Publications by authors named "Cecilia G Ethun"

90 Publications

Two-Stage Hepatectomy for Bilateral Colorectal Liver Metastases: A Multi-institutional Analysis.

Ann Surg Oncol 2021 Mar 3;28(3):1457-1465. Epub 2021 Jan 3.

Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.

Background: Two-stage hepatectomy (TSH) is an important tool in the management of bilateral colorectal liver metastases (CRLM). This study sought to examine the presentation, management, and outcomes of patients completing TSH in major hepatobiliary centers in the United States (US).

Methods: A retrospective review from five liver centers in the US identified patients who completed a TSH procedure for bilateral CRLM.

Results: From December 2000 to March 2016, a total of 196 patients were identified. The majority of procedures were performed using an open technique (n = 194, 99.5%). The median number of tumors was 7 (range 2-33). One-hundred and twenty-eight (65.3%) patients underwent portal vein embolization. More patients received chemotherapy prior to the first stage than chemotherapy administration preceding the second stage (92% vs. 60%, p = 0.308). Median overall survival (OS) was 50 months, with a median follow-up of 28 months (range 2-143). Hepatic artery infusion chemotherapy was administered to 64 (32.7%) patients with similar OS as those managed without an infusion pump (p = 0.848). Postoperative morbidity following the second-stage resection was 47.4%. Chemotherapy prior to the second stage did not demonstrate an increased complication rate (p = 0.202). Readmission following the second stage was 10.3% and was associated with a decrease in disease-free survival (p = 0.003). OS was significantly decreased by positive resection margins and increased estimated blood loss (EBL; p = 0.036 and p = 0.05, respectively).

Conclusion: This is the largest TSH series in the US and demonstrates evidence of safety and feasibility in the management of bilateral CRLM. Outcomes are influenced by margin status and operative EBL.
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http://dx.doi.org/10.1245/s10434-020-09459-6DOI Listing
March 2021

Impact of resection margin on outcomes in high-grade soft tissue sarcomas of the extremity-A USSC analysis.

J Surg Oncol 2021 Feb 4;123(2):479-488. Epub 2020 Nov 4.

Department of Surgery, Wake Forest University, Winston-Salem, North Carolina, USA.

Background: The optimal margin of resection for high-grade extremity sarcomas and its impact on survival has long been questioned in the setting of adjuvant radiotherapy. The objective of this study was to investigate the impact of resection status on recurrence and survival.

Methods: All patients with primary, nonmetastatic, high-grade extremity sarcomas that underwent surgical resection from January 2000 to April 2016 in the U.S. Sarcoma Collaborative (USSC) were retrospectively reviewed. Recurrence patterns, recurrence-free survival (RFS), and overall survival (OS) were examined in multivariate analyses (MVA).

Results: A cohort of 959 patients was identified with a median follow-up of 34.7 months from diagnosis. R0 resection was achieved in 86.7% (831) while R1 resection in 13.3% (128). Locoregional recurrence for R0 and R1 groups occurred in 9.1% (76) versus 14.8% (19; p = .05) while distant recurrence occurred in 24.7% (205) versus 26.6% (34; p = .65), respectively. Median RFS was 171.2 versus 48.5 (p = .01) while median OS was 149.8 versus 71.5 months (p = .02) for the R0 versus R1 group, respectively. On MVA, female gender (hazard ratio [HR] = 0.69, p = .007) and adjuvant radiotherapy (0.7, p = .04) were associated with improved OS, whereas older age (HR = 1.03, p < .001) and tumor size (HR = 1.01, p < .001) were associated with worse OS. R0 resection status was associated with improved locoregional RFS (HR = 0.56, p = .03) but not with distant RFS (HR = 0.84, p = .4) or OS (HR = 0.7, p = .052).

Conclusions: In high-grade extremity sarcomas, tumor size and gender are predictive of OS while R0 resection status is associated with improved locoregional recurrence rate without a significant impact on distant RFS or OS.
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http://dx.doi.org/10.1002/jso.26275DOI Listing
February 2021

Renal Function After Retroperitoneal Sarcoma Resection with Nephrectomy: A Matched Analysis of the United States Sarcoma Collaborative Database.

Ann Surg Oncol 2021 Mar 4;28(3):1690-1696. Epub 2020 Nov 4.

Department of Surgery, University of Wisconsin, Madison, WI, USA.

Background: Nephrectomy often is required during en bloc resection of a retroperitoneal sarcoma (RPS) to achieve an R0 or R1 resection. The impact of nephrectomy on postoperative renal function in this patient population, who also may benefit from subsequent nephrotoxic systemic therapy, is not well described.

Methods: The United States Sarcoma Collaborative (USSC) database was queried for patients undergoing RPS resection between 2000 and 2016. Patients with missing pre- or postoperative measures of renal function were excluded. A matched cohort was created using coarsened exact matching. Weighted logistic regression was used to control further for differences between the nephrectomy and non-nephrectomy cohorts. The primary outcomes were postoperative acute kidney injury (AKI), acute renal failure (ARF), and dialysis.

Results: The initial cohort consisted of 858 patients, 3 (0.3%) of whom required postoperative dialysis. The matched cohort consisted of 411 patients, 108 (26%) of whom underwent nephrectomy. The patients who underwent nephrectomy had higher rates of postoperative AKI (14.8% vs 4.3%; p < 0.01) and ARF (4.6% vs 1.3%; p = 0.04), but no patients required dialysis postoperatively. Logistic regression modeling showed that the risk of AKI (odds ratio [OR], 5.16; p < 0.01) and ARF (OR 5.04; p < 0.01) after nephrectomy persisted despite controlling for age and preoperative renal function.

Conclusions: Nephrectomy is associated with an increased risk of postoperative AKI and ARF after RPS resection. This study was unable to statistically assess the impact of nephrectomy on postoperative dialysis, but the risk of postoperative dialysis is 0.5% or less regardless of nephrectomy status.
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http://dx.doi.org/10.1245/s10434-020-09290-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897241PMC
March 2021

HSP90 expression and early recurrence in gastroenteropancreatic neuroendocrine tumors: Potential for a novel therapeutic target.

Surg Oncol 2020 Dec 7;35:460-465. Epub 2020 Oct 7.

Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA. Electronic address:

Background: Heat shock protein (HSP)-90 promotes tumor growth and is overexpressed in many malignancies. HSP90 expression profile and its potential as a therapeutic target in primary and metastatic neuroendocrine tumors (NETs) are not known.

Methods: HSP90 cytoplasmic expression and Ki-67 index were re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables for patients who underwent resection of primary and metastatic gastroenteropancreatic (GEP) neuroendocrine tumors at a single institution (2000-2013). Primary outcome was recurrence-free survival (RFS).

Results: Of 263 tumors reviewed, 73% (n = 191) were primary GEP NETs, and 12% (n = 31) were NET liver metastases. Of the primary GEP-NETs, mean age was 56 years, 42% were male; 53% (n = 103) were pancreatic and 23% (n = 44) were small bowel. HSP90 expression was high in 34% (n = 64) and low in 66% (n = 127). Compared to low expression, high HSP90 was associated with advanced T-stage (T3/T4) (47 vs 27%; p = 0.02). Among patients who underwent curative-intent resections for primary, non-metastatic NETs (n = 145), high HSP90 was independently associated with worse RFS (HR 5.09, 95% CI 1.65-15.74; p = 0.005), after accounting for positive margin, LN involvement, increased tumor size, site of primary tumor, and Ki-67. When assessing NET liver metastases, 13% (n = 4) had high HSP90 expression and 87% (n = 26) had low expression. Patients with liver metastases with high HSP90 tended to have worse 1- and 3-year progression-free survival (25%, 25%) compared to those with low HSP90 (69%, 49%; p = 0.059).

