Publications by authors named "Douglas L Fraker"

174 Publications

Ninety-day mortality after total gastrectomy for gastric cancer.

Surgery 2021 Mar 28. Epub 2021 Mar 28.

Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Pennsylvania, PA. Electronic address:

Background: Total gastrectomy for gastric cancer is associated with significant 30-day mortality, but this endpoint may underestimate the short-term mortality of the procedure.

Methods: Retrospective analysis was performed using the National Cancer Database (2004-2015). Patients who underwent total gastrectomy for stage I to III gastric adenocarcinoma were identified and divided into cohorts based on 90-day mortality. Predictors of mortality were analyzed using multivariable logistic regression, and annual trends in mortality rates were calculated by Joinpoint Regression.

Results: Of the 5,484 patients who underwent total gastrectomy, 90-day and 30-day mortality rates were 9.1% and 4.7%, respectively. Factors associated with 90-day mortality included increasing age (odds ratio 1.0, P < .001), income below the median (odds ratio 1.2, P = .039), Charlson-Deyo score ≥2 (odds ratio 1.4, P = .039), treatment at low-volume facilities (odds ratio 1.5, P < .001), N1 (odds ratio 2.0, P < .001), N2 (odds ratio 2.0, P < .001), or N3 (odds ratio 2.7, P < .001) stage disease, having <16 lymph nodes harvested (odds ratio 1.5, P < .001), and lack of treatment with chemotherapy (3.7, P < .001). Lack of health insurance (odds ratio 4.1, P = .080), and positive microscopic margins (odds ratio 1.3, P = .080) were correlated, but not significantly associated, with 90-day mortality. The 90-day mortality rate significantly declined from 14.3% in 2004 to 7.9% in 2015 (P = .006), and the 30-day mortality rate significantly declined from 7.7% in 2004 to 4.8% in 2015 (P = .009).

Conclusion: Nearly half of the deaths within 90 days after total gastrectomy for cancer occur beyond 30 days postoperative. Ninety-day mortality has improved over time, but rates remain high, suggesting the need for improved out-of-hospital postoperative care beyond 30 days.
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http://dx.doi.org/10.1016/j.surg.2021.02.010DOI Listing
March 2021

"Double-Down" Adrenal Vein Sampling Results in Patients with Apparent Bilateral Aldosterone Suppression: Utility of Repeat Sampling including Super-Selective Sampling.

J Vasc Interv Radiol 2021 Mar 26. Epub 2021 Mar 26.

Department of Radiology, Division of Interventional Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Purpose: To report outcomes of patients undergoing adrenal vein sampling (AVS) for primary aldosteronism with results indicating apparent bilateral adrenal suppression (ABAS), in which the adrenal aldosterone-to-cortisol ratios are decreased bilaterally ("double-down") compared to the non-adrenal sample, and evaluate repeat AVS results.

Materials And Methods: Between 2003 and 2020, 762 patients underwent AVS. Twenty patients (2.6%; male, 12; female, 8; age 50.3 ± 9.7 years) with ABAS on initial AVS were identified. Ten underwent repeat AVS. Super-selective AVS (SS-AVS) was employed in 6 of 10 repeat AVS (60%). Outcomes after AVS were analyzed. A lateralization index (LI) >4 was considered an indication for adrenalectomy.

Results: Repeat AVS was diagnostic in 70% of patients (n = 7), with 6 of 7 lateralizing with LI >4 (median LI = 32.3; range 4.6-54.8) and 1 of 7 nearly lateralizing (LI = 3.5). All 7 patients underwent adrenalectomy. ABAS was redemonstrated in 3 patients (30%): 2 with unilateral adenomas on cross-sectional imaging underwent adrenalectomy despite ABAS results and 1 was lost to follow-up. Four of 6 patients (66%) who underwent SS-AVS were diagnosed with unilateral disease (median LI = 43.3; range 23.9-54.8), with one patient's diagnosis reliant upon a single super-selective sample. In total, 9 patients underwent adrenalectomy after repeat AVS, all of whom had improved blood pressure control postoperatively. Ten patients did not undergo repeat AVS: 6 were lost to follow-up, 3 underwent medical management, and 1 underwent adrenalectomy.

Conclusions: AVS should be repeated when "double-down" ABAS results are encountered. Super-selective sampling may provide worthwhile diagnostic data when employed during repeat AVS.
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http://dx.doi.org/10.1016/j.jvir.2020.12.029DOI Listing
March 2021

Preoperative Biopsy in Patients with Retroperitoneal Sarcoma: Usage and Outcomes in a National Cohort.

Ann Surg Oncol 2021 Feb 16. Epub 2021 Feb 16.

Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Hospital of the University of Pennsylvania, Philadelphia, PA, 19104, USA.

Introduction: Preoperative biopsy (PBx) is often recommended for retroperitoneal sarcoma (RPS), but its utilization rate and impact on perioperative management and outcomes remains undefined.

Methods: Using the National Cancer Database, patients who underwent resection of non-metastatic RPS were identified (2006-2014). Patients who did and did not undergo PBx of the primary tumor were compared using propensity matching, and factors associated with survival were assessed by multivariable analysis.

Results: Of 2620 patients, 1110 (42.4%) underwent PBx. Factors significantly associated with performance of PBx included male sex [odds ratio (OR) 1.2, P = 0.035], tumor size ≤ 5 cm (OR 1.5, P = 0.012), tumor size > 5 to ≤ 10 cm (OR 1.3, P = 0.009), non-well-differentiated liposarcoma histology (OR 2.0, P ≤ 0.001), and treatment at a high-volume center (OR 1.3, P = 0.021). Receipt of PBx was significantly associated with administration of neoadjuvant radiation (OR 8.8, P < 0.001) or systemic therapy (OR 3.3, P < 0.001), radical surgical resection (OR 1.6, P < 0.001), and complete tumor resection (OR 1.5, P < 0.003). Neoadjuvant radiation [hazard ratio (HR) 0.7, P = 0.003] and complete tumor resection (HR 0.6, P < 0.001) were significantly associated with improved overall survival (OS). Performance of PBx was not associated with OS (HR 1.1, P = 0.070), and following propensity matching, 5-year OS did not differ between the two groups (56.5% PBx vs 58.4% no PBx, P = 0.247).

Conclusions: A minority of patients with non-metastatic RPS undergo PBx. PBx does not negatively impact survival, but may indirectly improve outcomes in select patients by virtue of receipt of neoadjuvant therapy and attainment of complete tumor resection.
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http://dx.doi.org/10.1245/s10434-021-09691-8DOI Listing
February 2021

Double adenoma as a cause of primary hyperparathyroidism: Asymmetric hyperplasia or a distinct pathologic entity?

Am J Surg 2021 Jan 19. Epub 2021 Jan 19.

Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA; Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA. Electronic address:

Background: Primary hyperparathyroidism (PHPT) caused by double adenoma may carry a higher risk of failure to cure. We compared outcomes in single adenoma (SA), double adenoma (DA) and four-gland hyperplasia (HP).

