Publications by authors named "Sanjay P Bagaria"

63 Publications

Treatment Contraindications Based on Comorbidity Status in Patients With Melanoma in the United States.

Anticancer Res 2021 Apr;41(4):2067-2070

Division of Plastic Surgery, Mayo Clinic, Jacksonville, FL, U.S.A.;

Background/aim: Melanoma incidence has increased in the United States over the past few decades, and disparities in patient treatment have been described. Although most patients with melanoma are good candidates for curative treatment, some are considered poor candidates for treatment because of comorbid conditions. We examined whether patient demographics influence treatment contraindication in melanoma.

Patients And Methods: The National Cancer Database (NCDB) was used to identify patients with melanoma from 2004 through 2015. Multivariate logistic regression was used to determine independent associations, adjusted for confounders. We excluded patients who did not receive treatment for reasons and patients with unknown treatment status.

Results: A total of 499,092 patients met the inclusion criteria. Of these, 525 (0.1%) had Treatment contraindicated because of comorbid conditions (TCBC) and 498,567 (99.9%) received treatment. Multivariate logistic regression showed higher odds of TCBC in patients with government insurance (OR=1.34, 95%CI=03-1.73; p=0.03) and patients without insurance (OR=2.75, 95%CI=1.76-4.29; p<0.001) than patients with private insurance.

Conclusion: Demographic disparities affects treatment decision in oncological patients. Our study demonstrated a significantly higher likelihood of "nontreatment because of comorbid conditions" among melanoma patients with government insurance or without insurance. Greater efforts are needed to address inequalities in melanoma treatment in the United States.
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http://dx.doi.org/10.21873/anticanres.14976DOI Listing
April 2021

Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.

Ann Surg Oncol 2021 Mar 19. Epub 2021 Mar 19.

Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Background: Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS.

Methods: In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes.

Results: Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042).

Conclusion: Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection.
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http://dx.doi.org/10.1245/s10434-021-09739-9DOI Listing
March 2021

A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis.

Sci Rep 2021 Mar 2;11(1):4946. Epub 2021 Mar 2.

Department of Gastroenterology, Mayo Clinic, Jacksonville, FL, USA.

Aberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC). During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for PC, HIVM was performed in both tumor and non-tumor areas. The primary outcome was HIVM feasibility to measure vessel characteristics. We secondarily evaluated associations between HIVM vessel characteristics and oncologic outcomes (RECIST response to neoadjuvant therapy and disease-specific survival). Thirty patients with PC were enrolled. Nineteen patients (63.3%) received neoadjuvant therapy. HIVM was feasible in all patients. Compared to non-tumor (control) areas, PC areas had a lower density of functional vessels, higher proportion of non-functional vessels, smaller lumenal diameters, and lower blood flow velocity. Qualitative differences in these vessel characteristics were observed among patients who had partial response, stable disease, or progressive disease after receiving neoadjuvant therapy. However, no statistically significant relationships were found between HIVM vessel characteristics and oncologic outcomes. These novel findings comprise the first-in-human, real-time evidence of the microscopic differences between normal and tumor-associated vessels and form the basis for our larger, ongoing clinical trial appropriately powered to determine the clinical utility of HIVM (NCT03823144).
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http://dx.doi.org/10.1038/s41598-021-84430-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925603PMC
March 2021

Distal Pancreatectomy for Primary Retroperitoneal Sarcoma-Clinical Implications and Future Directions.

Ann Surg Oncol 2021 Feb 26. Epub 2021 Feb 26.

Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

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http://dx.doi.org/10.1245/s10434-021-09766-6DOI Listing
February 2021

Clinical significance of SLN benign capsular nevi in patients with melanoma.

J Surg Oncol 2020 Nov 22;122(6):1043-1049. Epub 2020 Jul 22.

Department of Surgery, Mayo Clinic, Rochester, Minnesota.

Background: Benign capsular nevi (BCN) are not infrequent in sentinel lymph nodes (SLN) of patients with melanoma. Their prognostic significance is unknown and the literature is limited. This study evaluated the clinical significance of incidentally found BCN in these patients.

Methods: A multi-institutional retrospective review of patients undergoing SLN biopsy for cutaneous melanoma between 2000 and 2016. Patients were divided into the following groups: (a) negative SLN and no BCN, (b) negative SLN and presence of BCN, (c) positive SLN seen only on immunohistochemistry (IHC), and (d) positive SLN via hematoxylin and eosin (H&E). Outcomes measured were overall survival and any recurrence.

