Publications by authors named "Kenneth Cardona"

120 Publications

Postoperative Morbidity After Resection of Recurrent Retroperitoneal Sarcoma: A Report from the Transatlantic Australasian RPS Working Group (TARPSWG).

Ann Surg Oncol 2021 Jan 2. Epub 2021 Jan 2.

Department of Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.

Background: This study aimed to evaluate perioperative morbidity after surgery for first locally recurrent (LR1) retroperitoneal sarcoma (RPS). Data concerning the safety of resecting recurrent RPS are lacking.

Methods: Data were collected on all patients undergoing resection of RPS-LR1 at 22 Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) centers from 2002 to 2011. Uni- and multivariable logistic models were fitted to study the association between major (Clavien-Dindo grade ≥ 3) complications and patient/surgery characteristics as well as outcome. The resected organ score, a method of standardizing the number of organs resected, as previously described by the TARPSWG, was used.

Results: The 681 patients in this study had a median age of 59 years, and 51.8% were female. The most common histologic subtype was de-differentiated liposarcoma (43%), the median resected organ score was 1, and 83.3% of the patients achieved an R0 or R1 resection. Major complications occurred for 16% of the patients, and the 90-day mortality rate was 0.4%. In the multivariable analysis, a transfusion requirement was found to be a significant predictor of major complications (p < 0.001) and worse overall survival (OS) (p = 0.010). However, having a major complication was not associated with a worse OS or a higher incidence of local recurrence or distant metastasis.

Conclusions: A surgical approach to recurrent RPS is relatively safe and comparable with primary RPS in terms of complications and postoperative mortality when performed at specialized sarcoma centers. Because alternative effective therapies still are lacking, when indicated, resection of a recurrent RPS is a reasonable option. Every effort should be made to minimize the need for blood transfusions.
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http://dx.doi.org/10.1245/s10434-020-09445-yDOI Listing
January 2021

Primary mesenteric sarcomas: Collaborative experience from the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

J Surg Oncol 2021 Mar 23;123(4):1057-1066. Epub 2020 Dec 23.

Midlands Abdominal and Retroperitoneal Sarcoma Unit, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, UK.

Background: Primary mesenteric soft tissue sarcomas (STS) are rare and limited evidence is available to inform management. Surgical resection is challenging due to the proximity of vital structures and a need to preserve enteric function.

Objectives: To determine the overall survival (OS) and recurrence-free survival (RFS) for patients undergoing primary resection for mesenteric STS.

Methods: The Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) is an intercontinental collaborative comprising specialist sarcoma centers. Data were collected retrospectively for all patients with mesenteric STS undergoing primary resection between 2000 and 2019.

Results: Fifty-six cases from 15 institutions were included. The spectrum of pathology was similar to the retroperitoneum, although of a higher grade. R0/R1 resection was achieved in 87%. Median OS was 56 months. OS was significantly shorter in higher-grade tumors (p = .018) and extensive resection (p < .001). No significant association between OS and resection margin or tumor size was detected. Rates of local recurrence (LR) and distant metastases (DM) at 5 years were 60% and 41%, respectively. Liver metastases were common (60%), reflecting portal drainage of the mesentery.

Conclusion: Primary mesenteric sarcoma is rare, with a modest survival rate. LR and DM are frequent events. Liver metastases are common, highlighting the need for surveillance imaging.
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http://dx.doi.org/10.1002/jso.26353DOI Listing
March 2021

Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional study from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

Cancer 2021 Mar 18;127(5):729-738. Epub 2020 Nov 18.

Sarcoma Service, Departments of Surgery and Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Background: In patients with retroperitoneal sarcoma (RPS), the incidence of recurrence after surgery remains high. Novel treatment approaches are needed. This retrospective study evaluated patients with primary, high-risk RPS who received neoadjuvant systemic therapy followed by surgery to 1) determine the frequency and potential predictors of radiologic tumor responses and 2) assess clinical outcomes.

Methods: Clinicopathologic data were collected for eligible patients treated at 13 sarcoma referral centers from 2008 to 2018. Univariable and multivariable logistic models were performed to assess the association between clinical predictors and response. Overall survival (OS) and crude cumulative incidences of local recurrence and distant metastasis were compared.