Conclusion: HSP90 exhibits differential expression in resected GEP-NETs and liver metastases. High cytoplasmic expression is associated with early disease recurrence, even after accounting for other adverse pathologic factors. HSP90 inhibition may be a potential therapeutic target for neuroendocrine tumors.
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http://dx.doi.org/10.1016/j.suronc.2020.09.018DOI Listing
December 2020

Outcomes in Patients with Renal Cell Carcinoma Undergoing Inferior Vena Cava Ligation without Reconstruction versus Thrombectomy: A Retrospective, Case Controlled Study.

J Urol 2021 02 9;205(2):383-391. Epub 2020 Sep 9.

Department of Urology, Emory University, Atlanta, Georgia.

Purpose: Radical nephrectomy with tumor thrombectomy is considered standard of care in patients with renal cell carcinoma. However, surgical ligation and interruption of the inferior vena cava is sometimes necessary when the tumor thrombus invades the inferior vena cava wall. This study assesses the outcomes in patients with renal cell carcinoma undergoing inferior vena cava ligation compared to inferior vena cava thrombectomy.

Materials And Methods: We conducted a case controlled, retrospective study at a high volume single-center institution. All patients with renal cell carcinoma who underwent ligation without reconstruction were matched with patients undergoing thrombectomy in a 1:2 ratio based on preoperative renal function, renal cell carcinoma stage and intraoperative thrombus level. Endpoints were complications, change in renal function and mortality.

Results: A total of 26 patients with renal cell carcinoma who underwent inferior vena cava ligation between 2005 and 2019 were matched with 52 patients who underwent inferior vena cava thrombectomy in the same time period. When compared to thrombectomy, patients undergoing ligation had higher 90-day readmission rate (19% vs 4%, p0.025). The ligation group also had a higher postoperative complication rate (73% vs 39%, p0.004) and higher rates of lymphedema (23% vs 8%, p0.055) However, by 1-month followup the rate of persistent overall and major complications for both ligation and thrombectomy groups were comparable at 49% vs 31% (p0.497) ad 8% vs 8% (p1.000), respectively. Importantly, at 18-month followup, mean estimated glomerular filtration rate declines were similar between ligation group (8.5 ml/min/1.73 m) and thrombectomy group (9.9 ml/min/1.73 m; p0.834). Differences in cancer-specific mortality (p0.993 and all-cause mortality (p0.756) were also not statistically significant.

Conclusions: The outcomes of inferior vena cava ligation compared to inferior vena cava thrombectomy for renal cell carcinoma are similar. Patients with inferior vena cava ligation initially face a more complicated postoperative course but in the longer term have similar renal function recovery, complication rates and survival.
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http://dx.doi.org/10.1097/JU.0000000000001354DOI Listing
February 2021

Defining and Predicting Early Recurrence after Resection for Gallbladder Cancer.

Ann Surg Oncol 2021 Jan 5;28(1):417-425. Epub 2020 Sep 5.

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

Background: The optimal time interval to define early recurrence (ER) among patients who underwent resection of gallbladder cancer (GBC) is not well defined. We sought to develop and validate a novel GBC recurrence risk (GBRR) score to predict ER among patients undergoing resection for GBC.

Patients And Methods: Patients who underwent curative-intent resection for GBC between 2000 and 2018 were identified from the US Extrahepatic Biliary Malignancy Consortium database. A minimum p value approach in the log-rank test was used to define the optimal cutoff for ER. A risk stratification model was developed to predict ER based on relevant clinicopathological factors and was externally validated.

Results: Among 309 patients, 103 patients (33.3%) had a recurrence at a median follow-up period of 15.1 months. The optimal cutoff for ER was defined at 12 months (p = 3.04 × 10). On multivariable analysis, T3/T4 disease (HR: 2.80; 95% CI 1.58-5.11) and poor tumor differentiation (HR: 1.91; 95% CI 1.11-3.25) were associated with greater hazards of ER. The GBRR score was developed using β-coefficients of variables in the final model, and patients were classified into three distinct groups relative to the risk for ER (12-month RFS; low risk: 88.4%, intermediate risk: 77.9%, high risk: 37.0%, p < 0.001). The external validation demonstrated good model generalizability with good calibration (n = 102: 12-month RFS; low risk: 94.2%, intermediate risk: 59.8%, high risk: 42.0%, p < 0.001). The GBRR score is available online at https://ktsahara.shinyapps.io/GBC_earlyrec/ .

Conclusions: A novel online calculator was developed to help clinicians predict the probability of ER after curative-intent resection for GBC. The proposed web-based tool may help in the optimization of surveillance intervals and the counselling of patients about their prognosis.
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http://dx.doi.org/10.1245/s10434-020-09108-yDOI Listing
January 2021

A closer look at the natural history and recurrence patterns of high-grade truncal/extremity leiomyosarcomas: A multi-institutional analysis from the US Sarcoma Collaborative.

Surg Oncol 2020 Sep 30;34:292-297. Epub 2020 Jun 30.

Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA. Electronic address:

Background/objective: Natural history and outcomes for truncal/extremity (TE) soft tissue sarcoma (STS) is derived primarily from studies investigating all histiotypes as one homogenous cohort. We aimed to define the recurrence rate (RR), recurrence patterns, and response to radiation of TE leiomyosarcomas (LMS).

Methods: Patients from the US Sarcoma Collaborative database with primary, high-grade TE STS were identified. Patients were grouped into LMS or other histology (non-LMS). Primary endpoints were locoregional recurrence-free survival (LR-RFS), distant-RFS (D-RFS), and disease specific survival (DSS).

Results: Of 1215 patients, 93 had LMS and 1122 non-LMS. In LMS patients, median age was 63 and median tumor size was 6 cm. In non-LMS patients, median age was 58 and median tumor size was 8 cm. In LMS patients, overall RR was 42% with 15% LR-RR and 29% D-RR. The 3yr LR-RFS, D-RFS, and DSS were 84%, 65%, and 76%, respectively. When considering high-risk (>5 cm and high-grade, n = 49) LMS patients, the overall RR was 45% with 12% LR-RR and 35% D-RR. 61% received radiation. The 3yr LR-RFS (78vs93%, p = 0.39), D-RFS (53vs63%, p = 0.27), and DSS (67vs91%, p = 0.17) were similar in those who did and did not receive radiation. High-risk, non-LMS patients had a similar overall RR of 42% with 15% LR-RR and 30% D-RR. 60% of non-LMS patients received radiation. There was an improved 3yr LR-RFS (82vs75%, p = 0.030) and DSS (77vs65%,p = 0.007) in non-LMS patients who received radiation.

Conclusions: In our cohort, patients with LMS have a low local recurrence rate (12-15%) and modest distant recurrence rate (29-35%). However, LMS patients had no improvement in local control or long-term outcomes with radiation. The value of radiation in these patients merits further investigation.
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http://dx.doi.org/10.1016/j.suronc.2020.06.003DOI Listing
September 2020

High neutrophil-lymphocyte ratio is not independently associated with worse survival or recurrence in patients with extremity soft tissue sarcoma.

Surgery 2020 10 28;168(4):760-767. Epub 2020 Jul 28.