Results: A total of 1253 patients were identified (group 1 = 978, group 2 = 56, group 3 = 32, and group 4 = 187). Fifty-seven percent were male and the mean age was 59.3 years. BCN was identified in 77 patients (6.2%), of which the majority was in the node-negative group (72%). Multivariable analysis showed that BCN was associated with lower recurrence rates, though not statistically significant (hazard ratio [HR] = 0.5; P = .06). IHC- and H&E-positive SLNs were associated with a higher risk of recurrence (HR = 2.4; P = .02 and 2.0, P < .0001, respectively).

Conclusion: Patients with BCN and negative SLN had lower recurrence rates than patients with negative SLN and no BCN. Our data suggest a possible protective effect against recurrence.
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http://dx.doi.org/10.1002/jso.26135DOI Listing
November 2020

Clinicopathologic Characteristics and Prognosis of Invasive Papillary Carcinoma of the Breast.

J Surg Res 2021 May 7;261:105-112. Epub 2021 Jan 7.

Department of Surgery, Brandon Regional Hospital, HCA Healthcare/ USF Morsani College of Medicine GME, Brandon, Florida.

Background: Invasive papillary carcinoma (IPC) of the breast is thought to carry a more favorable prognosis than invasive ductal carcinoma (IDC). The aim of this study is to investigate the clinicopathological characteristics between IPC and IDC and their prognosis using a large nationwide data set.

Methods: Female patients diagnosed with malignant IPC and IDC between 2005 and 2014 were analyzed. Patients with incomplete survival data, stage 0/IV, unknown stage, or recurrent disease were excluded. Five-year overall survival was compared between IPC and IDC.

Results: Among 308,426 patients, 1147 had IPC and 307,279 had IDC. IPC presented more in older postmenopausal women, black Americans, and people who had government insurance. IPC had larger tumor size, lower-grade, and earlier-stage disease, less node-positive disease, higher hormone positivity, and lower human epidermal growth factor receptor 2 amplification. Adjuvant radiation and chemotherapy rates were lower in IPC than those in IDC. IPC had a similar 5-year overall survival as compared with IDC overall (86.8% versus 88.7%) (P = 0.06). Age, pathologic stage, and radiation treatment were shown to be independent prognostic factors of IPC.

Conclusions: IPC has a similar prognosis as IDC, suggesting that these patients should follow the same treatment protocols.
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http://dx.doi.org/10.1016/j.jss.2020.12.026DOI Listing
May 2021

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

Ann Surg Oncol 2021 May 2;28(5):2705-2714. 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
May 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

Comparative Analysis of Acral Melanoma in Chinese and Caucasian Patients.

J Skin Cancer 2020 6;2020:5169051. Epub 2020 Oct 6.

Department of General Surgery, Mayo Clinic Florida, Jacksonville, FL, USA.

Background: Acral melanoma (AM) is a rare subtype of melanoma, which is one of the least common in Caucasian patients but is a common subtype of melanoma in Chinese patients. It is unclear if prognosis differs between Chinese and Caucasian patients diagnosed with AM. The aim of our study is to investigate patient characteristics and survival differences between Chinese and Caucasian AM patients.

Methods: Two large institutional melanoma databases from Fudan University Shanghai Cancer Center (FUSCC) and Mayo Clinic enterprise were retrospectively reviewed from 2009 to 2015. Clinicopathologic and survival data were collected and analyzed between the two groups. The primary outcome was disease-specific survival (DSS) and was calculated using the Kaplan Meier (KM) method.

Results: The Chinese group presented with more advanced disease compared with Caucasians: thicker Breslow depth (median 3.0 mm vs. 1.2 mm, =0.003), more ulcerated disease (66.1% vs. 29%; < 0.001), and advanced stages (stage II/III 84.3% vs. 37.1%; < 0.001). No significant difference was identified in terms of age at diagnosis, location, histologic subtypes, or node positive rate. The 5-year DSS rate was 68.4% and 73% (=0.56) in Chinese and Caucasians AM patients, respectively. Male gender, Breslow thickness, ulceration, and positive sentinel lymph nodes were independent poor prognostic factors on multivariate analysis.

Conclusions: There appears to be no difference in stage-stratified survival between Chinese and Caucasians, supporting the implementation of clinical trials for AM that could include both Chinese and Caucasian patients.
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http://dx.doi.org/10.1155/2020/5169051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557897PMC
October 2020

Amelanotic melanoma of the head and neck: analysis of tumor characteristics from the National Cancer Database.

Int J Dermatol 2021 Mar 11;60(3):347-351. Epub 2020 Oct 11.

Division of Plastic Surgery, Mayo Clinic, Jacksonville, FL, USA.

Background: Amelanotic melanoma is an extremely rare subtype of cutaneous melanoma. The tumor characteristics are still not well understood, especially for those located in the head and neck.

Methods: Tumor characteristics of patients diagnosed with amelanotic melanoma of the head and neck (AMHN) from January 1, 2004, to December 31, 2015, were analyzed by querying the National Cancer Database. Characteristics of AMHN were subsequently compared with common malignant melanoma of the head and neck (CMMHN).