Results: Data on 158 patients were analyzed. A median of 3 cycles of neoadjuvant systemic therapy (interquartile range, 2-4 cycles) were given. The regimens were mostly anthracycline based; however, there was significant heterogeneity. No patients demonstrated a complete response, 37 (23%) demonstrated a partial response (PR), 88 (56%) demonstrated stable disease, and 33 (21%) demonstrated progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Only a higher number of cycles given was positively associated with PR (P = .005). All patients underwent complete resection, regardless of the tumor response. Overall, patients whose tumors demonstrated PD before surgery showed markedly worse OS (P = .005). An indication of a better clinical outcome was seen in specific regimens given for grade 3 dedifferentiated liposarcoma and leiomyosarcoma.

Conclusions: In patients with high-risk RPS, the response to neoadjuvant systemic therapy is fair overall. Disease progression on therapy may be used to predict survival after surgery. Subtype-specific regimens should be further validated.
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http://dx.doi.org/10.1002/cncr.33323DOI 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

The STRASS trial: an important step in the right direction.

Authors:
Kenneth Cardona

Lancet Oncol 2020 10 14;21(10):1257-1258. Epub 2020 Sep 14.

Winship Cancer Institute, Emory University, Atlanta, GA, USA; Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Emory University Atlanta, GA 30322, USA. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(20)30429-0DOI Listing
October 2020

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

Differences in outcome for patients with cholangiocarcinoma: Racial/ethnic disparity or socioeconomic factors?

Surg Oncol 2020 Sep 9;34:126-133. Epub 2020 Apr 9.

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

Background: Inequities in cancer survival are well documented. Whether disparities in overall survival (OS) result from inherent racial differences in underlying disease biology or socioeconomic factors (SEF) is not known. Our aim was to define the association of race/ethnicity and SEF with OS in pts with cholangiocarcinoma (CCA).

Methods: Patients with CCA of all sites and stages in the National Cancer Data Base (2004-13) were included. Racial/ethnic groups were defined as non-Hispanic White (NH-W), non-Hispanic Black (NH-B), Asian, and Hispanic. Income and education were based on census data for patients' zip code. Income was defined as high (≥$63,000) vs low (<$63,000). Primary outcome was OS.

Results: 27,151 patients were included with a mean age of 68 yrs; 51% were male. 78% were NH-W, 8% NH-B, 8% Hispanic, and 6% Asian. 56% had Medicare, 33% private insurance, 7% Medicaid, and 4% were uninsured. 67% had low income. 19% lived in an area where >20% of adults did not finish high school. NH-B and Hispanic patients had more unfavorable SEF including uninsured status, low income, and less formal education than NH-W and Asian pts (all p < 0.001). They were also younger, more likely to be female and to have metastatic disease (all p < 0.001). Despite this, NH-B race and Hispanic ethnicity were not associated with decreased OS. Male sex, older age, non-private insurance, low income, lower education, non-academic facility, location outside the Northeast, higher Charlson-Deyo score, worse grade, larger tumor size, and higher stage were all associated with decreased OS (all p < 0.001). On MV analysis, along with adverse pathologic factors, type of insurance (p = 0.003), low income (p < 0.001), and facility type and location of treatment (p < 0.001) remained associated with decreased OS; non-white race/ethnicity was not.

Conclusions: Disparities in survival exist in CCA, however they are not driven by race/ethnicity. Non-privately insured and low-income patients had decreased OS, as did patients treated at non-academic centers and outside the Northeast. This suggests that decreased ability to access and afford care results in worse outcomes, rather than biological differences amongst racial/ethnic groups.
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http://dx.doi.org/10.1016/j.suronc.2020.04.007DOI Listing
September 2020

Patterns of recurrence and survival probability after second recurrence of retroperitoneal sarcoma: A study from TARPSWG.

Cancer 2020 Nov 14;126(22):4917-4925. Epub 2020 Aug 14.

Division of General Surgery, Mount Sinai Hospital, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.

Background: In this series from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), the authors examined longitudinal outcomes of patients with a second recurrence of retroperitoneal sarcoma (RPS) after complete resection of a first local recurrence (LR).

Methods: Data from patients undergoing resection of a first LR from January 2002 to December 2011were collected from 22 sarcoma centers. The primary outcome was overall survival (OS) after second recurrence.

Results: Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first locally recurrent RPS. Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55 patients (13.75%), and both LR and DM in 22 patients (5.5%). The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re-resection (61.9%). The 5-year OS rate varied significantly based on the pattern of failure (P < .001): 45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM. The only factors found to be associated with improved OS on multivariable analysis were both time between second surgery and the development of the second recurrence (32 months vs 8 months: hazard ratio, 0.44 [P < .001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [P < .001]). The 5-year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the patients not deemed suitable for surgical resection.