Methods: Patients undergoing initial parathyroidectomy for PHPT were categorized by diagnosis. The primary outcome was persistent/recurrent disease postoperatively.

Results: Of 3408 patients, 81.3% had SA, 9.5% had DA, and 9.3% had HP. Rates of persistence/recurrence were 2.9%, 5.3%, and 4.5% in SA, DA, and HP, respectively (p = 0.281). Patients with persistence/recurrence had higher preoperative calcium (11.0 vs 10.7 mg/dl, p = 0.028) and PTH (96 vs 77 pg/ml, p = 0.015), and lower rates of IOPTH normalization (77% vs 96%, p < 0.001). On multivariable analysis, DA was associated with increased risk of persistent/recurrent disease (OR 3.0, p = 0.017).

Conclusions: Most patients with DA are cured with removal of two glands, but approximately 5% experience disease persistence/recurrence. Low-normal final IOPTH was associated with lower risk of persistent/recurrent disease.
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http://dx.doi.org/10.1016/j.amjsurg.2021.01.021DOI Listing
January 2021

National trends in the presentation of surgically resected appendiceal adenocarcinoma over a decade.

J Surg Oncol 2021 Feb 10;123(2):606-613. Epub 2020 Nov 10.

Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Rates of nonoperative management of acute appendicitis and appendiceal adenocarcinoma have increased over a decade, but the presentation and outcomes of appendiceal adenocarcinoma over this period is not well-characterized.

Methods: Patients with surgically resected Stage I-III appendiceal adenocarcinoma were identified from the 2006 to 2015 National Cancer Data Base and classified into two cohorts, 2006-2010 and 2011-2015, based on year of diagnosis. Three-year overall survival (OS) was analyzed using Cox proportional hazards regression and Kaplan-Meier survival estimates.

Results: Of 4233 patients, 1369 (32.3%) and 2864 (67.7%) were diagnosed in 2006-2010 and 2011-2015, respectively. Following multivariable analysis, patients in 2011-2015 were more likely to be <40 years of age (6.4% vs. 4.7%, odds ratio [OR] 1.53, p .015), present with pT4 tumors (40.2% vs. 34.4%, OR 1.46, p .004), and undergo hyperthermic intraperitoneal chemotherapy (4.4% vs. 2.4%, OR 1.97, p .001). Comparing patients diagnosed in 2011-2015 to 2006-2010, adjusted 3-year OS was no different among all patients (81.1% vs. 79%, p .778).

Conclusions: There has been an increase in the proportion of patients with pT4 appendix tumors over time, primarily among older (≥60 years) patients. Even so, these shifts in presentation have not resulted in differences in survival outcomes.
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http://dx.doi.org/10.1002/jso.26295DOI Listing
February 2021

Are Volume Pledge Standards Worth the Travel Burden for Major Abdominal Cancer Operations?

Ann Surg 2020 Oct 14. Epub 2020 Oct 14.

Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania.

Objective: The study objective is to determine the association between travel distance and surgical volume on outcomes after esophageal, pancreatic, and rectal cancer resections.

Summary Of Background Data: "Take the Volume Pledge" aims to centralize esophagectomies, pancreatectomies, and proctectomies to hospitals meeting minimum volume standards. The impact of travel, and possible care fragmentation, on potential benefits of centralized surgery is not well understood.

Methods: Using the National Cancer Database (2004-2016), patients who underwent esophageal, pancreatic, or rectal resections at far HVH meeting volume standards versus local intermediate (IVH) and low-volume (LVH) hospitals were identified. Perioperative outcomes and 5-year OS were compared.

Results: Of 49,454 patients, 17,544 (34.5%) underwent surgery at far HVH, 11,739 (23.7%) at local IVH, and 20,171 (40.8%) at local LVH. The median (interquartile range) travel distances were 77.1 (51.1-125.4), 13.2 (5.8-27.3), and 7.8 (3.1-15.5) miles to HVH, IVH, and LVH, respectively. By multivariable analysis, LVH was associated with increased 30-day mortality for all resections compared to HVH, but IVH was associated with mortality only for proctectomies [odds ratio 1.90, 95% confidence interval (CI) 1.31-2.75]. Compared to HVH, both IVH (hazard ratio 1.25, 95% CI 1.19-1.31) and LVH (hazard ratio 1.35, 95% CI 1.29-1.42) were associated with decreased 5-year OS.

Conclusions: Compared to far HVH, 30-day mortality was higher for all resections at LVH, but only for proctectomies at IVH. Five-year OS was consistently worse at local LVH and IVH. Improving long-term outcomes at IVH may provide opportunities for greater access to quality cancer care.
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http://dx.doi.org/10.1097/SLA.0000000000004361DOI Listing
October 2020

Racial Disparities in Primary Hyperparathyroidism.

World J Surg 2021 Jan 25;45(1):180-187. Epub 2020 Sep 25.

Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street 4 Silverstein Pavilion, Philadelphia, PA, 19104, USA.

Background: Racial disparities in surgery are increasingly recognized. We evaluated the impact of race on presentation, preoperative evaluation, and surgical outcomes for patients undergoing parathyroidectomy for primary hyperparathyroidism (PHPT).

Methods: We performed a retrospective cohort study of patients undergoing parathyroidectomy for PHPT at a single center (1997-2015). Patients were classified by self-identified race, as African-American or White. The primary outcome was disease severity at referral. The secondary outcome was completeness of preoperative evaluation. Operative success and surgical cure were evaluated.

Results: A total of 2392 patients were included. The majority of patients (87.6%) were White. African-American patients had higher rates of comorbid disease as well as higher preoperative calcium (10.9 vs.10.8 mg/dl, p < 0.001) and PTH levels (122 vs. 97 pg/ml, p < 0.001). White patients were more likely to have history of bone loss documented by DXA and nephrolithiasis. African-American patients had lower rates of complete preoperative evaluation including DXA scan. Operatively, African-American patients had larger glands by size (1.7 vs. 1.5 cm, p < 0.001) and mass (573 vs. 364 mg, p < 0.001). We observed similar operative success (98.9 vs. 98.0%, p = 0.355) and cure rates (98.3 vs. 97.0%, p = 0.756).

Conclusions: At the time of surgical referral, African-American patients with PHPT have more biochemically severe disease and higher rates of incomplete evaluation. Operative success and cure rates are comparable.
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http://dx.doi.org/10.1007/s00268-020-05791-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906108PMC
January 2021

Defining postoperative weight change after pancreatectomy: Factors associated with distinct and dynamic weight trajectories.

Surgery 2020 Dec 14;168(6):1041-1047. Epub 2020 Sep 14.

Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. Electronic address:

Background: Weight change offers the simplest indication of a patient's recovery after an operation. There have been no studies that have thoroughly investigated postoperative weight dynamics after pancreatectomy. The aim of this study was to define postoperative weight change after a pancreatectomy and determine factors associated with optimal and poor weight trajectories.