Department of Surgery, Medical College of Wisconsin, Milwaukee, WI. Electronic address:

Background: Soft tissue sarcomas are a heterogenous group of neoplasms without well-validated biomarkers. Cancer-related inflammation is a known driver of tumor growth and progression. Recent studies have implicated a high circulating neutrophil-lymphocyte ratio as a surrogate marker for the inflammatory tumor microenvironment and a poor prognosticator in multiple solid tumors, including colorectal and pancreatic cancers. The impact of circulating neutrophil-lymphocyte ratio in soft tissue sarcomas has yet to be elucidated.

Methods: We performed a retrospective analysis of patients undergoing curative resection for primary or recurrent extremity soft tissue sarcomas at academic centers within the US Sarcoma Collaborative. Neutrophil-lymphocyte ratio was calculated retrospectively in treatment-naïve patients using blood counts at or near diagnosis.

Results: A high neutrophil-lymphocyte ratio (≥4.5) was associated with worse survival on univariable analysis in patients with extremity soft tissue sarcomas (hazard ratio 2.07; 95% confidence interval, 1.54-2.8; P < .001). On multivariable analysis, increasing age (hazard ratio 1.03; 95% confidence interval, 1.02-1.04; P < .001), American Joint Committee on Cancer T3 (hazard ratio 1.89; 95% confidence interval, 1.16-3.09; P = .011), American Joint Committee on Cancer T4 (hazard ratio 2.36; 95% confidence interval, 1.42-3.92; P = .001), high tumor grade (hazard ratio 4.56; 95% confidence interval, 2.2-9.45; P < .001), and radiotherapy (hazard ratio 0.58; 95% confidence interval, 0.41-0.82; P = .002) were independently predictive of overall survival, but a high neutrophil-lymphocyte ratio was not predictive of survival (hazard ratio 1.26; 95% confidence interval, 0.87-1.82; P = .22).

Conclusion: Tumor inflammation as measured by high pretreatment neutrophil-lymphocyte ratio was not independently associated with overall survival in patients undergoing resection for extremity soft tissue sarcomas.
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http://dx.doi.org/10.1016/j.surg.2020.06.017DOI Listing
October 2020

Analysis of textbook outcomes among patients undergoing resection of retroperitoneal sarcoma: A multi-institutional analysis of the US Sarcoma Collaborative.

J Surg Oncol 2020 Nov 21;122(6):1189-1198. Epub 2020 Jul 21.

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

Background: The novel composite metric textbook outcome (TO) has increasingly been used as a quality indicator but has not been reported among patients undergoing surgical resection for retroperitoneal sarcoma (RPS) using multi-institutional collaborative data.

Methods: All patients who underwent resection for RPS between 2000 to 2016 from eight academic institutions were included. TO was defined as a patient with R0/R1 resection that discharged to home and was without transfusion, reoperation, grade ≥2 complications, hospital-stay >50th percentile, or 90-day readmission or mortality. Univariate and multivariable analyses were performed.

Results: Among 627 patients, 56.1% were female and the median age was 59 years. A minority of patients achieved a TO (34.9%). Factors associated with achieving a TO were tumor size <20 cm and low tumor grade, while ASA class ≥3, history of a prior cardiac event, resection of left colon/rectum, distal pancreatic resection, major venous resection and drain placement were associated with not achieving a TO (all P < .05). Achievement of a TO was associated with improved survival (median:12.7 vs 5.9 years, P < .01).

Conclusions: Among patients undergoing resection for RPS, failure to achieve TO is common and associated with significantly worse survival. The use of TO may inform patient expectations and serve as a measure for patient-level hospital performance.
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http://dx.doi.org/10.1002/jso.26136DOI Listing
November 2020

Neoadjuvant radiation improves margin-negative resection rates in extremity sarcoma but not survival.

J Surg Oncol 2020 Jun 30;121(8):1249-1258. Epub 2020 Mar 30.

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

Background And Objectives: Radiation improves limb salvage in extremity sarcomas. Timing of radiation therapy remains under investigation. We sought to evaluate the effects of neoadjuvant radiation (NAR) on surgery and survival of patients with extremity sarcomas.

Materials And Methods: A multi-institutional database was used to identify patients with extremity sarcomas undergoing surgical resection from 2000-2016. Patients were categorized by treatment strategy: surgery alone, adjuvant radiation (AR), or NAR. Survival, recurrence, limb salvage, and surgical margin status was analyzed.

Results: A total of 1483 patients were identified. Most patients receiving radiotherapy had high-grade tumors (82% NAR vs 81% AR vs 60% surgery; P < .001). The radiotherapy groups had more limb-sparing operations (98% AR vs 94% NAR vs 87% surgery; P < .001). NAR resulted in negative margin resections (90% NAR vs 79% surgery vs 75% AR; P < .0001). There were fewer local recurrences in the radiation groups (14% NAR vs 17% AR vs 27% surgery; P = .001). There was no difference in overall or recurrence-free survival between the three groups (OS, P = .132; RFS, P = .227).

Conclusion: In this large study, radiotherapy improved limb salvage rates and decreased local recurrences. Receipt of NAR achieves more margin-negative resections however this did not improve local recurrence or survival rates over.
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http://dx.doi.org/10.1002/jso.25905DOI Listing
June 2020

Is a Nomogram Able to Predict Postoperative Wound Complications in Localized Soft-tissue Sarcomas of the Extremity?

Clin Orthop Relat Res 2020 03;478(3):550-559

M. Bedi, J. Charlson, D. M. King, Departments of Radiation Oncology, Medical Oncology, and Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.

Background: Postoperative wound complications are challenging in patients with localized extremity soft-tissue sarcomas. Various factors have been associated with wound complications, but there is no individualized predictive model to allow providers to counsel their patients and thus offer methods to mitigate the risk of complications and implement appropriate measures.

Questions/purposes: We used data from multiple centers to ask: (1) What risk factors are associated with postoperative wound complications in patients with localized soft-tissue sarcomas of the extremity? (2) Can we create a predictive nomogram that will assess the risk of wound complications in individual patients after resection for soft-tissue sarcoma?

Methods: From 2000 to 2016, 1669 patients undergoing limb-salvage resection for a localized primary or recurrent extremity soft-tissue sarcoma with at least 120 days of follow-up at eight participating United States Sarcoma Collaborative institutions were identified. Wound complications included superficial wounds with or without drainage, deep wounds with drainage because of dehiscence, and intentional opening of the wound within 120 days postoperatively. Sixteen variables were selected a priori by clinicians and statisticians as potential risk factors for wound complications. A univariate analysis was performed using Fisher's exact tests for categorical predictors, and Wilcoxon's rank-sum tests were used for continuous predictors. A multiple logistic regression analysis was used to train the prediction model that was used to create the nomogram. The prediction performance of the datasets was evaluated using a receiver operating curve, area under the curve, and calibration plot.

Results: After controlling for potential confounding factors such as comorbidities, functional status, albumin level, and chemotherapy use, we found that increasing age (odds ratio 1.02; 95% confidence interval, 1.00-1.03; p = 0.008), BMI (OR 1.05; 95% CI, 1.02-1.09; p = 0.004), lower-extremity location (OR 6; 95% CI, 2.87-12.69; p < 0.001), and neoadjuvant radiation (OR 2; 95% CI, 1.47-3.16; p < 0.001) were associated with postoperative wound complications (area under the curve 69.2% [range 62.8%-75.6%]).

Conclusions: We found that age, BMI, tumor location, and timing of radiation are associated with the risk of wound complications. Based on these factors, a validated nomogram has been established that can provide an individualized prediction of wound complications in patients with a resected soft-tissue sarcoma of the extremity. This may allow for proactive management with nutrition and surgical techniques, and help determine the delivery of radiation in patients with a high risk of having these complications.