Conclusions: Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and treatment. Durable disease-free survivors were identified after surgery for second LR in patients selected for this intervention.
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http://dx.doi.org/10.1002/cncr.33139DOI Listing
November 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

Relationship between Cancer Diagnosis and Complications Following Pancreatoduodenectomy for Duodenal Adenoma.

Ann Surg Oncol 2021 Feb 20;28(2):1097-1105. Epub 2020 Jul 20.

Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.

Background: Pancreatoduodenectomy (PD) for duodenal adenoma (DA) resection may be associated with excessive surgical risk for patients with potentially benign lesions, given the absence of pancreatic duct obstruction. We examined factors associated with final malignant pathology and evaluated the postoperative course of patients with DA versus pancreatic ductal adenocarcinoma (PDAC).

Methods: We retrospectively analyzed patients with DA who underwent PD from 2008 to 2018 and assessed the accuracy rate of preoperative biopsy and factors associated with final malignant pathology. Complications for DA patients were compared with those of matched PDAC patients.

Results: Forty-five consecutive patients who underwent PD for DA were identified, and the preoperative biopsy false negative rate was 29. Factors associated with final malignant pathology included age over 70 years, preoperative biliary obstruction, and common bile duct diameter > 8 mm (p < 0.05). Compared with patients with PDAC (n = 302), DA patients experienced more major complications (31% vs. 15%, p < 0.01), more grade C postoperative pancreatic fistulas (9% vs. 1%, p < 0.01), and greater mortality (7% vs. 2%, p < 0.05). Propensity score matched patients with DA had more major complications following PD (32% vs. 12%, p < 0.05).

Conclusions: Preoperative biopsy of duodenal adenomas is associated with a high false-negative rate for malignancy, and PD for DA is associated with higher complication rates than PD for PDAC. These results aid discussion among patients and surgeons who are considering observation versus PD for DA, especially in younger patients without biliary obstruction, who are less likely to harbor malignancy.
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http://dx.doi.org/10.1245/s10434-020-08767-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856223PMC
February 2021

The accuracy of a novel sonographic scanning and reporting protocol to survey for soft tissue sarcoma local recurrence.

Skeletal Radiol 2020 Dec 29;49(12):2039-2049. Epub 2020 Jun 29.

Department of Surgery, Division of Oncology, Emory University Hospital, Atlanta, GA, USA.

Objective: This study aims to determine the accuracy of a novel ultrasonography (US) scanning and reporting protocol to detect recurrences. The secondary aim is to compare US and MRI accuracy and agreement.

Materials And Methods: In this IRB-approved prospective study, consecutive patients presenting for MRI surveillance after resection were enrolled and underwent same-day US. Blinded to clinical information and the MRI, the US scanner characterized lesions using a proposed novel lexicon. Outcome was defined either by histology or a subsequent MRI scan confirming the presence or absence of recurrence. Fisher's exact test and Kappa test were performed to assess of the significance and agreement between US, MRI, and outcome.

Results: A total of 68 US scans were performed on 55 patients. The overall accuracy to diagnose recurrence was the same for US and MRI (92.6%) while US was less sensitive (75.0% vs. 91.7%) but more specific (97.6% vs. 92.9%) than MRI. The two lesions missed by US but not MRI were an entirely intraosseous metastasis and a subcentimeter skin nodule. There was strong agreement between US and MRI with outcome (k = 0.787 and 0.801, respectively).

Conclusions: These pilot data suggest the accuracy of this novel US local recurrence surveillance method is comparable to MRI. A multi-institutional prospective trial would increase power and determine reproducibility.
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http://dx.doi.org/10.1007/s00256-020-03520-xDOI Listing
December 2020

Retroperitoneal sarcoma perioperative risk stratification: A United States Sarcoma Collaborative evaluation of the ACS-NSQIP risk calculator.

J Surg Oncol 2020 Jun 17. Epub 2020 Jun 17.

Department of Surgery, Division of Surgical Oncology, University of Wisconsin, Madison, Wisconsin.

Background: The ACS-NSQIP risk calculator predicts perioperative risk. This study tested the calculator's ability to predict risk for outcomes following retroperitoneal sarcoma (RPS) resection.

Methods: The United States Sarcoma Collaborative database was queried for adults who underwent RPS resection. Estimated risk for outcomes was calculated twice in the risk calculator, once using sarcoma-specific CPT codes and once using codes indicative of most comorbid organ resection (eg nephrectomy). ROC curves were generated, with area under the curve (AUC) and Brier scores reported to assess discrimination and calibration. An AUC < 0.6 was considered ineffective discrimination. A negative ▲ Brier indicated improved performance relative to baseline outcome rates.