Results: Three hundred and sixty-eight patients were diagnosed with AMHN, and 69,267 were diagnosed with CMMHN. Of those with AMHN, 128 (34.8%) had melanoma located on the scalp and neck, and 172 (46.7%) were diagnosed with an early disease stage (i.e., 0, I, or II). When compared with CMMHN, patients with AMHN were more likely to be diagnosed after 80 years of age (25.3% vs. 18.2%; odds ratio [OR], 3.28; 95% CI, 1.09-9.84; P = 0.03), when Breslow depth was between 2.01 and 4.00 mm (28.5% vs. 6.5%; OR, 1.92; 95% CI, 1.15-3.19; P = 0.01), when ulceration was present (36.7% vs. 9.0%; OR, 1.99; 95% CI, 1.34-2.97; P = 0.001), and when mitotic count was 1 or more/mm (40.5% vs. 12.8%; OR; 2.53; 95% CI, 1.09-5.89; P = 0.03). No statistical difference was found for sex, specific location, stage, or lymph node involvement.

Conclusion: Our study determined that AMHN is associated with older age, increased Breslow depth, presence of ulceration, and greater mitotic count when compared with CMMHN.
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http://dx.doi.org/10.1111/ijd.15243DOI Listing
March 2021

Intravital Microscopy (IVM) in Human Solid Tumors: Novel Protocol to Examine Tumor-Associated Vessels.

JMIR Res Protoc 2020 Oct 9;9(10):e15677. Epub 2020 Oct 9.

Division of Surgical Oncology, Department of Surgery, Mayo Clinic, Jacksonville, FL, United States.

Background: Intravital microscopy (IVM) allows the real-time, direct visualization of microscopic blood vessels. This pilot clinical trial will elucidate the physical and functional characteristics of vessels associated with solid tumors.

Objective: The main objective of this study is to determine the feasibility of performing IVM in patients with solid tumors during the standard course of surgical resection. IVM will also be performed when vasopressors or fluid boluses are administered during the standard course of the operation.

Methods: This is an open-label, nonrandomized, single-center, pilot study of IVM observation in subjects with solid tumors undergoing surgical resection.

Results: This study was active on January 1, 2019 (NCT03823144) and funded by the Mayo Clinic Florida Cancer Focused Research Team Award. As of September 27, 2020, we had enrolled 20 patients. Accrual period is expected to end by December 31, 2021.

Conclusions: This trial will support the development of interventions to improve patient treatment by extending the application of IVM to the tumor microenvironment. IVM observations during volume and pressor management at the time of surgery may aid in the development of strategies to augment responses to systemic treatments.

International Registered Report Identifier (irrid): PRR1-10.2196/15677.
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http://dx.doi.org/10.2196/15677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584984PMC
October 2020

Identification of stage I/IIA melanoma patients at high risk for disease relapse using a clinicopathologic and gene expression model.

Eur J Cancer 2020 11 5;140:11-18. Epub 2020 Oct 5.

Mayo Clinic, Rochester, MN, USA. Electronic address:

Purpose: Patients with stage I/IIA cutaneous melanoma (CM) are currently not eligible for adjuvant therapies despite uncertainty in relapse risk. Here, we studied the ability of a recently developed model which combines clinicopathologic and gene expression variables (CP-GEP) to identify stage I/IIA melanoma patients who have a high risk for disease relapse.

Patients And Methods: Archival specimens from a cohort of 837 consecutive primary CMs were used for assessing the prognostic performance of CP-GEP. The CP-GEP model combines Breslow thickness and patient age, with the expression of eight genes in the primary tumour. Our specific patient group, represented by 580 stage I/IIA patients, was stratified based on their risk of relapse: CP-GEP High Risk and CP-GEP Low Risk. The main clinical end-point of this study was five-year relapse-free survival (RFS).

Results: Within the stage I/IIA melanoma group, CP-GEP identified a high-risk patient group (47% of total stage I/IIA patients) which had a considerably worse five-year RFS than the low-risk patient group; 74% (95% confidence interval [CI]: 67%-80%) versus 89% (95% CI: 84%-93%); hazard ratio [HR] = 2.98 (95% CI: 1.78-4.98); P < 0.0001. Of patients in the high-risk group, those who relapsed were most likely to do so within the first 3 years.

Conclusion: The CP-GEP model can be used to identify stage I/IIA patients who have a high risk for disease relapse. These patients may benefit from adjuvant therapy.
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http://dx.doi.org/10.1016/j.ejca.2020.08.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655519PMC
November 2020

Age-Based Trends of Gastric Adenocarcinoma in the United States.