Level Of Evidence: Level III, therapeutic study.
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http://dx.doi.org/10.1097/CORR.0000000000000959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145071PMC
March 2020

Outcomes of palliative-intent surgery in retroperitoneal sarcoma-Results from the US Sarcoma Collaborative.

J Surg Oncol 2020 Jun 13;121(7):1140-1147. Epub 2020 Mar 13.

Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin.

Background And Objectives: Outcomes of palliative-intent surgery in retroperitoneal sarcomas (RPS) are not well understood. This study aims to define indications for and outcomes after palliative-intent RPS resection.

Methods: Using a retrospective 8-institution database, patients undergoing resection of primary/recurrent RPS with palliative intent were identified. Logistic regression and Cox-proportional hazards models were constructed to analyze factors associated with postoperative complications and overall survival (OS).

Results: Of 3088 patients, 70 underwent 87 palliative-intent procedures. Most common indications were pain (26%) and bowel obstruction (21%). Dedifferentiated liposarcoma (n = 17, 24%), leiomyosarcoma (n = 13, 19%) were predominant subtypes. Median OS was 10.69 months (IQR, 3.91-23.23). R2 resection (OR, 8.60; CI, 1.42-52.15; P = .019), larger tumors (OR, 10.87; CI, 1.44-82.11; P = .021) and low preoperative albumin (OR, 0.14; CI, 0.04-0.57; P = .006) were associated with postoperative complications. Postoperative complications (HR, 1.95; CI, 1.02-3.71; P = .043) and high-grade histology (HR, 6.56; CI, 1.72-25.05; P = .006) rather than resection status were associated with reduced OS. However, in R2-resected patients, development of postoperative complications significantly reduced survival (P = .042).

Conclusions: Postoperative complications and high-grade histology rather than resection status impacts survival in palliative-intent RPS resections. Given the higher incidence of postoperative complications which may diminish survival, palliative-intent R2 resection should be offered only after cautious consideration.
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http://dx.doi.org/10.1002/jso.25890DOI Listing
June 2020

The Prognostic Value of Lymphovascular Invasion in Truncal and Extremity Soft Tissue Sarcomas: An Analysis from the National Cancer Database.

Ann Surg Oncol 2019 Dec 9;26(13):4723-4729. Epub 2019 Sep 9.

Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.

Objective: The aim of this study was to determine the association between lymphovascular invasion (LVI) and overall survival (OS) in truncal/extremity soft tissue sarcomas (STS).

Methods: The National Cancer Database (NCDB) was queried for all patients, ages 18-85 years, who underwent resection of primary, truncal/extremity STS between 2010 and 2012, and had LVI data. The primary endpoint was OS.

Results: Among 6169 patients identified, the most common histology groups were (1) liposarcoma (LPS, 24%), (2) undifferentiated pleiomorphic sarcoma (UPS, 19%), and (3) leiomyosarcoma (LMS, 15%); 449 patients (7%) were LVI-positive. There were no differences in demographics or comorbidities between the LVI groups. Compared with LVI-negative patients, LVI-positive patients were more likely to have larger (> 5 cm: 80% vs. 66%), deep (80% vs. 68%), and high-grade tumors (82% vs. 57%). They were also more likely to have positive margins (27% vs. 17%), nodal (16% vs. 2%) and metastatic disease (21% vs. 4%), and receive chemotherapy (37% vs. 18%; all p < 0.001). LVI was associated with worse median OS (39 months vs. MNR; p < 0.001), which persisted on stratum-specific analyses for all tumor grades, size categories, and stages I-III, but not stage IV. On multivariable Cox regression, LVI was associated with worse OS (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.39-2.44), while accounting for other significant prognostic factors. Among non-metastatic, curative-intent resections (n = 5696), LVI was still associated with worse OS (HR 1.79, 95% CI 1.28-2.49).

Conclusions: LVI appears to be an important adverse pathologic factor in truncal and extremity STS. Even when taking into account other established prognostic factors, LVI was predictive of worse OS. Knowledge of LVI status may help to better risk-stratify patients and guide management strategies, and should be considered in future prognostic classification schemes and nomograms.
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http://dx.doi.org/10.1245/s10434-019-07805-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958703PMC
December 2019

Trends in the Use of Adjuvant Chemotherapy for High-Grade Truncal and Extremity Soft Tissue Sarcomas.

J Surg Res 2020 01 5;245:577-586. Epub 2019 Sep 5.

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

Background: In the randomized controlled trial (RCT) EORTC 62931, adjuvant chemotherapy failed to show improvement in relapse-free survival (RFS) or overall survival (OS) for patients with resected high-grade soft tissue sarcoma (STS). We evaluated whether the negative results of this 2012 RCT have influenced multidisciplinary treatment patterns for patients with high-grade STS undergoing resection at seven academic referral centers.

Methods: The U.S. Sarcoma Collaborative database was queried to identify patients who underwent curative-intent resection of primary high-grade truncal or extremity STS from 2000 to 2016. Patients with recurrent tumors, metastatic disease, and those receiving neoadjuvant chemotherapy were excluded. Patients were divided by treatment era into early (2000-2011, pre-European Organisation for Research and Treatment of Cancer [EORTC] trial) and late (2012-2016, post-EORTC trial) cohorts for analysis. Rates of adjuvant chemotherapy and clinicopathologic variables were compared between the two cohorts. Univariate and multivariate regression analyses were used to determine factors associated with OS and RFS.

Results: 949 patients who met inclusion criteria were identified, with 730 patients in the early cohort and 219 in the late cohort. Adjuvant chemotherapy rates were similar between the early and late cohorts (15.6% versus 14.6%; P = 0.73). Patients within the early and late cohorts demonstrated similar median OS (128 months versus median not reached, P = 0.84) and RFS (107 months versus median not reached, P = 0.94). Receipt of adjuvant chemotherapy was associated with larger tumor size (13.6 versus 8.9 cm, P < 0.001), younger age (53.3 versus 63.7 years, P < 0.001), and receipt of adjuvant radiation (P < 0.001). On multivariate regression analysis, risk factors associated with decreased OS were increasing American Society of Anesthesiologists class (P = 0.02), increasing tumor size (P < 0.001), and margin-positive resection (P = 0.01). Adjuvant chemotherapy was not associated with OS (P = 0.88). Risk factors associated with decreased RFS included increasing tumor size (P < 0.001) and margin-positive resection (P = 0.03); adjuvant chemotherapy was not associated with RFS (P = 0.23).

Conclusions: Rates of adjuvant chemotherapy for resected high-grade truncal or extremity STS have not decreased over time within the U.S. Sarcoma Collaborative, despite RCT data suggesting a lack of efficacy. In this retrospective multi-institutional analysis, adjuvant chemotherapy was not associated with RFS or OS on multivariate analysis, consistent with the results from EORTC 62931. Rates of adjuvant chemotherapy for high-grade STS were low in both cohorts but may be influenced more by selection bias based on clinicopathologic variables such as tumor size, margin status, and patient age than by prospective, randomized data.
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http://dx.doi.org/10.1016/j.jss.2019.08.002DOI Listing
January 2020

Role of radiation therapy for retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative.

J Surg Oncol 2019 Dec 4;120(7):1227-1234. Epub 2019 Sep 4.

Division of Surgical Oncology, Department of Surgery, Wake Forest University, Winston-Salem, North Carolina.