Results: In total, 482 patients were identified with a 42.3% 90-day complication rate. Discrimination was poor for all outcomes except "all complications" and "renal failure." Baseline outcome rates were better predictors than calculator estimates except for "discharge to nursing or rehab facility" and "renal failure." Replacing sarcoma-specific CPT codes with resection-specific codes did not improve performance.

Conclusion: The ACS-NSQIP risk calculator poorly predicted outcomes following RPS resection. Changing sarcoma-specific CPT to resection-specific codes did not improve performance. Comorbidities in the calculator may not effectively capture perioperative risk. Future work should evaluate a sarcoma-specific calculator.
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http://dx.doi.org/10.1002/jso.26071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744355PMC
June 2020

Should Signet Ring Cell Histology Alter the Treatment Approach for Clinical Stage I Gastric Cancer?

Ann Surg Oncol 2021 Jan 10;28(1):97-105. Epub 2020 Jun 10.

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

Background: Surgery alone is standard-of-care for stage I gastric adenocarcinoma; however, clinicians can offer preoperative therapy for clinical stage I disease with signet ring cell histology, given its presumed aggressive biology. We aimed to assess the validity of this practice.

Methods: The National Cancer Database (2004-2015) was reviewed for patients with clinical stage I signet ring cell gastric adenocarcinoma who underwent treatment with surgery alone, perioperative chemotherapy, neoadjuvant therapy, or adjuvant therapy. Analysis was stratified by preoperative clinical/pathologic stage. Primary outcome was overall survival (OS).

Results: Of 1018 patients, median age was 60 years (±14); 53% received surgery alone (n = 542), 5% received perioperative chemotherapy (n = 47), 12% received neoadjuvant therapy (n = 125), and 30% received adjuvant therapy (n = 304). For clinical stage I disease, surgery alone was associated with an improved 5-year OS rate (71%) versus perioperative chemotherapy (58%), neoadjuvant therapy (38%), or adjuvant therapy (52%) [overall p < 0.01]. For pathologic stage I, surgery alone had equivalent or improved survival compared with perioperative, neoadjuvant, and adjuvant therapy (5-year OS: 78% vs. 89% [p = 0.77] vs. 64% [p = 0.04] vs. 84% [p = 0.99]). Adjuvant therapy was associated with improved 5-year OS compared with pretreatment for those patients upstaged (37%) to pathologic stage II/III (55% vs. 36% and 34% vs. 7%; all p < 0.01).

Conclusions: This stage-specific study demonstrates improved survival with surgery alone for clinical stage I signet ring cell gastric adenocarcinoma. Despite 37% of clinical stage I patients being upstaged to pathologic stage II/III, adjuvant therapy offers a favorable rescue strategy, with improved outcomes compared with those treated preoperatively. Surgery alone also affords similar or improved survival for pathologic stage I disease versus multimodality therapy. This study challenges the bias to overtreat stage I signet ring cell gastric adenocarcinoma.
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http://dx.doi.org/10.1245/s10434-020-08714-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725995PMC
January 2021

Optimal timing and treatment strategy for pancreatic cancer.

J Surg Oncol 2020 Sep 29;122(3):457-468. Epub 2020 May 29.

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

Background: For pancreatic adenocarcinoma (PDAC), no studies have established any association between earlier treatment initiation and long-term outcomes. In addition, an optimal type of initial treatment for the localized disease remains ill-defined.

Methods: Patients in the National Cancer Database (2004-2015) with clinical stage I (CS-I) and II (CS-II) PDAC who underwent curative-intent resection were included. Optimal time from diagnosis-to-treatment including neoadjuvant chemotherapy, neoadjuvant chemoradiation, or upfront surgery was assessed. An optimal type of treatment was evaluated. The primary outcome was overall survival (OS).

Results: Among 29 167 patients, starting any treatment within 0 to 6 weeks was associated with improved median OS compared with 7 to 12 weeks (21.0 vs 20.1 months; P = .004). This persisted when accounting for sex, race, and Charlson-Deyo score (hazard ratio [HR], 0.94; P = 0.02) and on subset analysis for CS-I (23.5 vs 21.8 months; P = .04) and CS-II (19.4 vs 18.3 months; P = .03). Neoadjuvant chemotherapy was associated with improved OS compared with neoadjuvant chemoradiation (25.6 vs 22.7 months; P < .0001) or US (25.6 vs 20.1 months; P < .0001) even when accounting for sex, race, and Charlson-Deyo score (neoadjuvant chemoradiation: HR, 0.86; P < .001; US: HR, 0.79; P < .001). This improvement persisted in subset analysis with NC compared with neoadjuvant chemoradiation (CS-I: 28.6 vs 25.0 months; CS-II: 25.0 vs 22.9 months; both P < .0001) and to US (CS-I: 28.6 vs 22.9 months; CS-II: 24.7 vs 18.4 months; both P < .0001). On multivariable analysis for each CS-I/CS-II, NC remained associated with 20% improved survival compared with neoadjuvant chemoradiation or upfront surgery.