Am Surg 2020 Dec 31;86(12):1721-1727. Epub 2020 Aug 31.

Department of Surgery, Mayo Clinic, Jacksonville, FL, USA.

Background: Recent studies have shown an increase in the incidence of gastric cancer (GC) among young adults in Asia and Latin America. However, it is unknown if a similar trend is happening in the United States (US).

Methods: A retrospective review of the National Cancer Data Base was conducted to identify patients diagnosed with gastric adenocarcinoma between the years of 2004 and 2013.

Results: A total of 93 734 patients were included. The 2 age groups below 40 did not see a change in GC incidence; however, age groups above 40 had increasing incidence. Patients aged 18-25 had the largest proportion of stage 4 disease and a poor survival (median 11.5 months), compared to older patients.

Conclusion: Despite the increasing trend of GC among individuals, the incidence of GC among young adults is not increasing. However, this subpopulation presents at more advanced stages (clinical stage 4) and thus has worse survival.
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http://dx.doi.org/10.1177/0003134820947395DOI Listing
December 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

Dynamic control of tumor vasculature improves antitumor responses in a regional model of melanoma.

Sci Rep 2020 08 6;10(1):13245. Epub 2020 Aug 6.

Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

Despite advances in therapy for melanoma, heterogeneous responses with limited durability represent a major gap in treatment outcomes. The purpose of this study was to determine whether alteration in tumor blood flow could augment drug delivery and improve antitumor responses in a regional model of melanoma. This approach to altering tumor blood flow was termed "dynamic control." Dynamic control of tumor vessels in C57BL/6 mice bearing B16 melanoma was performed using volume expansion (saline bolus) followed by phenylephrine. Intravital microscopy (IVM) was used to observe changes directly in real time. Our approach restored blood flow in non-functional tumor vessels. It also resulted in increased chemotherapy (melphalan) activity, as measured by formation of DNA adducts. The combination of dynamic control and melphalan resulted in superior outcomes compared to melphalan alone (median time to event 40.0 vs 25.0 days, respectively, p = 0.041). Moreover, 25% (3/12) of the mice treated with the combination approach showed complete tumor response. Importantly, dynamic control plus melphalan did not result in increased adverse events. In summary, we showed that dynamic control was feasible, directly observable, and augmented antitumor responses in a regional model of melanoma. Early clinical trials to determine the translational feasibility of dynamic control are ongoing.
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http://dx.doi.org/10.1038/s41598-020-70233-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413248PMC
August 2020

Age-Based Trends of Gastric Adenocarcinoma in the United States.

Am Surg 2020 May;86(5):407-414

Department of Surgery, Mayo Clinic, Jacksonville, FL, USA.

Background: Recent studies have shown an increase in the incidence of gastric cancer (GC) among young adults in Asia and Latin America. However, it is unknown if a similar trend is happening in the United States.

Methods: A retrospective review of the National Cancer Database was conducted to identify patients diagnosed with gastric adenocarcinoma between the years of 2004 and 2013.

Results: A total of 93 734 patients were included. The two age groups below 40 did not see a change in GC incidence; however, age groups above 40 had increasing incidence. Patients aged 18 to 25 had the largest proportion of stage 4 disease and a poor survival (median 11.5 months), compared to older patients.

Conclusion: Despite the increasing trend of GC among individuals, the incidence of GC among young adults is not increasing. However, this subpopulation presents at more advanced stages (clinical stage 4) and thus has worse survival.
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http://dx.doi.org/10.1177/0003134820918250DOI Listing
May 2020

Completion lymph node dissection in patients with sentinel lymph node positive cutaneous head and neck melanoma.

J Surg Oncol 2020 Nov 11;122(6):1057-1065. Epub 2020 Jul 11.

Department of Surgical Oncology, Mayo Clinic, Jacksonville, Florida.

Background: Relatively few cutaneous head and neck melanoma (CHNM) patients with were included in the multicenter selective lymphadenectomy trial II (MSLT-II). Our objective was to investigate whether immediate completion lymph node dissection completion of lymph node dissection (CLND) was associated with survival benefit for sentinel lymph node (SLN) positive CHNM using the National Cancer Database.

Methods: SLN positive patients with CHNM from 2012 to 2014 were retrospectively analyzed. Patients were divided into two groups: those who underwent SLN biopsy (SLNB) only versus those who underwent SLNB followed by CLND (SLNB + CLND). The primary outcome was 5-year overall survival (OS).