Background: The use of radiation therapy in the treatment of retroperitoneal sarcomas has increased in recent years. Its impact on survival and recurrence is unclear.

Methods: A retrospective propensity score matched (PSM) analysis of patients with primary retroperitoneal soft tissue sarcomas, who underwent resection from 2000 to 2016 at eight institutions of the US Sarcoma Collaborative, was performed. Patients with metastatic disease, desmoid tumors, and palliative resections were excluded.

Results: Total 425 patients were included, 56 in the neoadjuvant radiation group (neo-RT), 75 in the adjuvant radiation group (adj-RT), and 294 in the no radiotherapy group (no-RT). Median age was 59.5 years, 186 (43.8%) were male with a median follow up of 31.4 months. R0 and R1 resection was achieved in 253 (61.1%) and 143 (34.5%), respectively. Overall 1:1 match of 46 adj-RT and 59 neo-RT patients was performed using histology, sex, age, race, functional status, tumor size, grade, resection status, and chemotherapy. Unadjusted recurrence-free survival (RFS) was 35.9 months (no-RT) vs 33.5 months (neo-RT) and 27.2 months (adj-RT), P = .43 and P = .84, respectively. In the PSM, RFS was 17.6 months (no-RT) vs 33.9 months (neo-RT), P = .28 and 19 months (no-RT) vs 27.2 months (adj-RT), P = .1.

Conclusions: Use of radiotherapy, both in adjuvent or neoadjuvent setting, was not associated with improved survival or reduced recurrence rate.
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http://dx.doi.org/10.1002/jso.25694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857791PMC
December 2019

Evaluation and management of incidental gallbladder cancer.

Chin Clin Oncol 2019 Aug 5;8(4):37. Epub 2019 Aug 5.

Division of Surgical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.

Given the ubiquity of laparoscopic cholecystectomy in the modern era, the incidence of incidentally diagnosed gallbladder cancers (GBCs) is rising. This unique clinical scenario poses specific challenges regarding the role of staging, re-resection, and adjuvant treatment for patients with this disease. This review will address these controversies with the latest published data.
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http://dx.doi.org/10.21037/cco.2019.07.01DOI Listing
August 2019

Lung Surveillance Strategy for High-Grade Soft Tissue Sarcomas: Chest X-Ray or CT Scan?

J Am Coll Surg 2019 11 1;229(5):449-457. Epub 2019 Aug 1.

Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Atlanta, GA. Electronic address:

Background: Given the propensity for lung metastases, National Comprehensive Cancer Network guidelines recommend lung surveillance with either chest x-ray (CXR) or CT in high-grade soft tissue sarcoma. Considering survival, diagnostic sensitivity, and cost, the optimal modality is unknown.

Methods: The US Sarcoma Collaborative database (2000 to 2016) was reviewed for patients who underwent resection of a primary high-grade soft tissue sarcoma. Primary end point was overall survival (OS). Cost analysis was performed.

Results: Among 909 patients, 83% had truncal/extremity and 17% had retroperitoneal tumors. Recurrence occurred in 48%, of which 54% were lung metastases. Lung surveillance was performed with CT in 80% and CXR in 20%. Both groups were clinically similar, although CT patients had more retroperitoneal tumors and recurrences. Regardless of modality, 85% to 90% of lung metastases were detected within the first 2 years with a similar re-intervention rate. When considering age, tumor size, location, margin status, and receipt of radiation, lung metastasis was independently associated with worse OS (hazard ratio 4.26; p < 0.01) and imaging modality was not (hazard ratio 1.01; p = 0.97). Chest x-ray patients did not have an inferior 5-year OS rate compared with CT (71% vs 60%; p < 0.01). When analyzing patients in whom no lung metastases were detected, both cohorts had a similar 5-year OS rate (73% vs 74%; p = 0.42), suggesting CXR was not missing clinically relevant lung nodules. When adhering to a guideline-specified protocol for 2018 projected 4,406 cases, surveillance with CXR for 5 years results in savings of $5 million to $8 million/year to the US healthcare system.

Conclusions: In this large multicenter study, lung surveillance with CXR did not result in worse overall survival compared with CT. With considerable savings, a CXR-based protocol can optimize resource use for lung surveillance in high-grade soft tissue sarcoma; prospective trials are needed.
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http://dx.doi.org/10.1016/j.jamcollsurg.2019.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815708PMC
November 2019

Assessing the Role of Neoadjuvant Chemotherapy in Primary High-Risk Truncal/Extremity Soft Tissue Sarcomas: An Analysis of the Multi-institutional U.S. Sarcoma Collaborative.

Ann Surg Oncol 2019 Oct 24;26(11):3542-3549. Epub 2019 Jul 24.

Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.

Background: The role of neoadjuvant chemotherapy (NCT) for high-risk soft tissue sarcoma (STS) is questioned. This study aimed to define which patients may experience a survival advantage with NCT.

Methods: All the patients from the U.S. Sarcoma Collaborative database (2000-2016) who underwent curative-intent resection of high-grade, primary truncal/extremity STS size 5 cm or larger were included in this study. The primary end points were recurrence-free survival (RFS) and overall survival (OS).

Results: Of the 4153 patients, 770 were included in the study. The median tumor size was 10 cm, and 669 of the patients (87%) had extremity tumors. The most common histology was undifferentiated pleomorphic sarcoma (UPS), found in 42% of the patients. Of the 770 patients, 216 (28%) received NCT. The patients who received NCT had deeper, larger tumors (p < 0.001). Of the patients with tumors 5 cm or larger and 8 cm or larger, NCT was not associated with improved RFS or OS. However for the patients with tumors 10 cm or larger, NCT was associated with improved 5-year RFS (51% vs 40%; p = 0.053) and 5-year OS (58% vs 47%; p = 0.043). By location, the patients with extremity tumors 10 cm or larger but not truncal tumors had improved 5-yearr RFS (54% vs 42%; p = 0.042) and 5-year OS (61% vs 47%; p = 0.015) with NCT. According to histology, no subtype had improved RFS or OS with NCT, although the patients with UPS had a trend toward improved 5-year RFS (56% vs 42%; p = 0.092) and 5-year OS (66% vs 52%; p = 0.103) with NCT.

Conclusion: For the patients with high-grade STS, NCT was associated with improved RFS and OS when tumors were 10 cm or larger and located in the extremity. However, no histiotype-specific advantage was identified. Future studies assessing the efficacy of NCT may consider focusing on these patients, with added focus on histology-specific strategies.
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http://dx.doi.org/10.1245/s10434-019-07639-7DOI Listing
October 2019

Predictors of Disease-Free and Overall Survival in Retroperitoneal Sarcomas: A Modern 16-Year Multi-Institutional Study from the United States Sarcoma Collaboration (USSC).

Sarcoma 2019 2;2019:5395131. Epub 2019 Jun 2.

University of Wisconsin, Madison, WI, USA.

Background: Retroperitoneal sarcomas (RPS) comprise approximately 15% of all soft-tissue sarcomas and frequently associated with significant morbidity and as little as 30% 5-year survival. Here, we provide a large, contemporary, and multi-institutional experience to determine which tumor, patient, and treatment characteristics are associated with long-term outcomes in RPS.

Methods: 571 patients with primary RPS were identified from the United States Sarcoma Collaboration (USSC). RPS patients who underwent resection from January 2000 to April 2016 were included with patient, tumor, and treatment-specific variables investigated as independent predictors of survival. Survival analyses for disease-free and overall survival were conducted using Kaplan-Meier and Cox proportional hazards model methods.

