Conclusion: Infectious complications were independently associated with an increased long-term risk of tumor recurrence and death. Patients with non-SSI versus SSI had a particularly worse oncologic outcome.
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http://dx.doi.org/10.1245/s10434-021-10565-2DOI Listing
August 2021

A contemporary reassessment of the US surgical workforce through 2050 predicts continued shortages and increased productivity demands.

Am J Surg 2021 Jul 24. Epub 2021 Jul 24.

Ohio State University Wexner Medical Center, Department of Surgery, Columbus, OH, USA; Center for Surgical Health Assessment, Research and Policy (SHARP), Ohio State Wexner Medical Center, Columbus, OH, USA. Electronic address:

Background: We aimed to predict practicing surgeon workforce size across ten specialties to provide an up-to-date, national perspective on future surgical workforce shortages or surpluses.

Methods: Twenty-one years of AMA Masterfile data (1997-2017) were used to predict surgeons practicing from 2030 to 2050. Published ratios of surgeons/100,000 population were used to estimate the number of surgeons needed. MGMA median wRVU/surgeon by specialty (2017) was used to determine wRVU demand and capacity based on projected and needed number of surgeons.

Results: By 2030, surgeon shortages across nine specialties: Cardiothoracic, Otolaryngology, General Surgery, Obstetrics-Gynecology, Ophthalmology, Orthopedics, Plastics, Urology, and Vascular, are estimated to increase clinical workload by 10-50% additional wRVU. By 2050, shortages in eight specialties are estimated to increase clinical workload by 7-61% additional wRVU.

Conclusions: If historical trends continue, a majority of surgical specialties are estimated to experience workforce deficits, increasing clinical demands substantially.
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http://dx.doi.org/10.1016/j.amjsurg.2021.07.033DOI Listing
July 2021

Timing and Severity of Postoperative Complications and Associated 30-Day Mortality Following Hepatic Resection: a National Surgical Quality Improvement Project Study.

J Gastrointest Surg 2021 Aug 6. Epub 2021 Aug 6.

Department of Surgery, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA.

Background: The effect of varying severity and timing of complications after hepatic resection on 30-day mortality has not been thoroughly examined.

Methods: National Surgical Quality Improvement Program Patient User Files (NSQIP-PUF) were used to identify patients who underwent elective hepatic resection between 2014 and 2019. The impact of number, timing, and severity of complications on 30-day mortality was examined.

Results: Among 25,084 patients who underwent hepatic resection, 7436 (29.9%) patients developed at least one NSQIP complication, while 2688 (10.7%) had multiple (≥2) complications. Overall, 30-day mortality was 1.7% (n=424), among whom 81.4% (n=345) patients had ≥2 complications. The 30-day mortality was highest among patients with three consecutive severe complications (47.8%), as well as patients with one non-severe and two subsequent severe complications (47.6%). The adjusted probability of 30-day mortality was 35.5% (95%CI: 29.5-41.4%) when multiple severe complications occurred within the first postoperative week and 16.2% (95%CI: 7.2-25.1%) when the second severe complication occurred at least one week apart. The adjusted risk of 30-day mortality after even two non-severe complications was as high as 5.3% (95%CI: 3.7-6.9%) when the second complication occurred within a week postoperatively.

Conclusion: Approximately 1 in 10 patients developed multiple complications following hepatectomy. Timing and severity of complications were independently associated with 30-day mortality.
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http://dx.doi.org/10.1007/s11605-021-05088-wDOI Listing
August 2021

Impact of Tumor Burden Score on Conditional Survival after Curative-Intent Resection for Hepatocellular Carcinoma: A Multi-Institutional Analysis.

World J Surg 2021 Aug 2. Epub 2021 Aug 2.

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

Background: The impact of tumor burden score (TBS) on conditional survival (CS) among patients undergoing curative-intent resection of hepatocellular carcinoma (HCC) has not been examined to date.

Methods: Patients who underwent liver resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS and other clinicopathologic factors on 3-year conditional survival (CS) was examined.

Results: Among 1,040 patients, 263 (25.3%) patients had low TBS, 668 (64.2%) had medium TBS and 109 (10.5%) had high TBS. TBS was strongly associated with OS; 5-year OS was 39.0% among patients with high TBS compared with 61.1% and 79.4% among patients with medium and low TBS, respectively (p < 0.001). While actuarial survival decreased as time elapsed from resection, CS increased over time irrespective of TBS. The largest differences between 3-year actuarial survival and CS were noted among patients with high TBS (5-years postoperatively; CS: 78.7% vs. 3-year actuarial survival: 30.7%). The effect of adverse clinicopathologic factors including high TBS, poor/undifferentiated tumor grade, microvascular invasion, liver capsule involvement, and positive margins on prognosis decreased over time.

Conclusions: CS rates among patients who underwent resection for HCC increased as patients survived additional years, irrespective of TBS. CS estimates can be used to provide important dynamic information relative to the changing survival probability after resection of HCC.
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http://dx.doi.org/10.1007/s00268-021-06265-3DOI Listing
August 2021

A narrative review: has regionalization truly achieved its intended goal in the surgical management of pancreatic cancer?