Results: Among 530 SLNB + patients, 342 patients underwent SLNB followed by CLND (SLNB + CLND). The SLNB only group had fewer positive SLN, less advanced pathologic stage, and a lower rate of adjuvant immunotherapy. There was no significant difference in 5-year OS between the two groups (51.0% vs 67%; P = .56). After adjusting for pathologic stage, there remained no difference in 5-year OS among patients with stage IIIA (63.0% vs. 73.6%, P = 0.22) or IIIB/IIIC disease (39.1% vs 57.8%; P = .52). Conclusions Using a large nationwide database, CLND was not shown to be associated with improved OS for patients with SLNB positive CHNM, validating the results of MSLT-II.
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http://dx.doi.org/10.1002/jso.26119DOI Listing
November 2020

National Comprehensive Analysis of Characteristics of Acral Lentiginous Melanoma.

Anticancer Res 2020 Jun;40(6):3411-3415

Division of Plastic Surgery, Mayo Clinic, Jacksonville, FL, U.S.A.

Background/aim: Acral lentiginous melanoma (ALM) is the least common subtype of cutaneous melanoma and typically occurs on the palms, soles, and nails. Tumor characteristics and disease severity in the US population are not well understood. Our aim was to analyze the characteristics of ALM of the extremities.

Patients And Methods: We queried the National Cancer Database to identify patients with the diagnosis of ALM and common malignant melanoma located in the extremities (CMME). We compared demographic, tumor, and treatment characteristics between patients with ALM and those with CMME. Statistical analysis was performed with chi-squared test and multivariate logistic regression models.

Results: We identified 5,203 patients with ALM and 118,485 with CMME. When compared with patients with CMME, those with ALM were more likely to be older than 80. years at diagnosis [odds ratio (OR)=2.85, 95% confidence intervaI (CI)=2.12-3.82; p<0.001], have stage III disease (OR=4.22, 95% CI=1.47-12.16; p=0.01), and have ulceration (OR=1.52, 95% CI=1.33-1.74; p<0.001). Moreover, patients with ALM were less likely to have a mitotic count of 1/mm or greater (OR=0.57, 95% CI=0.48-0.67; p<0.001). No statistical difference was found for sex, lymph node involvement, regression, and use of surgery, radiotherapy, and immunotherapy between groups.

Conclusion: Age, disease stage, ulceration, and mitotic count are independent factors associated with ALM. Knowledge of the disease characteristics may allow for better diagnosis and understanding of disease pathophysiology.
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http://dx.doi.org/10.21873/anticanres.14325DOI Listing
June 2020

Breast cancer in women: a descriptive analysis of the national cancer database.

Acta Biomed 2020 May 11;91(2):332-341. Epub 2020 May 11.

Division of Plastic Surgery and Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Jacksonville, Florida.

Background And Aim Of The Work: Breast cancer is the most common cancer in women in the United States. National Cancer Database (NCDB) is one of the largest tumor databases of the United States. This study aimed to evaluate the features of breast cancer in women from a large updated database.

Methods: We describe and analyze the frequencies and percentages of the clinical and pathological features of women diagnosed with breast cancer registered in NCDB, in a period from 2004 to 2015.

Results: A total of 2,423,875 women were diagnosed with breast cancer between 2004 and 2015. The nationally representative analysis demonstrated that the incidence of breast cancer among women increased over the years. Upper-outer quadrant was the most frequent primary tumor site, and the intraductal carcinoma was the most frequent histology. The prevalence of breast cancer increased with age. The most frequent grade at diagnosis was grade II. Broadly, invasive characteristics were noted more frequently in younger patients. Left and right breast were affected with almost the same frequency, with a slight predominance of the left breast. The most frequent surgical treatment was a partial mastectomy. Reconstruction with implant was the most frequent choice. Post-mastectomy radiation therapy was administered in the majority of patients.

Conclusions: To the authors' knowledge, the current study is the largest descriptive analysis to date on the clinical and pathological features of breast cancer in a population-based database. The increase in incidence over the years indicates an important need for etiologic research and innovative approaches to improve breast cancer prevention.
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http://dx.doi.org/10.23750/abm.v91i2.8399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569667PMC
May 2020

Model Combining Tumor Molecular and Clinicopathologic Risk Factors Predicts Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

JCO Precis Oncol 2020 14;4:319-334. Epub 2020 Apr 14.

Mayo Clinic, Rochester, MN, USA.

Purpose: More than 80% of patients who undergo sentinel lymph node (SLN) biopsy have no nodal metastasis. Here we describe a model that combines clinicopathologic and molecular variables to identify patients with thin and intermediate thickness melanomas who may forgo the SLN biopsy procedure due to their low risk of nodal metastasis.

Patients And Methods: Genes with functional roles in melanoma metastasis were discovered by analysis of next generation sequencing data and case control studies. We then used PCR to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 754 consecutive thin and intermediate thickness primary cutaneous melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. A penalized maximum likelihood estimation algorithm was used to train logistic regression models in a repeated cross validation scheme to predict the presence of SLN metastasis from molecular, clinical and histologic variables.