Results: The study cohort was 55% female, with a median age of 58.9 years (IQR: 48.6-70.0). The most common tumor histiotypes were liposarcoma (34%) and leiomyosarcoma (28%). Median follow-up was 30.6 months (IQR: 11.2-60.4). Median disease-free survival was 35.3 months (95% CI: 27.6-43.0), with multivariate predictors of poorer disease-free survival including higher grade tumors, nodal-positive disease, and multivisceral resection. Median overall survival was 81.6 months (95% CI: 66.3-96.8). Multivariate predictors of shorter overall survival included higher grade tumors, nodal-positive and multifocal disease, systemic chemotherapy, and grossly positive margins (2) following resection.

Conclusions: The strongest predictors of disease-free and overall survival are tumor-specific characteristics, while surgical factors are less impactful. Nonsurgical therapies are not associated with improved outcomes despite persistent interest and utilization. Complete macroscopic resection (0/1) remains a persistent potentially modifiable risk factor associated with improved overall survival in patients with retroperitoneal sarcomas.
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http://dx.doi.org/10.1155/2019/5395131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589263PMC
June 2019

Recurrence patterns after resection of retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative.

J Surg Oncol 2019 Sep 27;120(3):340-347. Epub 2019 Jun 27.

Division of Surgical Oncology, Department of Surgery, Wake Forest University, Winston-Salem, North Carolina.

Background And Objectives: Resection of primary retroperitoneal sarcomas (RPS) has a high incidence of recurrence. This study aims to identify patterns of recurrence and its impact on overall survival.

Methods: Adult patients with primary retroperitoneal soft tissue sarcomas who underwent resection in 2000-2016 at eight institutions of the US Sarcoma Collaborative were evaluated.

Results: Four hundred and ninety-eight patients were analyzed, with 56.2% (280 of 498) having recurrences. There were 433 recurrences (1-8) in 280 patients with 126 (25.3%) being locoregional, 82 (16.5%) distant, and 72 (14.5%) both locoregional and distant. Multivariate analyses revealed the following: Patient age P = .0002), tumor grade (P = .02), local recurrence (P = .0003) and distant recurrence (P < .0001) were predictors of disease-specific survival. The 1-, 3-, and 5-year survival rate for patients who recurred vs not was 89.6% (standard error [SE] 1.9) vs 93.5% (1.8), 66.0% (3.2) vs 88.4% (2.6), and 51.8% (3.6) vs 83.9% (3.3), respectively, P < .0001. Median survival was 5.3 years for the recurrence vs 11.3+ years for the no recurrence group (P < .0001). Median survival from the time of recurrence was 2.5 years.

Conclusions: Recurrence after resection of RPS occurs in more than half of patients independently of resection status or perioperative chemotherapy and is equally distributed between locoregional and distant sites. Recurrence is primarily related to tumor biology and is associated with a significant decrease in overall survival.
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http://dx.doi.org/10.1002/jso.25606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743490PMC
September 2019

The impact of unplanned excisions of truncal/extremity soft tissue sarcomas: A multi-institutional propensity score analysis from the US Sarcoma Collaborative.

J Surg Oncol 2019 Sep 6;120(3):332-339. Epub 2019 Jun 6.

Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.

Objective: Our aim was to compare outcomes in patients who underwent unplanned excisions (UE) of soft-tissue sarcomas (STS) against patients with planned excisions (PE).

Methods: The retrospective 7-institution US Sarcoma Collaborative database was used. Patients with curative-intent resection of truncal/extremity STS between 2000 and 2016 were included. Propensity score weighting analysis (PSWA) was performed. Endpoints were locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-specific survival (DSS).

Results: One thousand five hundred and ninety-six patients were included. Eighty-two percent (n = 1315) underwent PE and 18% (n = 281) underwent UE. Compared with PE, patients with UE were younger with smaller tumors with similar tumor grade. Unmatched analysis revealed PE was associated with worse DMFS (hazard ratio [HR] 1.95, P = .009) and DSS (HR 1.78, P = .039), but not LRFS compared with UE. On PSWA, UE had earlier LRFS (3-year LRFS: 80.5% vs 89.8%, P = .039), but not DMFS or DSS. By grade, patients with high-grade tumors and UE had worse LRFS (1-year LRFS: 90% vs 94%, P = .015), but similar DMFS and DSS compared with PE. In low-grade patients, UE and PE had similar LRFS, DMFS, or DSS.

Conclusions: UE of STS is not associated with worse prognosis compared to PE, though UE is associated with earlier locoregional recurrence in patients with high-grade tumors. Multimodality therapy is needed to achieve improved outcomes in these patients.
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http://dx.doi.org/10.1002/jso.25521DOI Listing
September 2019

The role of radiation therapy and margin width in localized soft-tissue sarcoma: Analysis from the US Sarcoma Collaborative.

J Surg Oncol 2019 Sep 6;120(3):325-331. Epub 2019 Jun 6.

Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.

Background And Objectives: Soft-tissue sarcomas (STSs) are often treated with resection and radiation (RT)±chemotherapy. The role of RT in decreasing resection width to achieve local control is unclear. We evaluated RT on margin width to achieve local control and local recurrence (LR).

Methods: From 2000 to 2016, 514 patients with localized STS were identified from the US Sarcoma Collaborative database. Patients were stratified by a margin and local control was compared amongst treatment groups.

Results: LR was 9% with positive, 4.2% with ≤1 mm, and 9.3% with >1 mm margins (P = .315). In the ≤1 mm group, LR was 5.7% without RT, 0% with preoperative RT, and 0% with postoperative RT (P < .0001). In the >1 mm group, LR was 10.2%, 0%, and 3.7% in the no preoperative and postoperative RT groups, respectively (P = .005). RT did not influence LR in patients with positive margins. In stage I-III and II-III patients, local recurrence-free survival was higher following RT (P = .008 and P = .05, respectively).

Conclusions: RT may play a larger role in minimizing LR than margin status. In patients with positive margins, RT may decrease LR to similar rates as a negative margin without RT and may be considered to decrease the risk of LR with anticipated close/positive margins.
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http://dx.doi.org/10.1002/jso.25522DOI Listing
September 2019

STAT3 Inhibition for Gastroenteropancreatic Neuroendocrine Tumors: Potential for a New Therapeutic Target?

J Gastrointest Surg 2020 05 29;24(5):1138-1148. Epub 2019 May 29.

Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road NE, 2nd Floor, Atlanta, GA, 30322, USA.

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly vascular neoplasms treated similarly, irrespective of tumor location. The expression of pro-angiogenic factors (STAT3, VEGF, and HIF-1α) and their association with adverse pathologic factors and disease recurrence following resection remains unclear.

Methods: All patients with non-metastatic GEP-NETs who underwent curative-intent resection from 2000 to 2013 were included. Immunohistochemistry was performed for pro-angiogenic factors, Ki-67 index, and CD31 using tissue microarrays made in triplicate by a pathologist blinded to other clinicopathologic variables. Primary outcome was a 3-year recurrence-free survival (3-yrRFS); secondary outcomes were correlation of pro-angiogenic factors with Ki-67 index, adverse pathologic factors, and CD31 expression, a marker of microvascular density.