Methods: From 2004 to 2019, 1,090 proximal (65%) and distal (35%) pancreatectomies were performed in patients with adequate data in the medical records. Patient weights were acquired preoperatively and at postoperative months 1, 3, and 12. Optimal (top quartile, weight restoration) and poor (bottom quartile, persistent weight loss) postoperative weight cohorts were identified at 1 year postoperatively.

Results: The median percentage weight change 1 year postpancreatectomy was -6.6% (interquartile range: -1.4% to -12.5%), -7.8% for proximal pancreatectomy, and -4.2% for distal pancreatectomy. For most patients (interquartile range cohort), the median percentage weight change at 1, 3, and 12 months was -6.2%, -7.2%, and -6.6%. The independent factors associated with weight restoration were age <65, nonobesity (body mass index <30kg/m), receiving total parenteral nutrition/total enteral nutrition preoperatively, experiencing preoperative weight loss >10%, distal pancreatectomy, not undergoing vascular resection, and no readmission within 30 days. Conversely, persistent weight loss was associated with American Society of Anesthesiologists classes III to IV, obesity, malignancy, proximal pancreatectomy, blood loss ≥350mL, and experiencing readmission within 30 days. Focusing on pancreatic ductal adenocarcinoma (n = 372) patients, the factors associated with persistent weight loss were obesity, proximal pancreatectomy, and experiencing recurrence within 1 year; however, weight cohorts were not associated with overall survival for pancreatic ductal adenocarcinoma patients.

Conclusion: These data define weight kinetics after pancreatectomy. Ultimately, postoperative weight trajectories appear to be largely predetermined but may be mitigated by limiting readmissions and complications. Clinicians should use these data to identify patients who continue to lose weight between the first and third month postoperatively with a high suspicion for the requirement of nutritional monitoring or other interventions.
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http://dx.doi.org/10.1016/j.surg.2020.07.056DOI Listing
December 2020

Predicting Metastatic Potential in Pheochromocytoma and Paraganglioma: A Comparison of PASS and GAPP Scoring Systems.

J Clin Endocrinol Metab 2020 12;105(12)

University of Colorado School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism and Diabetes and the Division of Biomedical Informatics and Personalized Medicine, Aurora, Colorado.

Purpose: The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict metastatic potential in pheochromocytomas (PCC) and paragangliomas (PGLs). The goal of this study is to assess PASS and GAPP as metastatic predictors and to correlate with survival outcomes.

Methods: The cohort included PCC/PGL with ≥5 years of follow-up or known metastases. Surgical pathology slides were rereviewed. PASS and GAPP scores were assigned. Univariable and multivariable logistic regression, Kaplan-Meier survival analysis, and Cox proportional hazards were performed to assess recurrence-free survival (RFS) and disease-specific survival (DSS).

Results: From 143 subjects, 106 tumors were PCC and 37 were PGL. Metastases developed in 24%. The median PASS score was 6.5 (interquartile range [IQR]: 4.0-8.0) and median GAPP score was 3.0 (IQR: 2.0-4.0). Interrater reliability was low-moderate for PASS (intraclass correlation coefficient [ICC]: 0.6082) and good for GAPP (ICC 0.7921). Older age (OR: 0.969, P = .0170) was associated with longer RFS. SDHB germline pathogenic variant (OR: 8.205, P = .0049), extra-adrenal tumor (OR: 6.357, P < .0001), Ki-67 index 1% to 3% (OR: 4.810, P = .0477), and higher GAPP score (OR: 1.537, P = .0047) were associated with shorter RFS. PASS score was not associated with RFS (P = .1779). On Cox regression, a GAPP score in the moderately differentiated range was significantly associated with disease recurrence (HR: 3.367, P = .0184) compared with well-differentiated score.

Conclusion: Higher GAPP scores were associated with aggressive PCC/PGL. PASS score was not associated with metastases and demonstrated significant interobserver variability. Scoring systems for predicting metastatic PCC/PGL may be improved by incorporation of histopathology, clinical data, and germline and somatic tumor markers.
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http://dx.doi.org/10.1210/clinem/dgaa608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553245PMC
December 2020

Do microscopic surgical margins matter for primary gastric gastrointestinal stromal tumor?

Surgery 2021 02 27;169(2):419-425. Epub 2020 Aug 27.

Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA.

Background: Although tumor size and mitotic rate are established prognostic factors for worse survival in patients undergoing surgical resection for gastric gastrointestinal stromal tumors, the impact of microscopic margins, or R1 resection, is not completely established.

Methods: Patients who received no neoadjuvant therapy and underwent surgical resection for stage I to III gastric gastrointestinal stromal tumors were identified from the 2010 to 2013 National Cancer Database and divided into 2 cohorts, R0 and R1 resections. Cox proportional hazards ratio and Kaplan Meier survival estimates were utilized to analyze 5-y overall survival.

Results: Of 2,084 patients, those with R1 resection (57, 2.7%) were more likely to have tumors >10 cm (28.1% vs 11.9%, odds ratio 3.51, P = .017) and stage III disease (26.3% vs 11.2%, odds ratio 2.26, P = .047). Although margin status was associated with higher risk tumors, it was not associated with receipt of adjuvant therapy. After multivariate Cox regression, R1 and R0 patients did not have a difference in 5-y overall survival (82.5% vs 88.6%, hazards ratio 1.26, P = .49). When stratified by stage of disease, there remained no difference in survival across all stages when comparing R1 and R0 patients.

Conclusion: Positive microscopic margins are uncommon but do not appear to impact survival outcomes in patients with resected localized gastric gastrointestinal stromal tumors.
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http://dx.doi.org/10.1016/j.surg.2020.07.018DOI Listing
February 2021

A case of tumor-to-tumor metastasis of cutaneous malignant melanoma.

J Cutan Pathol 2020 Dec 6;47(12):1196-1199. Epub 2020 Sep 6.

Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

We report a case of tumor-to-tumor metastasis of a cutaneous malignant melanoma to a synchronous thyroid Hurthle cell carcinoma. A 42-year-old male underwent a biopsy of right inguinal lymphadenopathy which showed metastatic melanoma. The primary lesion was identified on his right posterior leg, and staging workup discovered a synchronous left thyroid lobe nodule concerning for a follicular neoplasm. He underwent excision of the primary melanoma, right inguinal lymphadenectomy, and total thyroidectomy. The resected thyroid contained a 6.6-cm, well-encapsulated left-sided nodule, red-brown in color and homogenous in consistency, with areas of focal hemorrhage and no grossly identifiable calcification. Microscopically, large tumor cells with distinct cell borders were present, with deeply eosinophilic and granular cytoplasm, large nuclei with prominent nucleoli, and loss of polarity consistent with oncocytes. A microscopic single focus of vascular invasion was identified, and a diagnosis of angioinvasive Hurthle cell carcinoma was made. Within the Hurthle cell carcinoma, multiple deposits of metastatic melanoma were seen. These findings were indicative of tumor-to-tumor metastasis of the cutaneous melanoma to the angioinvasive Hurthle cell carcinoma. Our findings show the ability of melanoma to metastasize to a pre-existing neoplasm.
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http://dx.doi.org/10.1111/cup.13829DOI Listing
December 2020

Does multicenter care impact the outcomes of surgical patients with gastrointestinal malignancies requiring complex multimodality therapy?