Conclusions: For PDAC, initiation of therapy within 6 weeks from diagnosis is associated with improved survival, with neoadjuvant chemotherapy associated with the best survival compared with neoadjuvant chemoradiation or upfront surgery.
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http://dx.doi.org/10.1002/jso.25976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396281PMC
September 2020

Should adenosquamous esophageal cancer be treated like adenocarcinoma or squamous cell carcinoma?

J Surg Oncol 2020 Sep 27;122(3):412-421. Epub 2020 May 27.

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

Background: Esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) have distinct outcomes, treatment strategies, and response profiles to therapy. Adenosquamous carcinoma (ASC) is thought to behave more aggressively than each of its counterparts. The aim of this study is to determine ifASC is best managed as AC or SCC.

Methods: National Cancer Database (2004-2015) was queried for patients with nonmetastatic esophageal ASC. The analysis was stratified by clinical node-negative (cN0) or clinical node-positive (cN1-3). Treatment was categorized into chemoradiation alone, surgery alone, or preoperative chemoradiation followed by surgery. The primary outcome was 5-year overall survival (OS).

Results: Among 352 patients, 43% were cN0 (n = 151), 57% were cN1-3 (n = 201) and 55% had chemoradiation alone (n = 194), 15% surgery alone (n = 53), and 30% preoperative chemoradiation (n = 105). Among patients who had preoperative chemoradiation, 20% had pathologic complete response (n = 17). For either cN0 or cN1-3, Charlson-Deyo Comorbidity Index did not differ among the treatment groups(all p > 0.05). On Kaplan-Meier analysis for cN0, treatment with surgery alone had comparable OS to preoperative chemoradiation (47% vs 34%; P = .5) and each had improved OS compared to chemoradiation alone (30%; P = .02; P = .06). On univariate analysis for cN0, clinical T category was not associated with OS. For cN1-3, however, preoperative chemoradiation was associated with improved OS when compared to chemoradiation alone or surgery alone (27% vs 19% vs 0%; P < .001). This persisted when accounting for age and clinical T category (hazard ratio: 0.45; P < .001).

Conclusion: Esophageal ASC behaves more like AC in response to chemoradiation and survival based on treatment modality. A complete response to chemoradiation is only 20% unlike what has been shown for SCC, where chemoradiation is an acceptable definitive therapy. Esophageal ASC should be managed more like AC.
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http://dx.doi.org/10.1002/jso.25990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396283PMC
September 2020

Soft Tissue Tumors of the Abdomen and Retroperitoneum.

Surg Clin North Am 2020 Jun 15;100(3):649-667. Epub 2020 Apr 15.

Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 550 Peachtree Street, Northeast, 9th Floor, Suite 900, Atlanta, GA 30308, USA. Electronic address:

Soft tissue tumors of the abdomen and retroperitoneum encompass a wide range of benign and malignant neoplasms. Retroperitoneal sarcomas, the most common, are composed of rare malignancies with numerous histiotypes. Surgery remains the cornerstone of treatment and the only curative option for retroperitoneal sarcomas. With histiotype-dependent local and distant recurrences, it is imperative these cases are discussed in a multidisciplinary tumor board setting at specialized sarcoma centers. This review discusses the current evidence for the management of abdominal and retroperitoneal soft tissue tumors, with particular focus on retroperitoneal sarcomas and desmoid tumors.
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http://dx.doi.org/10.1016/j.suc.2020.02.011DOI Listing
June 2020

Impact of Genomic Mutation and Timing of Y90 Radioembolization in Colorectal Liver Metastases.

Cardiovasc Intervent Radiol 2020 Jul 4;43(7):1006-1014. Epub 2020 May 4.

Department of Radiology and Imaging Sciences, Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, 1364 Clifton Rd. NE, Suite #D112, Atlanta, GA, USA.

Purpose: To investigate timing of Yttrium-90 radioembolization (Y90) during treatment course, genomics, and other clinical factors as predictors of overall survival (OS) in colorectal liver metastasis (CRLM) that have progressed on at least one line of chemotherapy.