Results: Expression of genes with roles in epithelial-to-mesenchymal transition (glia derived nexin, growth differentiation factor 15, integrin β3, interleukin 8, lysyl oxidase homolog 4, TGFβ receptor type 1 and tissue-type plasminogen activator) and melanosome function (melanoma antigen recognized by T cells 1) were associated with SLN metastasis. The predictive ability of a model that only considered clinicopathologic or gene expression variables was outperformed by a model which included molecular variables in combination with the clinicopathologic predictors Breslow thickness and patient age; AUC, 0.82; 95% CI, 0.78-0.86; SLN biopsy reduction rate of 42% at a negative predictive value of 96%.

Conclusion: A combined model including clinicopathologic and gene expression variables improved the identification of melanoma patients who may forgo the SLN biopsy procedure due to their low risk of nodal metastasis.
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http://dx.doi.org/10.1200/po.19.00206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220172PMC
April 2020

Wide Excisional Surgery in Invasive Melanoma Treatment: Factors Driving Non-compliance With National Guidelines.

Anticancer Res 2020 Feb;40(2):1065-1069

Division of Plastic Surgery and Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Jacksonville, FL, U.S.A.

Background/aim: Margin size during wide excisional surgery for invasive melanoma treatment have been established by national guidelines. This study identified factors associated with wider than recommended excisional margins and its impact on survival.

Patients And Methods: The National Cancer Database was queried to identify patients with primary invasive melanoma. Statistical analysis was performed using univariate and multivariate analysis. Overall survival was compared using Kaplan-Meier method.

Results: A total of 26,440 patients were included in the analysis. Melanomas located on the trunk were more likely to be treated using wider than recommended excisional margins for certain Breslow depth groups (p<0.05), while the opposite was true for those being treated in an academic/research program (p<0.05). The practice of taking wider than recommended margins was not associated with improved survival.

Conclusion: Tumor location and facility type influence non-compliance with the National Comprehensive Cancer Network guidelines. Lack of survival benefit in patients with wider excisional margins seems to support guideline recommendations.
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http://dx.doi.org/10.21873/anticanres.14044DOI Listing
February 2020

Residual Tumor on Wide Excisional Margins After Treatment of Invasive Melanoma.

Anticancer Res 2020 Feb;40(2):1059-1063

Division of Plastic Surgery and Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Jacksonville, FL, U.S.A.

Background/aim: The surgical management of invasive melanoma has been debated for many years and recommended excisional margins have been established. We aimed to describe the factors and survival related to the presence of residual tumor in patients with invasive melanoma lymph nodes negative.

Patients And Methods: We performed a retrospective study by querying the National Cancer Database from 2004 to 2015. Associations were tested using a multivariate analysis. Overall survival was compared using the Kaplan-Meier method.

Results: A total of 26,440 patients met the inclusion criteria. For Breslow depth groups ≤1 mm and >2 mm, older age and location in the head and neck were factors associated to residual tumor in margins (p<0.05), whereas only location in the head and neck was associated to residual tumor for patients with Breslow depth between 1.01-2.00 mm (p<0.05).

Conclusion: Knowledge of the factors associated with the residual tumor will help establish a patient-centered management and decrease the recurrence of disease.
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http://dx.doi.org/10.21873/anticanres.14043DOI Listing
February 2020

National Analysis of Patients With Ulcerated Melanoma in the United States.

Anticancer Res 2020 Feb;40(2):1055-1058

Division of Plastic Surgery, Mayo Clinic, Jacksonville, FL, U.S.A.

Background/aim: Ulceration is associated with unfavorable prognosis in patients with melanoma. The present study aimed to analyze the characteristics associated with ulcerated melanoma in the United States. It was hypothesized that patient disparities associated with increased odds of ulceration exist.

Patients And Methods: We searched the National Cancer Database for melanoma patients from 2004 to 2015. Data regarding patient demographics, facility characteristics, and tumor characteristics were analyzed.

Results: There were higher odds of ulceration in non-white patients, 50 years of age or older, and melanoma on the trunk and extremities. Lower odds were found in women, zip codes with higher income and education levels, and Metro or Urban counties.

Conclusion: Age above 49 years, male sex, non-white race, living in rural areas, and living in zip codes with low income and low education were independently associated with ulcerated melanoma.
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http://dx.doi.org/10.21873/anticanres.14042DOI Listing
February 2020

Racial Disparities in Outcomes Among Asians With Gastric Cancer in the USA.

Anticancer Res 2020 Feb;40(2):881-889

Department of Surgery, Mayo Clinic, Jacksonville, FL, U.S.A.

Background/aim: We aimed to evaluate disparities in presentation and treatment of gastric cancer (GC), including time between diagnosis and treatment, based on race, focusing on Japanese patients within the USA.