J Surg Oncol 2020 Jun 20. Epub 2020 Jun 20.

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Regionalization of oncologic care has increased, but less is known whether patient outcomes are influenced by receipt of multimodality care through multicenter care (MCC) or single-center care (SCC).

Methods: Patients from 2004 to 2015 National Cancer Data Base diagnosed with stage II-III esophageal (EA), stage II-III pancreatic (PA), and stage II-IV rectal (RA) adenocarcinoma who underwent resection at a high volume center (HVC) and required radiation and/or chemotherapy were included. MCC (care at 2+ facilities) and SCC patients were propensity-score matched 1:2 and Cox proportional hazards regression used to analyze survival.

Results: On multivariable regression analysis, MCC in RA patients (N = 325/2097, 15.5%) was more associated with residing ≥40 miles from the HVC (odds ratio [OR] = 2.37; P = .044) and receipt of neoadjuvant chemotherapy (1.42, P = .040). In PA patients (N = 75/380, 19.7%), residing ≥40 miles from the HVC (OR = 3.22; P = .001), and in EA patients (N = 88/534, 16.5%), younger patients (<50 years: OR = 2.96; P = .011) were associated with MCC. Following propensity score matching, EA (N = 147), PA (N = 133), and RA (N = 661) patients had no difference in 1-year and 3-year overall survival when comparing MCC to SCC.

Conclusions: The use of MCC appears safe without a difference in survival and may offer significant advantages in convenience to patients as they undergo their complex oncologic care.
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http://dx.doi.org/10.1002/jso.26075DOI Listing
June 2020

Preoperative Transfusion for Anemia in Patients Undergoing Abdominal Surgery for Malignancy.

J Gastrointest Surg 2020 May 27. Epub 2020 May 27.

Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Background: Transfusion guidelines have been established for severe anemia, but limited data is available regarding the utility of preoperative transfusion. This study evaluates the predictive factors and relative value of preoperative transfusion in oncologic patients with moderate anemia undergoing abdominal surgery.

Methods: Using the American College of Surgeons National Surgical Quality Improvement Program database, adult patients with moderate anemia (hematocrit 21-27%) who underwent non-emergent abdominal oncologic resection from 2005 to 2017 were identified. Preoperative transfusion and non-transfused patients were propensity score matched based on baseline covariates. Outcomes were compared using univariate and Poisson regression analysis.

Results: Of 6222 patients, preoperative transfused (N = 1000, 16.1%) patients were more likely to have bleeding disorders (12.1% vs 6.7%, p < 0.0001) and baseline thrombocytopenia (12% vs 7.3%, p < 0.0001) and had shorter operative length (< 180 min: 69.4% vs 59.8%, p < 0.0001). After matching (N = 987/group), preoperative transfusion was associated with higher rates of intraoperative/postoperative transfusion (odds ratio 1.24, p 0.017) and surgical site infections (odds ratio 1.67, p 0.004) and longer length of stay (incidence rate ratio 1.06, p < 0.0001).

Conclusions: Preoperative transfusion is associated with increased surgical site infections and longer hospital stay and should be carefully considered in oncologic patients given the absence of improvement in outcomes.
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http://dx.doi.org/10.1007/s11605-020-04656-wDOI Listing
May 2020

National trends in ventral hernia repairs for patients with intra-abdominal metastases.

Surgery 2020 09 18;168(3):509-517. Epub 2020 May 18.

Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia PA.

Background: Ventral hernias in patients with intra-abdominal metastases may not be addressed owing to other oncologic priorities, but they can affect quality of life and lead to sequelae necessitating an emergency operation. We compared the national trends and perioperative outcomes for elective and nonelective ventral hernia repairs for patients with intra-abdominal metastases.

Methods: Patients were identified from the National Inpatient Sample (2003-2015). Temporal trends were described using average annual percent change. Perioperative outcomes between elective and nonelective ventral hernia repairs were compared using multivariable regressions.

Results: An estimated 947,112 ventral hernia repairs were performed nationally, including 5,602 (0.6%) in patients with intra-abdominal metastases. Among patients with intra-abdominal metastases, 40.1% had a nonelective ventral hernia repair, mean (standard deviation) age was 64 (12) years, and 65.1% were women. Between 2003 and 2015, the total number of ventral hernia repairs performed nationally did not change (average annual percent change 0.062, P = .84). For patients with intra-abdominal metastases, although there was no change in the number of elective ventral hernia repairs (average annual percent change 0.65, P = .59), the number of nonelective ventral hernia repairs increased significantly (average annual percent change 2.7, P = .025). By multivariable analyses, patients with intra-abdominal metastases who underwent a nonelective repair were more likely to experience complications (odds ratio 1.76, P = .001), nonroutine discharge (odds ratio 1.93, P < .001), and mortality (odds ratio 2.27, P = .035). Nonelective ventral hernia repairs was also associated with a 38.5% (P < .001) longer hospital stay and 24.4% (P < .001) higher charges.

Conclusion: The number of nonelective ventral hernia repairs, which is associated with substantial perioperative morbidity, has increased significantly among patients with intra-abdominal metastases. Surgeons should consider a nonemergency operation for select patients to mitigate the burden of nonelective ventral hernia repairs.
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http://dx.doi.org/10.1016/j.surg.2020.04.005DOI Listing
September 2020

Adrenalectomy for Secondary Malignancy: Patients, Outcomes, and Indications.

Ann Surg 2020 May 18. Epub 2020 May 18.

Massachusetts General Hospital, Department of Surgery, Boston MA.

Objective: The goal of this study was to examine a multi-institutional experience with adrenal metastases to describe survival outcomes and identify subpopulations who benefit from adrenal metastasectomy.

Background: Adrenalectomy for metastatic disease is well-described, although indications and outcomes are incompletely defined.

Methods: A retrospective cohort study was performed of patients undergoing adrenalectomy for secondary malignancy (2002-2015) at 6 institutions. The primary outcomes were disease free survival (DFS) and overall survival (OS). Analysis methods included Kaplan-Meier and Cox proportional hazards.

Results: Of 269 patients, mean age was 60.1 years; 50% were male. The most common primary malignancies were lung (n = 125, 47%), renal cell (n = 38, 14%), melanoma (n = 33, 12%), sarcoma (n = 18, 7%), and colorectal (n = 12, 5%). The median time to detection of adrenal metastasis after initial diagnosis of the primary tumor was 17 months (interquartile range: 6-41). Post-adrenalectomy, the median DFS was 18 months (1-year DFS: 54%, 5-year DFS: 31%). On multivariable analysis, lung primary was associated with longer DFS [hazard ratio (HR): 0.49, P = 0.008). Extra-adrenal oligometastatic disease at initial presentation (HR: 1.84, P = 0.016), larger tumor size (HR: 1.07, P = 0.013), chemotherapy as treatment of the primary tumor (HR: 2.07 P = 0.027) and adjuvant chemotherapy (HR: 1.95, P = 0.009) were associated with shorter DFS. Median OS was 53 months (1-year OS: 83%, 5-year OS: 43%). On multivariable analysis, extra-adrenal oligometastatic disease at adrenalectomy (HR: 1.74, P = 0.031), and incomplete resection of adrenal metastasis (R1 margins; HR: 1.62, P = 0.034; R2 margins; HR: 5.45, P = 0.002) were associated with shorter OS.