Materials And Methods: This was a retrospective study from 2013 to 2018 of patients with CRLM and genomic analysis prior to Y90 at a multihospital tertiary referral center. OS from liver metastasis diagnosis and predictors of OS were analyzed using Kaplan-Meier estimation with log-rank and Cox regression analyses.

Results: Overall, 58 patients with CRLM who progressed on at least one line of chemotherapy who had genomic analysis prior to Y90 were identified. Median OS after hepatic metastasis was 29.9 months. Of these, 16 (28%) patients received Y90 after failure of the first-line systemic chemotherapy. There was significantly prolonged OS in patients receiving Y90 immediately following failure of the first-line chemotherapy folinic acid, fluorouracil, oxaliplatin ((FOLFOX) ± bevacizumab) versus following multiple lines of chemotherapy (median OS of 46.3 vs. 26.6 months, P = 0.005). The presence of genetic mutation in tumor, MAPK pathway wild type, left-sided primary tumor, low MELD score, and non-diffuse unilobar disease were also found to be predictors prolonged survival on log-rank analysis (P's < 0.05). On multivariate analysis, receiving Y90 after failure of the first line of chemotherapy, low baseline MELD score, and baseline ECOG performance score of 0 were all found to be independent predictors of prolonged OS from the time of metastatic disease diagnosis (P's < 0.05).

Conclusion: In patients with CRLM, receiving Y90 after failing the first line of chemotherapy, lack of genetic mutation, low MELD score, and lower tumor burden appear to be independent predictors of prolonged OS.

Level Of Evidence: Level 4, case-control study.
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http://dx.doi.org/10.1007/s00270-020-02463-zDOI Listing
July 2020

Variant anatomy of the biliary system as a cause of pancreatic and peri-ampullary cancers.

HPB (Oxford) 2020 Dec 24;22(12):1675-1685. Epub 2020 Apr 24.

Department of Pathology, Koç University Hospital, Istanbul, Turkey; Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey. Electronic address:

Background: The cause of most pancreatic and periampullary cancers (PAC) is unknown. Recently, anatomic variations such as pancreatobiliary maljunction have been recognized as risk factors, similar to Barrett-related gastro-esophageal cancers.

Methods: Pre-operative MRI from 860 pancreatic/biliary resections, including 322 PACs, were evaluated for low-union (cystic duct joining the common hepatic duct inside of the pancreas or within 5 mm of the pancreatic border) RESULTS: Low-union, seen <10% of the population, was present in 44% of PACs (73% distal bile duct/cholangiocarcinoma, 42% pancreatic head, and 34% ampullary). It was significantly lower(11%) in conditions without connection to the ductal system (thus not exposed to the ductal/biliary tract contents), namely mucinous cystic neoplasms and intrahepatic cholangiocarcinomas(p < 0.0001). Intra-pancreatic type low-union was seen in 16% of PACs versus 2% of controls(p < 0.0001).

Discussion: This study establishes an association between low-union and PACs, and points to an anatomy-induced chemical/bilious carcinogenesis. This may explain why most pancreas cancers are in the head. It is possible that the same chemical milieu, caused by conditions other than low-union/insertion, may also play a role in the remaining half of PACs. This opens various treatment opportunities including milieu modifications (chemoprevention), focused screening of at-risk patients, and early detection with possible corrective actions.
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http://dx.doi.org/10.1016/j.hpb.2020.03.014DOI Listing
December 2020

Soft-tissue sarcoma in adults: An update on the current state of histiotype-specific management in an era of personalized medicine.

CA Cancer J Clin 2020 05 10;70(3):200-229. Epub 2020 Apr 10.

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

Soft-tissue sarcomas (STS) are rare tumors that account for 1% of all adult malignancies, with over 100 different histologic subtypes occurring predominately in the trunk, extremity, and retroperitoneum. This low incidence is further complicated by their variable presentation, behavior, and long-term outcomes, which emphasize the importance of centralized care in specialized centers with a multidisciplinary team approach. In the last decade, there has been an effort to improve the quality of care for patients with STS based on anatomic site and histology, and multiple ongoing clinical trials are focusing on tailoring therapy to histologic subtype. This report summarizes the latest evidence guiding the histiotype-specific management of extremity/truncal and retroperitoneal STS with regard to surgery, radiation, and chemotherapy.
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http://dx.doi.org/10.3322/caac.21605DOI Listing
May 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

PLR and NLR Are Poor Predictors of Survival Outcomes in Sarcomas: A New Perspective From the USSC.