Chin Clin Oncol 2021 Jul 30. Epub 2021 Jul 30.

Department of General Surgery, Division of Surgical Oncology, The Ohio State University College of Medicine, Columbus, OH, USA.

Objective: The purpose of this narrative review is to present the data to date on the volume-outcome association in pancreas cancer surgery and describe the prevalence of and barriers to regionalized pancreas cancer care in western health systems.

Background: Numerous studies have demonstrated an association between increasing hospital or surgeon volume and improved patient morbidity and mortality in patients undergoing surgery for pancreas cancer. However, since the initial promotion of minimum volume standards, regionalization has remained difficult to establish.

Methods: A PubMed literature search for years 1995-2020 was conducted to target original research on the volume-outcome association in pancreas cancer and the prevalence of associated regionalized care systems. Peer reviewed original research studies were selected based on their study design and potential to inform meaningful conclusions from the data.

Conclusions: Increasing hospital or surgeon volume is associated with improved short and long-term survival in pancreas cancer patients undergoing surgical resection. Despite the knowledge that increasing hospital and surgeon volume is associated with improved operative mortality and long term survival in pancreas cancer, the majority of patients undergo surgery at low volume hospitals with low volume surgeons. Barriers to regionalization are complex and involve the interaction of many conflicting factors and processes on human, health system, and national levels. Better understanding of the barriers to regionalization in pancreas cancer care is needed before this model of care becomes feasible.
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http://dx.doi.org/10.21037/cco-21-54DOI Listing
July 2021

Patient Perspectives on Defining Textbook Outcomes Following Major Abdominal Surgery.

J Gastrointest Surg 2021 Jul 29. Epub 2021 Jul 29.

Division of Surgical Oncology, James Cancer Center and Solove Research Institute, The Ohio State University Wexner Medical Center, OH, Columbus, USA.

Background: The composite metric textbook outcome (TO) has recently gained interest as a novel quality measure. However, the criteria for defining a TO have not been rigorously defined and patient perspectives on the characteristics of TO are unknown.

Methods: Patients who underwent major abdominal surgery at a single tertiary care center were administered a customized survey designed to ascertain their perspectives on defining TOs. The relationship between patient-reported and clinically defined TO rates was compared.

Results: Among 79 patients who underwent gastrointestinal (51%), pancreatic (29%), hepatic (18%), or other major abdominal (3%) operations, 57% were female and 86% had an ASA class ≥3. Most patients underwent surgery for malignancy (87%) with 60% undergoing an open operation. Patients most commonly valued no mortality following surgery (96%), no reoperation (75%), and having a margin negative resection (73%) as "extremely important." In contrast, those outcomes that were most commonly valued as "not important at all" or "minimally important" were receiving a blood transfusion (24%) and not having any complications (13%). Using previously published criteria for TOs, 47 (60%) patients were classified as having a clinically defined TO; in contrast, 68 patients (86%) self-reported their outcome was textbook. Self-reported responses were concordant with clinically defined TO criteria 63% of the time (McNemar's test: S=15.2, p<0.01, evidence of disagreement).

Conclusion: There was significant discordance between patient-reported versus clinically defined measures of TOs, suggesting patients value other considerations beyond traditional factors when evaluating the success of their surgery. Future studies should delineate these relationships and incorporate these factors to refine TO definitions.
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http://dx.doi.org/10.1007/s11605-021-05093-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321005PMC
July 2021

Optimal hepatic surgery: Are we making progress in North America?

Surgery 2021 Jul 26. Epub 2021 Jul 26.

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ.

Background: The aim of this analysis was to determine whether optimal outcomes have increased in recent years. Hepatic surgery is high risk, but regionalization and minimally invasive approaches have evolved. Best practices also have been defined with the goal of improving outcomes.

Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried. Analyses were performed separately for partial (≤2 segments), major (≥3 segments), and all hepatectomies. Optimal hepatic surgery was defined as the absence of mortality, serious morbidity, need for a postoperative invasive procedure or reoperation, prolonged length of stay (<75th percentile) or readmission. Tests of trend, χ, and multivariable analyses were performed.

Results: From 2014 to 2018, 17,082 hepatectomies, including 11,862 partial hepatectomies and 5,220 major hepatectomies, were analyzed. Minimally invasive approaches increased from 25.6% in 2014 to 29.6% in 2018 (P < .01) and were performed more frequently for partial hepatectomies (34.2%) than major hepatectomies (14.4%) (P < .01). Operative time decreased from 220 minutes in 2014 to 208 minutes in 2018 (P < .05) and was lower in partial hepatectomies (189 vs 258 minutes for major hepatectomies) (P < .01). Mortality (0.7%) and length of stay (4 days) were lower for partial hepatectomies compared with major hepatectomies (1.9%; 6 days), and length of stay decreased for both partial hepatectomies (5 days in 2014 to 4 days in 2018) and major hepatectomies (6 days in 2014 to 6 days in 2018) (all P < .01). Postoperative sepsis (2.9% in 2014 and 2.4% in 2018), bile leaks (6% in 2014 and 4.8% in 2018), and liver failure (3.7% in 2014 and 3.3% in 2018) decreased for all patients (<.05). On multivariable analyses, overall morbidity decreased for major hepatectomies (OR 0.95, 95% CI 0.91-0.99) and all hepatectomies (OR 0.97, 95% CI 0.94-0.99, both P < .01), and optimal hepatic surgery increased over time for partial hepatectomies (OR 1.05, 95% CI 1.02-1.09) and all hepatectomies (OR 1.04, 95% CI 1.02-1.07, both P < .01).