Conclusions: Durable survival is observed in patients undergoing adrenal metastasectomy and should be considered for subjects with isolated adrenal metastases.
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http://dx.doi.org/10.1097/SLA.0000000000003876DOI Listing
May 2020

Patterns of Metastasis in Merkel Cell Carcinoma.

Ann Surg Oncol 2021 Jan 13;28(1):519-529. Epub 2020 May 13.

Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Background: Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a propensity for regional and distant spread. Because of the relative infrequency of this disease, the patterns of metastasis in MCC are understudied.

Methods: Patients with American Joint Committee on Cancer (8th edition) stage I-IV MCC treated at our institution were identified (1/1/2008-2/28/2018). The first site of metastasis was classified as regional [regional lymph node (LN) basin, in-transit] or distant. Distant metastasis-free (DMFS) and MCC-specific (MSS) survival were estimated.

Results: Of 133 patients, 64 (48%) had stage I, 13 (10%) stage II, 48 (36%) stage III, and 8 (6%) stage IV disease at presentation. The median follow-up time in patients who remained alive was 36 (interquartile range 20-66) months. Regional or distant metastases developed in 78 (59%) patients. The first site was regional in 87%, including 73% with isolated LN involvement, and distant in 13%. Thirty-seven (28%) patients eventually developed distant disease, which most commonly involved the abdominal viscera (51%) and distant LNs (46%) first. The lung (0%) and brain (3%) were rarely the first distant sites. Stage III MCC at presentation was significantly associated with worse DMFS (hazard ratio 4.87, P = 0.001) and stage IV disease with worse MSS (hazard ratio 6.30, P = 0.002).

Conclusions: Regional LN metastasis is the most common first metastatic event in MCC, confirming the importance of nodal evaluation. Distant disease spread appears to have a predilection for certain sites. Understanding these patterns could help to guide surveillance strategies.
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http://dx.doi.org/10.1245/s10434-020-08587-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220648PMC
January 2021

Predictors of lymph node metastases in patients with mucinous appendiceal adenocarcinoma.

J Surg Oncol 2020 Sep 28;122(3):399-406. Epub 2020 Apr 28.

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Lymph node metastasis (LN+) is a prognostic factor in appendiceal cancers, but predictors and outcomes for LN+  in mucinous appendiceal adenocarcinoma (MAC) remain poorly defined.

Methods: Patients were identified from the 2010 to 2016 NCDB who underwent surgical resection as first-line management for Stage I-III mucinous appendiceal cancer. A LN+ risk-score model was developed using multivariable regression on a training data set and internally validated using a testing data set. Three-year overall survival (OS) was analyzed by Cox proportional hazards regression.

Results: Of 1158 patients, LN+ (N = 244, 21.1%) patients were more likely to have higher pT group and grade of disease, lymphovascular invasion (LVI), and positive margins on univariate analyses. Predictive factors associated with LN+ on multivariable analysis included positive surgical margins (odds ratio [OR] 3.00, P <.0001), higher grade (moderately differentiated: OR, 2.16, P < .0001; poorly or undifferentiated: OR, 3.07, P < .0001), and LVI (OR, 7.28, P < .0001). A validated risk-score model using these factors was developed with good performance (AUC 0.749). LN+ patients had a worse 3-year OS compared with LN- patients (17.4% vs 82.6%, hazard ratio 1.96, P = .001).

Conclusions: LN+ is associated with worse survival in patients with MAC. A risk-score model using margin status, LVI, and grade can accurately risk stratify patients for LN+.
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http://dx.doi.org/10.1002/jso.25963DOI Listing
September 2020

Surgical Outcomes in Patients With Malignant Small Bowel Obstruction: A National Cohort Study.

Ann Surg 2020 Mar 20. Epub 2020 Mar 20.

Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Objective: The study objectives were to characterize surgical outcomes for malignant small bowel obstruction (MaSBO) as compared to other small bowel obstructions (SBO) and to develop a prediction model for postoperative mortality for MaSBO.

Summary Background Data: MaSBO is a morbid complication of advanced cancers for which the optimal management remains undefined.

Methods: Patients who underwent surgery for MaSBO or SBO were identified from the National Surgical Quality Improvement Program (2005-2017). Outcomes [30-day morbidity, unplanned readmissions, mortality, postoperative length of stay (LOS)] were compared between propensity score-matched MaSBO and SBO patients. An internally validated prediction model for mortality in MaSBO patients was developed.

Results: Of 46,706 patients, 1612 (3.5%) had MaSBO. Although MaSBO patients were younger than those with SBO (median 63 vs 65 years, P < 0.001), they were otherwise more clinically complex, including a higher proportion with recent weight loss (22.0% vs 4.0%, P < 0.001), severe hypoalbuminemia (18.6% vs 5.2%, P < 0.001), and cytopenias. After matching (N = 1609/group), MaSBO was associated with increased morbidity [odds ratio (OR) 1.2, P = 0.004], but not readmission (OR 1.1, P = 0.48) or LOS (incidence rate ratio 1.0, P = 0.14). The odds of mortality were significantly higher for MaSBO than SBO (OR 3.3, P < 0.001). A risk-score model predicted postoperative mortality for MaSBO with an optimism-adjusted Brier score of 0.114 and area under the curve of 0.735. Patients in the highest-risk category (11.5% of MaSBO population) had a predicted mortality rate of 39.4%.

Conclusion: Surgery for MaSBO is associated with substantial morbidity and mortality, necessitating careful patient evaluation before operative intervention.
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http://dx.doi.org/10.1097/SLA.0000000000003890DOI Listing
March 2020

Single Gland, Ectopic Location: Adenomas are Common Causes of Primary Hyperparathyroidism in Children and Adolescents.

World J Surg 2020 05;44(5):1518-1525

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Background: Primary hyperparathyroidism (PHPT) in children and adolescents is uncommon. Data-driven guidelines for management in pediatric patients are limited.

Methods: We performed a retrospective cohort analysis of all patients (1997-2017) with PHPT ≤ 21 years of age who underwent parathyroidectomy at three institutions. Clinical and demographic variables were analyzed. Primary operative outcome was cure (normocalcemia > 6 months after surgery); secondary outcome was operative success (intraoperative parathyroid hormone decrease of ≥ 50%).