J Surg Res 2020 07 12;251:228-238. Epub 2020 Mar 12.

Division of Surgical Oncology, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Electronic address:

Background: Elevations in inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), are reportedly associated with decreased overall survival (OS) or recurrence-free survival (RFS) in patients with numerous cancers. A large multicenter sarcoma data set was used to determine if elevated NLR or PLR was associated with worse survival and can guide treatment selection.

Materials And Methods: A total of 409 patients with a primary retroperitoneal sarcoma (n = 268) or truncal (n = 141) sarcoma from 2000 to 2015 were analyzed using the US Sarcoma Collaboration database. Binary NLR and PLR values were developed using receiver operating characteristic curves. Kaplan-Meier model and Cox proportional hazards model identified predictors of decreased OS and RFS. Point biserial analyses were used to correlate binary and continuous data.

Results: Neither elevated NLR nor PLR was predictive of decreased OS or RFS. These findings persisted despite exclusion of comorbid inflammatory conditions. Further, NLR and PLR were not correlated with tumor grade. In multivariate models, decreased RFS was associated with tumor factors (e.g., positive margins, tumor grade, tumor size, necrosis, positive nodes); decreased OS was associated with histologic subtype, male gender, and nodal involvement.

Conclusions: Although several small studies have suggested that elevated NLR and PLR are associated with decreased survival in patients with abdominal or truncal sarcoma, this large multicenter study demonstrates no association with decreased OS, decreased RFS, or tumor grade. Rather, survival outcomes are best predicted using previously established tumoral factors.
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http://dx.doi.org/10.1016/j.jss.2020.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765565PMC
July 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

Association of ABO blood group with survival following pancreatoduodenectomy for pancreatic ductal adenocarcinoma.

HPB (Oxford) 2020 Nov 4;22(11):1557-1562. Epub 2020 Mar 4.

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

Background: Existing research suggests patients with blood group O are less likely to develop pancreatic ductal adenocarcinoma (PDAC) compared to those with non-O blood groups, and that survival from PDAC may be affected by ABO blood type. This study assessed survival outcomes in PDAC patients who underwent pancreatoduodenectomy (PD) in one health system.

Methods: From 2010 to 2017, demographic, operative, chemotherapy and survival data for patients undergoing PD at Emory Healthcare were reviewed. Patients with blood type AB were excluded due to small sample size. The relationship between ABO blood group and survival was analyzed using Kaplan-Meier survival curves and multivariate cox proportional regression analysis.

Results: Of 449 PDAC patients assessed, 204 (45.4%), 60 (13.4%) and 185 (41.2%) were blood groups A, B and O, respectively. Patients were well matched in clinicopathologic characteristics. Median survival did not differ by blood group (p = 0.82), and this relationship remained insignificant on cox regression analysis (p = 0.15). On multivariate analysis, lymph node positivity (p < 0.001) and increasing age (p = 0.001) were associated with reduced survival.

Conclusion: In contrast to recent reports, this larger study found that blood group did not impact overall survival among patients undergoing PD for PDAC.
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http://dx.doi.org/10.1016/j.hpb.2020.01.004DOI Listing
November 2020

Emergency department visits after pancreatoduodenectomy: examining a novel quality metric.

HPB (Oxford) 2020 May 14;22(5):757-763. Epub 2019 Nov 14.

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

Background: Postoperative emergency department (ED) visits represent fragmented care, are costly, and often evolve into readmission. Readmission rates after pancreatoduodenectomy (PD) are defined, while ED visits following PD are not. We examined the pattern of 30-day post-discharge ED visits for PD patients.

Methods: A quaternary institutional database analysis of adult patients who underwent PD between 2010-2017 was reviewed for ED utilization within 30 days from discharge.

Results: Of the 1,004 patients who underwent PD, 12% (N = 117) patients sought care in the ED within 30 days from postoperative discharge. The median time to ED presentation was 5 days post-discharge (IQR 3-9). Half of ED visits occurred during nights and weekends (N = 59, 50%). Of ED-utilizing patients, 64% (N = 76) were admitted to the hospital and 29% (N = 34) were discharged from the ED. ED visits were associated with a Clavien-Dindo Classification of 0 in 10.2% (N = 13) of patients, I-II in 62.4% (N = 73), and III-V in 26.5% (N = 31).