Results: Of 144 GEP-NETs resected, STAT3 expression was high in 12 (8%) and low in 132 (92%) pts. High STAT3 expression was associated with worse 3-yrRFS compared to low expression (55% vs 84%; p = 0.003). High VEGF expression had a 3-yrRFS of 76% vs 82% for low expression (p = 0.09). HIF-1α expression was not associated with RFS. Ki-67 ≥ 3% was associated with worse 3-yrRFS (≥ 3%: 51% vs < 3%: 84%; p < 0.001), as was the presence of increased microvascular density (CD31 > median: 75% vs CD31 < median: 86%; p = 0.04). High STAT3 expressing tumors were more likely to have a Ki-67 ≥ 3% (42% vs 7%; p < 0.001). LVI was present in 82% of high STAT3 tumors compared to only 50% with low STAT3 (p = 0.058). CD31 expression was similar between groups (58% vs 49%; p = 0.5).

Conclusions: In resected GEP-NETs, high STAT3 expression is associated with an increased Ki-67 index, presence of lymphovascular invasion and worse 3-yr RFS. STAT3 may be a novel therapeutic target for patients undergoing resection of high-risk tumors.
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http://dx.doi.org/10.1007/s11605-019-04261-6DOI Listing
May 2020

The conundrum of < 2-cm pancreatic neuroendocrine tumors: A preoperative risk score to predict lymph node metastases and guide surgical management.

Surgery 2019 07 6;166(1):15-21. Epub 2019 May 6.

Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA. Electronic address:

Background: Management of <2-cm pancreatic neuroendocrine tumors is controversial. Although often indolent, the oncologic heterogeneity of these tumors particularly related to lymph node metastases poses challenges when deciding between resection versus surveillance.

Methods: We analyzed all patients who underwent resection of primary nonfunctional <2-cm with curative-intent at 8 institutions of the US Neuroendocrine Tumor Study Group from 2000 to 2016. Pancreatic neuroendocrine tumors with poor differentiation and Ki-67 > 20% were excluded. Our primary aim was to create a lymph node risk score that predicted lymph node metastases accurately for <2-cm pancreatic neuroendocrine tumors, utilizing readily available preoperative data.

Results: Of 695 patients with resected pancreatic neuroendocrine tumors, 309 were <2 cm. Of these small pancreatic neuroendocrine tumors, 25% were proximal (head/uncinate), 23% had a Ki-67 > 3%, and only 8% were moderately differentiated. Also, only 9% of all <2-cm pancreatic neuroendocrine tumors were lymph node (+). Indeed lymph node positivity was associated with worse 5-year recurrence-free survival compared with lymph node (-) disease (80% vs 96%; P = .007). Factors known preoperatively to be associated with lymph node metastases were proximal location (odds ratio 4.0; P = .002) and Ki-67 ≥3% (odds ratio 2.7; P = .05). Moderate differentiation was not associated with lymph node (+) disease. Location and Ki-67 were assigned a value weighted by their odds ratio: (distal= 1, proximal= 4, and Ki-67 < 3% = 1 and Ki-67 ≥ 3% = 3), which formed a lymph node risk score ranging 1-7. Scores were categorized into low (1-2), intermediate (3-4), and high (5-7) risk groups. Incidence of lymph node metastases increased progressively based on risk group, with low = 3.2%, intermediate = 13.8%, and high = 20.5%. Only 3.4% of pancreatic neuroendocrine tumors with a Ki-67 < 3% in the distal pancreas were lymph node (+) compared with 21.4% of pancreatic neuroendocrine tumors with a Ki-67 ≥ 3% in the head/uncinate.

Conclusion: This simple and novel lymph node risk score utilizes readily available preoperative factors (tumor location and Ki-67) to stratify risk of lymph node metastases accurately s for < 2-cm pancreatic neuroendocrine tumors and may help guide management strategy.
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http://dx.doi.org/10.1016/j.surg.2019.03.008DOI Listing
July 2019

Association of Perioperative Transfusion with Recurrence and Survival After Resection of Distal Cholangiocarcinoma: A 10-Institution Study from the US Extrahepatic Biliary Malignancy Consortium.

Ann Surg Oncol 2019 Jun 15;26(6):1814-1823. Epub 2019 Mar 15.

Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.

Background: Perioperative allogeneic blood transfusion is associated with poor oncologic outcomes in multiple malignancies. The effect of blood transfusion on recurrence and survival in distal cholangiocarcinoma (DCC) is not known.

Methods: All patients with DCC who underwent curative-intent pancreaticoduodenectomy at 10 institutions from 2000 to 2015 were included. Primary outcomes were recurrence-free (RFS) and overall survival (OS).

Results: Among 314 patients with DCC, 191 (61%) underwent curative-intent pancreaticoduodenectomy. Fifty-three patients (28%) received perioperative blood transfusions, with a median of 2 units. There were no differences in baseline demographics or operative data between transfusion and no-transfusion groups. Compared with no-transfusion, patients who received a transfusion were more likely to have (+) margins (28 vs 14%; p = 0.034) and major complications (46 vs 16%; p < 0.001). Transfusion was associated with worse median RFS (19 vs 32 months; p = 0.006) and OS (15 vs 29 months; p = 0.003), which persisted on multivariable (MV) analysis for both RFS [hazard ratio (HR) 1.8; 95% confidence interval (CI) 1.1-3.0; p = 0.031] and OS (HR 1.9; 95% CI 1.1-3.3; p = 0.018), after controlling for portal vein resection, estimated blood loss (EBL), grade, lymphovascular invasion (LVI), and major complications. Similarly, transfusion of ≥ 2 pRBCs was associated with lower RFS (17 vs 32 months; p < 0.001) and OS (14 vs 29 months; p < 0.001), which again persisted on MV analysis for both RFS (HR 2.6; 95% CI 1.4-4.5; p = 0.001) and OS (HR 4.0; 95% CI 2.2-7.5; p < 0.001). The RFS and OS of patients transfused 1 unit was comparable to patients who were not transfused.

Conclusion: Perioperative blood transfusion is associated with decreased RFS and OS after resection for distal cholangiocarcinoma, after accounting for known adverse pathologic factors. Volume of transfusion seems to exert an independent effect, as 1 unit was not associated with the same adverse effects as ≥ 2 units.
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http://dx.doi.org/10.1245/s10434-019-07306-xDOI Listing
June 2019

Staging laparoscopy among three subtypes of extra-hepatic biliary malignancy: a 15-year experience from 10 institutions.

J Surg Oncol 2019 Mar 26;119(3):288-294. Epub 2018 Dec 26.

Department of Surgery, Barnes-Jewish Hospital, Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.

Background: Staging laparoscopy (SL) is used to avoid resection failure and thus increase the curative resection rate. SL utilization in extra-hepatic biliary tumors (EHBT) is variable.

Methods: Data from 1090 patients with potentially resectable EHBT including gallbladder (GBC), distal (DC), and hilar (HC) subtypes were retrospectively collected from 10 academic centers (2000-2015).

Results: The SL utilization rate increased over time and was significantly higher in GBC than DC and HC. SL yield was 16.8% and did not differ between groups or over time. In patients undergoing attempted resection with prior SL, the curative resection rate did not differ between subtypes. In patients undergoing attempted resection without prior SL, the curative resection rate was less in GBC compared with DC or HC. After matching cohorts by inverse probability weighting, prior SL was associated with curative resection in GBC only (odds ratio [OR], 2.41, 95% CI, 1.36-4.27). On multivariable regression analysis, elevated carbohydrate antigen 19-9 (CA 19-9), low serum albumin, and GBC were strong predictors of distant disease on SL. After categorizing patients undergoing SL into low, intermediate, and high-risk groups based on these parameters, SL yield improved progressively from 10.0% to 19.6% to 52.6%.