Conclusion: Over a 5-year period in North America, minimally invasive hepatectomies have increased, while operative time, postoperative sepsis, bile leaks, liver failure, and prolonged length of stay have decreased. Optimal hepatic surgery has increased for partial and all hepatectomies and is achieved more often in partial than in major resections.
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http://dx.doi.org/10.1016/j.surg.2021.06.028DOI Listing
July 2021

MG53 suppresses NF-κB activation to mitigate age-related heart failure.

JCI Insight 2021 Sep 8;6(17). Epub 2021 Sep 8.

Department of Surgery, Division of Cardiac Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Aging is associated with chronic oxidative stress and inflammation that affect tissue repair and regeneration capacity. MG53 is a TRIM family protein that facilitates repair of cell membrane injury in a redox-dependent manner. Here, we demonstrate that the expression of MG53 was reduced in failing human hearts and aged mouse hearts, concomitant with elevated NF-κB activation. We evaluated the safety and efficacy of longitudinal, systemic administration of recombinant human MG53 (rhMG53) protein in aged mice. Echocardiography and pressure-volume loop measurements revealed beneficial effects of rhMG53 treatment in improving heart function of aged mice. Biochemical and histological studies demonstrated that the cardioprotective effects of rhMG53 are linked to suppression of NF-κB-mediated inflammation, reducing apoptotic cell death and oxidative stress in the aged heart. Repetitive administration of rhMG53 in aged mice did not have adverse effects on major vital organ functions. These findings support the therapeutic value of rhMG53 in treating age-related decline in cardiac function.
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http://dx.doi.org/10.1172/jci.insight.148375DOI Listing
September 2021

Variation in outcomes across surgeons meeting the Leapfrog volume standard for complex oncologic surgery.

Cancer 2021 Jul 22. Epub 2021 Jul 22.

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

Background: A large body of evidence supports regionalization of complex oncologic surgery to high-volume surgeons at high-volume hospitals. However, whether there is heterogeneity of outcomes among high-volume surgeons at high-volume hospitals remains unknown.

Methods: Patients who underwent esophagectomy, lung resection, pancreatectomy, or proctectomy for primary cancer were identified within the Medicare 100% Standard Analytic File (2013-2017). Mixed-effects analyses assessed the association between Leapfrog annual volume standards for surgeons (esophagectomy ≥7, lung resection ≥15, pancreatectomy ≥10, proctectomy ≥6) and hospitals (esophagectomy ≥20, lung resection ≥40, pancreatectomy ≥20, proctectomy ≥16) relative to postoperative complications and 90-day mortality. Additional analyses using New York's all-payer Statewide Planning and Research Cooperative System (2004-2015) were performed.

Results: Among 112,154 Medicare beneficiaries, high-volume surgeons at high-volume hospitals were associated with lower adjusted odds of complications (esophagectomy: odds ratio [OR], 0.73 [95% CI, 0.61-0.86]; lung resection: OR, 0.88 [95% CI, 0.82-0.94]; pancreatectomy: OR, 0.73 [95% CI, 0.66-0.80]; proctectomy: OR, 0.92 [95% CI, 0.85-0.99]) and 90-day mortality (esophagectomy: OR, 0.60 [95% CI, 0.44-0.76]; lung resection: OR, 0.82 [95% CI, 0.73-0.93]; pancreatectomy: OR, 0.66 [95% CI, 0.56-0.76]; proctectomy: OR, 0.74 [95% CI, 0.65-0.85]). For the average patient at the average high-volume hospital, there was a 2-fold difference in the adjusted complication rate between the best-performing and worst-performing high-volume surgeon for all operations (esophagectomy, 28%-55%; lung resection, 7%-21%; pancreatectomy, 16%-35%; proctectomy, 16%-28%). Wide variation was also present in adjusted 90-day mortality for esophagectomy (3.5%-9.3%). Results from New York's all-payer database were similar.

Conclusions: Even among high-volume surgeons meeting the Leapfrog volume standards, wide variation in postoperative outcomes exists. These findings suggest that volume alone should not be used as a quality indicator, and quality metrics should be continuously evaluated across all surgeons and hospital systems.

Lay Summary: Previous studies have demonstrated a surgical volume-outcome relationship for high-risk operations-that is high-volume surgeons and hospitals that perform a specific surgical procedure more frequently have better outcomes for that operation. Although most high-volume surgeons had better outcomes, this study demonstrated that some high-volume surgeons did not have better outcomes. Therefore, volume is an important factor but should not be the only factor considered when assessing the quality of a surgeon and a hospital for cancer surgery.
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http://dx.doi.org/10.1002/cncr.33766DOI Listing
July 2021
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