Results: We identified 86 patients with a median age of 17 years (IQR: 14, 19); 64% (n = 55) were female. The mean preoperative serum calcium was 11.7 mg/dL, median parathyroid hormone (PTH) was 110 pg/mL, and median urine calcium was 4.1 mg/kg/24 h. Preoperatively, sestamibi scan localized in 41/71 patients (58%); neck ultrasound localized in 19/44 (43%). The most common pathology at surgery was a single ectopic parathyroid adenoma in 71% (n = 61). A high incidence of ectopic adenomas (25%, n = 22) was observed, most commonly intrathymic (n = 13), followed by tracheoesophageal groove (n = 5), carotid sheath (n = 2), and intrathyroidal (n = 2). Of 56 patients with retrievable data > 6 months postoperatively, cure was achieved in 55 of 56 patients (98%). One patient who presented to us with parathyromatosis require subsequent reoperation.

Conclusion: In this multi-institutional series of PHPT in children and adolescents, the majority were sporadic PHPT and were due to a single adenoma. We observed a high incidence of ectopic parathyroid adenomas, most commonly intrathymic. Given the high risk for ectopic adenoma in pediatric patients, parathyroid surgery in children and adolescents should be performed by experienced surgeons.
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http://dx.doi.org/10.1007/s00268-019-05362-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124981PMC
May 2020

Clinical presentation and surgical outcomes in primary aldosteronism differ by race.

J Surg Oncol 2020 Mar 19;121(3):456-464. Epub 2019 Dec 19.

Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension; early diagnosis and intervention correlate with outcomes. We hypothesized that race may influence clinical presentation and outcomes.

Methods: We conducted a retrospective analysis of patients with PA (1997-2017) who underwent adrenal vein sampling (AVS). Patients were classified by self-reported race as black or non-black. Improvement was defined as postoperative decrease in mean arterial pressure (MAP), antihypertensive medications (AHM), or both.

Results: Among patients undergoing AVS (n = 443), 287 underwent adrenalectomy. Black patients (28.2%) had higher body mass index (33.9 vs 31.8 kg/m ; P = .01), longer median duration of hypertension (12 vs 10 years; P = .003), higher modified Elixhauser comorbidity index (2 vs 1; P = .004), and lower median income ($47 134 vs $78 280; P < .001). Black patients had similar aldosterone:renin ratios (150 vs 135.6 [ng/dL]/[ng·mL· hr ]; P = .23) compared to non-blacks. At long-term follow-up, black patients had a similar requirement for AHM (1 vs 0; P = .13) but higher MAP (100.6 vs 95.3 mm Hg; P = .004).

Conclusion: Black patients present with longer duration of hypertension and more comorbidities. They are equally likely to lateralize on AVS, suggesting similar disease phenotype. However, black patients demonstrate less improvement with adrenalectomy; this may reflect a delay in diagnosis or concomitant essential hypertension.
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http://dx.doi.org/10.1002/jso.25806DOI Listing
March 2020

Opioid Use Disorder is Associated With Complications and Increased Length of Stay After Major Abdominal Surgery.

Ann Surg 2019 Nov 27. Epub 2019 Nov 27.

Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Objective: The objective of this study was to determine the impact of opioid use disorder (OUD) on perioperative outcomes after major upper abdominal surgeries.

Summary Of Background Data: OUD, defined as dependence/abuse, is a national health epidemic. Its impact on outcomes after major abdominal surgery has not been well characterized.

Methods: Patients who underwent elective esophagectomy, total/partial gastrectomy, major hepatectomy, and pancreatectomy were identified using the National Inpatient Sample (2003-2015). Propensity score matching by baseline characteristics was performed for patients with and without OUD. Outcomes measured were in-hospital complications, mortality, length of stay (LOS), and discharge disposition.

Results: Of 376,467 patients, 1096 (0.3%) had OUD. Patients with OUD were younger (mean 53 vs 61 years, P < 0.001) and more often male (55.1% vs 53.2%, P < 0.001), black (15.0% vs 7.6%, P < 0.001), Medicaid beneficiaries (22.0% vs 6.4%, P < 0.001), and in the lowest income quartile (32.6% vs 21.3%, P < 0.001). They also had a higher rate of alcohol (17.2% vs 2.8%, P < 0.001) and nonopioid drug (2.2% vs 0.2%, P = 0.023) dependence/abuse. After matching (N = 1077 OUD, N = 2164 no OUD), OUD was associated with a higher complication rate (52.9% vs 37.3%, P < 0.001), including increased pain [odds ratio (OR) 3.5, P < 0.001], delirium (OR 3.0, P = 0.004), and pulmonary complications (OR 2.0, P = 0.006). Additionally, OUD was associated with increased LOS (mean 12.4 vs 10.6 days, P = 0.015) and nonroutine discharge (OR 1.6, P < 0.001). In-hospital mortality did not differ (OR 2.4, P = 0.10).

Conclusion: Patients with OUD more frequently experienced complications and increased LOS. Close postoperative monitoring may mitigate adverse outcomes.
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http://dx.doi.org/10.1097/SLA.0000000000003697DOI Listing
November 2019

Grade is a Dominant Risk Factor for Metastasis in Patients with Rectal Neuroendocrine Tumors.

Ann Surg Oncol 2020 Mar 7;27(3):855-863. Epub 2019 Nov 7.

Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Background: Small (< 2 cm) and diminutive (< 1 cm) rectal neuroendocrine tumors (RNETs) are often described as indolent lesions. A large single-center experience was reviewed to determine the incidence of metastasis and the risk factors for its occurrence.

Methods: Cases of RNET between 2010 and 2017 at a single institution were retrospectively reviewed. The rate of metastasis was determined, and outcomes were stratified by tumor size and grade. Uni- and multivariable predictors of metastasis were identified, and a classification and regression tree analysis was used to stratify the risk for distant metastasis.

Results: The study identified 98 patients with RNET. The median follow-up period was 28 months. Of the 98 patients, 79 had primary tumors smaller than 1 cm, 8 had tumors 1 to 2 cm in size, and 11 had tumors 2 cm in size or larger. In terms of grade, 86 patients had grade 1 (G1) tumors, 8 patients had grade 2 (G2) tumors, and 4 patients had grade 3 (G3) tumors. Twelve patients developed metastatic disease. Both size and grade were associated with distant metastasis in the uni- and multivariable analyses, but when stratified by grade, size was predictive of metastasis only for G1 tumors (p < 0.001). Among the 12 patients with metastatic disease, 3 (25%) had diminutive primary tumors, and 9 (75%) had primary tumors 2 cm in size or larger. Diminutive tumors that metastasized were all G2.

Conclusions: Patients with diminutive and small RNETs are at risk for metastatic disease. Tumor grade is a dominant predictor of dissemination. More rigorous staging, closer surveillance, or more aggressive initial management may be warranted for patients with G2 tumors, irrespective of size.
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http://dx.doi.org/10.1245/s10434-019-07848-0DOI Listing
March 2020

Defining the Safety Profile for Performing Pancreatoduodenectomy in the Setting of Hyperbilirubinemia.

Ann Surg Oncol 2020 May 5;27(5):1595-1605. Epub 2019 Nov 5.

Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Background: Hyperbilirubinemia is commonly observed in patients requiring pancreatoduodenectomy (PD). Thus far, literature regarding the danger of operating in the setting of hyperbilirubinemia is equivocal. What remains undefined is at what specific level of bilirubin there is an adverse safety profile for undergoing PD. The aim of this study is to identify the optimal safety profile of patients with hyperbilirubinemia undergoing PD.

Patients And Methods: The present work analyzed 803 PDs from 2004 to 2018. A generalized additive model was used to determine cutoff values of total serum bilirubin (TB) that were associated with increases in adverse outcomes, including 90-day mortality. Subgroup comparisons and biliary stent-specific analyses were performed for patients with TB below and above the cutoff.

Results: TB of 13 mg/dL was associated with an increase in 90-day mortality (P = 0.043) and was the dominant risk factor on multivariate logistic regression [odds ratio (OR) 8.193, P = 0.001]. Increased TB levels were also associated with reoperations, number of complications per patient, and length of stay. Patients with TB greater than or equal to 13 mg/dL (TB ≥ 13) who received successful biliary decompression through stenting had less combined death and serious morbidity (P = 0.048).

Conclusions: Preoperative TB ≥ 13 mg/dL was associated with increased 90-day mortality after PD. Reducing a TB ≥ 13 is generally recommended before proceeding to surgery.
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http://dx.doi.org/10.1245/s10434-019-08044-wDOI Listing
May 2020

Challenges in obesity and primary aldosteronism: Diagnosis and treatment.

Surgery 2020 01 18;167(1):204-210. Epub 2019 Sep 18.

Department of Surgery, Division of Endocrine and Oncologic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA. Electronic address:

Background: Obese patients may have unrecognized primary aldosteronism due to high rates of concomitant hypertension. We hypothesized that obesity impacts the diagnosis and management of patients with primary aldosteronism.

Methods: We conducted a retrospective analysis of all primary aldosteronism patients (n = 418) who underwent adrenal vein sampling (1997-2017). Patients were classified by body mass index as obese (body mass index ≥35) or nonobese (body mass index <35) and diagnostic evaluation was compared between groups. Within the operative cohort (n = 285), primary outcomes were changes in both blood pressure and antihypertensive medications after adrenalectomy. Secondary outcome was clinical resolution by Primary Aldosteronism Surgery Outcomes criteria.

Results: Thirty-five percent of patients were obese. Obese patients were more likely to be male (67.8% vs 56.1%, P = .025), somewhat younger (51.5 vs 54.4 years old, P < .012), and require more preoperative antihypertensive medications (6.7 vs 5.7, P = .04) than nonobese patients. Obese patients had lesser rates of radiologic evidence of adrenal tumors (68.4 vs 77.9%, P = .038) despite similar rates of lateralization on adrenal vein sampling. In the operative subset, obese patients had somewhat smaller tumors on final pathology (1.1 vs 1.5 cm, P = .014) but similar rates of complete and partial clinical resolution (P = 1.000).

Conclusion: Obese primary aldosteronism patients have lesser rates of localization by imaging, likely due to smaller tumor size, however, experience similar benefit from adrenalectomy.
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http://dx.doi.org/10.1016/j.surg.2019.03.036DOI Listing
January 2020

Practice Patterns and Prognostic Value of Sentinel Lymph Node Biopsy for Thick Melanoma: A National Cancer Database Study.

Ann Surg Oncol 2019 Dec 4;26(13):4651-4662. Epub 2019 Sep 4.

Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Background: Sentinel lymph node biopsy (SLNB) has been somewhat controversial for patients with a diagnosis of thick (> 4 mm) melanoma. This study aimed to characterize the national practice pattern in performing SLNB for this patient population and to determine the predictors and prognostic value of nodal positivity using population-level data.

Methods: Patients with a diagnosis of clinically node-negative, thick melanoma (2010-2015) were identified using the National Cancer Database. Factors associated with performing regional nodal evaluation were characterized. Predictors of nodal positivity were determined using multivariable logistic regression. Overall survival (OS) was estimated using standard statistical methods.

Results: Of 9847 study patients, 7513 (76.3%) underwent SLNB. The patients who underwent nodal evaluation were younger (median age, 66 vs 81 years; P < 0.001), less likely to have comorbid conditions (19.6% vs 26.0%; P < 0.001), more often privately insured (40.4% vs 16.4%; P < 0.001), and more frequently treated at an academic center (49.5% vs 43.9%; P < 0.001). Among those who underwent nodal evaluation, 25.5% had metastatic nodes. Multivariable regression identified age, Charlson-Deyo score, primary location, ulceration, mitoses, vertical growth phase, and lymphovascular invasion as independent predictors of nodal positivity, but with only moderate predictive accuracy (optimism-adjusted area under the curve, 0.684). Furthermore, compared with node negativity, node positivity was significantly associated with decreased OS (hazard ratio, 2.05; P < 0.001).

Conclusion: Although nodal status provides important prognostic information, at a national level, nearly one fourth of patients with clinically node-negative, thick melanoma do not undergo SLNB. Appropriate pathologic staging would allow these high-risk patients to be candidates for effective adjuvant therapy.
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http://dx.doi.org/10.1245/s10434-019-07783-0DOI Listing
December 2019

Intraoperative Parathyroid Hormone Monitoring in Parathyroidectomy for Tertiary Hyperparathyroidism.

J Surg Res 2019 12 4;244:77-83. Epub 2019 Jul 4.

Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: Tertiary hyperparathyroidism (THPT) is characterized by hypercalcemia and hyperparathyroidism after renal allograft. Limited data exist regarding the use of intraoperative parathyroid hormone (IOPTH) for THPT. We examined our series of parathyroidectomies performed for THPT to determine clinical outcomes with respect to IOPTH.

Materials And Methods: Patients who underwent parathyroidectomy for THPT (1999-2017) were identified for inclusion. Retrospective chart review was performed. Cure was defined as eucalcemia ≥6 mo after surgery. Statistical analysis was performed.

Results: Of 41 patients included in the study, 41% (n = 17) were female. The median duration of dialysis before renal allograft was 34 mo (interquartile interval [IQI]:6-60). Preoperatively, the median calcium level was 10.4 mg/dL (IQI:10.0-11.2), median parathyroid hormone was 172 pg/mL (IQI:104-293), and renal function was minimally abnormal with median glomerular filtration rate 58 mL/min/1.73 m2 (IQI:49-71). At surgery, the median final IOPTH was 40 pg/mL (IQI:29-73), and median decrease in IOPTH was 78% (IQI:72-87), with 88% (n = 36) of patients demonstrating >50% decrease. Median calcium level ≥6 mo after surgery was 9.4 mg/dL (IQI:8.8-9.7), and only one patient had recurrent hypercalcemia. Failure to achieve >50% decrease in IOPTH was not significantly associated with recurrent hypercalcemia (P = 1.000). With a median follow-up time of 41 mo (IQI:25-70), only three patients had graft failure. The positive predictive value of IOPTH for cure was 89% (95% confidence interval: 0.752-0.971), with 0% negative predictive value and 87% accuracy (95% confidence interval: 0.726-0.957).