Conclusions: We recommend routine SL for patients with GBC, particularly with elevated CA19-9 level and/or decreased serum albumin.
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http://dx.doi.org/10.1002/jso.25323DOI Listing
March 2019

Actual 5-Year Survivors After Surgical Resection of Hilar Cholangiocarcinoma.

Ann Surg Oncol 2019 Feb 11;26(2):611-618. Epub 2018 Dec 11.

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

Background: The prevalence and characteristics of actual 5-year survivors after surgical treatment of hilar cholangiocarcinoma (HC) have not been described previously.

Methods: Patients who underwent resection for HC from 2000 to 2015 were analyzed through a multi-institutional registry from 10 U.S. academic medical centers. The clinicopathologic characteristics and both the perioperative and long-term outcomes for actual 5-year survivors were compared with those for non-survivors (patients who died within 5 years after surgery). Patients alive at last encounter who had a follow-up period shorter than 5 years were excluded from the study.

Results: The study identified 257 patients with HC who underwent curative-intent resection with an actuarial 5-year survival of 19%. Of 194 patients with a follow-up period longer than 5 years, 23 (12%) were 5-year survivors. Compared with non-survivors, the 5-year survivors had a lower median pretreatment CA 19-9 level (116 vs. 34 U/L; P = 0.008) and a lower rate of lymph node involvement (42% vs. 15%; P = 0.027) and R1 margins (39% vs. 17%; P = 0.042). However, the sole presence of these factors did not preclude a 5-year survival after surgery. The frequencies of bile duct resection alone, major hepatectomy, caudate lobe resection, portal vein or hepatic artery resection, preoperative biliary sepsis, intraoperative blood transfusion, serious postoperative complications, and receipt of adjuvant chemotherapy were comparable between the two groups.

Conclusions: One in eight patients with HC reaches the 5-year survival milestone after resection. A 5-year survival can be achieved even in the presence of traditionally unfavorable clinicopathologic factors (elevated CA 19-9, nodal metastasis, and R1 margins).
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http://dx.doi.org/10.1245/s10434-018-7075-4DOI Listing
February 2019

Outcomes of Elderly Patients Undergoing Curative Resection for Retroperitoneal Sarcomas: Analysis From the US Sarcoma Collaborative.

J Surg Res 2019 01 22;233:154-162. Epub 2018 Aug 22.

Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address:

Background: The postoperative outcomes of elderly patients undergoing resection of retroperitoneal sarcomas (RPS) have not been widely studied.

Methods: Patients undergoing surgical resection for primary or recurrent RPS between 2000 and 2015 at participating US Sarcoma Collaborative institutions were identified. Patient demographics, perioperative morbidity, mortality, length of stay, discharge to home, disease-specific survival, and disease-free survival were compared between elderly (≥70 y, n = 171) and nonelderly (<70 y, n = 494) patients.

Results: There was no difference in perioperative morbidity (total and major complications elderly versus nonelderly: 39% versus 35%; P = 0.401 and 18% versus 17%; P = 0.646, respectively) or mortality between elderly and nonelderly patients with each group experiencing a 1% 30-d mortality rate. Length of stay and 30-d readmission rates were similar (elderly versus nonelderly; 7 d interquartile range [IQR: 5-9] versus 6 d [IQR: 4-9], P = 0.528 and 11% versus 12%, P = 0.667). Elderly patients were more likely to be discharged to a skilled nursing or rehabilitation facility (elderly versus nonelderly; 19% versus 7%, P < 0.001). There was no difference in 3-y disease-free survival between the elderly and nonelderly patients (41% versus 43%, P = 0.65); however, elderly patients had a lower 3-y disease-specific survival (60% versus 76%, P < 0.001). In elderly patients, the presence of multiple comorbidities and high-grade tumors were most predictive of outcomes.

Conclusions: Advanced age was not associated with an increased risk of perioperative morbidity and mortality following resection of RPS in this multi-institutional review. Although short-term oncologic outcomes were similar in both groups, the risk of death after sarcoma recurrence was higher in elderly patients and may be related to comorbidity burden and tumor histology.
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http://dx.doi.org/10.1016/j.jss.2018.07.050DOI Listing
January 2019

Identifying the barriers to gastric cancer care at safety-net hospitals: A novel comparison of a safety-net hospital to a neighboring quaternary referral academic center in the same healthcare system.

J Surg Oncol 2019 Jan 27;119(1):64-70. Epub 2018 Nov 27.

Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.

Background: The three-delays model describes delays in seeking, reaching, and receiving care for vulnerable populations needing treatment. The dominant delay for patients with gastric adenocarcinoma (GAC) is unknown. We aimed to define patients with GAC who reached and received care at our regional safety-net hospital (Grady Memorial Hospital [GMH]) and our neighboring quaternary referral hospital (Emory University Hospital [EUH]).

Methods: Clinicopathologic data from National Cancer Database (NCDB) participating academic centers were compared with GMH from 2004 to 2014. Outcomes of patients undergoing surgery at GMH were compared to those at EUH.

Results: At presentation, compared to NCDB centers (n = 69 662), GMH patients (n = 154) were more often black (85.1 vs 17.2%; P < 0.001), uninsured (30.5 vs 4.7%; P < 0.001), have stage IV disease (43.5 vs 30.1%; P = 0.017), and received no treatment (40.3 vs 18.4%; P < 0.001). When only comparing patients who underwent curative-intent resection at GMH (n = 23) to EUH (n = 137), median overall survival was similar between both groups (GMH: median not reached; EUH: 59.8 mos; P = 0.785).

Conclusion: Although vulnerable patients with GAC within a safety-net hospital present with later stages of the disease, those who received surgery have acceptable outcomes. Thus, efforts should be made to overcome barriers in seeking care.
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http://dx.doi.org/10.1002/jso.25299DOI Listing
January 2019

The value of a cross-discipline team-based approach for resection of renal cell carcinoma with IVC tumor thrombus: A report of a large, contemporary, single-institution experience.

J Surg Oncol 2018 Dec 17;118(8):1219-1226. Epub 2018 Oct 17.

Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia.

Introduction: We report the evolution of the largest, contemporary, single-institution experience with this complex procedure to highlight the value of a cross-discipline, team-based approach.

Methods: Patients from a prospectively maintained database who underwent resection of renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus from 2005 to 2016 at a single-institution were included for analysis.

Results: Of 140 patients, 102 (73%) had tumor thrombus below the level of the hepatic vein confluence, and 96 (69%) were performed for curative-intent, while 43 (31%) were cytoreductive procedures for clinical trial consideration. Median overall survival (OS) of the entire cohort was 43.8 months (5-year OS:43%), and 73.6 months (5-year OS:59%) for those without metastatic disease. Fifty-one patients underwent resection from 2005 to 2010 and 89 from 2011 to 2016. All procedures since 2011 were performed by the same cross-discipline dedicated team of two surgeons, composed of a surgical and urological oncologist. When comparing the two time-periods, the team-approach after 2011 had shorter operative-times (5.3 vs 6.7 hours; P = 0.009), decreased ICU-utilization (25% vs 72%; P < 0.001), and decreased ICU length-of-stay (0.4 vs 2.2 days; P = 0.001). This group also trended towards less blood loss (1.2 vs 1.8 L), shorter average hospital length-of-stay (10 vs 11 days), and decreased 90-day mortality (6% vs 10%).

Conclusion: Resection of RCC with IVC tumor thrombus yields long-term survival. A dedicated, cross-discipline, and team-based approach optimizes patient outcomes and may improve value of care by reducing utilization of expensive hospital resources.
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http://dx.doi.org/10.1002/jso.25271DOI Listing
December 2018