Discussion: Post-discharge ED utilization is a novel quality metric and represents a potential target population for reducing hospital readmissions. Over two-thirds (72%) of ED visits were associated with low acuity complications, and promoting institutional strategies addressing postoperative ED visits may improve patient care and efficient utilization of healthcare resources.
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http://dx.doi.org/10.1016/j.hpb.2019.10.004DOI Listing
May 2020

In-hospital 30-day mortality for older patients with pancreatic cancer undergoing pancreaticoduodenectomy.

J Geriatr Oncol 2020 05 6;11(4):660-667. Epub 2019 Nov 6.

Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.

Objective: Surgical resection remains the only potentially curative therapy for pancreatic ductal adenocarcinoma (PDAC). There is paucity of literature about morbidity and mortality in older patients with PDAC undergoing pancreaticoduodenectomy. This retrospective analysis evaluates the in-hospital 30-day mortality of this population utilizing the Nationwide Inpatient Sample (NIS) database.

Subjects And Methods: All US patients hospitalized for pancreaticoduodenectomy (Whipple procedure) were included. Data was obtained from the NIS provided by the Agency for Healthcare Research and Quality. Pancreaticoduodenectomy diagnoses were identified using Clinical Classifications Software codes based on ICD-9 between 2007 and 2010. Univariable and multivariable analyses were performed using the logistic model, weighted chi-square test, and generalized linear model.

Results: A total of 6149 patient discharges for pancreaticoduodenectomy were identified. Mean age was 64.9 years (SD ± 12.3); 21% of patients were ≥ 76 years of age. Majority were White (N = 5257, 77.9%) with a male:female ratio of 1. Patients aged 76 and older (OR: 1.76; 1.36-2.28; p < .001), Hispanics (OR: 1.40; 0.92-2.13; p = .12), and high comorbidity score (OR: 5.70; 3.44-9.46; p < .001) were found to be associated with a higher risk of 30-day in-hospital mortality. In the multivariable analysis, advanced age (>76) remained a significant predictor of longer in-hospital length of stay (OR: 1.09; 1.04-1.14; p < .001) and 30-day in-hospital mortality (OR 1.46; 1.07-2.00; p = .016). The 30-day in-hospital mortality rate for all patients across all years was 3.24%, for patients >76 years 4.11% and for patients <76 years 2.77%. Patients who underwent surgery at teaching hospitals (OR: 0.61; 0.42-0.88; p = .008) had a lower risk of 30-day in-hospital mortality compared to non-teaching hospitals.

Conclusion: In-hospital 30 day mortality was higher in selected older patients with PDAC undergoing pancreaticoduodenectomy. Mortality was lower at high volume and teaching centers. Further stringent selection criteria are needed to decrease mortality in the older population.
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http://dx.doi.org/10.1016/j.jgo.2019.10.012DOI Listing
May 2020

Bile cultures are poor predictors of antibiotic resistance in postoperative infections following pancreaticoduodenectomy.

HPB (Oxford) 2020 Jul 26;22(7):969-978. Epub 2019 Oct 26.

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

Background: Bile cultures (BC) have routinely been used to guide empiric antibiotic therapy for developing postoperative infections. The ability of BCs to predict sensitivity and resistance patterns (SRP) of site of infection cultures (SOIC) remains controversial. The aim was to assess the concordance of pathogens and SRPs between paired BC/SOICs.

Methods: Medical records of consecutive patients undergoing pancreaticoduodenectomy were reviewed between 2014 and 2018. BC/SOIC pathogens and SRPs were compared on a patient-by-patient basis and concordance (K) was assessed.

Results: Common patient characteristics of 522 included patients were 65-years-old, Caucasian (75.5%), male (54.2%), malignant indication (79.3%), and preoperative biliary stent (59.0%). Overall, 275 (89.6%) BCs matured identifiable isolates with 152 (55.2%) demonstrating polymicrobial growth. Ninety-two (17.6%) SOICs were obtained: 48 and 44 occurred in patients with and without intraoperative BCs. Stents were associated with bacteriobilia (85.7%, K = 0.947, p < 0.001; OR 22.727, p < 0.001), but not postoperative infections (15.2%; K = 0.302, p < 0.001; OR 1.428, p = 0.122). Forty-eight patients demonstrated paired BC/SOICs to evaluate. Pathogenic concordance of this group was 31.1% (K = 0.605, p < 0.001) while SRP concordance of matched pathogens was 46.7% (K = 0.167, p = 0.008).

Conclusion: Bile cultures demonstrate poor concordance with the susceptibility/resistance patterns of postoperative infections following pancreaticoduodenectomy and may lead to inappropriate antibiotic therapies.
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http://dx.doi.org/10.1016/j.hpb.2019.10.016DOI Listing
July 2020