Patients And Methods: The National Cancer Database was queried for patients diagnosed with GC between 2004-2013. Clinical and treatment variables were summarized by race (White, non-Japanese Asian, Japanese). The association between race and overall survival (OS) was evaluated using the log-rank test.

Results: A total of 79,481 patients were included. Japanese patients received surgery the earliest after diagnosis in all stages. Regarding radiotherapy, white patients had the shortest waiting time followed by Asian and Japanese patients. Asian patients had better OS at both 3 and 5 years of follow-up. White patients were associated with the lowest OS.

Conclusion: Japanese and Asian GC patients have better OS compared to White patients. Moreover, there were disparities in time to both GC diagnosis and treatment, with Japanese patients being sooner diagnosed and surgically treated, which may ultimately impact patient experience.
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http://dx.doi.org/10.21873/anticanres.14021DOI Listing
February 2020

Trends in utilization of sentinel node biopsy and adjuvant radiation in women ≥ 70.

Breast J 2020 07 6;26(7):1321-1329. Epub 2020 Jan 6.

Department of Surgery, Mayo Clinic, Jacksonville, Florida.

Background And Objectives: Omission of routine axillary staging and adjuvant radiation (XRT) in women ≥ 70 years old with early stage, hormone receptor-positive, clinically node-negative breast cancer has been endorsed based on several landmark studies. We sought to determine how much omission of axillary staging/XRT has been adopted.

Methods: Using the National Cancer Data Base, we selected malignant breast cancer cases in women ≥ 70 with ER + tumors, ≤2 cm with clinically negative lymph nodes who underwent breast conservation and had known XRT status in 2005-2015. The use of sentinel lymph node biopsy (SNB) and XRT status was summarized by year to determine trends over time.

Results: In total, 57 230/69 982 patients underwent SNB. Of the 12 752 patients in whom SNB was omitted, 6296 were treated at comprehensive community cancer programs. Regarding XRT, 33 891/70 114 received adjuvant XRT. There were no significant trends with regards to patients receiving SNB or those receiving XRT.

Conclusion: Since 2005, there has been no change in SNB or XRT for early stage ER + breast tumors. However, there was a difference in omission of SNB based on facility type and setting. Future monitoring is needed to determine if these trends persist following the recently released Choosing Wisely recommendations.
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http://dx.doi.org/10.1111/tbj.13750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335676PMC
July 2020

Desmoplastic Melanoma: Clinical Characteristics and Survival in the US Population.

Cureus 2019 Jun 18;11(6):e4931. Epub 2019 Jun 18.

Plastic Surgery, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic Florida, Jacksonville, USA.

Objective Desmoplastic melanoma (DM) is a rare variant of invasive malignancy of the skin pigmented cells. We present a comprehensive study reporting on US demographics, disease characteristics, and survival, to contribute to the current knowledge and raise awareness of this rare disease. Materials and methods The demographics of DM patients diagnosed from January 1, 2004, to December 31, 2015, were obtained by querying the National Cancer Database. The characteristics of DM were compared with common malignant melanoma (CMM) using univariate and multivariate regression models. Five-year overall survival (OS) curves were estimated using Kaplan-Meier analyses and the Cox proportional regression model. Results Our query found 5,895 patients diagnosed with DM and 292,939 patients with CMM. DM tended to present at an older age, a more advanced stage, and with a Breslow depth greater than 4 mm at diagnosis (P<.05). The Kaplan-Meier survival analysis demonstrated a five-year OS for DM and CMM of 75% and 76%, respectively, without any statistical difference (P=.07). Cox regression analysis demonstrated that age at diagnosis and comorbidities were independent predictors of five-year OS for DM (P<.001). Conclusions Older age, advanced stage, and higher Breslow depth were found to be independent positive factors associated with DM.
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http://dx.doi.org/10.7759/cureus.4931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695240PMC
June 2019

Sexual dimorphism in the incidence of human cancers.

BMC Cancer 2019 Jul 12;19(1):684. Epub 2019 Jul 12.

Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Griffin 210, Jacksonville, FL, 32224, USA.

Background: Sex differences in the incidences of cancers become a critical issue in both cancer research and the development of precision medicine. However, details in these differences have not been well reported. We provide a comprehensive analysis of sexual dimorphism in human cancers.

Methods: We analyzed four sets of cancer incidence data from the SEER (USA, 1975-2015), from the Cancer Registry at Mayo Clinic (1970-2015), from Sweden (1970-2015), and from the World Cancer Report in 2012.

Results: We found that all human cancers had statistically significant sexual dimorphism with male dominance in the United States and mostly significant in the Mayo Clinic, Sweden, and the world data, except for thyroid cancer, which is female-dominant.