Conclusions: Subtotal parathyroidectomy is a successful operation with durable cure of THPT. IOPTH fails to predict long-term cure in THPT despite minimally abnormal renal function.
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http://dx.doi.org/10.1016/j.jss.2019.06.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179078PMC
December 2019

Survival Outcomes of Patients with Clinical Stage III Melanoma in the Era of Novel Systemic Therapies.

Ann Surg Oncol 2019 Dec 3;26(13):4621-4630. Epub 2019 Jul 3.

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Background: Immune checkpoint and BRAF-targeted inhibitors have demonstrated significant survival benefits for advanced melanoma patients within the context of clinical trials. We sought to determine their impact on overall survival (OS) at a population level in order to better understand the current landscape for patients diagnosed with clinical stage III melanoma.

Methods: A retrospective study was performed using the National Cancer Database. Patients diagnosed with clinical stage III melanoma were categorized by diagnosis year into two cohorts preceding the advent of novel therapies (P1: 2004-2005, P2: 2008-2009) and a contemporary group (P3: 2012-2013). OS was estimated using standard time-to-event statistical methods.

Results: Of 3720 patients, 525 (14%) were diagnosed in P1, 1375 (37%) in P2, and 1820 (49%) in P3. Median age at diagnosis increased over time (58, 59, and 61 years in P1, P2, and P3, respectively, P = 0.004). OS increased between P2 (median 49.3 months) and P3 (median 58.2 months, Bonferroni-corrected log-rank P < 0.001) but did not differ between P1 (median 50.5 months) and P2 (Bonferroni-corrected log-rank P > 0.99). These differences persisted on multivariable analysis. OS improved for patients diagnosed in P3 compared with P1 [hazard ratio (HR) 0.76, P < 0.001] but not P2 compared with P1 (HR 0.96, P = 0.52).

Conclusions: OS has significantly improved nationally for patients newly diagnosed with clinical stage III melanoma in the era of novel melanoma therapies. OS outcomes will likely continue to evolve as these agents are increasingly utilized in the adjuvant setting. These data may help to better inform affected patients with respect to prognosis.
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http://dx.doi.org/10.1245/s10434-019-07599-yDOI Listing
December 2019

Isolated limb perfusion and infusion in the treatment of melanoma and soft tissue sarcoma in the era of modern systemic therapies.

J Surg Oncol 2019 Sep 2;120(3):540-549. Epub 2019 Jul 2.

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Background And Objectives: Isolated limb perfusion (ILP) and infusion (ILI) are treatment modalities for unresectable melanoma in-transit metastases and extremity soft tissue sarcomas (STS). We sought to characterize the national trend in their utilization in the context of novel melanoma therapies introduced in 2011.

Methods: Using the National Inpatient Sample (2005-2014), patients with a primary diagnosis of limb melanoma or STS who underwent ILP/ILI were identified by diagnosis and procedure codes. Annual percent change (APC) in ILP/ILI procedures was determined.

Results: From 2005 through 2014, 670 and 130 ILP/ILI procedures were performed for melanoma and STS, respectively. Mean age was 64 (SD 15) years for melanoma and 59 (SD 18) years for STS. Over time, procedures for melanoma decreased with an APC of -17 (P = .019). Comparing 2005-2010 and 2011-2014, the mean number of procedures for melanoma decreased from 91 to 32 per year (P = .007). In contrast, there was no change for STS (APC 6.5, P = .39; mean 11 and 16 per year in 2005-2010 and 2011-2014, respectively, P = .46).

Conclusions: ILI/ILP utilization has decreased for melanoma, but not for STS. Whether trends for ILP and ILI differed could not be determined. ILP/ILI remains an important option to consider for regional disease control.
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http://dx.doi.org/10.1002/jso.25600DOI Listing
September 2019

The impact of surgery for metastatic pancreatic neuroendocrine tumor: a contemporary evaluation matching for chromogranin a level.

HPB (Oxford) 2020 01 22;22(1):83-90. Epub 2019 Jun 22.

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Background: Studies supporting surgical management of metastatic pancreatic neuroendocrine tumor (PNET) are limited by selection bias. Chromogranin A (CgA) has been used as a biomarker for PNET and may reflect disease burden or biology. This study aimed to correlate CgA level with overall survival and to use it to match patients selected for different treatment approaches in an analysis of the impact of surgical management.

Methods: 1478 patients diagnosed with PNET in the National Cancer Database (2004-2014) were retrospectively identified, and logistic regression analyses were used to evaluate associations between the presence of metastatic disease and CgA level. After matching patients by CgA level and other factors predictive of surgical management, Kaplan-Meier survival analysis was performed.

Results: Median CgA level was significantly higher in metastatic versus localized PNET(169 ng/mL versus 66 ng/mL, p < 0.001). On multivariate logistic regression, CgA level was predictive of metastatic disease(OR 1.002, p < 0.001) and survival in metastatic and non-metastatic patients. After matching for CgA level, surgery was associated with improved overall survival.

Discussion: CgA level is predictive of the presence of distant metastatic disease and overall survival in PNET. When matched by CgA and other predictors of treatment approach, patients with metastatic PNET undergoing surgery have improved survival.
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http://dx.doi.org/10.1016/j.hpb.2019.05.011DOI Listing
January 2020

National trends in centralization and perioperative outcomes of complex operations for cancer.

Surgery 2019 11 21;166(5):800-811. Epub 2019 Jun 21.

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA.

Background: Complex cancer operations performed at high-volume and teaching hospitals have been associated with better outcomes. The purpose of this study was to determine the national trends in the performance of these operations at large teaching hospitals.

Methods: Patients who underwent elective esophagectomies, gastrectomies, pancreatectomies, and hepatectomies for cancer (2003-2015) were identified using the National Inpatient Sample. We determined average annual percent change (AAPC) in the proportion of operations at large teaching hospitals, inpatient complications, length of stay (LOS), and inpatient mortality.

Results: Between 2003 and 2015, 38,932 esophageal, 104,941 gastric, 96,098 hepatic, and 137,440 pancreatic cancer resections were performed. The proportion at large teaching hospitals increased with an AAPC of 2.5 for esophagectomies (P < .001), 3.6 for gastrectomies (P < .001), and 1.5 for pancreatectomies (P = .039), but did not change for hepatectomies (AAPC 0.48, P = .50). During the study period, mean LOS and inpatient mortality rates at large teaching hospitals decreased across hospital types. By 2013 to 2015, the operations at large hospitals were associated with decreased mortality only for pancreatectomies (odds ratio, 0.62, 95% confidence interval, 0.43-0.91, P = .015).

Conclusions: Complex cancer operations are performed increasingly at large teaching hospitals, but perioperative outcomes have improved nationally across hospital types. Further studies should identify actionable areas for improvement to ensure accessible quality cancer care.
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http://dx.doi.org/10.1016/j.surg.2019.03.025DOI Listing
November 2019