Conclusions: Sexual dimorphism is a clear but mostly neglected phenotype for most human cancers regarding the clinical practice of cancer. We expect that our study will facilitate the mechanistic studies of sexual dimorphism in human cancers. We believe that fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of individualized precision medicine beginning from the sex-specific diagnosis, prognosis, and treatment.
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http://dx.doi.org/10.1186/s12885-019-5902-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625025PMC
July 2019

Intraoperative fluid restriction in hyperthermic intraperitoneal chemotherapy.

J Surg Res 2018 11 9;231:77-82. Epub 2018 Jun 9.

Department of Surgery, Mayo Clinic, Jacksonville, Florida. Electronic address:

Background: Multiple studies highlight the importance of liberal fluid administration in cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Over-resuscitation can delay recovery and wound healing. We report an intraoperative protocol that restricts fluid administration and minimizes morbidity.

Materials And Methods: Retrospective analysis of 35 patients that underwent CRS-HIPEC for curative intent under fluid restriction protocol from June 2015 to July 2017 was performed. Protocol consists of continuous infusion of vasopressin 0.02 units/h and maintaining urine output at 0.5 mL/kg/h via crystalloid and colloid. Endpoint was Clavien-Dindo ≥3 events within 30 d of CRS-HIPEC.

Results: Median age was 56 y; 71% were female. Malignancies treated: appendix (49%), colon (31%), and other (20%). Median peritoneal cancer index was 15, complete cytoreduction was achieved in 91% of patients. Median time for return of bowel function was 5 d, median length of hospital stay was 7 d. There were 28 bowel anastomoses. Median intraoperative crystalloid, colloid, and packed red blood cells were (1900, 1500, and 700 mL), respectively. Clavien-Dindo grade 3-4 events occurred in five patients. There were no deaths 30 d after surgery.

Conclusions: A fluid restriction protocol appears to be safe and feasible in the setting of CRS-HIPEC for curative intent.
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http://dx.doi.org/10.1016/j.jss.2018.05.015DOI Listing
November 2018

Regulation of sex hormone receptors in sexual dimorphism of human cancers.

Cancer Lett 2018 12 14;438:24-31. Epub 2018 Sep 14.

Department of Cancer Biology, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. Electronic address:

Gender differences in the incidences of cancers have been found in almost all human cancers. However, the mechanisms that underlie gender disparities in most human cancer types have been under-investigated. Here, we provide a comprehensive overview of potential mechanisms underlying sexual dimorphism of each cancer regarding sex hormone signaling. Fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of precision medicine. Our discussions of potential mechanisms underlying sexual dimorphism in each cancer will be instructive for future cancer research on gender disparities.
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http://dx.doi.org/10.1016/j.canlet.2018.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287770PMC
December 2018

The Volume-Outcome Relationship in Retroperitoneal Soft Tissue Sarcoma: Evidence of Improved Short- and Long-Term Outcomes at High-Volume Institutions.

Sarcoma 2018 24;2018:3056562. Epub 2018 Jul 24.

Department of Surgery, Section of Surgical Oncology, Mayo Clinic, Phoenix, AZ, USA.

Background: We sought to study the association between RPS case volume and outcomes. Although a relationship has been demonstrated between case volume and patient outcomes in some cancers, such a relationship has not been established for retroperitoneal sarcomas (RPSs).

Study Design: The National Cancer Database (NCDB) was queried for patients undergoing treatment for primary RPS diagnosed between 2004 and 2013. Mean annual patient volume for RPS resection was calculated for all hospitals and divided into low volume (<5 cases/year), medium volume (5-10 cases/year), and high volume (>10 cases/year). Risk-adjusted regression analyses were performed to identify predictors of 30-day surgical mortality, 0 margin status, and overall survival (OS).

Results: Our study population consisted of 5,407 patients with a median age of 61 years, of whom 47% were male and 3,803 (70%) underwent surgical resection. Absolute 30-day surgical mortality and 0 margin rate following surgery for low-, medium-, and high-volume institutions were 2.4%, 1.3%, and 0.5% (=0.027) and 68%, 65%, and 82%, ( < 0.001), respectively. Five-year overall survival rates for low, medium, and high-volume institutions were 56%, 57%, and 66%, respectively ( < 0.001). Patients treated at low-volume institutions had a significantly higher risk of 30-day mortality (adjusted OR = 4.66, 95% CI 2.26-9.63) and long-term mortality (adjusted HR = 1.56, 95% CI 1.16-2.11) compared to high-volume institutions.

Conclusion: We demonstrate the existence of a hospital sarcoma service line volume-oncologic outcome relationship for RPS at the national level and provide benchmark data for cancer care delivery systems and policy makers.
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http://dx.doi.org/10.1155/2018/3056562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081523PMC
July 2018